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13,900 | 26,936,039 | There was no difference for changes in the incidence of renal replacement therapy , estimated glomerular filtration rate or serum creatinine .
CONCLUSIONS RIC might be beneficial for the prevention of investigator-defined AKI ; however , the effect is likely small .
Moreover , due to lack of an effect on use of renal replacement therapy , estimated glomerular filtration rate , RIFLE , AKIN , or KDIGO-defined AKI , and serum creatinine , the evidence for RIC is not robust .
Finally , recent large-scale RCTs of RIC focusing on patient-centered outcomes do not support the wider application of RIC | BACKGROUND Results from r and omized controlled trials ( RCTs ) concerning kidney effect of remote ischemic conditioning ( RIC ) are inconsistent . | OBJECTIVES This study sought to evaluate whether remote ischemic post-conditioning ( RIPC ) could reduce enzymatic infa rct size in patients with anterior ST-segment elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention ( pPCI ) . BACKGROUND Myocardial reperfusion injury may attenuate the benefit of pPCI . In animal models , RIPC mitigates myocardial reperfusion injury . METHODS One hundred patients with anterior ST-segment elevation myocardial infa rct ion and occluded left anterior descending artery were r and omized to pPCI + RIPC ( n = 50 ) or conventional pPCI ( n = 50 ) . RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb . The primary endpoint was infa rct size assessed by the area under the curve of creatinine kinase-myocardial b and release ( CK-MB ) . Secondary endpoints included the following : infa rct size assessed by cardiac magnetic resonance delayed enhancement volume ; T2-weighted edema volume ; ST-segment resolution > 50 % ; TIMI ( Thrombolysis In Myocardial Infa rct ion ) frame count ; and myocardial blush grading . RESULTS Four patients ( 2 RIPC , 2 controls ) were excluded due to missing sample s of CK-MB . A total of 96 patients were analyzed ; median area under the curve CK-MB was 8,814 ( interquartile range [ IQR ] : 5,567 to 11,325 ) arbitrary units in the RIPC group and 10,065 ( IQR : 7,465 to 14,004 ) arbitrary units in control subjects ( relative reduction : 20 % , 95 % confidence interval : 0.2 % to 28.7 % ; p = 0.043 ) . Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after r and omization , and 66 patients repeated a second scan after 4 months . T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects ( p = 0.049 ) . ST-segment resolution > 50 % was 66 % in RIPC and 37 % in control subjects ( p = 0.015 ) . We observed no significant differences in TIMI frame count , myocardial blush grading , and delayed enhancement volume . CONCLUSIONS In patients with anterior ST-segment elevation myocardial infa rct ion , RIPC at the time of pPCI reduced enzymatic infa rct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution > 50 % . ( Remote Postconditioning in Patients With Acute Myocardial Infa rct ion Treated by Primary Percutaneous Coronary Intervention [ PCI ] [ RemPostCon ] ; NCT00865722 ) BACKGROUND Whether remote ischemic preconditioning ( transient ischemia and reperfusion of the arm ) can improve clinical outcomes in patients undergoing coronary-artery bypass graft ( CABG ) surgery is not known . We investigated this question in a r and omized trial . METHODS We conducted a multicenter , sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG ( with or without valve surgery ) with blood cardioplegia . After anesthesia induction and before surgical incision , patients were r and omly assigned to remote ischemic preconditioning ( four 5-minute inflations and deflations of a st and ard blood-pressure cuff on the upper arm ) or sham conditioning ( control group ) . Anesthetic management and perioperative care were not st and ardized . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , coronary revascularization , or stroke , assessed 12 months after r and omization . RESULTS We enrolled a total of 1612 patients ( 811 in the control group and 801 in the ischemic-preconditioning group ) at 30 cardiac surgery centers in the United Kingdom . There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group ( 212 patients [ 26.5 % ] and 225 patients [ 27.7 % ] , respectively ; hazard ratio with ischemic preconditioning , 0.95 ; 95 % confidence interval , 0.79 to 1.15 ; P=0.58 ) . Furthermore , there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury ( assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours ) , inotrope score ( calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery ) , acute kidney injury , duration of stay in the intensive care unit and hospital , distance on the 6-minute walk test , and quality of life . CONCLUSIONS Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery . ( Funded by the Efficacy and Mechanism Evaluation Program [ a Medical Research Council and National Institute of Health Research partnership ] and the British Heart Foundation ; ERICCA Clinical Trials.gov number , NCT01247545 . ) Background : Two preconditioning stimuli should induce a more consistent overall cell protection . We hypothesized that remote ischemic preconditioning ( RIPC , second preconditioning stimulus ) applied during isoflurane inhalation ( first preconditioning stimulus ) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting . Methods : In this placebo-controlled r and omized controlled study , patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping . Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance . The primary outcome was high-sensitivity cardiac troponin T release . Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide , high-sensitivity C-reactive protein , S100 protein , and short- and long-term clinical outcomes . Gene expression profiles were obtained from atrial tissue using microarrays . Results : RIPC ( n = 27 ) did not reduce high-sensitivity cardiac troponin T release when compared with placebo ( n = 28 ) . Likewise , N-terminal pro-brain natriuretic peptide , a marker of myocardial dysfunction ; high-sensitivity C-reactive protein , a marker of perioperative inflammatory response ; and S100 , a marker of cerebral injury , were not different between the groups . The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infa rct ions was higher in the RIPC group than the placebo group ( 14/27 vs. 6/28 , P = 0.036 ) . However , there was no difference in the 6-month cardiovascular outcome . N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism ( P = 0.001 ) and DNA-damage signaling ( P < 0.001 ) , but not with RIPC-induced changes in gene expression . Conclusions : RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting BACKGROUND Remote ischemic preconditioning ( RIPC ) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery , but uncertainty about clinical outcomes remains . METHODS We conducted a prospect i ve , double-blind , multicenter , r and omized , controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol . The trial compared upper-limb RIPC with a sham intervention . The primary end point was a composite of death , myocardial infa rct ion , stroke , or acute renal failure up to the time of hospital discharge . Secondary end points included the occurrence of any individual component of the primary end point by day 90 . RESULTS A total of 1403 patients underwent r and omization . The full analysis set comprised 1385 patients ( 692 in the RIPC group and 693 in the sham-RIPC group ) . There was no significant between-group difference in the rate of the composite primary end point ( 99 patients [ 14.3 % ] in the RIPC group and 101 [ 14.6 % ] in the sham-RIPC group , P=0.89 ) or of any of the individual components : death ( 9 patients [ 1.3 % ] and 4 [ 0.6 % ] , respectively ; P=0.21 ) , myocardial infa rct ion ( 47 [ 6.8 % ] and 63 [ 9.1 % ] , P=0.12 ) , stroke ( 14 [ 2.0 % ] and 15 [ 2.2 % ] , P=0.79 ) , and acute renal failure ( 42 [ 6.1 % ] and 35 [ 5.1 % ] , P=0.45 ) . The results were similar in the per- protocol analysis . No treatment effect was found in any subgroup analysis . No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release , the duration of mechanical ventilation , the length of stay in the intensive care unit or the hospital , new onset of atrial fibrillation , and the incidence of postoperative delirium . No RIPC-related adverse events were observed . CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery . ( Funded by the German Research Foundation ; RIPHeart Clinical Trials.gov number , NCT01067703 . ) Background Remote ischemic preconditioning ( RIPC ) harnesses an innate defensive mechanism that protects against inflammatory activation and ischemia‐reperfusion injury , known sequelae of cardiac surgery with cardiopulmonary bypass . We sought to determine the impact of RIPC on clinical outcomes and physiological markers related to ischemia‐reperfusion injury and inflammatory activation after cardiac surgery in children . Methods and Results Overall , 299 children ( aged neonate to 17 years ) were r and omized to receive an RIPC stimulus ( inflation of a blood pressure cuff on the left thigh to 15 mm Hg above systolic for four 5‐minute intervals ) versus a blinded sham stimulus during induction with a st and ardized anesthesia protocol . Primary outcome was duration of postoperative hospital stay , with serial clinical and laboratory measurements for the first 48 postoperative hours and clinical follow‐up to discharge . There were no significant baseline differences between RIPC ( n=148 ) and sham ( n=151 ) . There were no in‐hospital deaths . No significant difference in length of postoperative hospital stay was noted ( sham 5.4 versus RIPC 5.6 days ; difference + 0.2 ; adjusted P=0.91 ) , with the 95 % confidence interval ( −0.7 to + 0.9 ) excluding a prespecified minimal clinical ly significant differences of 1 or 1.5 days . There were few significant differences in other clinical outcomes or values at time points or trends in physiological markers . Benefit was not observed in specific subgroups when explored through interactions with categories of age , sex , surgery type , Aristotle score , or first versus second half of recruitment . Adverse events were similar ( sham 5 % , RIPC 6 % ; P=0.68 ) . Conclusions RIPC is not associated with important improvements in clinical outcomes and physiological markers after cardiac surgery in children . Clinical Trial Registration URL : clinical trials.gov . Unique identifier : NCT00650507 BACKGROUND Although remote ischemic preconditioning ( RIPC ) has emerged as an attractive strategy to reduce cardiac injury in patients undergoing diverse cardiac surgical procedures , it is unclear whether RIPC has protective effects in patients undergoing aortic valve replacement surgery without coronary artery bypass grafting ( CABG ) . METHODS Hence , 100 adult patients undergoing elective aortic valve replacement for aortic valve stenosis , without combined surgery with CABG , were prospect ively r and omly assigned in a 1:1 ratio to either the RIPC group or the control group . The RIPC group underwent three cycles of 5-min inflation to 200mmHg and 5-min deflation of an automated upper-arm cuff inflator after induction of anesthesia . The control group had a deflated cuff placed on upper arm for 30min . The primary endpoint was 72-h area under curve ( AUC ) for troponin I ( cTnI ) . Secondary endpoints were 72-h AUC for creatine kinase-MB isoenzyme ( CK-MB ) release , incidence of acute kidney injury , extubation time , length of stay in intensive care unit , and simplified acute physiology score ( SAPS II ) . RESULTS There were no significant differences in cTnI AUC [ 195±190 arbitrary units ( a.u . ) in RIPC group vs. 169±117 a.u . in the control group ; p=0.41 ] and CK-MB AUC between groups . None of the other secondary endpoints differed between groups . Acute kidney injury occurred in 12 patients ( 24.5 % ) in the control group and in 13 ( 26.0 % ) in the RIPC group ( p=0.86 ) . CONCLUSIONS RIPC did not exhibit significant cardiac or kidney protective effects in patients undergoing aortic valve replacement surgery without CABG BACKGROUND Contrast medium-induced acute kidney injury ( CI-AKI ) is a cardiovascular complication after myocardial infa rct ion treated with emergency percutaneous coronary intervention . The aim of this r and omized , sham-controlled trial was to evaluate the impact of remote ischemic preconditioning ( RIPC ) on CI-AKI in patients with ST-elevation myocardial infa rct ion who received emergency primary percutaneous coronary intervention . METHODS AND RESULTS Patients with a suspected ST-elevation myocardial infa rct ion were r and omly assigned at a 1:1 ratio to receive percutaneous coronary intervention either with ( n=63 ) or without ( n=62 ) RIPC ( intermittent arm ischemia through three cycles of 5min of inflation and 5min of deflation of a blood pressure cuff ) . A total of 47 RIPC patients and 47 control patients met all study criteria . The primary endpoint was the incidence of CI-AKI , which was defined as an increase in serum creatinine > 0.5mg/dL or > 25 % over the baseline value 48 - 72h after administration of contrast medium . The incidence of CI-AKI was 10 % ( n=5 ) in the RIPC group and 36 % ( n=17 ) in the control group ( p=0.003 ) . The odds ratio of CI-AKI in patients who received RIPC was 0.18 ( 95 % confidence interval : 0.05 - 0.64 ; p=0.008 ) . CONCLUSIONS In patients with ST-elevation myocardial infa rct ion , RIPC before percutaneous coronary intervention reduced the incidence of CI-AKI Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease ( CKD ) . Remote ischemic preconditioning ( RIPC ) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI . We undertook a r and omized controlled trial of RIPC to prevent AKI in 86 patients with CKD ( estimated glomerular filtration rate under 60 ml/min per 1.73 m(2 ) ) undergoing coronary artery bypass graft ( CABG ) surgery . Forty-three patients each were r and omized to receive st and ard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion . The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery . Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C , neutrophil gelatinase-associated lipocalin ( NGAL ) , and interleukin-18 ( IL-18 ) , and urinary biomarkers including NGAL , IL-18 , and kidney injury molecule-1 measured at 6 , 12 , and 24 h after CABG , and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury . Clinical and operative characteristics were similar between the preconditioned and control groups . AKI developed in 12 patients in both groups within 48 h of CABG . There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG . Thus , RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD OBJECTIVES The aim of the present study was to assess the efficacy of remote ischemic post-conditioning ( RIPC ) by repeated intermittent balloon inflations in preventing acute kidney injury ( AKI ) in patients with a non-ST-segment elevation myocardial infa rct ion undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND AKI complicating PCI is associated with increased morbidity and mortality . Remote ischemic preconditioning , using cycles of upper limb ischemia-reperfusion as a conditioning stimulus , has been recently shown to prevent AKI in patients undergoing elective coronary angiography . METHODS Eligible patients were r and omized to receive RIPC by cycles of inflation and deflation of the stent balloon during PCI or a sham procedure ( control patients ) . The primary endpoint was AKI , defined as an increase of ≥ 0.5 mg/dl or ≥ 25 % in serum creatinine within 96 h from PCI . The 30-day rate of death or re-hospitalization for any cause was one of the secondary endpoints . RESULTS A total of 225 patients were included ( median age , 68 years ; 36 % female ) . The AKI rate in the RIPC group was 12.4 % versus 29.5 % in the control group ( p = 0.002 ; odds ratio : 0.34 ; 95 % confidence interval : 0.16 to 0.71 ) . The number needed to treat to avoid 1 case of AKI was 6 ( 95 % confidence interval : 3.6 to 15.2 ) . The 30-day rate of death or re-hospitalization for any cause was 22.3 % in the control group versus 12.4 % in RIPC patients ( p = 0.05 ) . CONCLUSIONS RIPC by serial balloon inflations and deflations during PCI was found to confer protection against AKI in patients with a non-ST-segment elevation myocardial infa rct ion undergoing PCI . The reduction in the rate of AKI translated into a clear trend ( of borderline significance ) toward better 30-day clinical outcome Background Novel treatment strategies are required to reduce the development of acute kidney injury ( AKI ) in patients undergoing cardiac surgery . In this respect , remote ischemic preconditioning ( RIPC ) , a phenomenon in which transient nonlethal ischemia applied to an organ or tissue protects another organ or tissue from subsequent lethal ischemic injury , is a potential renoprotective strategy . Study Design Secondary analysis of 2 r and omized trials . Setting & Participants 78 consenting selected nondiabetic patients in a university teaching hospital undergoing elective coronary artery bypass graft ( CABG ) surgery recruited to 2 previously reported r and omized studies . Intervention RIPC consisted of three 5-minute cycles of right forearm ischemia , induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg , with an intervening 5 minutes of reperfusion , during which time the cuff was deflated . The control consisted of placing an uninflated cuff on the arm for 30 minutes . Outcomes AKI measured using Acute Kidney Injury Network ( AKIN ) criteria , duration of hospital stay , in-hospital and 30-day mortality . Results Numbers of participants with AKI stages 1 , 2 , and 3 were 1 ( 3 % ) , 3 ( 8 % ) , and 0 in the intervention group compared with 10 ( 25 % ) , 0 , and 0 in the control group , respectively ( P = 0.005 ) . The decrease in AKI was independent of the effect of concomitant aortic valve replacement and cross-clamp times , which were distributed unevenly between the 2 groups . Limitations Retrospective analysis of data . More patients in the RIPC group underwent concomitant aortic valve replacement with CABG ; although we have corrected statistically for this imbalance , it remains an important confounding variable . Conclusions RIPC induced using transient forearm ischemia decreased the incidence of AKI in nondiabetic patients undergoing elective CABG surgery in this retrospective analysis . A large prospect i ve clinical trial is required to study this effect and clinical outcomes in patients undergoing cardiac surgery Background — We assessed whether remote ischemic preconditioning ( RIPC ) improves myocardial , renal , and lung protection after on-pump coronary surgery . Methods and Results — This was a single-center , prospect i ve , r and omized ( 1:1 ) , placebo-controlled trial . Patients , investigators , anesthetists , surgeons , and critical care teams were blinded to group allocation . Subjects received RIPC ( or placebo ) stimuli ( ×3 upper limb ( or dummy arm ) , 5-minute cycles of 200 mm Hg cuff inflation/deflation ) before aortic clamping . Anesthesia , perfusion , cardioplegia , and surgical techniques were st and ardized . The primary end point was 48-hour area under the curve ( AUC ) troponin T ( cTnT ) release . Secondary end points were 6-hour and peak cTnT , ECG changes , cardiac index , inotrope and vasoconstrictor use , renal dysfunction , and lung injury . Hospital survival was 99.4 % . Comparing placebo and RIPC , median ( interquartile range ) AUC 48-hour cTnT ( ng/mL−1/48 h−1 ) ; 28 ( 19 , 39 ) versus 30 ( 22 , 38 ) , 6-hour cTnT ( ng/mL−1 ) ; 0.93(0.59 , 1.35 ) versus 1.01(0.72 , 1.43 ) , peak cTnT ( ng/mL−1 ) ; 1.02 ( 0.74 , 1.44 ) versus 1.04 ( 0.78 , 1.51 ) , de novo left bundle-branch block ( 4 % versus 0 % ) and Q waves ( 5.3 % versus 5.5 % ) , serial cardiac indices , intraaortic balloon pump usage ( 8.5 % versus 7.5 % ) , inotrope ( 39 % versus 50 % ) and vasoconstrictor usage ( 66 % versus 64 % ) were not different . Dialysis requirement ( 1.2 % versus 3.8 % ) , peak creatinine ( median [ interquartile range ] , 1.2 mg/dL−1 ( 1.1 , 1.4 ) versus 1.2 ( 1.0 , 1.4 ) ) , and AUC urinary albumin-creatinine ratios 69 ( 40 , 112 ) versus 58 ( 32 , 85 ) were not different . Intubation times ; median ( interquartile range ) , 937 minutes(766 , 1402 ) versus 895(675 , 1180 ) , 6-hour ; 278 ( 210 , 338 ) versus 270 ( 218 , 323 ) and 12-hour pO2:FiO2 ratios 255 ( 195 , 323 ) versus 263 ( 210 , 308 ) were similar . Conclusions — In contrast to prior smaller studies , RIPC did not reduce troponin release , improve hemodynamics , or enhance renal or lung protection . Clinical Trial Registration — URL : http://www.ukcrn.org.uk . Unique identifier : 4659 In a double-blinded r and omized controlled trial , Anja Haase-Fielitz and colleagues find that an infusion of sodium bicarbonate during open heart surgery did not reduce the risk for acute kidney injury , compared with saline control Objectives Remote ischaemic preconditioning ( RIPC ) , using brief cycles of limb ischaemia/reperfusion , is a non-invasive , low-cost intervention that may reduce perioperative myocardial injury ( PMI ) in patients undergoing cardiac surgery . We investigated whether RIPC can also improve short-term clinical outcomes . Methods One hundred and eighty patients undergoing elective coronary artery bypass graft ( CABG ) surgery and /or valve surgery were r and omised to receive either RIPC ( 2–5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation ; N=90 ) or control ( uninflated cuffs placed on the upper arm and thigh ; N=90 ) . The study primary end point was PMI , measured by 72 h area under the curve ( AUC ) serum high-sensitive troponin-T ( hsTnT ) ; secondary end point included short-term clinical outcomes . Results RIPC reduced PMI magnitude by 26 % ( −9.303 difference ( CI −15.618 to −2.987 ) 72 h hsTnT-AUC ; p=0.003 ) compared with control . There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54 % ( 11 % RIPC vs 24 % control ; p=0.031 ) and decreased the incidence of acute kidney injury by 48 % ( 10.0 % RIPC vs 21.0 % control ; p=0.063 ) , and intensive care unit stay by 1 day ( 2.0 days RIPC ( CI 1.0 to 4.0 ) vs 3.0 days control ( CI 2.0 to 4.5 ) ; p=0.043 ) . In a post hoc analysis , we found that control patients administered intravenous glyceryl trinitrate ( GTN ) intraoperatively sustained 39 % less PMI compared with those not receiving GTN , and RIPC did not appear to reduce PMI in patients given GTN . Conclusions RIPC reduced the extent of PMI in patients undergoing CABG and /or valve surgery . RIPC may also have beneficial effects on short-term clinical outcomes , although this will need to be confirmed in future studies . Trial registration number Clinical Trials.gov ID : NCT00397163 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 There is conflicting evidence regarding the effectiveness of remote ischemic preconditioning ( RIPC ) in patients undergoing elective percutaneous coronary intervention ( PCI ) . Therefore , we prospect ively enrolled elderly patients with coronary heart disease ( CHD ) with diabetes mellitus ( DM ) undergoing elective drug-eluting stent ( DES ) implantation . They were r and omized to receive RIPC within 2 hours before PCI ( n = 102 ) or not ( controls , n = 98 ) . Baseline clinical characteristics were similar between the 2 groups . Despite a trend toward decline , the median high-sensitivity cardiac troponin I ( hscTnI ) level ( P = .256 ) and the incidence of myocardial infa rct ion ( MI ) type 4a ( P = .106 ) in the RIPC group 16 hours after PCI procedure was not significantly different from the control group . The RIPC could attenuate the release of a myocardial biomarker but failed to show a significant effect on hscTnI level or MI type 4a incidence after PCI procedure in elderly patients with CHD having DM undergoing elective DES implantation OBJECTIVE To determine the pathological mechanism and prevent heart-renal syndrome after heart valve replacement surgery . METHODS A total of 46 patients were admitted for selective valve replacement , and divide into 3 groups r and omly : a control group ( Con , n=16 ) , a remote ischemic perconditioning ( RIPerC ) group ( n=15 ) and a remote ischemic postconditioning ( RIPostC ) group ( n=15 ) . The serum creatinine ( SCr ) , blood urea nitrogen ( BUN ) , serum heme oxygennase-1 ( HO-1 ) , serum iron and urinary neutrophil gelatinase associated lipocalin ( NGAL ) level in the 3 groups were compared preoperatively and 6 , 12 , 24 , 48 h after aortic cross-release . RESULTS Compared with the preoperative level , the SCr , BUN , urinary NGAL , serum iron ( 6 and 12 h ) and serum HO-1 values were significantly increased after the heart valve replacement surgery in the control patients , RIPreC and RIPostC groups ( P<0.05 ) . Compared with the control group , the serum HO-1 was significantly increased at 6 , 12 , 24 , 48 h after the heart valve replacement surgery in both the RIPerC and RIPostC groups ( P<0.05 ) ; the SCr , BUN , urinary NGAL and serum iron values were decreased at 6 , 12 , 24 , 48 h after the heart valve replacement surgery in both the RIPerC and RIPostC groups ( P>0.05 ) . CONCLUSION Abnormal change in urinary NGAL , serum iron and HO-1 can be used as early warning indicators of acute kidney injury when cardio-renal syndrome occurrs among patients under heart valve replacement surgery . Remote ischemic conditioning plays a preventive role in the occurrence of cardio-renal syndrome and renal protection BACKGROUND To evaluate the impact of remote ischemic preconditioning ( RIPC ) on clinical outcome , biological markers of myocardial injury , and its safety in patients undergoing on-pump coronary artery bypass grafting ( CABG ) . MATERIAL AND METHODS This study was conducted at Ch . Pervaiz Elahi Institute of Cardiology ( CPEIC ) in Multan . The study took place from March 2012 to June 2013 . Patients were r and omly placed into two groups . Group A ( N = 32 ) did not undergo RIPC ; Group B ( N = 35 ) received RIPC after induction of anesthesia . Similar st and ard general anesthesia , cardiopulmonary technique , myocardial protection strategies , and surgical techniques were used in both groups except the protocol for RIPC . Following postoperative outcome , i.e. cardiac defibrillation after removal of aortic cross clamp during the period of rewarming , dem and for intra-aortic balloon pump ( IABP ) , dem and for antiarrhythmic before leaving the operation room , postoperative creatine kinase-myocardial b and ( CK-MB ) level ( at 1h , 12h , 24h , and 48h after surgery ) , postoperative serum creatinine level on first postoperative day , postoperative ejection fraction ( EF ) on third postoperative day , in-hospital mortality , and one-year mortality were noted , prospect ively . Safety of protocol of RIPC was estimated by limb ischemia monitored by pulse oximetry during and after procedure of RIPC and postoperative neurapraxia by nerve examination of right upper limb . RESULTS Post aortic cross clamp release cardiac defibrillation , dem and for IABP , dem and for high inotropes , and use of antiarrhythmic in the operation room were statistically insignificant in the non-RIPC and RIPC group with P values of .54 , .78 , .16 , and .16 , respectively . Mean postoperative CK-MB level ( IU/L ) showed the following results : At 1h ( Group A 20.94 + 1.66 , Group B 20.57 + 1.54 , P = .35 ) , at 12h ( Group A 27.13 + 1.85 , Group B 28.05 + 3.04 , P = .135 ) , at 24h ( Group A 27.63 + 1.7 , Group B 27.85 + 2.2 , P = .63 ) , and at 48h ( Group A 22.95 + 2.76 , Group B 23.27 + 3.6 , P = .69 ) . First postoperative day serum creatinine ( Group A 1.29 + 0.395 , Group B 1.33 + 0.57 , P = .77 ) and postoperative ejection fraction percentage on the third postoperative day ( Group A 50.78 + 8.72 , Group B 50.57 + 8.38 , P = .92 ) showed no statistical difference between two groups . Postoperative low cardiac output state , in-hospital mortality , and one-year mortality also were statistically insignificant between the groups with P values of .93 , .29 , and .33 , respectively . None of the patients in either group showed evidence of limb ischemia and neurapraxia of the right upper limb . CONCLUSION RIPC is a safe technique , but it does not have additional clinical benefit after on-pump CABG surgery in the presence of a st and ard myocardial protective strategy AIMS The aim of this study was to evaluate whether remote ischaemic preconditioning ( RIPC ) combined with remote ischaemic postconditioning ( RIPostC ) improves the clinical outcomes of patients undergoing cardiac surgery . METHODS AND RESULTS From June 2009 to November 2010 , 1280 patients who underwent elective cardiac surgery were r and omized into the RIPC with RIPostC group or the control group in the morning of the surgery . In the RIPC with RIPostC group , four cycles of 5-min ischaemia and 5-min reperfusion were administered twice to the upper limb-before cardiopulmonary bypass ( CPB ) or coronary anastomoses for RIPC and after CPB or coronary anastomoses for RIPostC. The primary endpoint was the composite of major adverse outcomes , including death , myocardial infa rct ion , arrhythmia , stroke , coma , renal failure or dysfunction , respiratory failure , cardiogenic shock , gastrointestinal complication , and multiorgan failure . Remote ischaemic preconditioning with RIPostC did not reduce the composite outcome compared with the control group ( 38.0 vs. 38.1 % , respectively ; P = 0.998 ) and there was no difference in each major adverse outcome . The intensive care unit and hospital stays were not different between the two groups . However , in the off-pump coronary artery bypass surgery subgroup , multivariate logistic regression analysis revealed that RIPC with RIPostC was related to increased composite outcome ( odds ratio : 1.54 ; 95 % confidence interval : 1.02 - 2.30 ; P = 0.038 ) . CONCLUSION Remote ischaemic preconditioning with RIPostC by transient upper limb ischaemia did not improve clinical outcome in patients who underwent cardiac surgery OBJECTIVE The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery . No studies have examined this technique in neonates . The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group . METHODS A preliminary , r and omized , controlled trial was conducted to investigate whether remote ischemic preconditioning in cyanosed neonates undergoing cardiac surgery confers protection against cardiopulmonary bypass . Two groups of neonates undergoing cardiac surgery were recruited for the present study : patients with transposition of the great arteries undergoing the arterial switch procedure and patients with hypoplastic left heart syndrome undergoing the Norwood procedure . The subjects were r and omized to the remote ischemic preconditioning or sham control groups . Remote ischemic preconditioning was induced by four 5-minute cycles of lower limb ischemia and reperfusion using a blood pressure cuff . Troponin I and the biomarkers for renal and cerebral injury were measured pre- and postoperatively . RESULTS A total of 39 neonates were recruited-20 with transposition of the great arteries and 19 with hypoplastic left heart syndrome . Of the 39 neonates , 20 were r and omized to remote ischemic preconditioning and 19 to the sham control group . The baseline demographics appeared similar between the r and omized groups . The cardiopulmonary bypass and crossclamp times were not significantly different between the 2 groups . The troponin I levels were not significantly different at 6 hours after cardiopulmonary bypass nor were the postoperative inotrope requirements . Markers of renal ( neutrophil gelatinase-associated lipocalin ) and cerebral injury ( S100b , neuron-specific enolase ) were not significantly different between the 2 groups . CONCLUSIONS Our data suggest that remote ischemic preconditioning in hypoxic neonates undergoing cardiopulmonary bypass surgery does not provide myocardial , renal , or neuronal protection . Additional studies are needed to examine the relationships among developmental age , hypoxia , and the molecular mechanisms of ischemic preconditioning BACKGROUND Despite the increasing use of pre- and post-hydration protocol s and low osmolar instead of high osmolar iodine containing contrast media , the incidence of contrast induced nephropathy ( CIN ) is still significant . There is evidence that contrast media cause ischemia reperfusion injury of the renal medulla . Remote ischemic preconditioning ( RIPC ) is a non-invasive , safe , and low cost method to reduce ischemia reperfusion injury . The aim of this study is to investigate whether RIPC , as an adjunct to st and ard preventive measures , reduces contrast induced acute kidney injury in patients at risk of CIN . METHODS The RIPCIN study is a multicenter , single blinded , r and omized controlled trial in which 76 patients at risk of CIN received st and ard hydration combined with RIPC or hydration with sham preconditioning . RIPC was applied by four cycles of 5 min ischemia and 5 min reperfusion of the forearm . The primary outcome measure was the change in serum creatinine from baseline to 48 to 72 hours after contrast administration . RESULTS With regard to the primary endpoint , no significant effect of RIPC was found . CIN occurred in four patients ( 2 sham and 2 RIPC ) . A pre-defined subgroup analysis of patients with a Mehran risk score ≥11 , showed a significantly reduced change in serum creatinine from baseline to 48 to 72 hours in patients allocated to the RIPC group ( Δ creatinine -3.3 ± 9.8 μmol/L ) compared with the sham group ( Δ creatinine + 17.8 ± 20.1 μmol/L ) . CONCLUSION RIPC , as an adjunct to st and ard preventive measures , does not improve serum creatinine levels after contrast administration in patients at risk of CIN according to the Dutch guideline . However , the present data indicate that RIPC might have beneficial effects in patients at a high or very high risk of CIN ( Mehran score ≥ 11 ) . The RIPCIN study is registered at : http://www.controlled-trials.com/IS RCT N76496973 The aim of this study was to evaluate the protective effect of remote ischemic postconditioning ( RIPostC ) on graft function and acute kidney injury ( AKI ) after living donor liver transplantation ( LT ) . Recipients undergoing elective living donor LT were r and omly assigned to either the RIPostC group or the control group . Immediately after reperfusion , 4 cycles of ischemia and reperfusion lasting for 5 minutes each were performed on 1 upper limb in the RIPostC group . Graft function was assessed through evaluations of the serum levels of total bilirubin and liver enzymes and the prothrombin time for 28 days after surgery . The incidence of AKI , as defined by the Risk , Injury , Failure , Loss , and End-Stage Kidney Disease classification , was evaluated within 28 days of the operation . In addition , the incidences of graft dysfunction , acute cellular rejection , and major complications ; the 1- , 3- , and 6-month mortality rates ; the length of stay in the intensive care unit ; and the length of hospital stay were also investigated . In all , 78 patients were enrolled in the analysis ( n = 39 in each group ) . No differences in graft function or clinical outcomes were observed between the groups . The incidences of postoperative AKI were 38 % ( n = 15 ) in the RIPostC group and 72 % ( n = 28 ) in the control group ( P = 0.006 ) . Despite no improvements in postoperative graft function , RIPostC decreased the incidence of postoperative AKI after living donor LT in this study . However , no other clinical benefits with respect to the complication rate , length of hospital stay , or short-term mortality rate were observed . Thus , further studies will be needed to evaluate the clinical efficacy of RIPostC in LT fully Remote ischemic conditioning ( RIC ) is at a pivotal point in its evolution , both in terms of its adoption as a therapy and its viability commercially . The most usual way of inducing RIC , with a st and ard blood pressure cuff and a stopwatch , is time-consuming and potentially inaccurate and unsafe . Development of automated devices have facilitated large-scale r and omized trials and will make clinical deployment of the technique more straightforward . Both the medical and commercial future of RIC will depend on the results of upcoming phase 3 pivotal trials Acute kidney injury , a common complication of cardiac surgery with cardiopulmonary bypass , is associated with increased morbidity and mortality . Ischemic preconditioning at a remote site mitigates ischemia-reperfusion injury and may prevent acute kidney injury after cardiac surgery , thus providing clinical benefit . To further study this , we enrolled 120 adult patients undergoing elective cardiac surgery for whom cardiopulmonary bypass was anticipated in a r and omized , single-blind , and controlled pilot trial . Patients were stratified for the type of surgery and equally assigned to a control group or to receive remote ischemic preconditioning by an automated thigh tourniquet consisting of three 5-min intervals of lower extremity ischemia separated by 5-min intervals of reperfusion . The primary end point was acute kidney injury defined as an elevation of serum creatinine of ≥0.3 mg/dl or ≥50 % within 48 h after surgery . Fifty-nine patients in each group were analyzed on an intention-to-treat basis . Acute kidney injury occurred in 12 remote ischemic preconditioned and 28 control patients , reflecting an absolute risk reduction of 0.27 and a significantly reduced relative risk due to preconditioning of 0.43 . Hence , remote ischemic preconditioning prevents acute kidney injury in patients undergoing cardiopulmonary bypass-assisted cardiac surgery INTRODUCTION There are some clinical trials showing that short-term ischemia in one organ can protect different organs against higher intensity and longer ischemic insult . We design ed a study to assess whether remote ischemic preconditioning ( RIPC ) on one organ can decrease the rate of contrast-induced acute kidney injury ( AKI ) in diabetic patients who undergo coronary artery angiography ( CAA ) . MATERIAL S AND METHODS This r and omized control trial included 96 diabetic patients who were c and i date s for CAA . Exclusion criteria were congestive heart failure and complications during CAA . All of the patients received 1000 mL of normal saline before CAA . The RIPC group underwent 3 cycles of 5-minute ischemia in their right arm . Serum creatinine was measured before and 24 hours after CAA . RESULTS Contrast-induced AKI was reported in 5 cases in the control group and 1 case in the RIPC group ( P = .13 , odds ratio , 5.4 ) . The differences in serum creatinine level before and after the procedure was significantly lower in RIPC group than that in the control group ( P = .04 , odds ratio , 0.08 ) . Serum creatinine rise significantly correlated with contrast dose ( P = .02 ) and a history of hypertension ( P = .02 ) in both groups . CONCLUSIONS Ischemic preconditioning had a protective effect on contrast-induced AKI in our study . Since this method is harmless and cost effective , further studies on patients with chronic kidney disease is required to evaluate addition of ischemic preconditioning to our clinical practice for prevention of contrast-induced AKI We aim ed to determine whether remote ischemic preconditioning ( IP ) reduces renal damage following elective open infrarenal abdominal aortic aneurysm ( AAA ) repair . Sequential common iliac clamping was used to induce remote IP in r and omized patients . Urinary retinol binding protein ( RBP ) and albumin-creatinine ratio ( ACR ) were measured following induction and 3 , 24 , and 48 hours postoperatively . In controls ( n = 22 ) , median urinary RBP increased from 112 µg/mL ( interquartile range [ IQR ] 96 - 173 µg/mL ) preoperatively to 5919 µg/mL ( IQR 283 - 17 788 µg/mL ) at 3 hours . Preoperative urinary RBP in preconditioned patients was 96 µg/mL ( IQR 50 to 229 µg/mL ) preoperatively , rising to 1243 µg/mL ( IQR 540 to 15400 µg/mL ) at 3 hours . Although control patients ’ median urinary RBP level was 5 times greater at 3 hours , there were no statistically significant differences in renal outcome indices . This trial could not confirm that remote IP reduces renal injury following elective open aneurysm surgery OBJECTIVE Open abdominal aortic aneurysm ( AAA ) repair is associated with a high risk of renal injury with few known strategies demonstrating a reduction in this risk . Remote ischemic preconditioning ( RIPC ) has been identified as having the potential to minimize organ injury following major vascular surgery . This trial investigated the potential for RIPC to attenuate renal and myocardial injury in patients undergoing elective open AAA repair . DESIGN Prospect i ve , r and omized double-blinded control trial . SETTING Tertiary referral hospital . PARTICIPANTS Sixty-two patients undergoing elective open AAA repair . INTERVENTION RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control ( sham cuff ) . MEASUREMENTS Primary outcome was the occurrence of renal injury , as measured by an increase in creatinine during the first 4 postoperative days . Secondary outcomes included urinary neutrophil-gelatinase-associated lipocalin ( NGAL ) , occurrence of acute kidney injury ( AKI ) , occurrence of myocardial injury as defined by troponin rise , incidence of postoperative complications , and mortality . There was no difference in postoperative creatinine levels , NGAL levels , or the occurrence of AKI between the groups at any postoperative time point . Similarly , there was no difference in the occurrence of myocardial injury or mortality . Of note , 6 patients in the RIPC group , while no patient in the control group , experienced postoperative complications that required repeat surgical laparotomy , potentially masking any renoprotective effects of RIPC . CONCLUSION RIPC did not reduce the risk of postoperative renal failure or myocardial injury in patients undergoing open AAA repair . The authors ' results do not support the introduction of this technique to routine clinical practice BACKGROUND Myocardial injury is associated with an adverse outcome after off-pump coronary artery bypass graft surgery ( OPCAB ) . The authors conducted a r and omized controlled trial to evaluate whether remote ischemic preconditioning ( RIPC ) with remote ischemic postconditioning ( RIPostC ) reduces myocardial injury in patients undergoing OPCAB . METHODS AND RESULTS Seventy patients scheduled for OPCAB were r and omly assigned to an RIPC+RIPostC group ( n=35 ) or a control group ( n=35 ) . In the RIPC+RIPostC group , 4 cycles of 5-min ischemia and 5-min reperfusion were done on a lower limb before anastomoses ( RIPC ) and after anastomoses ( RIPostC ) . RIPC+RIPostC significantly reduced postoperative serum troponin I levels ( P=0.001 ) . The area under the curve for postoperative troponin I was 48.7 % lower in the RIPC+RIPostC group ( median [ interquartile range ] , 21.3 h·ng⁻¹·ml⁻¹ , 16.5 - 53.1 h·ng⁻¹·ml⁻¹ vs. 41.5 h·ng⁻¹·ml⁻¹ , 24.6 - 90.2 h·ng⁻¹·ml⁻¹ , P=0.020 ) . There was no significant difference in creatinine levels and PaO₂/F(i)O₂ ratios between the 2 groups . CONCLUSIONS RIPC+RIPostC by lower limb ischemia decreased postoperative myocardial enzyme elevation by almost half postoperatively in patients undergoing OPCAB The efficacy of remote ischemic preconditioning ( RIPC ) in high-risk cardiac surgery is uncertain . In this study , 96 adults undergoing high-risk cardiac surgery were r and omised to RIPC ( 3 cycles of 5 min of upper-limb ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion ) or control . Main endpoints were plasma high-sensitivity troponin T ( hsTNT ) levels at 6 and 12 h , worst post-operative acute kidney injury ( AKI ) based on RIFLE criteria , and noradrenaline duration . hsTNT levels were log-normally distributed and higher with RIPC than control at 6-h post cross-clamp removal [ 810 ng/ml ( IQR 527–1,724 ) vs. 634 ng/ml ( 429–1,012 ) ; ratio of means 1.41 ( 99.17 % CI 0.92–2.17 ) ; P=0.04 ] and 12 h [ 742 ng/ml ( IQR 427–1,700 ) vs. 514 ng/ml ( IQR 356–833 ) ; ratio of means 1.56 ( 99.17 % CI 0.97–2.53 ) ; P=0.01 ] . After adjustment for baseline confounders , the ratio of means of hsTNT at 6 h was 1.23 ( 99.17 % CI 0.88–1.72 ; P=0.10 ) and at 12 h was 1.30 ( 99.17 % CI 0.92–1.84 ; P=0.05 ) . In the RIPC group , 35/48 ( 72.9 % ) had no AKI , 5/48 ( 10.4 % ) had AKI risk , and 8/48 ( 16.7 % ) had either renal injury or failure compared to the control group where 34/48 ( 70.8 % ) had no AKI , 7/48 ( 14.6 % ) had AKI risk , and 7/48 ( 14.6 % ) had renal injury or failure ( Chi-squared 0.41 ; two degrees of freedom ; P = 0.82 ) . RIPC increased post-operative duration of noradrenaline support [ 21 h ( IQR 7–45 ) vs. 9 h ( IQR 3–19 ) ; ratio of means 1.70 ( 99.17 % CI 0.86–3.34 ) ; P=0.04 ] . RIPC does not reduce hsTNT , AKI , or ICU-support requirements in high-risk cardiac surgery BACKGROUND Myocardial necrosis occurs frequently in elective percutaneous coronary intervention ( PCI ) and is associated with subsequent major adverse cardiovascular events ( MACEs ) . This study assessed the protective effect of remote ischemic preconditioning ( RIPC ) in patients undergoing successful drug-eluting stent implantation with normal baseline troponin values . METHODS We analyzed 205 participants with normal baseline troponin values undergoing successful coronary stent implantation . Subjects were r and omized to 2 groups : The RIPC group ( n = 101 ) , whose members received RIPC ( created by three 5-minute inflations of a pneumatic medical tourniquet cuff to 200 mm Hg around the upper arm , interspersed with 5-minute intervals of reperfusion ) < 2 hours before the PCI procedure , and the control group ( n = 104 ) . RESULTS The primary outcomes were high sensitive cardiac troponin I ( hscTnI ) levels and incidence of myocardial infa rct ion ( MI 4a , defined as hscTnI > 0.20 ng/mL ) at 16 hours after the PCI procedure . The median hscTnI at 16 hours after PCI was lower in the RIPC group compared with the unpreconditioned , control group ( 0.11 vs 0.21 ng/mL ; P < 0.01 ) . The incidence of MI 4a was lower in the RIPC group compared with the control group ( 39 % vs 54 % , P < 0.05 ) . Index of renal function showed no difference between the 2 groups at 16 hours after PCI ( P > 0.05 ) . CONCLUSION RIPC reduced post-PCI TnI release and incidence of MI 4a in patients undergoing elective coronary stent implantation OBJECTIVE The objective of this study was to evaluate whether remote ischemic preconditioning can protect kidney function in children undergoing operation for complex congenital heart disease . METHODS Children ( n = 113 ) aged 0 to 15 years admitted for complex congenital heart disease were r and omly allocated according to age to remote ischemic preconditioning and control groups . After exclusion of 8 patients , we conducted the analysis on 105 patients ( remote ischemic preconditioning group , n = 54 ; control group , n = 51 ) . Before surgery , remote ischemic preconditioning was performed as 4 cycles of 5 minutes of ischemia by inflating a cuff around a leg to 40 mm Hg above the systolic pressure . End points were development of acute kidney injury , initiation of dialysis , plasma creatinine , estimated glomerular filtration rate , plasma cystatin C , plasma and urinary neutrophil gelatinase-associated lipocalin , and urinary output . Secondary end points included postoperative blood pressure , inotropic score , and mortality , as well as morbidity reflected by reoperation and stays in the intensive care unit and hospital . RESULTS Overall , 57 of the children ( 54 % ) had acute kidney injury develop , with 27 ( 50 % ) in the remote ischemic preconditioning group and 30 ( 59 % ) in the control group ( P > .2 ) . Remote ischemic preconditioning was not associated with improvement in either any of the renal biomarkers or any of the secondary end points . CONCLUSIONS We found no evidence that remote ischemic preconditioning provided protection of kidney function in children undergoing operation for complex congenital heart disease Background We evaluated whether remote ischemic postconditioning ( RiPoC ) could improve initial graft function in living donor kidney transplantation ( KT ) . Methods Patients undergoing living donor KT were r and omly assigned to either RiPoC ( n=30 ) or control group ( n=30 ) . Immediately after reperfusion in the RiPoC group , three cycles of ischemia and reperfusion , lasting 5 min each , were performed on one upper limb . Renal function was assessed before surgery , 2 hr after surgery , and at 12-hr intervals for 96 hr postsurgery by measuring serum creatinine ( sCr ) and the estimated glomerular filtration rate ( eGFR ) . Urine output and urine creatinine were assessed until postoperative day 7 , and hospital stay and complication rates were compared . Results The time for sCr to reach 50 % of its preoperative level was significantly shorter in the RiPoC group than in the control group [ 12 ( 12–24 ) hr for RiPoC vs. 24 ( 21–36 ) hr for the control , P=0.005 ] . The number of patients whose sCr was reduced by 50 % within 24 hr was significantly greater in the RiPoC group than in the control group [ n=26 ( 87 % ) in RiPoC vs. n=18 ( 60 % ) in control , P=0.020 ] . However , there were no differences in sCr and eGFR thereafter , the incidence of graft dysfunction or complication rates between groups . Conclusion In this study , RiPoC appeared to hasten the recovery of graft function within 24 hr but did not affect the graft function thereafter . However , considering most recipients had immediate graft function , further studies with deceased donors or studies powered to detect a smaller difference are needed Background —Remote ischemic preconditioning may result in reduction in infa rct size during percutaneous coronary intervention ( PCI ) . It is unclear whether remote ischemic postconditioning ( RIPost ) will reduce the incidence of myocardial injury after PCI , and whether ischemic conditioning of a larger remote organ ( thigh versus arm ) would provide further myocardial protection . Methods and Results —We r and omized 360 patients presenting with stable or unstable angina ( 28 % of patients ) and negative Troponin T at baseline to 3 groups : 2 groups received RIPost ( induced by ischemia to upper or lower limb ) , and a third was the control group . RIPost was applied during PCI immediately after stent deployment , by three 5-minute cycles of blood pressure cuff inflation to > 200 mm Hg in the arm or thigh ( 20 mm Hg in the control ) with 5-minute breaks between each cycle . The primary end-point was the proportion of patients with Troponin T levels > 3 × ULN postprocedure ( at 6 or 18–24 hours ) , where ULN st and s for upper limit of normal . A total of 120 patients were r and omized to each group . There were no differences in baseline characteristics between the 3 groups . The primary outcome occurred in 30 % , 35 % , and 35 % of the arm , thigh , and control groups , respectively ( P=0.64 ) . There were no differences in creatine kinase or high sensitivity C-reactive protein levels after PCI or in the incidence of acute kidney injury between the groups . Conclusions —RIPost during PCI did not reduce the incidence of periprocedural myocardial injury . Similar effect was obtained when remote ischemia was induced to the upper or lower limb . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00970827 OBJECTIVE Acute kidney injury after cardiac surgery with cardiopulmonary bypass is closely related to systemic inflammatory reactions and oxidative stresses . Remote ischemic preconditioning is a systemic protective strategy whereby brief limb ischemia confers systemic protection against prolonged ischemia and inflammatory reactions in distant organs . This study investigated whether remote ischemic preconditioning provides systemic protective effect on kidneys that are not directly exposed to ischemia-reperfusion injury during complex valvular heart surgery . METHODS Seventy-six adult patients undergoing complex valvular heart surgery were r and omly assigned to either remote ischemic preconditioning group ( n = 38 ) or control group ( n = 38 ) . Remote ischemic preconditioning consisted of 3 10-minute cycles of lower limb ischemia and reperfusion with an automated cuff inflator . Primary end points were comparisons of biomarkers of renal injury including serum creatinine , cystatin C and neutrophil gelatinase-associated lipocalin , and incidence of acute kidney injury . Secondary end points were comparisons of myocardial enzyme release and pulmonary parameters . RESULTS There were no significant differences in serum levels of biomarkers of renal injury between groups throughout the study period . The incidence of acute kidney injury did not differ between groups . Creatine kinase isoenzyme MB at 24 hours after surgery was lower , and intensive care unit stay was shorter in the remote ischemic preconditioning group than in the control group . CONCLUSIONS In patients undergoing complex valvular heart surgery , remote ischemic preconditioning did not reduce degree of renal injury or incidence of acute kidney injury whereas it did reduce myocardial injury and intensive care unit stay Background — Contrast medium – induced acute kidney injury is associated with substantial morbidity and mortality . The underlying mechanism has been attributed in part to ischemic kidney injury . The aim of this r and omized , double-blind , sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast medium – induced acute kidney injury . Methods and Results — Patients with impaired renal function ( serum creatinine > 1.4 mg/dL or estimated glomerular filtration rate < 60 mL · min−1 · 1.73 m−2 ) undergoing elective coronary angiography were r and omized in a 1:1 ratio to st and ard care with ( n=50 ) or without ischemic preconditioning ( n=50 ; intermittent arm ischemia through 4 cycles of 5-minute inflation and 5-minute deflation of a blood pressure cuff ) . Overall , both study groups were at high risk of developing contrast medium – induced acute kidney injury according to the Mehran risk score . The primary end point was the incidence of contrast medium – induced kidney injury , defined as an increase in serum creatinine ≥25 % or ≥0.5 mg/dL above baseline at 48 hours after contrast medium exposure . Contrast medium – induced acute kidney injury occurred in 26 patients ( 26 % ) , 20 ( 40 % ) in the control group and 6 ( 12 % ) in the remote ischemic preconditioning group ( odds ratio , 0.21 ; 95 % confidence interval , 0.07–0.57 ; P=0.002 ) . No major adverse events were related to remote ischemic preconditioning . Conclusions — Remote ischemic preconditioning before contrast medium use prevents contrast medium – induced acute kidney injury in high-risk patients . Our findings merit a larger trial to establish the effect of remote ischemic preconditioning on clinical outcomes . Clinical Trial Registration — URL : http://www.germanctr.de . Unique identifier : U1111 - 1118 - 8098 Background Despite the increasing use of pre- and posthydration protocol s and low-osmolar instead of high-osmolar iodine-containing contrast media , the incidence of contrast-induced nephropathy ( CIN ) is still significant . There is evidence that contrast media cause ischemia-reperfusion injury of the medulla . Remote ischemic preconditioning ( RIPC ) is a non-invasive , safe , and low-cost method to reduce ischemia-reperfusion injury . Methods The RIPCIN study is a multicenter , single-blinded , r and omized controlled trial in which 76 patients at risk of CIN will receive st and ard hydration combined with RIPC or hydration with sham preconditioning . RIPC will be applied by four cycles of 5 min ischemia and 5 min reperfusion of the forearm by inflating a blood pressure cuff at 50 mmHg above the actual systolic pressure . The primary outcome measure will be the change in serum creatinine from baseline to 48 to 72 h after contrast administration . Discussion A recent pilot study reported that RIPC reduced the incidence of CIN after coronary angioplasty . The unusual high incidence of CIN in this study is of concern and limits its generalizability . Therefore , we propose a r and omized controlled trial to study whether RIPC reduces contrast-induced kidney injury in patients at risk for CIN according to the Dutch guidelines .Trial registration Current Controlled Trials IS RCT |
13,901 | 19,218,473 | In an exploratory meta- analysis , short-term mortality was higher after CABG compared to PCI .
A substantial number of patients died over a subsequent 1 to 5 yr , with no difference in mortality after CABG compared to PCI . | BACKGROUND AND OBJECTIVES Patients receiving dialysis have a high burden of cardiovascular disease .
Some receive coronary artery revascularization but the optimal method is controversial . | 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 Purpose : To compare percutaneous coronary intervention ( PCI ) using stent implantation versus coronary artery bypass graft ( CABG ) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery ( LAD ) . Methods : 230 patients with multiple vessel disease and severe stenosis of the proximal LAD ( 113 with PCI , 117 with CABG ) . They were a cohort of patients from the r and omised ERACI ( Argentine r and omized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease ) II study . Results : Both groups had similar baseline characteristics . There were no significant differences in 30 day major adverse cardiac events ( death , myocardial infa rct ion , stroke , and repeat procedures ) between the strategies ( PCI 2.7 % v CABG 7.6 % , p = 0.18 ) . There were no significant differences in survival ( PCI 96.4 % v CABG 95 % , p = 0.98 ) and survival with freedom from myocardial infa rct ion ( PCI 92 % v CABG 89 % , p = 0.94 ) at 41.5 ( 6 ) months ’ follow up . However , freedom from new revascularisation procedures ( CABG 96.6 % v PCI 73 % , p = 0.0002 ) and frequency of angina ( CABG 9.4 % v PCI 22 % , p = 0.025 ) were superior in the CABG group . Conclusion : Patients with multivessel disease and significant disease of the proximal LAD r and omly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infa rct ion at long term follow up . Repeat revascularisation procedures were higher in the PCI group Background —R and omized trials comparing coronary artery bypass graft surgery ( CABG ) with percutaneous coronary interventions ( PCIs ) for patients with multivessel coronary disease ( MVD ) report similar long-term survival for CABG and PCI . These studies used a highly selected population of patients and providers , and their results may not be generalizable to actual care . Our goal in this study was to compare long-term survival of MVD patients treated with CABG vs PCI in contemporary practice . Methods and Results —From our northern New Engl and registries of consecutive coronary revascularizations , we identified 10 198 CABG and 4295 PCI patients with MVD who may have been eligible for either procedure between 1994 and 2001 . Vital status was obtained by linkage to the National Death Index . Proportional-hazards regression was used to calculate hazard ratios ( HRs ) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics . CABG patients were older ; had more comorbidities , more 3-vessel disease , and lower ejection fractions ; and were more completely revascularized . Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI ( HR , 0.60 ; P<0.01 ) but not for patients with 2-vessel disease ( HR , 0.98 ; P=0.77 ) . The survival advantage of CABG for 3-vessel disease patients was present in all patient population s , including women , diabetics , and the elderly and in the era of high stent utilization . Conclusions —In contemporary practice , survival for patients with 3-vessel coronary disease is better after CABG than PCI , an observation that patients and physicians should carefully consider when deciding on a revascularization strategy Background —The optimal method of coronary revascularization in dialysis patients is controversial . The purpose of this study was to compare the long-term survival of dialysis patients in the United States after PTCA , coronary stenting , or CABG . Methods and Results —Dialysis patients hospitalized from 1995 to 1998 for first coronary revascularization procedures after renal replacement therapy initiation were identified from the US Renal Data System data base . All-cause and cardiac survival was estimated by the life-table method and compared by the log-rank test . The impact of independent predictors on survival was examined in a Cox regression model . The in-hospital mortality was 8.6 % for 6668 CABG patients , 6.4 % for 4836 PTCA patients , and 4.1 % for 4280 stent patients . The 2-year all-cause survival ( mean±SEM ) was 56.4±1.4 % for CABG patients , 48.2±1.5 % for PTCA patients , and 48.4±2.0 % for stent patients ( P < 0.0001 ) . After comorbidity adjustment , the relative risk ( RR ) for CABG ( versus PTCA ) patients was 0.80 ( 95 % CI 0.76 to 0.84 , P < 0.0001 ) for all-cause death and 0.72 ( 95 % CI 0.67 to 0.77 , P < 0.0001 ) for cardiac death . For stent ( versus PTCA ) patients , the RR was 0.94 ( 95 % CI 0.88 to 0.99 , P = 0.03 ) for all-cause death and 0.92 ( 95 % CI 0.85 to 0.99 , P = 0.04 ) for cardiac death . In diabetic ( versus PTCA ) patients , the RR for CABG surgery was 0.81 ( 95 % CI 0.75 to 0.88 , P < 0.0001 ) for all-cause death and 0.71 ( 95 % CI 0.64 to 0.78 , P < 0.0001 ) for cardiac death , and the RR for the stent procedure was 0.99 ( 95 % CI 0.91 to 1.08 , P = NS ) for all-cause death and 0.99 ( 95 % CI 0.89 to 1.11 , P = NS ) for cardiac death . Conclusions —In this retrospective study , dialysis patients in the United States had better long-term survival after CABG surgery than after percutaneous coronary intervention . Stent outcomes were relatively worse in diabetic patients . Our data support the need for large clinical registries and prospect i ve trials of surgical and percutaneous coronary revascularization procedures in dialysis patients The objective of this study was to compare the outcomes of angina , myocardial infa rct ion ( MI ) , cardiac death , and all-cause death following percutaneous transluminal coronary angioplasty ( PTCA ) or coronary artery bypass grafting ( CABG ) . The study design was based on retrospective , nonr and omized analysis and was set in referral teaching hospitals and community hospitals . Eighty-four chronic dialysis patients with symptomatic coronary artery disease without prior revascularization were included in the study . Twenty-four patients underwent PTCA of one or more vessels , and 60 patients underwent CABG . Recurrence of angina , MI , cardiac death , and all-cause death following revascularization as well as the number of inpatient days preprocedure and postprocedure were recorded . The two patient groups were comparable in terms of age , sex , history of MI , left ventricular mass and function , and angina severity . Diabetes mellitus was more prevalent in the PTCA group . The CABG group had more severe coronary artery disease . The 2-year survival rate of the CABG patients ( 66 % ; 95 % confidence interval = 53.79 ) did not differ from that of the PTCA patients ( 51 % ; 95 % confidence interval = 27.65 ) . Thirteen PTCA patients were restudied 106 + /- 108 days after recurrence of angina ; nine ( 69 % ) of these patients were found to have angiographic restenosis . The postprocedure risk of angina and the combined endpoints of angina , MI , and cardiovascular death were significantly greater following PTCA than CABG . Percutaneous transluminal coronary angioplasty was the only consistent predictor of outcomes ; the adjusted relative risks ( compared with CABG ) of postprocedure angina and combined endpoints were 16.4 and 10.2 , respectively , and were several-fold higher than the unadjusted risks . We conclude that in chronic dialysis patients with symptomatic coronary disease , patients undergoing PTCA have a higher risk of subsequent angina and combined angina , MI , and cardiovascular death than those undergoing CABG . The optimal approach to coronary revascularization in this patient population remains to be determined Previous retrospective studies showed high periprocedure mortality rate and poor outcome after percutaneous transluminal coronary angioplasty ( PTCA ) or coronary artery bypass grafting ( CABG ) among renal dialysis patients . The purpose of this study was to compare mortality and clinical event rates in renal dialysis patients after PTCA or CABG . We identified 252 patients from the Emory Cardiovascular Data base who were on dialysis and who received PTCA ( 122 patients ) or CABG ( 130 patients ) at Emory University Hospital and Crawford W. Long Hospital between March 1987 and December 1997 . Baseline and angiographic characteristics , in-hospital , and 1-year outcome were compared between the 2 groups . Left main disease and 3-vessel coronary artery disease were significantly more common in the CABG group . There was a higher periprocedure and in-hospital mortality in the CABG group ( 6.9 % vs 1.6 % , p = 0.04 ) . Patients in the PTCA group underwent repeat revascularization 11 times more frequently within 1 year ( 22 % vs 2 % ) . At 1 year , mortality was 23 % in the PTCA group and 27 % in the CABG group , with no statistical difference between the 2 groups . This nonr and omized comparison reveals that PTCA and CABG can be performed in selected renal dialysis patients with an acceptable in-hospital major complication rate ; however , 1-year mortality remains high in dialysis patients after coronary revascularization . Therefore , attempts at improving outcome in dialysis patients should focus on the prevention and treatment of coronary artery disease before they require coronary revascularization Cardiovascular disease ( CVD ) is the most common cause of death in patients with end-stage renal disease ( ESRD ) . The optimal management strategy in this population is unknown . We studied 640 patients with ESRD and acute myocardial infa rct ion during 1994 to 1995 as part of the Health Care Financing Administration 's Cooperative Cardiovascular Project . The majority of patients were treated with medical therapy alone , 46 patients ( 7 % ) were treated with percutaneous transluminal coronary angioplasty ( PTCA ) , and 29 patients ( 5 % ) underwent coronary artery bypass grafting ( CABG ) . Patient characteristics and comorbid conditions were similar among the three groups . The overall 1-year mortality rate was 53 % . Advanced age , low or high body mass index , history of peripheral vascular disease or stroke , the inability to walk independently , and several indicators of cardiac dysfunction were associated with an increased relative risk ( RR ) for death . Survival curves differed significantly by treatment modality , with 1-year survival rates of 45 % , 54 % , and 69 % in the medical therapy alone , PTCA , and CABG groups , respectively ( P = 0.03 ) . After adjustment for confounding variables , the RR for death was less ( but not significantly so ) in the CABG group ( RR , 0.6 ; 95 % confidence interval , 0.3 to 1.1 ) . There are no r and omized clinical trial data to guide therapy of CVD in patients with ESRD . On the basis of these and other available data , CABG may be the optimal therapy for CVD in ESRD . In light of the exceptionally poor outcomes observed for patients treated with medical therapy alone , it may be premature to dismiss PTCA as a therapeutic option in this population Background —Although dialysis patients are undergoing CABG with increasing frequency , large studies specifically comparing patient characteristics and procedure-related risks in this population have not been performed . Methods and Results —We conducted a regional prospect i ve cohort study of 15 500 consecutive patients undergoing CABG in northern New Engl and from 1992 to 1997 . We used multiple logistic regression analysis to examine associations between preoperative dialysis-dependent renal failure and postoperative events and to adjust for potentially confounding variables . The 279 dialysis-dependent renal failure patients ( 1.8 % ) were 4.4 times more likely to experience in-hospital mortality than were other CABG patients ( 12.2 % versus 3.0 % , respectively;P < 0.001 ) . Dialysis-dependent renal failure patients were older and had more comorbidities and more severe cardiac disease than did other CABG patients . After adjusting for these factors in multivariate analysis , however , dialysis-dependent renal failure patients remained 3.1 times more likely to die after CABG ( adjusted odds ratio [ OR ] 3.1 , 95 % CI 2.1 to 4.7;P < 0.001 ) . Dialysis-dependent renal failure patients compared with other CABG patients also had a substantially increased risk of postoperative mediastinitis ( 3.6 % versus 1.2 % , respectively ; adjusted OR 2.4 , 95 % CI 1.2 to 4.7;P = 0.011 ) and postoperative stroke ( 4.3 % versus 1.7 % , respectively ; adjusted OR 2.1 , 95 % CI 1.1 to 3.9;P = 0.016 ) , even after controlling for potentially confounding variables . Risks of reexploration for bleeding were similar for patients with and without dialysis-dependent renal failure . Conclusions —Preoperative dialysis-dependent renal failure is a strong independent risk factor for in-hospital mortality and mediastinitis after CABG BACKGROUND The optimal method of coronary revascularization in dialysis patients is controversial , as previous small retrospective studies have reported increased cardiac events after percutaneous transluminal coronary angioplasty ( PTCA ) compared with coronary artery bypass ( CAB ) surgery . The purpose of this study was to compare the long-term survival of chronic dialysis patients in the United States following PTCA or CAB surgery . METHODS Dialysis patients hospitalized from 1978 to 1995 for first coronary revascularization procedure after initiation of renal replacement therapy were retrospectively identified from the United States Renal Data System data base . Survival for the endpoints of all-cause death , cardiac death , myocardial infa rct ion , and cardiac death or myocardial infa rct ion was estimated by the life-table method and was compared by the log-rank test . The impact of independent predictors on survival was examined in a Cox regression model with comorbidity adjustment . RESULTS The in-hospital mortality was 5.4 % for 6887 PTCA patients and 12.5 % for 7419 CAB patients . The two-year event-free survival ( + /-SE ) of PTCA patients was 52.9 + /- 0.7 % for all-cause death , 72.5 + /- 0.7 % for cardiac death , and 62.0 + /- 0.7 % for cardiac death or myocardial infa rct ion . In CAB patients , the comparable survivals were 56.9 + /- 0.6 , 75.8 + /- 0.6 , and 71.3 + /- 0 . 6 % , respectively ( P < 0.02 for PTCA vs. CAB surgery for all endpoints ) . After comorbidity adjustment , the relative risk of CAB surgery ( vs. PTCA ) performed 1990 to 1995 for all-cause death was 0 . 91 ( 95 % CI , 0.86 to 0.97 ) ; cardiac death , 0.85 ( 95 % CI , 0.78 to 0 . 92 ) ; myocardial infa rct ion , 0.37 ( 95 % CI , 0.32 to 0.43 ) ; and cardiac death or myocardial infa rct ion 0.69 ( 95 % CI , 0.64 to 0.74 ) . CONCLUSIONS In this retrospective study , dialysis patients in the United States had better survival after CAB surgery compared with PTCA , but our study does not exclude the possibility of more unfavorable coronary anatomy in the PTCA patients at baseline . Our data support the need for prospect i ve trials of newer percutaneous coronary revascularization procedures in dialysis patients OBJECTIVES The long-term ( five-year ) comparative results of treatment of multivessel coronary artery disease with stenting or coronary artery bypass grafting ( CABG ) is at present unknown . BACKGROUND The Arterial Revascularization Therapies Study ( ARTS ) was design ed to compare CABG and stenting in patients with multivessel disease . METHODS A total of 1,205 patients with the potential for equivalent revascularization were r and omly assigned to CABG ( n = 605 ) or stent implantation ( n = 600 ) . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events ( MACCE ) at one year ; MACCE at five-year follow-up constituted the final secondary end point . RESULTS At five years , there were 48 and 46 deaths in the stent and CABG groups , respectively ( 8.0 % vs. 7.6 % ; p = 0.83 ; relative risk [ RR ] , 1.05 ; 95 % confidence interval [ CI ] , 0.71 to 1.55 ) . Among 208 diabetic patients , mortality was 13.4 % in the stent group and 8.3 % in the CABG group ( p = 0.27 ; RR , 1.61 ; 95 % CI , 0.71 to 3.63 ) . Overall freedom from death , stroke , or myocardial infa rct ion was not significantly different between groups ( 18.2 % in the stent group vs. 14.9 % in the surgical group ; p = 0.14 ; RR , 1.22 ; 95 % CI , 0.95 to 1.58 ) . The incidence of repeat revascularization was significantly higher in the stent group ( 30.3 % ) than in the CABG group ( 8.8 % ; p < 0.001 ; RR , 3.46 ; 95 % CI , 2.61 to 4.60 ) . The composite event-free survival rate was 58.3 % in the stent group and 78.2 % in the CABG group ( p < 0.0001 ; RR , 1.91 ; 95 % CI , 1.60 to 2.28 ) . CONCLUSIONS At five years there was no difference in mortality between stenting and surgery for multivessel disease . Furthermore , the incidence of stroke or myocardial infa rct ion was not significantly different between the two groups . However , overall MACCE was higher in the stent group , driven by the increased need for repeat revascularization When several independent groups have conducted studies to estimate a procedure 's success rate , it is often of interest to combine the results of these studies in the hopes of obtaining a better estimate for the true unknown success rate of the procedure . In this paper we present two hierarchical methods for estimating the overall rate of success . Both methods take into account the within- study and between- study variation and assume in the first stage that the number of successes within each study follows a binomial distribution given each study 's own success rate . They differ , however , in their second stage assumptions . The first method assumes in the second stage that the rates of success from individual studies form a r and om sample having a constant expected value and variance . Generalized estimating equations ( GEE ) are then used to estimate the overall rate of success and its variance . The second method assumes in the second stage that the success rates from different studies follow a beta distribution . Both methods use the maximum likelihood approach to derive an estimate for the overall success rate and to construct the corresponding confidence intervals . We also present a two-stage bootstrap approach to estimating a confidence interval for the success rate when the number of studies is small . We then perform a simulation study to compare the two methods . Finally , we illustrate these two methods and obtain bootstrap confidence intervals in a medical example analysing the effectiveness of hyperdynamic therapy for cerebral vasospasm |
13,902 | 29,974,489 | Diazoxide [ -15 ( -20.6 , -9.4 ) ] , nicardipine [ -11.8 ( -22.3 , -1.2 ) ] , nifedipine/celastrol [ -19.3 ( -27.4 , -11.1 ) ] , nifedipine/vitamin D [ -17.1 ( -25.7 , -9.7 ) ] , nifedipine/resveratrol [ -13.9 ( -22.6 , -5.2 ) ] and glyceryl trinitrate [ -33.8 ( -36.7 , -31 ) ] were observed to achieve the target BP ( in minutes ) more rapidly than hydralazine .
Nifedipine required fewer doses than hydralazine for achieving the target BP .
Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine .
Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol .
The present evidence suggests similar efficacy between nifedipine , hydralazine and labetalol in the treatment of severe hypertension in pregnancy .
Subtle differences may exist in their safety profile . | AIMS Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy .
The present study is a network meta- analysis comparing the efficacy and safety of these drugs . | The effect of intravenous infusion of labetalol and of dihydralazine in increasing doses was compared in 12 women with severe hypertension in pregnancy . In 5 our of 6 women labetalol produced a smooth , progressive fall in blood pressure to normal levels with minimal side effects . In 2 our of 6 women on dihydralazine the blood pressure control was satisfactory but in the remaining 4 patients treatment had to by discontinued because of unpredictable , sudden falls in blood pressure . One of the 6 infants of mothers treated with labetalol manifested signs of adrenergic blockade . Continuous infusion of labetalol appears to offer significant advantages in the management of severe hypertension in pregnancy and merits further trial Summary : The results of a prospect i ve trial to evaluate the use of diazoxide and labetalol given intravenously in the management of severe hypertensive disease in pregnancy are presented OBJECTIVE Determine the definitive position of ketanserin and dihydralazine for treatment of severe hypertension in pregnancy . STUDY DESIGN A single centre double blind r and omized controlled trial was performed at the obstetrical tertiary high care unit of the University Medical Centre in Rotterdam , the Netherl and s. Women with severe hypertension in pregnancy ( diastolic blood pressure (DBP)≥110mmHg ) , and significant proteinuria ( ≥300mg/24h ) , and gestational age≤32 weeks were eligible for the study . All patients ( n=30 ) received two infusions ( double dummy technique ) : one contained the active ingredient ( ketanserin or dihydralazine ) , the other was used for placebo . Nicardipine was used as rescue medication . The main outcome measures were persistent severe hypertension ( DBP>100mmHg>120min ) despite maximum dosage of study medication and prolongation of pregnancy . RESULTS Dihydralazine was significantly more effective in lowering blood pressure than ketanserin . No significant difference in prolongation of pregnancy was seen between the two groups . After 30 inclusion s , the study was stopped because of the high rate of persistent hypertension using ketanserin and the high rate of maternal side effects using dihydralazine and the apparent succesful use of the rescue drug nicardipine . CONCLUSIONS Our results do not support the use of either dihydralazine or ketanserin for the treatment of severe hypertension in pregnancy . Future research is needed to compare nicardipine with other antihypertensive drugs currently in use for treatment of severe hypertension in pregnancy OBJECTIVES The purpose s of this study were to compare the efficacy of sublingual nifedipine with intravenous hydrallazine in the control of acute hypertension of pregnancy and to make a preliminary assessment whether sublingual nifedipine could be recommended for use by midwives faced with severe hypertension in pregnancy in a rural setting . METHODS Subjects were 200 consecutive patients admitted to Kuala Tereng-ganu General Hospital , Malaysia with severe hypertension in pregnancy between August 1989 and June 1990 . Admission criteria were an ongoing viable pregnancy more than 28 weeks and diastolic blood pressure ( DBP ) more than 120 mmHg . The patients were r and omly divided into 2 groups . In group I , sublingual nifedipine 5 mg was administered and repeated after 15 minutes if DBP > 120 mmHg ; and in group II hydrallazine 5 mg was intravenously injected and repeated after 15 minutes if DBP > 120 mmHg . Both groups were put on hydrallazine infusion if DBP > 120 mmHg after 30 minutes . The Chi-square test was used for analysis with significance at p < 0.05 . RESULTS There was no statistical difference in the efficacy of therapy for decreasing blood pressure between the 2 groups . The groups were comparable by age , parity , gestational age at presentation , birth weight of infants , incidence of postpartum haemorrhage and fetal distress . Caesarian section rates were similar . In the observational studies on nurses administering the drugs , no significant difficulties were observed . CONCLUSION Sublingual nifedipine was comparable to IV hydrallazine in the treatment of acute hypertension of pregnancy . Nurses were able to administer lingual nifedipine without difficulty Objective Preeclampsia ( PE ) is a complication affecting pregnant women worldwide , which usually manifests as severe maternal hypertension . Resveratrol ( RESV ) , a naturally existing polyphenol , is known to exhibit beneficial effects in cardiovascular disease including hypertension . We evaluated the outcome of treatment combining oral nifedipine ( NIFE ) and RESV against PE . Design and methods Using a r and omized group assignment , 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo . Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis . Secondary endpoints were defined as the number of doses needed to control blood pressure , maternal and neonatal adverse effects . Results Compared with the NIFE + placebo group , the time needed to control blood pressure was significantly reduced in NIFE + RESV group , while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group . The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group . No differences in maternal or neonatal adverse effects were observed between the two treatment groups . Conclusion Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients AIMS Diazoxide is one of few available agents for treatment of hypertensive emergencies in pregnancy . From previous studies , there is a question concerning safety after moderate-dose administration caused episodes of hypotension . Rapid control of severe hypertension is necessary to reduce maternal morbidity , for example , stroke and placental abruption . This study was design ed to compare the efficacy of mini-bolus diazoxide with intravenous ( i.v . ) hydralazine . DESIGN A r and omised controlled trial . SETTING Tertiary referral maternity hospital , Royal Prince Alfred Women and Babies , Sydney Australia . POPULATION Antenatal and postnatal women with severe hypertension . METHODS One hundred and twenty-four hypertensive women were r and omised to either i.v . hydralazine ( 5 mg doses ) or mini-bolus diazoxide ( 15 mg doses ) . PRIMARY OUTCOME MEASURE Achievement of target blood pressure reduction ; secondary measures included requirement for Caesarean section because of fetal deterioration as determined by non-reassuring cardiotocograph ( CTG ) . RESULTS Reduction in systolic and diastolic blood pressure was 34 min for hydralazine and 19 min for diazoxide ( P < 0.001 ) . There were no episodes of hypotension after diazoxide and one after hydralazine ( after epidural ) . Episodes of persistent severe hypertension were more common with hydralazine ( 38 % ) than with diazoxide ( 16 % ) , P < 0.01 . The Caesarean section rate for no-reassuring CTG was no different between the two groups . Neonatal outcomes were similar . CONCLUSION Diazoxide and hydralazine are safe and effective antihypertensives , showing a controlled and comparable blood pressure reduction in women with hypertensive emergencies in pregnancy . The mini-bolus doses of 15 mg of diazoxide did not precipitate maternal hypotension as previously described and reduces episodes of persistent severe hypertension Vitamin D ( VD ) has exhibited immunomodulatory role in the pathogenesis of preeclampsia . We hypothesize VD potentiate nifedipine treatment for preeclampsia by shortened the time to control blood pressure and prolong time before subsequent hypertensive crisis . We conduct a r and omized trial of 683 primigravid women with preeclampsia , who were assigned to different treatment groups , either nifedipine+placebo or nifedipine+VD orally , by r and om after screening . Primary endpoints include time to control hypertension and time before another hypertensive crisis . Maternal adverse effects including nausea , vomiting , chest pain , mild headache , dizziness , maternal tachycardia , hypotension or shortness of breath , and neonatal parameters including birth weight and Apgar scores , as well as the minimum number of dosages needed to control hypertension were defined as secondary endpoints . Serum levels of cytokines tumor necrosis factor-α ( TNF-α ) and interleukin-10 ( IL-10 ) were also examined . There was a marked reduction of the time required to control hypertension and a significant lengthening ( p = 0.013 ) of the time before a new hypertensive crisis in participants received nifedipine+VD treatments ( 41.8 ± 18.3 min ) , in comparison with the nifedipine+placebo controls ( 61.1 ± 15.9 min ) . In women treated with nifedipine+VD , the minimum number of dosages needed to control hypertension was also lower . With regard to adverse effects , no statistical difference was observed between the two treatment groups . Moreover , treatment with VD increased IL-10 and reduced TNF-α serum levels . VD possesses the potential of serving as a safe and effective adjuvant to oral nifedipine in treating women with preeclampsia against hypertension , possibly through the upregulation of IL-10 and the downregulation of TNF-α OBJECTIVE The objective was to compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in pregnancy . STUDY DESIGN Two hundred women with severe hypertension in pregnancy were r and omized to receive hydralazine ( 5 mg as a slow bolus dose given intravenously , and repeated every 20 min up to a maximum of five doses ) or labetalol ( 20-mg intravenous bolus dose followed by 40 mg if not effective within 20 min , followed by 80 mg every 20 min up to a maximum dose of 300 mg ) . The primary end point was successful lowering of blood pressure and maternal hypotension . RESULTS Women were similar with respect to characteristics at r and omization . No significant differences were observed for maternal hypotension or persistent severe hypertension ; only two patients in the hydralazine group presented with hypotension . Palpitations ( p=0.01 ) and maternal tachycardia ( p=0.05 ) occurred significantly more often in patients treated with hydralazine . The main neonatal outcomes were very similar per group ; however , hypotension and bradycardia were significantly more frequent in the labetalol group . There were two neonatal deaths per antihypertensive drug group . CONCLUSIONS This r and omized clinical trial shows that labetalol and hydralazine fulfill the criteria required for an antihypertensive drug to treat severe hypertension in pregnancy Abstract Objective : Using noninvasive bedside impedance cardiography ( ICG ) , we compared the effectiveness and the hemodynamic impact of intravenous labetalol versus hydralazine for the reduction of acute-onset severe hypertension to ACOG-recommended blood pressure levels ( ACOG Committee Opinion 514 ) . Study design : In this prospect i ve r and omized pilot study of acutely severe systolic hypertension ( ≥160 mmHg ) , pregnant women received either labetalol ( L ) or hydralazine ( H ) intravenously and underwent thoracic ICG before and after treatment . Data analysis were performed using STATA software ( StataCorp LP , College Station , TX ) ; data are expressed as mean ± SD . Results : About 29 patients completed the study . There was no significant difference in mean arterial pressure ( MAP ) between groups [ H = 119.4 mmHg , L = 117.7 mmHg , mean difference ( MD ) = 1.73 ) ; the estimated MD between baseline and follow-up ICG was −9.17 ( p = 0.001 , 95 % CI : −14.39 to −3.95 ) . There were no significant differences in total peripheral resistance ( TPR ) between groups ( H = 1771.3 , L = 1976.97 , MD = 205.62 ) or cardiac output ( CO ) between groups ( H = 5.7 , L = 5.1 , MD = 0.64 ) or a significant MD between these at baseline and follow-up . Conclusion : Both drugs performed similarly to achieve ACOG-recommended initial blood pressure reduction safely without side effects or excessive acute hemodynamic profile correction toward normal pregnancy values OBJECTIVE This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension ( http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext ) to provide a reasonable approach to the diagnosis , evaluation , and treatment of the hypertensive disorders of pregnancy . EVIDENCE Published literature was retrieved through search es of Medline , CINAHL , and The Cochrane Library in March 2012 using appropriate controlled vocabulary ( e.g. , pregnancy , hypertension , pre-eclampsia , pregnancy toxemias ) and key words ( e.g. , diagnosis , evaluation , classification , prediction , prevention , prognosis , treatment , postpartum follow-up ) . Results were restricted to systematic review s , r and omized control trials , controlled clinical trials , and observational studies published in French or English between January 2006 and February 2012 . Search es were up date d on a regular basis and incorporated in the guideline to September 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology-related agencies , clinical practice guideline collection s , clinical trial registries , and national and international medical specialty societies . VALUES The quality of evidence in the guideline summarized here was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care ( Table 1 ) BACKGROUND The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage . In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy , because it now has been used safely for about 30 years , and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards . In some other countries combined alpha- and beta-blockers are also used . Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia , there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine . METHODS Urapidil is a post-synaptic alpha 1 adrenoceptor antagonist , which is widely used to control hypertensive crises unrelated to pregnancy . Since it is known that pre-eclampsia is associated with increased sympathetic activity , administration of an alpha 1 adrenoceptor antagonist provides a reasonable therapeutic basis . So far there is only one report describing the i.v . use of urapidil in the treatment of hypertension in pregnancy unresponsive to dihydralazine and one report which describes the oral use of urapidil . In an earlier pilot study we examined the dose range for i.v . application of urapidil necessary for adequate blood pressure control in patients with pre-eclampsia . In the present r and omized controlled study 26 white women with pre-eclampsia and hypertension in pregnancy were included . Treatment was not blinded . During the initial period of intensive intravenous treatment all subjects were under constant surveillance by a physician and a nurse . RESULTS Effective prolonged control of blood pressure ( values below 150/100 mmHg ) was achieved in all patients of the two groups . In one patient of the dihydralazine group signs of lightheadedness and near syncope were noted . After this side-effect of dihydralazine the patient was treated with urapidil . At the end of the observation period the maternal heart rate in the dihydralazine group was higher than in the urapidil group . CONCLUSIONS Since urapidil decreased the high blood pressure in patients with pre-eclampsia without serious side-effects urapidil appears preferable superior to dihydralazine . The haemodynamic effects of urapidil were more predictable than those of dihydralazine . The reduction of intracerebral pressure could be an additional advantage of urapidil in the treatment of patients with pre-eclampsia Background Changes during the puerperium are still unclear , particularly in women with hypertension . The choice of antihypertensives , both to control very high blood pressure episodes and to keep blood pressure stable , also requires further elucidation . Currently , there are no clear data to guide the decision for the choice of postpartum antihypertensives . Captopril plays an important role in the treatment of very high blood pressure episodes and may be used postpartum . Clonidine has been used as an alternative in pregnant or postpartum women with contraindications to captopril , with satisfactory effect . The objective of the present study was to evaluate the effectiveness and safety of clonidine compared to captopril for treating severe postpartum hypertension . Methods and findings A r and omized , drug-controlled , triple-blind clinical trial evaluating postpartum women receiving captopril or clonidine . Inclusion criteria consisted of : women with hypertensive disorders of pregnancy systolic blood pressure ( SBP ) ≥180 mmHg and /or diastolic blood pressure ( DBP ) ≥110 mmHg ] , requiring magnesium sulfate . Exclusion criteria were : heart disease , smoking , illicit drug use , contraindications to captopril , clonidine or oral medication , and having used captopril/clonidine previously . The primary outcome was the frequency of very high blood pressure episodes while in the obstetric intensive care unit . A total of 90 postpartum women met the study inclusion criteria , with 45 r and omized to each group . There were fewer very high blood pressure episodes during hospitalization ( 2.1 ± 2.1 vs. 3.5 ± 4.7 , p = 0.08 ) , greater percentage reduction in SBP ( 14.0 % ± 8.6 % vs. 10.8 % ± 8.8 % , p = 0.08 ) and fewer women requiring sodium nitroprusside ( 2.3 % vs. 13.3 % ; RR : 0.17 ; 95%CI : 0.02–1.39 ; p = 0.06 ) in the clonidine group compared to the captopril group ; however , these differences were not significant . The groups were similar regarding daily mean SBP or DBP ; however , on the third postpartum day , mean SBP was lower in the clonidine compared to the captopril group ( 151.9 ± 11.8 mmHg vs. 158.1 ± 13.6 mmHg , p = 0.02 ) . Although not statistically significant , adverse reactions were more common in the captopril group ( 28.8 % ) compared to the clonidine group ( 18.6 % ) . Conclusion Clonidine and captopril represent safe , effective treatments for severe postpartum hypertension . Trial registration clinical trials.gov : www . clinical trial.gov , NCT01761916 The effect of nifedipine ( Adalat ; Bayer-Miles)--a calcium channel blocker , which has a well-established place in nonobstetric hypertension -- was compared with dihydralazine in 33 primigravidas with severe hypertension of pregnancy . Patients with a diastolic blood pressure greater than 110 mmHg before drug administration were r and omly assigned to treatment with either nifedipine or dihydralazine . Both drugs were found to be equally efficacious . Nifedipine , however , showed an earlier onset of action in lowering systolic blood pressure and had the advantage of oral administration The objective was to compare the fetal and maternal effects between parenteral hydralazine and sublingual nifedipine used like antihypertensive drugs in the management of severe preeclampsia . Study design was prospect i ve , comparative , longitudinal , r and omized clinical trial . It was carried out at Centro Medico Nacional IMSS Torreon , Coah . Gynecology and Obstetrics Department . The patients were women in the last trimester of pregnancy with severe preeclampsia were r and omized to receive parenteral hydralazine or sublingual nifedipine as antihypertensive drugs . The only difference observed in this study was the Apgar of neonates whose mothers received hydralazine , that was significatively lesser than the Apgar of neonates whose mothers received nifedipine . Both medicaments are a good alternative as antihypertensive drugs in severe preeclampsia . Neonates whose mothers received Nifedipine had a higher Apgar OBJECTIVE : To compare the effectiveness of orally administered nifedipine and intravenously administered labetalol for acute blood pressure control in hypertensive emergency of pregnancy . METHODS : In this double-blind , r and omized , controlled trial , pregnant women with sustained increase in systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 110 mm Hg or higher were r and omized to receive nifedipine ( 10 mg tablet orally up to five doses ) and intravenous placebo saline injection or intravenous labetalol injection in escalating doses of 20 , 40 , 80 , 80 , and 80 mg and a placebo tablet every 20 minutes until the target blood pressure of 150 mm Hg systolic and 100 mm Hg diastolic , or lower , was achieved . Crossover treatment was administered if the initial treatment failed . The primary endpoint of the study was time necessary to achieve target blood pressure . Secondary endpoints were number of dosages required , adverse maternal and neonatal effects , side effect profile , and perinatal outcome . RESULTS : From October 2012 to April 2013 , we enrolled 60 patients . The median time taken to achieve target blood pressure was 40 minutes ( interquartile range , 20–60 minutes ) compared with 60 minutes ( interquartile range 40–85 minutes ) for nifedipine and labetalol , respectively ( P=.008 ) . The median dose required was two ( interquartile range 1–3 ) compared with three ( interquartile range 2–4.25 ) for nifedipine and labetalol , respectively ( P=.008 ) . No serious adverse maternal or perinatal side effects were witnessed in either group . CONCLUSION : As administered in this trial , oral nifedipine lowered blood pressure more quickly than did intravenous labetalol during hypertensive emergency in pregnancy . CLINICAL TRIAL REGISTRATION : Clinical Trials Registry — India , www.ctri.nic.in , CTRI/2013/02/003350 . LEVEL OF EVIDENCE : OBJECTIVE We sought to compare the efficacies of oral nifedipine and intravenous labetalol in the acute management of hypertensive emergencies of pregnancy . STUDY DESIGN We performed a r and omized double-blind trial of oral nifedipine ( 10 mg ) and intravenous labetalol ( 20 mg ) in 50 peripartum patients with sustained systolic blood pressure of > /=170 mm Hg or diastolic blood pressure of > /=105 mm Hg . Both agents were repeated at sequentially escalating dosages every 20 minutes until a therapeutic goal of systolic blood pressure of < 160 mm Hg and diastolic blood pressure of < 100 mm Hg was achieved . Crossover occurred if the treatment goal was not achieved after 5 doses . Primary outcome was time to achievement of the therapeutic goal . Secondary outcome variables were agent failure , urinary output , and adverse effects . Data were analyzed by unpaired t test , Mann-Whitney U test , and analysis of variance for repeated measures . RESULTS The time to achieve the blood pressure goal was significantly shorter with nifedipine ( mean + /- SD , 25 + /- 13.6 minutes ) than with labetalol ( 43.6 + /- 25.4 minutes ; P = .002 ) . No patients required crossover therapy . Urine output was significantly increased ( P < .001 ) at 1 hour after nifedipine dosing ( 99 + /- 99 mL ) compared with labetalol ( 44.8 + /- 19.1 mL ) and remained significantly increased at 2 , 6 , 12 , 18 , and 24 hours after initial administration . Adverse effects were infrequent . There were no differences in maternal age , gestational age , number of antepartum patients , or enrollment blood pressures between groups . CONCLUSIONS Both oral nifedipine and intravenous labetalol are effective in the management of acute hypertensive emergencies of pregnancy ; however , nifedipine controls hypertension more rapidly and is associated with a significant increase in urinary output Background There is a paucity of good quality evidence regarding the best therapeutic option for acute control of blood pressure during acute hypertensive emergency of pregnancy . Objective We sought to compare the efficacy of intravenously administered hydralazine and oral nifedipine for acute blood pressure control in acute hypertensive emergency of pregnancy . Study Design In this double‐blind , r and omized , controlled trial , pregnant women ( ≥24 weeks period of gestation ) with sustained increase in systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg were r and omized to receive intravenous hydralazine injection in doses of 5 , 10 , 10 , and 10 mg and a placebo tablet or oral nifedipine ( 10 mg tablet up to 4 doses ) and intravenous saline injection every 20 minutes until the target blood pressure of 150 mm Hg systolic and ≤100 mm Hg diastolic was achieved . Crossover treatment was administered if the initial treatment failed . The primary outcome of the study was time necessary to achieve target blood pressure . The secondary outcomes were the number of dosages required , adverse maternal and neonatal effects , and perinatal outcome . Results From December 2014 through September 2015 , we enrolled 60 patients . The median time to achieve target blood pressure was 40 minutes in both groups ( intravenous hydralazine and oral nifedipine ) ( interquartile interval 5 and 40 minutes , respectively , P = .809 ) . The median dose requirement in both groups was 2 ( intravenous hydralazine and oral nifedipine ) ( interquartile range 1 and 2 doses , respectively , P = .625 ) . Intravenous hydralazine was associated with statistically significantly higher occurrence of vomiting ( 9/30 vs 2/30 , respectively , P = .042 ) . No serious adverse maternal or perinatal side effects were witnessed in either group . Conclusion Both intravenous hydralazine and oral nifedipine are equally effective in lowering of blood pressure in acute hypertensive emergency of pregnancy OBJECTIVE To compare the efficacy and safety of intravenous dihydralazine with ketanserin in the management of severe hypertension in the third trimester . STUDY DESIGN A double blind r and omised controlled trial , comparing 5 mg dihydralazine with 10 mg ketanserin after an intravenous infusion of 500 ml of a crystalloid solution . Medication was repeated every 20 min till the therapeutic goal of 90 mm Hg was reached , to a maximum of 4 dosages . Main outcome measures were treatment failures and emergency deliveries for fetal distress . RESULTS The therapeutic goal was met more often in patients receiving dihydralazine ( 36/38 compared to 27/42 ; P < 0.01 ) . The need for delivery for fetal distress did not differ ( 3 after dihydralazine , 1 after ketanserin , P = 0.29 ) No therapy related perinatal loss occurred , but one mother with an undiagnosed phaechromocytoma died 24 h after receiving dihydralazine . CONCLUSION Ketanserin in this dosage is less effective to lower diastolic blood pressure . The place of a fluid load prior to dihydralazine needs to be further investigated , as fetal heart rate decelerations were less common than previously reported Labetalol ( Tr and ate ; Allen & Hanburys ) , a combined alpha- and beta-adrenergic blocking agent , was compared with the more commonly used peripheral vasodilator , dihydrallazine ( Nepresol ; Ciba ) , each administered as an infusion , in the treatment of severe hypertension in 20 primigravidas at greater than or equal to 32 weeks ' gestation . With the dosage regimen used in this study there was a tendency towards more effective blood pressure control with dihydrallazine . The pulse rate was unaffected by labetalol therapy and there were no harmful effects on the neonate or fetus directly attributable to either drug Sixty peripartum patients with diastolic blood pressures ( BP ) 110 mmHg or higher were r and omized in a 2:1 ratio to receive repeated intravenous injections of either labetalol ( 20 - 80 mg ) or hydralazine ( 5 mg ) until the diastolic BP was below 100 mmHg . There were four treatment failures in the labetalol group ( N = 40 ) and none in the hydralazine group ( N = 20 ) . Hydralazine lowered mean arterial pressure ( MAP ) more than did labetalol ( 33.3 + /- 13.2 versus 25.5 + /- 11.2 mmHg ; mean + /- SD ) , but labetalol had a more rapid effect . There was considerable interpatient variability in the dose of labetalol required to control BP , which could not be predicted by any clinical characteristic before therapy . The duration of action also varied in the labetalol group , with the shortest duration occurring in those patients who required the highest dosage for BP control . No significant fetal or neonatal problems ascribable to drug treatment were noted in the 13 instances in which labetalol was given before delivery . However , fetal distress occurred in two of the six cases involving antenatal hydralazine . We conclude that labetalol appears to be a safe and effective alternative to hydralazine for treating hypertension in the peripartum period , but serious rare side effects have not yet been quantified Abstract Objectives . To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy . Design . R and omized prospect i ve study . Setting . The obstetric ward of the teaching hospital of Monastir Tunisia . Patients . Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension . Intervention . Patients were r and omly assigned to receive intravenously for 1 h either labetalol ( n=30 ) or nicardipine ( n=30 ) . Treatment was titrated to achieve a 20 % lowering of blood pressure ( BP ) . Measurements . Maternal BP and heart rate were measured at inclusion and repeatedly during the first hour following the drugs administration . Fetal heart rate was recorded throughout the study period . The main outcome endpoints were the success rate and the length of time needed to achieve the therapeutic goal . The rate of maternal and fetal adverse events and dose adjustments were also analyzed . Results . Labetalol and nicardipine achieved the 20 % lowering in BP in the same proportion ( 63 % and 70 % success rates , respectively ) . Overall nicardipine caused a significantly greater decrease in systolic and diastolic BP . No patient had any episode of hypotension . The length of time to achieve the BP goal was also similar ( 12 vs. 11 min , respectively ) . Both drugs were well tolerated except for a moderate tachycardia observed with the use of nicardipine . Conclusion . Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy BACKGROUND Drug treatment is imperative for pregnant women with pregnancy-induced hypertension ( PIH ) and pre-eclampsia . For more than 40 years , dihydralazine has been the drug of choice for this indication . Another particularly effective and better tolerable antihypertensive is urapidil . Yet only a few studies on limited patient collectives have been published on the clinical experience with urapidil in PIH . METHODS Urapidil was interindividually compared to dihydralazine in a total of 42 patients , at six participating clinical centres . Patients were r and omly assigned to the treatment groups . Urapidil was administered at an initial dose of 12.5 - 25 mg , dihydralazine was administered at a uniform initial dose of 5 mg . Patients were closely monitored for the initial 24h of therapy . Until delivery and in the postpartal phase , mother and baby underwent four additional follow-up checks at regular intervals . RESULTS Either drug was effective in lowering BP . Urapidil treatment proved to be better controllable . There were clear differences as to tolerability . In the urapidil group , one patient complained of headaches . In the dihydralazine group , six patients experienced adverse occurrences . Under dihydralazine treatment , some marked HR increases occurred , interpretable as reflectory tachycardia . CONCLUSIONS Urapidil proved to be equally effective as dihydralazine in lowering BP in patients with pre-eclampsia , but showed a better controllability and tolerability . Urapidil can hence be recommended as a promising alternative for patients with PIH Preeclampsia , a disease mainly manifesting as serious hypertension during pregnancy , affects expectant mothers around the globe . Celastrol , a naturally existing triterpenoid , is known to exhibit beneficial effects attenuating cardiovascular symptoms including hypertension . We here assessed the treatment outcome against preeclampsia with a combined use of celastrol and nifedipine . A total of 626 patients with preeclampsia were enrolled , screened , and assigned by r and om to groups receiving either nifedipine + placebo or nifedipine + celastrol orally . Time required to control hypertension as well as time before another hypertensive crisis were defined as primary end points . Secondary end points include the number of dosages required to control hypertension , as well as maternal and neonatal adverse effects . The time to control hypertension showed a marked reduction in nifedipine + celastrol group , while time before a new hypertensive crisis was significantly lengthened with the treatment , compared with the nifedipine + placebo group . The number of dosages required to control hypertension was also lower in the nifedipine + celastrol group . The two treatment groups were not statistically different regarding adverse effects , either maternal or neonatal . Results from the current study provide evidence for the potential role of celastrol serving as an effective and safe adjuvant to oral nifedipine against hypertension in patients with preeclampsia OBJECTIVE To compare the antihypertensive effects of epoprostenol sodium ( prostacyclin ) with that of dihydralazine in acute hypertensive crises of pregnancy . DESIGN A prospect i ve r and omized study . A minimum of 20 patients per group was considered statistically acceptable ( alpha = 0.05 , power = 0.9 ) . SETTING A large urban tertiary hospital . SUBJECTS Forty-seven pregnant patients with diastolic blood pressures of > 100 mmHg were studied . INTERVENTION Lowering of high blood pressure with either dihydralazine ( n = 25 ) , the st and ard drug for this purpose , or epoprostenol ( n = 22 ) . MAIN OUTCOME MEASURE A significant drop in high blood pressure was regarded as a fall of 15 mmHg diastolic and 30 mmHg systolic blood pressure . RESULTS There were no statistically significant differences in the antihypertensive effects between the two treatment groups . Epoprostenol infusion caused less tachycardia ; the mean pulse rate changed from 81.77 beats/min , before treatment to 88.36 at stabilization , compared with a change from 80.96 beats/min to 102.68 in the group treated with dihydralazine ( P = 0.0024 ) . CONCLUSION The place of epoprostenol in pregnancy might be in patients with severe hypertension and tachycardia and in those requiring acute control of severe hypertension on the operating table before general anaesthesia OBJECTIVES To compare ketanserin with hydralazine in the treatment of hypertension in late pregnancy . STUDY DESIGN R and omised control trial . Ten milligrams ketanserin were compared with 5 mg hydralazine , both given intravenously to 10 patients in each group . Blood pressure , maternal and fetal heart rate and umbilical and arcuate artery Doppler flow velocimetry waveforms were recorded before and every 10 minutes after administration of the drug . RESULTS No significant differences were found between the two drugs in respect of initial blood pressures and readings taken 10 minutes after each 30-minute administration . One patient in the hydralazine group developed severe hypotension and fetal distress for which a caesarean section was performed . No change in the flow velocity waveforms of umbilical and arcuate arteries was noticed . CONCLUSION No unforeseen complications followed the administration of ketanserin . No major differences in the effects of the two drugs could be detected . Ketanserin appears to be safer as no hypotension occurred , and it reduced blood pressure more gradually . As ketanserin could become an alternative to hydralazine , more studies with larger numbers of patients are needed to compare it with hydralazine Intravenous hydralazine is a commonly administered arteriolar vasodilator that is effective for hypertensive emergencies associated with pregnancy . Oral nifedipine is an alternative in management of these patients . In this study the efficacy of nifedipine and hydralazine in pregnancy was compared in a group of Iranian patients . Fifty hypertensive pregnant women were enrolled in the study . A r and omized clinical trial was performed , in which patients in two groups received intravenus hydralazine or oral nifedipine to achieve target blood pressure reduction . The primary outcomes measured were the time and doses required for desired blood pressure achievement . Secondary measures included urinary output and maternal and neonatal side effects . The time required for reduction in systolic and diastolic blood pressure was shorter for oral nifedipine group ( 24.0 ± 10.0 min ) than intravenus Hydralazine group ( 34.8 ± 18.8 min ) ( P ≤ 0.016 ) . Less frequent doses were required with oral nifedipine ( 1.2 ± 0.5 ) compared to intravenus hydralazine ( 2.1 ± 1.0 ) ( P ≤ 0.0005 ) . There were no episodes of hypotension after hydralazine and one after nifedipine . Nifedipine and hydralazine are safe and effective antihypertensive drugs , showing a controlled and comparable blood pressure reduction in women with hypertensive emergencies in pregnancy . Both drugs reduce episodes of persistent severe hypertension . Considering pharmacokinetic properties of nifedipine such as rapid onset and long duration of action , the good oral bioavailability and less frequent side effects , it looks more preferable in hypertension emergencies of pregnancy than hydralazine We evaluated 16 pregnant women with gestational age between 20 and 32 weeks in acute severe hypertension which were r and omly allocated to receive either hydralazine or labetalol . Blood pressure and Doppler ultrasound parameters from maternal uterine and fetal middle cerebral and umbilical arteries were assessed during acute severe hypertension and after treatment . A significant reduction in systolic and diastolic blood pressure was observed in both groups . A significant change in Doppler parameters was observed only in pregnant women who received hydralazine : an increase in uterine arteries resistance index . We concluded that both drugs were highly effective in reducing blood pressure in these women . Despite the observed increase in resistance index of uterine arteries associated with hydralazine , the use of hydralazine and labetalol were not related to any significant changes in fetal Doppler , which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy Summary : Doppler studies of the uterine and umbilical arteries were performed in 24 acutely hypertensive pregnant women . Women were divided into 2 groups : Group 1 ( diastolic blood pressure (DBP)>110 mm Hg ) received placebo ( n = 6 ) or 10 mg oral nifedipine ( n = 9 ) ; Group 2 ( DBP ≥ 110 mm Hg ) received 10 mg oral nifedipine ( n = 5 ) or 10 mg intravenous hydralazine ( n = 4 ) . Treatment allocations were r and om within groups and the investigator and patient were blind to the treatments . Baseline flow velocity waveforms ( FVW ) and posttreatment FVW 's at 30 , 60 and 120 minutes were recorded . There was no significant difference between baseline and posttreatment FVW indices within or between groups . Placebo was as effective as nifedipine in lowering blood pressure over 2 hours of study . There were no significant adverse effects of treatment Background . Pre‐eclampsia is one of the most serious and common complications of pregnancy . Nifedipine , a calcium channel blocker , and the vasodilator hydralazine have both been used as antihypertensive agents in this condition . The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre‐eclampsia Objective To compare the haemodynamic efficacy of ketanserin ( a selective serotonin2‐receptor blocker ) with dihydralazine in the management of severe early‐onset hypertension in pregnancy Objective : To compare the intravenous Labetalol versus intravenous hydralazine in patients having severe Pregnancy induced hypertension ( PIH ) and pre eclampsia ( PE ) in pregnancy . Methods : Seventy eight women admitted in the Department of Gynecology and Obstetrics , Civil Hospital Karachi , having severe PIH/PE and fulfilling the inclusion criteria were included in the study . R and om selection of patients was performed using sealed opaqe envelop for administration of either intravenous noted ( IV ) Labetalol or Hydrallazine . The mean fall in the MAP in each group was noted . This data was analyzed by applying SPSS version 13 . The study was conducted from November 2012 to April 2013 . Results : The mean ( ±SD ) age of the labetalol group was 27.46 ( ±5.28 ) years while that in the hydralazine group was 26.28 ( ±5.17 ) years . The mean fall in MAP observed in the labetalol group was 29.10 ± 7.21 mmHg and that in the hydralazine group was 25.05 ± 10.15 mmHg which was statistically significant with the p value being 0.046 . Conclusion : Intra Venous labetalol lowered MAP more than hydralazine , when administered to pregnant females with severe Pregnancy induced hypertension and pre eclampsia in pregnancy We conducted a r and omized clinical trial in which patients with severe preeclampsia between 26 - 36 weeks of gestation received either nifedipine ( 10 - 30 mg sublingually , then 40 - 120 mg/day orally ; N=24 ) or hydralazine ( 6.25 - 12.5 mg intravenously , then 80 - 120 mg/day orally ; N=25 ) . Effective control of blood pressure was achieved with nifedipine in 95.8 % of subjects and with hydralazine in 68 % , a statistically significant difference ( P<.05 ) . Maternal side effects were minor in both groups . Acute fetal distress developed in one nifedipine subject and in 11 treated with hydralazine . Mean prolongation of gestation was 15.5 ± 10 days with nifedipine and 9.5 ± 11 days with hydralazine , a difference that did not reach statistical significance ( P<.07 ) . Infants born to women treated with nifedipine were delivered at more advanced gestational ages ( 34.6 ± 2.3 versus 33.6 ± 2.4 weeks ; statistically not significant ) , weighed more ( 1826 ± 456 versus 1580 ± 499 g ; statistically not significant ) , and tended to have fewer , mainly minor , complications . The average number of days spent in the neonatal intensive care unit was significantly lower in the nifedipine group ( 15.1 versus 32.7 days ; P<.005 ) , leading to an average 31 % reduction in total ( maternal and neonatal ) hospitalization related charges for each nifedipine-treated pregnancy . We conclude that nifedipine is an effective , convenient , and low-cost treatment for patients with severe preeclampsia , and is not associated with undesirable side Objective : To compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in the puerperium . Design : R and omized clinical trial . Setting : Critical care unit of gynecology and obstetrics department in the Complejo hospitalario “ Dr. AAM ” de la Caja de Seguro Social in Panama . Population : Eighty-two women with severe hypertension during the postpartum period . Methods : Patients were r and omized to receive hydralazine ( 5 mg as a slow bolus dose given intravenously , and repeated every 20 minutes to a maximum of five doses ) or labetalol ( 20 mg in an intravenous bolus dose followed by 40 mg if not effective within 20 minutes , followed by 80 mg every 20 minutes to a maximum dose of 300 mg ) . The primary endpoint was the successful lowering of blood pressure . Secondary endpoints were maternal complications and side-effects . Results : Forty-two women were enrolled in the hydralazine group and 40 in the labetalol group . Women were similar with respect to characteristics at r and omization . No significant differences were observed for persistent severe hypertension or maternal side-effects . There was only one case of persistent severe hypertension in the labetalol group . There were no maternal deaths in any of the women studied . Conclusions : This r and omized clinical trial shows that intravenous hydralazine and intravenous labetalol are effective and safe in the management of severe hypertension in the postpartum period OBJECTIVE Our purpose was to compare the hemodynamic effects of orally administered nifedipine and intravenously administered labetalol in preeclamptic hypertensive emergencies . STUDY DESIGN Our study was a r and omized , double-blind evaluation of nifedipine and labetalol in women with preeclampsia and a systolic blood pressure > 170 mm Hg or a diastolic blood pressure > 105 mm Hg . Nifedipine or labetalol and placebo were given , so patients received both tablet and intravenous solution . Hemodynamic parameters at dosing and at 15 , 30 , 60 , and 120 minutes were recorded . Outcome measures were cardiac index , systemic vascular resistance index , mean arterial pressure , and heart rate . Data were analyzed by repeated- measures analysis of variance ( Friedman test ) with Dunn posttests , the Mann-Whitney U test , and the chi(2 ) test with the Yates correction . Significance was set at P < .05 . RESULTS At dosing , the nifedipine group ( n = 6 ) had a cardiac index of 3.08 + /- 0.51 L/min per square meter . There was a 43 % increase in the cardiac index after nifedipine administration ( P = .0008 ) . There was no significant effect in the labetalol group ( P = .697 ) . There was a significant decrease in the systemic vascular resistance index after nifedipine dosing ( P = .002 ) but no significant effect on this index after labetalol use ( P = .479 ) . The mean arterial pressure was significantly affected in both groups as follows : nifedipine , P = . 001 ; labetalol , P = .004 . The post analysis showed significance at 60 minutes for both . An insignificant increase in heart rate with nifedipine ( P = .147 ) and a significant decrease with labetalol ( P = . 034 ) were noted . CONCLUSIONS Nifedipine increases cardiac index , whereas labetalol may not do so Please cite this paper as : Raheem I , Saaid R , Omar S , Tan P. Oral nifedipine versus intravenous labetalol for acute blood pressure control in hypertensive emergencies of pregnancy : a r and omised trial . BJOG 2012;119:78–85 Background There is no consensus about the better intravenous drug between Hydralazine and Labetalol to control hypertension in cases of severe hypertension in pregnancy . Both drugs have their own advantages and disadvantages . Methods This is a prospect i ve r and omized controlled trial comparing the efficacy and safety of intravenous Labetalol versus Hydralazine for management of severe hypertension in pregnancy . A total of 152 eligible subjects were r and omised in two groups consisting 76 subjects each by envelope method . Both the groups were comparable with respect to systolic , diastolic and mean arterial blood pressure at admission . One group received Labetalol and the other Hydralazine . The number of drug doses , the time taken to achieve target blood pressure and side-effects were noted . Results With a single dose , Labetalol ( 81.5 % ) was able to achieve target blood pressure in a significantly higher number of cases as compared to Hydralazine ( 69.5 % ) . Labetalol could help in achieving the target blood pressure faster than Hydralazine . The incidence of maternal adverse effects was comparable between the groups . Fetal outcome was comparable in both groups . Conclusion Hydralazine and Labetalol both were found to be equally efficacious in reducing blood pressure in cases of severe hypertension in pregnancy . Labetalol achieved the target blood pressure faster than Hydralazine . The adverse effects of both the drugs were comparable Background : Hypertensive crisis is an important cause of maternal and perinatal morbidity and mortality . Aim : To compare the efficacy of oral nifedipine and intravenous labetalol . Material s and methods : One hundred women with hypertensive crisis were r and omized to receive either oral nifedipine 10 mg or intravenous labetalol 20 mg . Oral nifedipine was given 10 mg stat followed by 10 mg every 30 minutes up to a maximum of 50 mg . Intravenous labetalol was given 20 mg stat followed by 40 mg 30 minutes later then two more doses of 80 mg every 30 minutes up to a maximum of 220 mg . The primary outcome was the number of doses required to achieve target blood pressure ( BP ) and time required to reduce the mean arterial pressure by 25 % . Secondary outcomes analysed included additional drugs required , resurgence of hypertensive crisis . Data were analysed using repeated measures analysis of variance ( ANOVA ) , mixed ANOVA , unpaired t-test and chi square test and P value ≤0.05 was considered significant . Results : Systolic ( SBP ) , diastolic ( DBP ) and mean arterial blood pressure ( MAP ) were lower than baseline at all time points of follow-up in both nifedipine and labetalol groups ( P < 0.01 ) . P < 0.05 by repeated measures ANOVA for overall trend of changes in SBP , DBP and MAP for within-group effects in both nifedipine and labetalol groups and P < 0.05 by mixed ANOVA for between-group effects during entire observation period . The magnitude of fall in SBP , DBP and MAP was greater in the labetalol group compared with the nifedipine group ( P < 0.05 ) . Target BP was achieved in 90 % in the nifedipine group and 92 % in the labetalol group . Maternal and fetal adverse effects were infrequent . Conclusion : Both oral nifedipine and intravenous labetalol are effective in the treatment of hypertensive crisis . Intravenous labetalol may have benefits because it is more effective in reducing the SBP , DBP and MAP to target levels with a lower number of doses |
13,903 | 30,306,610 | Best evidence synthesis determined moderate positive evidence for using the ARAT with people without limb spasticity : intra-rater reliability ( ICC 0.71 ( 95 % CI 0.53 - 0.89 ) to 0.99 ( 95 % CI 0.98 , 0.99 ) ) ; responsiveness ( ROC curve 0.72 - 0.88 , SRM 0.89 ) ; and regarding construct validity , it is a valid measure of activity limitation .
Gaps in evidence were found for inter and test-retest reliability , measurement error , content validity , structural validity , floor and ceiling effects .
CONCLUSIONS The ARAT is an appropriate measure of activity limitation post-stroke and should be considered for use with people with TBI ; evidence for people with upper limb spasticity is limited . | BACKGROUND / AIM The Action Research Arm Test ( ARAT ) measures upper limb activity limitations in people with acquired brain injuries .
Evidence relating to the use of this test in neurorehabilitation is scattered .
This review identifies , rates and synthesis es evidence on the original 1981 ARAT use within neurorehabilitation .
Psychometric properties are review ed , including specific examination of participants with upper limb spasticity . | Objective To explore potential predictors of self-reported paretic arm use at baseline and after task-specific training ( TST ) in survivors of stroke . Design Data were obtained from a r and omized controlled trial of somatosensory stimulation and upper limb TST in chronic stroke . Setting University laboratory . Participants Chronic ( ≥3mo ) survivors of stroke ( N=33 ; mean age , 62y ; mean stroke duration , 38mo ) . Interventions Participants received 12 sessions of TST preceded by either active ( n=16 ) or sham ( n=17 ) somatosensory stimulation to all 3 peripheral nerves . Main Outcome Measures Demographic and clinical characteristics were entered stepwise into multiple linear regression analyses to determine the factors that best predict baseline Motor Activity Log ( MAL ) amount of use rating and change 3 months after TST . Results The Action Research Arm Test ( ARAT ) score predicted the amount of use at baseline ( R2=.47 , P<.001 ) ; in using this model , an ARAT score of 54 ( maximum of 57 ) is required to score 2.5 on the MAL ( use described as between rarely and sometimes ) . After TST the change in the ARAT score predicted the change in the amount of use ( R2=.31 , P=.001 ) . The predictive power of the model for change at 3 months increased if the Fugl-Meyer Assessment wrist component score was added ( R2=.41 , P=.001 ) . Conclusions Utilization of the paretic upper limb in activities of daily living requires high functional ability . The increase in self-reported arm use after TST is dependent on the change in functional ability . These results provide further guidance for rehabilitation decisions OBJECTIVE To estimate minimal clinical ly important difference ( MCID ) values of several upper-extremity measures early after stroke . DESIGN Data in this report were collected during the Very Early Constraint-induced Therapy for Recovery of Stroke trial , an acute , single-blind r and omized controlled trial of constraint-induced movement therapy . Subjects were tested at the prer and omization baseline assessment ( average days poststroke , 9.5d ) and the first posttreatment assessment ( average days poststroke , 25.9d ) . At each time point , the affected upper extremity was evaluated with a battery of 6 tests . At the second assessment , subjects were also asked to provide a global rating of perceived changes in their affected upper extremity . Anchor-based MCID values were calculated separately for the affected dominant upper extremities and the affected nondominant upper extremities for each of the 6 tests . SETTING Inpatient rehabilitation hospital . PARTICIPANTS Fifty-two people with hemiparesis poststroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Estimated MCID values for grip strength , composite upper-extremity strength , Action Research Arm Test ( ARAT ) , Wolf Motor Function Test ( WMFT ) , Motor Activity Log ( MAL ) , and duration of upper-extremity use as measured with accelerometry . RESULTS MCID values for grip strength were 5.0 and 6.2 kg for the affected dominant and nondominant sides , respectively . MCID values for the ARAT were 12 and 17 points , for the WMFT function score were 1.0 and 1.2 points , and for the MAL quality of movement score were 1.0 and 1.1 points for the 2 sides , respectively . MCID values were indeterminate for the dominant ( composite strength ) , the nondominant ( WMFT time score ) , and both affected sides ( duration of use ) for the other measures . CONCLUSIONS Our data provide some of the first estimates of MCID values for upper-extremity st and ardized measures early after stroke . Future studies with larger sample sizes are needed to refine these estimates and to determine whether MCID values are modified by time poststroke This study explored relationships between upper-limb ( UL ) functional limitations and self-reported disability in stroke patients with relatively pure motor hemiparesis who were enrolled in an acute rehabilitation treatment trial . All participants were enrolled in the VECTORS ( Very Early Constraint Treatment for Recovery from Stroke ) study . VECTORS is a single-center pilot clinical trial of early application of constraint-induced movement therapy ( CIMT ) . All 39 subjects who completed 90 days of VECTORS were included in this analysis . Trained study personnel who were blinded to the treatment type performed all evaluations . Data in this article examine relationships between assessment s performed 90 days after stroke . Functional limitation measures included the Action Research Arm ( ARA ) test and Wolf Motor Function Test ( WMFT ) , and self-reported disability measures included the Functional Independence Measure ( FIM ) and Motor Activity Log ( MAL ) ( by telephone ) . Mean plus or minus st and ard deviation time from stroke onset to r and omization was 9.4 plus or minus 4.3 days , and median time to follow-up was 99 days ( range 68 - 178 ) . Subjects with perfect or near-perfect scores on the ARA test or WMFT reported residual disability on the FIM and MAL . Quality of movement on the WMFT ( functional ability score ) was not strongly associated with self-reported frequency , and speed of movement on the WMFT ( timed score ) was not associated with self-reported frequency ( MAL amount of use ) . In this early UL intervention trial , we found that perceived disability measures captured information that was not assessed by functional limitation and impairment scales . Our results indicate that excellent motor recovery as measured by functional limitation and impairment scales did not equal restoration of everyday productive UL use and speed of task completion did not translate to actual use . Our results confirm the need for a measurement strategy that is sensitive to change , assesses a broad performance range , and detects meaningful clinical improvements in early rehabilitation intervention trials BACKGROUND AND PURPOSE Of all stroke survivors , 30 % to 66 % are unable to use their affected arm in performing activities of daily living . Although forced use therapy appears to improve arm function in chronic stroke patients , there is no conclusive evidence . This study evaluates the effectiveness of forced use therapy . METHODS In an observer-blinded r and omized clinical trial , 66 chronic stroke patients were allocated to either forced use therapy ( immobilization of the unaffected arm combined with intensive training ) or a reference therapy of equally intensive bimanual training , based on Neuro-Developmental Treatment , for a period of 2 weeks . Outcomes were evaluated on the basis of the Rehabilitation Activities Profile ( activities ) , the Action Research Arm ( ARA ) test ( dexterity ) , the upper extremity section of the Fugl-Meyer Assessment scale , the Motor Activity Log ( MAL ) , and a Problem Score . The minimal clinical ly important difference ( MCID ) was determined at the onset of the study . RESULTS One week after the last treatment session , a significant difference in effectiveness in favor of the forced use group compared with the bimanual group ( corrected for baseline differences ) was found for the ARA score ( 3.0 points ; 95 % CI , 1.3 to 4.8 ; MCID , 5.7 points ) and the MAL amount of use score ( 0.52 points ; 95 % CI , 0.11 to 0.93 ; MCID , 0.50 ) . The other parameters revealed no significant differential effects . One-year follow-up effects were observed only for the ARA . The differences in treatment effect for the ARA and the MAL amount of use scores were clinical ly relevant for patients with sensory disorders and hemineglect , respectively . CONCLUSIONS The present study showed a small but lasting effect of forced use therapy on the dexterity of the affected arm ( ARA ) and a temporary clinical ly relevant effect on the amount of use of the affected arm during activities of daily living ( MAL amount of use ) . The effect of forced use therapy was clinical ly relevant in the subgroups of patients with sensory disorders and hemineglect , respectively Stroke is a leading cause of adult disability and the recovery of motor function is important for independence in activities of daily living . Predicting motor recovery after stroke in individual patients is difficult . Accurate prognosis would enable realistic rehabilitation goal - setting and more efficient allocation of re sources . The aim of this study was to test and refine an algorithm for predicting the potential for recovery of upper limb function after stroke . Forty participants were prospect ively enrolled within 3 days of ischaemic stroke . First , shoulder abduction and finger extension strength were grade d 72 h after stroke onset to compute a shoulder abduction and finger extension score . Secondly , transcranial magnetic stimulation was used to assess the functional integrity of descending motor pathways to the affected upper limb . Third , diffusion-weighted magnetic resonance imaging was used to assess the structural integrity of the posterior limbs of the internal capsules . Finally , these measures were combined in the PREP algorithm for predicting an individual 's potential for upper limb recovery at 12 weeks , measured with the Action Research Arm Test . A cluster analysis was used to independently group patients according to Action Research Arm Test score at 12 weeks , for comparison with predictions from the PREP algorithm . There was excellent correspondence between the cluster analysis of Action Research Arm Test score at 12 weeks and predictions made with the PREP algorithm . The algorithm had positive predictive power of 88 % , negative predictive power of 83 % , specificity of 88 % and sensitivity of 73 % . This study provides preliminary data in support of the PREP algorithm for the prognosis of upper limb recovery in individual patients . PREP may enable tailored planning of rehabilitation and more accurate stratification of patients in clinical trials In this study , we compared the responsiveness and validity of the Box and Block Test ( BBT ) , the Nine-Hole Peg Test ( NHPT ) , and the Action Research Arm Test ( ARAT ) . We r and omized 59 patients with stroke into one of three rehabilitation treatments for 3 weeks . We administered six outcome measures ( BBT , NHPT , ARAT , Fugl-Meyer Assessment [ FMA ] , Motor Activity Log [ MAL ] , and Stroke Impact Scale [ SIS ] h and function domain ) pretreatment and posttreatment . We used the st and ardized response mean ( SRM ) to examine responsiveness and the Spearman rank correlation coefficient ( rho ) to examine concurrent validity . The BBT , NHPT , and ARAT were moderately responsive to change and not significantly different ( SRM = 0.64 - 0.79 ) . The correlations within the BBT , NHPT , and ARAT were moderate to good at pretreatment ( rho = -0.55 to -0.80 ) and posttreatment ( rho = -0.57 to -0.71 ) . The BBT and ARAT showed fair to moderate correlations with the FMA , MAL , and SIS h and function domain at pretreatment and posttreatment ( rho = 0.31 - 0.59 ) , whereas the NHPT demonstrated low to fair correlations with the FMA and MAL ( rho = -0.16 to -0.33 ) and moderate correlations with the SIS h and function domain ( rho = -0.58 to -0.66 ) . Our results indicate that the BBT , NHPT , and ARAT are suitable to detect changes over time . While simultaneously considering the responsiveness and validity attributes , the BBT and ARAT can be considered more appropriate for evaluating dexterous function than the NHPT . Further studies with larger sample s are needed to vali date these findings OBJECTIVES To determine the intra- and interrater reliability of the Action Research Arm ( ARA ) test , to assess its ability to detect a minimal clinical ly important difference ( MCID ) of 5.7 points , and to identify less reliable test items . DESIGN Intrarater reliability of the sum scores and of individual items was assessed by comparing ( 1 ) the ratings of the laboratory measurements of 20 patients with the ratings of the same measurements recorded on videotape by the original rater , and ( 2 ) the repeated ratings of videotaped measurements by the same rater . Interrater reliability was assessed by comparing the ratings of the videotaped measurements of 2 raters . The result ing limits of agreement were compared with the MCID . PATIENTS Stratified sample , based on the intake ARA score , of 20 chronic stroke patients ( median age , 62yr ; median time since stroke onset , 3.6yr ; mean intake ARA score , 29.2 ) . MAIN OUTCOME MEASURES Spearman 's rank-order correlation coefficient ( Spearman 's rho ) ; intraclass correlation coefficient ( ICC ) ; mean difference and limits of agreement , based on ARA sum scores ; and weighted kappa , based on individual items . RESULTS All intra- and interrater Spearman 's rho and ICC values were higher than .98 . The mean difference between ratings was highest for the interrater pair ( .75 ; 95 % confidence interval , .02 - 1.48 ) , suggesting a small systematic difference between raters . Intrarater limits of agreement were -1.66 to 2.26 ; interrater limits of agreement were -2.35 to 3.85 . Median weighted kappas exceeded .92 . CONCLUSION The high intra- and interrater reliability of the ARA test was confirmed , as was its ability to detect a clinical ly relevant difference of 5.7 points To test the clinical counterpart of the learned nonuse theory , 25 chronic hemiplegic stroke and head-injured patients with minimal to moderate upper extremity extensor muscle function were required to keep their uninvolved upper extremities within a h and -enclosed sling during waking hours over a 2-week interval . During this forced use period and for 1 year thereafter , changes in force or time-based measures among 21 functional tasks were compared to values at the sixth baseline session , a preintervention time when relearning had plateaued . Significant ( P less than 0.05 , Friedman 's repeated measures followed by Tukey multiple comparison tests ) changes were seen in 19 of the 21 tasks with most persisting at the 1-year follow-up . There were no apparent differences between right- and left-sided involvement or between stroke versus head injury clients ( Mann-Whitney procedure ) . Ratings for quality of movement scored from videotapes presented in r and om order showed no change over time . These data suggest that learned nonuse does occur in select neurological patients and that this behavior can be reversed through application of a forced use paradigm OBJECTIVE To assess the construct , concurrent , and predictive validity of dynamic computerized h and dynamometry . DESIGN Prospect i ve correlational study between dynamometry and functional upper limb performance . SETTING Hospital outpatient spasticity clinics . PARTICIPANTS Adults with upper motor neuron syndrome affecting the upper limb after acquired brain injury ( ABI ) ( n=38 ; median age , 50 y ; range , 18 - 81 y ) and healthy adult control participants ( n=27 ; median age , 37 y ; range , 22 - 62 y ) . INTERVENTION Not applicable . MAIN OUTCOME MEASURES Dynamic computerized dynamometry elements of h and performance ( isometric force , force velocity , isometric grip work , contraction and relaxation duration ) and the Action Research Arm Test . RESULTS Motor elements of h and performance objective ly measured by the dynamic computerized dynamometry protocol achieved moderate to good validity when correlated with st and ardized measures of functional h and performance . Dynamic computerized dynamometry identified clear differences in h and performance between participants with and without ABI . Within the ABI group , dynamic computerized h and dynamometry achieved fair to moderate predictive validity with regards to whether a participant would be referred for botulinum toxin A injections . CONCLUSIONS This study provides support for the construct , concurrent , and predictive validity of the dynamic computerized dynamometry protocol OBJECTIVE To examine the internal consistency , validity , responsiveness , and advantages of the Wolf Motor Function Test ( WMFT ) and compare these results to the Action Research Arm Test ( ARAT ) in participants with mild to moderate hemiparesis within the first few months after stroke . DESIGN Data were collected as part of the Very Early Constraint-Induced Therapy for Recovery from Stroke ( VECTORS ) trial , an acute , single-blind r and omized controlled trial of constraint-induced movement therapy . Subjects were studied at baseline ( day 0 ) , after treatment ( day 14 ) , and after 90 days ( day 90 ) poststroke . SETTING Inpatient rehabilitation hospital ; follow-up 3 months poststroke . PARTICIPANTS Hemiparetic subjects ( N=51 ) enrolled in the VECTORS trial . INTERVENTION None . MAIN OUTCOME MEASURES At each time point , subjects were tested on ( 1 ) the WMFT and ARAT , ( 2 ) clinical measures of sensorimotor impairments , ( 3 ) reach and grasp movements performed in the kinematics laboratory , and ( 4 ) clinical measures of disability . Blinded raters performed all evaluations . Analyses at each time point included calculating effect size as indicators of responsiveness , and correlation analyses to examine relationships between WMFT scores and other measures . RESULTS The WMFT is internally consistent , valid , and responsive in the early stages of stroke recovery . Sensorimotor and kinematic measures of reach and grasp support the construct validity of the WMFT . CONCLUSIONS In an acute stroke population , the WMFT has acceptable reliability , validity , and responsiveness to change over time . However , when compared with the ARAT , the higher training and testing burdens may not be offset by the relatively small psychometric advantages OBJECTIVE To examine the responsiveness and validity of the Action Research Arm Test ( ARAT ) in a population of subjects with mild-to-moderate hemiparesis within the first few months after stroke . DESIGN Data were collected as part of the Very Early Constraint-Induced Therapy for Recovery from Stroke trial , an acute , single-blind r and omized controlled trial of constraint-induced movement therapy . Subjects were studied at baseline ( day 0 ) , after treatment ( day 14 ) , and after 90 days ( day 90 ) poststroke . SETTING Inpatient rehabilitation hospital ; follow-up 3 months poststroke . PARTICIPANTS Fifty hemiparetic subjects . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES At each time point , subjects were tested on : ( 1 ) the ARAT , ( 2 ) clinical measures of sensorimotor impairments , ( 3 ) in the kinematics laboratory where they performed reach and grasp movements , and ( 4 ) clinical measures of disability . Blinded raters performed all evaluations . Analyses at each time point included calculating effect size as indicators of responsiveness , and correlation and regression analyses to examine relationships between ARAT scores and other measures . RESULTS The ARAT is responsive to change , with effect sizes greater than 1.0 and responsiveness ratios of 7.0 at 3 months poststroke . ARAT scores were related to sensorimotor impairment measures , 3-dimensional kinematic measures of movement performance , and disability measures at all 3 time points . CONCLUSIONS The ARAT is a responsive and valid measure of upper-extremity functional limitation and therefore may be an appropriate measure for use in acute upper-extremity rehabilitation trials Purpose : This study examined the role of anxiety and upper limb dysfunction , amongst other variables , as predictors of health related quality of life ( HRQOL ) 6 months after stroke . Method : Participants : Stroke survivors ( n = 85 ) who had previously participated in a r and omised controlled trial of a physiotherapy intervention . Dependent variable : HRQOL – Nottingham Health Profile ( NHP ) . Predictor variables : Mood – Hospital Depression and Anxiety Scale ; Upper Limb Functioning - Action Research Arm Test ; Rivermead Motor Assessment ; Activities of Daily Living – Modified Barthel Index ; Clinical and demographic factors . Results : Anxiety and depression significantly predicted 49 % of variance in overall HRQOL ( p < 0.05 ) , but only anxiety significantly predicted NHP pain ( 13 % variance , p < 0.001 ) , emotional reactions ( 41 % variance , p < 0.001 ) , sleep ( 19 % variance , p = 0.02 ) and social isolation ( 23 % variance , p = 0.02 ) . Depression and anxiety together significantly predicted 30 % variance in energy level ( p < 0.001 ) . UL motor impairment and activities of daily living predicted 36 % of variance in NHP physical activity score ( p < 0.001 ) . Conclusions : This study indicates that where anxiety is assessed , it appears more important in determining HRQOL than depression . UL impairment and ADL independence predicted perceived physical activity . Management strategies for anxiety and therapy for UL recovery long after stroke onset are likely to benefit perceived HRQOL . Implication s for Rehabilitation Anxiety is a major predictor of quality of life six months after stroke . Post-stroke anxiety should be routinely assessed in rehabilitation . Appropriate management strategies for anxiety should occur during rehabilitation with follow-up into the chronic post-stroke period . Upper limb impairment is a stronger predictor of perceptions of physical activity than independence in activities daily living six months after stroke . Rehabilitation of the upper limb should continue into the chronic post-stroke period Background : Functional limitation of the upper extremities is common in patients with stroke . An upper-extremity measure with sound psychometric properties is indispensable for clinical and research use . Objective : The purpose of this study was to compare the psychometric properties of 4 clinical measures for assessing upper-extremity motor function in people with stroke : the upper-extremity subscale of the Fugl-Meyer Motor Test ( UE-FM ) , the upper-extremity subscale of the Stroke Rehabilitation Assessment of Movement , the Action Research Arm Test ( ARAT ) , and the Wolf Motor Function Test . Design : This was a prospect i ve , longitudinal study . Methods : Fifty-three people with stroke were evaluated with the 4 measures at 4 time points ( 14 , 30 , 90 , and 180 days after stroke ) . Thirty-five participants completed all of the assessment s. The ceiling and floor effects , validity ( concurrent validity and predictive validity ) , and responsiveness of each measure were examined . Interrater reliability and test-retest reliability also were examined . Results : All measures , except for the UE-FM , had significant floor effects or ceiling effects at one or more time points . The Spearman ρ correlation coefficient for each pair of the 4 measures was ≥.81 , indicating high concurrent validity . The predictive validity of the 4 measures was satisfactory ( Spearman ρ , ≥.51 ) . The responsiveness of the 4 measures at 14 to 180 days after stroke was moderate ( .52 ≤ effect size ≤ .79 ) . The 4 measures had good interrater reliability ( intraclass correlation coefficient [ ICC ] , ≥.92 ) and test-retest reliability ( ICC , ≥.97 ) . Only the minimal detectable changes of the UE-FM ( 8 % of the highest possible score ) and the ARAT ( 6 % ) were satisfactory . Limitations : The sample size was too small to conduct data analysis according to type or severity of stroke . In addition , the timed component of the Wolf Motor Function Test was not used in this study . Conclusions : All 4 measures showed sufficient validity , responsiveness , and reliability in participants with stroke . The UE-FM for assessing impairment and the ARAT for assessing disability had satisfactory minimal detectable changes , supporting their utility in clinical setting OBJECTIVE To assess the relative responsiveness of 2 commonly used upper-extremity motor scales , the Action Research Arm Test ( ARAT ) and the Fugl-Meyer Assessment ( FMA ) , in evaluating recovery of upper-extremity function after an acute stroke in patients undergoing inpatient rehabilitation . DESIGN Prospect i ve . SETTING An acute stroke rehabilitation unit . PARTICIPANTS One hundred four consecutive admissions ( 43 men , 61 women ; mean age + /- st and ard deviation , 72+/-13y ) to a rehabilitation unit 16+/-9 days after acute stroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The following assessment s were completed within 72 hours of admission and 24 hours before discharge : ARAT , upper-extremity motor domain of the FMA , National Institutes of Health Stroke Scale , FIM instrument total score , and FIM activities of daily living ( FIM-ADL ) subscore . RESULTS The Spearman rank correlation statistic indicated that the 2 upper-limb motor scales ( ARAT , FMA ) correlated highly with one another , both on admission ( rho = .77 , P < .001 ) and on discharge ( rho = .87 , P < .001 ) . The mean change in score from admission to discharge was 10+/-15 for the ARAT and 10+/-13 for the FMA motor score . The responsiveness to change as measured by the st and ard response mean was .68 for the ARAT and .74 for the FMA motor score . The Spearman rank correlation of each upper-limb motor scale with the FIM-ADL at the time of admission was as follows : ARAT , rho equal to .32 ( P < .001 ) and FMA motor score , rho equal to .54 ( P < .001 ) . CONCLUSIONS Both the FMA motor score and the ARAT were equally sensitive to change during inpatient acute rehabilitation and could be routinely used to measure recovery of upper-extremity motor function Objective : To vali date results obtained from using the Action Research Arm Test ( ARAT ) at tables of a common height for persons who have experienced a stroke . Design : Each subject was tested three times with the ARAT while sitting at three different tables : a table specially design ed for the test and two generally available tables similar in height to the st and ard table . The patients were r and omly and equally assigned to three different raters and to three different tables in accordance with a counterbalanced design . All evaluations were completed within a two-day period . Subjects : Sixty-one patients who had had only one stroke ( mean age 63.3 years ; median time since stroke onset 81 days ; mean ARAT score administered at the st and ard table 33.8 ) participated in this study . Results : The intraclass correlation coef”cient ( ICC ) for the total scores obtained using the ARAT at the different tables was 0.99 , indicating very high agreement . The ICCs were also very high in each of the subscales . Conclusion : The results of this study support the use of the ARAT at ordinary tables roughly similar in height to that specially design ed for use with the ARAT |
13,904 | 31,464,955 | RESULTS This systematic review and meta- analysis will provide a high- quality comprehensive evaluation of the efficacy and safety based on current literature evidence of CHM intervention for stable COPD .
The conclusion of this study will present the evidence of whether CHM is an effective and safe intervention for stable COPD patients | BACKGROUND Chinese herbal medicine ( CHM ) has been shown to be effective in the treatment of stable chronic obstructive pulmonary disease ( COPD ) by published meta-analyses .
However , disease outcomes were inconsistent and heterogeneity was observed attributed to placebo-controlled studies .
We present a protocol for a systematic review aim ing to evaluate the clinical efficacy and safety of CHM comparing to placebo in the treatment of stable COPD , to provide robust evidence for the use of CHM in COPD . | In traditional Chinese medicine ( TCM ) , the Yiqigubiao pill is commonly used to enhance physical fitness . The current clinical trial was design ed to evaluate the efficacy and safety of the Yiqigubiao pill as an adjuvant therapy for patients with stable chronic obstructive pulmonary disease ( COPD ) . The current trial was a r and omized , double-blind , placebo-controlled superiority trial . The participants were recruited from out patients at the Traditional Chinese Medicine Hospital affiliated with Xinjiang Medical University ( Ürümqi , China ) between February and September 2012 . All participants were patients with stable COPD that were r and omized to the Yiqigubiao pill ( YQGB ; n=84 ) or placebo ( Pb ; n=87 ) groups . The occurrences of acute exacerbation ( AE ) of COPD during the trial were recorded . Lung function value assessment s , scoring of life quality and exercise endurance , arterial blood gas analysis and serum inflammatory cytokines level determination were performed prior to and throughout the study . A total of 139 participants completed the intervention and 132 participants completed the study . The interval between the initial intervention and the first AE COPD was greater in the YQGB group compared with the Pb group ( P<0.01 ) . The incidence rate of AE COPD was lower in the YQGB group than in the Pb group ( P<0.01 ) . Subsequent to the intervention or at the end of the study , the 6-min walking distance difference was longer in the YQGB group compared with the Pb group ( P<0.01 ) . The scores reflecting life quality decline became lower in the YQGB group ( P<0.01 ) . The serum levels of proinflammatory factors were downregulated to a greater extent in the YQGB group compared with the Pb group . Thus , the Yiqigubiao pill is an efficient and safe adjuvant therapy for the treatment of stable patients with COPD Abstract The aim of this study was to determine if components of the COPD Assessment Test ( CAT ) , a vali date d health status impairment instrument , had additional utility in identifying patients at risk for COPD in whom spirometry testing is appropriate . This study was part of the Canadian Obstructive Lung Disease prevalence study . Consenting participants ≥ 40 years of age were identified by r and om digit dialing . Smoking history , 8-item CAT scores , and post-bronchodilator spirometry were recorded for each . Stepwise logistic regression analysis was used to identify variables related to the presence of airway obstruction and a final logistic model was developed which best predicted COPD in this sample . Of the 801 individuals approached , 532 were included : 51 ( 9.6 % ) had COPD , the majority ( 92 % ) of whom fit GOLD I or II severity criteria . Items that correlated significantly with a COPD diagnosis included the CAT total score ( p = 0.01 ) and its breathlessness ( p < 0.0001 ) and phlegm ( p = 0.001 ) components . The final logistic model included : age ( < 55 or ≥55 years ) , smoking status ( current , former , never ) and the CAT breathlessness score ( ordinal scale 0–5 ) . The area under the receiver-operating characteristic curve for this model was 0.77 , sensitivity was 77.6 % , specificity was 64.9 % and the positive likelihood ratio was 2.21 . In summary , the triad of smoking history , age at least 55 years and the presence of exertional breathlessness were key elements of a simple model which had reliable measurement properties when tested in a r and om population . This may help identify patients at risk for COPD for whom spirometry testing is recommended This study aim ed to evaluate the efficacy of comprehensive therapy based on traditional Chinese medicine ( TCM ) patterns on older patients with chronic obstructive pulmonary disease ( COPD ) through a four-center , open-label , r and omized controlled trial . Patients were divided into the trial group treated using conventional western medicine and Bu-Fei Jian-Pi granules , Bu-Fei Yi-Shen granules , and Yi-Qi Zi-Shen granules based on TCM patterns respectively ; and the control group treated using conventional western medicine . A total of 136 patients ⩾ 65 years completed the study , with 63 patients comprising the trial group and 73 comprising the control group . After the six-month treatment and the 12-month follow-up period , significant differences were observed between the trial and control groups in the following aspects : frequency of acute exacerbation ( P ⩽ 0.040 ) , duration of acute exacerbation ( P = 0.034 ) , symptoms ( P ⩽ 0.034 ) , 6-min walking distance ( 6MWD ) ( P ⩽ 0.039 ) , dyspnea scale ( P ⩽ 0.036 ) ; physical domain ( P ⩽ 0.019 ) , psychological domain ( P ⩽ 0.033 ) , social domain ( P ⩽ 0.020 ) , and environmental domain ( P ⩽ 0.044 ) of the WHOQOL-BREF question naire ; and daily living ability domain ( P ⩽ 0.007 ) , social activity domain ( P ⩽ 0.018 ) , depression symptoms domain ( P ⩽ 0.025 ) , and anxiety symptoms domain ( P ⩽ 0.037 ) of the COPD -QOL . No differences were observed between the trial and control groups with regard to FVC , FEV1 , and FEV1 % OBJECTIVE To study the therapeutic effect Bufei granule , which is a traditional Chinese drug that can enhance the immune function of the lung , on patients with stable chronic obstructive pulmonary disease ( COPD ) . METHODS This is a r and omized , double blinded , placebo-controlled , and multicenter clinical study . Three medical centers in Tianjin , China , participated in the trial . A total of 140 patients with stable COPD were enrolled and r and omized into two groups , with 70 patients in each . The treatment group was treated with Bufei granule , while the control group received Bufei placebo . The pharmacological treatment lasted for 12 weeks from the date of enrollment . Then , the indexes of patients were observed . Data were analyzed to study the effect of Bufei granule , with the frequency of acute exacerbation as the primary outcome . Traditional Chinese Medicine syndromes , Modified British Medical Research Council dyspnea scale score , St. George 's respiratory question naire scores , pulmonary function , and serum inflammatory marker levels [ including interleukin-6 ( IL-6 ) , interleukin-8 , tumor necrosis factor-alpha , and transformation growth factor-beta1 ] were the secondary outcomes . RESULTS During the 12-week treatment , treatment and control groups had no adverse reactions . The analysis of the indexes obtained from all patients showed that the therapeutic effect in the treatment group was significantly better than that in the control group because most of the similar probabilities of primary and secondary outcomes were less than 0.05 , except for the level of IL-6 . CONCLUSION Bufei granule can treat patients with stable COPD by lowering the frequency of acute exacerbation , improving the quality of life , and alleviating the severity of inflammation Background : A Chinese herb formula Yufeining ( YFN ) has showed promise in the treatment of stable chronic obstructive pulmonary disease ( COPD ) , less is known that the impact of YFN in combination with st and ard Western treatments on lung inflammation . This study evaluated the safety and efficacy of YFN as a treatment for stable COPD and as an anti-inflammatory agent . Methods : Sixty patients with stable COPD were r and omly assigned to two treatment groups ( YFN treatment , N = 30 ; placebo treatment , N = 30 ) . Both groups received inhaled steroids and bronchodilators during an 8-week intervention , and patient status was assessed at 8 weeks later and 4 months after treatment . The primary outcome included clinical efficacy . The secondary outcomes involved CAT score , mMRC grade , six-minute walking distance ( 6MWD ) . IL-8 , TNF-&agr ; , IL-17A , LTB4 , TGF-&bgr;1 and CRP were also detection in peripheral serum , as well as adverse reaction conditions . Results : The YFN group demonstrated a significant improvement in clinical efficacy ( compare 89.3 % to 63.3 % in the placebo group ; P < 0.05 ) . CAT scores and mMRC grade s significantly decreased ( P < 0.05 , P < 0.01 ) , and 6MWD significantly increased ( P<0.05 ) , after YFN treatment . The levels of IL-8 , TNF-&agr ; , LTB4 and CRP decreased significantly after 8 weeks of treatment compared to baseline levels in both groups . Only in the YFN treatment group , the levels of IL-17A decreased significantly after treatment compared to baseline levels ( P < 0.05 ) . No changes were observed inTGF-&bgr;1 from pre-to post-treatment in either group ( P > 0.05 ) . Serum levels of IL-8 , TNF-&agr ; , IL-17A , LTB4 and CRP decreased significantly after YFN treatment compared to the placebo group ( P < 0.05 ) . Conclusion : A combinatorial treatment approach with YFN , inhaled steroids and bronchodilators produced a clinical ly effective treatment for stable COPD , leading to a significant decrease in circulating inflammatory mediators . The study appeared YFN was safety . Clinical trial registration number : No. ChiCTR-IOR-17013577 Purpose Recurrence of acute exacerbations has a major impact on patients with COPD . Therefore , effective prevention and treatment of exacerbation is crucial in the management of COPD , especially for patients with moderate to severe disease . This study evaluated the effectiveness of YuPingFeng granule administration in preventing exacerbation and improving symptom score , as well as its long-term ( 1 year ) safety profile , in patients with COPD . Patients and methods This was a r and omized , double-blind , parallel , placebo-controlled study of 240 patients from eight centers in China . Participants were eligible if they had mild to severe COPD as defined by Global Initiative for Chronic Obstructive Lung Disease , had a history of at least two COPD exacerbations or one hospitalization within the previous year , and had remained clinical ly stable for over 4 weeks before the study . They were r and omly assigned to receive 5 g of YuPingFeng or placebo , three times per day , for 1 year . The primary end point was the exacerbation rate over 1 year , and the analysis was by intention to treat . Secondary end points included symptom score , which was assessed by COPD assessment test ( CAT ) score and safety profiles . This trial was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ; registration number : ChiCTR-IPR-15007023 ) . Results The YuPingFeng group had a significantly lower exacerbation rate than the placebo group ( 1.15 vs 1.55 ; risk ratio=0.677 [ 95 % CI 0.531–0.863 ] ; P=0.002 ) and a significantly reduced risk of second exacerbation ( 95 % CI 0.326–0.772 ; P=0.002 ) . After treatment , the mean change in the CAT score in the YuPingFeng group ( −4.41±7.01 ) differed significantly from that in the placebo group ( −2.49±5.31 ; P=0.001 ) . YuPingFeng was well tolerated . Conclusion YuPingFeng granules can be considered as a treatment option for COPD ; this treatment prevents acute exacerbations of COPD and has a good safety profile |
13,905 | 29,630,715 | Pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on recurrence of ARTI or cure rates in children .
We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children . | BACKGROUND Acute respiratory tract infections ( ARTIs ) are common and may lead to complications .
Most children experience between three and six ARTIs each year .
Although these infections are self limiting , the symptoms can be distressing .
Many treatments are used to control symptoms and shorten the duration of illness .
They often have minimal benefit and may lead to adverse effects .
Oral homeopathic medicinal products could play a role in the treatment of ARTIs for children if evidence for effectiveness is established .
OBJECTIVES To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat acute respiratory tract infections in children . | BACKGROUND Influenza and its complications are common at all ages , especially in children . Vaccines and anti-influenza drugs aim to prevent it . Preventative approaches with favorable risk profiles should be considered for flu , particularly since the evidence of the efficacy of anti-viral drugs is debated . METHODS This pragmatic clinical trial was conducted in the Brazilian Public Health System in Petrópolis ( BPHSP ) with children aged from 1 to 5 years old . The medications used were mainly selected based on in vitro experiments ( InfluBio ) , and in successful qualitative clinical experiences ( Homeopathic Complex ) . Following informed parental consent , subjects were r and omly distributed , in a blind manner , to three experimental groups : Homeopathic Complex , Placebo , and InfluBio . BPHSP health agents collected flu and acute respiratory infection symptomatic episodes monthly following the established protocol . The number of these episodes was registered in one year ( 2009 - 2010 ) . RESULTS Out of the 600 children recruited , 445 ( 74.17 % ) completed the study ( 149 : Homeopathic complex ; 151 : Placebo ; 145 : InfluBio ) . The number of flu and acute respiratory infection symptomatic episodes detected in this clinical trial was low ; however , it was different between homeopathic groups and placebo ( p < 0.001 ) . In the first year post-intervention , 46/151 ( 30.5 % ) of children in the placebo group developed 3 or more flu and acute respiratory infection episodes , while there was no episode in the group of 149 children who used Homeopathic Complex , and only 1 episode in the group of 145 ( 1 % ) children who received InfluBio . CONCLUSION These results suggested that the use of homeopathic medicines minimized the number of flu and acute respiratory infection symptomatic episodes in children , signalizing that the homeopathic prophylactic potential should be investigated in further studies OBJECTIVE To assess the effectiveness of a homeopathic ear drop for treatment of otalgia in children with acute otitis media ( AOM ) . METHODS Children with AOM were enrolled in the study at the time of diagnosis and r and omized to receive either st and ard therapy alone or st and ard therapy plus a homeopathic ear drop solution that was to be used on as needed basis for up to 5 days . Parents of children in both treatment groups rated the severity of 5 AOM symptoms twice daily for 5 days in a symptom diary . A symptom score was computed for each assessment with lower scores denoting less severe symptoms . Parents of children r and omized to receive ear drops also recorded information regarding symptoms being treated and response to treatment . RESULTS A total of 119 eligible children were enrolled in the study ; symptom diaries were received from 94 ( 79 % ) . Symptom scores tended to be lower in the group of children receiving ear drops than in those receiving st and ard therapy alone ; these differences were significant at the second and third assessment s ( P = 0.04 and P = 0.003 , respectively ) . In addition , the rate of symptom improvement was faster in children in the ear drop group compared with children in st and ard therapy alone group ( P = 0.002 ) . The most common reason for administration of ear drops was ear pain , recorded for 93 doses ; improvement was noted after 78.4 % of doses for this indication . There were no significant side effects related to use of the ear drops . CONCLUSIONS This study suggests that homeopathic ear drops were moderately effective in treating otalgia in children with AOM and may be most effective in the early period after a diagnosis of AOM . Pediatricians and other primary health care providers should consider homeopathic ear drops a useful adjunct to st and ard therapy OBJECTIVE To pilot a model for determining whether homoeopathic treatment of children suffering from glue ear is more effective than st and ard GP care at producing a return to normal hearing ( a hearing loss of less than 20 dB ) within 12 months . DESIGN Non-blind , r and omized controlled trial . SETTING General practice in two locations in southern Engl and . SUBJECTS Thirty-three children aged 18 months to 8 years with otitis media with effusion , hearing loss > 20 dB and an abnormal tympanogram . OUTCOME MEASURES Hearing loss , tympanogram , referrals to specialists and number of courses of antibiotics at 12 month follow-up . RESULTS A higher proportion of children receiving homoeopathic care had a hearing loss less then 20 dB at follow-up ( 64 vs 56 % ) , though this difference did not reach statistical significance ( 95 % confidence interval for the difference between means of -25 and 42 % ) . More homoeopathy patients than controls had a normal tympanogram ( 75 vs 31 % , P = 0.015 ) . Referrals to specialists and antibiotic consumption was lower in the homoeopathy group , though differences between groups did not reach statistical significance . CONCLUSION Further research comparing homoeopathy to st and ard care is warranted . Assuming recovery rates of 50 and 30 % in homoeopathy and st and ard care groups respectively , 270 patients would be needed for a definitive trial Background The present study was initiated to investigate the effectiveness , safety and tolerability of complex homeopathic CalSuli-4 - 02 tablets on prevention of recurrent acute upper respiratory tract infections ( URTIs ) in children , in comparison to another complex homeopathic product . Methods The study was design ed as a prospect i ve , multicenter , r and omized , open , clinical trial with two parallel treatment groups at four outpatient pediatric clinics in Russia . Children aged ≤ 6 years with susceptibility to acute URTIs ( ≥ three occasions during the last 6 months ) were r and omized to receive either CalSuli-4 - 02 or a comparator homeopathic product ( control group ) for 3 weeks . Primary outcome was the frequency of acute URTIs after 3 and 6 months post-treatment follow-up . Secondary endpoints were changes in complaints and symptoms ( total and individual scores ) , treatment satisfaction , antibiotic use , safety and tolerability . Results The intention-to-treat analysis involved 200 children ( CalSuli-4 - 02 : N = 99 , Control : N = 101 ) . In both treatment groups , the median number of acute URTIs was one for 3 months and two , respectively , for the full 6 months post-treatment ( Relative Risk : 0.86 ( 95 % -CI : 0.72–1.03 ) , p = 0.1099 ) . Seasons had no influence on the outcome . At the end of study , CalSuli-4 - 02 had overall higher odds of getting lower complaints severity total score ( Odds ratio : 1.99 ( 95 % -CI : 1.31–3.02 ) , p = 0.0012 ) and showing symptom improvement ( Odds ratio : 1.93 ( 95 % -CI : 1.25–3.00 ) , p = 0.0033 ) . Specifically , the complaint “ appetite disorder ” and the symptom “ child ’s activities ” significantly improved more in the CalSuli-4 - 02 group ( p = 0.0135 and p = 0.0063 , respectively ) . Antibiotic use was decreased in both treatment groups at the study end . Overall assessment for satisfaction with and tolerability of treatment was higher with CalSuli-4 - 02 . A low number of non-serious adverse drug reactions was reported ( CalSuli-4 - 02 : N = 4 , Control : N = 1 ) . Conclusions Both complex homeopathic products led to a comparable reduction of URTIs . In the CalSuli-4 - 02 group , significantly less URTI-related complaints and symptoms and higher treatment satisfaction and tolerability were detected . The observation that the use of antibiotics was reduced upon treatment with the complex homeopathic medications , without the occurrence of complications , is interesting and warrants further investigations on the potential of CalSuli-4 - 02 as an antibiotic sparing option . Clinical trial registration numberRoszdravnadzor : Study No BACKGROUND Acute viral tonsillitis is an upper respiratory tract infection prevalent in school-aged children . Because this condition is self-limiting , conventional treatment options are usually palliative . Homeopathic remedies are a useful alternative to conventional medications in acute uncomplicated upper respiratory tract infections in children , offering earlier symptom resolution , cost-effectiveness , and fewer adverse effects . This study aim ed to determine the efficacy of a homeopathic complex on the symptoms of acute viral tonsillitis in African children in South Africa . METHODS This was a r and omized , double-blind , placebo-controlled , 6-day pilot study . Thirty children , age 6 to 12 years , with acute viral tonsillitis were recruited from a primary school in Gauteng , South Africa . Participants took two tablets of the medication four times daily . The treatment group received lactose tablets medicated with the homeopathic complex ( Atropa belladonna D4 , Calcarea phosphoricum D4 , Hepar sulphuris D4 , Kalium bichromat D4 , Kalium muriaticum D4 , Mercurius protoiodid D10 , and Mercurius biniodid D10 ) . The placebo consisted of the unmedicated vehicle only . The Wong-Baker FACES Pain Rating Scale measured pain intensity , and a Symptom Grading Scale assessed changes in tonsillitis signs and symptoms . RESULTS The treatment group had a statistically significant improvement in the following symptoms compared with the placebo group : pain associated with tonsillitis , pain on swallowing , erythema and inflammation of the pharynx , and tonsil size . CONCLUSION The homeopathic complex used in this study exhibited significant anti-inflammatory and pain-relieving qualities in children with acute viral tonsillitis . No patients reported any adverse effects . These preliminary findings are promising ; however , the sample size was small and therefore a definitive conclusion can not be reached . A larger , more inclusive research study should be undertaken to verify the findings of this study We investigated the clinical effectiveness of a homeopathic add-on therapy in a pediatric sub population with upper respiratory tract infections ( URTI ) in a r and omized , controlled , multinational clinical trial . Patients received either on-dem and symptomatic st and ard treatment ( ST-group ) or the same ST plus a homeopathic medication ( Influcid ; IFC-group ) for 7 days . Outcome assessment was based on symptom and fever resolution and the Wisconsin Upper Respiratory Symptom Survey–21 ( WURSS-21 ) . A total of 261 pediatric ( < 12 years ) patients ( 130 IFC-group ; 131 ST-group ) were recruited in Germany and the Ukraine . The IFC-group used less symptomatic medication , symptoms resolved significantly earlier ( P = .0001 ) , had higher proportions of fever-free children from day 3 onwards , and the WURSS-assessed global disease severity was significantly less ( P < .0001 ) during the entire URTI episode . One adverse event ( vomiting ) was possibly related to IFC . IFC as add-on treatment in pediatric URTI reduced global disease severity , shortened symptom resolution , and was safe in use Cough is a frequent symptom associated to upper respiratory tract infections ( URTIs ) and , although being self-limiting , it might deeply affect the quality of life . Homeopathic products are often employed by patients to treat cough , but the evidence on their efficacy is scarce . Thus , we tested the efficacy of a homeopathic syrup in treating cough arising from URTIs with a r and omized , double blind , placebo controlled clinical trial . Patients were treated with either the homeopathic syrup or a placebo for a week , and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks . Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment ; patients were also asked to provide a subjective evaluation of viscosity . Eighty patients were r and omized to receive placebo ( n = 40 ) or the homeopathic syrup ( n = 40 ) . All patients completed the study . In each group cough scores decreased over time , however , after 4 and 7 days of treatment , cough severity was significantly lower in the homeopathic group than in the placebo one ( p < 0.001 and p = 0.023 , respectively ) . Sputum was collected from 53 patients : in both groups its viscosity significantly decreased after 4 days of treatment ( p < 0.001 ) ; however , viscosity was significantly lower in the homeopathic group ( p = 0.018 ) . Instead , the subjective evaluation did not significantly differ between the two groups ( p = 0.059 ) . No adverse events related to any treatment were reported . We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity , thereby representing a valid remedy for the management of acute cough induced by URTIs BACKGROUND The use of antibiotics in the initial treatment of acute otitis media is currently being question ed . Homeopathy has been used historically to treat this illness , but there have been no method ologically rigorous trials to determine whether there is a positive treatment effect . METHODS A r and omized double blind placebo control pilot study was conducted in a private pediatric practice in Seattle , WA . Seventy-five children ages 18 months to 6 years with middle ear effusion and ear pain and /or fever for no more than 36 h were entered into the study . Children received either an individualized homeopathic medicine or a placebo administered orally three times daily for 5 days , or until symptoms subsided , whichever occurred first . Outcome measures included the number of treatment failures after 5 days , 2 weeks and 6 weeks . Diary symptom scores during the first 3 days and middle ear effusion at 2 and 6 weeks after treatment were also evaluated . RESULTS There were fewer treatment failures in the group receiving homeopathy after 5 days , 2 weeks and 6 weeks , with differences of 11.4 , 18.4 and 19.9 % , respectively , but these differences were not statistically significant . Diary scores showed a significant decrease in symptoms at 24 and 64 h after treatment in favor of homeopathy ( P < 0.05 ) . Sample size calculations indicate that 243 children in each of 2 groups would be needed for significant results , based on 5-day failure rates . CONCLUSIONS These results suggest that a positive treatment effect of homeopathy when compared with placebo in acute otitis media can not be excluded and that a larger study is justified BACKGROUND There is little evidence that the decongestant , antihistamine , or cough suppressant medications commonly used to treat cold symptoms in preschool children are effective . One option for treating cold symptoms in young children is with homeopathy . This study was conducted to determine if a homeopathic syrup was effective in treating cold symptoms in preschool children . METHODS Children 2 - 5 years old diagnosed with an upper respiratory tract infection were r and omized to receive a commercial homeopathic cold syrup or placebo . Parents administered the study medication as needed for 3days . The primary outcome was change in symptoms one hour after each dose . Parents also assessed the severity of each of the symptoms of runny nose , cough , congestion and sneezing at baseline and twice daily for 3days , using a 4-point rating scale . A composite cold score was calculated by combining the values for each of the four symptoms . RESULTS Among 261 eligible participants , data on 957 doses of study medication in 154 children were analyzed . There was no significant difference in improvement one hour after the dose for any symptom between the two groups . Analysis of twice daily data on the severity of cold symptoms compared to baseline values found that improvements in sneezing , cough and the composite cold score were significantly greater at both the first and second assessment s among those receiving the cold syrup compared to placebo recipients . CONCLUSION The homeopathic syrup appeared to be effective in reducing the severity of cold symptoms in the first day after beginning treatment Abstract Objective : To investigate the intrinsic effects of individually prescribed homoeopathic medicines . Design : R and omised double blind placebo controlled study . Setting : Paediatric outpatient department of university hospital . Patients : 175 children with frequently recurring upper respiratory tract infections . Of the 170 children evaluable , 86 were r and omised to homoeopathic medicines ( 47 boys , 39 girls ; median age at start 4.2 years ; median number of episodes in past year 4 ) and 84 to placebo ( 43 boys , 41 girls ; median age at start 3.6 years ; median number of episodes in past year 4 ) . Main outcome measures : Mean score for daily symptoms , number of antibiotic courses , and number of adenoidectomies and tonsillectomies over one year of follow up . Results : The mean daily symptom score was 2.61 in the placebo group and 2.21 in the treatment group ( difference 0.41 ; 95 % confidence interval -0.02 to 0.83 ) . In both groups the use of antibiotics was greatly reduced compared with that in the year before entering the trial ( from 73 to 33 in the treatment group and from 69 to 43 in the placebo group ) . The proportion of children in the treatment group having adenoidectomies was lower in the treatment group ( 16 % , 8/50 ) than in the placebo group ( 21 % , 9/42 ) . The proportion having tonsillectomies was the same in both groups ( 5 % ) . Conclusion : Individually prescribed homoeopathic medicines seem to add little to careful counselling of children with recurrent upper respiratory tract infection in reducing the daily burden of symptoms , use of antibiotics , and need for adenoidectomy and tonsillectomy BACKGROUND Otitis media with effusion ( OME ) is the most common cause of paediatric hearing loss . No single treatment has proved its effectiveness . There is a lack of evidence -based medicine studies in the area of homeopathy . METHOD A prospect i ve r and omized , double blinded interventional placebo control study was conducted . Patients , from 2 months to 12 years , with OME diagnosed by pneumatic otoscopy ( PNO ) and tympanometry , were r and omized into two groups . Both groups received aerosol therapy ( mucolytics and corticosteroids ) . In addition , the experimental group ( EG ) received homeopathy ( Agraphis nutans 5CH , Thuya Occidentalis 5CH , Kalium muriaticum 9CH and Arsenicum iodatum ) , and the placebo group ( PG ) placebo , both of them for 3 months . Patients were evaluated by PNO examination and tympanometry at baseline , at 45 and 90 days . RESULTS 97 patients were enrolled . In the EG , 61.9 % of individuals were cured ( PNO went from negative in the 1st visit to positive in the 3rd visit ) compared with 56.8 % of patients treated with placebo . 4.8 % of patients in the EG suffered a recurrence ( positive PNO in the 2nd visit changed to negative in the 3rd visit ) while 11.4 % did in the PG . No significant difference was found . Adverse events were distributed similarly , except in the case of upper respiratory tract infections , which were less frequent in EG ( 3 vs. 13 , p : 0.009 ) . CONCLUSION The homeopathic scheme used as adjuvant treatment can not be cl aim ed to be an effective treatment in children with OME . TRIAL REGISTRATION EUDRACT number : 2011 - 006086 - 17 , PROTOCOL code : 55005646 OBJECTIVE In clinical trials , patients become available for treatment sequentially . Especially in trials with a small number of patients , loss of power may become an important issue , if treatments are not allocated equally or if prognostic factors differ between the treatment groups . We present a new algorithm for sequential allocation of two treatments in small clinical trials , which is concerned with the reduction of both selection bias and imbalance . STUDY DESIGN AND SETTING With the algorithm , an element of chance is added to the treatment as allocated by minimization . The amount of chance depends on the actual amount of imbalance of treatment allocations of the patients already enrolled . The sensitivity to imbalance may be tuned . We performed trial simulations with different numbers of patients and prognostic factors , in which we quantified loss of power and selection bias . RESULTS With our method , selection bias is smaller than with minimization , and loss of power is lower than with pure r and omization or treatment allocation according to a biased coin principle . CONCLUSION Our method combines the conflicting aims of reduction of bias by predictability and reduction of loss of power , as a result of imbalance . The method may be of use in small trials AIMS Homeopathic medicines are frequently purchased over the counter ( OTC ) . Respiratory complaints are the most frequent reason for such purchases . Children with upper respiratory tract infection ( URTI ) are frequent users of homeopathy . This study investigates the effect of self treatment with one of three self selected ultramolecular homeopathic medicines for the prevention of childhood URTI . METHODS A double-blind r and omized parallel group placebo controlled trial was carried out in 251 children below the age of 10 years , recruited by post from those previously diagnosed with URTI when attending a casualty department . The children were r and omly assigned to receive either placebo or ultramolecular homeopathic medicines in C-30 potency ( diluted 10(-60 ) ) administered twice weekly for 12 weeks . Parents chose the medicine based on simplified constitutional indications for the three medicines most frequently prescribed by Norwegian homeopaths for this group of patients . The main outcome measure relates to the prevention of new episodes of URTI measured with median total symptom score over 12 weeks . RESULTS There was no difference in the predefined primary outcome between the two groups ( P = 0.733 ) . Median URTI scores over 12 weeks in the homeopathic medicine group were 26.0 ( 95 % confidence interval ( CI ) 16.3 , 43.7 ) and for placebo 25.0 ( 95 % CI 14.2 , 38.4 ) . There was no statistical difference between the two groups in median number of days with URTI symptoms or in the use of conventional medication/care . CONCLUSIONS In this study there was no effect over placebo for self treatment with one of three self selected , ultramolecular homeopathic medicines in preventing childhood URTI . This can be due to the lack of effect of the highly diluted homeopathic medicines or the process of selection and type of medicines OBJECTIVE To investigate whether individualised treatment by homeopaths is effective in preventing childhood upper respiratory tract infection ( URTI ) . METHODS Open , pragmatic , r and omised parallel-group trial with waiting-list group as control . One hundred and sixty-nine children below the age of 10 years , recruited by post from children previously diagnosed with URTI , were r and omly assigned to receive either pragmatic homeopathic care from one of five homeopaths for 12 weeks or to a waiting-list control using self-selected , conventional health care . RESULT There was a significant difference in median total symptom score in favour of homeopathic care ( 24 points ) compared to the control group ( 44 points ) ( p = 0.026 ) . The difference in the median number of days with URTI symptoms was statistically significant with 8 days in the homeopathic group and 13 days in the control group ( p = 0.006 ) . There was no statistical difference in the use of conventional medication or care between the two groups . CONCLUSION In this study , there was a clinical ly relevant effect of individualised homeopathic care in the prevention of URTI in children Background Homeopathic medicine is a branch of integrative medicine that has been gaining increasing popularity . However , its clinical application remains controversial . To improve the underst and ing of homeopathy , observational studies -which monitor the effects of homeopathy in real-life clinical setting s-are a helpful adjunct to r and omized controlled trials . The goal of this controlled observational study was to investigate the role of the homeopathic medicine in preventing respiratory tract infections ( RTIs ) . Methods This retrospective analysis of patients ’ medical records focused on a single centre from 2002 to 2011 , and examined 459 patients , out of whom 248 were treated with homeopathic medicine ( specific extract of duck liver and heart ) and 211 were not treated . All patients were followed-up for at least 1 year , and up to a maximum of 10 years . Results A significant reduction in the frequency of onset of RTIs was found in both the homeopathic medicine and untreated groups . The reduction in the mean number of RTI episodes during the period of observation vs. the year before inclusion in the study was significantly greater in the homeopathic-treated group than in untreated patients ( -4.76 ± 1.45 vs. -3.36 ± 1.30 ; p = 0.001 ) . The beneficial effect of the homeopathic medicine was not significantly related to gender , age , smoking habits or concomitant respiratory diseases when compared to the effect observed in untreated patients . Conclusion These results suggest that homeopathic medicine may have a positive effect in preventing RTIs . However , r and omized studies are needed before any firm conclusion can be reached BACKGROUND AND OBJECTIVE This study investigates ( 1 ) whether treatment by homeopaths is more efficacious than self-selected conventional health care and ( 2 ) whether self-treatment with self-selected homeopathic medicines is more efficacious than placebo in preventing childhood upper respiratory tract infections ( URTIs ) . DESIGN A four-arm r and omized controlled trial involving two independent investigations , one open and pragmatic ( evaluating the effect of treatment by homeopaths including homeopathic medicines ) and one double-blinded ( evaluating the effect of self-treatment with homeopathic medicine ) . PATIENTS The planned sample size is 420 children below the age of 10 , recruited by a postal invitation to all children diagnosed with URTIs when attending a casualty department in Trondheim , Norway . INTERVENTIONS The children are r and omly assigned to receive either ( 1 ) self-selected homeopathic medicine or placebo ( 270 patients ) , ( 2 ) treatment by one of four different homeopaths who could prescribe any homeopathic medicine ( 75 patients ) , or ( 3 ) waiting list control using self-selected conventional health care ( 75 patients ) . MAIN OUTCOME MEASURE Total URTI symptom scores from patients ' diary over 12 weeks . PLAN : The results of these two studies ( available at the end of 2004 ) have the potential to provide information about the efficacy of treatment by homeopaths independently from the efficacy of homeopathic medicines in children with URTIs OBJECTIVES The aim of this study was to explore the context ual effect of homeopathic consultation by investigating the effect of homeopathic care compared to self-treatment with self prescribed homeopathic medicine in the prevention of childhood upper respiratory tract infections ( URTI ) . METHODS R and omised parallel group trial with 208 children below the age of 10 . The children were r and omly assigned to receive either homeopathic care ( HC : individual homeopathic consultations with any homeopathic medicine in any potency being prescribed ) or one of three self-prescribed homeopathic medicines ( SPH ) in C-30 administered twice weekly , for 12 weeks . RESULTS There were no significant differences in clinical effects between SPH and HC for primary outcomes . Mean URTI scores over 12 weeks were 39.0 in the HC group and 43.9 in the SPH group ( p=0.782 , difference -5.0 points ( 95 % C.I. ; -20.5 to + 10.5 ) ) . The mean number of days where the parents rated their child as ' ill with URTI ' was 10.0 in the HC group and 13.7 in the SPH group ( p=0.394 ) . There was a trend in favour of HC for other outcomes . CONCLUSIONS In this innovative and exploratory study , there was no evidence for a clinical ly relevant effect of homeopathic care vs. a homeopathic medicine given by the child 's parents and based on a pre-agreed homeopathic treatment protocol The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
13,906 | 26,297,099 | Among them , genetic testing in the early detection of LQTS was cost-effective compared with no testing in symptomatic cases and not cost-effective when compared with watchful waiting in asymptomatic first-degree relatives of patients with established LQTS although it reached cost-effectiveness in higher risk subgroups , whereas ECG testing in neonates was highly cost-effective when compared with any screening strategy .
LQTS profiling and patients ' stratification have the potential to improve the disease management . | BACKGROUND Recent improvements in the identification of the genetic basis of long QT syndrome ( LQTS ) have led to significant changes in the diagnosis and management of this life-threatening condition .
Genetic and electrocardiogram ( ECG ) tests are the most relevant examples among testing strategies for LQTS , yet their cost-effectiveness remains controversial .
OBJECTIVE The aim of this work was to review the available evidence on the cost-effectiveness of genetic and ECG testing strategies for the diagnosis of LQTS . | Background —The congenital long-QT syndrome ( LQTS ) is caused by mutations on several genes , all of which encode cardiac ion channels . The progressive underst and ing of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies . Preliminary observations suggested that the conditions ( “ triggers ” ) associated with cardiac events may in large part be gene specific . Methods and Results —We identified 670 LQTS patients of known genotype ( LQT1 , n=371 ; LQT2 , n=234 ; LQT3 , n=65 ) who had symptoms ( syncope , cardiac arrest , sudden death ) and examined whether 3 specific triggers ( exercise , emotion , and sleep/rest without arousal ) differed according to genotype . LQT1 patients experienced the majority of their events ( 62 % ) during exercise , and only 3 % occurred during rest/sleep . These percentages were almost reversed among LQT2 and LQT3 patients , who were less likely to have events during exercise ( 13 % ) and more likely to have events during rest/sleep ( 29 % and 39 % ) . Lethal and nonlethal events followed the same pattern . Corrected QT interval did not differ among LQT1 , LQT2 , and LQT3 patients ( 498 , 497 , and 506 ms , respectively ) . The percent of patients who were free of recurrence with & bgr;-blocker therapy was higher and the death rate was lower among LQT1 patients ( 81 % and 4 % , respectively ) than among LQT2 ( 59 % and 4 % , respectively ) and LQT3 ( 50 % and 17 % , respectively ) patients . Conclusions —Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner . These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches BACKGROUND beta-blockers are routinely prescribed in congenital long-QT syndrome ( LQTS ) , but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated . METHODS AND RESULTS The study population comprised 869 LQTS patients treated with beta-blockers . Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy , and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers . After initiation of beta-blockers , there was a significant ( P<0.001 ) reduction in the rate of cardiac events in prob and s ( 0.97+/-1.42 to 0.31+/-0.86 events per year ) and in affected family members ( 0 . 26+/-0.84 to 0.15+/-0.69 events per year ) during 5-year matched periods . On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers ( n=598 ) had a hazard ratio of 5.8 ( 95 % CI , 3.7 to 9.1 ) for recurrent cardiac events ( syncope , aborted cardiac arrest , or death ) during beta-blocker therapy compared with asymptomatic patients ; 32 % of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers . Patients with a history of aborted cardiac arrest before starting beta-blockers ( n=113 ) had a hazard ratio of 12.9 ( 95 % CI , 4.7 to 35.5 ) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients ; 14 % of these patients will have another arrest ( aborted or fatal ) within 5 years on beta-blockers . CONCLUSIONS beta-blockers are associated with a significant reduction in cardiac events in LQTS patients . However , syncope , aborted cardiac arrest , and LQTS-related death continue to occur while patients are on prescribed beta-blockers , particularly in those who were symptomatic before starting this therapy BACKGROUND Eight r and omized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator ( ICD ) improves survival among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia . We assessed the cost-effectiveness of the ICD in the population s represented in these primary -prevention trials . METHODS We developed a Markov model of the cost , quality of life , survival , and incremental cost-effectiveness of the prophylactic implantation of an ICD , as compared with control therapy , among patients with survival and mortality rates similar to those in each of the clinical trials . We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials . RESULTS Use of the ICD increased lifetime costs in every trial . Two trials -- the Coronary Artery Bypass Graft ( CABG ) Patch Trial and the Defibrillator in Acute Myocardial Infa rct ion Trial (DINAMIT)--found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy . For the other six trials -- the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) I , MADIT II , the Multicenter Unsustained Tachycardia Trial ( MUSTT ) , the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) trial , the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) trial , and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)--the use of an ICD was projected to add between 1.01 and 2.99 quality -adjusted life-years ( QALY ) and between 68,300 dollars and 101,500 dollars in cost . Using base-case assumptions , we found that the cost-effectiveness of the ICD as compared with control therapy in these six population s ranged from 34,000 dollars to 70,200 dollars per QALY gained . Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years . CONCLUSIONS Prophylactic implantation of an ICD has a cost-effectiveness ratio below 100,000 dollars per QALY gained in population s in which a significant device-related reduction in mortality has been demonstrated INTRODUCTION Implantable cardioverter defibrillators ( ICDs ) are increasingly being used in high-risk long QT syndrome ( LQTS ) patients , but there are limited data regarding clinical experience with this therapeutic modality . The aim of this study is to describe the clinical characteristics of 125 LQTS patients treated with ICDs compared with LQTS patients having similar risk indications who were not treated with ICDs . Among 125 LQTS patients with ICDs , there were 54 cardiac arrest survivors , 19 patients who had ICDs implanted due to recurrent syncope despite beta-blocker therapy , and 52 patients with ICDs implanted due to other reasons , including syncope and LQTS-related sudden death in a close family member . Patients with cardiac arrest and those with recurrent syncope despite beta-blocker therapy ( n = 73 ) were compared to 161 LQTS patients who had similar indications ( 89 cardiac arrest and 72 recurrent syncope despite beta-blocker therapy ) but did not receive ICDs . Total mortality was the endpoint of the analysis . There was 1 ( 1.3 % ) death in 73 ICD patients followed an average of 3 years , whereas there were 26 deaths ( 16 % ) in non-ICD patients during mean 8-year follow-up ( P = 0.07 from log rank test from Kaplan-Meier curves ) . CONCLUSION ICDs provide an important therapeutic option to prevent sudden arrhythmic death in high-risk LQTS patients . A long-term prospect i ve study is needed to determine the benefit of this therapeutic modality in LQTS patients Background The Long QT Syndrome ( LQTS ) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to veiltricular tachyarrhythmic syncope and sudden death . We prospect ively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS ( QTc > 0.44 sec½ ) . Methods and Results The first member of a family to be identified with LQTS , the prob and , was usually brought to medical attention because of a syncopal episode during childhood or teenage years . Prob and s ( n = 328 ) were younger at first contact ( age 21 ± 15 years ) , more likely to be female ( 69%o ) , and had a higher frequency of preenroilment syncope or cardiac arrest with resuscitation ( 80 % ) , congenital deafness ( 7 % ) , a resting heart rate less than 60 beats/min ( 31 % ) , QTc ≥ 0.50 sec½ ( 52 % ) , and a history of ventricular tachyarrhythmia ( 47 % ) than other affected ( n = 688 ) and unaffected ( n = 1,004 ) family members . Arrhythmogenic syncope often occurred in association with acute physical , emotional , or auditory arousal . The syncopal episodes were frequently misinterpreted as a seizure disorder . By age 12 years , 50 % of the prob and s had experienced at least one syncopal episode or death . The rates of postenrollment syncope ( one or more episodes ) and probable LQTS-related death ( before age 50 years ) for prob and s ( n = 235 ; average follow-up 54 months per patient ) were 5.0 % per year and 0.9 % per year , respectively ; these event rates were considerably higher than those observed among affected and unaffected family members . Conclusions Among 232 prob and s and 1,264 family members with prospect i ve follow-up , three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years , whichever occurred first ( Cox hazard ratio ; 95 % confidence limits ) : 1 ) QTc ( 1.052 ; 1.017 , 1.088 ) , 2 ) history of cardiac event ( 3.1 ; 1.3 , 7.2 ) , and 3 ) heart rate ( 1.017 ; 1.004 , 1.031 ) . The findings from this prospect i ve longitudinal study highlight the clinical features , risk factors , and course of LQTS AIMS To evaluate the effect of beta-blockers in children with long QT syndrome ( LQTS ) we review ed the outcome of 122 patients ( pts ) . METHODS LQTS was diagnosed in 24 neonates and in 98 pts aged 0.5 - 15 years . Diagnosis was made because of syncope in 51 pts , bradycardia in 10 neonates and family history in 61 pts . The longest QTc ranged from 400 to 700 ms . Thirteen pts had 2:1 atrioventricular block and /or ventricular arrhythmias . Screening for mutations was performed in 118 pts . All children were treated with beta-blockers , annually checked by exercise testing and /or 24 h ECG monitoring . RESULTS Four pts died . Survivors were followed-up for 1 - 18 years ( 7.5 + /- 5.3 years ) . Five neonates and 3 older pts received a prophylactic pacemaker ( 1 death ) so that only 111/122 pts survived and were followed-up with beta-blockers alone . None of them died and five experienced a non-fatal cardiac event . There was no cardiac event among pts who were diagnosed because of familial history and among symptomatic KCNQ1 pts who were effectively treated with beta-blockers . CONCLUSION The outcome of children with LQTS under effective beta-blockers is favourable . Persisting arrhythmia or symptoms despite beta-blockers should aim at identifying other genotypes than KCNQ1 |
13,907 | 18,559,129 | RESULTS Parental modelling and parental intake were consistently and positively associated with children 's fruit and fruit , juice and vegetable ( FJV ) consumption .
There were also positive associations between home availability , family rules and parental encouragement and children 's fruit and vegetable consumption .
Parental intake was positively associated with adolescents ' fruit and vegetable consumption .
There were also positive associations between parental occupational status and adolescent fruit consumption and between parental education and adolescents ' FJV consumption . | OBJECTIVES To review associations between the family environment and young people 's fruit and vegetable consumption . | Background Fruit and vegetable consumption is traditionally low in Icel and . The results of the Pro Children cross-Europe survey showed that the consumption was lowest among children in Icel and . The aim of this study was to identify determinants of fruit and vegetable intake among 11-year-old schoolchildren in Icel and . Methods A cross-sectional survey was performed in Icel and in the autumn of 2003 as a part of the Pro Children cross-Europe survey . The survey was design ed to provide information on actual consumption levels of vegetables and fruits by 11-year-old school children and to assess potential determinants of consumption patterns . A total of 1235 Icel and ic children ( 89 % ) from 32 r and omly chosen schools participated . Hierarchical regression analyses were performed to determine the explained variance of the children 's fruit and vegetable intake . In these analyses socio-demographic background variables were entered as a first block , perceived physical-environmental variables as a second block , perceived socio-environmental variables as a third block and personal variables as a fourth block . Results 64 % of the children ate fruit less than once a day , and 61 % ate vegetables less than once a day . Respectively , 31 % and 39 % of the variance in children 's fruit and vegetable intake was explained by the determinants studied . About 7 % and 13 % of the variance in fruit and vegetable intake was explained by the perceived physical-environmental determinants , mainly by availability at home . About 18 % and 16 % of the variance in fruit and vegetable intake was explained by the personal determinants . For both fruit and vegetable intake , the significant personal determinants were preferences , liking , knowledge of recommendations and self-efficacy . Conclusion Interventions to increase fruit and vegetable intake among children should aim at both environmental factors such as greater availability of fruit and vegetables , and personal factors as self-efficacy and knowledge levels concerning nutrition Study objective : To examine associations between food and nutrient intake , measured in childhood , and adult cancer in a cohort with over 60 years follow up . Design and setting : The study is based on the Boyd Orr cohort . Intake of fruit and vegetables , energy , vitamins C and E , carotene , and retinol was assessed from seven day household food inventories carried out during a study of family diet and health in 16 rural and urban areas of Engl and and Scotl and in 1937–39 . Participants : 4999 men and women , from largely working class background s , who had been children in the households participating in the pre-war survey . Analyses are based on 3878 traced subjects with full data on diet and social circumstances . Main results : Over the follow up period there were 483 incident malignant neoplasms . Increased childhood fruit intake was associated with reduced risk of incident cancer . In fully adjusted logistic regression models , odds ratios ( 95 % confidence intervals ) with increasing quartiles of fruit consumption were 1.0 ( reference ) , 0.66 ( 0.48 to 0.90 ) , 0.70 ( 0.51 to 0.97 ) , 0.62 ( 0.43 to 0.90 ) ; p value for linear trend=0.02 . The association was weaker for cancer mortality . There was no clear pattern of association between the other dietary factors and total cancer risk . Conclusions : Childhood fruit consumption may have a long term protective effect on cancer risk in adults . Further prospect i ve studies , with individual measures of diet are required to further eluci date these relations OBJECTIVE Guided by theory , this study explored cross-sectional differences in factors influencing adolescent eating behaviour including gender and socio-economic status ( SES ) , and subsequently tested the longitudinal predictive power of the models . DESIGN / SETTING /SUBJECTS Data were collected by question naires in a longitudinal study of adolescents ( age 13 years at baseline ) and their parents from Hordal and County , Norway . Association of personal and environmental variables ( family , friends , school/society ) with the consumption of fruit and vegetables ( FV ) and selected sources of fat and of sugar were assessed at age 15 The final cross-sectional models were subsequently employed in groups stratified by gender/SES and to predict consumption at age 21 RESULTS The model explained more of the variation in the sugar score ( 21 % ) and the FV score ( 13.5 % ) than in the fat score ( 5 % ) . SES was associated with both the sugar and FV scores . The strongest associations with the sugar score and FV were for antisocial behaviour and evaluation of own diet , respectively . The former association was significant in all gender/SES groups , whereas the latter association was only significant in the low SES groups . For all three types of food , the strongest significant predictors in the longitudinal models were frequency of consumption at age 15 . CONCLUSION The model 's ability to explain variation in eating behaviours differed by food type , and possibly by gender/SES , but previous eating behaviour was an important predictor for all three foods . Prospect i ve studies should carefully operationalize theoretical constructs when further investigating the influences of and interrelationships between these factors and gender/SES on the development of eating behaviours Objective : The present study aim ed at investigating the influence of food availability , rules and television viewing habits on eating behaviours in adolescents . Design : Cross-sectional study . Setting : Four r and omly selected middle schools . Subjects : A sample of 534 seventh and eighth grade rs . Interventions : Vali date d question naires were used to measure the family environment and fat , soft drink and fruit consumption . Hierarchical regression analyses on fat , soft drink and fruit consumption , with demographic and psychosocial variables entered as the first and environmental factors as the second block were conducted in boys and girls . Results : Boys with more unhealthy products available at home consumed more fat ( P⩽0.001 , 95 % CI : 8.2–29.4 ) and more soft drinks ( P⩽0.01 , 95 % CI : 0.2–1.4 ) . Boys who reported better television viewing habits ate more fruit ( P⩽0.001 , 95 % CI : −1.7 to −0.5 ) . Girls who reported better television viewing habits consumed less fat ( P⩽0.01 , 95 % CI : 1.4–9.0 ) and more fruit ( P⩽0.05 , 95 % CI : −1.0 to −0.1 ) . Girls who reported higher availability of healthy products at home ( P⩽0.05 , 95 % CI : 0.3–3.1 ) and more food rules ( P⩽0.001 , 95 % CI : −1.8 to −0.5 ) , consumed more fruit . Environmental factors were poor predictors of soft drink consumption among girls . Conclusion : Availability of (un)healthy food products , family food rules and TV viewing habits were related to one or more eating behaviours in boys or girls . Although home environmental factors can play an important role in influencing adolescents ’ eating behaviours , these factors were generally less predictive than demographic and psychosocial variables . Sponsorship : Ghent University and Policy Research Centre Sport , Physical Activity and Health funded by the Flemish Government Background The first aim of the present study was to investigate differences in correlates of vegetable intake between the normal weight and the overweight boys in the Pro Children Cross Sectional Study . The second aim was to explore whether the association between vegetable intake and potential correlates is different in overweight boys compared with normal weight boys . Methods R and om sample s of mainly 11-year old children were recruited in 9 European countries . The total sample size consisted of 3960 boys ( 16.5 % overweight ) . A vali date d self-report question naire was used to measure vegetable intake , and personal , social and environmental factors related to vegetable intake in the classroom . Weight and height were reported by the parents of the children in parents ' question naires . Results Regression analyses explained 23 % to 28 % of the variance in vegetable intake by potential correlates . Liking , self-efficacy and bringing vegetables to school were related to intake in both normal weight and overweight boys ( β's>0.10 ) . Active parental encouragement and availability at home was only related to intake in overweight boys ( β's>0.10 ) , whereas knowledge about recommendations was only related to vegetable consumption in normal weight boys ( β>0.10 ) Conclusion Intervention strategies to increase vegetable intake should focus on increase in liking and preferences , increase in self-efficacy , and increase in bringing vegetables to school in both normal weight and overweight boys . Further research should investigate whether advising parents of overweight boys to encourage their child to eat vegetables every day , to insist as far as possible that their child eats vegetables regularly and to make vegetables easily available at home is effective in changing vegetable intake OBJECTIVE This paper identifies the anthropometric , parental , and psychosocial characteristics and meal practice s ( e.g. , breakfast skipping and number of meals and snacks consumed ) associated with consumption of total energy , percent energy from fat , fruit , 100 % fruit juice , vegetables , sweetened beverages , and water among 8- to 10-year-old African-American girls . RESEARCH METHODS AND PROCEDURES This study included 114 8- to 10-year-old African-American girls and a parent or primary caregiver . Girls and a parent or primary caregiver completed several dietary question naires . Two 24-hour dietary recalls were conducted with each girl . Height and weight were measured . Separate hierarchical regression analyses were conducted for each dependent dietary variable ; potential field center differences were examined . RESULTS The number of meals and snacks consumed was correlated with energy intake . Lower BMI was related to higher vegetable consumption , and the number of snacks consumed was positively related to sweetened beverage consumption . Greater low-fat food preparation practice s reported by parents were related to lower consumption of fat as a percentage of total energy . DISCUSSION Dietary behavior differed across geographic areas . Low-fat food preparation practice s in the home seemed to be an important influence on the percentage of energy consumed from fat . Greater vegetable consumption was associated with lower BMI . Interventions to prevent excessive weight gain in African-American girls should encourage low-fat food preparation in the home and greater consumption of vegetables OBJECTIVE To determine factors associated with the consumption of fruit and vegetables among 11-year-old schoolchildren in Belgium-Fl and ers and the Netherl and s. DESIGN In total , 2468 school children from 98 r and omly selected schools participated in a cross-sectional survey . VARIABLES MEASURED Frequency of fruit and vegetable intake and potential personal , social and environmental correlates were measured by means of self-administered , school-based , written question naires . ANALYSIS Hierarchical multiple regression analyses were conducted to assess potential correlates of schoolchildren 's fruit and vegetable consumption . Separate analyses were conducted for boys and girls . RESULTS Bringing fruit to school , modeling behavior of parents and friends , parents dem and ing that their child eat fruit , knowledge about recommended intake levels , liking fruit , and self-efficacy to eat fruit were the strongest correlates of fruit intake . For vegetables , gender , parental dem and , parents facilitating the consumption of vegetables by cutting them for their child , modeling behavior of parents and friends , and preferences for vegetables emerged as strongest correlates . No substantial differences in significant correlates were found according to gender . The percentage of explained variance was 33.7 % for fruit and 28.4 % for vegetable intake . CONCLUSIONS Interventions need to be focused on personal ( taste preferences ) , social ( parental influences ) , and environmental factors ( availability ) OBJECTIVE To examine socio-demographic correlates of dietary habits at 15 and 18 years . DESIGN First and second sweeps of a longitudinal survey , based on a two-stage stratified clustered r and om sample . SETTING Central Clydeside Conurbation , in the West of Scotl and . SUBJECTS A r and om sample of 1682 households containing 15-year-olds was approached by Strathclyde Regional Council , 70 % of whom agreed to have their names passed on to the MRC . 1009 ( 86 % ) of this target sample were interviewed at baseline . 908 ( 90 % ) were re-interviewed at age 18 . Analyses are restricted to respondents who took part in both data collection sweeps . MEASURES Questions on meal patterns and food choices were included in the interviews : self-complete question naires included a dietary inventory . Social class was measured by reference to the head of household at baseline : information on own labour market position and place of residence was obtained at 18 . RESULTS At 18 there was clear differentiation in food choices and meal patterns according to sex and both parental social class and own current labour market position . Controlling for class , dietary habits at 15 were independently related to future labour market position . Overall changes in eating habits between 15 and 18 were slight , though females were more likely to have increased consumption of foods consistent with current recommendations , while the un/non-employed reduced their consumption of a midday meal . CONCLUSIONS Dietary habits are established in mid-teens and closely associated with lifestyle , facts which need to be taken into consideration in design ing effective nutrition education programmes OBJECTIVES To examine the food patterns and diet quality of elementary schoolchildren in New York State ( outside of New York City ) and to determine sociodemographic characteristics correlated with diet quality . DESIGN A nonquantitative 24-hour recall administered to students and a brief question naire completed by parents . SAMPLE 1,797 second and fifth grade rs ( 51 % of those asked ) in 51 r and omly selected schools ( 46 % of those asked ) in New York State outside of New York City . STATISTICAL ANALYSES Multiple regression analyses , chi 2 , and t tests . RESULTS On the day they were surveyed , 40 % of students did not eat vegetables , except for potatoes or tomato sauce ; 20 % did not eat fruit ; 36 % ate at least four different types of snack foods , and 16 % of fifth grade rs did not eat breakfast . Children who ate a school lunch ate significantly more dairy foods and fruits and vegetables , and fewer snack-foods than those who brought lunch from home . Fifth grade rs ate significantly more snack foods and were more likely to skip breakfast than second grade rs ; boys had lower food-group pattern scores than girls ; children of lower socioeconomic status had less diverse diets but ate less snack foods than children of higher socioeconomic status ; children with single parents were more likely to skip breakfast and to eat fewer vegetables than those with two parents ; and children with mothers employed outside the home had less diverse diets than those with mothers at home . APPLICATIONS/ CONCLUSIONS The findings indicate that nutrition interventions are clearly needed for this age group and that targeted messages should be based on sociodemographic characteristics Objective : To assess nutrient intakes relevant in the prevention of cardiovascular diseases ( CVD ) among young adults in Finl and and to find past and present determinants of quality of diet . Design : Prospect i ve study , 21 years of follow-up . Setting : The Cardiovascular Risk in Young Finns Study , Finl and .Subjects : At baseline in 1980 : 3569 children aged 3–18 y participated ( 83 % of those invited ) , and every second of them ( 1780 ) were selected to the dietary study . At follow-ups in 1986 and 2001 : 1200 and 1037 of the original sample , respectively , participated . Methods : Food consumption was assessed using 48-h dietary recall . Intakes in 2001 were compared with those obtained in 1980 and 1986 . Nutrients selected for further examination were those implicated in the risk of CVD : saturated , monounsaturated , polyunsaturated and n-3 fatty acids , fibre and salt . An index describing the quality of adulthood diet was constructed . Multivariate logistic regression was used to identify independent childhood and adulthood determinants of the quality index . Results : The average intakes showed substantial changes since 1980 . Intakes of fat and saturated fat had decreased , while the consumption of vegetables and fruit had increased . However , a great disparity was present between the recommended levels and actual intakes for many of the nutrients , particularly salt , saturated fat and fibre . Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of the cardiovascular quality of the adult diet . Socio-demographic factors , including education of the subject and their parents , had no significant associations with diet . Conclusions : While intakes of energy and nutrients have changed favourably in Finnish young adults between 1980 and 2001 with regard to the risk of CVD , they are still far from recommended levels . Childhood diet is a significant determinant of adult diet even after 21 y . Sponsorship : This study was supported by the Academy of Finl and ( grant 77841 ) and Juho Vainio Foundation Previous research has demonstrated that family members ' eating habits are similar . We hypothesized that family members ' eating habits would be predicted by the eating habits of the person who prepares the majority of the family 's meals and the number of meals the family shares . Participants were 282 members of religious organizations who identified themselves as family food preparers ( FFPs ) , and provided information about their own and their family members ' eating habits . Results revealed that FFP fruit and vegetable intake predicted the fruit and vegetable intake of spouses , children , and adolescents ( p<0.01 ) , and that FFP consumption of high-fat foods predicted the consumption of high-fat foods of spouses and children ( p<0.01 ) . Child fruit and vegetable consumption was also influenced by shared meals : the more meals the child shared with the FFP , the stronger the relationship of FFP fruit and vegetable intake with child fruit and vegetable intake ( p<0.05 ) . These findings indicate that dietary interventions targeting the FFP may benefit other family members |
13,908 | 18,978,605 | After critically review ing the literature for the impact of CT on high-level runners , we conclude that resistance training likely has a positive effect on endurance running performance or RE . | The current perception among highly competitive endurance runners is that concurrent resistance and endurance training ( CT ) will improve running performance despite the limited research in this area .
The purpose of this review was to search the body of scientific literature for original research addressing the effects of CT on distance running performance in highly competitive endurance runners . | To investigate the effects of simultaneous explosive-strength and endurance training on physical performance characteristics , 10 experimental ( E ) and 8 control ( C ) endurance athletes trained for 9 wk . The total training volume was kept the same in both groups , but 32 % of training in E and 3 % in C was replaced by explosive-type strength training . A 5-km time trial ( 5 K ) , running economy ( RE ) , maximal 20-m speed ( V20 m ) , and 5-jump ( 5J ) tests were measured on a track . Maximal anaerobic ( MART ) and aerobic treadmill running tests were used to determine maximal velocity in the MART ( VMART ) and maximal oxygen uptake ( VO2 max ) . The 5 K time , RE , and VMART improved ( P < 0.05 ) in E , but no changes were observed in C. V20 m and 5J increased in E ( P < 0.01 ) and decreased in C ( P < 0.05 ) . VO2 max increased in C ( P < 0.05 ) , but no changes were observed in E. In the pooled data , the changes in the 5 K velocity during 9 wk of training correlated ( P < 0.05 ) with the changes in RE [ O2 uptake ( r = -0.54 ) ] and VMART ( r = 0.55 ) . In conclusion , the present simultaneous explosive-strength and endurance training improved the 5 K time in well-trained endurance athletes without changes in their VO2 max . This improvement was due to improved neuromuscular characteristics that were transferred into improved VMART and running economy Fifteen highly trained distance runners ( & OV0312;O2max 71.1 ± 6.0 ml·min−1·kg−1 , mean ± SD ) were r and omly assigned to a plyometric training ( PLY ; n = 7 ) or control ( CON ; n = 8) group . In addition to their normal training , the PLY group undertook 3 × 30 minutes PLY sessions per week for 9 weeks . Running economy ( RE ) was assessed during 3 × 4 minute treadmill runs ( 14 , 16 , and 18 km·h−1 ) , followed by an incremental test to measure & OV0312;O2max . Muscle power characteristics were assessed on a portable , unidirectional ground reaction force plate . Compared with CON , PLY improved RE at 18 km·h−1 ( 4.1 % , p = 0.02 ) , but not at 14 or 16 km·h−1 . This was accompanied by trends for increased average power during a 5-jump plyometric test ( 15 % , p = 0.11 ) , a shorter time to reach maximal dynamic strength during a strength quality assessment test ( 14 % , p = 0.09 ) , and a lower & OV0312;O2-speed slope ( 14 % , p = 0.12 ) after 9 weeks of PLY . There were no significant differences in cardiorespiratory measures or & OV0312;O2max as a result of PLY . In a group of highly-trained distance runners , 9 weeks of PLY improved RE , with likely mechanisms residing in the muscle , or alternatively by improving running mechanics Abstract The purpose of this study was to investigate the effect of concurrent strength and endurance training on strength , endurance , endocrine status and muscle fibre properties . A total of 45 male and female subjects were r and omly assigned to one of four groups ; strength training only ( S ) , endurance training only ( E ) , concurrent strength and endurance training ( SE ) , or a control group ( C ) . Groups S and E trained 3 days a week and the SE group trained 6 days a week for 12 weeks . Tests were made before and after 6 and 12 weeks of training . There was a similar increase in maximal oxygen consumption ( V˙O2max ) in both groups E and SE ( P < 0.05 ) . Leg press and knee extension one repetition maximum ( 1 RM ) was increased in groups S and SE ( P < 0.05 ) but the gains in knee extension 1 RM were greater for group S compared to all other groups ( P < 0.05 ) . Types I and II muscle fibre area increased after 6 and 12 weeks of strength training and after 12 weeks of combined training in type II fibres only ( P < 0.05 ) . Groups SE and E had an increase in succinate dehydrogenase activity and group E had a decrease in adenosine triphosphatase after 12 weeks of training ( P < 0.05 ) . A significant increase in capillary per fibre ratio was noted after 12 weeks of training in group SE . No changes were observed in testosterone , human growth hormone or sex hormone binding globulin concentrations for any group but there was a greater urinary cortisol concentration in the women of group SE and decrease in the men of group E after 12 weeks of training ( P < 0.05 ) . These findings would support the contention that combined strength and endurance training can suppress some of the adaptations to strength training and augment some aspects of capillarization in skeletal muscle The purpose of this study was to investigate effects of concurrent strength and endurance training ( SE ) ( 2 plus 2 days a week ) versus strength training only ( S ) ( 2 days a week ) in men [ SE : n=11 ; 38 ( 5 ) years , S : n=16 ; 37 ( 5 ) years ] over a training period of 21 weeks . The resistance training program addressed both maximal and explosive strength components . EMG , maximal isometric force , 1 RM strength , and rate of force development ( RFD ) of the leg extensors , muscle cross-sectional area ( CSA ) of the quadriceps femoris ( QF ) throughout the lengths of 4/15–12/15 ( Lf ) of the femur , muscle fibre proportion and areas of types I , IIa , and IIb of the vastus lateralis ( VL ) , and maximal oxygen uptake ( V̇O2max ) were evaluated . No changes occurred in strength during the 1-week control period , while after the 21-week training period increases of 21 % ( p<0.001 ) and 22 % ( p<0.001 ) , and of 22 % ( p<0.001 ) and 21 % ( p<0.001 ) took place in the 1RM load and maximal isometric force in S and SE , respectively . Increases of 26 % ( p<0.05 ) and 29 % ( p<0.001 ) occurred in the maximum iEMG of the VL in S and SE , respectively . The CSA of the QF increased throughout the length of the QF ( from 4/15 to 12/15 Lf ) both in S ( p<0.05–0.001 ) and SE ( p<0.01–0.001 ) . The mean fibre areas of types I , IIa and IIb increased after the training both in S ( p<0.05 and 0.01 ) and SE ( p<0.05 and p<0.01 ) . S showed an increase in RFD ( p<0.01 ) , while no change occurred in SE . The average iEMG of the VL during the first 500 ms of the rapid isometric action increased ( p<0.05–0.001 ) only in S. V̇O2max increased by 18.5 % ( p<0.001 ) in SE . The present data do not support the concept of the universal nature of the interference effect in strength development and muscle hypertrophy when strength training is performed concurrently with endurance training , and the training volume is diluted by a longer period of time with a low frequency of training . However , the present results suggest that even the low-frequency concurrent strength and endurance training leads to interference in explosive strength development mediated in part by the limitations of rapid voluntary neural activation of the trained muscles Abstract .Previous research has reported that plyometric training improves running economy ( RE ) and ultimately distance-running performance , although the exact mechanism by which this occurs remains unclear . This study examined whether changes in running performance result ing from plyometric training were related to alterations in lower leg musculotendinous stiffness ( MTS ) . Seventeen male runners were pre- and post-tested for lower leg MTS , maximum isometric force , rate of force development , 5-bound distance test ( 5BT ) , counter movement jump ( CMJ ) height , RE , V˙O2max , lactate threshold ( Thla ) , and 3-km time . Subjects were r and omly split into an experimental ( E ) group which completed 6 weeks of plyometric training in conjunction with their normal running training , and a control ( C ) group which trained as normal . Following the training period , the E group significantly improved 3-km performance ( 2.7 % ) and RE at each of the tested velocities , while no changes in V˙O2max or Thla were recorded . CMJ height , 5BT , and MTS also increased significantly . No significant changes were observed in any measures for the C group . The results clearly demonstrated that a 6-week plyometric programme led to improvements in 3-km running performance . It is postulated that the increase in MTS result ed in improved RE . We speculate that the improved RE led to changes in 3-km running performance , as there were no corresponding alterations in V˙O2max or Thla The purpose of this study was to compare the physiologic effects of a program of combined running and weight training ( RUN-CWT ) with a program of circuit weight training ( CWT ) . Thirty-six females ( X age = 35.7 yr ) and 41 males ( X age = 36.1 yr ) were r and omly assigned to RUN-CWT , CWT , and control groups . The training groups participated in 12-wk programs , 3 d . wk-1 . Three circuits of 10 weight-training exercises were completed with 12 - 15 repetitions performed in 30 s at 40 % of one-repetition maximum at each station . The 30-min RUN-CWT program included 30 s of running on an indoor track following each CWT station , whereas the 22.5 min CWT program included a 15-s rest period between stations . The RUN-CWT groups had a significant ( + 17 % ) increase in VO2max ( females 30.5 - 35.7 ml . kg-1 . min-1 and males 39.7 - 46.3 ml . kg-1 . min-1 ) and strength ( females + 24 % and males + 21 % ) , and a significant decrease in body fat percentage ( females -3.2 % and males -4.1 % ) . The CWT groups also increased significantly in VO2max ( + 12 % ) and strength ( + 17 % ) and decreased in body fat ( -3.0 % ) . The controls did not change significantly in any variable . Statistically , one training program was not shown to be superior to the other ; thus , both programs of RUN-CWT and CWT were effective in improving measures of physical fitness PURPOSE It has been suggested that endurance training influences the running economy ( CR ) and the oxygen uptake ( .VO(2 ) ) kinetics in heavy exercise by accelerating the primary phase and attenuating the .VO(2 ) slow component . However , the effects of heavy weight training ( HWT ) in combination with endurance training remain unclear . The purpose of this study was to examine the influence of a concurrent HWT+endurance training on CR and the .VO(2 ) kinetics in endurance athletes . METHODS Fifteen triathletes were assigned to endurance+strength ( ES ) or endurance-only ( E ) training for 14 wk . The training program was similar , except ES performed two HWT sessions a week . Before and after the training period , the subjects performed 1 ) an incremental field running test for determination of .VO(2max ) and the velocity associated ( V(.VO2max ) ) , the second ventilatory threshold ( VT(2 ) ) ; 2 ) a 3000-m run at constant velocity , calculated to require 25 % of the difference between .VO(2max ) and VT(2 ) , to determine CR and the characteristics of the VO(2 ) kinetics ; 3 ) maximal hopping tests to determine maximal mechanical power and lower-limb stiffness ; 4 ) maximal concentric lower-limb strength measurements . RESULTS After the training period , maximal strength were increased ( P < 0.01 ) in ES but remained unchanged in E. Hopping power decreased in E ( P < 0.05 ) . After training , economy ( P < 0.05 ) and hopping power ( P < 0.001 ) were greater in ES than in E. .VO(2max ) , leg hopping stiffness and the .VO(2 ) kinetics were not significantly affected by training either in ES or E. CONCLUSION Additional HWT led to improved maximal strength and running economy with no significant effects on the .VO(2 ) kinetics pattern in heavy exercise The purpose of this research was to determine the effects of high intensity endurance training ( ET ) and resistance training ( RT ) alone and in combination on various military tasks . Thirty-five male soldiers were r and omly assigned to one of four training groups : total body resistance training plus endurance training ( RT + ET ) , upper body resistance training plus endurance training [ UB + ET ) , RT only , and ET only . Training was performed 4 days per week for 12 weeks . Testing occurred before and after the 12-week training regimen . All groups significantly improved push-up performance , whereas only the RT + ET group did not improve sit-up performance . The groups that included ET significantly decreased 2-mile run time , however , only RT + ET and UB + ET showed improved loaded 2-mile run time . Leg power increased for groups that included lower body strengthening exercises ( RT and RT + ET ) . Army Physical Fitness Test performance , loaded running , and leg power responded positively to training , however , it appears there is a high degree of specificity when concurrent training regimens are implemented The aim of this experiment was to examine the effects of maximal strength training with emphasis on neural adaptations on strength- and endurance-performance for endurance trained athletes . Nineteen male cross-country skiers about 19.7 + /- 4.0 years of age and a maximal oxygen uptake ( VO(2 max ) ) of 69.4 + /- 2.2 mL x kg(-1 ) x min(-1 ) were r and omly assigned to a training group ( n = 9 ) or a control group ( n = 10 ) . Strength training was performed , three times a week for 8 weeks , using a cable pulley simulating the movements in double poling in cross-country skiing , and consisted of three sets of six repetitions at a workload of 85 % of one repetition maximum emphasizing maximal mobilization of force in the concentric movement . One repetition maximum improved significantly from 40.3 + /- 4.5 to 44.3 + /- 4.9 kg . Time to peak force ( TPF ) was reduced by 50 and 60 % on two different submaximal workloads . Endurance performance measured as time to exhaustion ( TTE ) on a double poling ski ergometer at maximum aerobic velocity , improved from 6.49 to 10.18 min ; 20.5 % over the control group . Work economy changed significantly from 1.02 + /- 0.14 to 0.74 + /- 0.10 mL x kg(-0.67 ) x min(-1 ) . Maximal strength training with emphasis on neural adaptations improves strength , particularly rate of force development , and improves aerobic endurance performance by improved work economy This study determined whether a 6-week regimen of plyometric training would improve running economy ( i.e. , the oxygen cost of submaximal running ) . Eighteen regular but not highly trained distance runners ( age = 29 ± 7 [ mean ± SD ] years ) were r and omly assigned to experimental and control groups . All subjects continued regular running training for 6 weeks ; experimental subjects also did plyometric training . Dependent variables measured before and after the 6-week period were economy of running on a level treadmill at 3 velocities ( women : 2.23 , 2.68 , and 3.13 m-s1 ; men : 2.68 , 3.13 , and 3.58 m-s1 ) , Vo2max , and indirect indicators of ability of muscles of lower limbs to store and return elastic energy . The last were measurements during jumping tests on an inclined ( 20 ° ) sled : maximal jump height with and without countermovement and efficiencies of series of 40 sub-maximal countermovement and static jumps . The plyometric training improved economy ( p < 0.05 ) . Averaged values ( m-ml-kg“1 ) for the 3 running speeds were : ( a ) experimental subjects—5.14 ± 0.39 pretraining , 5.26 ± 0.39 posttrain-ing ; and ( b ) control subjects—5.10 ± 0.36 pretraining , 5.06 ± 0.36 posttraining . The Vo2max did not change with training . Plyometric training did not result in changes in jump height or efficiency variables that would have indicated improved ability to store and return elastic energy . We conclude that 6 weeks of plyometric training improves running economy in regular but not highly trained distance runners ; the mechanism must still be determined Thirty-five healthy men were matched and r and omly assigned to one of four training groups that performed high-intensity strength and endurance training ( C ; n = 9 ) , upper body only high-intensity strength and endurance training ( UC ; n = 9 ) , high-intensity endurance training ( E ; n = 8) , or high-intensity strength training ( ST ; n = 9 ) . The C and ST groups significantly increased one-repetition maximum strength for all exercises ( P < 0.05 ) . Only the C , UC , and E groups demonstrated significant increases in treadmill maximal oxygen consumption . The ST group showed significant increases in power output . Hormonal responses to treadmill exercise demonstrated a differential response to the different training programs , indicating that the underlying physiological milieu differed with the training program . Significant changes in muscle fiber areas were as follows : types I , IIa , and IIc increased in the ST group ; types I and IIc decreased in the E group ; type IIa increased in the C group ; and there were no changes in the UC group . Significant shifts in percentage from type IIb to type IIa were observed in all training groups , with the greatest shift in the groups in which resistance trained the thigh musculature . This investigation indicates that the combination of strength and endurance training results in an attenuation of the performance improvements and physiological adaptations typical of single-mode training BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . To determine the effects of 12 wk of strength training on lactate threshold ( LT ) and endurance performance , 18 healthy untrained males between 25 and 34 yr of age were r and omly assigned to either strength training ( N = 10 ) or control ( N = 8) groups . Despite no changes in treadmill VO2max or cycle peak VO2 , a 33 + /- 5 % increase ( P less than 0.001 ) in cycling time to exhaustion at 75 % of peak VO2 was observed following training . No significant changes in cycling time were observed in the control group . There were significant reductions in plasma lactate concentration at all relative exercise intensities ranging between 55 and 75 % of peak VO2 training . The improved endurance performance was associated with a 12 % increase in LT ( r = 0.78 , P less than 0.001 ) . The strength training program result ed in significant improvements ( P less than 0.001 ) of 31 + /- 5 % and 35 + /- 7 % in isokinetic peak torque values for leg extension and flexion , respectively , at a velocity of 30 degrees.s-1 . There were also significant increases in 1-RM values of 30 + /- 4 % ( P less than 0.001 ) for leg extension , 52 + /- 6 % ( P less than 0.001 ) for leg flexion , and 20 + /- 4 % ( P less than 0.001 ) for the bench press . These findings indicate that strength training improves cycle endurance performance independently of changes in VO2max . This improved performance appears to be related to increases in LT and leg strength |
13,909 | 24,077,813 | Conclusion Data suggest that SC treatment for SUI is safe and effective in the short term . | Purpose To systematic ally evaluate the current evidence on the safety and efficacy of stem cell therapy ( SCT ) in stress urinary incontinence ( SUI ) to allow objective comparison with existing surgical techniques . | In the last years pre clinical studies have paved the way for the use of adult muscle derived stem cells for reconstruction of the lower urinary tract . Between September 2002 and October 2004 , 42 women and 21 men suffering from urinary stress incontinence ( age 36 - 84 years ) were recruited and subsequently treated with transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies . The fibroblasts were injected into the urethral submucosa , while the myoblasts were implanted into the rhabdosphincter . In parallel , 7 men and 21 women ( age 39 - 83 years ) also diagnosed with urinary stress incontinence were treated with st and ard transurethral endoscopic injections of collagen . Patients were r and omly assigned to both groups . After a follow-up of 12 months incontinence was cured in 39 women and 11 men after injection of autologous myoblasts and fibroblasts . Mean quality of life score ( 51.38 preoperatively , 104.06 postoperatively ) , thickness of urethra and rhabdosphincter ( 2.103 mm preoperatively , 3.303 mm postoperatively ) as well as contractility of the rhabdosphincter ( 0.56 mm preoperatively , 1.462 mm postoperatively ) were improved postoperatively . Only in two patients treated with injections of collagen incontinence was cured . The present clinical results demonstrate that , in contrast to injections of collagen , urinary incontinence can be treated effectively with ultrasonography-guided injections of autologous myo- and fibroblasts Purpose : To compare short-term results of autologous pubovaginal sling and synthetic transobturator ( TOT ) SAFYRE sling in the treatment of female stress urinary incontinence ( SUI ) . Methods : Twenty women referred for surgical treatment of SUI were assigned r and omly to autologous pubovaginal sling or synthetic TOT sling . Inclusion criteria were primary treatment of SUI and urodynamic study showing SUI without detrusor overactivity . Pre- and postoperative quantification of the severity of incontinence was done by pad test and a vali date d question naire ( King ’s Health Question naire ) . Results : There were no differences in patients ’ mean age , parity , body mass index , rate of postmenopausal state , pelvic floor defects and mean Valsalva leak point pressure in the preoperative urodynamic study . Mean operating time ( 21.1 ± 3.8 vs. 69.5 ± 23.7 min ; P<0.001 ) and hospital stay ( 28.8 ± 8.4 vs. 44.4 ± 5.8 h ; P<0.001 ) was shorter in the TOT than the autologous group . The postoperative pad test ( 39.4 ± 12.5 vs. 8.4 ± 5.2 g ; P=0.01 ) and the absent in the improvement in the quality of life were significantly higher in the TOT group . Conclusion : Our initial results suggest that the synthetic TOT technique had worse effectiveness for treating female SUI compared to autologous pubovaginal sling OBJECTIVE To assess the feasibility and safety of ultrasound-guided autologous myoblast injections into the external urethral sphincter followed by electrical stimulation ( ES ) as a possible 2-step treatment for stress urinary incontinence ( SUI ) . METHODS Autologous myoblasts isolated from a biceps muscle sample were injected under transurethral ultrasound guidance into the external urethral sphincter of 38 female patients . The patients also underwent ES postoperatively to enhance cell integration . Treatment feasibility , as well as possible intraoperative and postoperative complications , was assessed 6weeks after the injections . Additionally , the effects of the myoblast injections followed by an ES cycle were compared to those of a preoperative ES cycle undergone by the same patients . RESULTS No serious adverse events or complications were noted and the procedure was well tolerated . Compared with the objective and subjective measurements collected after the preoperative ES cycle , the corresponding measurements obtained 6weeks postoperatively , after the completion of a second ES cycle , indicated considerable improvement . The results to the stress test were negative for 29 ( 78.4 % ) of the patients , 5 ( 13.5 % ) considered their SUI cured , and 29 ( 78.4 % ) reported improvement . CONCLUSION Intrasphincteric autologous myoblast injections followed by ES is minimally invasive and feasible , and safely produced promising initial results . EU Clinical Trials EudraCT No. 2009 - 012389 - 30 Clinical Trials.gov identifier : NCT01355133 Introduction and hypothesisCell therapy for stress urinary incontinence ( SUI ) management has been experienced with encouraging results . Methods We conducted an open prospect i ve study on 12 women presenting severe SUI with fixed urethra , after previous failed surgical management . Patients underwent intrasphincteric injections of autologous progenitor muscular cells isolated from a biopsy of deltoid muscle . Primary endpoint focused on safety ( measurement of Qmax variation after 3 months ) . Secondary endpoints assessed side effects and efficacy . Results No variation was diagnosed on Qmax measurements . Efficacy data show that three of 12 patients are dry at 12 months , seven other patients are improved on pad test but not on voiding diary , and two patients were slightly worsened by the procedure . Quality of life was improved in half of patients . Conclusions Cell therapy for severe multioperated cases of SUI is a mini-invasive , feasible , and safe procedure that can improve urinary condition in as a second line therapy Objective . To evaluate long-term effectiveness and safety of conservative and minimally invasive outpatient treatments for female stress urinary incontinence ( SUI ) through a review of the literature . Methods . PubMed was search ed for reports on prospect i ve clinical trials with at least 12-month follow-up of minimally invasive treatments , pelvic floor rehabilitation , or pharmacotherapy in women with SUI . Each report was examined for long-term rates of effectiveness and safety . Results . Thirty-two clinical trial reports were included . Prospect i ve long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months . Poor initial tolerability with duloxetine result ed in substantial discontinuation . Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements , generally good tolerability , and safety . Conclusions . Conservative therapy is an appropriate initial approach for female SUI , but if therapy fails , radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery OBJECTIVE This study was undertaken to compare tension-free vaginal tape ( TVT ) with colposuspension as the primary treatment for stress incontinence . STUDY DESIGN The trial was conducted in gynecology or urology departments in 14 centers in the United Kingdom and Irel and . Three hundred forty-four women with urodynamic stress incontinence were r and omly assigned to groups : 175 to TVT and 169 to colposuspension . Patients were assessed using the Short Form-36 health status question naire , the Bristol Female Lower Urinary Tract Symptoms question naire , clinical examination , and a 1-hour perineal pad test . Unpaired and paired data were analyzed with the Wilcoxon rank sum and matched pairs tests , respectively , and proportions were compared with the Fisher exact test . RESULTS When data were analyzed on an intention-to-treat basis , assuming patients with missing data to be treatment failures , 63 % of the TVT group and 51 % of the colposuspension group were objective ly cured at 2 years ( odds ratio 1.67 , 95 % CI 1.09 - 2.58 ) . CONCLUSION The TVT procedure appears to be as effective as colposuspension for the treatment of urodynamic stress incontinence at 2 years We hereby report a 1-year follow-up on eight women in the first North America trial in which stress urinary incontinence ( SUI ) was treated with muscle-derived stem cell injections . Mean and median follow-up in this group was 16.5 and 17 months ( range 3–24 months ) . Improvement in SUI was seen in five of eight women , with one achieving total continence . Onset of improvement was between 3 and 8 months after injection . Cure or improvement continued at a median of 10 months . No serious adverse events were reported To assess the maintenance of efficacy of duloxetine beyond 3 months , using data from several long‐term , open‐label studies , as the efficacy of duloxetine 40‐mg twice daily for treating women with stress urinary incontinence ( SUI ) for up to 3 months has been established in several r and omized , placebo‐controlled clinical trials |
13,910 | 24,176,100 | However , there is evidence of some convergence around a small number of high-performing instruments and identification of the components of a high- quality evaluation approach , including AUC analysis .
The upper limits ( AUC ≥ 0.85 ) of instrument-based prediction have probably been achieved and are unlikely to be exceeded using instruments alone . | BACKGROUND This review systematic ally examines the research literature published in the period 2002 - 8 on structured violence risk assessment instruments design ed for use in mental health services or the criminal justice system .
It adopted much broader inclusion criteria than previous review s in the same area in order to capture and summarise data on the widest possible range of available instruments .
OBJECTIVES To address two questions : ( 1 ) what study characteristics are associated with a risk assessment instrument score being significantly associated with a violent outcome ?
and ( 2 ) which risk assessment instruments have the highest level of predictive validity for a violent outcome ? | Background Patient aggression is a common problem in acute psychiatric wards and calls for preventive measures . The timely use of preventive measures presupposes a preceded risk assessment . The Norwegian Brøset-Violence-Checklist ( BVC ) is one of the few instruments suited for short-time prediction of violence of psychiatric in patients in routine care . Aims of our study were to improve the accuracy of the short-term prediction of violence in acute inpatient setting s by combining the Brøset-Violence-Checklist ( BVC ) with an overall subjective clinical risk- assessment and to test the application of the combined measure in daily practice . Method We conducted a prospect i ve cohort study with two sample s of newly admitted psychiatric patients for instrument development ( 219 patients ) and clinical application ( 300 patients ) . Risk of physical attacks was assessed by combining the 6-item BVC and a 6-point score derived from a Visual Analog Scale . Incidents were registered with the Staff Observation of Aggression Scale-Revised SOAS-R. Test accuracy was described as the area under the receiver operating characteristic curve ( AUCROC ) . Results The AUCROC of the new VAS-complemented BVC-version ( BVC-VAS ) was 0.95 in and 0.89 in the derivation and validation study respectively . Conclusion The BVC-VAS is an easy to use and accurate instrument for systematic short-term prediction of violent attacks in acute psychiatric wards . The inclusion of the VAS-derived data did not change the accuracy of the original BVC Positive psychotic symptoms , such as threat/"control-override " delusions or comm and hallucinations , have been related to aggression in patients with schizophrenia . However , retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior . In this study , we monitored aggressive behavior and psychopathology prospect ively and in close temporal proximity in 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial . Aggressive behavior was rated with the overt aggression scale ( OAS ) . Psychopathology was assessed using the positive and negative syndrome scale ( PANSS ) . At baseline , subjects who would be aggressive during the study had higher scores on only two PANSS items : hostility and poor impulse control . During the study PANSS positive subscale scores were significantly higher in aggressive subjects . Total PANSS scores were higher within 3 days of an aggressive incident , as were positive and general psychopathology subscale scores . However , in a smaller sub sample for whom PANSS ratings were available within 3 days before aggressive incidents , only scores on the PANSS positive subscale were significantly higher . These findings in chronic , treatment resistant in patients support the view that positive symptoms may lead to aggression Objective : This study examined the predictive validity of the German translation of the Psychopathy Checklist-Screening Version ( PCL-SV ) for negative events during the course of the prison sentence of German prisoners . Method : Using the PCL-SV , we investigated 145 offenders in a German prison at the start of their sentences . We then compared the extreme groups identified by the PCL-SV — the high and low scorers — using a prospect i ve design with respect to negative events and factors during the course of the sentences . This involved the st and ardized collection of data on both objective records of disciplinary incidents and subjective impressions from prison staff on the basis of operationalized criteria . Results : The high scorers were involved in significantly more disciplinary incidents and were also rated significantly less favourably by prison staff than the low scorers . Conclusion : Until now , the PCL has only been shown to predict recidivism following release from prison . The results of our study show that the PCL also has predictive validity for problems during the course of the sentence . It is therefore recommended that the PCL be used routinely at the start of the prison sentence to estimate the likelihood of subsequent difficulties If clinicians in forensic psychiatry want to reduce risk of reoffending in their patients , they require insight into dynamic risk factors , and evidence that these add predictive power to static risk indicators . Predictors need to be evaluated under clinical ly realistic circumstances . This study aim ed to vali date dynamic and static variables as predictors of reconviction in a naturalistic outcome study . Data on static and dynamic risk factors were collected for 151 patients discharged from Dutch forensic psychiatric hospitals . Community follow-up was prospect i ve , with a 5.5 year minimum . A prediction model was developed using Cox regression analysis . The magnitude of the predictive power of this model was estimated using receiver operating characteristic ( ROC ) analysis . The final prediction model contained four static and no dynamic predictors . The model 's ROC area under the curve was .79 ( 95 % CI .69–.89 ) . Clinical risk ratings were non-predictive . Post hoc analyses exploring the influence of subgroups of patients did not yield better models . It is concluded that a small set of static predictors yielded a good estimate of future reconvictions ; inclusion of dynamic predictors did not add predictive power OBJECTIVE Outward-directed violence and impulsivity in humans and primates has frequently been related to abnormal brain monoaminergic turnover . Self-rated aggression is likely to be clinical ly relevant , and its psychobiological basis needs investigation . SUBJECTS Sixty-six patients ( 40 women and 26 men ) with persistent depressive disorder ( PDD ) were compared with 497 control subjects from the general Swedish population . METHODS We administered the Aggression Question naire - Revised Swedish Version ( AQ-RSV ) to patients and control subjects . In patients , CSF 5-hydroxyindoleacetic acid ( 5-HIAA ) and 3-methoxy-5-hydroxyphenylglycol ( MHPG ) in CSF were analyzed . Total Aggression score and Aggression subfactors ' Physical Aggression','Verbal Aggression','Anger ' , and ' Hostility'were correlated with CSF concentrations of 5-hydroxyindoleacetic acid ( 5-HIAA ) , and 3-methoxy-5-hydroxyphenylglycol ( MHPG ) . RESULTS Overall , Hostility was positively related to CSF MHPG ( t=2.27 , p=0.015 ) . Split by sex , Hostility was related with 5-HIAA in males ( r=0.62,p=0.003 ) , and with MHPG in females ( r=0.38 , p=0.03 ) . Comparing self rated aggression with age- and sex-matched data from the general Swedish population , the most prominent deviation was increased Hostility score among PDD patients . Among patients , all aggression factors were nominally higher in women than in men , with the most pronounced sex difference in Hostility ( t=-1.89 , p=0.04 ) . CONCLUSIONS Results suggest a clinical ly meaningful sex difference in a positive relationship between hostility and serotonergic/noradrenergic turnover in PDD patients BACKGROUND A critical step for improving the prediction of on-ward violence is the identification of variables that are not only consistently associated with an increased risk of aggression but also easily evaluated during the admission interview . The goal of this prospect i ve study was to assess the predictive utility of hostility during admission interview . METHOD The sample consisted of 80 newly admitted male patients with heterogeneous DSM-IV psychiatric diagnoses recruited from the psychiatric ward of an urban public hospital . Psychiatric symptoms at admission were assessed with the Brief Psychiatric Rating Scale ( BPRS ) . Aggressive behavior during the first week of hospitalization was measured with the Modified Overt Aggression Scale . Data were collected between January and June 1998 . RESULTS In a multiple regression model , BPRS items hostility and tension-excitement emerged as significant predictors of verbal aggression , whereas thinking disturbance ( high ) and suspiciousness-uncooperativeness ( low ) emerged as significant predictors of aggression against objects . In contrast , when aggression was treated as a binary dependent variable in a logistic model , hostility during the admission interview had no utility in predicting on-ward aggressive behavior . CONCLUSION This study confirms the importance of distinguishing between different types of aggression to improve the accuracy of predictions of violence . The findings suggest that the question whether hostility is a useful short-term predictor of aggression in psychiatric in patients can not be answered conclusively . The predictive utility of hostility was relatively high for predicting verbal aggression but was negligible for predicting other types of aggressive behavior BACKGROUND Risk assessment of future violent acts is of great importance for both public protection and care planning . Structured clinical assessment s offer a method by which accurate assessment s could be achieved . AIMS To test the efficacy of the Historical , Clinical and Risk Management Scales ( HCR-20 ) structured risk assessment scheme on a large sample of male forensic psychiatric patients discharged from medium secure units in the UK . METHOD In a pseudo- prospect i ve study , 887 male patients were followed for at least 2 years . The HCR-20 was completed using only pre-discharge information , and violent and other offending behaviour post-discharge was obtained from official records . RESULTS The HCR-20 total score was a good predictor of both violent and other offences following discharge . The historical and risk sub-scales were both able to predict offences , but the clinical sub-scale did not produce significant predictions . The predictive efficacy was highest for short periods ( under 1 year ) and showed a modest fall in efficacy over longer periods ( 5 years ) . CONCLUSIONS The results provide a strong evidence base that the HCR-20 is a good predictor of both violent and non-violent offending following release from medium secure units for male forensic psychiatric patients in the UK The author investigated the acute effects of alcohol intoxication on anger experience and expression among 46 maritally violent ( MV ) and 56 maritally nonviolent ( NV ) men r and omly assigned to receive alcohol , placebo , or no alcohol . Participants completed an anger-arousing articulated thoughts in simulated situations ( ATSS ) paradigm and imagined marital conflict scenarios . Anger experience was operationalized as subjective ratings of anger experienced during ATSS , and anger expression was measured as ATSS anger statements and aggression verbalizations . MV men given alcohol articulated significantly more aggressive verbalizations than all other groups , with high trait anger and increased anger experience predicting more aggressive verbalizations . Thus , alcohol may exert proximal effects on abusive behavior among individuals already prone to respond to conflict with increased anger This study evaluated the predictive validity of violence risk assessment s conducted using the HCR-20 , the Psychopathy Checklist : Screening Version ( PCL : SV ) , and by the Violence Screening Checklist ( VSC ) in a sample of 268 involuntarily hospitalized male and female psychiatric patients . Information pertaining to violence and crime was coded from medical charts and correctional records . The HCR-20/PCL : SV evidence d modest non-significant associations in postdictive assessment s of inpatient violence among men . Moderate to strong significant associations were found between the HCR-20/PCL : SV and inpatient violence among women . Pseudo- prospect i ve assessment s using the HCR-20 and PCL : SV result ed in moderate to large relationships with violence and crime in men and women following community discharge . It is concluded that the VSC is a promising tool for assessing acute inpatient violence risk with men . Findings offer preliminary validation of the predictive validity of the HCR-20 and PCL : SV with female civil psychiatric patients Prospect i ve longitudinal studies have shown strong predictions from conduct disorders ( CDs ) in childhood to antisocial personality disorder ( ASPD ) and violence in adults . However , little is known of the childhood antecedents of serious violence nor whether these may vary depending on the context in which the violence occurs . In this study , 54 men aged 21 - 40 years serving prison sentences for violent crime were assessed . St and ardized interviews of ASPD and violence were conducted independently of interviews covering retrospective recall of childhood psychiatric disorders and adverse experiences . Analyses of the predictors of overall violence suggested a pathway involving childhood CD and adult ASPD associated with interparental discord , and an additional pathway associated with experiencing interparental violence in childhood . Different results were however obtained when account was taken of the context of the violence . The CD-ASPD pathway was associated with social violence , but not with partner violence . Partner violence was predicted by retrospective reports of having been exposed to interparental violence during childhood but not by reports of childhood CD or adult ASPD . Thus developmental pathways to serious violence may be different depending on the social domain in which the violence occurs This prospect i ve study explores the predictive value of insight for suicide , violence , hospitalization , and social adjustment for a group of schizophrenic out patients over 1 year . The Schedule of Assessment of Insight ( SAI ) and its exp and ed version ( SAI-E ) were used to provide a baseline insight score for 74 schizophrenic out patients considered to be in remission or to have minimal psychopathology . Subjects were reassessed at the end of the period to determine the predictive value of initial insight rating by comparison . Insight into treatment was associated with less hospitalization and better social adjustment , but insight into mental illness or psychotic experience was not . It was also found that insight could neither predict suicidal behavior or violent tendencies . Therefore , some dimension of insight may predict hospitalization and social adjustment in schizophrenics , although its predictive efficacy for other clinical outcomes and behaviors may be limited BACKGROUND The MacArthur Violence Risk Assessment Study ( MacVRAS ) in the USA provided strong evidence to support an actuarial approach in community violence risk assessment . AIMS To examine the predictive accuracy of the MacVRAS measures , in addition to structured professional judgement , in a UK sample of patients discharged from in-patient care in the north-west of Engl and . METHOD A prospect i ve study of 112 participants assessed pre-discharge and followed up at 24 weeks post-discharge . Pre-discharge measures were compared with prevalence of violent behaviour to determine predictive validity of risk factors . RESULTS Historical measures of risk and measures of psychopathy , impulsiveness and anger were highly predictive of community violence . The more dynamic clinical and risk management factors derived from structured professional judgement ( rated at discharge ) added significant incremental validity to the historical factors in predicting community violence . CONCLUSIONS Although static measures of risk relating to past history and personality make an important contribution to assessment of violence risk , consideration of current dynamic factors relating to illness and risk management significantly improves predictive accuracy Objective The aim of the present study was to find out the extent of hostility and violence and the factors that are associated with such hostility and violence in a psychiatric intensive care unit . Methods Retrospective analysis of data prospect ively collected in a 6-year period . Results No hostility was observed in 56.1 % , hostility in 40.9 % , and violence in 3.0 % of the admitted cases . Seclusion was never used . Six cases ( 2,5‰ ) required physical restraint . Risk factors associated with violence were younger age , suicidal risk , and diagnosis of schizophrenia . Risk factors associated with hostile and violent behavior were younger age at the onset of the disorder , being single , having no children , lower GAF scores , higher BPRS hostility , SAPS , and CGI scores , lower BPRS anxiety-depression score , higher doses of psychoactive drugs , more frequent use of neuroleptics , diagnosis of mania , personality disorder , substance and alcohol related disorders , no diagnosis of depression . Conclusion The study confirms the low rate of violence among Italian psychiatric in- patients , the major relevance of clinical rather than socio-demographic factors in respect of aggressive behavior , the possibility of a no seclusion-no physical restraint policy , not associated either with higher rates of hostility or violence or with more severe drug side effects Little research has been conducted to vali date available instruments for assessing the risk of domestic violence reoffending , especially research using some form of prospect i ve design . This study uses a prospect i ve design to determine the reliability and validity of the Domestic Violence Screening Instrument ( DVSI ) . The analysis is based on a sample of 1,465 male domestic violence offenders selected consecutively over a 9-month period . Data on reoffending were collected in a 6-month follow-up period from a sub sample of the victims ( N = 125 ) of these perpetrators and from official records for all perpetrators during an 18-month follow-up period . The empirical results suggest that the DVSI was administered reliably , and they provide significant evidence of the concurrent , discriminant , and predictive validity of this instrument . Implication s for further research and utilization of the DVSI are discussed We examined discriminant and convergent validity of theoretically relevant Rorschach Comprehensive System ( CS ) variables ( Exner , 2003 ) and Meloy and Gacono 's ( 1992 ) aggression variables in distinguishing between imprisoned violent offenders ( VO ) who were psychopathic ( P – VO ) and nonpsychopathic ( NP – VO ) under psychiatric treatment , schizophrenic in patients ( ISs ) , and university students ( USs ) . A total of 7 of 12 variables discriminated significantly between P – VO and NP – VO , which suggests more aggressive , cognitive , and interpersonal disturbances among P – VO . We also found significant differences between VOs , ISs , and USs . Logistic regression analyses revealed that AgPast accumulated incrementally in the classification of P – VO versus NP – VO , and AgC accumulated incrementally in the classification of VO versus IS when entered after CS variables . The findings support the view that psychopathy is a distinctive form of antisocial personality disorder ( Diagnostic and Statistical Manual of Mental Disorders ; American Psychiatric Association , 1994 ) organized at a more severe pathological level OBJECTIVES We examined whether frequent drug use increases the likelihood of subsequent sexual or physical intimate partner violence ( IPV ) and whether IPV increases the likelihood of subsequent frequent drug use . METHODS A r and om sample of 416 women on methadone was assessed at baseline ( wave 1 ) and at 6 months ( wave 2 ) , and 12 months ( wave 3 ) following the initial assessment . Propensity score matching and multiple logistic regression were employed . RESULTS Women who reported frequent crack use at wave 2 were more likely than non-drug using women to report IPV at wave 3 ( odds ratio [OR]=4.4 ; 95 % confidence interval [CI]=2.1 , 9.1 ; P<.01 ) , and frequent marijuana users at wave 2 were more likely than non-drug users to report IPV at wave 3 ( OR=4.5 ; 95 % CI=2.4 , 8.4 ; P<.01 ) . In addition , women who reported IPV at wave 2 were more likely than women who did not report IPV to indicate frequent heroin use at wave 3 ( OR=2.7 ; 95 % CI=1.1 , 6.5 ; P=.04 ) . CONCLUSIONS Our findings suggest that the relationship between frequent drug use and IPV is bidirectional and varies by type of drug Background An important risk factor for suicide is psychiatric illness , but only a limited amount of work has been directed at assessing the use of firearms and other weapons by select psychiatric population s at high risk for violent acts . Method Patients with combat-related posttraumatic stress disorder ( PTSD ) , patients with schizophrenia , and patients undergoing rehabilitation for substance abuse were asked to complete a weapons-use survey and measures of psychopathology . Results The PTSD patients surveyed related owning more than four times as many firearms as other subjects and reported significantly higher levels of potentially dangerous firearm-related behaviors than the other psychiatric subjects surveyed . Conclusion High levels of aggression , impulsive and dangerous weapon use , and ready weapon availability may be significant factors in gun-related violence in the PTSD patient population . Additional prospect i ve research is needed to determine whether gun ownership or certain types of weapon use in this population is associated with future acts of violence BACKGROUND Relatively little is known about the relationships between medication adherence and long-term functional outcomes in the treatment of schizophrenia . To extend previous research , we prospect ively examined the relationships between adherence with any antipsychotic medication and functional outcomes among schizophrenia patients treated over a 3-year period , assessed the stability of adherence over time , and examined whether adherence in the first year predicts changes in functional outcomes over the following 2 years . METHOD Analyses included 1906 participants with DSM-IV diagnoses of schizophrenia or schizoaffective or schizophreniform disorder in a multi-site , 3-year , prospect i ve , naturalistic study conducted in the United States between July 1997 and September 2003 . Outcome measures were assessed at 6-month intervals using systematic medical record abstract ion and structured interview of patients . Adherence with antipsychotic regimen was assessed using patient-reported adherence and the medication possession ratio ( percent days with prescription for any antipsychotic ) , dichotomized into adherence and non-adherence . Analyses employed generalized estimating equations and mixed models with repeated measures . RESULTS Nonadherence was associated with poorer functional outcomes , including greater risks of psychiatric hospitalizations , use of emergency psychiatric services , arrests , violence , victimizations , poorer mental functioning , poorer life satisfaction , greater substance use , and more alcohol-related problems ( all p < .001 ) . Adherence was relatively stable , with 77.3 % of patients maintaining the same adherence status from the first year to the second year . Nonadherence in the first year predicted significantly poorer outcomes in the following 2 years . CONCLUSIONS Findings highlight the importance of adherence with antipsychotic medication in the long-term treatment of schizophrenia and its potential beneficial impact on the mental health and criminal justice delivery systems BACKGROUND Antisocial personality disorder ( ASPD ) identifies adults with persistent offending behaviour and social dysfunction . However , it lacks discrimination within high-risk and criminal population s and gives little indication of an individual 's history of violence . Existing measures of violence have significant limitations . The Liverpool Violence Assessment ( LiVA ) is an investigator-based st and ardized interview for measuring patterns of violence . METHOD A total of 61 male prisoners who had been sentenced for serious violent offences were interviewed using the LiVA and the Structured Clinical Interview for DSM IV antisocial personality disorder and alcohol and drug dependence . Official records of offending were examined . RESULTS The inter-rater reliability for the LiVA was high . There were significant correlations between histories of violence assessed by the LiVA and official records , but the frequency of self-reported violence was much higher than in the official records . Antisocial personality disorder was associated with increased violence . However , analyses revealed marked variability of the levels of violence among those with antisocial personality disorder and contrasting patterns of association of violence with antisocial personality disorder depending on the context . CONCLUSION The LiVA is a reliable and valid measure of the patterns and characteristics of violence . The findings suggest that the causes of violence should be studied in their own right and not only as a feature of ASPD Aggression by a r and om sample of female soldiers ( N = 1,185 ) toward their employed ( n = 840 ) and unemployed ( n = 345 ) civilian husb and s was measured by the Conflict Tactics Scale . When age , race , rank , years married , and the number of previous marriages were held constant , severe aggression toward unemployed male spouses was significantly greater than toward employed spouses Psychological and Physical Aggression scales met internal consistency and agreement st and ards on the Revised Conflict Tactics Scales ( CTS2 ) in a r and omly recruited sample of 453 married community couples with children . Moreover , partners agreed on the extent of psychological and physical aggression as much or more than they did on CTS2 Negotiation scale and positive behaviors assessed on the Dyadic Adjustment Scale . On the other h and , the CTS2 Sexual Coercion and Injury scales had much lower internal consistencies as measured by Cronbach 's alpha , and agreement was generally very low . Men and women reported less abusive behavior and consequent injury than partners reported about them . Correction factors were provided for prevalence estimates of abusive behavior and injury when only perpetrator reports were available The relationship between violence directed at the self and violence directed at others has intrigued psychiatrists for several decades . The goal of this study was to examine the relationship between suicide and violence against others in patients with major psychiatric disorders and to compare psychiatric symptoms associated with suicide in violent and non-violent patients . Subjects included physically assaultive psychiatric in patients and a non-violent comparison group . Physical and verbal assaults were recorded prospect ively for 4 weeks . History of suicide attempts was obtained through chart review and patient interviews . The Brief Psychiatric Rating Scale was administered at the end of the 4 weeks by raters who were blind to both suicidal and violent behavior . The suicide attempters did not differ from the non-attempters on any measure of violent behavior or hostility . Suicide attempts were not accompanied by different symptoms in violent and non-violent patients ; however , violence and suicide attempts were accompanied by dissimilar psychiatric symptoms . The physically assaultive patients presented with more severe positive psychotic symptoms than the non-assaultive patients . The suicide attempters , on the other h and , did not differ from non-attempters on psychotic symptoms , but presented with more severe depression and anxiety . The relationship between these symptoms and suicide attempts was noteworthy in its temporal stability , as most of the patients had attempted suicide many years prior to this study The predictive accuracy of the Psychopathy Checklist-Revised , Level of Service Inventory-Revised , Violence Risk Appraisal Guide , and the General Statistical Information on Recidivism were compared to four instruments r and omly generated from the total pool of original items . None of the four original instruments better predicted post-release failure than the four r and omly generated instruments . These results suggest two conclusions : ( a ) the instruments are only measuring criminal risk , and ( b ) no single instrument has captured sufficient risk assessment theory to result in better prediction than r and omly derived instruments measuring criminal risk . A two-stage factor analysis was completed on 1614 cases . This analysis of the risk items indicated a 4-factor solution and all 4 factors were equal to the original instruments in predicting post-release failure . Thus , the original instruments did not improve prediction over r and omly structured scales , nor did the restructuring of items improve risk assessment , suggesting substantial deficiencies in the conceptualization of risk assessment and instrumentation . We argue that developing a risk-based construct , which involves hypothesis testing and an explanation of behavior , is the optimal method to advance risk assessment within the criminal justice and mental health systems . Such an approach would provide targeted areas for clinical intervention that are salient to risk BACKGROUND The impact of comorbid personality disorder on the occurrence of violence in psychosis has not been fully explored . AIMS To examine the association between comorbid personality disorder and violence in community-dwelling patients with psychosis . METHOD A total of 670 patients with established psychotic illness were screened for comorbid personality disorder . Physical assault was measured from multiple data sources over the subsequent 2 years . Logistic regression was used to assess whether the presence of comorbid personality disorder predicted violence in the sample . RESULTS A total of 186 patients ( 28 % ) were rated as having a comorbid personality disorder . Patients with comorbid personality disorder were significantly more likely to behave violently over the 2-year period of the trial ( adjusted odds ratio=1.71 , 95 % CI 1.05 - 2.79 ) . CONCLUSIONS Comorbid personality disorder is independently associated with an increased risk of violent behaviour in psychosis Paraphilic disorders ( PAs ) and sexual preoccupation are known risk factors for recidivism in sexual offenders . Nonparaphilic sexual excessive behaviors-so-called paraphilia-related disorders ( PRDs ) , like paraphilias , are also characterized by sexual preoccupation and volitional impairment and can be diagnosed in paraphilic men . The prevalence and clinical significance of PRDs in sexual homicide perpetrators , however , is unknown . We investigated the relationship between PAs and PRDs retrospectively in a sample of 161 sexual murderers . Four groups were compared : men without a PA or a PRD diagnosis , men with at least one PRD but no PA , men with at least one PA but no PRD , and finally , those with a combination of both ( PA+PRD ) . The PA+PRD group had the most lifetime cumulative sexual impulsivity disorders , more developmental problems , the highest persistent frequency of sexual activity , the highest number of previous sexual offences , more sexual sadism , and compulsive masturbation . Men of the PRD sub sample had suffered more from childhood sexual abuse , showed more promiscuity , psychopathy , and alcohol problems . The use of the PRD concept in this special offender group should be further investigated with prospect ively design ed studies This exploratory study examined the extent to which substance use and criminality influence perceptions of social support . A stratified r and om sample of 100 incarcerated women in one Kentucky prison participated in face-to-face interviews . Overall , findings indicate that perceptions of social support significantly and negatively correlated with women 's severity of substance use and criminal involvement . In addition , the breadth of a respondent 's social network was negatively related to the age of first incarceration and to the severity of alcohol and drug use . Findings from this study suggest there is a relationship between severity of substance use , criminality , and perceptions of social support . Implication s for substance use research and practice are discussed The purpose of the present study was to determine the characteristics of repeatedly secluded female in patients . Fifty female in patients in a typical mental hospital were retrospectively investigated from the viewpoint of their recent history of seclusion , age , psychiatric symptoms rated by the Positive and Negative Syndrome Scale , doses of antipsychotics , and serum prolactin levels . The patients were divided into three groups ( none , once , twice or more ) by the frequency of seclusion in the most recent year . The three groups were significantly different in terms of positive symptoms , general psychopathological symptoms and serum prolactin levels . Unexpectedly , the seclusion frequency was negatively associated with serum prolactin levels . The present findings suggest that repeatedly secluded female in patients suffered from relatively low prolactin levels as well as more positive and psychopathological symptoms . Further prospect i ve studies are warranted to confirm these findings and to investigate whether low prolactin levels are useful in predicting the risk of frequent seclusion in female in patients This study prospect ively evaluated perpetrator risk factors for sexual assault perpetration , including peer influences , beliefs and attitudes about sexuality , alcohol use , and token resistance . Perpetration of sexual assault was evaluated at three time periods : pretest , 3-month follow-up , and 7-month follow-up . Retrospective and prospect i ve analyses yielded differential predictors of sexually aggressive behavior . However , perpetration of sexual assault at any particular assessment period was a predictor of perpetration during the subsequent follow-up period . Furthermore , several variables that have previously been demonstrated in the literature to be related to the perpetration of sexual assault were not significant in regression analyses , indicating that these variables may be rendered insignificant when accounting for past perpetration in prospect i ve analyses . These findings may have significant potential impact on development of sexual assault prevention programming with men Treatment efficacy is described for a sample of sexual offenders who had undertaken treatment in United Kingdom prisons ( N = 647 ) and for a retrospectively selected comparison group ( N = 1,910 ) . The outcomes under observation in this study were sexual , sexual and /or violent , and general reconviction . Treatment impact was also examined in relation to offenders ' risk of reconviction . The treatment group had slightly lower 2-year sexual reconviction rates than the comparison group , but these differences were not statistically significant . Significant differences were found between the treatment and comparison group for sexual and /or violent reconviction . Further analysis suggested that treatment produced a reduction in the probability of sexual and /or violent reconviction ( p < .05 ) when other relevant variables were controlled for . General reconviction rates were consistently lower in the treatment group , but these differences were not significant The present study was design ed to examine putative risk factors of driving anger , traffic citations , and traffic-related injuries as a function of gender . Participants included 785 ( 65 % men ) drivers identified by the Washington State Department of Licensing . Just over half of participants ( 55 % ) were identified as high-risk drivers based on multiple traffic violations , whereas 45 % were recruited from a r and om sample of drivers . Participants completed a mailed survey assessing indicators of risky driving and risk factors including sensation seeking , stressful events , negative affect , tobacco use , and drinking behavior . Hierarchical regression analysis was used to evaluate risky driving outcomes as a function of theoretically prioritized risk factors and to evaluate gender as a moderator . Overall , men reported more traffic citations and injuries , but did not differ from women in reported driving anger . All putative risk factors were associated with one or more indicators of risky driving . Moderation results revealed that the positive relationship between drinking frequency and driving anger was stronger for women . In contrast , typical number of drinks consumed was negatively associated with driving anger , which was also more evident for women . In addition , the positive association between sensation seeking and number of traffic citations was stronger among women The relationship between psychopathy and violence is well-established . However , few studies have examined the extent to which this relationship is influenced by sociodemographic predictors of violent criminality . In this prospect i ve study we examine the power of psychopathy to predict criminal violence across ethnicity and levels of socioeconomic status in 199 European American and African American U.S. county jail inmates . A Psychopathy × SES × Ethnicity interaction was identified such that among European Americans psychopathy predicted recidivism at lower levels of SES but was unrelated to recidivism at higher levels of SES . The predictive power of psychopathy was relatively stable across SES among African Americans . The implication s of our results for psychopathy and violence prediction are discussed There is a need for a brief specific measure of anger for use in assessment of posttraumatic mental health problems . One unpublished short scale is the Dimensions of Anger Reactions ( DAR ; R. Novaco , 1975 ) . This study examined the psychometric properties of the DAR using intake and 12-month data for 192 Australian Vietnam veterans with combat-related PTSD . Results showed the DAR to be unidimensional , reliable , and sensitive to change over time , and removal of two items improved the scale 's properties . The DAR measures anger disposition directed towards others . Assessment of convergent validity indicated that the DAR primarily measures Trait Anger . Results suggest that the DAR is a psychometrically strong measure , potentially useful for the evaluation of anger in PTSD OBJECTIVES The co-occurrence of severe mental illness and substance use disorder , or dual diagnosis , is prevalent and is associated with significant clinical and social problems . Most studies have treated persons with a dual diagnosis as a homogeneous population , grouping together different substances of misuse . This study investigated whether subgroups defined by their main substances of misuse were heterogeneous . The primary hypothesis was that users of stimulants , such as cocaine or amphetamines , would be characterized by especially high rates of inpatient admission , violence , and self-harm . METHODS Case managers ' ratings were used to identify individuals with serious mental illness and comorbid substance abuse or dependence who were being treated by 13 community mental health teams in South London . St and ardized instruments were used to elicit sociodemographic , clinical , social , and service use data . RESULTS A total of 233 cases of comorbid substance use disorder and psychotic illness were identified . On the basis of best available information , 78 ( 34 percent ) patients were classified as alcohol misusers only , 52 ( 22 percent ) as alcohol and cannabis users , 29 ( 12 percent ) as users of cannabis only , and 55 ( 24 percent ) as stimulant users ; 19 patients ( 8 percent ) were excluded from the analysis . No significant differences were found between subgroups in the use of inpatient services and lifetime history of self-harm , but there was a significant difference in lifetime history of violence , which was more frequent among stimulant users . The alcohol users were older and more likely to be white , but otherwise few differences between subgroups were suggested by exploratory analyses . CONCLUSIONS Apart from differences in history of violence , little heterogeneity was found among subgroups of patients with different types of substance misuse This study aim ed to identify the incidence and clinical correlates of aggression and violence in first episode psychosis . We prospect ively recruited subjects with a first episode of DSM-psychosis presenting from a geographically defined catchment area to a secondary referral psychiatric service over a four-year period ( n = 157 ) . We used the Modified Overt Aggression Scale to retrospectively assess aggression ( a hostile or destructive mental attitude , including verbal aggression , physical aggression and /or violence ) and violence ( the exercise of physical force ) , blind to diagnosis . One in three patients with psychosis was aggressive at the time of presentation . One patient in 14 engaged in violence that caused , or was likely to cause , injury to other people . Aggression was independently associated with drug misuse ( odds ratio ( OR ) 2.80 , 95 % confidence interval 1.12 - 6.99 ) and involuntary admission status ( OR = 3.62 , 95 % CI 1.45 - 9.01 ) . Violence in the week prior to presentation was associated with drug misuse ( OR = 2.75 , CI 1.04 - 7.24 ) and involuntary admission status ( OR = 3.21 , CI 1.21 - 8.50 ) . Violence in the week following presentation was associated with poor insight ( OR 2.97 , CI 1.03 - 8.56 ) and pre-contact violence ( OR 3,82 , CI 1.34 - 10.88 ) . In patients with schizophrenia , violence in the week following presentation was associated with drug misuse ( OR = 7.81 , CI 1.33 - 45.95 ) and high psychopathology scores ( OR = 20.59 , CI 1.66 - 254.96 ) . Overall , despite a high rate of verbal aggression , physical violence towards other people is uncommon in individuals presenting with first episode psychosis OBJECTIVE This paper examines whether exposure to interparental violence in childhood predicts subsequent involvement in interpartner violence and violent crime after controlling for potentially confounding factors . METHOD The investigation analyses data from the Christchurch Health and Development Study , a prospect i ve , longitudinal study of a birth cohort of over 1000 New Zeal and young adults studied at multiple assessment points from birth to the age of 25 . RESULTS After controlling for potentially confounding risk factors , observed associations between exposure to interparental violence in childhood and increased risks of both ( a ) psychological interpartner violence perpetration and victimization and ( b ) violent crime , were reduced to statistical non- significance . No statistically significant associations were observed between exposure to interparental violence in childhood and increased risk of physical interpartner violence perpetration or victimization . CONCLUSIONS It is concluded that the effects of childhood exposure to interparental violence on subsequent interpartner violence are weak and largely explained by the psychosocial context within which childhood exposure to interparental violence occurs Primary objective : To establish the prevalence , severity , recurrence and sequelae of past traumatic brain injury ( TBI ) among individuals recently received into custody . Research design : Cross-sectional r and om sample of men recently received into the New South Wales ’ ( NSW ) criminal justice system . Procedures : Participants were screened for a history of TBI including the injury setting , severity , treatment and sequelae of up to five separate TBI episodes . Outcomes and results : Of 200 study participants , 82 % endorsed a history of at least one TBI of any severity and 65 % a history of TBI with a loss of consciousness ( LOC ) . Multiple past TBIs were common , as were ongoing sequelae . Treatment for the TBI was more common among those TBIs with a LOC compared with no LOC ( 66 % vs. 39 % ) . Conclusions : Among individuals entering the criminal justice system , past TBI is common and often associated with ongoing neuropsychiatric and social sequelae . Screening for TBI at the point of reception may be warranted to better underst and and treat those with ongoing neuropsychiatric sequelae arising from the TBI BACKGROUND Of the 2 reports in the literature on anger attacks in bipolar depression , one found them to be uncommon ( 12 % ) compared with the rate in bipolar mixed states and unipolar depression ( 40%-60 % ) , whereas the other found them to be common ( 62 % ) . We examined anger attacks among participants in an 8-week trial of open-label citalopram added to mood stabilizer for the treatment of bipolar depression . We also examined trait anger , hypomanic symptoms , and depressive symptoms as predictors of anger attacks . We hypothesized that if anger attacks were related to hypomanic symptoms they would respond unfavorably to citalopram , whereas if they were related to trait anger or depressive symptoms they would respond favorably . METHOD In 45 participants with a DSM-IV diagnosis of bipolar I or II depression , anger attacks , hypomanic symptoms , and depressive symptoms were assessed using a modified Anger Attacks Question naire , Young Mania Rating Scale , and Hamilton Rating Scale for Depression , respectively . Trait anger was measured using the State-Trait Anger Inventory . Posttreatment data were collected at the end of 8 weeks of treatment with citalopram or at dropout from the trial . The first participant study visit was in November 1998 , and the final participant study visit was in December 2000 . RESULTS Before treatment with citalopram , 17 ( 38.6 % ) of 44 participants reported anger attacks ( data on anger attacks were missing for 1 participant before treatment and 4 after treatment ) . Significantly fewer participants reported anger attacks after treatment ( 6 of 41 , 14.6 % ; McNemar test , p < .05 , 2-tailed ) . At pretreatment and post-treatment , trait anger was the only significant predictor of anger attacks ( p < .05 ) . CONCLUSIONS These findings suggest that in bipolar depression anger attacks are common , may respond favorably to acute treatment with citalopram added to mood stabilizer , and are better predicted by trait anger than hypomanic or depressive symptoms . Further studies are needed to clarify the diagnostic and treatment implication s of anger attacks in bipolar depression The power of scales based on the Psychopathy Checklist ( PCL ; R. D. Hare , 1980 ) for prediction of violent behavior is well established . Although evidence suggests that this relationship is chiefly due to the impulsive and antisocial lifestyle component ( Factor 2 ) , the predictive power of psychopathy for violence may also reflect the multiplicative effects of this component with interpersonal and unemotional traits ( Factor 1 ) . The determination of the extent to which psychopathy subcomponents interact to predict violence has theoretical and practical implication s for PCL-assessed psychopathy . However , the relationship between violence and the interactive effects of psychopathy subcomponents remains largely undetermined . The authors used prospect i ve and cross-sectional design s to examine the independent and interactive effects of the factors of PCL-assessed psychopathy in 2 sample s : ( a ) 199 county jail inmates and ( b ) 863 civil psychiatric patients . The Factor 1 x Factor 2 interaction predicted violence in both sample s , such that the predictive power of Factor 2 was attenuated at lower levels of Factor 1 The majority of studies evaluating the relationship between childhood sexual assault and subsequent sexual assault perpetration by men have been conducted retrospectively and with incarcerated population s. The present study seeks to improve on previous research by prospect ively investigating the relationship between childhood sexual assault and subsequent perpetration of dating violence in adulthood in men . Although there is a significant relationship between childhood sexual abuse and history of sexual assault perpetration at baseline , prospect i ve analyses indicate that childhood sexual assault is not predictive of perpetration during the follow-up period . The role of family factors , including parental conflict resolution , is implicated in subsequent sexual aggression . These results are supportive of the idea that the effects of childhood sexual abuse may be mediated by a variety of factors Cross-sectional investigations , using the five-factor model of personality have evinced relationships among neuroticism , agreeableness , and psychotic symptoms . The current study examined these relationships via a prospect i ve follow-up study with remitted first-episode psychosis patients . Baseline five-factor model personality profiles , diagnoses , symptom ratings , and premorbid adjustment ratings were followed by nine monthly ratings on Brief Psychiatric Rating Scale psychosis items in 60 first-episode patients . Valid baseline personality profiles were completed by 40 patients . Patients who had a return of symptoms scored higher on baseline neuroticism and agreeableness than those who remained in remission . Premorbid adjustment also predicted return of symptoms . After premorbid adjustment was controlled for , the agreeableness differences remained significant , but the neuroticism scores were no longer significantly different . It is concluded that lower agreeableness acts as a mediating variable in relapse . Further studies should clarify whether agreeableness is associated with specific biases in processing interpersonal information , and interpersonal behaviors Abstract : The subjects were 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week , double-blind trial . Incidents of overt aggression were recorded and their severity was scored . The Positive and Negative Syndrome Scale was administered . Atypical antipsychotics showed an overall superiority over haloperidol , particularly after the first 24 days of the study when the dose escalation of clozapine was completed . Once an adequate therapeutic dose of clozapine was reached , it was superior to haloperidol in reducing the number and severity of aggressive incidents . Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients . There was an interaction between aggressiveness , medication type , and antipsychotic response : risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior ; the opposite was true for clozapine . Clozapine appears to have superior antiaggresive effects in treatment-resistant patients ; this superiority develops after the patient has been exposed to an adequate dose regimen Advances in treatment technologies and development of evidence -based st and ards of care dem and better methods for routine assessment of outcomes for schizophrenia in systems of care . This article describes the development and psychometrics of a new instrument to assess outcomes of routine care for persons with schizophrenia in service systems . C and i date items for the Schizophrenia Care and Assessment Program Health Question naire ( SCAP-HQ ) were drawn from existing measures . Domains covered include disease outcomes ( symptoms , subjective medication effects , substance abuse ) , functional status , health status , quality of life , and public safety . A sample of 1,584 patients with schizophrenia or schizoaffective disorder who were recruited into a large prospect i ve , naturalistic study on the course of treatment for schizophrenia completed the SCAP-HQ at baseline and 1 year later ( n = 434 ) , providing data for factor analysis , assessment of internal consistency , convergent validity , and responsiveness to change . A sub sample of 121 patients completed a test-retest protocol . Fifteen scales were derived by factor analysis from 55 outcome items on the SCAP-HQ . These factors covered psychiatric symptoms , life satisfaction , instrumental activities of daily living , health-related disability , subjective medication side effects , vitality , legal problems , social relations , mental health-related disability , suicidality , drug and alcohol use , daily activities , victimization , violence , and employment . For most scales , st and ard psychometric parameters , including internal consistency and test-retest reliability , convergent validity , and responsiveness to change , were acceptable for application to large sample evaluations of care systems . This new measure represents an advance in the development of outcome measures for schizophrenia for use in large-scale studies of routine care OBJECTIVE Men are more violent than women in the general population , but this has not been found to be the case among psychiatric in patients . The reason for this exception is poorly understood . The present study investigated gender differences in violent behaviors among patients with major psychiatric disorders . It examined various clinical symptoms and psychosocial factors to determine their differential impact on violence in men and women . METHOD Physical assaults and verbal assaults committed by psychiatric in patients were recorded prospect ively . Patients whose violent incident occurred during their first 2 months of hospitalization were eligible for the study . Patient history of community violence was also obtained . Psychiatric symptoms and ward behaviors were assessed upon entry into the study and after 4 weeks . RESULTS A similar percentage of women and men had an incident of physical assault in the hospital . Among the patients entered into the study , the women had a much higher level of verbal assaults throughout the evaluation period and a higher level of early physical assaults ( i.e. , within the first 10 days of the 4-week study period ) . Positive psychotic symptoms were more likely to result in assaults in women than in men . Physical assaults in the community , on the other h and , were more common in men and were associated with substance abuse , property crime , and a history of school truancy . CONCLUSIONS There are gender differences in the patterns of violent behavior among patients with major psychiatric disorders . Furthermore , psychiatric symptoms and psychosocial risk factors have a different impact on this behavior in men and women . This has important implication s for the prediction and differential treatment of violent behavior Objective : To consider the extent to which the presence of psychopathy , as indicated by the psychopathy checklist : screening version ( PCL : SV ) , can predict intramural behaviour in offenders with mental disorders serving compulsory treatment at a German forensic psychiatric hospital . Method : The PCL : SV was used with 48 offenders detained at a forensic psychiatric hospital in Germany . In a prospect i ve design , objective and subjective measures of behaviour were compared for those identified as high and low scorers on the PCL : SV . Data were obtained from hospital records of disciplinary incidents ( objective ) and from interviews with case managers and therapists ( subjective ) , according to predefined criteria and in st and ardized forms . Results : The hospital records of the high scorers indicated they had been involved in significantly more disciplinary incidents than low scorers . Their behaviour was also rated significantly more negative by therapists than the low scorers . Conclusion : Numeorus studies found the psychopathy checklist ( PCL ) score to be a reliable predictor of recidivism in offenders after release . The present study has demonstrated that the PCL score has also predictive validity for intramural behaviour problems in individuals serving compulsory treatment at a forensic psychiatric hospital . As a result , we recommend the routine use of the PCL with offenders starting a period of compulsory detention to identify those at increased risk for problem behaviour Acute benzodiazepine administrations typically decrease aggressive responding , but increases in aggression have been reported in some studies . The benzodiazepine lorazepam has been studied less frequently than other benzodiazepines in aggression research , although it is often used to suppress violent aggression in patients . The present study was design ed to investigate the effects of acute administrations of lorazepam on aggressive responding in adult humans on a laboratory aggression task . Eight adult males participated in experimental sessions on the Point Subtraction Aggression Paradigm ( PSAP ) , which provided subjects with aggressive , escape and monetary-reinforced response options . Acute oral doses ( 1 , 2 and 4 mg ) of lorazepam decreased both aggressive responding and monetary-reinforced responding in seven of eight subjects . In one subject , lorazepam produced dose-dependent increases in aggressive responding . The effects of lorazepam on escape responding were the same as the effects on aggressive responding . The results are consistent with prior research using the PSAP and clinical data showing that benzodiazepines generally decrease aggression , and contrast with other studies that have shown that benzodiazepines can increase aggression . Since lorazepam affected both aggressive and escape responding , it is suggested that while lorazepam often produces sedation , it also modifies human aggressive responding , in part , by suppressing reactions to aversive stimuli |
13,911 | 29,340,191 | Conclusions Several patient-reported outcome measures are now available for assessing Italian people with non-specific neck pain .
While the Neck Disability Index is the one most widely used , the Neck Bournemouth Question naire appears the most promising tool from a psychometric point of view | Background Patient-reported outcome measures can improve the management of patients with non-specific neck pain .
The choice of measure greatly depends on its content and psychometric properties .
Most question naires were developed for English-speaking people , and need to undergo cross-cultural validation for use in different language context s. To help Italian clinicians select the most appropriate tool , we systematic ally review ed the vali date d Italian- language outcome measures for non-specific neck pain , and analyzed their psychometric properties and clinical utility . | OBJECTIVE To assess the sensitivity to change of three algofunctional scales for neck pain . METHODS Observational , prospect i ve study . Patients with neck disorders were included . Pain and patients ' perceived h and icap assessed on visual analogue scales ( VAS Pain , VAS H and icap ) , and functional disability measures ( Neck Disability Index , Neck Pain and Disability Scale , Northwick Park Neck Pain Question naire ) were recorded twice , at baseline and at an 11-month follow-up assessment . Sensitivity to change was assessed using the effect size ( ES ) and the st and ardised response mean ( SRM ) , and the non-parametric Spearman 's rank correlation coefficient ( r ) was used to assess the correlation between quantitative variable changes and patients ' overall opinion . Analysis of variance ( ANOVA ) followed by a Tukey-test was performed to determine if the scales distinguished improved , stable , and deteriorated patients . RESULTS Seventy-one patients ( 43 women , mean age 49 years ) were included and evaluated twice at an interval of 11 + /- 2 months . The three scales showed good sensitivity to change . The ANOVA showed a group effect , and individual changes in the scales scores were statistically different in two-by-two comparisons ( improved , stable or deteriorated patients ) . Changes in NPDS scores had the highest correlation with patient 's overall assessment ( r = 0.592 ) . CONCLUSION The three scales can detect changes in patients with neck disorders . Changes in NPDS score had the best correlation with patients ' overall opinion concerning their neck disorder and this question naire should be given preference in clinical trials STUDY DESIGN Prospect i ve , single-group observational design . OBJECTIVES To determine the minimal clinical ly important difference ( MCID ) for the Disabilities of the Arm , Shoulder and H and ( DASH ) outcome measure and its shortened version ( QuickDASH ) in patients with upper-limb musculoskeletal disorders , using a triangulation of distribution- and anchor-based approaches . BACKGROUND Meaningful threshold change values of outcome tools are crucial for the clinical decision-making process . METHODS The DASH and QuickDASH were administered to 255 patients ( mean ± SD age , 49 ± 15 years ; 156 women ) before and after a physical therapy program . The external anchor administered after the program was a 7-point global rating of change scale . RESULTS The test-retest reliability of the DASH and QuickDASH was high ( intraclass correlation coefficient model 2,1 = 0.93 and 0.91 , respectively ; n = 30 ) . The minimum detectable change at the 90 % confidence level was 10.81 points for the DASH and 12.85 points for the QuickDASH . After triangulation of these results with those of the mean-change approach and receiver-operating-characteristic-curve analysis , the following MCID values were selected : 10.83 points for the DASH ( sensitivity , 82 % ; specificity , 74 % ) and 15.91 points for the QuickDASH ( sensitivity , 79 % ; specificity , 75 % ) . After treatment , the MCID threshold was reached/surpassed by 61 % of subjects using the DASH and 57 % using the QuickDASH . CONCLUSION The MCID values from this study for the DASH ( 10.83 points ) and the QuickDASH ( 15.91 points ) could represent the lower boundary for a range of MCID values ( reasonably useful for different population s and context ual characteristics ) . The upper boundary may be represented by the 15 points for the DASH and 20 points for the QuickDASH proposed by the DASH website OBJECTIVE This study compares the sensitivity to change of the Neck Disability Index ( NDI ) and the Neck Bournemouth Question naire ( NBQ ) in patients with chronic uncomplicated neck pain . METHODS This prospect i ve longitudinal study was completed in an outpatient physical therapy clinic . Subjects , with uncomplicated neck pain ( no concurrent shoulder pain or nerve root symptoms ) for more than a 3-month duration , participated in a 4-week course of therapy that included moist heat , neck exercises , and either mobilization or massage . Outcome measures included st and ardized response means ( sensitivity to change ) , Cronbach alpha ( internal consistency ) , and 2-way Spearman correlations between the 2 question naires and between a pain Visual Analog Scale and each question naire ( convergent validity ) . RESULTS Mean ( SD ) score change of the NDI was 6.22 ( 5.12 ) , and of the NBQ , 14.00 ( 11.99 ) . St and ardized response means were 1.21 and 1.17 , respectively . Both question naires were more sensitive to change than the pain Visual Analog Scale ( 0.68 ) . There was moderate correlation between the change scores of all 3 outcome tools ( Spearman 0.46 - 0.57 ) . The NBQ had higher internal consistency than the NDI . CONCLUSIONS The NDI and the NBQ performed comparably in this group of patients with chronic uncomplicated neck pain . Both are sensitive to change and would be efficient outcome tools in studies of chronic neck pain . Both had acceptable internal consistency and are appropriate for use as single- outcome scales Self question naires are an important aspect of the management of neck pain patients . The Bournemouth Question naire ( BQ ) , based on the biopsychosocial model , is design ed to evaluate patients with neck pain . The vali date d English version of this question naire ( BQc-English ) has psychometric properties that range from moderate to excellent . The goal of this study is to translate and vali date a French version of the Bournemouth Question naire for neck pain patients ( BQc-f ) . Its translation and adaptation are performed using the translation back-translation method , generating a consensus among the translators . This validation study was performed on 68 subjects ( mean age 41 years old ) who participated in a r and omized controlled trial regarding the efficiency of manual therapy for neck pain patients . This experimental protocol was design ed to generate data in order to evaluate the construct validity , longitudinal validity , test-retest reliability and responsiveness . The BQc-f psychometric properties of construct validity ( r = 0.67 , 0.61 , 0.42 ) for pre treatment , post treatment and longitudinal validity , respectively ) , test-retest reliability ( r = 0.97 ) and responsiveness ( effect size = 0.56 and mean st and ardized response = 0.61 ) are sufficient to suggest it could be used in the management of patients with neck pain Study Design . Observational prospect i ve study . Objective . Vali date the Spanish version of the Neck Disability Index ( NDI ) . Summary of Background Data . The NDI is the most widely used neck pain scale in the largest number of population s and has been vali date d most often against multiple measurements of function , pain , and clinical signs and symptoms . Methods . The Spanish version of the NDI was administered 2 or 3 times to 175 individuals with neck pain ( including those requesting or not requesting specific healthcare at a given time and those with acute and subacute/chronic nonspecific or post-traumatic neck pain ) . After establishing the factorial structure by extracting the main components , the internal consistency was assessed with the Cronbach alpha method , the test-retest reliability was assessed with the Bl and -Altman plot and the intraclass correlation coefficient methods , and the validity was established by calculating Pearson correlation coefficient with pain visual analogue scale values and with Northwick Park Neck Pain Question naire ( Spanish version ) values . Sensitivity to change was estimated while comparing the mean difference between the first application of the NDI score and the one after the treatment in the patients who improved , felt the same , or worsened . Results . A single factor explained 51.6 % of the variance , the Cronbach alpha score was 0.89 , the intraclass correlation coefficient was 0.98 , the Pearson correlation coefficient with pain visual analogue scale was r = 0.65 and with Northwick Park Neck Pain Question naire was r = 0.89 . In the subgroup of 147 subjects in whom the sensitivity to change was studied , those who reported an improvement in neck pain showed a decrease in the NDI score of 8.20 , those who felt the same showed a decrease of 0.23 , and those who felt worse showed an increase of 5.55 . Conclusion . This first Spanish version of the Neck Disability Index is reliable , valid , and sensitive to change Study Design . A prospect i ve cohort study with a 7‐week follow‐up of 113 patients with chronic neck pain undergoing physiotherapy . Objective . To examine the responsiveness of the Portuguese Version of the Neck Disability Index ( NDI‐PT ) , and to determine the minimal clinical ly important difference ( MCID ) , minimal detectable change ( MDC ) , and floor/ceiling effects . Summary of Background Data . Studies that determine MDC and MCID are needed to provide more accurate outcome evaluation and critically assess potential relevant sources for differences in the minimal important change values for the NDI . Methods . The NDI‐PT was administered twice : at the baseline and after 7 weeks of physiotherapy treatment . A Global Transition Scale was used as an external criterion measure to distinguish between improved and nonimproved patients ’ scores between baseline and follow‐up . The responsiveness of the NDI‐PT was assessed through anchor‐based methods ( correlation coefficient and receiver operating characteristics curves — ROC curves ) . The MCID was estimated by the ROC curve method , and the MDC through the st and ard Error of Measurement ( SEM ) . Results . The NDI‐PT revealed moderate responsiveness when applied to patients with chronic neck pain undergoing physiotherapy ( & rgr ; = 0.328 and area under the curve of 0.595 , 95 % confidence interval : 0.484–0.706 ) . The MDC achieved 12 points , whereas the MCID was found to be 5.5 points . A complementary ROC analysis based on percentage differences in NDI‐PT scores from baseline revealed an optimal cutoff point of 27 % . The optimal cutoff point was found to be dependent of disability baseline scores . Conclusion . The NDI‐PT demonstrated moderate levels of responsiveness . The amount of change in question naire scores perceived by the patient to be meaningful is smaller than the amount of change required to be statistically 95 % confident that score change is not just measurement error . Level of Evidence : PURPOSE Report the test-retest reliability , construct validity , minimum clinical ly important difference ( MCID ) , and minimal detectable change ( MDC ) for the Neck Disability Index ( NDI ) . STUDY DESIGN / SETTING Cohort study of patients presenting to outpatient physical therapy clinics . PATIENT SAMPLE Ninety-one subjects with a primary complaint of neck pain , with or without concomitant upper extremity ( UE ) symptoms , who were participants in a r and omized clinical trial . OUTCOME MEASURES NDI and the 15-point Global Rating of Change ( GRC ) self-report measures . METHODS All subjects completed the NDI at baseline and at a 3-week follow-up . Additionally , subjects completed the GRC scale , which was used to dichotomize patients into improved or stable groups . Changes in the NDI were used to assess test-retest reliability , construct validity , MCID , and MDC . RESULTS Test-retest reliability was moderate for the NDI ( intraclass correlation coefficient , 0.64 ; 95 % confidence interval , 0.19 - 0.84 ) . For the NDI , the MCID was 7.5 points and the MDC was 10.2 points . CONCLUSIONS The NDI appears to demonstrate adequate responsiveness based on statistical reference criteria when used in a sample that approximates the high percentage of patients with neck pain and concomitant UE referred symptoms . Because the MCID is within the bounds of measurement error , a 10-point change ( the MDC ) should be used as the MCID A prospect i ve cohort study with a 1 week follow-up . To examine the reliability and responsiveness of the Dutch version of the Neck Disability Index ( NDI ) in patients with acute neck pain in general practice . An increasing number of studies on treatment options is published in which the NDI is used . Reports of the ability of the NDI to detect change over time , often called responsiveness , however have not yet been published . At baseline 187 patients ( 119 women , 68 men ) were included . They completed a question naire on demographic variables , self-reported cause of their complaints and the NDI . After 1 week , 86 patients were sent the NDI again together with the perceived recovery scale which was used as our external criterion . The scale ranged from 1 ( complete recovery ) to 7 ( complaints are worse than ever ) . Response rate was 93 % . Test – retest scores on reliability were good ( ICC = 0.90 ) . A Bl and and Altman plot and a graph of total sum score differences showed no visible tendency towards unequal spreading of the data . For patients that reported on the perceived recovery scale that they were “ stable ” we found a responsiveness ratio of 1.82 . The st and ard error of measurement ( SEM ) was 0.60 what result ed in a minimal detectable change ( MDC ) of 1.66 . The NDI has shown to be a reliable and responsive instrument in patients with acute neck pain in general practice Study Design . Prospect i ve , single-cohort study . Objective . To assess the minimal clinical ly important change ( MCIC ) on the Neck Disability Index ( NDI ) and the Numerical Rating Scale ( NRS ) for pain in patients with neck pain . Summary of Background Data . Both measurement instruments are frequently used in research and clinical practice , but which changes are clinical ly relevant is still unknown . Methods . The MCIC was estimated with 2 different methods , both integrating an anchor-based and distribution-based approach : the minimal detectable change ( MDC ) and the optimal cutoff point of the ROC curve . The study population consisted of 183 patients with nonspecific neck pain . Results . The results show an MDC of 10.5 points for the NDI ( scale range , 0–50 ) and 4.3 points for the NRS ( scale range , 0–10 ) , and optimal cutoff points of the ROC curve of 3.5 for the NDI and 2.5 for the NRS . Conclusion . The estimated MCIC should be used as an indication for relevant changes in clinical practice . Using the optimal cutoff point of the ROC curve , false positives and false negatives are equally weighted ; and if there are no objections doing so , the optimal cutoff point of the ROC curve may be a good choice Study Design . Prospect i ve , single-cohort study . Objective . To determine the relative sensitivity of a range of outcome measures used in evaluating treatment interventions in patients with neck pain and the magnitude of change scores on the neck Bournemouth Question naire and the cutoff score on the Patients ’ Global Impression of Change scale associated with clinical ly significant improvement . Summary of Background Data . Traditionally , evaluation of treatment interventions using subjective outcome measures has been based on the statistical significance of the difference between group mean values . To be clinical ly meaningful , however , information is required from sensitive outcome measures on the proportion of patients undergoing a clinical ly important improvement and from this , the number needed to treat for a single patient to benefit . Methods . Patients with nonspecific neck pain from a number of treatment centers completed a battery of self-report question naires , including the Bournemouth Question naire , before and after chiropractic treatment . After treatment , patients also completed a retrospective analysis of their overall improvement since the start of treatment ( Patients ’ Global Impression of Change ) . The a priori definition of clinical ly significant improvement was defined as a Reliable Change Index on the Bournemouth Question naire of > 1.96 . Results . The best cutoffs with a balance between the highest sensitivity and highest specificity in detecting clinical improvement were a score of 2 or less on the Patients ’ Global Impression of Change ( 11-point Numerical Rating Scale : 0 = much better , 5 = no change , and 10 = much worse ) and a raw change score of three or more points on each of the seven 11-point Numerical Rating Scale subscales of the Bournemouth Question naire . For the total score of the Bournemouth Question naire , raw change scores of 13 or more points , percentage change scores of 36 % or more , and individual effect sizes of 1.0 or more were all associated with clinical ly significant improvement . The sensitivity of the Bournemouth Question naire in terms of its effect size was comparable with that of pain intensity scales and the Neck Disability Index . Conclusions . The present findings will assist in the choice of outcome measures in trials on neck pain . The study also illustrates a method ologic framework for interpreting change scores in terms of clinical improvement , facilitating the process of making sense of research data in the clinical setting Study Design . Patients enrolled in a r and omized controlled trial were asked to complete various question naires , which were then compared to establish validity for a new neck pain question naire . Objectives . To vali date a new and brief outcome measure for use with patients with mechanical neck pain . Summary of Background Data . Neck pain is a very common problem and one that clinicians will be required to treat with some regularity . In today ’s climate of evidence -based practice and the need to quantify and justify clinical intervention , a quick and easy method to evaluate progress is required . Such a measure has already been produced for those experiencing back pain , but as yet , there is no such measure for neck pain and this needs to be addressed . Methods . The back pain measure was adapted to enable its use with patients with neck pain . Repeatability was assessed by using a 1-week test/retest on 104 patients who were enrolled in a neck pain trial . Validity was assessed by comparing the new question naire against other already well vali date d measures ( i.e. , the Neck Disability Index and a Visual Analogue Scale for pain ) with 133 patients . Results . The test/retest showed excellent repeatability with high intraclass correlations and P < 0.001 for each question tested . The Core Neck Pain Question naire also showed good validity , giving close agreement to the other comparison measures . Conclusion . The short Core Neck Pain Question naire has been demonstrated to be repeatable and valid as a brief outcome measure for use with patients with mechanical neck pain Study Design . Cultural translation and psychometric testing . Objective . To translate and vali date the Iranian versions of the Neck Disability Index ( NDI-IR ) and the Neck Pain and Disability Scale ( NPDS-IR ) . Summary of Background Data . The widely used the NDI and the NPDS scales have not been translated and vali date d for Persian-speaking patients with neck pain . This was to provide a vali date d instrument to measure functional status in patients with neck pain in Iran . Methods . The translation and cultural adaptation of the original question naires were carried out in accordance with the published guidelines . One hundred and eighty-five patients with neck pain were participated in the study . Patients were asked to complete a question naire booklet including the NDI-IR , the NPDS-IR , the Iranian SF-36 , and a visual analog scale ( VAS ) of pain . To carry out the test-retest reliability , 30 r and omly selected patients with neck pain were asked to complete the question naire booklet 48 hours later for the second time . Results . Cronbach & agr ; coefficient for the NDI-IR was 0.88 and for the 4 subscales of the NPDS-IR was found to be satisfactory ( ranging from 0.74 to 0.94 ) . The NDI-IR and the NPDS-IR subscales showed excellent test-retest reliability ( intraclass correlation coefficient ranged from 0.90 to 0.97 ; P < 0.01 ) . The correlation between the NDI-IR and the NPDS-IR subscales and functional scales of the SF-36 showed desirable results , indicating a good convergent validity ( Pearson correlation coefficients ranged from −0.31 to −0.70 ) . The correlation between the NDI-IR and the VAS was 0.71 and between the NPDS-IR subscales and the VAS ranged from 0.63 to 0.79 ( P < 0.01 ) . Conclusion . The Iranian versions of the NDI and NPDS are reliable and valid instruments to measure functional status in Persian-speaking patients with neck pain in Iran . They are simple and easy to use and now can be applied in clinical setting s and future outcome studies in Iran and other Persian speaking communities OBJECTIVE To modify an existing outcome measure ( Bournemouth Question naire [ BQ ] ) for use in patients with nonspecific neck pain and test its psychometric properties . DESIGN Prospect i ve longitudinal study in which the question naire was administered on 3 occasions ( pretreatment , retest , and posttreatment ) . SETTING Anglo-European College of Chiropractic outpatient clinic and 8 field chiropractic practice s. METHOD Seven core items relating to the biopsychosocial model of pain were included in the original question naire ( back BQ ) . The wording of one of these items ( disability in activities of daily living ) was modified to include activities likely to be affected by neck pain . Testing of the neck BQ was carried out in 102 patients with nonspecific neck pain . RESULTS The instrument demonstrated high internal consistency on 3 administrations ( Cronbach 's alpha = 0.87 , 0.91 , 0.92 ) . All 7 items were retained on the basis that they each significantly contributed to the total score ( item-corrected total score correlations > 0.43 ) and to the instrument 's responsiveness to clinical change ( item change-corrected total change score correlations > 0.42 ) . The instrument was reliable in test-retest administrations in stable subjects ( ICC = 0.65 ) . The instrument demonstrated acceptable construct validity and longitudinal construct validity with established external measures . The treatment effect size of the instrument was found to be high ( 1.67 ) . CONCLUSION The neck BQ covers the salient dimensions of the biopsychosocial model of pain , is quick and easy to complete , and has been shown to be reliable , valid , and responsive to clinical ly significant change in patients with nonspecific neck pain . Its use as an outcome measure in clinical trials and outcomes research is recommended A method is described for evaluating the progress of patients with back pain . Various symptoms were scored on analogue scales and spinal motion was measured by various techniques . These data were integrated to make subjective and objective indices respectively . Reasonable reproducibility of the measurements was obtained . This technique was used to eluci date the role of the lumbar support in surgical corsets in relief of back pain . Sufferers from back pain were r and omly allocated to corsets with and without lumbar supports . There was significant improvement in those with a support compared with those without . On the other h and objective changes measured with the corset removed did not differ between the 2 groups . This study indicates that the spinal support in a lumbosacral corset makes a significant contribution towards the relief of symptoms STUDY DESIGN Prospect i ve cohort study . OBJECTIVES To establish the major clinical ly important improvement ( MCII ) of the timed up- and -go test ( TUG ) , 40-meter self-paced walk test ( 40-m SPWT ) , 30-second chair st and ( 30 CST ) , and a 20-cm step test in patients with hip osteoarthritis ( OA ) undergoing physiotherapy treatment . As a secondary aim , a comparison of methods was employed to evaluate the effect of method on the reported MCII . BACKGROUND Minimal clinical ly important difference scores are commonly used by rehabilitation professionals to determine patient response following treatment . A gold st and ard for calculating MCII has yet to be determined , which has result ed in problems of interpretation due to varied results . METHODS As part of a r and omized controlled trial , 65 patients were r and omized into a physiotherapy treatment group for hip OA , in which they completed 4 physical performance measures at baseline and 9 weeks . Upon completion of physiotherapy , patients assessed their response to treatment on a 15-point global rating of change scale ( GRCS ) . MCII was estimated using 3 variations of an anchor-based method , based on the patient 's opinion . RESULTS A comparison of 3 methods result ed in the following change scores being best associated with our definition of MCII : a reduction equal to or greater than 0.8 , 1.4 , and 1.2 seconds for the TUG ; an increase equal to or greater than 0.2 , 0.3 , and 0.2 m/s for the 40-m SPWT ; an increase equal to or greater than 2.0 , 2.6 , and 2.1 repetitions for the 30 CST ; an increase equal to or greater than 5.0 , 12.8 , and 16.4 steps for the 20-cm step test . CONCLUSION The variation in methods provided very different results . This illustrates the importance of comparing method ologies and reporting a range of values associated with the MCII , as such values vary , depending upon the methodology chosen |
13,912 | 16,246,984 | Combination therapy also significantly improved liver histologic response .
The effects on quality of life are unclear .
However , combination therapy significantly increased the risk of hematological , dermatological , gastrointestinal , and several other types of adverse events .
In conclusion , the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection .
However , combination therapy is associated with increased risk for adverse events | Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40 % of patients with chronic hepatitis C infection , but the effects on clinical outcomes are unclear .
We evaluated the beneficial and harmful effects of ribavirin plus interferon vs interferon alone for treatment of patients with chronic hepatitis C infection . | BACKGROUND Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy . We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 912 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with ribavirin ( 1000 or 1200 mg orally per day , depending on body weight ) for 24 or 48 weeks . Efficacy was assessed by measurements of serum hepatitis C virus ( HCV ) RNA and serum aminotransferases and by liver biopsy . RESULTS The rate of sustained virologic response ( defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed ) was higher among patients who received combination therapy for either 24 weeks ( 70 of 228 patients , 31 percent ) or 48 weeks ( 87 of 228 patients , 38 percent ) than among patients who received interferon alone for either 24 weeks ( 13 of 231 patients , 6 percent ) or 48 weeks ( 29 of 225 patients , 13 percent ) ( P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment ) . Among patients with HCV genotype 1 infection , the best response occurred in those who were treated for 48 weeks with interferon and ribavirin . Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks ( 57 percent ) or 48 weeks ( 61 percent ) than in those who were treated with interferon alone for either 24 weeks ( 44 percent ) or 48 weeks ( 41 percent ) . The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy . CONCLUSIONS In patients with chronic hepatitis C , initial therapy with interferon and ribavirin was more effective than treatment with interferon alone BACKGROUND / AIMS Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter r and omized trial , we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C. METHODS Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were r and omized to receive either ribavirin ( 800 mg/day ) plus leucocytic interferon-alpha ( 3 mega units thrice weekly ) or the same dose of interferon-alpha alone , for 6 months . Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies . RESULTS At the end of treatment , aminotransferase levels become normal in 9/26 patients receiving combination therapy ( 35 % [ confidence interval , 16 % to 53 % ] ) and in 2/24 receiving interferon-alpha alone ( 8 % [ confidence interval , -3 % to 19 % ] ) ( p = 0.03 ) . Aminotransferase normalization was never associated with hepatitis C virus RNA clearance . All patients with normal aminotransferase relapsed after discontinuation of therapy . At the end of treatment , mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy , but returned to pretreatment values 6 months thereafter . No histological improvement was observed in either group . CONCLUSIONS There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha 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 BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy , but most subsequently relapse . We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment . A total of 173 patients were r and omly assigned to receive st and ard-dose recombinant interferon alfa-2b concurrently with ribavirin ( 1000 to 1200 mg orally per day , depending on body weight ) for six months , and 172 patients were assigned to receive interferon and placebo . RESULTS At the completion of treatment , serum levels of hepatitis C virus ( HCV ) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone ( 82 percent vs. 47 percent , P<0.001 ) . Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients ( 49 percent ) in the combination-therapy group , but in only 8 patients ( 5 percent ) in the interferon group ( P<0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response . Base-line serum HCV RNA levels of 2 x 10(6 ) copies per milliliter or less were associated with higher rates of response in both treatment groups . Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group . Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone . CONCLUSIONS In patients with chronic hepatitis C who relapse after treatment with interferon , therapy with interferon and oral ribavirin results in higher rates of sustained virologic , biochemical , and histologic response than treatment with interferon alone BACKGROUND Only 15 - 20 % of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy . The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone , for treatment of chronic infection with hepatitis C virus ( HCV ) . METHODS 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin , were enrolled and r and omly allocated one of three regimens : 3 mega units ( MU ) interferon alpha2b three times a week plus 1000 - 1200 mg ribavirin per day for 48 weeks ; 3 MU interferon alpha2b three times a week plus 1000 - 1200 mg ribavirin per day for 24 weeks ; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks . All patients were assessed for safety , tolerance , and efficacy at the end of weeks 1 , 2 , 4 , 6 , and 8 , and every 4 weeks during treatment . After treatment was completed patients were followed up on weeks 4 , 8 , 12 , and 24 . The primary endpoint was loss of detectable HCV-RNA ( serum HCV-RNA < 100 copies/mL ) at week 24 after treatment . FINDINGS Sustained virological response at 24 weeks after treatment , was found in 119 ( 43 % ) of the 277 patients treated for 48 weeks with the combination regimen , 97 ( 35 % ) of the 277 patients treated for 24 weeks with the combination regimen ( p = O.055 ) , and 53 ( 19 % ) of the 278 patients treated for 48 weeks with interferon alone ( p<0.001 vs both combination regimens , intention-to-treat analysis ) . Logistic regression identified five independent factors significantly associated with response : genotype 2 or 3 , viral load less than 2 million copies/mL , age 40 years or less , minimal fibrosis stage , and female sex . Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 ( 95 % Cl 1.4 - 4.8 ; p=0.002 ) for the 48 week combination regimen compared with 24 weeks of the combination regimen . Discontinuation of therapy for adverse events was more frequent with combination ( 19 % ) and monotherapy ( 13 % ) given for 48 weeks than combination therapy given for 24 weeks ( 8 % ) . INTERPRETATION An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile . Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND / AIM Fifty percent of patients infected with hepatitis C virus ( HCV ) show no response to alpha-interferon , and no alternative therapy has thus far proven to be effective . Therapeutic combination with ribavirin and alpha-interferon has shown promising results in naive patients and in relapsers , but based on limited series , it was reported to be inefficient in non-responders . The aim of our study was therefore to explore and compare , in a r and omized trial , the tolerance and potential efficacy of alpha-interferon alone with a sequential combination of ribavirin and the same alpha-interferon regimen in those patients . METHODS Sixty-four non-responder patients were r and omized in the alpha2b-interferon group ( a 6-month course at a dosage of 6 MU followed by a 6-month course of 3 MU three times weekly subcutaneously ) and 62 in the " combination " group ( sequential combination of the same alpha2b-interferon therapy preceded by a 2-month course of ribavirin which was then associated for 2 months with alpha2b-interferon at a daily dosage of 1.0 or 1.2 g ) . RESULTS Treatment withdrawal was necessary for six patients from the alpha-interferon and eight patients from the combination group . Normalization of aminotransferase activities was significantly more frequent after the 4-month course of ribavirin with 2 months of interferon than after 2 months of interferon alone ( 52.8 vs. 26.2 % , p<0.01 ) , but this difference was not maintained after ribavirin withdrawal . Disappearance of serum HCV RNA ( PCR ) was significantly more frequent at the end of treatment in the combination group ( 24.5 vs. 7.7 % , p=0.02 ) , but did not differ 6 months after the end of therapy ( 9.8 and 8.3 % , respectively ) . The long-term response was not associated with liver status ( cirrhosis vs. absence of cirrhosis ) or genotype . Mean viremia was significantly lower in long-term responders than in non-responders or relapsers in both groups ( p<0.001 for the interferon group and p<0.05 for the combination group ) , but the large extent of viral load precluded reliable prediction . The pre- and post-treatment hepatitis activity index did not differ between the two groups . While a crude histopathological improvement in the hepatitis activity index for a given patient was more frequently observed in the combination group ( 69.2 vs. 35.9 % , p<0.01 ) , improvement as defined by a decrease of at least 2 in the hepatitis activity index was significant only for lobular necrosis and degeneration . CONCLUSIONS This study demonstrates the efficacy of the combination of ribavirin/alpha-interferon in non-responders . Indeed , ( i ) it is fairly tolerated ; ( ii ) it increases the rate of the initial biological response , and of the virological response by decreasing breakthrough , though this benefit is not sustained ; and ( iii ) it induces a significant histological improvement in necrosis . A simultaneous and prolonged combination of ribavirin/alpha-interferon should be further evaluated in non-responders BACKGROUND & AIMS Sustained response to interferon treatment for chronic hepatitis C is unsatisfactory . This study examined whether combining interferon alfa with ribavirin induces a better sustained efficacy than interferon alone in the treatment of chronic hepatitis C. METHODS Sixty noncirrhotic patients with chronic hepatitis C were r and omly assigned to three groups . Group 1 received 1200 mg oral ribavirin daily plus 3 million units of recombinant interferon alfa 2a thrice weekly for 24 weeks , group 2 received the same dose of interferon alfa 2a alone for 24 weeks , and group 3 received no treatment . The patients were then followed up for an additional 96 weeks . RESULTS At the end of treatment , a complete response ( normal serum alanine aminotransferase level and undetectable serum hepatitis C virus RNA ) was achieved in 16 of the 21 patients in group 1 ( 76 % ) , as compared with 6 of 19 in group 2 ( 32 % ) and none in group 3 . At 96 weeks after the end of treatment , patients in group 1 sustained a higher complete response rate than patients in group 2 ( 43 % vs. 6 % ) . CONCLUSIONS Combined treatment with ribavirin and interferon alfa 2a for 24 weeks is more effective than interferon alfa 2a alone for the treatment of chronic hepatitis C. The biochemical and virological responses were sustained in about one half of the treated patients for at least 2 years after cessation of the therapy BACKGROUND / AIMS Few data are available concerning the short and long-term effects of beta-IFN in patients with chronic hepatitis C. METHODOLOGY We r and omized 61 consecutive patients with HCV-related cirrhosis to receive : a ) natural beta-IFN with a 6 MU/tiw for 6 months followed by 3 MU/tiw for 6 months schedule or b ) no treatment . Biochemical and virological response was defined by normalization of ALT and negativization of serum HCV-RNA . Patients were followed-up for 5 years . RESULTS A biochemical end-of-therapy response ( ETR ) was observed in 5/38 patients ( 13 % ) who received beta-IFN compared to 2/23 ( 9 % ) of untreated cases , but a virological ETR appeared only in 4/38 ( 11 % ) treated cases . At long-term follow-up , 6 cases ( 16 % ) who received beta-IFN and 4 untreated ( 17 % ) developed a persistent normalization of alanine aminotransferase ( ALT ) but only 2 ( 5 % ) and 1 ( 4 % ) , respectively , were also HCV-RNA negative . The cumulative probability of liver decompensation ( variceal bleeding ascites or hepatic encephalopathy ) at 60 months was 24 % in treated and 35 % in untreated cases . Hepatocellular carcinoma developed in 2 treated and in 1 untreated patients . CONCLUSIONS beta-IFN therapy was not associated with a significant improvement either in biochemical or virological response in cirrhotic patients with chronic hepatitis C. No significant reduction of cirrhosis related clinical events was linked to treatment BACKGROUND Chronic hepatitis C may lead to cirrhosis and hepatocellular carcinoma in a subset of patients . Because response rates with interferon alfa therapy are unsatisfactory , new therapies are needed . METHODS We conducted a three-arm , r and omized trial in 45 interferon-naive men ( mean age 40.6 + /- 12 years ) with chronic hepatitis C to compare treatments : group A , ribavirin alone ( 15 mg/kg daily for 6 months ) ; group B , interferon alone ( 3 MU thrice weekly for 6 months ) ; and group C , interferon plus ribavirin at the above doses . Histologic outcomes of therapy were assessed by pretreatment and post-treatment liver biopsies . RESULTS In group A , alanine aminotransferase levels normalized during therapy in 66 % of those with HCV-1b and 34 % of those with HCV-2a , but all patients relapsed after treatment ended . In group B , alanine aminotransferase levels normalized during treatment in 66 % , 75 % , and 100 % of patients infected with HCV-1b , HCV-2a , and HCV-3 , respectively ; however , a sustained response was noted in only 25 % of those with HCV-3 . In group C , a sustained normalization of alanine aminotransferase with negative serum HCV RNA was seen in 20 % of those with HCV-1b , 40 % of those with HCV-2a , and 75 % of those with HCV-3 12 months after therapy . One year after therapy ended , group C demonstrated a significant sustained response ( 47 % ) as well as a significant reduction in piecemeal necrosis and portal inflammation ( p < 0.05 ) . CONCLUSIONS Combination therapy was significantly superior to ribavirin or interferon monotherapy in producing a sustained response in interferon-naive patients with chronic hepatitis C ( p < 0.05 ) . The results of our study suggest that ribavirin potentiates the effect of interferon therapy in chronic hepatitis Compared to either drug alone , therapy with the combination of ribavirin and interferon-α leads to improved rates of response in patients with chronic hepatitis C. Side effects often m and ate downward dose adjustment or cessation of therapy , and the optimal dose of ribavirin has not been established . The aim of this study was to learn whether 600 mg ribavirin per day would prove as efficacious as 1000–1200 mg/day when combined with interferon ( 3 million units thrice weekly ) for therapy of patients previously treated with st and ard interferon who had failed to respond or who had relapsed . We enrolled 69 patients with chronic hepatitis C and compensated liver disease : 45 were men , 65 were Caucasian , 48 were infected with genotype 1 hepatitis C virus . By r and om assignment , 35 received 600 mg ribavirin/day ( group A ) , whereas the other 34 received 1000 mg ( ≤75 kg body wt ) or 1200 mg/day ( > 75 kg body wt ) ( group B ) . At baseline , the two groups were well matched for demographic and laboratory features . In both groups , mean serum levels of alanine aminotransferase ( ALT ) and hepatitis C viral ( HCV ) RNA levels fell promptly and remained significantly lower than baseline throughout 24 weeks of therapy . There was no significant difference in mean levels of ALT or HCV RNA during therapy or at the end of follow-up ( 24 weeks after cessation of therapy ) . At the end of 24 weeks of posttherapy follow-up , 12 patients in each group had undetectable HCV RNA in serum , whereas 11 ( 31 % ) in group A and 9 ( 26.5 % ) in group B had normal serum ALT levels . The lower doses of ribavirin ( group A ) were tolerated better . % In conclusion , in previous nonresponders or relapsers to interferon done , combination therapy with interferon-α2b ( 3 MU thrice weekly ) + 600 mg ribavirin/day is tolerated better and is as effective as interferon plus higher ( st and ard ) doses of ribavirin ( 1000–1200 mg/day ) BACKGROUND / AIMS Data on hepatitis C virus ( HCV ) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection . We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin . METHODS We r and omly assigned 321 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b ( 3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks ) and ribavirin ( 36 week treatment ) . RESULTS The rate of sustained virologic response ( defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment ) was higher in patients who received combination therapy with three times weekly interferon ( 51.7 % ) or daily interferon ( 46.1 % ) than in patients who received interferon alone ( 25 % ) ( P=0.0001 and P=0.002 , respectively ) . Independent predictive factors for sustained virologic response were combination therapy , weight , genotype and viral load . In conclusion , in patients with chronic hepatitis C , combination therapy with induction treatment ( daily interferon for 12 weeks ) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment . CONCLUSIONS Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective BACKGROUND Treatment with pegylated interferon ( peginterferon ) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or st and ard dose of ribavirin . DESIGN R and omized , double-blind trial . SETTING 99 international centers . PATIENTS 1311 patients with chronic hepatitis C. INTERVENTION Peginterferon-alpha2a , 180 microg/wk , for 24 or 48 weeks plus a low-dose ( 800 mg/d ) or st and ard weight-based dose ( 1000 or 1200 mg/d ) of ribavirin . MEASUREMENT Sustained virologic response : undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up . RESULTS Overall and in patients infected with HCV genotype 1 , 48 weeks of treatment was statistically superior to 24 weeks and st and ard-dose ribavirin was statistically superior to low-dose ribavirin . In patients with HCV genotype 1 , absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2 % ( 95 % CI , 3.6 % to 18.9 % ) and 11.9 % ( CI , 4.7 % to 18.9 % ) , respectively , between st and ard- and low-dose ribavirin . Sustained virologic response rates for peginterferon-alpha2a and st and ard-dose ribavirin for 48 weeks were 63 % ( CI , 59 % to 68 % ) overall and 52 % ( CI , 46 % to 58 % ) in patients with HCV genotype 1 . In patients with HCV genotypes 2 or 3 , the sustained virologic response rates in the 4 treatment groups were not statistically significantly different . CONCLUSION Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype . Patients with HCV genotype 1 require treatment for 48 weeks and a st and ard dose of ribavirin ; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks BACKGROUND / AIMS In chronic hepatitis C , interferon-alpha ( alpha-IFN ) and ribavirin combination therapy improves sustained response compared to alpha-IFN monotherapy , both in naive patients and in previous alpha-IFN relapsers , but the efficacy of such therapy remains limited in non-responder cases . The aim of this study was to assess whether the pattern of response to alpha-IFN alone may predict sustained response to combination therapy during retreatment . METHODS Fifty previous alpha-IFN relapsers and 50 previous alpha-IFN non-responders were retreated with a high alpha-IFN dose ( 6 MU/thrice weekly for 2 months ; induction phase ) and then r and omised to continue with alpha-IFN alone ( 3 MU/thrice weekly ) or to receive combination therapy ( 3 MU/thrice weekly of alpha-IFN and 1000 - 1200 mg/daily of ribavirin ) for an additional 6 months according to the biochemical response to alpha-IFN shown after the induction phase . All patients were also evaluated for virological and histological response . RESULTS Eleven of 25 ( 44 % ) relapsers treated with combination therapy and 4/25 ( 16 % ) treated with alpha-IFN alone achieved a sustained response . The corresponding figures among non-responders were 1/25 ( 4 % ) and 0/25 , respectively . Among 26 patients with a complete ALT and HCV-RNA response after 2 months of alpha-IFN , sustained response was seen in 11/14 ( 79 % ) treated with combination therapy and in 4/12 ( 33 % ) treated with alpha-IFN alone ( p=0.05 ) . On the other h and , of 74 cases still HCV-RNA positive after 2 months of alpha-IFN alone , biochemical and virological end of therapy response was better with combination therapy ( 11/36 ; 30.5 % ) compared to alpha-IFN alone ( 4/38 ; 10.5 % ) , but only one patient developed a sustained response ( 1/36 ; 3 % ) . CONCLUSIONS The retreatment with a 6-month combination therapy was associated with a high rate of sustained response only in patients showing a complete biochemical and virological response to alpha-IFN alone . Longer retreatment with combination therapy may be needed to achieve a sustained response in patients without a prompt virological response to alpha-IFN |
13,913 | 10,796,871 | Treatment provided a significant reduction in albumin excretion rate in both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus .
Treatment with either captopril , enalapril or lisinopril reduced albumin excretion rate in comparison with control patients .
A greater lowering of blood pressure was experienced by initially normotensive patients in the angiotensin converting enzyme inhibitor than in the placebo group .
Pooled end-of- study mean blood pressures for the treated group were significantly lower than for the untreated group , although this was not so for all individual studies .
The apparent ( treatment - placebo ) ' effect ' on systolic and diastolic pressures had a larger st and ard error for longer lasting studies .
Average haemoglobin fell a little in the treated patients and rose in the controls but neither this nor the difference in changes in glomerular filtration rate reached statistical significance .
REVIEW ER 'S CONCLUSIONS Inhibition of angiotensin converting enzyme can arrest or reduce the albumin excretion rate in microalbuminuric normotensive diabetics , as well as reduce or prevent an increase in blood pressure .
But , given the drop in blood pressure in patients on angiotensin converting enzyme inhibitors , it is not possible to be certain that the reduction of albumin excretion rate is due to a separate renal effect .
A direct link with postponement of end-stage renal failure has not been demonstrated .
There appear to be no substantial side effects | OBJECTIVES To examine whether the progression of early diabetic renal disease to end-stage renal failure may be slowed by the use of angiotensin converting enzyme inhibitors for reasons other than their antihypertensive properties , so that they have value in the treatment of normotensive diabetics with microalbuminuria . | OBJECTIVE --To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy ( albuminuria greater than 300 mg/24h ) . DESIGN --Open r and omised controlled study of four years ' duration . SETTING --Outpatient diabetic clinic in tertiary referral centre . PATIENTS --44 normotensive ( mean blood pressure 127/78 ( SD 12/10 ) mm Hg ) insulin dependent diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24h ) . INTERVENTIONS --The treatment group ( n = 21 ) was initially given captopril ( 25 mg/24 h ) . The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months . The remaining 23 patients were left untreated . MAIN OUTCOME MEASURES --Albuminuria , kidney function , development of diabetic nephropathy ( albuminuria greater than 300 mg/24 h ) , and arterial blood pressure . RESULTS -- Clinical and laboratory variables were comparable at baseline . Urinary excretion of albumin was gradually reduced from 82 ( 66 - 106 ) to 57 ( 39 - 85 ) mg/24 h ( geometric mean ( 95 % confidence interval ) ) in the captopril treated group , whereas an increase from 105(77 - 153 ) to 166 ( 83 - 323 ) mg/24 h occurred in the control group ( p less than 0.05 ) . Seven of the untreated patients progressed to diabetic nephropathy , whereas none of the captopril treated patients developed clinical overt diabetic nephropathy ( p less than 0.05 ) . Systemic blood pressure , glomerular filtration rate , haemoglobin A1c concentration , and urinary excretion of sodium and urea remained practically unchanged in the two groups . CONCLUSIONS --The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria Abstract This study tested the hypothesis that passive exposure to posters containing essential information on cardiopulmonary resuscitation ( CPR ) displayed on lavatory walls improves theoretical knowledge and the performance of CPR . There was a significant increase in both knowledge and performance of CPR after exposure to the posters . This technique is inexpensive and simple , and it warrants more widespread use as a means of maintaining knowledge and proficiency in CPR Recent studies utilizing converting enzyme inhibitors ( CEI ) in diabetic rats document reductions in both renal hypertrophy and albuminuria . Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction . The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive , hyperfiltering insulin-dependent diabetic ( IDDM ) patients . Fifteen IDDM patients were r and omized to either placebo or the CEI , lisinopril . Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate ( GFR ) to < or = 2.33 mL/sec . Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size ( 16.9 + /- 1.1 , baseline versus 12.8 + /- 0.9 cm , 18 months ; p < 0.05 ) and microalbuminuria ( 92 + /- 11 micrograms/min , baseline versus 23 + /- 26 micrograms/min , 18 months ; p < 0.05 ) . No change in renal size was noted in the placebo group ( 15.4 + /- 0.8 , baseline versus 14.9 + /- 0.7 cm , 18 months ; NS ) and albuminuria increased ( 118 + /- 15 micrograms/min , baseline versus 293 + /- 32 micrograms/min , 18 months ; p < 0.05 ) . Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo ( 102 + /- 4 , placebo versus 87 + /- 6 mm Hg , CEI , p < 0.05 ) . This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI . The overall impact of these findings on preservation of renal function can not be assessed , however , in this short-term study PURPOSE To determine whether angiotensin-converting enzyme ( ACE ) inhibition with captopril reduces the progression of microalbuminuria to overt proteinuria in normotensive patients with insulin-dependent diabetes mellitus ( IDDM ) . PATIENTS AND METHODS This study was a prospect i ve r and omized , double-blind , placebo-controlled trial involving 26 centers in the United States and Canada . One hundred forty-three subjects , 14 to 57 years of age , with IDDM for 4 to 33 years , blood pressure < 140/90 mm Hg in the absence of antihypertensive therapy , and persistent albumin excretion 20 to 200 micrograms/min were r and omized to double-blind treatment with captopril 50 mg or placebo BID . Albumin excretion rate ( AER ) , blood pressure , and glycohemoglobin were determined every 3 months , and creatinine clearance ( CrCl ) and urea excretion were measured every 6 months . RESULTS Within 24 months , 6.0 % ( 4/67 ) of captopril-treated subjects and 18.6 % ( 13/70 ) of placebo-treated subjects progressed to clinical proteinuria , defined as AER > 200 micrograms/min and at least 30 % above baseline ( risk reduction = 67.8 % , P = 0.037 ) . AER increased at an annual rate of 11.8 % ( 95 % confidence interval [ CI ] -3.3 % to 29.1 % ) in the placebo group , while it declined by 17.9 % ( CI -29.6 % to -4.3 % ) in the captopril group ( P = 0.004 ) . CrCl decreased by 4.9 mL/min per 1.73 m2 per year in the placebo group , while it remained stable in the captopril group ( 0.9 mL/min per 1.73 m2 per year , P = 0.039 between groups ) . Ten subjects required treatment for hypertension ; 8 in the placebo group and 2 in the captopril group . There was little correlation between the 24-month changes in mean arterial blood pressure and AER in either group . Glycohemoglobin and urinary urea excretion did not differ between groups . CONCLUSIONS After 24 months of therapy with captopril , compared with placebo , normotensive subjects with IDDM experienced significantly less progression of microalbuminuria to clinical proteinuria , reduced albumin excretion , and preserved CrCl rate . The ACE inhibitor , captopril , was well tolerated The effect of long term , aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospect ively in 11 insulin dependent diabetics ( mean age 30 ) . During the mean pretreatment period of 32 ( range 23 - 66 ) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly . During the 72 ( range 32 - 91 ) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min . The rate of decline in the glomerular filtration rate decreased from 0.89 ( range 0.44 - 1.46 ) ml/min/month before treatment to 0.22 ( range 0.01 - 0.40 ) ml/min/month during treatment . The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment ( greater than or equal to 6 years ) . One patient died from acute myocardial infa rct ion ( glomerular filtration rate 46 ml/min/1.74 m2 ) . Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy The effects of a long term reduction in blood pressure on the kidney function of normotensive diabetic patients who had persistent microalbuminuria ( 30 - 300 mg albumin/24 hours ) were studied in two groups of 10 such patients before and during six months of treatment with either 20 mg enalapril or placebo daily . Treatments were assigned r and omly in a double blind fashion . Before treatment both groups had similar clinical characteristics , weight , diet , total glycosylated haemoglobin , median albumin excretion rate ( enalapril group 124 mg/24 h , placebo group 81 mg/24 h ) , and mean arterial pressure ( enalapril group 100 ( SD 8) mm Hg , placebo group 99 ( 6 ) mm Hg ) . During treatment weight , urinary urea excretion , and total glycosylated haemoglobin remained unchanged . The mean arterial pressure decreased in the enalapril group but not in the placebo group ( enalapril group 90 ( 10 ) mm Hg , placebo group 98 ( 8) mm Hg ) . The median albumin excretion rate also fell in the enalapril group but not in the placebo group ( enalapril group 37 mg/24 h , placebo group 183 mg/24 h. ) The glomerular filtration rate rose in the enalapril group from 130 ( 23 ) ml/min/1.73 m2 to 141 ( 24 ) ml/min/1.73 m2 , and total renal resistances and fractional albumin clearance decreased while fractional albumin clearance increased in the placebo group . These results show that in patients who have diabetes but not hypertension a reduction in blood pressure by inhibition of converting enzyme for six months can reduce persistent microalbuminuria , perhaps by decreasing the intraglomerular pressure OBJECTIVE To study the effect of Captopril on ambulatory blood pressure , renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients . DESIGN R and omized , double blind placebo controlled study of two years duration . SETTING University clinic . PATIENTS Twenty-two patients without hypertension . INTERVENTION Patients received 50 mg Captopril or placebo twice a day . MEASUREMENTS Ambulatory blood pressure , renal function , extracellular volume , and echocardiographic indices of cardiac function and dimensions were assessed annually . Clinic blood pressure and urinary albumin excretion were measured every 3 months . RESULTS Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group ( mean + /- SD ) ( baseline 93 + /- 4 and follow up 91 + /- 8 mmHg ) and in the placebo group ( 96 + /- 7 and 97 + /- 10 mmHg , NS ) . Night/day ratio of blood pressure was unaffected . Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril ( 557 + /- 97 and 600 + /- 112 ml min-1 ) versus the placebo group ( 574 + /- 85 and 535 ml min-1 , p = 0.05 ) . Filtration fraction was reduced in the Captopril versus the placebo group ( p < 0.05 ) . Extracellular volume and echocardiographically derived parameters were unaffected . The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion ( Spearmans r = 0.85 , p < 0.05 ) unlike clinic mean arterial blood pressure ( r = 0.33 , p = 0.35 ) . CONCLUSION Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril . Renal plasma flow was increased and filtration fraction reduced . A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements Based on animal experiments it has been proposed that antihypertensive agents may differentially influence albuminuria through their divergent effects on glomerular haemodynamics or glomerular sieving properties and may beneficially influence the progression of diabetic nephropathy even without an effect on blood pressure . However , to date this hypothesis has not been tested in normotensive patients with diabetic nephropathy . The main aim of this study was therefore to investigate the effects of the administration of two antihypertensive agents on albuminuria during rest and exercise . The study consisted of 3 x 3 r and omised , cross-over periods with five days double blind administration of enalapril ( E : 2.5 mg bid ) , nitrendipine ( N : 5 mg bid ) and placebo ( P ) on 18 Type 1 normotensive ( blood pressure < 140/90 mmHg ) diabetic patients with incipient diabetic nephropathy ( albuminuria 30 - 300 mg/24 h , normal glomerular filtration rate , diabetes duration > 6 years and presence of diabetic reinopathy . The aim of this study was to investigate the effect of enalapril and nitrendipine on blood pressure values and albuminuria during exercise challenge ( bicycle ergometry : 20 min at 75 W and 20 min at 100 W ) in comparison to the placebo . Albumin excretion rates during pre-exercise rest ( mean + /- SD ; E : 6.2 + /- 6.0 ; N : 7.1 + /- 8.0 ; P : 7.7 + /- 7.0 mg/mmol creatinine ) and during exercise ( E : 8.7 + /- 9.4 ; N : 8.2 + /- 8.2 ; P : 11.1 + /- 11.4 mg/mmol creatinine ) were comparable between the drugs and not significantly different after administration of placebo . Blood pressure values were significantly different between the medications ( systolic blood pressure : p = 0.0269 ; diastolic blood pressure : p = 0.0021 , ANOVA for repeated measurements ) . There were no significant correlations between blood pressure values and albuminuria at any time . In normotensive patients with incipient diabetic nephropathy low-dose administration of enalapril , nitrendipine and placebo does not result in clear cut differences in albuminuria STUDY OBJECTIVE --To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy . DESIGN --R and omised follow up study of normotensive diabetics with persistent microalbuminuria ( 30 - 300 mg/24 hours ) treated with enalapril or its matched placebo for one year . Double blind for first six months , single blind for last six months . SETTING --Diabetic clinic in tertiary referral centre . PATIENTS --Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria . INTERVENTIONS --Treatment group was given enalapril 20 mg daily and controls matched placebo . Patients were given antihypertensive treatment after one year . END POINT -- Albumin excretion , arterial pressure , and renal function . MAIN RESULTS --In last three months of trial three of 10 patients taking placebo had diabetic nephropathy ( albumin excretion greater than 300 mg/24 hours ) . No patients taking enalapril developed nephropathy and five showed normal albumin excretion ( less than 30 mg/24 hours ) ( p = 0.005 , Mann-Whitney test ) . Mean arterial pressure was reduced by enalapril throughout study ( p less than 0.005 ) but increased linearly with placebo ( p less than 0.05 ) . Albumin excretion decreased linearly with enalapril but not placebo . An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure ( r = 0.709 , p less than 0.05 , Spearman 's rank test ) . With enalapril total renal resistances and fractional albumin clearances improved progressively ( time effect , p = 0.0001 ) . CONCLUSION --Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria . This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure . Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs Several studies have suggested that ACE-inhibition may be effective in postponing the onset of nephropathy in insulin-dependent diabetic subjects . In contrast , other drugs might have opposing effects . To study the long term effects of either captopril or nifedipine in normotensive , microalbuminuric patients with insulin-dependent diabetes mellitus , eighteen subjects received either placebo ( n = 5 , P ) , 20 mg nifedipine daily ( n = 7 , N ) or 50 mg captopril daily ( n = 6 , C ) for one year . Baseline clinical and laboratory variables were comparable in the three groups . Glomerular filtration rate ( GFR ) , effective renal plasma flow ( ERPF ) and blood pressure did not differ between groups before and after one years medication . UAER did not change in the captopril and the placebo group ( C : -12.6 % ( -58.1 to 51.8 % ) ' P : -17.3 ( -55.9 to 99.3 % ) , medians and ranges . In contrast , in the patients that received nifedipine , UAER rose by 43.1 % ( -8.5 to 261.8 % ) , ( p < 0.05 Baseline vs one year , and one year nifedipine vs captopril and placebo ) . We therefore conclude , that long-term use of nifedipine increases UAER in normotensive microalbuminuric insulin-dependent subjects , in contrast to captopril or placebo . Whether this enhancement of microalbuminuria exerts an adverse effect on renal function in the long-term is yet unknown , but caution seems warranted The effect of early aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospect ively in ten insulin-dependent diabetics ( mean age 29 years ) . During the mean pretreatment period of 29 ( range 23 - 38 ) months the glomerular filtration rate ( GFR ) decreased significantly and the urinary albumin excretion rate and arterial blood pressure rose significantly . During the 39 month ( range 28 - 48 ) period of antihypertensive treatment with metoprolol , hydralazine , and frusemide ( furosemide ) or thiazide , arterial blood pressure fell from 144/97 mm Hg ( mean of all pretreatment values ) to 128/84 mm Hg ( mean of all post-treatment values ) , urinary albumin excretion from 977 micrograms/min to 433 micrograms/min , and GFR from 80 to 62 ml/min/1 . 73 m2 . The rate of decline in GFR decreased from 0.91 ml/min/month before treatment to 0.39 ml/min/month ( range 0.08 to 0.68 ml/min/month ) during treatment OBJECTIVE --To compare the efficacy of angiotensin converting enzyme inhibition with calcium antagonism in diabetic patients with microalbuminuria . DESIGN --R and omised study of diabetic patients with microalbuminuria treated with perindopril or nifedipine for 12 months and monitored for one or three months after stopping treatment depending on whether they were hypertensive or normotensive . Patients were r and omised separately according to whether they were hypertensive or normotensive . SETTING --Diabetic clinics in three university teaching hospitals . PATIENTS --50 diabetic patients with persistent microalbuminuria . In all , 43 completed the study : 30 were normotensive and 13 hypertensive ; 19 had type I diabetes and 24 had type II diabetes . INTERVENTIONS --For 12 months 20 patients were given perindopril 2 - 8 mg daily and 23 were given nifedipine 20 - 80 mg daily . MAIN OUTCOME MEASURES --Albumin excretion rate , blood pressure , and glomerular filtration rate . RESULTS --Both perindopril and nifedipine significantly reduced mean blood pressure . During treatment there was no significant difference between those treated with perindopril and those treated with nifedipine with respect to albuminuria or mean blood pressure . Stopping treatment with both drugs was associated with a sustained increase in albuminuria and mean blood pressure . There was a significant correlation between mean blood pressure and albuminuria and also between the reduction in mean blood pressure and the decrease in albuminuria during treatment with both drugs . In hypertensive patients both drugs caused significant decreases in mean blood pressure and albuminuria . In normotensive patients there was no significant reduction in albuminuria with either regimen . CONCLUSIONS --In diabetic patients with microalbuminuria blood pressure seems to be an important determinant of urinary albumin excretion . Perindopril and nifedipine have similar effects on urinary albumin excretion , both preventing increases in albuminuria in normotensive patients and decreasing albuminuria in hypertensive patients The beneficial effect of long-term treatment with an angiotensin-converting enzyme ( ACE ) inhibitor on urinary microalbumin excretion ( UAE ) and renal function was investigated in a 4 year , r and omized prospect i ve study in normotensive patients with non-insulin-dependent ( Type 2 ) diabetes mellitus . Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were r and omized to receive either enalapril 5 mg day-1 or no treatment . In the enalapril-treated patients , UAE was reduced from 115.4 + /- 80.1 to 95.6 + /- 61.7 mg 24 h-1 after 12 months ( p < 0.05 ) and to 75.3 + /- 44.8 mg 24 h-1 after 48 months ( p < 0.001 ) . In the untreated group , UAE increased slowly from 93.9 + /- 69.9 to 150.0 + /- 144.5 mg 24 h-1 after 48 months . No changes in creatinine clearance , blood pressure or HbA1C were seen in either group during the 4-year period . In normotensive Type 2 diabetic patients with early stage of diabetic microalbuminuria . This effect is long-lasting and probably independent of the antihypertensive action of the drug Microalbuminuria is a predictor of overt diabetic nephropathy and macrovascular disease . Thirty-one diabetic patients with persistent urinary albumin excretion rate ( AER ) of 20 - 200 mu g min-1 were r and omised to receive indapamide 2.5 mg or captopril 37.5 mg daily for 12 weeks . After a 4-week washout , patients received the alternate agent for 12 weeks . Resting blood pressure ( BP ) , AER , cholesterol , triglycerides , and HbA1c were measured at baseline , after 6 and 12 weeks of each treatment , and after a 4-week washout period following each treatment arm . Results from patients who completed at least one treatment arm were analysed by repeated- measures analysis of variance ( ANOVA ) . AER ( median value and interquartile range ) decreased significantly from baseline after treatment with indapamide and captopril [ 60(27 - 106 ) vs. 40(14 - 112 ) and 33(17 - 100 ) ; p < 0.005 ] , but there was no difference between the effects of the two agents . Mean systolic BP ( SBP ) was also significantly reduced with treatment , and no difference was noted between the effects of the two agents . No correlation between changes in AER and SBP was noted with either agent . Diastolic blood pressure ( DBP ) , cholesterol , triglycerides , and HbA1c did not change during the study . These results suggest that indapamide is an effective alternative to angiotensin-converting enzyme ( ACE ) inhibitors in the treatment of diabetic patients with microalbuminuria BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries . Duration of diabetes , blood pressure values , and metabolic status are the major determinants of the course of nephropathy , and microalbuminuria is the hallmark of its onset . Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus . Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy . METHODS Double-blinded ( first phase ) and open ( second phase ) r and omized controlled study of 7 years . Ninety-four normotensive patients with non-insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 mumol/L ( 1.4 mg/dL ) and who had microalbuminuria ( 30 to 300 mg/24 h ) were given enalapril maleate , 10 mg/d , or placebo , for 5 years . For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment . RESULTS In the enalapril-treated patients , albuminuria remained stable for 7 years . An increase from ( mean + /- SD ) 123 + /- 58 to 310 + /- 167 mg/24 h occurred in the untreated group after 5 years , and a further increase to ( mean + /- SD ) 393 + /- 223 mg/24 h occurred after 7 years . Reciprocal creatinine was unchanged in treated patients for 7 years ; in the untreated patients , the mean decline was 13 % at 5 years and 16 % at 7 years . Treatment with enalapril result ed in an absolute risk reduction of 42 % for nephropathy to develop during 7 years ( 95 % confidence interval , 15 % to 69 % ; P < .001 , Student 's t test ) . Glycosylated hemoglobin and body mass index remained unchanged . CONCLUSIONS Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with noninsulin-dependent diabetes mellitus who have microalbuminuria , and it stabilizes renal function in previously untreated patients with impaired renal function . Discontinuation of treatment results in renewed progression of nephropathy OBJECTIVE --To compare the effects of sodium depletion and of angiotensin I converting enzyme inhibition on microalbuminuria in insulin dependent diabetes . DESIGN --R and omised , double blind , double dummy parallel study of normotensive diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24 h ) treated with enalapril or hydrochlorothiazide for one year after a three month , single blind placebo period . SETTING --Diabetic clinic in a tertiary referral centre . PATIENTS --10 diabetic patients with low microalbuminuria ( 30 - 99 mg/24 h ) and 11 with high microalbuminuria ( 100 - 300 mg/24 h ) . INTERVENTIONS --11 subjects ( six with low microalbuminuria , five with high microalbuminuria ) were given enalapril 20 mg plus placebo hydrochlorothiazide once daily and 10 ( four with low microalbuminuria , six with high microalbuminuria ) hydrochlorothiazide 25 mg plus placebo enalapril once daily . MAIN OUTCOME MEASURES --Monthly assessment of urinary albumin excretion and mean arterial pressure ; plasma active renin and aldosterone concentrations and renal function studies at 0 , 6 , and 12 months . RESULTS --Median urinary albumin excretion decreased from 59 ( range 37 - 260 ) to 38 ( 14 - 146 ) mg/24 h with enalapril and from 111 ( 33 - 282 ) to 109 ( 33 - 262 ) mg/24 h with hydrochlorothiazide ( analysis of variance , p = 0.0436 ) . During the last three months of treatment with enalapril five patients had persistent normoalbuminuria ( 2 - 3 times below 30 mg/24 h ) , five low microalbuminuria , and one high microalbuminuria ; in the hydrochlorothiazide group one had normoalbuminuria , three low microalbuminuria , and six high microalbuminuria ( chi 2 test = 6.7 ; p = 0.03 ) . Mean arterial pressure did not differ before ( 98 ( SD 7 ) with enalapril v 97 ( 9 ) mm Hg with hydrochlorothiazide ) or during treatment ( 88 ( 7 ) with enalapril v 90 ( 7 ) mm Hg with hydrochlorothiazide ( analysis of variance , p = 0.5263 ) ) . Glomerular filtration rate did not vary . The aldosterone to active renin ratio was decreased by angiotensin I converting enzyme inhibition and increased by sodium depletion , showing treatment efficacy . CONCLUSION --Angiotensin I converting enzyme inhibition by enalapril effectively reduces microalbuminuria in normotensive diabetic patients whereas hydrochlorothiazide is not effective . Changes in blood pressure and activity of the renin-angiotensin-aldosterone system may contribute to these different effects OBJECTIVE --To assess whether inhibition of angiotensin converting enzyme protects kidney function in diabetic nephropathy . DESIGN --Open , r and omised follow up study of normotensive insulin dependent diabetics with nephropathy either treated or not with captopril for one year . SETTING --Outpatient diabetic clinic in a tertiary referral centre . PATIENTS --32 Normotensive patients with insulin dependent diabetes complicated by nephropathy who were r and omised either to the treatment group ( n = 15 ) or to the control group ( n = 17 ) . INTERVENTIONS --The treatment group was given captopril ( 25 - 100 mg/day ) for 12 months , the average dose during the second six months of the study being 40 mg daily . Controls were not treated . MAIN OUTCOME MEASURES --Albuminuria , arterial blood pressure , and the glomerular filtration rate . RESULTS --Mean arterial blood pressure fell by 3 ( SE 2 ) mm Hg in the captopril treated group and rose by 6 ( 1 ) mm Hg in the controls . In addition , albuminuria declined by 11 % in the captopril treated group and rose by 55 % in the controls , fractional albumin clearance fell by 17 % in the captopril treated group and increased by 66 % in the controls , and the glomerular filtration rate declined by 3.1 (2.8)ml/min/1.73 m2 with captopril and by 6.4 ( 3.1 ) ml/min/1.73 m2 in the controls . CONCLUSION --Inhibition of angiotensin converting enzyme arrests the progressive rise in albuminuria in normotensive insulin dependent diabetics with nephropathy OBJECTIVE This study determines the long-term efficacy of the ACE inhibitor , enalapril , in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate ( AER ) 20–200 micrograms/min and normal renal function followed for 5 years in a prospect i ve r and omized single-blind placebo-controlled trial . AER , blood pressure , fasting plasma glucose , and HbA1 were measured every 3–4 months and glomerular filtration rate ( GFR ) , renal plasma flow ( RPF ) , and urinary urea every 12 months . RESULTS In the patients treated with enalapril , AER decreased from 55 ± 33 to 20 ± 59 micrograms/min ( geometric mean ± SD ) , whereas in the placebo group , AER increased from 53 ± 31 to 85 ± 90 micrograms/min after 5 years . Within 5 years , 7.7 % ( 4/52 ) of enalapril-treated subjects and 23.5 % ( 12/51 ) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34 % above baseline ( risk reduction = 66.7 % , P < 0.001 ) . AER increased at an annual rate of 12.3 % ( 95 % CI 9.8–14.9 ) in the placebo group , while it declined by 16.7 % ( 95 % CI −18.3 to −15.2 ) in the enalapril group ( P < 0.001 ) . In addition , 8 of the 12 placebo-treated patients had evidence of coronary artery disease . The rest of the parameters remained practically unchanged in the two groups . CONCLUSIONS After 5 years of therapy with enalapril , compared with placebo , normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria , reduced AER , and preserved GFR Diabetic nephropathy is the single most important cause of end-stage renal failure in the western world . It accounts for 15 % to 25 % of all renal failure in patients receiving chronic dialysis [ 1 ] . About 40 % of type I and 20 % of type II diabetics develop clinical ly important nephropathy [ 2 - 4 ] . However , the ratio of type II to type I diabetics is 10 to 1 , and the number of patients with chronic renal failure due to type II disease exceeds that of type I [ 4 - 6 ] . Therefore , an obvious need exists to evaluate treatments that may delay the progress of nephropathy in type II diabetes . However , most studies of diabetic renal disease have hitherto focused on type I diabetes . Available data suggest that effective antihypertensive treatment is the best inhibitor of diabetic nephropathy [ 7 - 10 ] . Angiotensin-converting enzyme inhibitors have been found more effective than placebo and -adrenergic blocking agents in hypertensive as well as in normotensive diabetics with early and advanced nephropathy [ 11 - 15 ] . Some classes of calcium antagonists effectively decrease urinary protein excretion and may preserve renal function . However , analysis of several studies shows that , although the effects of angiotensin-converting enzyme inhibitors are consistent , those of calcium antagonists vary [ 16 - 18 ] . Short-term studies showed a clear antiproteinuric effect of captopril and of enalapril on the diabetic kidney , probably independent of the antihypertensive effect of these agents [ 14 , 15 , 19 ] . However , the outcome of long-term intervention and the possibility of a true alteration of the natural course of the disease were unknown . We did a relatively long-term , 5-year study of the effect of the angiotensin-converting enzyme inhibitor , enalapril , on the course of diabetic nephropathy in normotensive , type II diabetic patients with microalbuminuria and normal renal function . Our report describes a r and omized , placebo-controlled , double-blind study on 94 diabetic patients . Methods Patients A total of 108 patients with type II diabetes mellitus , diagnosed according to World Health Organization criteria [ 20 ] who attended six clinics in the Tel Aviv area were recruited during 1986 and gave informed consent to participate in the study . The inclusion criteria were as follows : age less than 50 years ; duration of diabetes mellitus of less than 10 years with no evidence of systemic , renal , cardiac , or hepatic diseases ; body mass index less than 27 kg/m2 ; normal blood pressure values on two consecutive examinations ( systolic , 140 mm Hg ; diastolic , 90 mm Hg ; mean blood pressure < 107 mm Hg ) ; serum creatinine , < 123 mol/L ( 1.4 mg/dL ) ; and microalbuminuria ( urinary protein excretion of 30 to 300 mg/24 h ) on two consecutive visits without evidence of urinary tract infection . Initially , there were 49 men and 59 women , ages 34 to 49 years ( mean age [ SD ] , 44 4 years ) . The duration of diabetes was 0.5 to 9.1 years ( mean duration [ SD ] , 6.7 1.6 years ) . Sixteen patients received insulin , 43 were taking oral hypoglycemic agents , and 49 were using diet to control their diabetes . Protocol The protocol was approved by the hospital review board . After a 2-month pretreatment period , the patients were r and omly allocated to receive either 10 mg enalapril ( Teva Pharmaceutical Industries , Ltd. , Petach Tikwa , Israel ) daily or placebo in a double-blind manner . The placebo tablets were similar but not identical to enalapril . R and omization was done using a table of r and om numbers [ 21 ] . The follow-up period was terminated , for each patient , exactly 5 years after his or her r and omization , and the data were su bmi tted for evaluation . The patients were seen by their family physicians approximately every 3 to 4 months . On these visits , fasting blood glucose , glycosylated hemoglobin , serum creatinine , serum electrolyte levels , and albuminuria in 24-hour urine sample s were determined . Blood pressure was measured by mercury sphygmomanometers with the patients sitting after a 5-minute rest ; the average of two determinations was recorded . The diastolic pressure was determined at Korotkoff phase V. If systolic blood pressure values of 145 mm Hg , or diastolic values of 95 mm Hg , were found on two consecutive occasions , treatment with long-acting nifedipine ( Pressolate , Agis Industries Ltd. , Yeruham , Israel ) was initiated . Funduscopy was done yearly by an ophthalmologist , and the presence of diabetic retinopathy was recorded . Measurements Glucose and creatinine levels were determined by routine automated methods . Glycosylated hemoglobin levels were measured by affinity chromatography with a commercial kit ( Isolab , Biochemical Methodology , Drower 4350 , Akron , Ohio ) . The albumin excretion rate was measured on 24-hour urine sample s by an automated immunoturbidimetric assay [ 22 ] . Sixteen to 20 fasting blood glucose determinations and 15 to 20 glycosylated hemoglobin values were available for each patient . For each patient , the correlation coefficients between fasting blood glucose and glycosylated hemoglobin levels were between 0.60 and 0.84 . The mean blood pressure values were calculated for each patient ( mean pressure defined as diastolic value plus one third of the pulse pressure ) . The reciprocal creatinine value ( 100/creatinine value ) was calculated for each visit [ 23 ] , and the decline in renal function was expressed as a percentage of the initial value . The course of renal function , of the mean blood pressure , and of urinary protein excretion were plotted against time ( separately ) for the enalapril and the placebo groups . Statistical Analysis All data were expressed as mean ( SD ) and ranges . Significance was defined as P < 0.05 . To test for adequate r and omization , the enalapril and placebo groups were compared with respect to mean age , mean duration of diabetes , as well as mean baseline values of albuminuria , serum creatinine , glycosylated hemoglobin , and mean blood pressure using pooled variance Student t-tests for independent groups as well as one-way analysis of variance . To compare the annual means of the various measurements between the two groups and within each group , one between-group factor and one repeated measures factor were used in analysis of variance . The rate of decrease of reciprocal creatinine levels and the rate of increase of albuminuria were calculated by linear regression analysis . Results Five patients , 2 taking enalapril and 3 taking placebo left the study during the first year . Six patients ( 4 taking enalapril and 2 taking placebo ) developed a disturbing cough , and the treatment was discontinued . Three patients ( 1 on enalapril and 2 on placebo ) were lost to follow-up during the third and fourth years . The final analysis was therefore done on 94 patients , of whom 49 received enalapril and 45 received placebo . Age , male/female ratio , duration of diabetes , and the other baseline data of the two groups are shown in Table 1 . No statistically significant differences existed between the initial characteristics of the enalapril and the placebo groups . Table 1 . Baseline Data from 94 Type II Diabetic Patients with Microalbuminuria * During the first year of treatment , the urinary albumin excretion in the enalapril group decreased from an initial mean of 143 mg/24 h to an annual mean of 122 mg/24 h. Values greater than 300 mg/24 h were recorded in only two patients . Subsequently , a minimal but steady increase occurred in mean daily albumin excretion of these patients , with a fourth-year mean of 136 mg/24 h and a fifth-year mean of 140 mg/24 h. In six patients , albuminuria exceeded 300 mg/24 h. In contrast , among the placebo-treated patients , a steady , gradual increase occurred in mean daily albuminuria . The initial albumin value was 123 mg/24 h , the first-year mean was 134 mg/24 h , and the fifth-year value was 310 mg/24 h. Albumin values were greater than 300 mg/24 h in 19 patients and greater than 1 mg/24 h in three patients . The difference between the mean values of daily albuminuria in the two groups became statistically significant after the first year . However , the difference in the rate of change in proteinuria from baseline was statistically significant at the end of the first year ( P < 0.05 ) . These data are shown in Figure 1 and are numerically detailed in the Appendix Table . If the development of overt proteinuria ( 300 mg/24 h ) is considered clinical ly important , the risk for developing this degree of proteinuria within 5 years of follow-up was 19/45 ( 42 % ) in the placebo group compared with 6/49 ( 12 % ) in the enalapril group . Therefore , enalapril treatment result ed in an absolute risk reduction of 30 percentage points for the development of overt proteinuria ( 95 % CI , 15 % to 45 % ; P < 0.001 ) for a 5-year period . Appendix Table . Initial and Annual Averages of Blood Chemistry Values for the 5-Year Follow-up in the Enalapril- and Placebo-Treated Groups * Figure 1 . Proteinuria during 5-year follow-up in diabetics treated with enalapril or placebo . P P P Renal function , expressed as reciprocal creatinine ( 100/cr ) remained unchanged in the enalapril group during the first 2 years of follow-up . From the third year onward , a small , nonsignificant but systematic decrease was recorded . The decrease was 1 % of the initial value during the 5 years . In the placebo-treated group , a gradual , steady decrease of about 2 % occurred in renal function each year . The difference between the initial and mean fifth-year values was 13 % ( P < 0.05 ) . The difference between the mean rate of decrease of reciprocal creatinine among the enalapril- and the placebo-treated groups became significant after the second year . These data are shown in Figure 2 and are outlined in the Appendix Table . Figure 2 . Reciprocal creatinine ( 100/cr ) levels expressed as percentage of initial value , during 5 years of follow-up in placebo- and enalapril-treated type II diabetics . P P The mean blood pressure in the enalapril-treated patients decreased slightly from an initial value of 99 mm Hg to 96 mm Hg during the first Ninety-four normotensive type II diabetics with normal renal function and microalbuminuria were r and omized to receive enalapril 10 mg/day or placebo and were followed for five years . In the patients treated by enalapril plasma creatinine values and albuminuria remained stable throughout the observation period . Their plasma total cholesterol decreased from an initial value of 245 + /- 27 mg/dl to mean study value of 236 + /- 29 mg/dl , and to a fifth year value of 232 + /- 27 mg/dl ( P < 0.001 ) . The changes in HDL cholesterol and triglyceride values were nonsignificant . In the placebo group there was a significant increase in albuminuria and a mean decline of 13 % in reciprocal creatinine values during the five years . Plasma total cholesterol increased from an initial mean value of 246 + /- 24 to a mean study value of 252 + /- 25 mg/dl , and to a fifth year mean value of 259 + /- 32 mg/dl ( P < 0.001 ) . There was a significant correlation between both initial and mean plasma total cholesterol values , and the decline in renal function and the rise in albuminuria in the placebo treated patients . This correlation persisted after stratification for blood pressure . Treatment with enalapril did not eliminate these correlations . Cholesterol may be an additional risk factor for diabetic nephropathy . ACE inhibitors may have a modest cholesterol lowering effect in diabetic patients mediated , in part , through the decline in albuminuria BACKGROUND Renal function declines progressively in patients who have diabetic nephropathy , and the decline may be slowed by antihypertensive drugs . The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy . METHODS We performed a r and omized , controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was < or = 2.5 mg per deciliter ( 221 mumol per liter ) . Blood-pressure goals were defined to achieve control during a median follow-up of three years . The primary end point was a doubling of the base-line serum creatinine concentration . RESULTS Two hundred seven patients received captopril , and 202 placebo . Serum creatinine concentrations doubled in 25 patients in the captopril group , as compared with 43 patients in the placebo group ( P = 0.007 ) . The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole , 76 percent in the subgroup with a baseline serum creatinine concentration of 2.0 mg per deciliter ( 177 mumol per liter ) , 55 percent in the subgroup with a concentration of 1.5 mg per deciliter ( 133 mumol per liter ) , and 17 percent in the subgroup with a concentration of 1.0 mg per deciliter ( 88.4 mumol per liter ) . The mean ( + /- SD ) rate of decline in creatinine clearance was 11 + /- 21 percent per year in the captopril group and 17 + /- 20 percent per year in the placebo group ( P = 0.03 ) . Among the patients whose base-line serum creatinine concentration was > or = 1.5 mg per deciliter , creatinine clearance declined at a rate of 23 + /- 25 percent per year in the captopril group and at a rate of 37 + /- 25 percent per year in the placebo group ( P = 0.01 ) . Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death , dialysis , and transplantation that was independent of the small disparity in blood pressure between the groups . CONCLUSIONS Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone Microangiopathy characterizes both diabetic retinopathy and nephropathy . It is currently unclear which diabetic subjects should be treated with angiotensin-converting enzyme ( ACE ) inhibitors . A double-blind , placebo-controlled protocol was implemented using captopril to treat subjects with Type I diabetes , early diabetic nephropathy ( albumin excretion rates , 20 - 200 micrograms/min ) , and normal blood pressures . After two years , the final eye grade s were improved in two treated subjects but not in any of the controls . Three control and one treated subject showed worsening of their eye grade after two years ( P < .001 , by chi-square test ) . Significant differences in renal albumin excretion were not seen between the two groups . The distribution of changes in retinal grade s in the treatment group compared with the placebo group was improved after two years . Studies of larger numbers of patients will be necessary to determine if ACE inhibitors should be used routinely in subjects with diabetic retinopathy and to determine which subjects are most likely to respond A prospect i ve self-controlled evaluation of renal function in non-insulin-dependent diabetic patients with early nephropathy , mild to moderate hypertension , and retinopathy was undertaken over a 1-year period . Thereafter , the effects of treatment with captopril on blood pressure , albumin excretion , and renal function were assessed . Glomerular filtration rate ( GFR ) , effective renal plasma flow ( ERPF ) , and systolic and diastolic blood pressures remained stable during the pretreatment period ; 24-h urinary protein excretion increased progressively from 0.79 + /- 0.13 to 1.23 + /- 0.18 g/24 h ( p < 0.05 ) ( mean + /- st and ard error ) . Captopril ( 25 mg b.i.d . ) for 3 months reduced systolic and diastolic blood pressures significantly ( p < 0.01 ) . Simultaneously , 24-h urinary protein excretion declined by 41 + /- 2.4 % , to 0.70 + /- 0.12 g/24 h ( p < 0.05 ) while GFR , ERPF , and fractional filtration demonstrated small but insignificant changes . Subsequently , increase in captopril to 50 mg b.i.d . for the remaining 6 months did not produce further significant changes in renal hemodynamics , blood pressure , or urinary protein excretion ( 0.48 + /- 0.10 g/24 h at the termination of the study ) . Non-insulin-dependent diabetic patients with early nephropathy and mild to moderate hypertension demonstrate a progressive increase in urinary protein excretion . Administration of captopril result ed in prompt control of hypertension and reversal of the increase in urinary protein excretion To evaluate the effect of enalapril on proteinuria , 16 normotensive type II diabetics with persistent proteinuria were studied . At r and om , the patients were allocated to enalapril ( 5 mg once a day ) or placebo , in a double-blind fashion , for 12 months . Blood pressure , heart rate , urinary albumin excretion , plasma renin activity and aldosterone , blood glucose , serum fructosamine , urine urea and body weight were checked monthly during the run-in period and every 2 months during the treatment period . The kidney function was studied at the beginning of the study and during the sixth and 12th months . Enalapril decreased urinary albumin excretion in our patients in the absence of any effect on blood pressure and kidney function . Our data may be interpreted on the basis of a direct vascular effect of enalapril that is probably related to a tissue mechanism consisting of reduced angiotensin formation , increased kinins , or both , or of other unknown factors A r and omized comparison of enalapril and metoprolol in patients with type 1 diabetes and nephropathy showed that the decline in kidney function was 5.6 + /- 5.9 ml/min/year in the metoprolol-treated and 2.0 + /- 3.2 ml/min/year in the enalapril-treated patients ( P = 0.02 ) . In the present study , the enalapril treated patients have been studied for two additional years . In the metoprolol-treated group , only the endpoints of death or uremia have been recorded , and six of the patients have reached end-stage renal failure and three are dead , compared to three and two , respectively in the enalapril treated group . The mean fall in glomerular filtration rate in 18 enalapril-treated patients is 8.4 + /- 9.4 ml/min/1.73 m2 after four years ; 7.5 + /- 9.8 ml/min/1.73 m2 , occurred during the first six months treatment . The mean decline in kidney function was 1.7 + /- 2.4 ml/min/year over the whole study period and 0.3 + /- 3.9 ml/min/year after exclusion of the first six months . In this study , long-term enalapril treatment in diabetic nephropathy was associated with a low rate of decline in kidney function OBJECTIVE To determine whether long-term treatment with an angiotensinconverting enzyme ( ACE ) inhibitor has a beneficial effect on the urinary microalbumin excretion and renal function in non-insulin-dependent diabetes mellitus ( NIDDM ) patients , enalapril ( 5 mg/day ) was administered for 48 months . RESEARCH DESIGN AND METHODS Fifty-two patients with NIDDM who had persistent microalbuminuria in the range of 20–300 mg/24 h , serum creatinine < 106.1 μM 1.2 mg/dl ) , supine systolic blood pressure ( BP ) < 150 mmHg , supine diastolic BP < 90 mmHg , and HbA1c < 10 % were divided into four groups . Twenty-six patients with normotension were divided at r and om into two groups ; one group received enalapril ( 5 mg/day ) ( NE group ) , the other did not receive enalapril ( NC group ) . In the same way , 26 other patients who were already well-controlled with nifedipine ( 30 mg/day ) over a long-term period ( 4–6 years ) were divided at r and om into two groups ; one received enalapril ( 5 mg/day ) ( HE group ) , the other did not receive enalapril ( HC group ) . RESULTS After 48 months , urinary albumin excretion ( UAE ) was markedly reduced in group NE from 102.4 ×/÷ 1.3 to 55.5 ×/÷ 1.3 mg/24 h ( P < 0.005 ) , whereas no significant change occurred in group NC . In the well-controlled hypertensive groups , a significant reduction in UAE occurred in group HE ( P < 0.05 ) , whereas no significant change occurred in group HC . No changes in creatinine clearance , BP , or blood glucose control were seen during the study . CONCLUSIONS Treatment with enalapril for 48 months may have a beneficial effect on the decline of microalbumin excretion in NIDDM patients Ninety-four normotensive , type II diabetics with microalbuminuria and normal renal function were r and omized to receive enalapril or placebo and were followed for five years . In the patients treated with enalapril , albuminuria decreased initially from 143 + /- 64 ( mean + /- SD ) mg/24 hours to 122 + /- 67 mg/24 hours , then a slow increase was observed to 140 + /- 134 mg/24 hours after five years . In the placebo group albuminuria increased from 123 + /- 58 mg/24 hours to 310 + /- 167 mg/24 hours after five years . The difference between the rates of change in albuminuria over time in the two groups was highly significant ( P < 0.005 ) . Kidney function , expressed as mean reciprocal creatinine , declined by 13 % in the placebo group and remained stable ( -1 % ) in the enalapril group ( P < 0.05 ) . The initial value of daily albuminuria was a good predictor of the subsequent decline in renal function ( r = 0.86 , P < 0.001 and r = 0.72 , P < 0.001 for the enalapril and the placebo groups , respectively ) . Initial and subsequent mean values of cholesterol and LDL were lower in the enalapril than in the placebo group . There was a close correlation between mean cholesterol values and the decline in renal function ( r = -0.58 , P < 0.001 ) . The mean blood pressure was stable in the enalapril group ( initial group mean 99 + /- 2.1 mmHg , fifth year mean 100 + /- 3.2 mmHg ) and increased in the placebo group from 97 + /- 3.2 mmHg to 102 + /- 3.4 mm Hg at the end of the study ( P = 0.082 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Several studies have shown that long-term therapy with angiotensin-converting enzyme inhibitors may reduce urinary protein excretion and decrease the rate of progression of renal disease in patients with insulin-dependent diabetes mellitus more effectively than conventional antihypertensive drugs . Only few studies , however , have been performed in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . To compare the effects of captopril with more conventional drugs on proteinuria and progression of renal disease , we conducted a prospect i ve , 18-month study in 42 proteinuric ( > 500 mg/day ) NIDDM and , for comparison , in 31 nondiabetic patients with a variety of renal diseases ( NDRD ) . Twenty-four NIDDM patients were treated with captopril and 18 with conventional drugs . Eighteen NDRD patients received captopril , and 13 received conventional drugs . Baseline proteinuria and glomerular filtration rate ( GFR ) were not different among groups . The blood pressure decreased equally in all group of patients , irrespective of whether they received captopril or conventional drugs . Urinary protein excretion , however , decreased significantly only in NIDDM and NDRD patients treated with captopril . The GFR decreased only in patients treated with conventional drugs , but not in those treated with captopril . The rate of decline in GFR in NIDDM patients treated with captopril was significantly lower than in patients treated with conventional drugs . However , in NDRD patients treated with captopril , the rate of decline in GFR was not different from that in patients treated with conventional drugs . The reduction of urinary protein excretion was poorly correlated with changes in blood pressure or with changes in renal function and renal hemodynamics . Serum potassium increased significantly in patients treated with captopril . ( ABSTRACT TRUNCATED AT 250 WORDS |
13,914 | 18,646,085 | MAIN RESULTS Twenty-six comparisons ( 23 articles ) were included ( as compared to fifteen comparisons in the original review ) including a wide range of drugs in inpatient and outpatient setting s. Interventions usually targeted doctors although some studies attempted to influence prescriptions by pharmacists and nurses .
This review suggests that computerized advice for drug dosage has some benefits : it increased the initial dose of drug , increased serum drug concentrations and led to a more rapid therapeutic control .
It also reduced the risk of toxic drug levels and the length of time spent in the hospital .
However , it had no effect on adverse reactions .
In addition , there was no evidence to suggest that some decision support technical features ( such as its integration into a computer physician order entry system ) or aspects of organization of care ( such as the setting ) could optimise the effect of computerised advice | BACKGROUND Maintaining therapeutic concentrations of drugs with a narrow therapeutic window is a complex task .
Several computer systems have been design ed to help doctors determine optimum drug dosage .
Significant improvements in health care could be achieved if computer advice improved health outcomes and could be implemented in routine practice in a cost effective fashion .
This is an up date d version of an earlier Cochrane systematic review , by Walton et al , published in 2001 .
OBJECTIVES To assess whether computerised advice on drug dosage has beneficial effects on the process or outcome of health care . | To determine whether clinical errors can be reduced by prospect i ve computer suggestions about the management of simple clinical events , I studied the responses of nine physicians to computer suggestions generated by 390 protocol s in a controlled crossover design . These protocol s dealt primarily with conditions managed ( e.g. , elevated blood pressure ) or caused ( e.g. , liver toxicity ) by drugs . Physicians responded to 51 per cent of 327 events when given , and 22 per cent of 385 events when not given computer suggestions . Neither level of postgraduate training ( first-year postgraduate or third-year post-graduate ) nor the order in which physicians served as study and control subjects had statistically significant overall effect on the results . It appears that the prospect i ve reminders do reduce errors , and that many of these errors are probably due to man 's limitations as a data processor rather than to correctable human deficiencies In an examination of the relationships among plasma aminoglycoside concentrations , the minimal inhibitory concentration ( MIC ) for the infecting organism , and therapeutic outcome , data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin , tobramycin , and amikacin . Clinical response to therapy occurred in 188 ( 80 % ) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response ( P less than .00001 and P less than .0001 , respectively ) . A grade d dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy To determine the association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia , the case reports of 37 patients from four prospect i ve , r and omized , controlled trials of gentamicin , tobramycin , and amikacin were analyzed . Twenty ( 54 percent ) of these patients had a favorable outcome . Patients with maximal one-hour postinfusion ( peak ) levels of 7 micrograms/ml or greater for gentamicin and tobramycin or 28 micrograms/ml or greater for amikacin more often had successful outcomes ( 14 of 20 , 70 percent ) than those with levels less than this ( six of 19 , 32 percent ) ( p less than 0.006 ) . Patients with overall mean peak levels of 6 micrograms/ml or greater for gentamicin and tobramycin or 24 micrograms/ml or greater for amikacin more often had successful outcomes than those with levels less than this ( six of 17 , 35 percent ) ( p less than 0.04 ) . The initial patient temperature , serum urea nitrogen/creatinine ratio , initial polymorphonuclear leukocyte count , and age were also associated with outcome ; but by multivariate analysis , achieving an adequate peak concentration was the most important discriminating factor . These results suggest the potential importance of achieving adequate aminoglycoside levels in patients with gram-negative pneumonia To determine the association of aminoglycoside levels with mortality from gram-negative bacteremia , we analyzed the case reports of patients from four prospect i ve , r and omized , and controlled clinical trials of gentamicin , tobramycin , and amikacin . Twelve ( 13.5 % ) of 89 patients died . One ( 2.4 % ) death occurred in 41 patients with early ( 1-hr postinfusion ) peak concentrations of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml ; nine deaths ( 20.9 % ) occurred in 43 patients with lower concentrations . Five ( 8.3 % ) deaths occurred in 60 patients with mean peak concentrations for the entire course of therapy of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml ; five ( 20.8 % ) deaths occurred in 24 patients with lower concentrations . Stepwise discriminant analysis showed that therapeutic early peak concentration was a significant factor in the presence of three other factors : severity of underlying illness , peak temperature , and initial leukocyte count . The results suggest the importance of achieving adequate early aminoglycoside levels in patients with gram-negative bacteremia |
13,915 | 27,583,004 | The studies identified were unable to provide a clear indication of best intervention for shoulder arthritis .
Sparse evidence is available for all other interventions , regardless of whether operative or non-operative . | Background We explore the nature , extent and validity of research studies concerning the management of shoulder arthritis to identify whether current management recommendations are adequate . | The recovery of patients undergoing total shoulder arthroplasty ( TSA ) can be adversely affected by a number of complications . Autologous platelet gel ( APG ) , produced by activating platelet-rich plasma ( PRP ) , has been shown to improve hemostasis and wound healing and reduce infections in some surgical procedures . Activated platelet-poor plasma ( PPP ) has also been used as a hemostatic agent . This study examines the effects of APG and PPP treatment on TSA patients postoperatively . After Institutional Review Board ( IRB ) approval , 40 patients undergoing TSA at our institution were prospect ively enrolled in our study . They were r and omized into either a control ( n = 20 ) or study ( n = 20 ) group , with the study group receiving APG and PPP treatment . Preoperative demographic data , pre- and postoperative laboratory data , pain scores , pain medication , complications , pre- and postoperative range of motion measurements , and postoperative lengths of stay were recorded for each group . The preoperative internal rotation index was significantly higher in the control group compared with treatment patients ( 4.64 + /- 4.46 vs. 1.88 + /- 2.44 , p < .05 ) . The percent hemoglobin retained postoperatively was higher in the treatment group at 24 ( 84.54 + /- 5.32 vs. 79.87 + /- 8.73 ) and 72 hours ( 87.46 + /- 16.03 vs. 76.70 vs. 5.96 ) , but neither difference reached statistical significance . The treatment group had significantly lower pain scores ( p = .007 ) and total fentanyl requirements ( p < .05 ) compared with control patients . The internal rotation index improvement factor ( postoperative internal rotation index/preoperative internal rotation index ) was significantly higher in the treatment group vs. the control group ( p < .05 ) . Although it did not reach statistical significance , the treatment group was discharged almost 9 hours earlier than the control group ( 64.44 + /- 15.23 vs. 73.39 + /- 15.37 ) . APG and PPP treatment decreased pain and provided a greater increase in internal rotation measurements postoperatively OBJECTIVES The aim of this study was to evaluate the effects of moderately intensive pool exercise therapy on patients with rheumatoid arthritis ( RA ) . METHODS Forty-six patients with chronic RA were r and omly assigned to a treatment group and a control group . The treatment group ( n = 20 ) exercised in a temperate pool twice a week for 12 weeks . The control group ( n = 23 ) continued with their previous activities . Aerobic capacity , measured by means of a submaximum bicycle test , and the physical component of the SF-36 were chosen as the primary outcome measures . Two tests of muscle endurance were chosen as the secondary outcome measure . Additional functional tests and instruments were included . RESULTS No significant differences between the groups were found for the primary outcome measures . Significant improvements in the following aspects of muscular function ( P < 0.05 ) were found in the treatment group when their performance was compared with that of the control group : isometric shoulder endurance , grip force , dynamic endurance of lower extremities ( chair test ) and muscle function of lower extremities . Significant improvements were also found for vitality ( SF-36 ) compared with the control group . The improvements in the training group were maintained for 3 months . CONCLUSIONS Pool exercise therapy of moderate intensity significantly improved muscle endurance in the upper and lower extremities in patients with RA , while no impact on aerobic capacity was found . However , the study population was small and there is a need for further studies with larger population SUMMARY Objective : To evaluate the efficacy and safety of oxaprozin in comparison with diclofenac in patients with periarthritis pain of the shoulder previously unsuccessfully treated with nonsteroidal anti-inflammatory drugs other than diclofenac and oxaprozin . Methods : In this open , multicentre , r and omised , controlled study , eligible patients with periarthritis of the shoulder were r and omised to receive either oxaprozin 1200 mg once daily ( n = 49 ) or diclofenac 50 mg three times daily ( n = 47 ) . The treatment period was 15 ± 1 days . The study was planned on a hypothesis of equivalence between the two study drugs . The primary study endpoint was the change from baseline at day 15 in the patient-assessed shoulder pain score . Secondary efficacy variables included investigator-assessed shoulder function , patient-assessed quality of life on the Short-Form-36 ( SF-36 ) Acute Health Survey and both patients ’ and investigators ’ overall assessment of efficacy . Results : At day 15 , the mean changes in shoulder pain score from baseline in the oxaprozin and diclofenac groups were –5.85 ± SD 4.62 and –5.54 ± SD 4.41 , respectively . The difference between the two groups was not statistically significant , confirming the hypothesis of the study that oxaprozin is as effective as diclofenac . Investigator-assessed shoulder function improved in both groups but more so in the oxaprozin group ( p = 0.028 at day 15 ) . Quality of life as measured by SF-36 total score was also improved in both treatment groups , with a trend toward greater improvement in the oxaprozin group . Furthermore , a significantly more favourable effect on the SF-36 ‘ mental health ’ item was observed in oxaprozin compared with diclofenac-treated patients at day 15 ( p = 0.0202 ) . As assessed by investigators , the overall efficacy of oxaprozin was superior to that for diclofenac at visit 3 ( 8 ± 1 days ) ( p = 0.0067 ) . Patients also assessed the overall efficacy of oxaprozin as superior to that of diclofenac at visits 3 ( 8 ± 1 days ) ( p = 0.0235 ) and 4 ( 15 ± 1 days ) ( p = 0.0272 ) . Only six adverse events , all of which were mild or moderate in intensity and occurred in four diclofenac recipients , were observed in the study . Conclusions : As expected , once-daily oxaprozin proved to be as effective as diclofenac three times daily in reducing the primary efficacy variable of patient-assessed shoulder pain score in patients with periarthritis of the shoulder refractory to previous treatments with other NSAIDs . Oxaprozin was shown to be superior to diclofenac in improving shoulder function and was considered by investigators and patients to have greater overall efficacy than diclofenac . In addition , oxaprozin showed a trend toward superior results in improving patients ’ quality of life compared with diclofenac . A trend towards better tolerability results for oxaprozin compared with diclofenac was also noted HypothesisArthroscopic acromioclavicular joint ( ACJ ) resection for asymptomatic ACJ arthritis combined with rotator cuff repair leads to more satisfactory pain relief and decrease reoperation rate when inferiorly directed osteophytes present at the undersurface of ACJ . Material s and methods Between January 2006 and May 2008 , a total of 83 patients ( 83 shoulders ) , 40 males and 43 females , who were planned to have arthroscopic repair of a tear measuring 1–3 cm in the anterior-posterior dimension with advanced ACJ arthritis with inferiorly directed osteophytes at the undersurface of the ACJ on MRI were entered into this study . Patients were r and omized into two groups . Group 1 included 31 patients , who underwent arthroscopic distal clavicle resection combined with rotator cuff repair . Group 2 included 52 patients , who underwent isolated rotator cuff repair . Patients were evaluated preoperatively and postoperatively using the University of California Los Angeles ( UCLA ) score and the American Shoulder and Elbow Surgeons ( ASES ) score . Pain , tenderness on ACJ , and cross body adduction test were compared between groups . Results The mean follow-up was 31.7 months ( range 34–38 ) . The UCLA scores and ASES scores were lower in group 1 at week 6 ( p < .05 ) , and week 12 ( p < .05 ) , but higher at the last follow-up at 2 years ( p < .05 ) postoperatively . VAS score was higher in group 1 at week 6 ( p < .05 ) , and at week 12 ( p < .05 ) , but lower in group 2 at the last follow-up ( p < .05 ) . Only in group 2 , two ( 3.8 % ) cases developed ACJ pain during follow-up and one ( 1.9 % ) case underwent reoperation for additional ACJ resection . Conclusions This study shows that distal clavicle resection combined with rotator cuff repair for asymptomatic ACJ arthritis with inferiorly directed osteophytes lower functional scores due to temporary pain in early postoperative periods , but better functional outcomes with satisfactory pain relief and no reoperation rate were observed after 2 years Multiple joint replacement in 1 operative session is frequently performed in the lower extremity but less often in the upper extremity . The purpose of the present study is to determine whether a 1-stage arthroplasty of the ipsilateral shoulder and elbow affects the clinical outcome . Replacement of the ipsilateral shoulder and elbow was performed in 34 rheumatoid patients ( 42 upper extremities ) . In 11 patients ( 13 upper limbs ) , the shoulder and elbow arthroplasty was a 1-stage procedure . The average follow-up of the whole group was 4.5 years ( range , 2 - 12 years ) . The patients were in a prospect i ve study and evaluated clinical ly and radiographically . With a 1-stage procedure , the hospitalization time was shorter . The overall Hospital for Special Surgery shoulder score and its items ( pain , function , and strength ) were similar at follow-up in the 2 groups , and only the motion score showed more improvement in the 1-stage group . The clinical outcome of elbow arthroplasty was similar in both groups , regardless of the sequence of surgery . From this study , it may be concluded that a 1-stage procedure for shoulder and elbow arthroplasty will reduce the hospitalization time and does not adversely affect the clinical outcome BACKGROUND Both total shoulder arthroplasty and hemiarthroplasty have been used commonly to treat severe osteoarthritis of the shoulder ; however , their effect on disease-specific quality -of-life outcome is unknown . The purpose of this study was to compare the quality -of-life outcome following hemiarthroplasty with that following total shoulder arthroplasty in patients with osteoarthritis of the shoulder . METHODS Forty-two patients with a diagnosis of osteoarthritis of the shoulder were r and omized to receive a hemiarthroplasty or a total shoulder arthroplasty . One patient died , and all others were evaluated preoperatively and at six weeks and three , six , twelve , eighteen , and twenty-four months postoperatively with use of a st and ardized format including a disease-specific quality -of-life measurement tool ( Western Ontario Osteoarthritis of the Shoulder [ WOOS ] index ) , general shoulder rating scales ( University of California at Los Angeles [ UCLA ] shoulder scale , Constant score , and American Shoulder and Elbow Surgeons [ ASES ] evaluation form ) , general pain scales ( McGill pain score and visual analogue scale ) , and a global health measure ( Short Form-36 [ SF-36 ] ) . When a patient required revision of a hemiarthroplasty to a total shoulder arthroplasty , the last score before he or she " crossed over " was used for the analysis . RESULTS Significant improvements in disease-specific quality of life were seen two years after both the total shoulder arthroplasties and the hemiarthroplasties . There were no significant differences in quality of life ( WOOS score ) between the group treated with total shoulder arthroplasty and that treated with hemiarthroplasty ( 90.6 + /- 13.2 and 81.5 + /- 24.1 points , respectively ; p = 0.18 ) . The other outcome measures demonstrated similar findings . Two patients in the hemiarthroplasty group crossed over to the other group by undergoing a revision to a total shoulder arthroplasty because of glenoid arthrosis . CONCLUSIONS Both total shoulder arthroplasty and hemiarthroplasty improve disease-specific and general quality -of-life measurements . With the small number of patients in our study , we found no significant differences in these measurements between the two treatment groups . LEVEL OF EVIDENCE Therapeutic Level HYPOTHESIS The correct implantation of the glenoid component is of paramount importance in total shoulder arthroplasty ( TSA ) . We hypothesized that the accuracy of the glenoid positioning in the transverse plane can be improved using intraoperative navigation . MATERIAL S AND METHODS This prospect i ve , r and omized clinical study comprised 2 groups of 10 patients each with osteoarthritis of the shoulder TSA , with or without intraoperative navigation . Glenoid version was measured on axial computed tomography scans preoperatively and 6 weeks postoperatively . RESULTS The operating time was significantly longer in the navigation group ( 169.5 + /- 15.2 vs 138 + /- 18.4 min ) . We found an average change of retroversion from 15.4 degrees + /- 5.8 degrees ( range , 3.0 degrees -24.0 degrees ) preoperatively to 3.7 degrees + /- 6.3 degrees ( range , -8.0 degrees to 15.0 degrees ) postoperatively in the navigation group compared with 14.4 degrees + /- 6.1 degrees ( range , 2.0 degrees -24.0 degrees ) preoperatively to 10.9 degrees + /- 6.8 degrees ( range , 0.0 degrees -19.0 degrees ) postoperatively in the group without navigation ( P = .021 ) . CONCLUSION We found an improved accuracy in glenoid positioning in the transverse plane using intraoperative navigation . The validity of the study is limited by the small number , which advocates continuation with more patients and longer follow-up . LEVEL OF EVIDENCE Level 2 ; Therapeutic study We undertook a prospect i ve study of 61 children in Malawi with septic arthritis of the shoulder . They were r and omised into two groups , treated by aspiration ( group 1 , 31 patients ) or arthrotomy ( group 2 , 30 patients ) . Both received antibiotics for six weeks . We studied the results of blood tests , microbiology , and the clinical and radiological outcome one year after diagnosis . Only one patient was sickle-cell positive and three were HIV-positive . Non-typhoidal Salmonella species accounted for 86 % ( 19/22 ) of the positive joint cultures in group 1 and 73 % ( 16/22 ) in group 2 . Of the 33 radiographs available for review at follow-up at six months , 23 ( 70 % ) showed evidence of glenohumeral damage . There was no statistical difference in radiological outcome for the two groups . We devised and vali date d a scoring system , the Blantyre Septic Joint Score , for the assessment of joints based upon swelling , tenderness , function and range of movement . Despite the radiological changes only one of the 24 joints examined at one year had any deficit in these parameters . There was no statistical difference in the clinical outcome for the two treatment groups at any stage during the period of follow-up In a prospect i ve study between 2000 and 2005 , 22 patients with primary osteoarthritis of the shoulder had a total shoulder arthroplasty with a st and ard five-pegged glenoid component , 12 with non-offset humeral head and ten with offset humeral head components . Over a period of 24 months the relative movement of the glenoid component with respect to the scapula was measured using radiostereometric analysis . Nine glenoids needed reaming for erosion . There was a significant increase in rotation about all three axes with time ( p < 0.001 ) , the largest occurring about the longitudinal axis ( anteversion-retroversion ) , with mean values of 3.8 degrees and 1.9 degrees for the non-offset and offset humeral head eroded subgroups , respectively . There was also a significant difference in rotation about the anteversion-retroversion axis ( p = 0.01 ) and the varus-valgus ( p < 0.001 ) z-axis between the two groups . The offset humeral head group reached a plateau at early follow-up with rotation about the z-axis , whereas the mean of the non-offset humeral head group at 24 months was three times greater than that of the offset group accounting for the highly significant difference between them Glenoid loosening is one reason for failure of total shoulder arthroplasty . Several factors , including radiographic lucency , have been shown to be associated with glenoid loosening . The purpose of this study was to assess the correlation between glenoid design and immediate radiographic lucency in a prospect i ve r and omized clinical trial . Total shoulder arthroplasty was performed in 43 patients over a 2-year period . Twenty-three patients were r and omized into the keel group and twenty patients into the pegged group . Postoperative radiographs obtained within 6 weeks of surgery were evaluated by 3 raters to determine glenoid lucency . On a scale from 0 ( no lucency ) to 5 ( gross lucency and component loosening ) , the rate of lucency was 39 % ( 9/23 ) in the keeled components , which was significantly higher than the rate of 5 % ( 1/20 ) observed in the pegged components ( P = .026 ) . Patient age , gender , and glenoid size did not significantly affect glenoid component lucency ( P > .05 ) . The consistency reliability among raters ( Cronbach alpha ) was 0.87 , and the intertester reliability was 0.87 . Pegged glenoid components have less radiographic lucency when compared with keeled glenoid components in the immediate postoperative period BACKGROUND Clinical ly evident neurologic injury of the involved limb after total shoulder arthroplasty is not uncommon , but the sub clinical prevalence is unknown . The purpose s of this prospect i ve study were to determine the sub clinical prevalence of neurologic lesions after reverse shoulder arthroplasty and anatomic shoulder arthroplasty , and to evaluate the correlation of neurologic injury to postoperative lengthening of the arm . METHODS All patients undergoing either a reverse or an anatomic shoulder arthroplasty were included during the period studied . This study focused on the clinical , radiographic , and preoperative and postoperative electromyographic evaluation , with measurement of arm lengthening in patients who had reverse shoulder arthroplasty according to a previously vali date d protocol . RESULTS Between November 2007 and February 2009 , forty-one patients ( forty-two shoulders ) underwent reverse shoulder arthroplasty ( nineteen shoulders ) or anatomic primary shoulder arthroplasty ( twenty-three shoulders ) . The two groups were similar with respect to sex distribution , preoperative neurologic lesions , and Constant score . Electromyography performed at a mean of 3.6 weeks postoperatively in the reverse shoulder arthroplasty group showed sub clinical electromyographic changes in nine shoulders , involving mainly the axillary nerve ; eight resolved in less than six months . In the anatomic shoulder arthroplasty group , a brachial plexus lesion was evident in one shoulder . The prevalence of acute postoperative nerve injury was significantly more frequent in the reverse shoulder arthroplasty group ( p = 0.002 ) , with a 10.9 times higher risk ( 95 % confidence interval , 1.5 to 78.5 ) . Mean lengthening ( and st and ard deviation ) of the arm after reverse shoulder arthroplasty was 2.7 ± 1.8 cm ( range , 0 to 5.9 cm ) compared with the normal , contralateral side . CONCLUSIONS The occurrence of peripheral neurologic lesions following reverse shoulder arthroplasty is relatively common , but usually transient . Arm lengthening with a reverse shoulder arthroplasty may be responsible for these nerve injuries BACKGROUND Aseptic glenoid component loosening remains a common problem in total shoulder arthroplasty ( TSA ) . This study presents long-term prospect i ve follow-up of 2 cemented all-polyethylene glenoid components with different backside design geometry and the effect on the presence and progression of radiolucent lines ( RLLs ) . MATERIAL S AND METHODS Fifty-six TSAs were performed for primary osteoarthritis . Two surgeons used an identical technique to implant 32 flat-back and 24 convex-back glenoids . In particular , the glenoid components were cemented after a minimal reaming and bone compaction . St and ardized postoperative radiologic and clinical follow-up was at 2 and 10 years . Three independent observers evaluated the x-ray images for RLLs around the base plate and keel . The results were analyzed for progression and influencing factors . RESULTS At 10 years , progression of RLL was seen in both components , but there was no difference between the 2 glenoid design s ( P = .16 ) . Younger patient age ( P = .03 ) , h and dominance ( P = .017 ) , and presence of early RLLs ( P = .018 ) were significant factors for progression of RLLs . Constant scores deteriorated with progression of RLLs ( P = .006 ) . The glenoid revision rate at 10 years was 5 % . CONCLUSION At 10 years there was no difference in the presence or progression of RRLs between a flat-back and a convex-back glenoid all-polyethylene design . Young age , h and dominance , and poor implantation technique influence glenoid RLLs and affect the clinical result of TSA Our objective was to examine the rate of revision and its predictive factors in patients undergoing total shoulder arthroplasty ( TSA ) . We used prospect ively collected data from the Mayo Clinic Total Joint Registry to examine five- , ten- and 20-year revision-free survival following TSA and the predictive factors . We examined patient characteristics ( age , gender , body mass index , comorbidity ) , implant fixation ( cemented versus uncemented ) , American Society of Anesthesiologists class and underlying diagnosis . Univariate and multivariable adjusted hazard rates were calculated using Cox regression analysis . A total of 2207 patients underwent 2588 TSAs . Their mean age was 65.0 years ( 19 to 91 ) and 1163 ( 53 % ) were women ; osteoarthritis was the underlying diagnosis in 1640 shoulders ( 63 % ) . In all , 212 TSAs ( 8.2 % ) were revised during the follow-up period . At five , ten and 20 years , survival rates were 94.2 % ( 95 % confidence interval ( CI ) 93.2 to 95.3 ) , 90.2 % ( 95 % CI 88.7 to 91.7 ) and 81.4 % ( 95 % CI 78.4 to 84.5 ) , respectively . In multivariable analyses men had a higher hazard ratio of revision of 1.72 ( 95 % CI 1.28 to 2.31 ) ( p < 0.01 ) compared with women , and those with rotator cuff disease had a hazard ratio of 4.71 ( 95 % CI 2.09 to 10.59 ) ( p < 0.001 ) compared with patients with rheumatoid arthritis . We concluded that male gender and rotator cuff disease are independent risk factors for revision after TSA . Future studies are needed to underst and the biological rationale for these differences BACKGROUND Considerable interest has been focused on the design of the glenoid component used in total shoulder arthroplasty in order to reduce the risk of loosening . One design -related feature that has attracted attention is whether to use pegged or keeled cemented glenoid components . The main purpose of this study was to compare the fixation of cemented keeled glenoid components with that of cemented in-line pegged glenoid components . METHODS In a prospect i ve r and omized study , we compared the stability of cemented , all-polyethylene , keeled glenoid components and cemented , all-polyethylene , in-line three-pegged glenoid components by radiostereometric analysis . Twenty-seven shoulders in twenty-five patients with osteoarthritis ( twenty-two shoulders had primary and five shoulders had secondary osteoarthritis ) were included . There were sixteen women and nine men , and the mean age was sixty-four years . Radiostereometric analysis and conventional radiographs were carried out at five days , at four months , and at one and two years postoperatively . RESULTS The mean Constant and Murley score preoperatively and two years postoperatively was 25 and 70 , respectively , for shoulders with the keeled glenoid component and 22 and 70 for the shoulders with a pegged component . No significant difference was detected between groups with regard to the average micromigration of the glenoid components at any of the time points . The average translation was < 1 mm , while the median value was < 0.3 mm at two years , with no significant difference between the different axes . In five shoulders ( three with the keeled component and two with the pegged component ) , translation at two years was > 1 mm . In fourteen shoulders ( eight with the keeled and six with the pegged component ) , the rotation around one or several axes was > 2 degrees . We were not able to detect any specific pattern with regard to movement for either type of component nor were we able to detect any difference between the two types of components in the way they migrated , if migration occurred . CONCLUSIONS Cemented all-polyethylene keeled or in-line three-pegged glenoid components appear to have similar stability during the first two years after surgery . Studies with a longer follow-up period are needed to relate these findings to long-term clinical and radiographic outcomes The analgesic-therapeutic efficacy and tolerability of a low-frequency electromagnetic field ( ELF ) , modulated at a frequency of 100 Hz with a sinusoidal waveform and mean induction of a few gauss , has been demonstrated by the authors in numerous previous studies of various hyperalgic pathologies , particularly of the locomotor apparatus . In the present study , the authors tested a new type of all-inclusive field , denoted TAMMEF , whose parameters ( frequency , intensity , waveform ) are modified in time , r and omly varying within the respective ranges , so that all the possible codes can occur during a single application . For the comparison , 150 subjects ( 118 women and 32 men , between 37 and 66 years of age ) were enrolled . They were affected by cervical spondylosis ( 101 cases ) or shoulder periarthritis ( 49 cases ) . Unbeknownst to them , they were r and omly divided into three groups of 50 subjects . One group was exposed to the new TAMMEF , another group to the usual ELF , and the third group to simulated treatment . The results show that the effects of the new TAMMEF therapy are equivalent to those obtained with the ELF Diagnostic and therapeutic st and ards relating to septic conditions of the shoulder are rarely documented in the literature . For this study , patients suffering from septic shoulder arthritis were prospect ively enrolled . Staging was based on the criteria of Gächter ( Stutz et al. , Knee Surg Sports Traumatol Arthrosc 8:270–274 , 2000 ) , and assessment of functional outcome was based on a self-assessed Constant score ( Boehm et al. , Unfallchirurg 107:397–402 , 2004 ) . Patients were separated into three groups according to the CEBI-classification reported by Pfeiffenberger and Meiss ( Arch Orthop Trauma Surg 115:325–331 , 1996 ) . Forty-three patients were enrolled . Group I contained 21 % of patients , while 23 % were assigned to group II , and 56 % to group III . Staphylococcus aureus was found in 71 % . Eight patients were treated arthroscopically , and 35 received open surgery . None of the implants could be preserved . The mean self-assessed Constant score after 26 ± 7 months was 74 ± 9 points in group I , 63 ± 14 points in group II , and 53 ± 14 points in group III . Diagnostic work-up consisted of laboratory analysis including CRP and joint aspiration . Arthroscopic procedures can be effective when implemented early . With regard to implants and chronic symptoms , primary removal should be critically reconsidered . RésuméLes arthrites septiques de l'épaule sont rarement documentées dans la littérature . Patients et méthode : un certain nombre d'arthrites septiques ont été évaluées avec l'utilisation d'un critère de classement ( Gächter ) et de critères fonctionnels avec le score de Constant . Les patients ont été séparés en trois groupes selon la classification CEBI . Résultats : 43 patients do nt 21 % affectés au groupe I , 23 % dans le groupe II et 56 % dans le groupe III . Un staphylocoque doré a été retrouvé dans 71 % des cas . 8 patients ont été traités par arthroscopie et 35 par chirurgie sanglante . Aucun implant n'a pu être conservé . La moyenne du score de Constant après 26 ± 7 mois de suivi a été de 74 ± 9 points dans le groupe I , de 63 ± 14 points dans le groupe II et de 53 ± 14 points dans le groupe III . En conclusion : le diagnostic nécessite des examens de laboratoire incluant la CRP et des prélèvements au niveau de l'épaule par aspiration . Le traitement par arthroscopie est un traitement qui peut avoir des effets positifs s'il est réalisé précocement . En ce qui concerne les implants , après une longue période d'évolution , ceux-ci doivent être enlevés . Néanmoins , cette ablation nécessite une analyse critique This prospect i ve r and omized study compared the immediate postoperative periglenoid radiolucencies among 3 glenoid-drying techniques used in total shoulder arthroplasty . Seventy-one consecutive patients with primary osteoarthritis underwent total shoulder arthroplasty by use of 1 prosthetic system with convex-back , keeled , polyethylene glenoid components ; the same modern , instrumented pressurization technique was used to cement all glenoids . Of the shoulders , 21 had glenoid implants cemented after bony preparation with thrombin-soaked gel foam , 24 after compressed gas lavage , and 26 after saline solution lavage with sponge drying . The immediate postoperative anteroposterior radiographs were examined to evaluate the presence of periglenoid radiolucencies . Of the patients , 29 ( 41 % ) had radiolucencies evident immediately postoperatively , with all radiolucencies occurring in the faceplate zones . The mean total radiolucent line score was 0.63 ( P = .94 ) , with no significant difference among cementing preparation techniques ( P = .89 ) . Prosthetic mismatch did not differ among glenoid preparation techniques ( P = .86 ) . There was no statistical association between prosthetic mismatch and radiolucent line score either across ( P = .62 ) or within ( P = .99 ) the glenoid preparation groups . The associated costs in the gel foam group and compressed gas lavage group were 70 times higher than the cost in the saline solution lavage group . All radiolucencies were noted in the faceplate zones , with no radiolucency greater than 2 mm . Preparation of the glenoid surface for cementing showed no significant difference among the 3 techniques studied , although the material costs were significantly higher in the gel foam and compressed gas lavage groups compared with the saline solution lavage group It is unclear whether humeral stems should be fixed with or without cement . We question whether press-fit fixation would provide similar results to cemented stem fixation . We prospect ively r and omized 26 shoulders in 24 patients with rheumatoid arthritis ( 20 women , 4 men ) to have either a cemented or press-fit stem . In the press-fit group , stems were matched to the medullary canal , while lavage , pressurizing and distal plugging were used in the cemented group . We followed patients with conventional radiographs and radiostereometric analysis ( RSA ) at 5 to 7 days , 4 months , 1 year , and 2 years after surgery . One patient died from unrelated causes before the 1-year followup , while the remaining patients were followed according to the protocol . All but two patients were very satisfied or satisfied at 2 years . No stem was radiographically loose . There was no difference in micromotion between groups . The average rotation for all axes was less than 0.25 ° for both groups and the average translation was less than 0.32 mm for all three axes including subsidence , which was less than 0.1 mm for the uncemented stems . We concluded at 2 years these stems provided similar fixation in rheumatoid shoulders . Level of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence OBJECTIVES The aim of this study was to evaluate the efficacy of acupuncture as a treatment for chronic shoulder pain and to compare the efficacy of individualized acupuncture to fixed , st and ard point acupuncture treatment . DESIGN The study was a single-blind r and omized , controlled trial . SETTING S/LOCATION The study was conducted in an outpatient rheumatology clinic at the VA Medical Center of Philadelphia . SUBJECTS The participants were adults with shoulder pain for at least 8 weeks with a diagnosis of osteoarthritis or rotator cuff tendonitis and a total Shoulder Pain and Disability Index ( SPADI ) score of > or = 30 . INTERVENTIONS Thirty-one ( 31 ) subjects were r and omized to one of three treatment groups : individualized acupuncture points according to the approaches of Traditional Chinese Medicine ; fixed , st and ard acupuncture points conventionally used for shoulder pain ; and sham nonpenetrating acupuncture . Subjects received 12 treatments over 6 weeks and were reassessed using the SPADI at the end of the 6 weeks . OUTCOME MEASURES The primary outcome evaluated was the mean change in total SPADI score in each group from baseline to 6 weeks . RESULTS After 6 weeks of treatment , the mean total SPADI score improved in all three groups , but the change was clinical ly significant ( > or = 10 points ) only in groups 1 and 2 ( -20.3 and -20.4 , respectively , versus -6.5 in group 3 ) . The treatment effects of groups 1 and 2 compared to the sham acupuncture group were -13.8 ( 95 % confidence interval : -2.2 to -25.4 , p < 0.015 ) and -13.9 ( -2.0 to -25.8 , p < 0.013 ) , respectively . There was no difference between the individualized acupuncture and st and ardized acupuncture treatments . CONCLUSIONS Acupuncture may be an effective treatment for chronic shoulder pain . There may be no difference in efficacy between individualized and st and ardized acupuncture treatment . This suggests that the use of st and ard points may make treatment easier for patient care and for further research studies In a prospect i ve , r and omized study between 2000 and 2004 , 20 patients with primary osteoarthritis of the shoulder had a total shoulder arthroplasty with radiostereometric analysis , 10 with keeled and 10 with pegged glenoid components . The relative movement of the glenoid component with respect to the scapula was measured over a 24-month period . Three keeled and five pegged glenoids needed reaming for erosion . The largest translations occurred along the longitudinal axis ( mean of 1.35 mm for keeled eroded components ) ( P = .017 for keeled vs pegged components and P = .013 for eroded vs non-eroded components ) . Both of the other translation axes showed no significant differences . The highest maximum total point movement at 24 months was 2.57 mm for keeled eroded components and 1.64 mm for pegged eroded components ( P = .029 for keeled vs pegged components and P = .023 for eroded vs non-eroded components ) . The largest rotation was anteversion , with mean values of 5.5 degrees for keeled eroded components and 4.8 degrees for pegged eroded components ( P = .658 for keeled vs pegged components and P = .90 for eroded vs non-eroded components ) . The mean varus tilt was 4.5 degrees for keeled eroded components compared with 2.3 degrees for pegged eroded components ( P = .004 for keeled vs pegged components and P = .016 for eroded vs non-eroded components ) , and finally , anterior-posterior rotation mean values were 3.5 degrees for keeled eroded components and 1.1 degrees for pegged eroded components ( P = .022 for keeled vs pegged components and P = .04 for eroded vs non-eroded components ) . In conclusion , whereas all components moved , radiostereometric analysis revealed increased migration with keeled components , exacerbated by glenoid erosion . Furthermore , a distinctive pattern of migration was identified over the 2-year period BACKGROUND Although cemented humeral fixation is recognized as the st and ard of care in total shoulder arthroplasty ( TSA ) , uncemented fixation has the potential to provide stable fixation , decrease operative time , and simplify potential revision procedures . This prospect i ve , r and omized , double-blind clinical trial compared cemented and uncemented humeral fixation in TSA for primary shoulder osteoarthritis . METHODS Patients with primary shoulder osteoarthritis requiring replacement were screened for eligibility . After providing informed consent , subjects received baseline clinical and radiologic assessment s , computed tomography scans , and st and ardized TSA . After glenoid component insertion , patients were r and omized to either a cemented or uncemented humeral component . The primary outcome was the WOOS ( Western Ontario Arthritis of the Shoulder Index ) score at 2 years . Other outcomes included the Short Form 12 score , American Shoulder and Elbow Surgeons score , McMaster-Toronto Arthritis Patient Preference Disability Question naire , operative time , complications , and revisions . Patients were assessed by a blinded evaluator at 2 and 6 weeks and 3 , 6 , 12 , 18 , and 24 months postoperatively . RESULTS In total , 161 patients consented to be included and were r and omized : 80 in the cemented group and 81 in the uncemented group . There were no significant differences in demographics or baseline evaluations between groups , except for gender . The 12- , 18- , and 24-month WOOS scores showed a significant difference in favor of the cemented group . The cemented group also had better strength and forward flexion . As expected , the operative time was significantly less for the uncemented group . CONCLUSIONS These findings provide level I evidence that cemented fixation of the humeral component provides better quality of life , strength , and range of motion than uncemented fixation Calcific periarticular disease is characterized by the deposition of calcium phosphate crystals in many tendons and particularly in the rotator cuff tendons . Calcifications of any size may be accompanied by painful shoulder syndrome and tendon tears . Ecographic assessment of changes in the size of calcifications may be a marker of tissue changes in evolving shoulder periarthropathies . The aim of this study was to compare variations in pain and ultrasound dimensions in the calcifications in the tendons of the rotator cuff in patients treated with disodium-clodronate compared with those treated with paracetamol and nimesulide . In all groups , pain reduction occurred over a 6-month period , but was significantly greater in patients administered disodium-clodronate than in those administered nimesulide or paracetamol . A significant reduction in the size of calcifications was also observed in all three groups , but this reduction was more marked in the disodium-clodronate group BACKGROUND Modern cementing techniques have improved glenoid fixation , reduced glenoid lucency seen with keeled components , and may eliminate differences attributable to glenoid design . The purpose of this study was to determine the effect of glenoid design on immediate and follow-up radiographic lucency of pegged and keeled glenoid components , using modern cementing techniques . MATERIAL AND METHODS Fifty-three total shoulder arthroplasties were performed in patients with primary glenohumeral osteoarthritis . Patients were r and omized prospect ively to receive either a pegged or keeled glenoid component . Three raters grade d radiographic glenoid lucencies . RESULTS On immediate radiographs , there was no significant difference in the rate of glenoid lucency between pegged ( 0 % ) and keeled ( 15 % ) glenoid components ( P = .128 ) . However , after an average of 26 months , the rate of glenoid lucency was significantly higher in patients with keeled components ( 46 % ) compared to patients with pegged components ( 15 % ) ( P = .003 ) . CONCLUSION Even with modern cementing techniques , pegged glenoid components remain radiographically superior to keeled glenoid components |
13,916 | 25,152,385 | Most studies showed superior passage of the gastric tube compared with the whole stomach .
Pyloric drainage is not significantly associated with the risk of developing delayed gastric emptying after esophagectomy . | Delayed gastric emptying is observed in 10 % to 50 % of patients after esophagectomy with gastric interposition . | Background Esophagectomy through cervico-thoraco-abdominal approach is a useful surgical technique in treating patients with esophageal cancer . However , the cervical reconstruction is also known to have a high rate of anastomotic leakage , as well as anastomotic stricture , intrathoracic stomach syndrome , reflux esophagitis and other complications , thereby influencing postoperative recovery and quality of life . Aims The objective of this study was to investigate whether tubular stomach is superior to whole stomach in reducing anastomotic leakage for esophageal reconstruction through the cervico-thoraco-abdominal ( 3-field ) approach . Methods A total of 850 patients undergoing the 3-field esophagectomy were retrospectively included in this study and divided into a tubular stomach reconstruction group ( Group A , n = 453 ) and a whole stomach reconstruction group ( Group B , n = 397 ) . All patients underwent esophagectomy through right thorax , left cervical part , abdominal triple incisions and done in esophageal reconstruction by h and -sewn two-layer anastomosis . Results Results revealed that in comparison with whole stomach , esophageal reconstruction with tubular stomach had a lower incidence of anastomotic leakage ( 5.5 vs. 9.3 % , P < 0.05 ) , less manifestation of intrathoracic syndrome ( 3.3 vs. 9.8 % , P < 0.001 ) and less occurence of reflux esophagitis ( 5.1 vs. 11.1 % , P < 0.01 ) . However , for the incidence of anastomotic stricture , there was no significant difference between the two groups ( 9.3 vs. 9.8 % ) . Conclusions This observation study suggests that for esophageal cancer patients undergoing the 3-field esophagectomy tubular stomach is better than whole stomach for esophageal reconstruction as reflected by a reduced postoperative anastomotic leakage , intrathoracic syndrome and reflux esophagitis Purpose The type of anastomosis and its outcome can affect postoperative morbidity , mortality , and quality of life after esophagectomy . We compared the outcomes of cervical h and -sewn anastomosis ( CHS ) and intrathoracic stapled anastomosis ( ITS ) performed after esophagectomy and gastric reconstruction . Methods Thirty-two patients with middle or lower thoracic esophageal cancer were prospect ively r and omized to undergo CHS ( n = 18 ) or ITS ( n = 14 ) after esophagectomy . We compared clinical data , postoperative symptoms , and long-term survival in the two groups . Results The rates of anastomotic leak and stricture in the CHS and ITS groups were 16.7 % versus 7.1 % and 0 % versus 14.2 % , respectively , which do not represent significant differences . The respective rates of recurrent laryngeal nerve palsy were 38.8 % versus 7.1 % ( P < 0.05 ) , and proximal esophageal resection was 15 mm longer ( P < 0.05 ) in the CHS group . There were no significant differences in symptoms 6 months after surgery , or in the overall 5-year survival rates ( 72.2 % and 85.7 % , respectively ) . Conclusions The two methods of anastomosis yielded similar anastomotic outcomes . Although the incidence of recurrent laryngeal nerve injury was higher after CHS , and proximal esophageal resection was longer , this had little impact on postoperative symptoms and long-term survival By radioisotope technique , we studied the emptying function of the vagotomized intrathoracic stomach after esophagectomy for carcinoma of the esophagus in 24 patients , and compared it with the preoperative emptying function . The patients were r and omized into a control group ( no pyloroplasty ) and a study group ( pyloroplasty ) . Gastric emptying was delayed in both groups , postoperatively ; however , the delay was greater in the control group than in the study group . Therefore , vagotomy delays the emptying of the thoracic stomach , and this delay is not completely corrected by pyloroplasty OBJECTIVE For patients undergoing oncologic surgery , the quality of life ( QoL ) is generally accepted as an important outcome parameter in addition to long-term survival , mortality and complication rates . This study focussed on the QoL in patients after oesophagectomy for cancer , comparing the method of reconstruction ( narrow gastric tube vs whole stomach ) . METHODS In a prospect i ve r and omised single-centre study from 2007 to 2008 , 104 patients underwent oesophagectomy for cancer . To assess the QoL , a question naire in reference to the EORTC-QLQ-C30 and the QLQ-OES24 was administered at 3 weeks , 6 months and 1 year after surgery . Clinical data were collected prospect ively , and follow-up was performed regularly . RESULTS There were no significant differences between the narrow gastric tube group ( NGT group , n=52 ) and the whole-stomach group ( WS group , n=52 ) with regard to patient and cancer characteristics , operative procedure , postoperative intensive care unit ( ICU ) hospitalisation , and overall survival at 1 year . Regarding the postoperative complication , there were more cases of postoperative reflux oesophagitis and impairment of pulmonary function in the WS group ( P<0.05 ) . Regarding the QoL investigation , the scores of QoL dropped for all patients at 3 weeks after surgery . Slowly , recovery was found at both 6 months and 1 year in both groups . Patients in the NGT group reported significantly ( P<0.05 ) better scores of QoL at both 6 months and 1 year . CONCLUSIONS Patients who underwent gastric tube reconstruction develop less postoperative digestive tract complications , and have a quicker recovery and a better QoL during the follow-up period . Further investigation and data collection will allow the assessment of this procedure beyond 1 year after operation AIM To assess the influence of the route of conduit transposition after transhiatal oesophagectomy on the postoperative morbidity and mortality and late outcome at 6 months . METHODS Patients with oesophageal carcinoma , undergoing transhiatal oesophagectomy ( gastric conduit ) , were r and omized to either anterior or posterior route of conduit transposition . Patients with advanced tumour , distant metastasis , extensive invasion of the stomach , previous gastric surgery , any anterior mediastinal abnormality detected on preoperative imaging , ASA grade III/IV and poor preoperative pulmonary function were excluded . Intraoperative complications , postoperative morbidity and mortality and late outcomes were compared . RESULTS Of the 49 patients ( 34 men ) , 24 patients were r and omized to the anterior mediastinal route and 25 to the posterior . The mean duration of the operative procedure ( anterior : 235min ; posterior : 225min ) and the mean blood loss ( anterior : 531ml ; posterior : 538ml ) were not statistically different . The most common complications were pulmonary and cardiac and comparable in both groups . Four patients died postoperatively . At 6-month follow-up the incidence of dysphagia , anastomotic stricture , anastomotic recurrence , aspiration and reflux symptoms and weight gain were similar . CONCLUSIONS The route of conduit transposition did not affect the outcome . However , an individualized approach depending upon the operative findings , radicality of the procedure , and perceived need for postoperative adjuvant therapy may be useful Background For patients undergoing oncologic surgery , the quality of life ( QoL ) is generally accepted as an important outcome parameter in addition to long-term survival , mortality , and complication rates . Our study focused on outcome in terms of QoL in patients with esophageal cancer , comparing the sites of anastomosis ( cervical versus thoracic anastomosis ) . Methods In a prospect i ve longitudinal single-center study from 1998 to 2005 , 105 patients underwent surgery for esophageal cancer . To assess QoL the EORTC-QLQ-C-30 and a tumor-specific module were administered before surgery , at discharge , and three , six , 12 , and 24 months after surgery . Clinical data were collected prospect ively and follow-up was performed every six months . Results The histological type was squamous cell carcinoma in 51.4 % of the cases , adenocarcinoma in 41.9 % , and some other type in 6.7 % . There was no significant difference between cervical and thoracic anastomosis with regard to morbidity , mortality , and survival rates ( 30 % five-year survival rate ) , whereas tumor stage was a significant ( p < 0.001 ) prognostic factor . Most QoL scores dropped significantly below baseline in the early postoperative period . Even though they recovered slowly during the follow-up period , they never reached preoperative levels again . There was no statistically significant difference in any of the QoL scales between patients with a cervical or a thoracic anastomosis . Conclusions Esophageal resections are associated with significant deterioration of QoL , which persists during the follow-up period . The surgical technique and position of the esophagogastrostomy did not affect QoL deterioration BACKGROUND We evaluated the impact of the size of gastric tubes on tissue blood flow of the anastomotic site , the frequency of leakage and the postoperative nutritional status . METHODS Forty-four patients were r and omly allocated to either reconstruction using subtotal stomach ( n = 22 ) or to reconstruction using slender gastric tube ( n = 22 ) after esophagectomy . The tissue blood flow at the anastomotic site was measured . The postoperative nutritional status of 17 patients without recurrence was examined . Possible correlations between the type of esophageal substitute and the tendency to leakage as well as postoperative nutritional status were examined . RESULTS There was no significant difference in the tissue blood and the frequency of leakage between the types of gastric tubes . There was no significant difference noted between the two in the postoperative nutritional status at 6 and 12 months after operation . CONCLUSIONS The width of gastric tube has no impact on tissue blood flow , the frequency of leakage , and the postoperative nutritional status after esophagectomy BACKGROUND The optimal management of the pylorus during esophagogastrectomy is unknown . Pyloromyotomy and pyloroplasty cause early edema and risk long-term bile reflux ; however , the lack of pyloric drainage might risk early aspiration . METHODS We performed a retrospective study with a prospect i ve data base on patients with esophageal cancer or high- grade dysplasia who underwent Ivor-Lewis esophagogastrectomy . All had one surgeon and similar stomach tubularization , h and -sewn anastomoses , nasogastric tube duration , and postoperative prokinetic agents . Outcomes of postoperative gastric emptying , aspiration , and swallowing symptoms were compared . RESULTS Between January 1997 and June 2008 , there were 221 patients . Seventy-one patients had a pyloromyotomy , and gastric emptying judged on postoperative day 4 was delayed in 93 % ( 52 % had any morbidity and 14 % had respiratory morbidity ) . Fifty-four patients had no drainage procedure , and gastric emptying was delayed in 96 % ( 59 % had any morbidity and 22 % had respiratory morbidity ) . Twenty-eight patients underwent pyloroplasty , and 96 % had delayed gastric emptying ( 50 % had any morbidity and 32 % had respiratory morbidity ) . Sixty-eight patients had botulinum toxin injection into the pylorus . Gastric emptying was delayed in only 59 % ( P = .002 , 44 % had any morbidity and 13 % had respiratory morbidity ) . Hospital length of stay ( P = .015 ) and operative times ( P = .037 ) were shorter in the botulinum toxin group . Follow-up ( mean , 40 months ) showed symptoms of biliary reflux to be lowest in the botulinum toxin group ( P = .024 ) . CONCLUSION Injection of the pylorus with botulinum toxin at the time of esophagogastrectomy is safe and decreases operative time when compared with pyloroplasty or pyloromyotomy . In addition , it can improve early gastric emptying , decrease respiratory complications , shorten hospital stay , and reduce late bile reflux . A prospect i ve multi-institutional r and omized trial is needed Objective A prospect i ve r and omized trial was performed to compare retrosternal and posterior mediastinal gastric tube reconstruction with regard to postoperative function and quality of life . Methods Twenty-six patients were r and omly allocated to either retrosternal ( n = 14 ) or posterior mediastinal ( n = 12 ) reconstruction after gastric tube formation . Radionuclide transit studies were applied to obtain objective functional data and a st and ardized quality -of-life assessment was performed . Results Retrosternal reconstruction showed an increased morbidity ( 15 vs 13 major complications ) and mortality ( 14.2 vs 8.3 % ) . Radionuclide clearance in the supine position was delayed in the gastric tube in general , compared with normal controls ( retention index > 40%vs < 10 % ) . There was a significantly higher retention ( p < 0.005 ) in the retrosternal group in the middle third of the tube and the whole tube after intake of the liquid tracer . The retention of the first solid tracer was also higher in the retrosternal group in the middle third of the tube ( p= n.s . ) and was significantly higher in the whole tube after 30 ( p < 0.05 ) and 60 ( p < 0.01 ) s. This had no significant impact on the patients ’ quality of life . Conclusions The posterior mediastinal route of reconstruction is recommended but curative resection ( R0 ) is m and atory to avoid possible complications due to local tumor relapse . After incomplete resection ( R1 or R2 ) we recommend retrosternal reconstruction for better palliation After potentially curative resection of oesophageal cancer and prevertebral gastric tube reconstruction , approximately one‐quarter of patients develop secondary dysphagia due to locoregional recurrence . In half of them dysphagia can be prevented by using an extra‐anatomical reconstruction route . The present r and omized study was conducted to compare the technical and functional results after prevertebral and retrosternal gastric tube reconstruction In a prospect i ve r and omized study of pyloroplasty versus no drainage , 200 patients ( 100 in each group ) in whom the whole stomach was used for reconstruction following resection for esophageal carcinoma were studied . Only patients who underwent the Lewis-Tanner operation and who had a normal pylorus were included . There was no morbidity from the pyloroplasty procedure . Thirteen patients without drainage developed symptoms of gastric outlet obstruction , requiring prolonged post-operative parenteral nutrition , and reoperation was required in one patient . Four patients developed pulmonary complications associated with gastric distension , which result ed in fatal aspiration in two patients . Five patients had symptoms of outlet obstruction with eating at the time of their death . Mean and st and ard deviation of daily gastric aspirate was 161 + /- 88 mL in the pyloroplasty group and 233 + /- 142 mL for the control group ( p = 0.23 ) . Gastric emptying test showed mean T1/2 + /- st and ard deviation of 6.6 + /- 7.5 minutes in the pyloroplasty group and 24.3 + /- 31.5 minutes in the control group ( p less than 0.001 ) . More patients in the pyloroplasty group were able to tolerate a solid diet and at normal or increased amounts than were patients in the control group in the early postoperative weeks ( p less than 0.01 ) . In addition , control patients were found to have increased symptoms with meals , which were more frequent and of greater severity than symptoms in patients in the pyloroplasty group , even at 6 months after surgery ( p less than 0.01 ) . Therefore , we recommend a pyloroplasty for patients in whom the whole stomach is used for reconstruction after esophagectomy Background : Little is known regarding the short-term quality of life ( QoL ) and predictive factors for QoL after esophagectomy for cancer in Eastern countries . Objective : The aims of this study were to assess QoL and symptoms within 1 and 6 months after surgery for esophageal cancer ( EC ) and to identify factors predictive of QoL within 6 months after esophagectomy in Taiwan . Methods : A longitudinal , prospect i ve design was used , where convenience sample s of 99 patients who had undergone esophagectomy for cancer were recruited from 2 medical centers in northern Taiwan . All participants responded to a question naire with a QLQ-C30 ( Quality of Life Question naire – Cancer ) core and a QLQ-OES18 ( esophageal module of the European Organization for Research and Treatment [ EORTC ] QLQ-C30 ) module in structured interviews at baseline and 1 and 6 months after surgery . Results : The results showed significant decline in social function and global QoL ; fatigue , insomnia , eating problems , reflux , and dry mouth were major problems within 6 months . Body mass index , body weight loss before surgery , activity performance status , and anastomosis site showed no significant association with the function and symptom aspect of QoL. Surgical complications , advanced cancer , neoadjuvant therapy before surgery , and tumor location other than at the EC junction had significant deleterious effects on several aspects of QoL. Conclusions : This study describes the demographics of EC and short-term changes in QoL and also the predictive impact factor for QoL after surgery for EC . Implication s for Practice : Knowledge of risk factors for poor postoperative QoL would be useful for health providers in detecting and prioritizing problems and treatment options in a busy clinical site BACKGROUND After " curative " resection of carcinoma of the esophagus , late secondary dysphagia almost invariably indicates locoregional tumor recurrence . The retrosternal reconstruction route is advocated to prevent ingrowth of tumor recurrence in the neoesophagus . STUDY DESIGN To evaluate the quality of palliation after " curative " resection of carcinoma of the esophagus and the possible benefit of the retrosternal reconstruction route , we retrospectively analyzed the records of patients who had resection of a malignant tumor of the esophagus , or the gastroesophageal junction , and a prevertebral reconstruction . The extra-anatomic route would have been only beneficial for patients with intrathoracic tumor recurrence distant from the anastomosis and causing gastrointestinal symptoms . RESULTS Between 1983 and 1989 , 209 patients ( mean age of 61.3 years at the time of operation ) had " curative " resection and prevertebral reconstruction in the institution of this study . Seventy-three patients ( 35 percent ) had locoregional tumor recurrence . Univariate and multivariate analysis of various risk factors for locoregional recurrence showed that the presence of positive lymph nodes ( pN1 ) , especially if located at the celiac trunk ( pM1 ) , and a macroscopically non-radical R2 resection were the most important risk factors . Forty-six patients ( 22 percent ) had secondary dysphagia as a result of locoregional tumor recurrence , mostly ( 18 percent ) within two years postoperatively . Dysphagia lasted on average 5.3 months ( range of 0.3 to 21.5 months ) before the patients died . In 27 patients ( 13 percent ) , dysphagia would probably have been prevented by using a retrosternal reconstruction route . CONCLUSIONS These data are an argument in favor of the extra-anatomic , retrosternal reconstruction route after limited transthoracic or transhiatal resection in the presence of positive lymph nodes . This method seems especially indicated if the nodes are located at the celiac trunk and in case of a macroscopically nonradical R2 resection A prospect i ve , r and omized , controlled trial comparing clinical outcome and emptying of a solid meal from the retrosternal stomach , with and without pyloroplasty is described . Forty consecutive patients with oesophageal cancer undergoing retrosternal gastric reconstruction of the oesophagus were studied . In 20 patients the pylorus was left intact ( group 1 ) and 20 patients underwent an Aust1 pyloroplasty ( group 2 ) . Nine patients in group 1 suffered postoperative symptoms of gastric stasis compared with only one patient in group 2 ( P = 0·0106 ) . Three patients in group 1 died from aspiration pneumonia before discharge from hospital . A gastric emptying test was performed on 24 patients between 1 and 3 months after surgery . By this time , most survivors had recovered from symptoms attributed to gastric stasis and no significant difference in gastric emptying could be demonstrated between the two groups . Selection of patients , a wide range of emptying times and improvement in gastric emptying on follow‐up may explain the lack of correlation between postoperative symptomatology and the gastric half‐emptying times . A pyloroplasty is advised to prevent the potentially lethal effects of gastric stasis in the early postoperative period following retrosternal reconstruction of the oesophagus BACKGROUND The motor activity of the gastric tube as an esophageal replacement after esophagectomy is poorly understood . The aims of the present study were to examine the gastropyloric motility of the gastric tube and the effects of erythromycin given orally . METHODS Interdigestive gastropyloric motility was recorded by manometry with a sleeve sensor in 23 esophagectomized patients . The 23 patients were classified into 3- , 12- , and 24-month groups according to postoperative follow-up time . Radiopaque markers were used in 8 patients to assess gastric emptying . The effects of erythromycin were studied after the patients received 600 mg during fasting and 1 g postpr and ially . RESULTS Compared with the 3-month group , the 12-month group and the 24-month group showed significantly increased pyloric and antral motility , respectively . During a fast , erythromycin induced phase III in 44.4 % of the patients with more than 12 months of follow-up . In contrast to the normal subjects , esophagectomized patients showed delayed gastric emptying at 3 and 4 hours . However , erythromycin significantly accelerated gastric emptying at 1 , 2 , 3 , and 4 hours . CONCLUSIONS The motor activity of the gastric tube returns towards normal in a progression over time from the pylorus cephalad . Erythromycin given orally might be used as a prokinetic agent in patients after esophagectomy A r and omized , prospect i ve , controlled trial compared the use of pyloroplasty ( study group ) with nonuse of the procedure ( control group ) in the treatment of 72 patients with carcinoma of the thoracic esophagus . In these patients , transthoracic esophagectomy was performed , and the whole stomach was used for reconstruction in the right side of the chest . No complications due to the pyloroplasty developed in any of the patients who underwent this procedure . Gastric emptying tests that were performed at the sixth postoperative month in 37 patients demonstrated a prolongation of emptying time in the control group ( p less than 0.01 ) . The patients ' symptoms , however , did not correlate well with gastric emptying time . Follow-up assessment showed that a higher proportion of patients who did not undergo pyloroplasty suffered from symptoms of incomplete emptying while eating , but the difference was not statistically significant . Moreover , the proportion of patients who were free of postoperative symptoms gradually increased in both groups and reached 100 % in the study group and 89 % in the control group at 2 years . In the control group , two of the three patients with prolonged gastric emptying time complained of persistent regurgitation and distending discomfort after meals ( 18 and 24 months after surgery ) . They were the only two patients who might have benefited from a drainage procedure at the initial operation . Since there apparently were no reliable operative criteria by which to identify patients who might require drainage , and since the risk associated with pyloroplasty was negligible , it would seem reasonable to perform a pyloroplasty on every patient in whom the whole stomach was used for reconstruction after esophagectomy . This procedure would benefit the few patients who might manifest symptomatic gastric stasis Thirty-eight patients who underwent oesophagogastrostomy for oesophageal carcinomas were included in this study . Nineteen cases had pyloroplasty or pyloromyotomy ( group A ) and the other 19 cases did not have drainage procedures of the intrathoracic stomach ( group B ) . Radionuclide labelled solid meals were used to calculate the gastric emptying times ( GET ) of the intrathoracic stomachs . The GET of the patients was compared with the normal GET ( 88.7 ± 14.2 min ) from 25 normal volunteers . In the 38 patients , 18 ( 47 % ) demonstrated prolonged GET , 10 ( 26 % ) shortened GET , and the remaining 10 ( 26 % ) cases GET was within the normal range . Based on Fisher 's tests , there was no significant difference ( P > 0.05 ) in the incidence of prolonged and normal GET but significantly shorter ( P < 0.05 ) GET between groups A and B. Our data suggest that the intrathoracic stomach appears to be of variable motility , different from the stomach located in the normal position . To preserve the better gastric emptying , a drainage procedure should be recommended for intrathoracic stomachs Objective : The purpose of the study was to compare in prospect i ve r and omized fashion a manually sutured esophagogastric anastomosis in the neck and a stapled in the chest after esophageal resection and gastric tube reconstruction . Summary Background Data : Despite the fact that all reconstructions after esophagectomy will result in a cervical or a thoracic anastomosis , controversy still exists as to the optimal site for the anastomosis . In uncontrolled studies , both neck and chest anastomoses have been advocated . The only reported r and omized study is difficult to evaluate because of varying routes of the substitute and different anastomotic techniques within the groups . The reported high failure rate of stapled anastomoses in the neck and the fact that most surgeons prefer to suture cervical anastomoses made us choose this technique for anastomosis in the neck . Our routine and the preference of most surgeons to staple high thoracic anastomoses became decisive for type of thoracic anastomoses . Methods : Between May 9 , 1990 and February 5 , 1996 , 83 patients undergoing esophageal resection were prospect ively r and omized to receive an esophagogastric anastomosis in the neck ( 41 patients ) or an esophagogastric anastomosis in the chest ( 42 patients ) . To evaluate selection bias , patients undergoing esophageal resection during the same period but not r and omized ( n = 29 ) were also followed and compared with those in the study ( n = 83 ) . Objective measurements of anastomotic level and diameter were assessed with an endoscope and balloon catheter 3 , 6 , and 12 months after surgery . The long-term survival rates were compared with the log-rank test . Results : Two patients ( 1.8 % ) died in hospital , and the remaining 110 patients were followed until death or for a minimum of 60 months . The genuine 5-year survival rate was 29 % for chest anastomoses and 30 % for neck anastomoses . The overall leakage rate was 1.8 % ( 2 cases of 112 ) with no relation to mortality or anastomotic method . All patients in the r and omized group had tumor-free proximal and distal resection lines , but 1 patient in the nonr and omized group had tumor infiltrates in the proximal resection margin . At 3 , 6 , and 12 months after operation , there was no difference in anastomotic diameter between the esophagogastric anastomosis in the neck and in the thorax ( P = 0.771 ) , and both increased with time ( P = 0.004 , ANOVA repeated measures ) . Body weight development was the same in the two groups . With similar results in r and omized and nonr and omized patients , study bias was eliminated . Conclusions : When performed in a st and ardized way , neck and chest anastomoses after esophageal resection are equally safe . The additional esophageal resection of 5 cm in the neck group did not increase tumor removal and survival ; on the other h and , it did not adversely influence morbidity , anastomotic diameter , or eating as reflected by body weight development Bile acid concentration and symptoms were evaluated in 24 patients after total oesophagectomy and gastric pull‐up . Patients were r and omly allocated to receive pyloroplasty or not . After operation all were followed for a minimum of 6 months . Bile acid concentration in the gastric juice was estimated . The mean(s.d . ) bile acid concentration 6 months after surgery was similar in patients with and without pyloroplasty ( 34.9(30.1 ) and 25.0(24.2 ) mg/dl respectively ) . Postpr and ial discomfort and bilious eructations were the two most commonly observed symptoms in both groups . Other features noted were vomiting , anaemia and anorexia . These did not however seem to be related to intragastric bile acid concentration of individual patients in either group and occurred irrespective of whether pyloroplasty was performed or not |
13,917 | 30,136,717 | AUTHORS ' CONCLUSIONS The addition of local anaesthesia to nasal packs ( if these are being used ) following septal surgery may reduce postoperative pain within the first 12 hours , compared to nasal packing with a placebo added .
Evidence was lacking for other outcomes , including adverse effects .
There is a lack of evidence about the effects of local anaesthesia added to nasal packing compared to no nasal packing .
There is also a lack of evidence about the effects of local anaesthesia given by injection and the effects of sphenopalatine ganglion block | BACKGROUND Septal surgery is a well-established procedure used to treat nasal obstruction due to deviation of the nasal septum , which is carried out under local or general anaesthesia .
Local anaesthesia is used for postoperative pain control , but its effectiveness and safety are unclear .
OBJECTIVES To assess the effectiveness of perioperative local anaesthesia for reducing pain in septal surgery and to evaluate the risk of associated complications . | To ascertain whether local anaesthetic use is of clinical benefit in nasal surgery , a prospect i ve double-blind r and omized controlled trial of topical bupivacaine on post-operative pain in patients packed after bilateral nasal surgery was carried out . Each patient received a bupivacaine-soaked and a saline-soaked Merocel pack , thereby acting as their own control . Power analysis ascertained the number of patients required to enter the trial to detect a statistically significant difference in pain . Fifty-seven patients completed the trial . Visual analogue scales determined the level of post-operative pain at different time points in each nostril . Less pain was demonstrated in nostrils containing bupivacaine-soaked packs compared with saline-soaked packs at two hours ( p < 0.0001 ) , four hours ( p = 0.0183 ) and six hours ( p = 0.0476 ) post-operatively . Although not statistically significant , less pain was noted on pack removal on the local anaesthetic sides . These results provide clinical -based evidence for the use of bupivacaine as a local anaesthetic in reducing pain following nasal surgery with packing Packing of the nasal cavity remains a common routine pre caution ary measure following septal surgery . The nasal pack and its removal 24 h later are often cited by patients as the most painful aspects of septal surgery . We present the results of a r and omized , prospect i ve controlled trial of the use of topical 5 % lignocaine ointment as a method of pain relief following post-operative nasal packing . Post-operative pain as measured using a visual analogue scale at 3 h post-operatively was halved in patients receiving a lignocaine impregnated nasal pack compared with those having a st and ard vaseline gauze pack ( P < 0.05 ) . Pain scores at 6 h post-operatively and at pack removal were also reduced , but these failed to reach significance . No patients suffered reactionary haemorrhage . The use of topical lignocaine ointment is safe and may have a place in the relief of pain due to post-operative nasal packing Background Septorhinoplasty is a traumatic procedure that is associated with epistaxis and postoperative pain . The primary objective of this r and omized double-blind controlled trial was to determine whether intranasal 5 % lidocaine plus naphazoline decreases postoperative pain and lessens the use of rescue analgesics . Methods After induction of general anesthesia and laryngeal topical anesthesia with 5 % lidocaine , 28 adult patients , scheduled to undergo septorhinoplasty , were r and omly assigned to one of two groups , either topical intranasal saline 20 ml ( control group ) or intranasal 5 % lidocaine plus naphazoline solution 0.2 mg ml−1 ( lidocaine group ) . The perioperative dose of sufentanil , the mean end-tidal concentration of isoflurane , and surgeon satisfaction with the operative field were recorded . In the lidocaine group , plasma lidocaine concentrations were sample d 15 , 20 , 25 , 35 , 45 , and 55 min after induction of anesthesia . Visual analogue scale pain scores were recorded 30 , 60 , 90 , and 120 min after the patients arrived in the postanesthesia care unit and 24 h after surgery . Consumption of morphine rescue analgesia and the occurrence of any side effects were recorded at the end of the 24-h study period . Results The intranasal lidocaine-naphazoline application decreased isoflurane requirements [ median values : 0.8 % ( 0.7–1.5 ) vs. 1.2 % ( 0.9–1.8 ) , respectively ; P = 0.04 ] and enhanced surgical conditions . Patients in the lidocaine group experienced less postoperative pain than the control group [ 1 h after surgery : median values of visual analogue scale : 0 ( 0–20 ) vs. 50 ( 30–80 ) , respectively ; P = 0.001 ] , and they required fewer doses of subcutaneous morphine . Total plasma concentrations of lidocaine remained below 4 μg ml−1 throughout the study period . Conclusions Intranasal lidocaine plus naphazoline is a simple and efficient technique for decreasing intra- and postoperative pain and for lessening rescue analgesic requirements in the postoperative period after septorhinoplasty . Toxic plasma concentrations of lidocaine were not reached . Résumé Context eLa rhinoseptoplastie est une procédure traumatisante associée à une épistaxis et des douleurs postopératoires . L’objectif primaire de cette étude r and omisée contrôlée à double insu était de déterminer si une solution intranasale de lidocaïne 5 % plus naphazoline réduisait la douleur postopératoire et diminuait l’utilisation d’analgésiques de sauvetage . MéthodeAprèsl’induction de l’anesthésie générale et une anesthésie laryngée topique avec de la lidocaïne 5 % , 28 patients adultes subissant une rhinoseptoplastie ont été r and omisés en deux groupes : 20 mL de solution saline intranasale topique ( groupe témoin ) ou solution de 5 % lidocaïne intranasale plus naphazoline 0,2 mg·mL−1 ( groupe lidocaïne ) . La dose périopératoire de sufentanil , la concentration d’isoflurane moyenne télo-expiratoire et la satisfaction du chirurgien quant au champ opératoire ont été enregistrés . Dans le groupe lidocaïne , les concentrations plasmatiques de lidocaïne ont été échantillonnées à 15 , 20 , 25 , 35 , 45 et 55 min aprèsl’induction de l’anesthésie . Les scores de douleur sur une échelle visuelle analogique ont été enregistrés 30 , 60 , 90 et 120 minutes aprèsl’arrivée des patients dans l’unité de soins postanesthésiques et 24 h après la chirurgie . La consommation de morphine en analgésie de sauvetage et la survenue d’effets secondaires ont été enregistrées à la fin de la période d’étude de 24 heures . RésultatsL’application de lidocaïne-naphazoline intranasale a diminué les besoins en isoflurane [ valeurs médianes : 0,8 % ( 0,7–1,5 ) vs 1,2 % ( 0,9–1,8 ) , respectivement ; P = 0,04 ] et amélioré les conditions chirurgicales . Les patients du groupe lidocaïne ont souffert de moins de douleurs postopératoires que ceux du groupe témoin [ une heure après la chirurgie : valeurs médianes sur l’échelle visuelle analogique : 0 ( 0–20 ) vs 50 ( 30–80 ) , respectivement ; P = 0,001 ] , et ont nécessité moins de doses de morphine sous-cutanée . Les concentrations plasmatiques totales de lidocaïne sont demeurées au dessous de 4 μg·mL−1 tout au long de la période d’étude . Conclusion La lidocaïne intranasale plus naphazoline est une technique simple et efficace pour diminuer la douleur per- et postopératoire et pour réduire les besoins en analgésiques de sauvetage durant la période postopératoire suivant une rhinoseptoplastie . Un niveau toxique de concentrations plasmatiques de lidocaïne n’a pas été atteint A double-blind investigation has been carried out using three different doses ( 20 , 35 and 50 mg ) of cocaine which were sprayed onto the nasal mucous membranes of forty-five patients for nasal surgery . The cocaine was administered after induction of general anaesthesia in all cases . The 20 mg dose of cocaine dissolved in 2 ml of saline without adrenaline was found to be safe and produced adequate nasal decongestion in the absence of other predominant factors . The efficacy of cocaine and its safety with regard to systemic absorption are assessed We aim ed to investigate the effects of local anesthetics soaked in Merocel nasal packs on hemorrhage and pain after septoplasty . The methodology includes a prospect i ve double-blind study that was conducted in patients undergoing septoplasty because of nasal septal deviation . The study included 143 patients . The patients were divided into four groups . Each group received 1 % lidocaine + 0.000625 % adrenalin , 0.375 % ropivacaine , 0.25 % bupivacaine as study groups or 0.9 % sodium chloride as a control group in their Merocel packs postoperatively . The local anesthetics or sodium chloride were reapplied at the eighth postoperative hour . Each patient was given a question naire where verbal analog score and amount of postoperative hemorrhage was noted . The statistical analysis was performed using two sided t test on each patient group at each time point . The results included the patients in the control group needing rescue drug most often . There was no statistically significant difference between bupivacaine and lidocaine plus adrenalin in the patients who requested rescue drug . The patients in the ropivacaine group requested rescue drug more frequently than the bupivacaine and lidocaine plus adrenalin groups . Bupivacaine group had significantly better pain scores versus control group at all intervals except for the first postoperative hour . The bupivacaine group had better pain scores versus ropivacaine and lidocaine plus adrenalin groups in the 4th , 8th and the 24th hours . The bupivacaine group had better pain scores versus lidocaine plus adrenalin in the 12th , 16th and the 20th hours . The ropivacaine group had significantly better pain scores versus control group in the 8th , 12th , 16th , 20th and 24th postoperative hours . The ropivacaine group scored better than lidocaine plus adrenalin group just in the 16th hour . The lidocaine plus adrenalin group had significantly better pain scores versus control group in 4th and 12th hours . There was no statistically significant difference between the study groups in terms of postoperative hemorrhage . We concluded that bupivacaine use in nasal surgery provides better analgesia at least in the first 8 h period and does not cause more bleeding . Topical bupivacaine application to nasal packs should be considered after septoplasty OBJECTIVES To compare the efficacy of Spiggle and Merocel foam packs following routine nasal surgery . DESIGN Prospect i ve , r and omised , single-blind , paired study . PARTICIPANTS Twenty adult patients undergoing elective nasal surgery . INTERVENTION At the end of nasal surgery patients were r and omised to have a Spiggle pack inserted in one nasal cavity and a Merocel pack in the other . Packs were removed the following morning . MAIN OUTCOME MEASURES The primary outcome measure was pain due to the presence of packs in the nose and pain associated with their removal . This was measured using a visual analogue scale . Secondary outcome measures were bleeding , crusting and adhesion formation . RESULTS Both packs were effective at preventing postoperative haemorrhage . Bleeding following removal was minimal . There were no significant differences between the packs in terms of levels of discomfort experienced 6 hours after surgery or the following morning prior to removal ( p = 0.3 and p = 0.3 respectively ) . However , the Spiggle foam pack caused significantly less pain on removal compared with the Merocel foam pack ( mean difference 1.4 ; 95 % CI 0.4 to 2.4 , p = 0.005 ) . There were no significant differences in terms of crust and adhesion formation . CONCLUSIONS In this study , both the Spiggle and Merocel foam nasal packs were well tolerated while in the nose . Both provided good postoperative haemostasis and were not associated with bleeding on removal . The Spiggle foam pack had the advantage of causing significantly less pain on removal . However , it must be borne in mind that in this study the Spiggle pack was more likely to be positioned in the non-incised nasal cavity , the side that would generally be expected to be associated with less pain BACKGROUND To maintain a high st and ard of patient care , it is essential to provide adequate pain management in patients who undergo nasal surgery . Levobupivacaine and ropivacaine are relatively new long-acting local anesthetics . OBJECTIVE The aim of this study was to compare the analgesic effect and blood loss of preincisional levobupivacaine HCl 0.25 % and ropivacaine HCl 0.375 % in patients undergoing septorhinoplasty . METHODS Sixty American Society of Anesthesiologists ( ASA ) I and II patients ( 18 - 55 years old ) who were scheduled for elective open technique septorhinoplasty under general anesthesia were recruited for this study . The anesthetic technique was st and ardized for both groups . Preoperative and postoperative hemoglobin levels were recorded for all patients . Patients were assigned r and omly to 1 of 2 study groups , and preincisional surgical field infiltration with 5 mL of 0.5 % levobupivacaine plus 5 mL of 0.9 % saline ( group L ; n = 30 ) or 5 mL of 0.75 % ropivacaine plus 5 mL of 0.9 % saline ( group R ; n = 30 ) was performed by the same surgeon . The degree of pain was measured by visual analogue scale ( VAS ) for pain and recorded at multiple time points in all patients after surgery . RESULTS The analgesic effect at 2 hours in the postanesthesia care unit ( PACU ) and at 24 hours postoperatively did not differ significantly between the 2 local anesthetics ( P > 0.05 ) . Pain scores of patients decreased after the 24 hours in levobupivacaine group and ropivacaine group when compared with 0-minute VAS values , and this was statistically significant ( P < 0.05 ) . No significant difference was observed between groups with respect to the preoperative and postoperative hemoglobin ( P = 0.767 and 0.824 , respectively ) values . CONCLUSIONS Local tissue infiltration with 0.25 % levobupivacaine or 0.375 % ropivacaine is similarly effective in reducing the postoperative pain associated with septorhinoplasty Objective : Obtaining adequate hemostasis during otolaryngology operations is necessary because a small amount of blood can be problematic and obscure the visual field . The authors aim ed to compare the efficacy of combined greater palatine canal ( GPC ) and transnasal injection of lidocaine + epinephrine to transnasal injection alone in patients who underwent septoplasty . Methods : Patients with nasal septum deviation who were eligible for surgical correction of deviations were enrolled . Transnasal injections of 2 mL of 1 % lidocaine + epinephrine 1:100,000 were performed in both groups and for patients in the combination group the same solution was also injected in the GPC . Objective ( amount of suctioned blood ) and subjective ( intraoperative bleeding score ) assessment s were done during operation . Close hemodynamic monitoring was performed for all patients . Results : A total of 50 patients were enrolled and r and omly allocated to study groups . No significant differences were observed in systolic and diastolic blood pressure , heart rate , and mean arterial pressure of study subjects between 2 groups . The amount of bleeding in patients who received GPC injection and their counterparts in the other arm of the trial were 34.64 ± 26.66 and 100.48 ± 20.90 mL , respectively ( P < 0.001 ) . The mean intraoperative bleeding score in combination group was 0.79 ± 0.42 and significantly lower than the corresponding figure in monotherapy group , which was 1.75 ± 0.41 ( P < 0.001 ) . Conclusions : Based on the findings of the current study , the authors suggest that combined GPC and transnasal injection of lidocaine and epinephrine is a safe and effective method for reducing bleeding during septoplasty Objective . Although topical decongestants and anesthetics are widely used in preparation for nasal endoscopy , no controlled trials have evaluated the effects of these agents on olfaction . Study Design . R and omized double-blinded controlled trial . Setting . Tertiary referral hospital . Material s and Methods . The authors recruited 72 healthy subjects and r and omly assigned them to 1 of 4 groups ( control , phenylephrine group , lidocaine group , and both agents ) . After baseline tests with the Korean version of Sniffin ’ Stick Test II ( KVSS II ) , topical agents were applied to each nostril . Fifteen minutes later , repeat tests were carried out . Pre- and postspray results of the olfactory tests were compared , and the differences among groups were analyzed . Results . The mean ± SD prespray KVSS II score of the study group was 30.2 ± 3.8 , and there were no statistically significant differences among the study groups ( P = .353 ) . Mean ± SD pre- and postspray KVSS II scores were 29.0 ± 3.5 and 30.7 ± 3.7 ( P = .128 ) in the control group , 30.6 ± 3.6 and 31.7 ± 3.3 ( P = .262 ) in the phenylephrine group , and 31.4 ± 3.6 and 32.1 ± 3.1 ( P = .557 ) in the lidocaine group , respectively . In the phenylephrine and epinephrine spray group , the mean ± SD pre- and postspray scores were 29.9 ± 4.4 and 31.3 ± 3.7 ( P = .071 ) , respectively . Conclusions . Neither topical intranasal phenylephrine nor lidocaine use affected the results of the olfactory test , even when the agents were used in combination OBJECTIVE : The aim of this study was to evaluate the efficacy of pharyngeal packing in reducing postoperative nausea and vomiting ( PONV ) after nasal surgery by taking into consideration the surgery types . STUDY DESIGN : A prospect i ve , r and omized , controlled trial . SETTING : A tertiary referral center . SUBJECTS AND METHODS : After the study was approved by the local ethics committee , this study was conducted in the Otorhinolaryngology clinic with the collaboration of the Anesthesiology clinic . The development of PONV within 24 hours after surgery was evaluated in patients who were applied a pharyngeal pack ( Group 1 ) or not ( Group 2 ) during nasal surgery . RESULTS : There were 104 adult patients for routine nasal surgery included in the current study , yielding 100 ( group 1 , n = 50 ; group 2 , n = 50 ) evaluable subjects . No significant difference was found in the incidence of PONV between the two groups at two ( P = 0.41 ) , four ( P = 0.54 ) , eight ( P = 0.51 ) , and 24 hours . According to surgery type , the incidence of PONV after two hours was 71 percent in septorhinoplasty , 68 percent in endoscopic sinus surgery , and 50 percent in septoplasty ; after four hours it was 59 percent in septorhinoplasty , 53 percent in endoscopic sinus surgery , and 37 percent in septoplasty ; and after eight hours it was 35 percent in septorhinoplasty , 39 percent in endoscopic sinus surgery , and 21 percent in septoplasty . PONV was not seen at 24 hours . Compared to the septoplasty group for which pharyngeal packing was used , significantly lower rates of PONV at four and eight hours were found in the septoplasty group in which pharyngeal packing was not used ( P = 0.02 ) . CONCLUSION : Pharyngeal packing in nasal surgery has no impact on PONV Background Our aim in this study was to investigate the effect of levobupivacaine and a levobupivacaine + tramadol combination on postoperative analgesia in intraoperative nerve block under st and ard general anesthetic . Methods Forty-five patients undergoing outpatient nasal surgery under general anesthesia were r and omized into 3 groups . Group L : 0.25 % levobupivacaine , group T : 0.25 % levobupivacaine and 50 mg tramadol , group S : normal saline solution ; 2 mL of each being injected into the infraorbital foramen . Intraoperative hemodynamic changes were recorded . Verbal numeric rating scale ( NRS ) values were checked at 30 minutes and 1 , 2 , 8 , and 12 hours postoperatively , and the need for rescue analgesic treatment in the first 12 hours of all patients was recorded . Also antiemetic drug requirement and side effects ( nausea , edema , erythema , hematoma , and sedation ) were recorded . Results At 30 minutes and 1 hour postoperatively , NRS pain scores were lower in group T than in group S ( P < 0.0001 , P = 0.01 , respectively ) . NRS pain score was lower in group T compared with group L at 1 hour postoperatively ( P = 0.01 ) . Effective analgesia time ( sec ) in the control group ( 142.67 ± 77.31 ) was shorter than levobupivacaine ( 240 ± 96.39 ) and levobupivacaine added to tramadol groups ( 277 ± 11.60 ) ( P < 0.05 ) . Additional analgesic requirement in the control group was higher than the other 2 groups in early postoperative period ( P < 0.05 ) . Conclusions Bilateral infraorbital nerve block with 0.25 % levobupivacaine is an effective , reliable , and simple technique in the treatment of postoperative pain in nasal surgery . In addition , the addition of tramadol as an adjuvant to local anesthetics in this technique is safe Background Only a few studies have so far compared the use of different local anesthetic agents in septoplasty procedure with regard to reduction in pain , effectiveness , and related complications . The aim of this study was to compare articaine and lidocaine as local anesthetics for septoplasty surgery , in terms of their efficacy and safety . Methods Seventy patients r and omized into two groups were included in this study . For local anesthesia , 35 patients received articaine and 35 received lidocaine . All patients were asked to rate their pain levels on a visual analog scale ( VAS ) at the 1st , 2nd , 4th , 6th , 8th , 12th , 18th , and 24th postoperative hours . In addition , analgesic consumption of each patient as well as postoperative complications was recorded in both groups . Results VAS scores for pain were significantly lower in the articaine group than in the lidocaine group at the 2nd , 6th , 8th , 12th , and 24th postoperative hours ( p < 0.05 ) . Comparison of the patients ’ usage of analgesics during the first 24 hours postoperatively showed that in the articaine group , the percentage of patients that had not used analgesics was 58.5 % , and in the lidocaine group the corresponding figure was 41.5 % . Conclusion Articaine is a safe local anesthetic agent with rapid onset of action . When compared with lidocaine , it is associated with improved tissue diffusion , rare postoperative complications , and less postoperative pain , thus , representing a safe and effective local anesthetic agent for septoplasty procedure The aim of this study was to determine whether infiltration of local anesthetics with adrenaline improved septoplasty procedure when compared to normal saline . Eight-two patients undergoing septoplasty were r and omized into two groups . In group 1 , septal mucoperichondrium was infiltrated with lidocaine with adrenaline , and normal saline was used in group 2 . Presence of intra-operative septal mucosal injuries , the amount of bleeding , arterial blood pressure , operation time as well as the quality of the surgical field and the convenience of finding the correct surgical plane as determined by the surgeon using a 5-point scale were compared between two groups . There were no significant differences for the amount of blood loss , mean arterial pressure , operation time , or scores for convenience of finding the correct surgical plane between the two groups . There was no significant difference for intra-operative simple ( P = 0.631 ) and total ( simple+severe ) ( P = 0.649 ) septal mucoperichondrial injuries between groups 1 and 2 , either . However , severe mucoperichondrial injury rate was higher in the patients infiltrated with lidocaine and adrenaline ( P = 0.026 ) , and the quality of the surgical field was worse in the patients injected with normal saline ( P = 0.0179 ) . Infiltration of septal mucoperichondrium with lidocaine and adrenaline instead of normal saline was not advantageous in terms of objective parameters tested , including bleeding amount and duration of surgery as well as the of the total mucosal injury rate in septoplasty procedure The aim of this study was to evaluate the analgesic efficacy of sphenopalatine ganglion block performed under general anesthesia in patients undergoing functional endoscopic sinus surgery ( FESS ) with operative blood loss and postoperative complications ( headache , visual disturbances , nausea , vomiting , sore throat , swallow difficulty ) . Forty-five consenting patients were r and omized to receive bilateral sphenopalatine ganglion block with saline ( Group S , n = 15 ) , bupivacaine 0.5 % ( Group B , n = 15 ) , or levobupivacaine 0.5 % ( Group L , n = 15 ) immediately following induction of general anesthesia . Esmolol was given during the intraoperative period for a 20 % increase in arterial mean pressure or heart rate . Postoperative pain scores were checked on arrival at the postanesthesia care unit , 2 , 6 , and 24 h after surgery and diclofenac was administered intramuscularly for pain score ≥4 . A statistically significant reduction was present in postoperative Visual Analog Scale scores between Group S and the block Groups B and L ( p < 0.05 ) . In Group L and B , fewer patients required additional analgesics in the postoperative 24 h ( p < 0.0001 ) . The comparison of postoperative complications was not statistically significant among the groups ( p > 0.05 ) . Sphenopalatine ganglion block with bupivacaine or levobupivacaine improved postoperative analgesia associated with better surgeon and patient satisfaction after FESS OBJECTIVE The aim of this prospect i ve , r and omized , double-blind study was to investigate the postoperative analgesic effects of levobupivacaine or tramadol infiltration administered prior to surgery in septorhinoplasty ( SRP ) or endoscopic sinus surgery ( ESS ) . MATERIAL AND METHODS Sixty ASA class I-III adult patients electively undergoing SRP or ESC were included the study . Induction of anesthesia was performed with propofol 2 - 2.5 mg/kg , rocuronium bromide 0.6 mg/kg and fentanyl 1 μg/kg i.v . Sevoflurane 2 % with an N2O/O2 mixture ( FiO2 : 35 % ) was used for maintenance . Tramadol 0.5 mg/kg ( Group T : n=20 ) , levobupivacaine 0.25 % ( Group L : n=20 ) and lidocaine 1 % ( Group C : n=20 ) in a 1/200,000 adrenaline solution was infiltrated into the surgical area 10 min before the operation ( 5 mL for ESS and 10 mL for SRP ) . All patients received fentanyl ( bolus dose : 15 μg and lockout interval : 10 min ) with a patient-controlled analgesia device during the postoperative period . Pain was assessed using an 11-point visual analogue scale ( VAS ) every 4 h for the first 24 h. Analgesic requirements , opioid consumption and side effects in the postoperative period were recorded . RESULTS There was a statistically significant decrease in postoperative fentanyl dem and and consumption in patients receiving tramadol . Fentanyl doses in the 24 h period were 345.2±168.8 μg , 221.1±120.6 μg and 184.1±130.3 μg ( p=0.002 ) for the Groups C , L and T , respectively . There were statistically significant differences in fentanyl requirements between the tramadol and control groups at the 16 , 20 and 24 h time points ( p=0.012 , p=0.004 and p=0.002 , respectively ) . The side effect profiles were similar . CONCLUSIONS Our study indicates that the preemptive tramadol infiltration technique is an efficient , practical and safe alternative to levobupivacaine in ESS or SRP operations Tramadol is a central ly acting opioid which is effective for moderate-severe pain and is being used for various acute and chronic pain scenarios . The primary endpoint of this controlled , r and omized double blind study was to evaluate the effect of submucosal tramadol on VAS scores after septoplasty operations and secondary endpoint was to investigate the effects on total opioid and additional analgesic consumption and patient satisfaction . 60 patients scheduled for septoplasty under general anaesthesia were enrolled . In Group T , at the end of surgery following hemostasis , 2 mg/kg tramadol was applied as submucosal infiltration to both surgical sites , 2 ml ( total 4 ml ) , by the surgeon . In Group P , at the end of surgery following hemostasis , 2 ml isotonic solution ( total 4 ml ) was applied as submucosal infiltration to both surgical sites by the surgeon . Total opioid consumption , VAS scores , patient satisfaction was evaluated at the end of 24 h VAS values were higher in Group P on the first and second postoperative hours . Patient controlled analgesia dem and and delivery values were higher in Group P on the postoperative 1 , 2 , 4 , 6 , 12 and 24th hours . Patient satisfaction was higher and opioid consumption was lower in Group T compared to Group P. There was no difference in additional analgesic consumption between two groups . The results show that patients receiving tramadol had lower VAS scores compared with the placebo groups postoperatively OBJECTIVE This prospect i ve , controlled study investigated the effect on patient anxiety of lidocaine infiltration into nasal packing following septoplasty . METHODS The study included 50 patients who underwent septoplasty operation . Patient anxiety levels were measured 24 hours pre-operatively ; 48 hours post-operatively , before saline or lidocaine infiltration ; and 15 minutes after lidocaine or saline infiltration into the packing . The patients were asked to mark their level of pain during pack removal on a visual analogue scale . RESULTS Hamilton Anxiety Scale scores for lidocaine infiltration patients were : 15.1 ± 7.4 pre-operatively ; 16 ±7.6 post-operatively , before infiltration ; and 13.7 ± 6.6 at 15 minutes after infiltration . The scores for saline infiltration patients were : 16.3 ± 6.8 pre-operatively , 16.4 ± 5.5 before infiltration and 16.1 ± 6.1 after infiltration . The visual analogue scale pain score was 5.3 ± 2.0 in the lidocaine study group and 7.5 ± 1.8 in the control saline group . CONCLUSION Infiltration of lidocaine into nasal packing significantly reduced patient pain . Patients developed mild to moderate anxiety before nasal packing removal . Use of techniques without nasal packing can be recommended after septoplasty to ease patient post-operative discomfort BACKGROUND Submucosal resection is accompanied by significant post-operative pain and discomfort . The aim of this r and omized , double-blinded clinical trial was to study the efficacy of a local block anaesthetic , delivered after induction of general anaesthesia , in reducing post-operative pain . METHODS Patients aged 16 years and over who were scheduled for elective submucosal resection were r and omly assigned to receive either st and ardized general anaesthesia , general anaesthesia with local anaesthetic infiltration or general anaesthesia with placebo infiltration . Haemodynamic stability , intra-operative blood loss , post-operative pain ( over a seven day follow-up period ) , analgesics consumption , hospital stay , and the patient 's and surgeon 's levels of satisfaction were assessed . RESULTS We found significantly lower results for pack removal pain score , volume of intra-operative blood loss , number of patients suffering from headache , altered dental sensation or nasal pain , number of patients who consumed analgesics , and length of hospital stay , comparing the infiltration group with the general anaesthesia and placebo groups ( p<0.05 ) . CONCLUSION This clinical trial showed that infiltration with the local anaesthetics fentanyl and clonidine substantially reduced post-operative pain and shortened patients ' hospital stay Background This study was design ed to compare differences in intraoperative blood loss , mean arterial blood pressure ( MABP ) , and duration of surgery when 0.25 % bupivacaine with 1:200000 epinephrine is injected , preoperatively , versus normal saline ( NS ) , during functional endoscopic sinus surgery ( FESS ) . Methods A prospect i ve , double-blind r and omized placebo-controlled study was performed . Part I involved 46 patients who were infiltrated with 0.25 % bupivacaine with 1:200000 epinephrine on one side of the nose and sterile NS on the other ( control ) . Part II involved 30 patients infiltrated with 0.25 % bupivacaine with 1:200000 epinephrine bilaterally and 30 patients with NS bilaterally ( control ) . Patient demographics , preoperative MABP , intraoperative MABP , duration of surgery , and total estimated blood loss ( EBL ) were recorded for each side ( part I ) and case ( part II ) . Results For part I , there were 46 patients ( mean age , 49 years ) , 24 women and 22 men . MABP was 72 mmHg for each side ( p = 0.97 ) . Preoperative MABP was 93 mmHg . Duration of surgery was 48 minutes for epinephrine side and 45 minutes for control ( p = 0.17 ) . Total EBL was 185 mL for the epinephrine side and 197 mL for control ( p = 0.53 ) . For part II , there were 60 patients ( mean age , 56 years ) , 28 women and 32 men . The MABP was 77 mmHg for the epinephrine group and 72 mmHg for control ( p = 0.048 ) . Preoperative MABP was 100 mmHg for the epinephrine group and 97 mmHg for control ( p = 0.37 ) . Duration of surgery was 2.25 hours for the epinephrine group and 2.08 hours for control ( p = 0.17 ) . Total EBL was 589 mL for the epinephrine group and 538 mL for control ( p = 0.64 ) . Conclusion There was no significant reduction in intraoperative blood loss during FESS when local anesthetic containing epinephrine was used compared with infiltration with NS . More importantly , part II shows a significantly higher MABP associated with infiltration of epinephrine . Parts I and II did not show a significant difference in preoperative MABP or duration of surgery Objective . The aim of this study was to evaluate the efficacy of rehydration of Merocel nasal packs with prilocaine or levobupivacaine on reducing pain and discomfort of nasal packing removal in patients who had undergone septoplasties or endoscopic sinus surgery . Study Design . Prospect i ve clinical study . Setting . Tertiary referral center . Methods . This prospect i ve study was conducted on 72 patients , aged 18 to 55 years , who had undergone septoplasty , bilateral functional endoscopic sinus surgery , or both . The patients were divided into 2 groups : prilocaine group ( group P , n = 36 ) , who received 2.5 mL of 2 % prilocaine , and levobupivacaine group ( group L , n = 36 ) , who received 2.5 mL of levobupivacaine hydrochloride dilution . These solutions were diluted with 2.5 mL saline to a final volume of 5 mL , which was then injected into the Merocel packing 15 minutes before removal of the pack . In both groups , 5 mL of saline was injected into the packing in the contralateral nostril as a control 15 minutes before removal of the pack . Visual analog score ( VAS ) and the Ramsay sedation score were recorded . Results . Statistically significant differences were found in VAS and Ramsay sedation scale scores of levobupivacaine and prilocaine groups compared to controls . No significant difference was noted between the groups in terms of levobupivacaine and prilocaine . Conclusions . Levobupivacaine or prilocaine infiltration before removal of nasal packs in patients who undergo septoplasties or endoscopic sinus surgery can decrease discomfort and improve patient tolerability INTRODUCTION We conducted a study to determine the efficacy of bilateral extraoral infraorbital and infratrochlear nerve blocks during outpatient rhinoseptoplasty under general anaesthesia . PATIENTS AND METHODS In this prospect i ve , double-blind , r and omised , controlled trial , 40 adult patients undergoing outpatient rhinoseptoplasty under general anaesthesia were assigned to receive bilateral infraorbital and infratrochlear nerve blocks with either 10mL of 0.25 % levobupivacaine ( Group LB ) or isotonic saline ( control group ) . Patients in Group LB received 0.1mL/kg of isotonic saline as a placebo and patients in the control group received 0.1mL/kg of morphine . The primary endpoint was total perioperative morphine consumption ( intraoperative and in the post-anaesthesia care unit ) . The secondary endpoints were pain scores , time spent in the post-anaesthesia care unit and the outpatient ward , block-related complications and patient satisfaction . RESULTS The total dose of perioperative morphine was lower in Group LB than in the control group ( 2.5±2.8 mg versus 9.5±3.5 mg , respectively , P<0.001 ) . The mean±SD or median [ IQR ] times spent in the post-anaesthesia care unit ( 60±10min and 78±33min , respectively , P<0.03 ) and in the outpatient ward ( 210 [ 178 - 223 ] min versus 275 [ 250 - 300 ] min , respectively , P<0.001 ) were lower in Group LB than in the control group . There were no differences between groups for other endpoints . CONCLUSION Bilateral extraoral infraorbital and infratrochlear nerve blocks performed with 0.25 % levobupivacaine during general anaesthesia combining remifentanil and desflurane reduce the perioperative dose of morphine and the time spent in the post-anaesthesia care unit and the outpatient ward in adult patients undergoing outpatient rhinoseptoplasty The aim of this study is to compare the efficacy of levo-bupivacaine , a long-acting local anesthetic and lidocaine in postoperative analgesia following septoplasty . 112 patients r and omized into two groups were included in the study . 56 patients were operated using levo-bupivacaine and 56 using lidocaine as the local anesthetic . All patients were asked to mark their pain levels on a Visual analogue scale ( VAS ) at 1st , 2nd , 4th , 6trh 8th , 12th , and 24th hours postoperatively . In addition , the amount of analgesics used by each patient was recorded . The results indicated that the VAS scores of the levo-bupivacaine patients were significantly lower within the postoperative 4 hours ( p < 0.05 ) compared to the lidocaine group . In the levobupivacaine patients the earliest time for analgesic need was delayed ( p < 0.001 ) and the total amount of analgesics used was significantly lower when compared to lidocaine group ( p < 0.001 ) . In conclusion , levo-bupivacaine is effective for obtaining postoperative analgesia following septoplasty with local anesthesia . When compared to lidocaine , it increases the postoperative comfort of the patients by reducing pain levels OBJECTIVE To compare the efficacy of lidocaine spray 10 % to tetracaine 2 % solution , as a local anaesthetic for patients undergoing monopolar submucosal diathermy of the inferior turbinate . METHODS A prospect i ve study was conducted on 48 patients undergoing submucosal diathermy of the inferior turbinate . Patients were r and omly assigned to receive tetracaine 2 % solution ( 24 patients ) or to receive lidocaine spray 10 % ( 24 patients ) . Patients were asked to evaluate the severity of pain during the procedure using a visual analogue scale . Patient data , pain scores , and potential complications were assessed statistically . RESULTS The tetracaine group had significantly lower mean pain scores compared to the lidocaine group : 2.29 vs. 3.04 ( p < 0.001 ) . There were no complications or side effects from tetracaine . CONCLUSION Tetracaine 2 % solution applied locally is an easy , safe , inexpensive , and effective analgesia for submucosal diathermy for inferior turbinate hypertrophy OBJECTIVE To search the efficacy of using Merocele ( Medtronic , Minneapolis , MN ) soaked with 5 mL of levobupivacaine hydrocloride as a nasal pack in control of postoperative pain after septoplasty . DESIGN The study was design ed as a prospect i ve , double-blind , r and omized , controlled study . Forty-one patients who underwent septoplasty operation were included in the analysis . SETTING A tertiary referral hospital in Turkey . MATERIAL AND METHODS Forty-one patients undergoing septoplasty were divided into two groups . At the end of the operation , Merocele packs were placed inside the nasal cavity . In the levobupivacaine group , each Merocele pack was soaked with 5 mL of levobupivacaine hydrochloride ( 25 mg/10 mL ) , and in the control group , Merocele packs were soaked with 5 mL of saline . MAIN OUTCOME MEASURES Postoperative pain levels were recorded using a visual analogue scale ( VAS score , 0 - 100 ) at 30 minutes and 1 , 2 , 8 , 12 , and 24 hours . RESULTS We did not find any significant difference between groups regarding age , gender , American Society of Anesthesiologists status , and body mass index . Postoperative VAS values at 30 minutes and 1 , 2 , 8 , and 12 hours were significantly lower in the levobupivacaine group compared with the control group ( p < .05 ) . The need for supplemental analgesia was significantly lower in the levobupivacaine group compared with the control group ( p < .01 ) . CONCLUSION Postoperative pain after septoplasty owing to nasal packing is an important problem , and using levobupivacaine-soaked Merocele as a nasal pack after septoplasty is an effective method for the control of this pain . It is a very easy , effective , and quick method and it improves patient comfort after septoplasty BACKGROUND Successful local anaesthesia is of critical importance for the success of septoplasty , and many surgeons prefer to use cocaine for this purpose . The aim of this study was to evaluate the efficacy of cocaine 4 per cent solution , compared with tetracaine 2 per cent plus adrenaline , as a local anaesthetic for patients undergoing septoplasty . METHODS From December 2002 to February 2005 , a prospect i ve , r and omized , controlled trial was conducted . One hundred and eight patients underwent septoplasty under local anaesthesia . Patients were r and omly classified into group A and group B , in which was used respectively cocaine 4 per cent solution and tetracaine 2 per cent solution plus adrenaline . A visual analogue scale was used to evaluate the severity of patients ' pain during their procedure . RESULTS Group B ( tetracaine ; mean rank=43.77 ) reported significantly less pain ( p<0.001 ) compared with group A ( cocaine ; mean rank=65.23 ) . CONCLUSIONS On the basis of these findings , we recommend tetracaine as the first choice anaesthetic for nasal septoplasty ; the use of cocaine should be limited Background This study investigates the effects of local anesthetics application on pain and hemorrhage caused by nasal pack removal . Methods The study included 140 patients . Of these , 72 were women and 68 were men . The mean age and weight of the patients were 33.67 ± 10.2 years ( range , 21–63 years ) and 69.6 ± 13.6 kg . The patients were divided r and omly into four groups . Three of the four groups received one of the local anesthetics studied in our trial ( lidocaine + adrenaline , 0.25 % bupivacaine , or 2 % prilocaine ) before removal of the nasal packing material and the control group received saline solution . Local anesthetics and 0.9 % saline solution were applied to Merocel nasal packs 15 minutes before removal . Each patient was given a question naire where verbal analog score and amount of postoperative hemorrhage was noted . Results The mean pain score was 3.5 ± 1.2 ( median , 4 ; range , 3–5 ) in the lidocaine group , 4.5 ± 1.2 ( median , 4 ; range 3–5 ) in the prilocaine group , 4.7 ± 1.3 ( median , 6 ; range , 3–5 ) in the bupivacaine group , and 6.35 ± 1.2 ( median , 6 ; range , 5–7 ) in the saline group during nasal packing removal . The lidocaine group had significantly better pain scores versus other groups ( p < 0.05 ) . Bupivacaine and prilocaine had significantly better pain scores versus the control group , respectively . Analysis of bleeding scores after pack removal showed that all three study groups had significantly better bleeding scores versus the control saline group ( p < 0.05 ) . The lidocaine group had significantly less bleeding score than bupivacaine and prilocaine groups ( p < 0.05 ) . Conclusion Topical lidocaine application before removal of nasal packs in patients who undergo nasal septal surgery can decrease discomfort and bleeding and improve patient tolerance UNLABELLED Anterior nasal packing is carried out in a number of nasal surgeries , especially in septoplasty . However , it is not an innocuous procedure and for this its benefit has been challenged . OBJECTIVE To assess the need for anterior nasal packing and the quality of life of patients su bmi tted to septoplasty . METHOD Patients su bmi tted to septoplasty with or without inferior turbinoplasty were r and omized to receive or not anterior nasal packing postoperatively . We recorded and compared postoperative data ( pain and bleeding ) . Quality of life was assessed before and after surgery . This is a r and omized prospect i ve study . RESULTS We had 73 patients ( 37 packed and 36 who did not receive a nasal packing ) with a minimum follow-up of 3 months . Patients with nasal packing complained more of nasal pain and headache in the immediate postoperative period . Of these patients , 75.7 % reported moderate/intense pain upon nasal packing removal . Bleeding was more frequent in those patients who did not receive a nasal packing , and only 1 patient required packing . All the patients enjoyed an improvement in quality of life . CONCLUSION Septoplasty improves the quality of life of patients with septal deviation and nasal obstruction . Routine use of anterior nasal packing should be challenged for not presenting proven benefit The aim of this prospect i ve study was to evaluate the efficacy of cocaine flakes compared to tetracaine with adrenaline solution , as a local anaesthetic for patients undergoing septoplasty . From January 2001 to December 2002 , 220 patients underwent septoplasty under local anaesthesia . Patients were r and omly classified in group A and group B , where cocaine and the solution of tetracaine/adrenaline were used respectively . A visual analogue scale was used to evaluate the severity of the patients ' pain during the procedure . The patients of group B showed a statistically significant lower pain score than patients of group A. We believe that the solution of tetracaine/adrenaline is an effective and safe anaesthetic for patients undergoing septoplasty under local anaesthesia BACKGROUND : In this study , we compared the use of preincisional lidocaine 2 % with epinephrine ( LA ) and levobupivacaine 0.25 % plain ( LB ) for postoperative analgesia and vasoconstriction in patients undergoing nasal surgery . METHODS : Sixty patients were r and omly assigned to receive preincisional local infiltration under general anesthesia . Group LB received levobupivacaine 0.25 % , and group LA received epinephrine plus lidocaine 2 % ( add volume injected ) . Intraoperative hemodynamic changes , pre- and postoperative hemoglobin and hematocrit values were recorded . Visual analog scale values 30 min and 1 , 2 , 8 , 12 , and 24 h postoperatively and the need for rescue analgesic treatment in the first 24 h of all patients was recorded . RESULTS : At 30 min and 1 , 2 , 8 , and 12 h postoperatively , visual analog scale values were lower in group LB than in group LA ( P < 0.0001 , P = 0.002 , P = 0.023 , P < 0.0001 , and P = 0.011 , respectively ) . The analgesic requirement was significantly lower in group LB when compared with that in group LA ( P = 0.038 ) . Group LB had significant differences between preoperative and postoperative hemoglobin and hematocrit values ( P = 0.014 and 0.025 ) . Group LA had significant differences between preoperative and postoperative hemoglobin and hematocrit values ( P = 0.031 and 0.024 ) . CONCLUSIONS : We conclude that postoperative analgesia in nasal surgery with local infiltration of levobupivacaine was significantly more potent and longer lasting than that achieved by lidocaine plus epinephrine |
13,918 | 30,176,176 | PK parameters from critically ill population s were reported with wider confidence intervals than those in healthy volunteers , indicating greater PK variability in critical illness .
The st and ard allometric size and sigmoidal maturation model adequately described increasing clearance in neonates , and a sigmoidal model was also used to describe decline in older age .
Changes in volume of distribution were well described by the st and ard allometric model , although amoxicillin data suggested a relatively higher volume of distribution in neonates .
Critical illness is associated with greater PK variability than in healthy volunteers . | AIMS Beta-lactam dose optimization in critical care is a current priority .
We aim ed to review the pharmacokinetics ( PK ) of three commonly used beta-lactams ( amoxicillin ± clavulanate , piperacillin-tazobactam and meropenem ) to compare PK parameters reported in critically and noncritically ill neonates , children and adults , and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life . | Background Meropenem is a carbapenem antibiotic commonly used in critically ill patients to treat severe infections . The available pharmacokinetic ( PK ) data has been mostly obtained from healthy volunteers as well as from clinical studies addressing selected population s , often excluding the elderly and also patients with renal failure . Our aim was to study PK of meropenem in a broader population of septic critically ill patients . Methods We characterized the PK of meropenem in 15 critically ill patients during the first 36 hrs of therapy . Aditionally , whenever possible , we collected a second set of late plasma sample s after 5 days of therapy to evaluate PK intra-patient variability and its correlation with clinical course . Patients received meropenem ( 1 g every 8 hrs IV ) . Drug plasma profiles were determined by high-performance liquid chromatography . The PK of meropenem was characterized and compared with clinical parameters . Results Fifteen septic critically ill patients ( 8 male , median age 73 yrs ) were included . The geometric mean of the volume of distribution at the steady state (Vss)/weight was 0.20 ( 0.15 - 0.27 ) L/kg . No correlation of Vss/weight with severity or comorbidity scores was found . However the Sequential Organ Failure Assessment score correlated with the Vss/weight of the peripheral compartment ( r2 = 0.55 , p = 0.021 ) . The median meropenem clearance ( Cl ) was 73.3 ( 45–120 ) mL/min correlated with the creatinine ( Cr ) Cl ( r2 = 0.35 , p = 0.033).After 5 days ( N = 7 ) although Vss remained stable , a decrease in the proportion of the peripheral compartment ( Vss2 ) was found , from 61.3 (42.5 - 88.5)% to 51.7 (36.6 - 73.1)% . No drug accumulation was noted . Conclusions In this cohort of septic , unselected , critically ill patients , large meropenem PK heterogeneity was noted , although neither underdosing nor accumulation was found . However , Cr Cl correlated to meropenem Cl and the Vss2 decreased with patient ’s improvement The pharmacokinetics of apalcillin and piperacillin , each administered intravenously as a single 2-g dose , were compared in 10 volunteers in a r and omized study of crossover design using bioassay and high-pressure liquid chromatographic procedures . The concentrations of both penicillins in serum were determined over a period of 12 h and in urine over 24 h. Concentrations of apalcillin and piperacillin at the end of the 15-min infusion were similar ; however , at 8 h , concentrations of piperacillin were below measurable levels , whereas concentrations of apalcillin were still measurable at 10 h. Pharmacokinetic parameters were calculated according to a two-compartment open model . The area under the curve and the half-life for apalcillin were larger than for piperacillin . On the other h and , renal clearance of piperacillin was substantially greater than that of apalcillin . Of the apalcillin excreted via the kidneys , approximately one-fifth was eliminated as two microbiologically inactive penicilloic acid derivatives . The nonrenal clearance of apalcillin was 79 % of total clearance . Binding of apalcillin to serum protein was almost twice that of piperacillin STUDY OBJECTIVE To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam . DESIGN Sequential selection of patients entered into a r and omized , open-label clinical efficacy trial . SETTING Los Angeles County-University of Southern California Medical Center . PARTICIPANTS Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial . INTERVENTIONS Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours . MEASUREMENTS AND MAIN RESULTS The estimated noncompartmental pharmacokinetic parameters ( mean + /- SD ) for piperacillin and tazobactam , respectively , were as follows : maximum concentration in plasma 218.7 + /- 48.9 micrograms/ml and 27.8 + /- 9.1 micrograms/ml ; half-life 1.07 + /- 0.22 hours and 1.00 + /- 0.27 hours ; elimination rate constant 0.67 + /- 0.13 hr-1 and 0.73 + /- 0.18 hr-1 ; area under the concentration-time curve from zero hour to infinity 288.5 + /- 71.25 mg.hr/L and 36.3 + /- 9.55 mg.hr/L ; total plasma clearance 14.75 + /- 3.93 L/hour and 14.78 + /- 4.39 L/hour ; renal clearance 5.69 + /- 1.94 L/hour and 7.85 + /- 3.37 L/hour ; volume of distribution at steady state 21.00 + /- 4.18 L and 22.47 + /- 8.27 L ; and mean residence time 1.72 + /- 0.29 hours and 1.79 + /- 0.35 hours . CONCLUSION Our findings were similar to those in other surgical patient models . The two-compartmental model best described piperacillin and tazobactam disposition in our patients . Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough , peak , and 2-hour postadministration levels without bias The pharmacokinetics of piperacillin and tazobactam were assessed after single-dose administration to 47 infants and children . Study subjects ranging in age from 2 months to 12 years were r and omized to receive one of two different doses of a piperacillin-tazobactam combination ( 8:1 ) : a low dose ( n = 23 ) of 50 and 6.25 mg of piperacillin and tazobactam per kg of body weight , respectively , or a high dose ( n = 24 ) of 100 and 12.5 mg , respectively . The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin , supporting the use of these two agents in a fixed-dose combination . No differences in the pharmacokinetics of piperacillin or tazobactam were observed between the two doses administered . The elimination parameters half-life and total body clearance decreased and increased , respectively , with increasing age , whereas volume parameters ( volume of distribution and steady-state volume of distribution ) remained relatively constant for both compounds . The primary metabolite of tazobactam , metabolite M1 , was measurable in the plasma of 18 of the 47 study subjects ; 17 of these 18 subjects received the high doses . More than 70 % of the administered piperacillin and tazobactam doses were excreted unchanged in the urine over a 6-h collection period . These data combined with the known in vitro susceptibilities of a broad range of pediatric bacterial pathogens indicate that a dose of 100 mg of piperacillin and 12.5 of mg tazobactam per kg of body weight administered as a fixed-dose combination every 6 to 8 h would be appropriate to initiate clinical efficacy studies in infants and children for the treatment of systemic infections arising outside of the central nervous system . ABSTRACT Meropenem is used to manage postneurosurgical meningitis , but its population pharmacokinetics ( PPK ) in plasma and cerebrospinal fluid ( CSF ) in this patient group are not well-known . Our aims were to ( i ) characterize meropenem PPK in plasma and CSF and ( ii ) recommend favorable dosing regimens in postneurosurgical meningitis patients . Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h ( q8h ) , 1 g q8h , or 1 g q6h for at least 3 days . Serial blood and CSF sample s were collected , and concentrations were determined and analyzed via population modeling . Probabilities of target attainment ( PTA ) were predicted via Monte Carlo simulations , using the target of unbound meropenem concentrations above the MICs for at least 40 % of dosing intervals in plasma and at least of 50 % or 100 % of dosing intervals in CSF . A two-compartment model plus another CSF compartment best described the data . The central , inter central /peripheral , and inter central /CSF compartment clearances were 22.2 liters/h , 1.79 liters/h , and 0.01 liter/h , respectively . Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters , respectively . The CSF compartment volume was fixed at 0.13 liter , with its clearance calculated by the observed drainage amount . The multiplier for the transfer from the central to the CSF compartment was 0.172 . Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases . A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml/day , which provides a PTA of > 90 % for MICs of ≤8 mg/liter in blood and of ≤0.5 mg/liter or 0.25 mg/liter in CSF , is recommended . ( This study has been registered at Clinical Trials.gov under identifier NCT02506686 . Objectives To develop population pharmacokinetic ( PK ) models for piperacillin/tazobactam in neonates and infants of less than 2 months of age in order to determine the appropriate dosing regimen and provide a rational basis for the development of preliminary dosing guidelines suitable for this population . Methods A two-stage , open-label study was conducted in neonates and infants less than 2 months of age in the neonatal intensive care unit ( NICU ) . A total of 207 piperacillin and 204 tazobactam concentration – time data sets from 71 patients were analyzed using a nonlinear mixed-effect modeling approach ( NONMEM VII ) . PK models were developed for piperacillin and tazobactam . The final models were evaluated using both bootstrap and visual predictive checks . External model evaluations were made in 20 additional patients . Results For neonates and young infants less than 2 months of age , the median central clearance was 0.133 and 0.149 L/h/kg for piperacillin and tazobactam , respectively . Postmenstrual age ( PMA ) was identified as the most significant covariate on central clearance of piperacillin and tazobactam . However , the combination of current bodyweight ( BW ) and postnatal age proved to be superior to PMA alone . BW was the most important covariate for apparent central volume of distribution . Both internal and external evaluations supported the prediction of the final piperacillin and tazobactam PK models . The dosing strategy 44.44/5.56 mg/kg/dose piperacillin/tazobactam every 8 or 12 h evaluated in this study achieved the pharmacodynamic target ( free piperacillin concentrations > 4 mg/L for more than 50 % of the dosing interval ) in about 67 % of infants . Conclusions Population PK models accurately described the PK profiles of piperacillin/tazobactam in infants less than 2 months of age . The results indicated that higher doses or more frequent dosing regimens may be required for controlling infection in this population in NICU Background : The antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock . We compared the pharmacokinetic , clinical , and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients . Methods : Patients admitted to the Intensive Care Unit ( ICU ) with severe sepsis or septic shock who received meropenem were r and omly assigned to either the continuous ( n = 25 ) or intermittent groups ( n = 25 ) . The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day ; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success , microbiological eradication , superinfection , ICU mortality , length of ICU stay , and duration of meropenem treatment were assessed . Serial plasma meropenem concentrations for the first and third dosing periods ( steady state ) were also measured . Results : Clinical success was similar in both the continuous ( 64 % ) and intermittent ( 56 % ) groups ( P = 0.564 ) ; the rates of microbiological eradication and superinfection ( 81.8 % vs. 66.7 % [ P = 0.255 ] and 4 % vs. 16 % [ P = 0.157 ] , respectively ) showed improvement in the continuous group . The duration of meropenem treatment was significantly shorter in the continuous group ( 7.6 vs. 9.4 days ; P = 0.035 ) , where a better steady-state concentration was also achieved . Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first ( Cmax : 19.8 mg/L vs. 51.8 mg/L , P = 0.000 ; Cmin : 11.2 mg/L vs. 0.5 mg/L , P = 0.000 ) and third dosing periods ( Cmax : 12.5 mg/L vs. 46.4 mg/L , P = 0.000 ; Cmin : 11.4 mg/L vs. 0.6 mg/L , P = 0.000 ) . For medium-susceptibility pathogens , continuous infusion concentrations above the minimal inhibitory concentration were 100 % , which was better than that in the intermittent group . Conclusions : Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration . Continuous infusion may be more optimal against intermediate-susceptibility pathogens ABSTRACT Ceftolozane-tazobactam has potent activity against Pseudomonas aeruginosa , a pathogen associated with cystic fibrosis ( CF ) acute pulmonary exacerbations ( APE ) . Due to the rapid elimination of many antibiotics , CF patients frequently have altered pharmacokinetics . In this multicenter , open-label study , we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h ( q8h ) in 20 adult CF patients admitted with APE . Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment ( PTA ) for the ceftolozane component at 1.5 g and 3 g of ceftolozane-tazobactam q8h across a range of MICs using a primary threshold exposure of 60 % free time above the MIC ( fT > MIC ) . In these 20 adult CF patients , ceftolozane and tazobactam concentration data were best described by 2-compartment models , and ceftolozane clearance ( CL ) was significantly correlated with creatinine clearance ( r = 0.71 , P < 0.001 ) . These data suggest that ceftolozane and tazobactam clearance estimates in CF patients are similar to those in adults without CF ( ceftolozane CF CL , 4.76 ± 1.13 liter/h ; tazobactam CF CL , 20.51 ± 4.41 liter/h ) . However , estimates of the volume of the central compartment ( Vc ) were lower than those for adults without CF ( ceftolozane CF Vc , 7.51 ± 2.05 liters ; tazobactam CF Vc , 7.85 ± 2.66 liters ) . Using a threshold of 60 % fT > MIC , ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of ≥90 % at MICs up to 4 and 8 μg/ml , respectively . Ceftolozane-tazobactam at 3 g q8h was well tolerated . These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients . ( This study has been registered at Clinical Trials.gov under identifier NCT02421120 . Amoxicillin is commonly used for the treatment of neonatal bacterial infection with intermittent dosing ( ID ) regimens . However , increasing bacterial resistance , in addition to a lack of new antimicrobial agents , urges the optimization of current therapeutic options . Clinical studies in adults suggest continuous infusion ( CI ) regimens of beta-lactam antibiotics to be superior to ID . There are as yet no guidelines concerning the CI dosing of amoxicillin . The present study was developed to describe the CI pharmacokinetics and -dynamics of amoxicillin during the first 3 days of life in search of the optimal dosing regimen . Neonates with a gestational age above 34 weeks , at risk of neonatal infection and requiring amoxicillin therapy , were included . Serum concentrations of amoxicillin were measured during CI on days 1 and 3 in the steady state . Twenty-two serum sample s of 11 patients were collected . All patients reached and retained serum concentrations of amoxicillin within the therapeutic range without exceeding the toxic concentration ( serum concentrations on day 1 mean 55.4 mg/l , range 30.9–69.5 , SD 10.5 , and on day 3 48.8 mg/l , range 25.5–92.4 , SD 18.4 ) . There was no significant decrease in concentration from day 1 to day 3 ( p = 0.38 ) . This study showed therapeutic , nontoxic concentrations of amoxicillin in neonates on CI of amoxicillin in the first 3 days of life . R and omized controlled trials should reveal whether the clinical benefits of the CI of amoxicillin exceed those of ID regimens Background and Objective For patients with intracranial infection , local intrathecal administration of meropenem may be a useful method to obtain a sufficient drug concentration in the cerebral spinal fluid ( CSF ) . However , a large inter-individual variability may pose treatment efficacy at risk . This study aim ed to identify factors affecting drug concentration in the CSF using population pharmacokinetics method . Methods After craniotomy , aneurysm patients with an indwelling lumbar cistern drainage tube who received a combined intravenous and intrathecal administration of meropenem for the treatment of suspected intracranial infection were enrolled . Venous blood and CSF specimens were collected for determining meropenem concentrations . Nonlinear mixed-effects modeling method was used to fit blood and CSF concentrations simultaneously and to develop the population pharmacokinetic model . The proposed model was applied to simulate dosage regimens . Results A three-compartmental model was established to describe meropenem in vivo behavior . Lumbar CSF drainage result ed in a drug loss , and drug clearance in CSF ( CLCSF ) was employed to describe this . The covariate analysis found that the drainage volume ( mL/day ) was strongly associated with CLCSF , and the effect of creatinine clearance was significant on the clearance of meropenem in blood ( CL ) . Visual predictive check suggested that the proposed pharmacokinetic model agreed well with the observations . Simulation showed that both intravenous and intrathecal doses should be increased with the increases of minimum inhibitory concentration and daily CSF drainage volume . Conclusion This model incorporates covariates of the creatinine clearance and the drainage volume , and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing Introduction Patients with febrile neutropenia ( FN ) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity . We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center . Methods This was an open , nonr and omized , observational , descriptive , and prospect i ve study . Sample s from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy . Five blood sample s were taken from each patient when the antibiotic level was at steady-state 10 , 60 , 120 , 180 , and 350 min after each dose . Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis . All study participants provided written informed consent . Results We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm3 ( st and ard deviation ( SD ) ± 603.2 ) . The following pharmacokinetic measurements were obtained : maximum concentration , 94.1–1133 mg/L ; minimum concentration , 0.47–37.65 mg/L ; volume of distribution , 0.08–0.65 L/kg ( mean , 0.34 L/kg ) ; drug clearance ( CL ) , 4.42–27.25 L/h ( mean , 9.93 L/h ) ; half-life ( t1/2 ) , 0.55–2.65 h ( mean , 1.38 h ) ; and area under the curve , 115.12–827.16 mg · h/L. Conclusion Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals ; specifically , FN patients demonstrated an increase in t1/2 and decreased CL Objective To evaluate and compare the pharmacokinetic profiles of imipenem and meropenem in a population of critically ill patients with sepsis to find possible differences that may help in selecting the most appropriate drug and /or dosage in order to optimise empiric antimicrobial therapy . Patients and methods This was a single-centre , r and omised , nonblind study of the pharmacokinetics of both intravenous imipenem 1 g and meropenem 1 g in 20 patients admitted to an intensive care unit with sepsis in whom antimicrobial therapy was indicated on clinical grounds . Patients were divided into two groups : group I received intravenous imipenem 1 g plus cilastatin 1 g , and group II received intravenous meropenem 1 g over 30 minutes . Peripheral blood sample s were collected at 0 , 0.5 ( end of infusion ) , 0.75 , 1 , 1.5 , 2 , 3 , 4 , 6 and 8 hours after the first dose and were centrifuged for 10 minutes at 4 ° C . Urine sample s were collected during the 8 hours after antimicrobial administration at 2-hour intervals : 0–2 , 2–4 , 4–6 and 6–8 hours . The total volume of urine was recorded ; the serum and urine sample s were immediately frozen and stored at −80 ° C until assayed . Pharmacokinetic analysis was carried out through computerised programs using the least-square regression method and a two-compartment open model . Statistical differences were evaluated by means of one-way ANOVA . Results The following pharmacokinetic differences between the two drugs were observed : the imipenem mean peak serum concentration was significantly higher than for meropenem ( 90.1 ± 50.9 vs 46.6 ± 14.6 mg/L , p < 0.01 ) ; the area under the serum concentration-time curve was significantly higher for imipenem than for meropenem ( 216.5 ± 86.3 vs 99.5 ± 23.9 mg · h/L , p < 0.01 ) , while the mean volume of distribution and mean total clearance were significantly higher for meropenem than for imipenem ( 25 ± 4.1 vs 17.4 ± 4.5L , p < 0.01 and 191 ± 52.2 vs 116.4 ± 42.3 mL/min , p < 0.01 , respectively ) . Conclusion The more favourable pharmacokinetic profile of imipenem compared with meropenem in critically ill patients with sepsis might balance the possibly greater potency demonstrated in vitro for meropenem against Gram-negative strains . Hence , the clinical efficacy of the two carbapenems depends mostly on their correct dosage Pulmonary infections in critically ill patients are common and are associated with high morbidity and mortality . Piperacillin – tazobactam is a frequently used therapy in critically ill patients with pulmonary infection . Antibiotic concentrations in the lung reflect target‐site antibiotic concentrations in patients with pneumonia . The aim of this study was to assess the plasma and intrapulmonary pharmacokinetics ( PK ) of piperacillin – tazobactam in critically ill patients administered st and ard piperacillin – tazobactam regimens . A population PK model was developed to describe plasma and intrapulmonary piperacillin and tazobactam concentrations . The probability of piperacillin exposures reaching pharmacodynamic end points and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored . The median piperacillin and tazobactam pulmonary penetration ratios were 49.3 and 121.2 % , respectively . Pulmonary piperacillin and tazobactam concentrations were unpredictable and negatively correlated with pulmonary permeability . Current piperacillin – tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin – tazobactam – susceptible organisms in some critically ill patients ABSTRACT Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates . We compared the steady-state pharmacokinetics ( PK ) of meropenem given as a short ( 30-min ) or prolonged ( 4-h ) infusion to very-low-birth-weight ( gestational age , < 32 weeks ; birth weight , < 1,200 g ) neonates to define the appropriate dosing regimen for a phase 3 efficacy study . Short ( n = 9 ) or prolonged ( n = 10 ) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5 , 1.5 , 4 , 8 , and 12 h after the 4th to 7th doses of meropenem , blood sample s were collected . Meropenem concentrations were measured by ultrahigh-performance liquid chromatography . PK analysis was performed with WinNonlin software , and modeling was performed with NONMEM software . A short infusion result ed in a higher mean drug concentration in serum ( Cmax ) than a prolonged infusion ( 89 versus 54 mg/liter ) . In all but two patients in the prolonged-infusion group , the free serum drug concentration was above the MIC ( 2 mg/liter ) 100 % of the time . Meropenem clearance ( CL ) was not influenced by postnatal or postmenstrual age . In population PK analysis , a one-compartment model provided the best fit and the steady-state distribution volume ( Vss ) was scaled with body weight and CL with a published renal maturation function . The covariates serum creatinine and postnatal and gestational ages did not improve the model fit . The final parameter estimates were a Vss of 0.301 liter/kg and a CL of 0.061 liter/h/kg . Meropenem infusions of 30 min are acceptable as they balance a reasonably high Cmax with convenience of dosing . In very-low-birth-weight neonates , no dosing adjustment is needed over the first month of life The pharmacokinetic parameters of amoxicillin were determined in 32 newborn infants aged 10 to 52 days ( mean postnatal age , 24.7 ± 12.4 days ) to improve amoxicillin dosing in this age group . Amoxicillin plasma concentrations were determined using reversed-phase high-performance liquid chromatography in surplus plasma sample s from routine gentamicin assays . Amoxicillin pharmacokinetic parameters ( mean ± SD ) were as follows : first-order elimination constant ( Kel ) = 0.27 ± 0.10 h−1 , volume of distribution corrected for body weight ( V/W ) = 0.66 ± 0.27 L/kg , total body clearance corrected for body weight ( CL/W ) = 0.18 ± 0.10 Lkg−1h−1 , and elimination half-life ( t½ ) = 3.0 ± 1.3 hours . Amoxicillin body clearance was approximately twofold greater in our patients compared with published values in younger neonates ( mean postnatal age , 0.76 ± 1.57 days ) . Simulation studies using the observed amoxicillin pharmacokinetic data suggest an amoxicillin dose of 40 mg/kg administered every 8 hours in infants older than 9 days postnatal age , independent of gestational age and postconceptional age , to achieve satisfactory target plasma amoxicillin concentrations less than 140 mg/L and time above minimum inhibitory concentration of at least 40 % . Prospect i ve evaluation of this suggested new dosage regimen is necessary before implementation in the care of ill neonates The efficacy and pharmacokinetics of piperacillin monotherapy were studied in 46 patients with cystic fibrosis . Two patients were dropped from the study within 24 hr of enrollment because of drug-associated nausea and vomiting . Initially fourteen older patients ( greater than 12 years ) receiving piperacillin 450 mg/kg/day underwent a preliminary evaluation . Based on the results , 30 younger patients ( less than or equal to 12 years ) r and omized in a double-blind fashion received either 600 or 900 mg/kg/day of piperacillin in six divided doses . Pharmacokinetic parameter estimates for t1/2 Vdss , and Cl were similar for first dose and steady-state evaluations . In 27 patients , approximately 43 % of the administered dose was recovered in the urine after 4 hr . Piperacillin CiR averaged 49 % of the total Cl . No difference in overall clinical efficacy could be identified between 600 and 900 mg/kg/day of piperacillin using two different objective scoring systems . Although a reduction in sputum Pseudomonas colony counts was greater following the 900 mg/kg/day regimen , this appeared to be independent of clinical effect . In 14 patients ( 32 % ) , a distinct adverse serum-sicknesslike reaction was observed . The incidence of this reaction appeared to increase as the dose of piperacillin increased . All signs and symptoms of this reaction resolved within 36 hr of discontinuing piperacillin administration but recurred immediately on rechallenge in four patients . All patients with the adverse reaction were subsequently treated with beta-lactam antibodies without ill effect . Overall , clinical improvement appeared to be independent of the piperacillin dose . Our data support the use of total daily piperacillin dosages not exceeding 600 mg/kg Imipenem/cilastatin and meropenem are carbapenem antibiotics that are infused intravenously ( IV ) over 30 to 45 min . We evaluated probability of target attainment and cumulative probability of target attainment of 30-min and 3-h infusions for imipenem/cilastatin and meropenem . Eighteen healthy adults in a r and omized , 4-phase , crossover study received 1000 mg of imipenem/cilastatin or meropenem as a single-dose IV over 30 min or 3 h. A population pharmacokinetics analysis using a 2-compartment IV infusion model was performed . Monte Carlo simulations using various dosage regimens at steady-state and 30-min and 3-h infusion rates were performed to evaluate the probabilities of attaining 20 % ( bacteriostatic ) , 30 % , and 40 % ( maximum kill ) time above the MIC . Three-hour infusions of imipenem/cilastatin and meropenem improved the cumulative probability of target attainment for a variety of population s of microorganisms compared to 30-min infusions . Prolonged infusions have the potential to optimize efficacy of imipenem/cilastatin and meropenem STUDY OBJECTIVE To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens . The regimens compared were piperacillin 4.0 g-tazobactam 0.5 g administered every 8 hours , and piperacillin 3.0 g-tazobactam 0.375 g administered every 6 hours . DESIGN Multiple-dose , open-label , r and omized , crossover study . SETTING Clinical research center at Hartford Hospital . SUBJECTS Twelve healthy volunteers . INTERVENTION The two dosing regimens for piperacillin-tazobactam were administered intravenously in crossover design . Blood was sample d after the third dose . MEASUREMENTS AND MAIN RESULTS Drug concentrations were determined by a vali date d high-performance liquid chromatography assay . The percentage of time above minimum inhibitory concentration ( % T > MIC ) for piperacillin was calculated for a range of MIC values . The maximum concentration ( Cmax ) , area under the concentration-time curve ( AUC0-tau ) , and total clearance of piperacillin differed significantly between the two study regimens , as did the Cmax , AUC0-tau , volume of distribution , and total clearance of tazobactam ( p<0.05 ) . The piperacillin 4.0 g-tazobactam 0.5 g regimen provided 40 - 50 % T > MIC for MIC values 8 - 16 microg/ml ; a similar value for the piperacillin 3.0 g-tazobactam 0.375 g regimen was 16 - 32 microg/ml . CONCLUSION Although statistically significant differences in the pharmacodynamic profile were noted for the regimens , both provide adequate T > MIC against commonly encountered pathogens considered susceptible to piperacillin-tazobactam . However , for treatment of Pseudomonas aeruginosa infection , combination therapy or higher-dosage regimens ( e.g. , piperacillin 3.0 g-tazobactam 0.375 g every 4 hours , piperacillin 4.0 g-tazobactam 0.5 g every 6 hours , or continuous-infusion piperacillin 12 g-tazobactam 1.5 g/day ) may be a prudent option when full MIC data are unavailable Introduction Increasingly , derived estimates of glomerular filtration , such as the modification of diet in renal disease ( MDRD ) equation and Cockcroft-Gault ( CG ) formula are being employed in the intensive care unit ( ICU ) . To date , these estimates have not been rigorously vali date d in those with augmented clearances , result ing in potentially inaccurate drug prescription . Methods Post-hoc analysis of prospect ively collected data in two tertiary level ICU 's in Australia and Portugal . Patients with normal serum creatinine concentrations manifesting augmented renal clearance ( ARC ) ( measured creatinine clearance ( CLCR ) > 130 ml/min/1.73 m2 ) were identified by chart review . Comparison between measured values and MDRD and CG estimates were then undertaken . Spearman correlation coefficients ( rs ) were calculated to determine goodness of fit , and precision and bias were assessed using Bl and -Altman plots . Results Eighty-six patients were included in analysis . The median [ IQR ] measured CLCR was 162 [ 145 - 190 ] ml/min/1.73 m2 , as compared to 135 [ 116 - 171 ] , 93 [ 83 - 110 ] , 124[102 - 154 ] , and 108 [ 87 - 135 ] ml/min/1.73 m2 estimated by CG , modified CG , 4-variable MDRD and 6-variable MDRD formulae . All of the equations significantly under-estimated the measured value , with CG displaying the smallest bias ( 39 ml/min/1.73 m2 ) . Although a moderate correlation was noted between CLCR and CG ( rs = 0.26 , P = 0.017 ) and 4-variable MDRD ( rs = 0.22 , P = 0.047 ) , neither had acceptable precision for clinical application in this setting . CG estimates had the highest sensitivity for correctly identifying patients with ARC ( 62 % ) . Conclusions Derived estimates of GFR are inaccurate in the setting of ARC , and should be interpreted with caution by the physician . A measured CLCR should be performed to accurately guide drug dosing Purpose Patients admitted to intensive care unit ( ICU ) with Klebsiella pneumoniae infections are characterized by high mortality . The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens . Methods Twenty-seven consecutive patients were included in the study . Meropenem was administered as 3-h intravenous ( i.v . ) infusions at doses of 1–2 g every 8 or 12 h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography ( HPLC ) method , and a population pharmacokinetics analysis was performed using NONMEM software . Meropenem plasma disposition was simulated for extended ( 3 h ; 5 h ) or continuous i.v . infusions , and the following parameters were calculated : time during which free drug concentrations were above minimum inhibitory concentration ( MIC ) ( fT > MIC ) , free minimum plasma concentrations above 4 × MIC ( fCmin > 4 × MIC ) , probability of target attainment ( PTA ) , and cumulative fraction of response ( CFR ) . Results Gender and severity of sepsis affected meropenem clearance , whose typical population values ranged from 6.22 up to 12.04 L/h ( mean ± st and ard deviation ( SD ) value , 9.38 ± 4.47 L/h ) . Mean Cmin value was 7.90 ± 7.91 mg/L , suggesting a high interindividual variability . The simulation confirmed that 88 and 97.5 % of patients achieved effective Cmin > 4 × MIC values after 3- and 5-h i.v . infusions of meropenem 2 g × 3/day , respectively . On the contrary , the same total daily doses reached the target Cmin > 4 × MIC values in 100 % of patients when administered as continuous i.v . infusions . Conclusions Several factors may influence meropenem pharmacokinetics in ICU patients . Continuous i.v . infusions of meropenem seem to be more effective than st and ard regimens to achieve optimal therapeutic targets OBJECTIVES We investigated the population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam in hospitalized patients . PATIENTS AND METHODS A multicentre , r and omized clinical trial was conducted in hospitalized patients with complicated intra-abdominal infection . Patients received piperacillin/tazobactam administered by either continuous infusion ( 13.5 g over 24 h , n = 130 ) or intermittent infusion ( 3.375 g every 6 h , n = 132 ) . NONMEM was used to perform population pharmacokinetic analysis in a subset of patients ( n = 56 ) who had serum sample s obtained at steady-state for drug concentration analyses . Classification and regression tree analysis was used to identify the breakpoints of piperacillin PK-PD indexes in 94 patients with causative pathogen 's MIC . RESULTS A one-compartment model was applied to fit the data . Creatinine clearance and body weight were the most significant variables to explain patient variability in piperacillin and tazobactam clearance and volume of distribution . The infusion method had no influence on PK parameters . For patients ( n = 30 ) receiving intermittent infusion in the pharmacokinetic study , mean Cmax and half-life were 122.22 mg/L and 1.17 h for piperacillin , and 15.74 mg/L and 1.81 h for tazobactam . For patients ( n = 26 ) receiving continuous infusion in the pharmacokinetic study , mean steady-state concentration was 35.31 + /- 12.15 mg/L for piperacillin and 7.29 + /- 3.28 mg/L for tazobactam . As a result of a low rate of failures ( < 11 % ) observed in the trial and the low MICs for infecting pathogens , no association could be established between clinical /microbiological outcome and drug exposure . CONCLUSIONS Intermittent infusion and continuous infusion of piperacillin and tazobactam provided sufficient drug exposure to treat those pathogens commonly implicated in intra-abdominal infections BACKGROUND AND OBJECTIVES Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today . This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A multicenter prospect i ve observational study in the intensive care units of two academic medical centers was performed , enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy . Pregnant women , children , and patients with end stage liver disease were excluded from enrollment . Plasma and continuous renal replacement therapy effluent sample s were analyzed for piperacillin and tazobactam levels using HPLC . Pharmacokinetic and pharmacodynamic parameters were calculated using st and ard equations . Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters . RESULTS Forty-two of fifty-five subjects enrolled had complete sampling . Volume of distribution ( median=0.38 L/kg , intraquartile range=0.20 L/kg ) and elimination rate constants ( median=0.104 h(-1 ) , intraquartile range=0.052 h(-1 ) ) were highly variable , and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters . Probability of target attainment for piperacillin was 83 % for total drug but only 77 % when the unbound fraction was considered . CONCLUSIONS There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy . Many patients did not achieve pharmacodynamic targets , suggesting that therapeutic drug monitoring might optimize therapy BACKGROUND Morbidity and mortality for critically ill patients with infections remains a global healthcare problem . We aim ed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome . METHODS This was a prospect i ve , multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics . Two blood sample s were taken from each patient during a single dosing interval . The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration ( MIC ) of the pathogen at both 50 % ( 50 % f T > MIC ) and 100 % ( 100 % f T > MIC ) of the dosing interval . We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome . RESULTS We included 384 patients ( 361 evaluable patients ) across 68 hospitals . The median age was 61 ( interquartile range [ IQR ] , 48 - 73 ) years , the median Acute Physiology and Chronic Health Evaluation II score was 18 ( IQR , 14 - 24 ) , and 65 % of patients were male . Of the 248 patients treated for infection , 16 % did not achieve 50 % f T > MIC and these patients were 32 % less likely to have a positive clinical outcome ( odds ratio [ OR ] , 0.68 ; P = .009 ) . Positive clinical outcome was associated with increasing 50 % f T > MIC and 100 % f T > MIC ratios ( OR , 1.02 and 1.56 , respectively ; P < .03 ) , with significant interaction with sickness severity status . CONCLUSIONS Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure ; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients Objective : To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units . Design : Cohort , multiple-center , observational study . Setting : One hundred and ninety-eight intensive care units in 24 European countries . Patients : All new adult admissions to a participating intensive care unit between May 1 and 15 , 2002 . Interventions : None . Measurements and Main Results : Demographic data , comorbid diseases , and clinical and laboratory data were collected prospect ively . Patients were followed up until death , until hospital discharge , or for 60 days . Of 3,147 adult patients , with a median age of 64 yrs , 1,177 ( 37.4 % ) had sepsis ; 777 ( 24.7 % ) of these patients had sepsis on admission . In patients with sepsis , the lung was the most common site of infection ( 68 % ) , followed by the abdomen ( 22 % ) . Cultures were positive in 60 % of the patients with sepsis . The most common organisms were Staphylococcus aureus ( 30 % , including 14 % methicillin-resistant ) , Pseudomonas species ( 14 % ) , and Escherichia coli ( 13 % ) . Pseudomonas species was the only microorganism independently associated with increased mortality rates . Patients with sepsis had more severe organ dysfunction , longer intensive care unit and hospital lengths of stay , and higher mortality rate than patients without sepsis . In patients with sepsis , age , positive fluid balance , septic shock , cancer , and medical admission were the important prognostic variables for intensive care unit mortality . There was considerable variation between countries , with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries . Conclusions : This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries . In addition to age , a positive fluid balance was among the strongest prognostic factors for death . Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission Objective : Kinetics of piperacillin ( pip ) , in combination with the beta-lactamase inhibitor tazobactam ( taz ) have been studied in volunteers and patients in relatively stable conditions . The fixed drug preparation appeared to have ideal pharmacokinetic properties if renal function was normal or slightly impaired , but no data are available for critically ill patients in anuric renal failure . This study should provide such data . Patients , design : We studied the pharmacokinetics in nine patients with multiple organ failure , including anuric renal failure , treated with continuous veno-venous hemofiltration ( CVVH ) . Patients received a st and ard schedule of 4 g pip and 0.5 g taz administered over 0.5 h intravenously , 8 hourly . During 2 consecutive days , the serum levels of both compounds were determined , and total clearance ( CIT ) was calculated from serum concentrations . Results : All nine patients completed day 1 , and 8 completed day 2 of the protocol . On day 1 , single-dose kinetics showed considerable spread , but pip/taz serum levels followed the pattern as expected , with a pip / taz concentration ratio of 20 : 1 . On day 2 , however , taz serum concentrations showed a relative increase as compared to pip , result ing in a change in the serum pip/taz concentration ratio to 10 : 1 on day 2 . The CIT of pip was 2.52 ± 1.38 l/h ( t 1/2 : 5.9 ± 2.9 h ) , and CIT of taz 4.44 ± 2.28 l/h ( t 1/2 : 8.1 ± 3.7 h ) . The CIT and t 1/2 of pip and taz correlated highly significantly with clearance by CVVH . Despite a higher CIT , taz has a longer half-life , because of a higher volume of distribution . Conclusion : In CVVH dependent patients , pip/taz fixed drug preparations can be used initially , but the pip dosage should be increased relative to that of taz ( or interval-adjusted ) to prevent cumulation of taz , as compared to the active antimicrobial agent pip Amoxicillin was studied in normal subjects after intravenous , oral , and intramuscular administration of 250- , 500- , and 1,000-mg doses . Serum drug levels were analyzed using a two-compartment open model , as well as area under the curve ( AUC ) and urinary recovery . The variations of these pharmacokinetic parameters were then examined using the three-way analysis of variance and linear regression equations . These results confirmed nearly complete oral absorption : AUC was 93 % of intravenous absorption , and urinary recovery was 86 % . The intramuscular administration of amoxicillin results in complete and reliable absorption with peak drug levels , AUCs , and urinary recovery equivalent to oral dosage . The absorption of lyophilized amoxicillin after intramuscular injection result ed in an AUC that was 92 % of intravenous absorption and urinary recovery of 91 % . The peak serum levels , time to peak , and other pharmacokinetic parameters for intramuscular injection were nearly identical to those for oral administration . Kinetics of both intramuscular and oral administration exhibited dose-dependent absorption ( absorption rate constant , 1.3/h for 250 mg and 0.7/h for 1,000 mg ) . This result ed in relatively later and lower peak serum levels for increasing dose . Total absorption , however , showed no dose dependence , as indicated by urinary recovery and AUC , which changed by less than 10 % OBJECTIVES The aim of this study was to compare the pharmacokinetics and pharmacodynamics of meropenem when administered by 3 h infusion or bolus injection regimens . PATIENTS AND METHODS The study was a r and omized three-way crossover study with a 1 week wash-out period in 12 healthy volunteers . Each subject received a single dose of meropenem in three regimens : ( i ) bolus injection of 1 g meropenem ; ( ii ) 3 h infusion of 1 g meropenem ; and ( iii ) 3 h infusion of 0.5 g meropenem . RESULTS Following bolus injection of 1 g meropenem , the mean + /- s.d . percentages of the t > MIC of 4 , 2 and 1 mg/L were 42.50 + /- 6.20 % , 54.38 + /- 7.64 % and 67.04 + /- 8.47 % of an 8 h dosing interval , respectively . For the 3 h infusion of 1 g meropenem , the percentages of the t > MIC of 4 , 2 and 1 mg/L were 59.27 + /- 7.34 % , 71.97 + /- 8.63 % and 86.07 + /- 9.41 % of an 8 h dosing interval , respectively . For the 3 h infusion of 0.5 g meropenem , the percentages of the t > MIC of 4 , 2 and 1 mg/L were 47.27 + /- 5.34 % , 59.36 + /- 6.60 % and 71.44 + /- 8.45 % of an 8 h dosing interval , respectively . CONCLUSIONS We conclude that a 3 h infusion of 0.5 g or 1 g of meropenem both give greater values for t > MIC than a 1 g bolus and that intermittent infusion may be a useful mode of administration in tropical countries where drug instability may prevent the use of continuous infusion STUDY OBJECTIVE To evaluate the pharmacokinetic and pharmacodynamic profiles of piperacillin-tazobactam administered as a 4-hour infusion in critically ill patients undergoing continuous renal replacement therapy ( CRRT ) . DESIGN Prospect i ve , observational , pharmacokinetic study . SETTING Intensive care unit of a tertiary care hospital in Montréal , Canada . PATIENTS Twenty critically ill adults who were undergoing continuous venovenous hemodiafiltration and receiving a 4-hour infusion of piperacillin 4 g-tazobactam 0.5 g every 8 hours for a documented or suspected infection . INTERVENTION Blood sample s were collected every hour over an 8-hour dosing interval . Prefilter and postfilter blood sample s , and effluent and urine sample s were also collected . MEASUREMENTS AND MAIN RESULTS The primary outcome was the proportion of patients who achieved an unbound piperacillin plasma concentration above a target minimum inhibitory concentration ( MIC ) of 64 mg/L ( MIC that inhibits 90 % of isolates for Pseudomonas aeruginosa ) for at least 50 % of the dosing interval ; 18 ( 90 % ) of the 20 patients achieved this outcome . In all patients , the free piperacillin concentrations were above the Pseudomonas aeruginosa breakpoint of 16 mg/L for the entire time interval . Regarding piperacillin pharmacokinetic parameters , the median ( interquartile range ) minimum unbound plasma concentration was 65.15 mg/L ( 51.30 - 89.30 ) , maximum unbound plasma concentration was 141.3 mg/L ( 116.75 - 173.90 ) , sieving coefficient was 0.809 ( 0.738 - 0.938 ) , total clearance was 65.82 ml/minute ( 53.79 - 102.87 ) , and renal clearance was 0.16 ml/minute ( 0.05 - 3.04 ) . The median CRRT dose was 32.0 ml/kg/h ( 25.0 - 39.8 ) . CONCLUSIONS Administration of a 4-hour infusion of piperacillin-tazobactam was associated with a favorable pharmacodynamic profile in patients undergoing CRRT . Concentrations associated with maximal activity were attained in our patients Objective To investigate the numbers , clinical characteristics , re source use , and outcomes of admissions who met precise clinical and physiologic criteria for severe sepsis ( as defined in the PROWESS trial ) in the first 24 hrs in the intensive care unit . Design Observational cohort study , with retrospective analysis of prospect ively collected data . Setting Ninety-one adult general intensive care units in Engl and , Wales , and Northern Irel and between 1995 and 2000 . Patients Patients were 56,673 adult admissions . Interventions None . Measurements and Main Results We found that 27.1 % of adult intensive care unit admissions met severe sepsis criteria in the first 24 hrs in the intensive care unit . Most were nonsurgical ( 67 % ) , and the most common organ system dysfunctions were seen in the cardiovascular ( 88 % ) and respiratory ( 81 % ) systems . Modeling the data for Engl and and Wales for 1997 suggested that 51 ( 95 % confidence interval , 46–58 ) per 100,000 population per year were admitted to intensive care units and met severe sepsis criteria in the first 24 hrs . Of the intensive care unit admissions who met severe sepsis criteria in the first 24 hrs , 35 % died before intensive care unit discharge and 47 % died during their hospital stay . Hospital mortality rate ranged from 17 % in the 16–19 age group to 64 % in those > 85 yrs . In Engl and and Wales in 1997 , an estimated 24 ( 95 % confidence interval , 21–28 ) per 100,000 population per year died after intensive care unit admissions with severe sepsis in the first 24 hrs . For intensive care unit admissions who met severe sepsis criteria in the first 24 hrs , median intensive care unit length of stay was 3.56 days ( interquartile range , 1.50–9.32 ) and median hospital length of stay was 18 days ( interquartile range , 8–36 days ) . These admissions used 45 % of the intensive care unit and 33 % of the hospital bed days used by all intensive care unit admissions . Conclusions Severe sepsis is common and presents a major challenge for clinicians , managers , and healthcare policymakers . Intensive care unit admissions meeting severe sepsis criteria have a high mortality rate and high re source use OBJECTIVES To evaluate the pharmacokinetics of piperacillin/tazobactam in critically ill patients undergoing continuous renal replacement therapy ( CRRT ) and to assess the success of the therapy against susceptible bacteria . PATIENTS AND METHODS Sixteen patients undergoing CRRT with different degrees of renal function were included in the study . Blood and ultrafiltrate sample s were drawn after administration of piperacillin/tazobactam ( 4/0.5 g ) every 4 , 6 or 8 h. The data were analysed by a population approach using NONMEM 7.2 . The probability of target attainment ( PTA ) of maintaining free piperacillin levels above the MIC during the entire dosing interval was estimated by simulation of intermittent and continuous infusions . RESULTS The pharmacokinetics of piperacillin and tazobactam were best described by two-compartment models where the elimination of both drugs was conditioned by renal [ dependent on creatinine clearance ( CLCR ) ] , non-renal and extracorporeal clearances . A 20 min infusion of piperacillin/tazobactam administered every 6 h provided high PTAs against MICs ≤ 32 mg/L in patients with severe renal failure . In patients with normal or moderate renal function PTAs ≥ 90 % were only obtained up to MICs ≤ 8 mg/L with short infusions . However , simulating continuous infusion , higher probabilities of success were obtained against MICs of 32 and 16 mg/L when CLCR was 50 and 100 mL/min , respectively . CONCLUSIONS Population pharmacokinetic models have been developed and vali date d for piperacillin and tazobactam . Based on the pharmacokinetic/pharmacodynamic analysis , dosing recommendations are given considering the residual renal function of the patient and the MIC for the isolated bacteria The study objective was to evaluate meropenem pharmacokinetics and pharmacodynamics in morbid obesity . Nine patients hospitalized in an intensive care unit with a body mass index ≥40 kg/m(2 ) received meropenem 500 mg or 1 g q6h , infused over 0.5 hours . Pharmacokinetic parameters were estimated , and Monte Carlo simulations were performed for 5 dosing regimens ( 500 mg q8h , 1 g q8h , 2 g q8h , 500 mg q6h , 1 g q6h ) infused over 0.5 and 3 hours . Probability of target attainment ( PTA ) was calculated using fT > MIC of 40 % and 54 % . Total body weight and body mass index were 152.3 ± 31.0 kg and 54.7 ± 8.6 kg/m(2 ) , respectively . Volume of distribution of the central compartment was 13.3 ± 6.7 L , volume of distribution at steady-state was 37.4 ± 14.7 L , and systemic clearance was 10.2 ± 5.0 L/h . At an MIC of 2 µg/mL , PTA was ≥90 % for 4/5 and 2/5 regimens infused over 0.5 hours and for 5/5 and 4/5 regimens infused over 3 hours at 40 % and 54 % fT > MIC , respectively . St and ard doses achieve adequate exposures for susceptible bacteria at a pharmacodynamic target of 40 % fT > MIC . Higher doses or prolonged infusion regimens are needed at the higher pharmacodynamic target ABSTRACT Antibiotic penetration to the infection site is critical for obtaining a good clinical outcome in patients with ventilator-associated pneumonia ( VAP ) . Surprisingly few studies have quantified the penetration of β-lactam agents into the lung , as measured by the ratio of area under the concentration-time curve ( AUC ) in epithelial lining fluid ( ELF ) to AUC in plasma ( AUCELF/AUCplasma ratio ) . These have typically involved noninfected patients . This study examines the penetration and pharmacodynamics of meropenem in the ELF among patients with VAP . Meropenem plasma and ELF concentration-time data were obtained from patients in a multicenter clinical trial . Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer ( big nonparametric adaptive grid [ BigNPAG ] ) . A Monte Carlo simulation was performed to estimate the range of ELF/plasma penetration ratios one would expect to observe in patients with VAP , as measured by the AUCELF/AUCplasma ratio . The range of AUCELF/AUCplasma penetration ratios predicted by the Monte Carlo simulation was large . The 10th percentile of lung penetration was 3.7 % , while the 90th percentile of penetration was 178 % . The variability of ELF penetration is such that if relatively high ELF exposure targets are required to attain multilog kill or resistance suppression for bacteria like Pseudomonas aeruginosa , then even receiving the largest licensed dose of meropenem with an optimal prolonged infusion may not result in target attainment for a substantial fraction of the population ABSTRACT The time that concentrations in serum are above the MIC ( T > MIC ) is the pharmacokinetic/pharmacodynamic parameter correlating with the therapeutic efficacy of β-lactam antibiotics . The aim of this study was to demonstrate the T > MIC of meropenem when administered by a 3-h infusion compared with that when administered by bolus injection . The study was conducted with nine patients with ventilator-associated pneumonia . Each subject received meropenem in three regimens consecutively : ( i ) bolus injection of 1 g every 8 h for 24 h ; ( ii ) 3-h infusion of 1 g every 8 h for 24 h ; and ( iii ) 3-h infusion of 2 g every 8 h for 24 h. Following bolus injection , the percentages of the T > MICs of 16 , 8 , 4 , and 1 μg/ml were 28.33 % ± 11.67 % , 45.89 % ± 22.90 % , 57.00 % ± 24.82 % , and 74.67 % ± 17.94 % of an 8-h interval , respectively . For the 3-h infusion of 1 g of meropenem , the percentages of the T > MICs of 16 , 8 , 4 , and 1 μg/ml were 37.78 % ± 20.57 % , 58.11 % ± 24.38 % , 72.67 % ± 21.97 % , and 93.56 % ± 6.84 % of an 8-h interval , respectively . For the 3-h infusion of 2 g of meropenem , the percentages of the T > MICs of 16 , 8 , 4 , and 1 μg/ml were 57.89 % ± 24.26 % , 72.89 % ± 22.40 % , 85.56 % ± 16.42 % , and 98.56 % ± 3.28 % of an 8-h interval , respectively . In conclusion , a 3-h infusion result ed in greater T > MICs than those after a bolus injection . For the treatment of infections caused by pathogens with intermediate resistance , a 3-h infusion of 2 g of meropenem every 8 h can provide concentrations in serum above the MIC of 16 μg/ml for almost 60 % of an 8-h interval Noncompartmental and compartmental analyses of meropenem disposition in patients receiving 1-g intravenous intermittent infusions every 8 h were performed . Twelve patients ( one woman and 11 men ) participated in the meropenem pharmacokinetic analysis . Operative findings included perforated appendicitis ( five patients ) , gangrenous appendicitis ( five patients ) , peri-appendical abscess ( one patient ) , and gunshot wound to the abdomen ( one patient ) . The most common associated adverse drug reactions to meropenem were diarrhea and increased liver enzymes . The estimated noncompartmental pharmacokinetic parameters , mean + /- st and ard deviation , are as follows : maximum drug concentration in plasma , 47.58 + /- 17.59 micrograms/ml ; half-life , 1.04 + /- 0.19 h ; elimination rate constant , 0.68 + /- 0.12 h-1 ; area under the concentration-time curve from 0 h to infinity , 57.5 + /- 20.12 micrograms x ml/h ; total plasma clearance , 315.40 + /- 71.94 ml/min ; renal clearance , 136.7 + /- 89.20 ml/min ; volume of distribution at steady state , 26.68 + /- 6.88 liters ; and mean residence time , 1.47 + /- 0.28 h. The two-compartment model best described meropenem disposition in our patients . Our findings differed from estimates for healthy volunteers possibly because of the physiologic changes as a result of surgery . Our findings suggest that meropenem ( 1,000 mg ) administered intravenously every 8 h provides adequate concentrations for most intra-abdominal infections ABSTRACT The steady-state concentrations of meropenem and the β-lactamase inhibitor RPX7009 in plasma , epithelial lining fluid ( ELF ) , and alveolar macrophage ( AM ) concentrations were obtained in 25 healthy , nonsmoking adult subjects . Subjects received a fixed combination of meropenem ( 2 g ) and RPX7009 ( 2 g ) administered every 8 h , as a 3-h intravenous infusion , for a total of three doses . A bronchoscopy and bronchoalveolar lavage were performed once in each subject at 1.5 , 3.25 , 4 , 6 , or 8 h after the start of the last infusion . Meropenem and RPX7009 achieved a similar time course and magnitude of concentrations in plasma and ELF . The mean pharmacokinetic parameters ± the st and ard deviations of meropenem and RPX7009 determined from serial plasma concentrations were as follows : Cmax = 58.2 ± 10.8 and 59.0 ± 8.4 μg/ml , Vss = 16.3 ± 2.6 and 17.6 ± 2.6 liters ; CL = 11.1 ± 2.1 and 10.1 ± 1.9 liters/h , and t1/2 = 1.03 ± 0.15 and 1.27 ± 0.21 h , respectively . The intrapulmonary penetrations of meropenem and RPX7009 were ca . 63 and 53 % , respectively , based on the area under the concentration-time curve from 0 to 8 h ( AUC0–8 ) values of ELF and total plasma concentrations . When unbound plasma concentrations were considered , ELF penetrations were 65 and 79 % for meropenem and RPX7009 , respectively . Meropenem concentrations in AMs were below the quantitative limit of detection , whereas median concentrations of RPX7009 in AMs ranged from 2.35 to 6.94 μg/ml . The results from the present study lend support to exploring a fixed combination of meropenem ( 2 g ) and RPX7009 ( 2 g ) for the treatment of lower respiratory tract infections caused by meropenem-resistant Gram-negative pathogens susceptible to the combination of meropenem-RPX7009 Objective : Extended daily dialysis ( EDD ) combines the advantage of both intermittent hemodialysis and continuous renal replacement therapy : excellent detoxification accompanied by cardiovascular tolerability . The aim of this study was to evaluate pharmacokinetics of meropenem and vancomycin in critically ill patients with renal failure undergoing EDD . Design : Prospect i ve clinical study . Setting : Surgical intensive care unit in a tertiary care center . Patients : We studied intensive care patients with anuric acute renal failure being treated with EDD and receiving meropenem ( n = 10 ) or vancomycin ( n = 10 ) therapy . Interventions : The antibiotics were administered 6 hrs ( 1.0 g meropenem ) or 12 hrs ( 1.0 g vancomycin ) before EDD was started in order to study the pharmacokinetics before and during EDD . In addition to the application of different methods to calculate pharmacokinetic parameters , the total dialysate concentration of both drugs was measured . Results : Based on the amount of the drug recovered from the collected spent dialysate , the fraction of drug removed by one dialysis treatment was 18 % for meropenem and 26 % for vancomycin . Dosing regimes for intermittent hemodialysis and continuous renal replacement therapy can not be used for critically ill patients treated with EDD . Conclusion : Our data suggest that patients treated with EDD by means of a high-flux dialyzer ( polysulphone ; surface area , 1.3 m2 ; blood and dialysate flow , 160 mL/min ; EDD time , 480 mins ) and current dosing regimens run the risk of being significantly underdosed , which may have detrimental effects on critically ill patients with life-threatening infections . The exact dose has to be tailored according to weight and severity of illness as well as the current minimal inhibitory concentration against the incriminated bacteria . Whenever possible , therapeutic drug monitoring should be performed The aim of this study was to determine whether concentration-dependent renal clearance of ampicillin and amoxycillin occurs . The drugs were given as single 20 min i.v . infusions in doses ranging from 1.9 to 2.8 g to nine healthy volunteers using a cross-over design . Plasma and urinary concentrations were determined by a selective liquid chromatographic method using frequent sampling up to 10 and 30 h respectively after termination of the infusion . The renal clearance of the drugs was independent of the plasma concentration . The mean ( s.d . ) renal clearances of ampicillin and amoxycillin were 167 ( 24 ) and 157 ( 20 ) ml min-1 1.73 m-2 respectively . The net secretion was about 50 % of the total renal clearance of both drugs . The plasma concentration and urinary excretion rate versus time curves indicated a polyexponential decline , which could be described by both a biexponential and a triexponential equation . The former proved to be more reliable , especially in the calculation of micro rate constants . There was a tendency to more sustained plasma concentrations after amoxycillin , also illustrated by a significantly lower mean ( s.d . ) plasma clearance of this drug , viz . 185 ( 30 ) ml min-1 1.73 m-2 , as compared to ampicillin , 210 ( 24 ) ml min-1 1.73 m-2 ( P less than 0.04 ) . There were no major differences in the disposition rate constants and the distribution volumes of ampicillin and amoxycillin . The mean ( s.d . ) plasma half-life was 1.7 ( 0.3 ) h for both drugs . The urinary excretion rate indicated a slower terminal disposition rate however , with ampicillin and amoxycillin half-lives of 3.4 ( 2.0 ) and 3.9 ( 1.2 ) h respectively . The longer half-life in the terminal phase may be due to increased tubular reabsorption at low urinary concentrations . It was not possible to determine in this study whether the half-life was affected by changes in clearance or volume of distribution . The urinary solubility of the drugs was dependent on pH. This could explain the massive macroscopic crystalluria seen in one subject after amoxycillin . Three hours after termination of the infusion , crystals could no longer be found in the sediment . There was no clinical or laboratory evidence of renal damage ABSTRACT Piperacillin in combination with tazobactam is one of the most commonly used intravenous antibiotics . There is evidence for a possible saturable elimination of piperacillin . Therefore , the saturable elimination and its impact on the choice of optimal dosage regimens were quantified . In a r and omized crossover study , 10 healthy volunteers received 1,500 mg and 3,000 mg of piperacillin as 5-min intravenous infusion . Population pharmacokinetics based on plasma and urine data were determined utilizing NONMEM and S-ADAPT . Probabilities of target attainment ( PTAs ) were compared for different models and dosage regimens , based on the target time of the non-protein-bound concentration above the MIC of at least 50 % of the dosing interval . Total clearance of piperacillin was 18 % ( geometric mean ratio , 90 % confidence interval , 11 to 24 % ) lower ( P < 0.01 ) , and renal clearance was 24 % ( 9 to 37 % ) lower ( P = 0.02 ) at the high compared to the low dose . The final model included first-order nonrenal elimination and parallel first-order and mixed-order renal elimination . Nonrenal clearance was 5.44 liter/h ( coefficient of variation , 18 % ) , first-order renal clearance was 4.42 liter/h ( 47 % ) , and the maximum elimination rate of mixed-order renal elimination was 219 mg/h ( 84 % ) , with a Michaelis-Menten constant of 36.1 mg/liter ( 112 % ) . Compared to models with saturable elimination , a linear model predicted up to 10 % lower population PTAs for high-dose short-term infusions ( 6 g every 8 h ) and up to 4 % higher population PTAs for low-dose continuous infusions ( 6 g/day ) . While renal elimination of piperacillin was saturable at therapeutic concentrations , the extent of saturation of nonrenal clearance was small . The influence of saturable elimination on PTAs for clinical ly relevant dosage regimens was relatively small BACKGROUND Underst and ing the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families . METHODS We analyzed prospect ively collected data on 6075 deaths among 22,248 live births , with gestational ages of 22 0/7 to 28 6/7 weeks , among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network . We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011 , with adjustment for baseline differences . RESULTS The number of deaths per 1000 live births was 275 ( 95 % confidence interval [ CI ] , 264 to 285 ) from 2000 through 2003 and 285 ( 95 % CI , 275 to 295 ) from 2004 through 2007 ; the number decreased to 258 ( 95 % CI , 248 to 268 ) in the 2008 - 2011 period ( P=0.003 for the comparison across three periods ) . There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008 - 2011 than in 2000 - 2003 and 2004 - 2007 ( 68 [ 95 % CI , 63 to 74 ] vs. 83 [ 95 % CI , 77 to 90 ] and 84 [ 95 % CI , 78 to 90 ] per 1000 live births , respectively ; P=0.002 ) . Similarly , in 2008 - 2011 , as compared with 2000 - 2003 , there were decreases in deaths attributed to immaturity ( P=0.05 ) and deaths complicated by infection ( P=0.04 ) or central nervous system injury ( P<0.001 ) ; however , there were increases in deaths attributed to necrotizing enterocolitis ( 30 [ 95 % CI , 27 to 34 ] vs. 23 [ 95 % CI , 20 to 27 ] , P=0.03 ) . Overall , 40.4 % of deaths occurred within 12 hours after birth , and 17.3 % occurred after 28 days . CONCLUSIONS We found that from 2000 through 2011 , overall mortality declined among extremely premature infants . Deaths related to pulmonary causes , immaturity , infection , and central nervous system injury decreased , while necrotizing enterocolitis-related deaths increased . ( Funded by the National Institutes of Health . ) The pharmacokinetics and pharmacodynamics of two multiple-dose regimens of piperacillin-tazobactam ( 3.375 g every 6 h and 4.5 g every 8 h ) were evaluated at steady state for 12 healthy adult volunteers . Inhibitory and bactericidal activities for the two regimens were determined with five American Type Culture Collection ( ATCC ) organisms ( Escherichia coli , Staphylococcus aureus , Klebsiella pneumoniae , Pseudomonas aeruginosa , and Bacteroides fragilis ) . The percentage of time that plasma concentrations remained above the MIC ( T > MIC ) for each organism and dosage regimen was calculated . Areas under the inhibitory ( AUIC0 - 24 ) and bactericidal activity ( AUBC0 - 24 ) curves were calculated with the trapezoidal rule by using the reciprocal of the inhibitory and bactericidal titers determined for each dosage regimen . In order to assess the validity of predicted measures of bactericidal ( AUC0 - 24/MBC ) and inhibitory ( AUC0 - 24/MIC ) activity to determine bacteriological response to beta-lactam antimicrobial agents , AUC0 - 24/MBC and AUC0 - 24/MIC values were compared with measured AUBC0 - 24 and AUIC0 - 24 values . Total body clearance values were equivalent for piperacillin ( 183.96 + /- 22.66 versus 181.72 + /- 19.54 ml/min/1.73 m2 , P > 0.05 ) and tazobactam ( 184.71 + /- 19.89 versus 184.87 + /- 18.35 ml/min/1.73 m2 , P > 0.05 ) following the administration of the 3.375-g-every-6-h and 4.5-g-every-8-h dosages , respectively . Comparison of area under the plasma concentration-time curve ( AUC0 - 24 ) for piperacillin ( 967.74 + /- 135.56 microg x h/ml versus 978.88 + /- 140.96 microg x h/ml ) and tazobactam ( 120.14 + /- 15.78 microg x h/ml versus 120.01 + /- 16.22 microg x h/ml ) revealed no significant differences ( P > 0.05 ) between the 3.375-g-every-6-h and 4.5-g-every-8-h regimens , respectively . Both regimens provided T > MIC values of > 60 % for all organisms tested . Measured values of bactericidal ( AUBC ) and inhibitory ( AUIC ) activity were significantly different ( P < 0.05 ) from predicted values ( AUC0 - 24/MBC and AUC0 - 24/MIC ) for all organisms studied with the exception of the bactericidal activity for P. aeruginosa and S. aureus . Additionally , ATCC organisms possessing the same MICs and MBCs exhibited great differences in measured AUBC0 - 24 and AUIC0 - 24 values . Reasons for this difference may be inherent differences in organism specific susceptibility When piperacillin/tazobactam has been used to treat hospitalized patients with serious infections , including nosocomial pneumonia caused by Pseudomonas aeruginosa , it has usually been dosed at 3.375 g q4h to provide serum concentrations above commonly encountered organisms ’ MICs ( T > MIC ) for at least 40–50 % of the dosing interval . Pharmacodynamic principles suggest that a similar efficacy can be realized with extended dosing intervals when a larger dose ( e.g. 4.5 g q6h ) is administered , which was the objective of this study . Twelve healthy volunteers , 29.4 ± 8.9 years of age , were enrolled in this multiple-dose , open-labeled , r and omized , two-period crossover study . Blood sample s were collected after the third dose and concentrations of piperacillin/tazobactam were determined with a vali date d HPLC method . Pharmacokinetic profiles were determined by noncompartment analysis . T > MIC of piperacillin was calculated for a range of MIC values . Piperacillin/tazobactam was well tolerated in 11 subjects who completed both regimens . The Cmax , T1/2 , K , and AUC of P were significantly different according to a paired t test ( p < 0.05 ) between two study regimens . Significant differences ( p < 0.05 ) in tazobactam regimens were noted for Cmax , and AUC . The piperacillin/tazobactam regimen of 4.5 g q6h achieved a 44 % T > MIC for MIC values of ≤16 µg/ml , while the 3.375-gram q4h regimen achieved 42 % T > MIC , for MIC values of ≤32 µg/ml . Dosage regimens for treating serious infections can be extended safely and effectively to 4.5 g q6h and obtain at least 40–50 % T > MIC in the coverage of pathogens implicated with serious infections , including P. aeruginosa BACKGROUND : Pharmacokinetic ( PK ) models are used to predict drug concentrations for infusion regimens for intraoperative displays and to calculate infusion rates in target-controlled infusion systems . For propofol , the PK models available in the literature were mostly developed from particular patient groups or anesthetic techniques , and there is uncertainty of the accuracy of the models under differing patient and clinical conditions . Our goal was to determine a PK model with robust predictive performance for a wide range of patient groups and clinical conditions . METHODS : We aggregated and analyzed 21 previously published propofol data sets containing data from young children , children , adults , elderly , and obese individuals . A 3-compartmental allometric model was estimated with NONMEM software using weight , age , sex , and patient status as covariates . A predictive performance metric focused on intraoperative conditions was devised and used along with the Akaike information criteria to guide model development . RESULTS : The data set contains 10,927 drug concentration observations from 660 individuals ( age range 0.25–88 years ; weight range 5.2–160 kg ) . The final model uses weight , age , sex , and patient versus healthy volunteer as covariates . Parameter estimates for a 35-year , 70-kg male patient were : 9.77 , 29.0 , 134 L , 1.53 , 1.42 , and 0.608 L/min for V1 , V2 , V3 , CL , Q2 , and Q3 , respectively . Predictive performance is better than or similar to that of specialized models , even for the sub population s on which those models were derived . CONCLUSIONS : We have developed a single propofol PK model that performed well for a wide range of patient groups and clinical conditions . Further prospect i ve evaluation of the model is needed Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections . In order to define meropenem dosing guidelines for children , an escalating , single-dose , pharmacokinetic study at 10 , 20 , and 40 mg/kg of body weight was performed . A total of 73 infants and children in four age groups were enrolled in the study : 2 to 5 months , 6 to 23 months , 2 to 5 years , and 6 to 12 years . The first patients enrolled were those in the oldest age group , who received the lowest dose . Subsequent enrollment was determined by decreasing age and increasing dose . Complete studies were performed on 63 patients . No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted . Mean pharmacokinetic parameter estimates were as follows : half-life , 1.13 + /- 0.15 h ; volume of distribution at steady state , 0.43 + /- 0.06 liters/kg ; mean residence time , 1.57 + /- 0.11 h ; clearance , 5.63 + /- 0.75 ml/min/kg ; and renal clearance , 2.53 + /- 0.50 ml/min/liters kg . Approximately 55 % of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing . No significant side effects were reported in any patients . By using the derived pharmacokinetic parameter estimates , a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90 % of strains tested for virtually all potentially susceptible bacterial pathogens Background : Antimicrobial pharmacokinetic and pharmacodynamic data are limited in obesity . Objective : To evaluate the steady-state pharmacokinetics and pharmacodynamics of doripenem and meropenem in obese patients hospitalized on a general ward . Methods : Patients with a body mass index ( BMI ) ≥40 kg/m2 or total body weight ( TBW ) ≥100 pounds over their ideal body weight r and omly received doripenem 500 mg ( 1-hour infusion ) or meropenem 1 g ( 0.5-hour infusion ) every 8 hours . Differences in pharmacokinetic parameters were determined by unpaired t test . Monte Carlo simulations were performed for 500 mg and 1 g every 8 hours , infused over 1 and 4 hours for doripenem and 0.5 and 3 hours for meropenem . Probability of target attainment ( PTA ) was calculated using a pharmacodynamic target of 40 % fT > MIC ( free drug concentrations above the minimum inhibitory concentration [ MIC ] ) , and cumulative fraction of response ( CFR ) was calculated using MIC data for 8 Gram-negative pathogens . Results : Twenty patients were studied . Volume of distribution at steady state , corrected for TBW , was significantly larger ( 0.18 ± 0.04 vs 0.13 ± 0.05 L/kg , P = .048 ) and systemic clearance was significantly faster for doripenem ( 11.7 ± 4.1 vs 8.1 ± 2.6 L/h , P = .03 ) . PTA was > 90 % for all regimens at MICs ≤2 µg/mL. CFR was > 90 % for all regimens against 6 enteric Gram-negative pathogens and for 3 of 4 regimens for each drug against Pseudomonas aeruginosa . Conclusions : Doripenem and meropenem pharmacokinetics differ in obesity . However , currently approved dosing regimens provide adequate pharmacodynamic exposures for susceptible bacteria in obese patients The aim of this study was to evaluate the effect of augmented renal clearance ( ARC ) on vancomycin serum concentrations in critically ill patients . This prospect i ve , single-centre , observational , cohort study included 93 consecutive , critically ill septic patients who started treatment that included vancomycin by continuous infusion , admitted over a 2-year period ( March 2006 to February 2008 ) . ARC was defined as 24-h creatinine clearance ( CL(Cr))>130 mL/min/1.73 m(2 ) . Two groups were analysed : Group A , 56 patients with a CL(Cr)≤130 mL/min/1.73 m(2 ) ; and Group B , 37 patients with a CL(Cr)>130 mL/min/1.73 m(2 ) . Vancomycin therapeutic levels were assessed on the first 3 days of treatment ( D(1 ) , D(2 ) and D(3 ) ) . Serum vancomycin levels on D(1 ) , D(2 ) and D(3 ) , respectively , were 13.1 , 16.6 and 18.6 μmol/L for Group A and 9.7 , 11.7 and 13.8 μmol/L for Group B ( P<0.05 per day ) . The correlation between CL(Cr ) and serum vancomycin on D(1 ) was -0.57 ( P<0.001 ) . ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment OBJECTIVE To test whether a prolonged 3-hour infusion of meropenem 500 mg achieves an equivalent proportion of time above the minimal inhibitory concentration ( MIC ) ( % TMIC ) to that of meropenem 1000 mg given over 30 minutes . DESIGN , SETTING AND PARTICIPANTS A r and omised crossover study in 10 critically ill patients . METHOD We administered meropenem as a 1000 mg , 30-minute infusion or as a 500 mg , 3-hour infusion . We determined serial plasma concentrations for each dosing episode and performed comparisons of % TMIC at different MICs . OUTCOME MEASURES The percentage of time that meropenem was above its MIC . RESULTS For low MICs ( ≤2 mg/L ) , both regimens attained a % TMIC > 40 % in all patients . For an MIC of 4mg/L , this target was attained in all but one patient , but with an MIC of 8mg/L , three patients in each group had a % TMIC < 40 % . There was no difference in target attainment between the two regimens for MICs up to 8mg/L. There was marked variability in the pharmacokinetic and hence the pharmacokinetic-pharmacodynamic parameters between individuals . Several patients had elevated creatinine clearances and , with both regimens , their target attainment was poor . CONCLUSIONS Meropenem at 1000 mg over 30 minutes achieved a similar % TMIC to meropenem at 500 mg given over 3 hours . Meropenem pharmacokinetics were highly variable from individual to individual Objective To determine the effects of severe trauma with hemorrhagic shock on amoxicillin and clavulanate concentrations in plasma and their pharmacokinetics . Design A prospect i ve , open , descriptive study . Setting A 12-bed , adult surgical intensive care unit in a university-affiliated hospital in France . SubjectsSubjects were 12 patients ( 10 men , 2 women ) with severe trauma : median ( range ) Injury Severity Score , 38 ( 17–48 ) ; Acute Physiology and Chronic Health Evaluation II , 16 ( 7–38 ) ; Simplified Acute Physiology Score II , 41 ( 23–77 ) . Also enrolled were 12 healthy volunteers who were matched on age ( ±5 yrs ) , gender , and body-surface area ( ±20 cm2 ) . All the trauma patients suffered hemorrhagic shock defined as the association of at least one episode of systolic blood pressure < 90 mm Hg and an intravascular volume expansion > 2000 mL between trauma and surgery . InterventionProphylactic perioperative administration of 2 g of amoxicillin and 0.2 g of clavulanate in combination during the first 12 hrs posttrauma in patients , and at the start of the pharmacokinetic study in volunteers . Measurements and Main Results Serial plasma sample s ( n = 13 ) were obtained after the first antibiotic administration to measure antibiotic levels by using high-performance liquid chromatography assays . Compared with volunteers , trauma patients had higher plasma amoxicillin and clavulanate concentrations , attributed to a reduction of the volume of distribution ( p = .001 and p = .06 , respectively ) and , to a lesser extent , of the total body clearance ( p = .09 and p = .20 , respectively ) . Consequently , amoxicillin and clavulanate elimination half-lives were similar for the two groups of subjects . The interindividual variabilities for all the amoxicillin pharmacokinetic parameters were higher in patients . Conclusions In trauma patients with hemorrhagic shock requiring surgery , the administration of 2 g of amoxicillin and 0.2 g of clavulanate seems adequate , according to the antibiotic concentrations observed in plasma for both drugs . However , further studies exploring antibiotic concentrations in tissues are warranted ABSTRACT Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics ( PK ) . The additional effect of obesity on PK potentially increases the challenge for effective dosing . The aim of this prospect i ve study was to describe the population PK of meropenem for a cohort of critically ill patients , including obese and morbidly obese patients . Critically ill patients prescribed meropenem were recruited into the following three body mass index ( BMI ) groups : nonobese ( 18.5 to 29.9 kg/m2 ) , obese ( 30.0 to 39.9 kg/m2 ) , and morbidly obese ( ≥40 kg/m2 ) . Serial plasma sample s were taken , and meropenem concentrations were determined using a vali date d chromatographic method . Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics . Nineteen critically ill patients with different BMI categories were enrolled . The patients ' mean ± st and ard deviation ( SD ) age , weight , and BMI were 49 ± 15.9 years , 95 ± 22.0 kg , and 33 ± 7.0 kg/m2 , respectively . A two-compartment model described the data adequately . The mean ± SD parameter estimates for the final covariate model were as follows : clearance ( CL ) , 15.5 ± 6.0 liters/h ; volume of distribution in the central compartment ( V1 ) , 11.7 ± 5.8 liters ; intercompartmental clearance from the central compartment to the peripheral compartment , 25.6 ± 35.1 liters h−1 ; and intercompartmental clearance from the peripheral compartment to the central compartment , 8.32 ± 12.24 liters h−1 . Higher creatinine clearance ( CLCR ) was associated with a lower probability of target attainment , with BMI having little effect . Although obesity was found to be associated with an increased V1 , dose adjustment based on CLCR appears to be more important than patient BMI The pathophysiology associated with major burns is complex and subject to a state of flux . The combination of beta-lactamase inhibitors with powerful penicillins is an interesting and an attractive potential solution to the emergence of bacterial resistance . The kinetics in serum and urine and the clinical safety of a fixed combination of 4 g of piperacillin ( PPR ) and 0.5 g of tazobactam ( TZB ) were studied in 10 patients ( 22 to 50 years old and weighing 45 to 105 kg ) with major burns who were infected with Pseudomonas aeruginosa and various entero-bacteria . All of them received additional antimicrobial drugs . Treatment involved one dose every 6 h. The mean body surface area affected by third-degree burns was 30.0 % + /- 4.0 % . The study took place in accordance with current ethical guidelines . Two series of blood sample s were drawn after the first ( day 1 ) and ninth ( day 3 at steady state ) doses ; urine was collected during the same periods . Levels of PPR and TZB in serum and urine were measured by high-pressure liquid chromatography . A noncompartmental method was used for kinetic and graphic analysis of concentration-time pairs . The safety of the treatment was excellent . There was no systemic accumulation of the beta-lactam combination . Residual concentrations measured on days 1 and 3 [ mean ( st and ard error of the mean ) ] were above the MIC for the organism responsible for infection ; i.e. , C(min)day1 = 26.3 ( 8.5 ) and C(min)day3 = 21.0 ( 9.1 ) for PPR and C(min)day1 = 1.9 ( 0.6 ) and C(min)day3 = 1.4 ( 0.3 ) for TZB . There was no statistically significant difference between pharmacokinetic parameters determined for day 1 and day 3 . Evidence was found in burn patients , in contrast to healthy subjects , of a marked increase in apparent volumes of distribution , in such a way that the apparent elimination half-lives of the combination were notably prolonged , i.e. , 1.8 ( 0.3 ) versus 1.5 ( 0.3 ) h for PPR in patients and healthy subjects , respectively , and 1.7 ( 0.3 ) versus 1.4 ( 0.3 ) h for TZB . These findings indicate the possibility of nonrenal translesional diffusion of PPR-TZB in burn patients . The polarity of the association would further support this hypothesis . It has been shown here that the recommended dosage regimen for administration of PPR-TZB must be high in major-burn patients , i.e. , 4 g/0.5 g every 6 h. The data obtained provide valuable information , which is suitable for immediate application in everyday clinical practice Objective : To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy . Design : A prospect i ve , clinical study . Setting : General intensive care unit of a university hospital . Patients : Ten critically ill adult patients being treated with meropenem and receiving continuous veno‐venous hemofiltration ( hemofiltration rates , 1‐2 L/hr ) ( n = 5 ) or continuous veno‐venous hemodiafiltration ( hemofiltration rates , 1‐1.5 L/hr ; dialysis rates , 1‐1.5 L/hr ) ( n = 5 ) via a polyacrylonitrile hollow fiber 0.9‐m2 filter . Interventions : Patients received a meropenem dose of 1 g iv every 12 hrs as a 5‐min bolus . Measurements and Main Results : Meropenem concentrations were measured by high‐performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration‐time profiles , derive pharmacokinetic variable estimates , and determine sieving coefficients and filter clearances . The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations ( MICs ) for pathogens that may be encountered in intensive care patients . Serum concentrations exceeded 4 mg/L ( MIC90 for Pseudomonas aeruginosa ) during 67 % of the dosage period in all patients . Sub‐MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment . Mean ( SD ) ( n = 10 ) pharmacokinetic variable estimates were as follows : elimination half‐life , 5.16 hrs ( 1.83 hrs ) ; volume of distribution , 0.35 L/kg ( 0.10 L/kg ) ; and total clearance , 4.30 L/hr ( 1.38 L/hr ) . A sieving coefficient of 0.93 ( 0.06 ) ( n = 9 ) indicated free flow across the filter . The fraction cleared by the extracorporeal route was 48 % ( 13 % ) ( n = 9 ) , which is clinical ly important . Conclusions : A meropenem dose of 1 g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno‐venous hemofiltration or continuous veno‐venous hemofiltration with a 0.9‐m2 polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr . A lower dose would not be sufficient for the empirical treatment of potentially life‐threatening infections in all patients The single-dose pharmacokinetics of azlocillin and piperacillin were compared by using a r and omized , crossover design . The concentrations of azlocillin in serum were consistently higher than those of piperacillin throughout an 8-h study . The area under the time-concentration curve of azlocillin was significantly greater than that of piperacillin , and the total body clearance of azlocillin was significantly lower than that of piperacillin The disposition of piperacillin was prospect ively evaluated in nine severely burned patients who had normal renal and hepatic function . Wide interpatient variations were demonstrated in the drug 's distribution volume , half-life , and clearance , with mean ( + /- SD ) values of 55.0 ( + /- 44.2 ) liters , 3.6 ( + /- 5.2 ) hours , and 14.9 ( + /- 6.3 ) liters/hour , respectively . Piperacillin clearance was best explained by patient factors other than age , renal function , and the percentage of body surface area burns . Piperacillin disposition was related to the patients ' serum albumin , total bilirubin , blood urea nitrogen , and the amount of urea nitrogen excreted daily in urine . Altered piperacillin disposition thus appeared to occur secondary to changes in the patients ' physiologic and metabolic state caused by injury-related stress and fluid therapy . The patient 's physiologic and metabolic response to injury , along with age and renal function , should be considered when instituting treatment with piperacillin or other agents cleared from the body in a similar manner BACKGROUND Extended infusion of beta-lactam antibiotics has been advocated as a method for optimizing antibiotic exposure in critically ill patients . The objective of this study was to compare the pharmacokinetics/pharmacodynamics of extended infusion versus bolus infusion of piperacillin and meropenem in critically ill patients with normal renal function . METHODS A prospect i ve study of 3 hours extended infusion of meropenem and piperacillin in critically ill patients without renal dysfunction . Results from the extended infusion cohort were compared to previously published bolus infusion data in critically ill patients . RESULTS Twenty extended infusion patients ( 15 piperacillin , 5 meropenem ) were compared with 13 bolus infusion patients ( 8 piperacillin , 5 meropenem ) . The demographic and clinical characteristics between both groups were not statistically different . Significant pharmacokinetic differences were observed in median ( interquartile range ) Cmax for both meropenem ( extended infusion 17 [ 12.6 - 21.9 ] vs. bolus 85.2 [ 66.7 - 140.3 ] ; P=0.01 ) and piperacillin ( extended infusion 76.2 [ 57.7 - 92.6 ] vs. bolus 240.2 [ 168.5 - 275.4 ] ; P=0.001 ) . Considerable pharmacokinetic variability existed in each group for both drugs . Compared to bolus infusion , fT > MIC using extended infusion was higher for both drugs : 96 % ( IQR 71 - 100 % ) compared to 77 % ( IQR 41 - 93 % ) for piperacillin ( P=0.05 ) and 82 % ( IQR 63 - 89 % ) compared to 51 % ( IQR 48 - 63 % ) for meropenem ( P=0.095 ) ; assuming a MIC of 16 mg/L and 2 mg/L respectively . CONCLUSION This study confirms that extended infusion in critically ill patients result in advantageous pharmacokinetic profiles by increasing the fT > MIC for piperacillin and meropenem . In a significant sub population of critically ill patients with normal renal function , a 100 % fT > MIC target is not reached , even with 3-hour extended infusions This prospect i ve pharmacokinetic study aim ed to describe plasma and interstitial fluid ( ISF ) pharmacokinetics of piperacillin and tazobactam in critically ill patients on continuous venovenous haemodiafiltration ( CVVHDF ) . Piperacillin/tazobactam ( 4g/0.5 g ) was administered every 8h and CVVHDF was performed as a 3 - 3.5L/h exchange using a polyacrylonitrile filter with a surface area of 1.05m(2 ) . Serial blood ( pre- and post-filter ) , filtrate/dialysate , urine and ISF concentrations were measured . Subcutaneous tissue ISF concentrations were determined using microdialysis . A total of 407 sample s were collected . Median peak plasma concentrations were 210.5 ( interquartile range=161.5 - 229.0 ) and 29.4 ( 27.9 - 32.0 ) mg/L and median trough plasma concentrations were 64.3 ( 49.0 - 68.9 ) and 12.3 ( 7.7 - 13.7 ) mg/L for piperacillin and tazobactam , respectively . The plasma elimination half-life was 6.4 ( 4.6 - 8.7 ) and 7.3 ( 4.6 - 11.8 ) h , volume of distribution 0.42 ( 0.29 - 0.49 ) and 0.32 ( 0.24 - 0.36 ) L/kg , total clearance 5.1 ( 4.2 - 6.2 ) and 3.8 ( 3.3 - 4.2 ) L/h and CVVHDF clearance 2.5 ( 2.3 - 3.1 ) and 2.5 ( 2.3 - 3.2 ) L/h for piperacillin and tazobactam , respectively . The tissue penetration ratio or ratio of area under the concentration-time curve of the unbound drug in ISF to plasma ( unbound AUCISF/AUCplasma ) was ca . 1 for both piperacillin and tazobactam . This is the first report of concurrent plasma and ISF concentrations of piperacillin and tazobactam during CVVHDF . For the CVVHDF setting s used in this study , a dose of 4.5 g piperacillin/tazobactam administered evry 8h result ed in piperacillin concentrations in plasma and ISF > 32mg/L throughout most of the dosing interval ABSTRACT Respiratory tract infections cause 90 % of premature mortality in patients with cystic fibrosis ( CF ) . Treatment of Pseudomonas aeruginosa infection is often very problematic . Piperacillin-tazobactam has good activity against P. aeruginosa , but its pharmacokinetics ( PK ) in CF patients has not been compared to the PK in healthy volunteers in a controlled clinical study . Therefore , we compared the population PK and pharmacodynamics ( PD ) of piperacillin between CF patients and healthy volunteers . We studied 8 adult ( median age , 20 years ) CF patients ( average total body weight [ WT ] , 43.1 ± 7.8 kg ) and 26 healthy volunteers ( WT , 71.1 ± 11.8 kg ) who each received 4 g piperacillin as a 5-min intravenous infusion . We determined piperacillin levels by high-performance liquid chromatography , and we used NONMEM for population PK and Monte Carlo simulation . We used a target time of nonprotein-bound concentration above the MIC of 50 % , which represents near-maximal bacterial killing . Unscaled total clearance was 25 % lower , and the volume of distribution was 31 % lower in CF patients . Allometric scaling by lean body mass reduced the unexplained ( r and om ) between-subject variability in clearance by 26 % compared to the variability of linear scaling by WT . A st and ard dosage regimen of 3 g/70 kg body WT every 4 h as a 30-min infusion ( daily dose , 18 g ) achieved a robust ( ≥90 % ) probability-of-target attainment ( PTA ) for MICs of ≤12 mg/liter in CF patients and ≤16 mg/liter in healthy volunteers . Alternative modes of administration allowed a marked dose reduction to 9 g daily . Prolonged ( 4-h ) infusions of 3 g/70 kg WT every 8 h and continuous infusion ( daily dose , 9 g ) , achieved a robust PTA for MICs of ≤16 mg/liter in both groups . Piperacillin achieved PTA expectation values of 64 % and 89 % against P. aeruginosa infection in CF patients , based on susceptibility data from two German CF clinics The purpose of this study was to investigate the disposition of two aminopenicillins and their intra- and inter-individual variation in pharmacokinetic parameters in healthy , elderly volunteers . Two groups , each of 12 active , community-dwelling volunteers between 69 and 83 years of age participated . One group was given 500 mg of amoxycillin , the other group 500 mg of ampicillin as single i.v . infusions . Within the drug groups each volunteer was given the infusion at two different occasions separated by a time-period of 1 week . Amoxycillin and ampicillin were determined in plasma and urine by modern column liquid chromatographic methods . The mean plasma clearance was about 200 ml min-1 1.73 m-2 for both drugs and renal clearance accounted for approximately 80 % of this . As expected , drug clearance was correlated to renal function as determined by 51Cr-EDTA . The volume of distribution at steady-state ( Vss ) was about 0.3 l kg-1 for both drugs . Compared to our previous results in younger subjects , plasma and renal clearances were essentially similar in this study , but slightly longer half-lives and higher Vss were seen for amoxycillin and ampicillin . The intra-individual variation , expressed as the error of a single determination ( CV ) , was small , for plasma clearance 3.7 % and 6.4 % after amoxycillin and ampicillin . The corresponding inter-individual variation in clearance was higher , 14.4 % after amoxycillin , and 11.9 % after ampicillin . The results confirm a higher relative efficiency of a crossover vs a completely r and omized parallel groups design in parenteral studies of these penicillins . In our elderly subjects there was only an approximately 30 % decrease in renal function . This was not enough to reduce the drug clearance and offers an explanation for the similarity between our present results in the elderly and our previous results in younger subjects . Elderly volunteers may be different from patients with disease as a confounding factor . Studies on elderly active and community-dwelling volunteers , as in this study , may therefore be more representative as to the effect of age per se on drug kinetics A multiple-dose , open-labelled , r and omized , two period crossover human volunteer study was performed ( i ) to describe the pharmacokinetic profile and safety profile of piperacillin and tazobactam ( P/T ) administered 6.0/0.75 g and 8.0/1.0 g q12h and ( ii ) to characterize the pharmacodynamic profile of these regimens against a variety of common targeted pathogens . Blood sample s were collected after the third dose and concentrations of P/T were determined by a vali date d high-performance liquid chromatography assay . Pharmacokinetic profiles of P/T were determined by non-compartment analysis . Percentage time above the MIC ( % T > MIC ) of piperacillin was calculated for a range of MICs . In this study , no adverse events were attributed after multiple administrations of either 6.0/0.75 g or 8.0/1.0 g dose regimens . The peak concentration , half-life and area under the curve ( AUC0-(0-tau ) ) of piperacillin were significantly different by a paired t-test ( P < 0.05 ) between the two study regimens . The trough concentration , half-life and area under the curve ( AUC0-(0-tau ) ) of tazobactam were substantially different from parameters reported previously for conventional regimens . The 8.0/1.0 g regimen provided 50 % T > MIC for MICs < or = 32 mg/L , while a similar value for the 6.0/0.75 g regimen was < or = 16 mg/L. High-dose P/T regimens with extended interval were well tolerated and provide adequate dynamic exposure for a variety of susceptible pathogens A population pharmacokinetic ( PK ) model for meropenem in Japanese pediatric patients with various infectious diseases was developed based on 116 plasma concentrations from 50 pediatric patients . The population PK parameters developed in this analysis are useful for calculation of the percent time above minimum inhibitory concentration ( % T > MIC ) and for optimal dosing of meropenem in pediatric patients . After dosing at 20 mg/kg t.i.d . by 0.5-h infusion ( approved st and ard dose for pediatric patients in Japan ) , the target value of 50%T > MIC was achieved , indicating that 20 mg/kg t.i.d . by 0.5-h infusion is effective for susceptible bacteria . In contrast , for bacteria with higher MICs such as Pseudomonas aeruginosa ( MIC ≥ 2 µg/mL ) , the probability of target attainment of 50%T > MIC was 60.7 % at a dose of 40 mg/kg t.i.d . by 0.5-h infusion ( highest dose approved for pediatric patients in Japan ) . The simulations described in this article indicated that 40 mg/kg t.i.d . with a longer infusion duration ( e.g. , 4 h ) is more effective against bacteria with a MIC higher than 2 µg/mL. The predicted probability of target attainment for 50%T > MIC ( 97.0 % ) was well correlated not only to the microbiological efficacy rate ( 97.0 % ) but also to the clinical efficacy rate ( 95.9 % ) in the present phase 3 study BACKGROUND To describe the population pharmacokinetics of the piperacillin component of piperacillin/tazobactam . PROCEDURE This pharmacokinetic study included 21 pediatric ( age 3 - 10 years ) patients receiving piperacillin/tazobactam to treat fever with neutropenia . Each patient contributed 1 - 3 blood sample s for piperacillin concentration determination . Population pharmacokinetic analyses were conducted using Pmetrics software . A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment ( PTA ) for multiple dosing regimens , using 50 % of free drug time above the minimum inhibitory concentration ( MIC ) as the primary pharmacodynamic threshold . RESULTS Mean ± SD body weight was 28.5 ± 9.7 kg . Piperacillin concentration data best fit a two-compartment model with linear clearance , using total body weight as a covariate for clearance ( CLθ ) and volume of the central compartment ( Vcθ ) . Population estimates for CLθ , Vcθ , and intercompartment transfer constants were 0.204 ± 0.076 L/h/kg , 0.199 ± 0.107 L/kg , 0.897 ± 1.050 h(-1 ) , and 1.427 ± 1.609 h(-1 ) , respectively . R(2 ) , bias , and precision for the Bayesian fit were 0.998 , -0.032 , and 2.2 µg/ml , respectively . At the MIC breakpoint of 16 µg/ml for Pseudomonas aeruginosa , PTAs for 50 mg/kg q4h as a 0.5 hr infusion was 93.9 % ; for 100 mg/kg q8h as 0.5 and 4 hr infusion : 64.6 % and 100 % ; for 100 mg/kg q6h as 0.5 and 3 hr infusion : 86.5 % and 100 % ; and for 400 mg/kg continuous infusion : 100 % , respectively . CONCLUSIONS In children with fever and neutropenia , piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure The pharmacokinetics of meropenem were studied in a group of 11 surgical patients ( four male , seven female ; mean age 63 years ; mean weight 72 kg ) all of whom had moderate or severe infection and who received a mean dose of 14.5 mg/kg + /- 2.7 meropenem 8-hourly iv for a minimum of 4 days . Venous blood sample s were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy . Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model . The mean pharmacokinetic parameters ( + /- st and ard deviation ) on day 1 were T1/2 84.6 + /- 24.1 min , Vdss 0.22 + /- 0.06 L/kg , AUC 6028 + /- 1983.2 mg.min/L , Cltot 188 + /- 67 mL/min and MRT 89.1 + /- 67.8 min . On the fourth or fifth days of therapy the values were T1/2 79.9 + /- 18.2 min , Vdss 0.17 + /- 0.8 L/kg , AUC 6000.7 + /- 2417 mg.min/L , Cltot 190 + /- 60 mL/min and MRT 67.8 + /- 30.4 min . Although the T1/2 , Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant ( Student 's t-test , P > 0.05 ) . Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy . Although the T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers , they were similar to those found in elderly volunteers . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES The study aim ed to characterize the pharmacokinetics ( PK ) of four β-lactams ( piperacillin , ceftazidime , cefepime , and meropenem ) in patients comedicated with amikacin ( AMK ) , and to confirm the predictive performance of AMK data , obtained from therapeutic drug monitoring ( TDM ) , on these PK , using a population modeling approach . DESIGN AND METHODS Serum sample s were collected in 88 critically ill septic patients . For each β-lactam , the covariate model was optimized using renal function . Furthermore , predictive performance of AMK concentrations and PK parameters was assessed on β-lactam PK . RESULTS A two-compartment model with first-order elimination best fitted the β-lactam data . Results supported the superiority of AMK concentrations , over renal function and AMK PK parameters , to assess the β-lactam PK . CONCLUSION The study confirmed the significant link between the exposure to AMK and to β-lactams , and presented population models able to guide β-lactam dosage adjustments using renal biomarkers or TDM-related aminoglycoside data The pharmacokinetics and serum bactericidal activities ( SBAs ) of imipenem and meropenem were investigated in a r and omized crossover study . Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem . The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography . Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique . At the end of infusion , the mean concentrations of imipenem and meropenem measured in serum were 61.2 + /- 9.8 and 51.6 + /- 6.5 mg/liter , respectively ; urinary recoveries were 48.6 % + /- 8.2 % and 60.0 % + /- 6.5 % of the dose in 12 h , respectively ; and the areas under the concentration-time curve from time zero to infinity were 96.1 + /- 14.4 and 70.5 + /- 10.3 mg.h/liter , respectively ( P < or = 0.02 ) . Imipenem had a mean half-life of 66.7 + /- 10.4 min ; that of meropenem was 64.4 + /- 6.9 min . The volumes of distribution at steady state of imipenem and meropenem were 15.3 + /- 3.3 and 18.6 + /- 3.0 liters/70 kg , respectively , and the mean renal clearances per 1.73 m2 were 85.6 + /- 17.6 and 144.6 + /- 26.0 ml/min , respectively . Both antibiotics were well tolerated in this single-dose administration study . The SBAs were measured by the microdilution method of Reller and Stratton ( L. B. Reller and C. W. Stratton , J. Infect . Dis . 136:196 - 204 , 1977 ) against 40 clinical ly isolated strains . Mean reciprocal bactericidal titers were measured 1 and 6 h after administration . After 1 and 6 h the median SBAs for imipenem and meropenem , were 409 and 34.9 and 97.9 and 5.8 , respectively , against Staphylococcus aureus , 19.9 and 4.4 and 19.4 and 4.8 , respectively , against Pseudomonas aeruginosa , 34.3 and 2.2 and 232 and 15.5 , respectively , against Enterobacter cloacae , and 13.4 and 2.25 and 90.7 and 7.9 , respectively , against Proteus mirabilis . Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination . Both carbapenems revealed high SBAs against clinical ly important pathogens at 1 h ; meropenem had a higher SBA against E. cloacae and P. mirabilis , and the SBA of imipenem against S. aureus was greater than the SBA of meropenem Meropenem , a carbapenem broad-spectrum antibiotic , is regularly used in patients undergoing continuous venovenous hemodiafiltration ( CVVHDF ) . Its disposition was studied over one dosage interval in 15 patients under CVVHDF on a steady regimen of 500 or 1000 mg every 8 to 12 hours . Meropenem levels were measured in plasma and filtrate-dialysate by high-performance liquid chromatography ( HPLC ) with UV detection . The mean CVVHDF flow rates were 7.1 + /- 0.9 L/h for blood ( mean + /- SD ) , 0.5 + /- 0.3 L/h for predilution solution , 1.2 + /- 0.3 L/h for countercurrent dialysate , and 1.8 + /- 0.5 L/h for the total filtrate-dialysate . The pharmacokinetic analysis was based both on a noncompartmental approach and on a four-compartment modeling . The mean ( coefficient of variation [ CV ] ) total body clearance , volume of distribution at steady state , and mean residence time were , respectively , 5.0 L/h ( 46 % ) , 14.3 L ( 29 % ) , and 4.8 h ( 36 % ) . The hemodiafiltration clearances calculated from plasma data alone and plasma with filtrate-dialysate data were 1.2 L/h ( 26 % ) and 1.6 L/h ( 39 % ) , respectively . The compartmental model was used to optimize the therapeutic schedule of meropenem , considering reference minimal inhibitory concentration ( MIC ) of sensitive strains ( 4 mg/L ) . The results indicate that two different therapeutic schedules of meropenem are equally applicable to patients receiving CVVHD : either 750 mg tid or 1500 bid The pharmacokinetics ( PK ) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospect i ve data ( N = 125 ) . The population PK was described by a 2‐compartment model with a priori birthweight ( BW ) based allometric scaling . Significant correlations were observed between clearance ( Cl ) and postnatal age ( PNA ) , gestational age ( GA ) , body temperature ( TEMP ) , and urine output ( UO ) . For a typical patient with GA 40 weeks , BW 3,000 g , 2 days PNA ( i.e. , TEMP 33.5 ° C ) , and normal UO , Cl was 0.26 L/h ( interindividual variability ( IIV ) 41.9 % ) and volume of distribution of the central compartment was 0.34 L/kg ( IIV of 114.6 % ) . For this patient , Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0 ° C . The respective contributions of both covariates were 23 % and 27 % . Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36–37 and 38–42 weeks , respectively CONTEXT Infection is a major cause of morbidity and mortality in intensive care units ( ICUs ) worldwide . However , relatively little information is available about the global epidemiology of such infections . OBJECTIVE To provide an up-to- date , international picture of the extent and patterns of infection in ICUs . DESIGN , SETTING , AND PATIENTS The Extended Prevalence of Infection in Intensive Care ( EPIC II ) study , a 1-day , prospect i ve , point prevalence study with follow-up conducted on May 8 , 2007 . Demographic , physiological , bacteriological , therapeutic , and outcome data were collected for 14,414 patients in 1265 participating ICUs from 75 countries on the study day . Analyses focused on the data from the 13,796 adult ( > 18 years ) patients . RESULTS On the day of the study , 7087 of 13,796 patients ( 51 % ) were considered infected ; 9084 ( 71 % ) were receiving antibiotics . The infection was of respiratory origin in 4503 ( 64 % ) , and microbiological culture results were positive in 4947 ( 70 % ) of the infected patients ; 62 % of the positive isolates were gram-negative organisms , 47 % were gram-positive , and 19 % were fungi . Patients who had longer ICU stays prior to the study day had higher rates of infection , especially infections due to resistant staphylococci , Acinetobacter , Pseudomonas species , and C and ida species . The ICU mortality rate of infected patients was more than twice that of noninfected patients ( 25 % [ 1688/6659 ] vs 11 % [ 682/6352 ] , respectively ; P < .001 ) , as was the hospital mortality rate ( 33 % [ 2201/6659 ] vs 15 % [ 942/6352 ] , respectively ; P < .001 ) ( adjusted odds ratio for risk of hospital mortality , 1.51 ; 95 % confidence interval , 1.36 - 1.68 ; P < .001 ) . CONCLUSIONS Infections are common in patients in contemporary ICUs , and risk of infection increases with duration of ICU stay . In this large cohort , infection was independently associated with an increased risk of hospital death Ceftolozane/tazobactam , a novel antibacterial with potent activity against Gram-negative pathogens , was developed for treatment of complicated urinary tract infections , including pyelonephritis , and intra-abdominal infections . A phase 1 pharmacokinetic ( PK ) study of ceftolozane/tazobactam in healthy Japanese , Chinese , and white volunteers was conducted to assess the potential effect of ethnicity on PK . The PK of ceftolozane , tazobactam , and tazobactam metabolite M1 was compared after single 1.5- and 3-g intravenous doses of ceftolozane/tazobactam . Ten Japanese , nine Chinese , and ten white subjects were enrolled , and 27 completed all doses of study medication . Dose-normalized PK parameters for ceftolozane and tazobactam were similar among Japanese , Chinese , and white subjects ( at 1.5-g and 3-g doses , ceftolozane area under the plasma concentration-time curve from zero to infinity [ AUC0-∞ ] = 166.3 , 165.9 , and 185.5 h μg/mL , respectively , and 157.7 , 158.5 , and 181.2 h μg/mL , respectively ; tazobactam AUC0-∞ = 48.5 , 43.2 , and 50.1 h μg/mL , respectively , and 47.3 , 43.7 , and 50.0 h μg/mL , respectively . The 90 % CIs of their ratio estimates were within the range 0.80 to 1.25 with the exception of AUC0-∞ for ceftolozane after the 3-g dose ( 0.79 ) . The cumulative amount of ceftolozane and tazobactam excreted in urine was similar among ethnic groups . For all groups , treatment-emergent adverse events ( AEs ) were mild ; no deaths or serious AEs were reported . The PK of ceftolozane/tazobactam was approximately dose proportional ( i.e. doubling the dose approximately doubles the exposure ) and similar among the groups . No dosage adjustment is needed for ceftolozane/tazobactam in Japanese and Chinese patients OBJECTIVES Given the high frequency of acute pulmonary exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis ( CF ) , piperacillin/tazobactam is commonly used in empirical regimens . While extended-infusion piperacillin/tazobactam has been employed as one strategy to optimize this agent 's pharmacodynamics , this approach has not been well characterized in patients with CF . The objectives of this study were to characterize the pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with CF and derive optimized piperacillin/tazobactam dosing recommendations . METHODS Six serum sample s were collected from nine adult patients with CF hospitalized for acute pulmonary exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for 4 h every 8 h. Population pharmacokinetic models were fitted to the data utilizing first-order , Michaelis-Menten ( MM ) and parallel first-order/MM clearance . Monte Carlo simulations were performed to determine the probability of target attainment ( PTA ) for regimens where free piperacillin concentrations were above the MIC for at least 50 % of the dosing interval . RESULTS The model incorporating MM clearance best described the data . Results of our simulation revealed that piperacillin/tazobactam dosed at 3 - 4 g for 30 min every 6 - 8 h led to < 90 % PTA against MIC values > 4 mg/L. More intensive prolonged infusion regimens than are commonly used in practice , such as continuous infusions or 3 h infusions every 6 h , were needed to maximize the PTA for MICs ≥ 8 mg/L. CONCLUSIONS Intensive prolonged infusion regimens are the best option to ensure optimal exposures against most susceptible isolates in adult patients with CF Continuous infusion of meropenem is a c and i date strategy for optimization of its pharmacokinetic/pharmacodynamic profile . However , plasma concentrations are difficult to predict in critically ill patients . Steady-state concentrations of meropenem were determined prospect ively during continuous infusion in 32 surgical ICU patients ( aged 21 - 85 years , body weight 55 - 125 kg , APACHE II 5 - 29 , measured creatinine clearance 22.7 - 297 mL/min ) . Urine was collected for the quantification of renal clearance of meropenem and creatinine . Cystatin C was measured as an additional marker of renal function . Population pharmacokinetic models were developed using NONMEM ( ® ) , which described total meropenem clearance and its relationship with several estimates of renal function ( measured creatinine clearance CLCR , Cockcroft-Gault formula CLCG , Hoek formula , 1/plasma creatinine , 1/plasma cystatin C ) and other patient characteristics . Any estimate of renal function improved the model performance . The strongest association of clearance was found with CLCR ( typical clearance = 11.3 L/h × [ 1 + 0.00932 × ( CLCR - 80 mL/min ) ] ) , followed by 1/plasma cystatin C ; CLCG was the least predictive covariate . Neither age , weight , nor sex was found to be significant . These models can be used to predict dosing requirements or meropenem concentrations during continuous infusion . The covariate CLCR offers the best predictive performance ; if not available , cystatin C may provide a promising alternative to plasma creatinine Meropenem is frequently prescribed in critically ill children receiving continuous renal replacement therapy ( CRRT ) . We previously used clinical trial simulations to evaluate dosing regimens of meropenem in this population and reported that a dose of 20 mg/kg every 12 hours optimizes target attainment . Meropenem pharmacokinetics were investigated in this prospect i ve , open-label study to vali date our previous in silico predictions . Seven patients received meropenem ( 13.8 - 22 mg/kg ) administered intravenously every 12 hours as part of st and ard care . A mean dose of 18.6 mg/kg of meropenem was administered , result ing in a mean peak concentration of 80.1 μg/mL. Meropenem volume of distribution was 0.35 ± 0.085 L/kg . CRRT clearance was 40.2 ± 6.6 mL/(min · 1.73 m(2 ) ) and accounted for 63.4 % of the total clearance of 74.8 ± 36.9 mL/(min · 1.73 m(2 ) ) . Simulations demonstrated that a dose of 20 mg/kg every 12 hours result ed in a time above the minimum inhibitory concentration ( % fT > MIC ) of 100 % in 5 out of 7 subjects , with a % fT > MIC of 93 % and 43 % in the remaining 2 subjects . We conclude that CRRT contributed significantly to the total clearance of meropenem . A dosing regimen of 20 mg/kg achieved good target attainment in critically ill children receiving CRRT , which is consistent with our previously published in silico predictions STUDY OBJECTIVE To evaluate the steady-state pharmacokinetic and pharmacodynamic parameters of piperacillin in morbidly obese , surgical intensive care patients . DESIGN Open-label single-center prospect i ve study . SETTING Level I trauma center and university-affiliated teaching institution . PATIENTS Nine morbidly obese ( body mass index [ BMI ] 40.0 kg/m² or higher ) hospitalized patients admitted to the trauma and surgical intensive care service who were treated with piperacillin-tazobactam between December 15 , 2010 , and April 18 , 2012 . INTERVENTION Patients received intravenous piperacillin-tazobactam 4.5 g every 6 hours , administered as a 30-minute infusion . MEASUREMENTS AND MAIN RESULTS Patients ' blood sample s were collected after the administration of the fourth , fifth , or sixth dose ( i.e. , at steady state ) . Serum piperacillin concentrations were determined by using a vali date d high-performance liquid chromatography assay ; these concentrations were used to estimate pharmacokinetic parameters , and 5000-patient Monte Carlo simulations were performed . The probability of target attainment for 50 % or higher of the dosing interval during which free ( unbound ) drug concentrations exceeded the minimum inhibitory concentration ( % fT > MIC ) of likely pathogens was calculated for piperacillin at various MICs . Patient demographic and clinical characteristics included a mean ± SD total body weight of 164 ± 50 kg , BMI of 57 ± 15.3 kg/m² , and age 57 ± 11 years , and a median Acute Physiology and Chronic Health Evaluation II score of 22 ( interquartile range 21 - 26 ) . Compared with values previously reported in other population s , the volume of distribution was increased in the study patients , and total system clearance was decreased . The net result was a mean ± SD half-life of 3.7 ± 1.2 hours compared with ~1 hour reported in other population s. This contributed to an extended % fT > MIC for likely pathogens . Results from all nine patients showed % fT > MIC of 100 % at the susceptibility breakpoint MIC of 16 mg/L and 85 % or higher at an MIC of 32 mg/L. CONCLUSION The pharmacokinetics of piperacillin is altered in morbidly obese , surgical intensive care patients . The use of st and ard-dosage piperacillin-tazobactam 4.5 g intravenously every 6 hours was shown to be an appropriate dosage for this study population |
13,919 | 30,244,206 | Evidence was concentrated in KS2 , with few evaluations in KS3 or KS4 , and evaluations had few consistent effects ; evaluations in KS3 and KS4 did not suggest effectiveness .
Evaluations did not shed light on the value of different approaches to integration | Objectives To systematic ally review evidence on the effectiveness of interventions including integration of academic and health education for reducing physical aggression and violence , and describe the content of these interventions . | A population -based r and omized intervention trial for the prevention of conduct problems ( i.e. , oppositional defiant disorder and conduct disorder ) is described . The LIFT ( Linking the Interests of Families and Teachers ) intervention was design ed for all first- and fifth- grade elementary school boys and girls and their families living in at-risk neighborhoods characterized by high rates of juvenile delinquency . The 10-week intervention strategy was carefully targeted at proximal and malleable antecedents in three social domains that were identified by a developmental model of conduct problems . From 12 elementary schools , 671 first and fifth grade rs and their families participated either in the theory-based universal preventive intervention or in a control condition . The intervention consisted of parent training , a classroom-based social skills program , a playground behavioral program , and systematic communication between teachers and parents . A multiple measure assessment strategy was used to evaluate participant satisfaction and participation , fidelity of implementation , and the immediate impacts of the program on targeted antecedents This study reports on aggressive outcomes from a cluster r and omized trial of the Promoting Alternative Thinking Strategies ( PATHS ) curriculum . Fourteen elementary schools were r and omly assigned to intervention or control condition and third grade students were followed through the fifth grade . Teacher and self-reports of student aggression , conduct problems , delinquency , acting out problems , and social information processing ( SIP ) variables were collected . Linear change for each of the SIP variables was noted with control students demonstrating increased normative beliefs about aggression , increased aggressive social problem solving , increased hostile attribution bias , and increased aggressive interpersonal negotiation strategies over time while PATHS students remained relatively stable . Teachers reported significant curvilinear change in student aggression , conduct problems , and acting out behavior problems ; all favoring PATHS students OBJECTIVE To report experimental impacts of a universal , integrated school-based intervention in social-emotional learning and literacy development on change over 1 school year in 3rd- grade children 's social-emotional , behavioral , and academic outcomes . METHOD This study employed a school-r and omized , experimental design and included 942 3rd- grade children ( 49 % boys ; 45.6 % Hispanic/Latino , 41.1 % Black/African American , 4.7 % non-Hispanic White , and 8.6 % other racial/ethnic groups , including Asian , Pacific Isl and er , Native American ) in 18 New York City public elementary schools . Data on children 's social-cognitive processes ( e.g. , hostile attribution biases ) , behavioral symptomatology ( e.g. , conduct problems ) , and literacy skills and academic achievement ( e.g. , reading achievement ) were collected in the fall and spring of 1 school year . RESULTS There were main effects of the 4Rs Program after 1 year on only 2 of the 13 outcomes examined . These include children 's self-reports of hostile attributional biases ( Cohen 's d = 0.20 ) and depression ( d = 0.24 ) . As expected based on program and developmental theory , there were impacts of the intervention for those children identified by teachers at baseline with the highest levels of aggression ( d = 0.32 - 0.59 ) on 4 other outcomes : children 's self-reports of aggressive fantasies , teacher reports of academic skills , reading achievement scaled scores , and children 's attendance . CONCLUSIONS This report of effects of the 4Rs intervention on individual children across domains of functioning after 1 school year represents an important first step in establishing a better underst and ing of what is achievable by a schoolwide intervention such as the 4Rs in its earliest stages of unfolding . The first-year impacts , combined with our knowledge of sustained and exp and ed effects after a second year , provide evidence that this intervention may be initiating positive developmental cascades both in the general population of students and among those at highest behavioral risk . ( PsycINFO Data base Record ( c ) 2010 APA , all rights reserved ) The Media Ready Program was design ed as a middle school , media literacy education , preventive intervention program to improve adolescents ' media literacy skills and reduce their intention to use alcohol or tobacco products . In a short-term efficacy trial , schools in North Carolina were r and omly assigned to conditions ( Media Ready : n = 214 ; control : n = 198 ) . Boys in the Media Ready group reported significantly less intention to use alcohol in the future than did boys in the control group . Also , students in the Media Ready group who had used tobacco in the past reported significantly less intention to use tobacco in the future than did students in the control group who had previously used tobacco . Multilevel multiple mediation analyses suggest that the set of logical analysis Message Interpretation Processing variables mediated the program 's effect on students ' intentions to use alcohol or tobacco in the future OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research Six schools were r and omly assigned to a multilevel bullying intervention or a control condition . Children in Grade s 3 - 6 ( N=1,023 ) completed pre- and posttest surveys of behaviors and beliefs and were rated by teachers . Observers coded playground behavior of a r and om sub sample ( n=544 ) . Hierarchical analyses of changes in playground behavior revealed declines in bullying and argumentative behavior among intervention-group children relative to control-group children , increases in agreeable interactions , and a trend toward reduced destructive byst and er behavior . Those in the intervention group reported enhanced byst and er responsibility , greater perceived adult responsiveness , and less acceptance of bullying/aggression than those in the control group . Self-reported aggression did not differ between the groups . Implication s for future research on the development and prevention of bullying are discussed This study examined the effects of the Positive Action ( PA ) programme in Chicago Public Schools on problem behaviours among a cohort of elementary school students from grade three through grade five . Using a matched-pair , r and omised control design with 14 elementary schools , approximately 510 fifth- grade rs self-reported lifetime substance use , serious violence-related behaviour , and current bullying and disruptive behaviours . Three-level ( i.e. students nested within schools within school pairs ) overdispersed Poisson models were used to examine programme effects on the number of items endorsed for each of the four outcomes . Findings indicated that students in the intervention endorsed 31 % fewer substance use behaviours ( incidence rate ratio [ IRR ] = 0.69 ) , 37 % fewer violence-related behaviours ( IRR = 0.63 ) and 41 % fewer bullying behaviours ( IRR = 0.59 ) , respectively , compared to students in the control schools . Reduction in reported disruptive behaviours was of a similar magnitude ( 27 % , IRR = 0.73 ) , but was not statistically significant . These results replicate findings of an earlier r and omised trial of the PA programme and extend evidence of its effectiveness to youth attending large urban school systems Study objective : The aim of this study was to determine the effect of a multilevel school based intervention on adolescents ’ emotional wellbeing and health risk behaviours . Design : School based cluster r and omised controlled trial . Students were surveyed using laptop computers , twice in the first year of intervention and annually thereafter for a further two years . Setting : Secondary schools . Participants : 2678 year 8 students ( 74 % ) participated in the first wave of data collection . Attrition across the waves was less than 3 % , 8 % , and 10 % respectively with no differential response rate between intervention and control groups at the subsequent waves ( 98 % v 96 % ; 92 % v 92 % , and 90 % v 89 % respectively ) . Main results : A comparatively consistent 3 % to 5 % risk difference was found between intervention and control students for any drinking , any and regular smoking , and friends ’ alcohol and tobacco use across the three waves of follow up . The largest effect was a reduction in the reporting of regular smoking by those in the intervention group ( OR 0.57 , 0.62 , and 0.72 at waves 2 , 3 , and 4 respectively ) . There was no significant effect of the intervention on depressive symptoms , and social and school relationships . Conclusions : While further research is required to determine fully the processes of change , this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours PURPOSE To evaluate the impact of the Second Step : Student Success Through Prevention ( SS-SSTP ) Middle School Program on reducing youth violence including peer aggression , peer victimization , homophobic name calling , and sexual violence perpetration and victimization among middle school sixth- grade students . METHODS The study design was a nested cohort ( sixth grade rs ) longitudinal study . We r and omly assigned 18 matched pairs of 36 middle schools to the SS-SSTP or control condition . Teachers implemented 15 weekly lessons of the sixth- grade curriculum that focused on social emotional learning skills , including empathy , communication , bully prevention , and problem-solving skills . All sixth grade rs ( n = 3,616 ) in intervention and control conditions completed self-report measures assessing verbal/relational bullying , physical aggression , homophobic name calling , and sexual violence victimization and perpetration before and after the implementation of the sixth- grade curriculum . RESULTS Multilevel analyses revealed significant intervention effects with regard to physical aggression . The adjusted odds ratio indicated that the intervention effect was substantial ; individuals in intervention schools were 42 % less likely to self-report physical aggression than students in control schools . We found no significant intervention effects for verbal/relational bully perpetration , peer victimization , homophobic teasing , and sexual violence . CONCLUSIONS Within a 1-year period , we noted significant reductions in self-reported physical aggression in the intervention schools . Results suggest that SS-SSTP holds promise as an efficacious prevention program to reduce physical aggression in adolescent youth We report results from a group-r and omized trial of a prevention program aim ed at preventing bullying and other aggressive behaviors . Fourth grade classrooms at 28 public elementary schools were assigned to receive selected modules of the Youth Matters prevention curriculum or to a no-treatment control condition . Cross-classified multilevel models were fitted to four waves of data collected over 2 years to test the effect of the intervention on self-reported bullying and bully victimization . No systematic change in bullying other students was observed . In a continuous outcome growth model , bully victim scale scores declined over the course of the study and the rate of decline in victimization was significantly higher in experimental schools relative to control schools . But the results from binary outcome growth models indicate no significant treatment effects on bully status or bully victim status over time . Implication s of findings for the implementation of anti-bullying strategies in urban public school setting s are discussed OBJECTIVES We sought to test the efficacy of an intervention that was design ed to promote social inclusion and commitment to education , in reducing among students health risk behaviors and improving emotional well-being . METHODS The design was a cluster-r and omized trial in 25 secondary schools in Victoria , Australia . The subjects were 8th- grade students ( aged 13 to 14 y ) in 1997 ( n=2545 ) and subsequent 8th- grade students in 1999 ( n=2586 ) and 2001 ( n=2463 ) . The main outcomes were recent substance use , antisocial behavior , initiation of sexual intercourse , and depressive symptoms . RESULTS At 4-year follow-up , the prevalence of marked health risk behaviors was approximately 20 % in schools in the comparison group and 15 % in schools in the intervention group , an overall reduction of 25 % . In ordinal logistic regression models a protective effect of intervention was found for a composite measure of health risk behaviors in unadjusted models ( odds ratio [OR]= 0.69 ; 95 % confidence interval [CI]= 0.50 , 0.95 ) and adjusted models ( OR= 0.71 ; CI = 0.52 , 0.97 ) for potential confounders . There was no evidence of a reduction in depressive symptoms . CONCLUSION The study provides support for prevention strategies in schools that move beyond health education to promoting positive social environments Improving children 's learning and development in conflict-affected countries is critically important for breaking the intergenerational transmission of violence and poverty . Yet there is currently a stunning lack of rigorous evidence as to whether and how programs to improve learning and development in conflict-affected countries actually work to bolster children 's academic learning and socioemotional development . This study tests a theory of change derived from the fields of developmental psychopathology and social ecology about how a school-based universal socioemotional learning program , the International Rescue Committee 's Learning to Read in a Healing Classroom ( LRHC ) , impacts children 's learning and development . The study was implemented in three conflict-affected provinces of the Democratic Republic of the Congo and employed a cluster-r and omized waitlist control design to estimate impact . Using multilevel structural equation modeling techniques , we found support for the central pathways in the LRHC theory of change . Specifically , we found that LRHC differentially impacted dimensions of the quality of the school and classroom environment at the end of the first year of the intervention , and that in turn these dimensions of quality were differentially associated with child academic and socioemotional outcomes . Future implication s and directions are discussed OBJECTIVES We assessed the effectiveness of a 5-year trial of a comprehensive school-based program design ed to prevent substance use , violent behaviors , and sexual activity among elementary-school students . METHODS We used a matched-pair , cluster-r and omized , controlled design , with 10 intervention schools and 10 control schools . Fifth- grade rs ( N = 1714 ) self-reported on lifetime substance use , violence , and voluntary sexual activity . Teachers of participant students reported on student ( N = 1225 ) substance use and violence . RESULTS Two-level r and om-effects count models ( with students nested within schools ) indicated that student-reported substance use ( rate ratio [ RR ] = 0.41 ; 90 % confidence interval [ CI ] = 0.25 , 0.66 ) and violence ( RR = 0.42 ; 90 % CI = 0.24 , 0.73 ) were significantly lower for students attending intervention schools . A 2-level r and om-effects binary model indicated that sexual activity was lower ( odds ratio = 0.24 ; 90 % CI = 0.08 , 0.66 ) for intervention students . Teacher reports substantiated the effects seen for student-reported data . Dose-response analyses indicated that students exposed to the program for at least 3 years had significantly lower rates of all negative behaviors . CONCLUSIONS Risk-related behaviors were substantially reduced for students who participated in the program , providing evidence that a comprehensive school-based program can have a strong beneficial effect on student behavior This study contributes to ongoing scholarship at the nexus of translational research , education reform , and the developmental and prevention sciences . It reports 2-year experimental impacts of a universal , integrated school-based intervention in social-emotional learning and literacy development on children 's social-emotional , behavioral , and academic functioning . The study employed a school-r and omized , experimental design with 1,184 children in 18 elementary schools . Children in the intervention schools showed improvements across several domains : self-reports of hostile attributional bias , aggressive interpersonal negotiation strategies , and depression , and teacher reports of attention skills , and aggressive and socially competent behavior . In addition , there were effects of the intervention on children 's math and reading achievement for those identified by teachers at baseline at highest behavioral risk . These findings are interpreted in light of developmental cascades theory and lend support to the value of universal , integrated interventions in the elementary school period for promoting children 's social-emotional and academic skills |
13,920 | 30,338,116 | The interventions showed consistently that requirements of insulin therapy , dosage , and latency to administration were improved in the exercise groups .
Less consistent results were observed for capillary blood glucose measurements ; however , both modalities and combination of modalities were effective at improving blood glucose control in already diagnosed patients and pregnant women with obesity .
Conclusion Exercising three times per week for 40 - 60 min at 65 - 75 % age-predicted heart rate maximum using cycling , walking or circuit training as a modality improved glycaemic control in GDM patients and reduced incidence of GDM in pregnant women with obesity . | Background / aim Exercise can be used as a strategy to attenuate hyperglycaemia experienced during gestational diabetes mellitus ( GDM ) .
To maximize its use for clinical management , the most effective modality should be identified .
The purpose of this review is to eluci date the most effective modality of exercise on insulin sensitivity and blood glucose control in pregnant women with or at risk of GDM . | OBJECTIVE : To investigate the effect of a supervised home-based exercise program on the recurrence and severity of gestational diabetes mellitus ( GDM ) together with other aspects of maternal health and obstetric and neonatal outcomes . METHODS : This r and omized controlled trial allocated women with a history of GDM to an exercise intervention ( 14-week supervised home-based stationary cycling program ) or to a control group ( st and ard care ) at 13±1 weeks of gestation . The primary outcome was a diagnosis of GDM . Secondary outcomes included maternal fitness , psychological well-being , and obstetric and neonatal outcomes . A sample size of 180 ( 90 in each group ) was required to attain 80 % power to detect a 40 % reduction in the incidence of GDM . RESULTS : Between June 2011 and July 2014 , 205 women provided written consent and completed baseline assessment s. Of these , 33 ( 16 % ) were subsequently excluded as a result of an elevated baseline oral glucose tolerance test ( OGTT ) , leaving 172 r and omized to exercise ( n=85 ) or control ( n=87 ) . Three women miscarried before the assessment of outcome measures ( control=2 ; exercise=1 ) . All remaining women completed the postintervention OGTT . The recurrence rate of GDM was similar between groups ( control 40 % [ n=34 ] ; exercise 40.5 % [ n=34 ] ; P=.95 ) and the severity of GDM at diagnosis was unaffected by the exercise program with similar glucose and insulin responses to the OGTT ( glucose 2 hours post-OGTT 7.7±1.5 compared with 7.6±1.6 mmol/L ; P>.05 ) . Maternal fitness was improved by the exercise program ( P<.01 ) and psychological distress was reduced ( P=.02 ) . There were no differences in obstetric and neonatal outcomes between groups ( P>.05 ) . CONCLUSION : Supervised home-based exercise started at 14 weeks of gestation did not prevent the recurrence of GDM ; however , it was associated with important benefits for maternal fitness and psychological well-being . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , https:// clinical trials.gov , NCT01283854 Recent guidelines on exercise for weight loss and weight maintenance include resistance training as part of the exercise prescription . Yet few studies have compared the effects of similar amounts of aerobic and resistance training on body mass and fat mass in overweight adults . STRRIDE AT/RT , a r and omized trial , compared aerobic training , resistance training , and a combination of the two to determine the optimal mode of exercise for obesity reduction . Participants were 119 sedentary , overweight or obese adults who were r and omized to one of three 8-mo exercise protocol s : 1 ) RT : resistance training , 2 ) AT : aerobic training , and 3 ) AT/RT : aerobic and resistance training ( combination of AT and RT ) . Primary outcomes included total body mass , fat mass , and lean body mass . The AT and AT/RT groups reduced total body mass and fat mass more than RT ( P < 0.05 ) , but they were not different from each other . RT and AT/RT increased lean body mass more than AT ( P < 0.05 ) . While requiring double the time commitment , a program of combined AT and RT did not result in significantly more fat mass or body mass reductions over AT alone . Balancing time commitments against health benefits , it appears that AT is the optimal mode of exercise for reducing fat mass and body mass , while a program including RT is needed for increasing lean mass in middle-aged , overweight/obese individuals PURPOSE The purpose of the study was to determine the effect of a home-based cycling program for women with a recent diagnosis of gestational diabetes mellitus ( GDM ) on aerobic fitness , weight gain , self-reported mobility , attitude , and intentions toward maternal exercise , and obstetric and neonatal outcomes . METHODS Forty women ( mean ± SD , 28.8 ± 0.9-wk gestation ) were r and omized to either a supervised , home-based exercise program , combining continuous steady-state and interval cycling at various intensities , in combination with unsupervised moderate intensity aerobic activity and conventional diabetic management ( EX ; n = 20 ) or to conventional management alone ( CON ; n = 20 ) . The program began following diagnosis until week 34 of pregnancy ( mean ± SD duration of training , 6 ± 1 wk ) . RESULTS Mean compliance to the training program was 96 % . Maternal aerobic fitness , and attitude and intentions toward exercise were improved in response to the home-based exercise intervention compared with CON ( P < 0.05 ) . No differences were observed between the groups with respect to maternal weight gain or obstetric and neonatal outcomes ( P > 0.05 ) . CONCLUSION A home-based exercise program of 6 ± 1 wk in duration commenced after diagnosis of GDM can improve aerobic fitness and attitude and intentions toward exercise , with no adverse effect on maternal and neonatal pregnancy outcomes BACKGROUND Exercise may influence glucose metabolism during pregnancy . We examined the effect of exercise intensity and duration on capillary glucose responses in pregnant women at low and high risk for gestational diabetes mellitus ( GDM ) who followed a modified GDM meal plan . METHODS R and omization occurred at study entry ( 16 - 20 weeks ' gestation ) into a low-intensity [ 30 % heart rate reserve , low risk-30%I , n = 12 ; high risk-30%I , n = 11 ] or vigorous-intensity ( 70 % heart rate reserve , low risk-70%I , n = 12 ; R-70%I , n = 11 ) exercise program with similar nutritional control . Exercise consisted of walking three to four times a week , gradually increasing time from 25 to 40 min/session . Free-living capillary glucose concentrations were measured once a week pre-exercise and post-exercise . RESULTS Capillary glucose responses to exercise were strongly influenced by an interaction between GDM risk , exercise duration and exercise intensity ( p = 0.006 ) . Decreases in glucose concentrations were observed after 25 ( 4 ± 13 % ) , 35 ( 21 ± 12 % ) and 40 min ( 15 ± 18 % ) of walking in high risk-30%I women , with the most noticeable decline after 35 and 40 min . In the high risk-70%I , glucose concentrations decreased significantly only after 25 ( 22 ± 14 % ) and 35 min ( 7 ± 23 % ) and increasing the exercise time attenuated glucose concentrations decline . In low risk women , regardless of exercise intensity and duration , decreases in glucose concentrations were significant and similar . CONCLUSION To achieve the best decline in glucose concentrations , pregnant women who follow a modified GDM meal plan should walk for 25 min/session at vigorous intensity or for 35 - 40 min/session at low intensity if they are at risk for GDM and for at least 25 min at either low or vigorous intensity if they are at low risk for GDM Objective To examine the effectiveness of a partially homebased , moderate-intensity aerobic exercise program for women with gestational diabetes . Methods This was a r and omized experimental design . Thirty-three women with gestational diabetes were r and omly assigned to the exercise or the no-exercise group . Subjects underwent hemoglobin A1C assay and submaximal cycle ergometer fitness tests at baseline and at study conclusion . Subjects kept diaries of home fasting and 2-hour postpr and ial blood glucose determinations . Exercise subjects were asked to exercise for 30 minutes three to four times weekly at 70 % of estimated maximal heart rate for the weeks of study participation . Two exercise sessions weekly were supervised by the investigator , and two were unsupervised at home . Control-group subjects were asked to maintain their current activity level . Results Daily fasting and postpr and ial blood glucose levels , hemoglobin A1C , incidence of exogenous insulin therapy , and incidence of newborn hypoglycemia were not different between the groups . There was a training effect in the exercise group ( P = .005 ) but not in the control group ( P = .25 ) . A significant decline in daily grams of carbohydrate consumed was observed in the control group ( P = .03 ) , but not in the exercise group ( P = .97 ) . No complications were found in the subjects who exercised . Conclusions A partially home-based exercise program did not reduce blood glucose levels , but did result in a modest increase in cardiorespiratory fitness . The intervention appeared safe OBJECTIVE Available insulin sensitivity ( IS ) methods based on the oral glucose tolerance test ( OGTT ) are empirical . We used a glucose-insulin model to derive an OGTT-based IS ( oral glucose insulin sensitivity [ OGIS ] ) index , which predicts glucose clearance in a glucose clamp . We vali date d OGIS against clamp data . RESEARCH DESIGN AND METHODS OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0 , 2 , and 3 h ( 3-h OGTT ) or at 0 , 1.5 , and 2 h ( 2-h OGTT ) . The formula includes six constants optimized to match the clamp results . For this purpose , 15 lean nondiabetic subjects ( BMI < 25 kg/m2 ) , 38 obese nondiabetic subjects ( BMI > 25 kg/m2 ) , and 38 subjects with type 2 diabetes r and omly underwent an OGTT and a 120 mU x min(-1 ) x m(-2 ) insulin infusion euglycemic clamp . Glucose clearance ( Cl CLAMP ) , calculated as the ratio of glucose infusion to concentration during the last hour of the clamp , was compared with OGIS . OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance ( IGT ) . RESULTS OGIS and Cl CLAMP were correlated in the whole group ( R = 0.77 , P < 0.0001 ) , in the subgroups ( lean : R = 0.59 ; obese : R = 0.73 ; type 2 diabetes : R = 0.49 ; P < 0.02 ) , and in the independent IGT group ( R = 0.65 , P < 0.02 ) . Reproducibility of OGIS and Cl CLAMP were similar ( coefficients of variation : OGIS 7.1 % , Cl CLAMP 6.4 % ) . OGIS was as effective as Cl CLAMP in discriminating between groups ( for OGIS , lean vs. obese : 440 + /- 16 vs. 362 + /- 11 ml x min(-1 ) x m(-2 ) , p < 0.001 ; lean vs. type 2 diabetes : 440 + /- 16 vs. 239 + /- 7 , P < 0.0001 ; obese vs. type 2 diabetes : 362 + /- 11 vs. 239 + /- 7 , P < 0.0001 ; results were similar for Cl CLAMP ) . The relationships between IS and BMI , fasting plasma insulin , and insulin secretion ( calculated from the OGTT insulin concentration ) were examined . OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles . The performance of the index for the 3-h and 2-h OGTT was similar . CONCLUSIONS OGIS is an index of IS in good agreement with the clamp . Because of its simplicity ( only three blood sample s required ) , this method has potential use for clinical investigation including large-scale epidemiological studies AIM The significant deterioration of insulin sensitivity and glucose tolerance during pregnancy can have serious health implication s for both the pregnant woman and her baby . Although it is well established that regular exercise benefits insulin sensitivity in the nonpregnant population , the effect on glucose tolerance in obese pregnant women is not known . The purpose of this study was to investigate the effect of a supervised 10-week , home-based , exercise programme , beginning at week 18 of gestation , on glucose tolerance and aerobic fitness in previously sedentary obese women . METHODS Twelve sedentary obese women were r and omized into an exercise ( EX ; n=6 ) or control ( CON ; n=6 ) group at 18 weeks of gestation . Those r and omized to EX engaged in 10 weeks of supervised home-based exercise ( three sessions a week of stationary cycling ) , while those in the CON group maintained their usual daily activity . Their glucose and insulin responses to an oral glucose tolerance test ( OGTT ) , as well as their aerobic fitness , were assessed both pre- and postintervention . RESULTS Reduced glucose tolerance in the CON , but not EX , group was indicated by a tendency postintervention towards higher blood glucose levels at 1h of the OGTT ( P=0.072 ) . Furthermore , at 2h of the postintervention OGTT , blood glucose tended to remain elevated from baseline in the CON ( P=0.077 ) . There was also a trend towards increased fitness in the EX ( P=0.064 ) , but not the CON group . CONCLUSION Regular aerobic exercise begun during pregnancy may have favourable effects on glucose tolerance and fitness in obese women , and warrants further investigation in a larger sample population Background The effectiveness of exercise training for preventing excessive gestational weight gain ( GWG ) and gestational diabetes mellitus ( GDM ) is still uncertain . As maternal obesity is associated with both GWG and GDM , there is a special need to assess whether prenatal exercise training programs provided to obese women reduce the risk of adverse pregnancy outcomes . Our primary aim was to assess whether regular supervised exercise training in pregnancy could reduce GWG in women with prepregnancy overweight/obesity . Secondary aims were to examine the effects of exercise in pregnancy on 30 outcomes including GDM incidence , blood pressure , blood measurements , skinfold thickness , and body composition . Methods and Findings This was a single-center study where we r and omized ( 1:1 ) 91 pregnant women with a prepregnancy body mass index ( BMI ) ≥ 28 kg/m2 to exercise training ( n = 46 ) or control ( st and ard maternity care ) ( n = 45 ) . Assessment s were done at baseline ( pregnancy week 12–18 ) and in late pregnancy ( week 34–37 ) , as well as at delivery . The exercise group was offered thrice weekly supervised sessions of 35 min of moderate intensity endurance exercise and 25 min of strength training . Seventeen women were lost to follow-up ( eight in the exercise group and nine in the control group ) . Our primary endpoint was GWG from baseline testing to delivery . The principal analyses were done as intention-to-treat analyses , with supplementary per protocol analyses where we assessed outcomes in the women who adhered to the exercise program ( n = 19 ) compared to the control group . Mean GWG from baseline to delivery was 10.5 kg in the exercise group and 9.2 kg in the control group , with a mean difference of 0.92 kg ( 95 % CI −1.35 , 3.18 ; p = 0.43 ) . Among the 30 secondary outcomes in late pregnancy , an apparent reduction was recorded in the incidence of GDM ( 2009 WHO definition ) in the exercise group ( 2 cases ; 6.1 % ) compared to the control group ( 9 cases ; 27.3 % ) , with an odds ratio of 0.1 ( 95 % CI 0.02 , 0.95 ; p = 0.04 ) . Systolic blood pressure was significantly lower in the exercise group ( mean 120.4 mm Hg ) compared to the control group ( mean 128.1 mm Hg ) , with a mean difference of −7.73 mm Hg ( 95 % CI −13.23 , −2.22 ; p = 0.006 ) . No significant between-group differences were seen in diastolic blood pressure , blood measurements , skinfold thickness , or body composition in late pregnancy . In per protocol analyses , late pregnancy systolic blood pressure was 115.7 ( 95 % CI 110.0 , 121.5 ) mm Hg in the exercise group ( significant between-group difference , p = 0.001 ) , and diastolic blood pressure was 75.1 ( 95 % CI 71.6 , 78.7 ) mm Hg ( significant between-group difference , p = 0.02 ) . We had planned to recruit 150 women into the trial ; hence , under-recruitment represents a major limitation of our results . Another limitation to our study was the low adherence to the exercise program , with only 50 % of the women included in the intention-to-treat analysis adhering as described in the study protocol . Conclusions In this trial we did not observe a reduction in GWG among overweight/obese women who received a supervised exercise training program during their pregnancy . The incidence of GDM in late pregnancy seemed to be lower in the women r and omized to exercise training than in the women receiving st and ard maternity care only . Systolic blood pressure in late pregnancy was also apparently lower in the exercise group than in the control group . These results indicate that supervised exercise training might be beneficial as a part of st and ard pregnancy care for overweight/obese women . Trial Registration Clinical Trials.gov The ten- to 16-year predictive value of body weight for diabetes mellitus was evaluated prospect ively in two groups of women with initially normal results of glucose tolerance tests . The incidence of diabetes in 602 high-risk ( previous transient gestational glucose intolerance ) participants was significantly higher for overweight subjects ( 46.7 % ) than for those of normal weight ( 25.6 % ) . In 328 concurrently selected negative control subjects ( without previous intolerance ) , the difference was not significant ( 4.5 % v 1.9 % ) . Another definition of diabetes , indicating further deterioration , gave similar results , although high-risk overweight women had disproportionately higher incidence rates . Being overweight had no substantial predictive value for diabetes mellitus during this period unless the additional evidence for a high-risk classification was present . Among such persons at high risk , excess weight also predicted the severity of the subsequent diabetic condition BACKGROUND : Obesity and being overweight are becoming epidemic , and indeed , the proportion of such women of reproductive age has increased in recent times . Being overweight or obese prior to pregnancy is a risk factor for gestational diabetes mellitus , and increases the risk of adverse pregnancy outcome for both mothers and their offspring . Furthermore , the combination of gestational diabetes mellitus with obesity/overweight status may increase the risk of adverse pregnancy outcome attributable to either factor alone . Regular exercise has the potential to reduce the risk of developing gestational diabetes mellitus and can be used during pregnancy ; however , its efficacy remain controversial . At present , most exercise training interventions are implemented on Caucasian women and in the second trimester , and there is a paucity of studies focusing on overweight/obese pregnant women . OBJECTIVE : We sought to test the efficacy of regular exercise in early pregnancy to prevent gestational diabetes mellitus in Chinese overweight/obese pregnant women . STUDY DESIGN : This was a prospect i ve r and omized clinical trial in which nonsmoking women age > 18 years with a singleton pregnancy who met the criteria for overweight/obese status ( body mass index 24≤28 kg/m2 ) and had an uncomplicated pregnancy at < 12 + 6 weeks of gestation were r and omly allocated to either exercise or a control group . Patients did not have contraindications to physical activity . Patients allocated to the exercise group were assigned to exercise 3 times per week ( at least 30 min/session with a rating of perceived exertion between 12‐14 ) via a cycling program begun within 3 days of r and omization until 37 weeks of gestation . Those in the control group continued their usual daily activities . Both groups received st and ard prenatal care , albeit without special dietary recommendations . The primary outcome was incidence of gestational diabetes mellitus . RESULTS : From December 2014 through July 2016 , 300 singleton women at 10 weeks ’ gestational age and with a mean prepregnancy body mass index of 26.78 ± 2.75 kg/m2 were recruited . They were r and omized into an exercise group ( n = 150 ) or a control group ( n = 150 ) . In all , 39 ( 26.0 % ) and 38 ( 25.3 % ) participants were obese in each group , respectively . Women r and omized to the exercise group had a significantly lower incidence of gestational diabetes mellitus ( 22.0 % vs 40.6 % ; P < .001 ) . These women also had significantly less gestational weight gain by 25 gestational weeks ( 4.08 ± 3.02 vs 5.92 ± 2.58 kg ; P < .001 ) and at the end of pregnancy ( 8.38 ± 3.65 vs 10.47 ± 3.33 kg ; P < .001 ) , and reduced insulin resistance levels ( 2.92 ± 1.27 vs 3.38 ± 2.00 ; P = .033 ) at 25 gestational weeks . Other secondary outcomes , including gestational weight gain between 25‐36 gestational weeks ( 4.55 ± 2.06 vs 4.59 ± 2.31 kg ; P = .9 ) , insulin resistance levels at 36 gestational weeks ( 3.56 ± 1.89 vs 4.07 ± 2.33 ; P = .1 ) , hypertensive disorders of pregnancy ( 17.0 % vs 19.3 % ; odds ratio , 0.854 ; 95 % confidence interval , 0.434–2.683 ; P = .6 ) , cesarean delivery ( except for scar uterus ) ( 29.5 % vs 32.5 % ; odds ratio , 0.869 ; 95 % confidence interval , 0.494–1.529 ; P = .6 ) , mean gestational age at birth ( 39.02 ± 1.29 vs 38.89 ± 1.37 weeks ’ gestation ; P = .5 ) ; preterm birth ( 2.7 % vs 4.4 % , odds ratio , 0.600 ; 95 % confidence interval , 0.140–2.573 ; P = .5 ) , macrosomia ( defined as birthweight > 4000 g ) ( 6.3 % vs 9.6 % ; odds ratio , 0.624 ; 95 % confidence interval , 0.233–1.673 ; P = .3 ) , and large‐for‐gestational‐age infants ( 14.3 % vs 22.8 % ; odds ratio , 0.564 ; 95 % confidence interval , 0.284–1.121 ; P = .1 ) were also lower in the exercise group compared to the control group , but without significant difference . However , infants born to women following the exercise intervention had a significantly lower birthweight compared with those born to women allocated to the control group ( 3345.27 ± 397.07 vs 3457.46 ± 446.00 g ; P = .049 ) . CONCLUSION : Cycling exercise initiated early in pregnancy and performed at least 30 minutes , 3 times per week , is associated with a significant reduction in the frequency of gestational diabetes mellitus in overweight/obese pregnant women . And this effect is very relevant to that exercise at the beginning of pregnancy decreases the gestational weight gain before the mid‐second trimester . Furthermore , there was no evidence that the exercise prescribed in this study increased the risk of preterm birth or reduced the mean gestational age at birth OBJECTIVE This study examines the effects of circuit-type resistance training on the need for insulin in women with gestational diabetes mellitus . STUDY DESIGN Thirty-two patients with gestational diabetes mellitus were r and omly assigned either to a group that was treated with diet alone or to a group that was treated with diet plus resistance exercise . RESULTS The number of women whose condition required insulin therapy was the same , regardless of treatment . However , a subgroup analysis that examined only overweight women ( prepregnant body mass index , > 25 kg/m(2 ) ) showed a lower incidence of insulin use in the diet-plus-exercise group ( P<.05 ) . Women in the diet-plus-exercise group were prescribed less insulin ( P<.05 ) and showed a longer delay from diagnosis to the initiation of insulin therapy ( P<.05 ) , compared with the diet-alone group . CONCLUSION Resistance exercise training may help to avoid insulin therapy for overweight women with gestational diabetes mellitus PURPOSE Regular maternal exercise may play an important role in the management of gestational diabetes mellitus ( GDM ) , yet specific exercise guidelines to achieve glycemic control have not been established . Furthermore , many women remain sedentary during pregnancy because of perceived barriers to exercise participation . This study examined the effectiveness of a home-based cycling program commenced upon diagnosis of GDM on daily fasting and postpr and ial blood glucose levels , glycosylated hemoglobin ( HbA1c ) , and the response of glucose and insulin to a 75-g oral glucose load . METHODS Forty sedentary women ( 28.8 ± 0.9 wk of gestation ) were r and omized to either home-based exercise training in combination with conventional management ( EX , n = 20 ) or to conventional management alone ( CON , n = 20 ) until week 34 of pregnancy . RESULTS Mean compliance to the supervised exercise training was 96 % , and no adverse effects were reported . Capillary glucose concentration was acutely reduced in response to each cycling session ( 6.3 ± 0.8 mM to 4.9 ± 0.7 mM , P < 0.001 ) . Overall , the EX group had lower mean daily postpr and ial glucose concentrations throughout the intervention compared with that in the CON group ( P < 0.05 ) despite consuming a greater proportion of dietary carbohydrate ( P < 0.05 ) . No differences were observed between groups with respect to HbA1c or the glucose and insulin response to oral glucose ingestion postintervention ( P > 0.05 ) . CONCLUSIONS A home-based cycling program may help to maintain daily postpr and ial normoglycemia in women with diet-controlled GDM OBJECTIVE To evaluate the influence of a twice-weekly progressive resistance training ( PRT ) program , without a concomitant weight loss diet , on abdominal fat and insulin sensitivity in older men with type 2 diabetes . RESEARCH DESIGN AND METHODS Nine older men ( aged 66.6 + /- 3.1 ) with type 2 diabetes participated in a 16-week PRT supervised program ( 50 - 80 % of the one repetition maximum ) , for all main muscle groups . Basal glycemia , HbA(1c ) , diet , habitual physical activity , body composition , and upper/lower maximal strength were measured . Insulin sensitivity was determined according to Bergman 's minimal model procedure and abdominal fat was obtained by computed tomography . The measurements were taken 4 weeks before training ( -4 ) , immediately before training ( 0 ) , and at 8-week intervals ( i.e. , weeks 8 and 16 ) during the 16-week training period . RESULTS No significant variation was observed in any of the above selected parameters during the 4-week control period . After PRT , both leg and arm maximal strength increased significantly by 17.1 and 18.2 % , respectively . Visceral and subcutaneous abdominal fat decreased significantly by 10.3 % ( from 249.5 + /- 97.9 to 225.6 + /- 96.6 cm(3 ) , P < 0.01 ) and by 11.2 % ( from 356.0 + /- 127.5 to 308.6 + /- 118.8 cm(3 ) , P < 0.01 ) , respectively , while no changes were observed in body mass . PRT significantly increased insulin sensitivity by 46.3 % ( from 2.0 + /- 1.2 to 2.8 + /- 1.6 . 10(4 ) . min(-1 ) . muU(-1 ) . ml(-1 ) , P < 0.01 ) , whereas it significantly decreased ( -7.1 % , P < 0.05 ) fasting blood glucose ( from 146.6 + /- 28.3 to 135.0 + /- 29.3 mg/dl ) . Finally , a 15.5 % increase in energy intake ( from 2,287.1 + /- 354.7 to 2,619.0 + /- 472.1 kcal/day , P < 0.05 ) was observed . CONCLUSIONS Two sessions per week of PRT , without a concomitant weight loss diet , significantly improves insulin sensitivity and fasting glycemia and decreases abdominal fat in older men with type 2 diabetes OBJECTIVE The objective of the study was to evaluate the effect of a resistance exercise program with an elastic b and on insulin requirement and glycemic control in patients with gestational diabetes mellitus ( GDM ) . STUDY DESIGN Sixty-four patients with gestational diabetes mellitus were r and omly assigned into 2 groups : an exercise group ( EG ; n = 32 ) and a control group not su bmi tted to the exercise program ( CG ; n = 32 ) . RESULTS A significant reduction in the number of patients who required insulin was observed in the EG ( 7/32 ) compared with the CG group ( 18/32 ) ( P = .005 ) . The percentage of time spent within the proposed target glucose range ( of at least 80 % of weekly measurements below the limits preestablished for the disease ) was significantly higher in EG compared with the CG group ( EG = 0.63 ± 0.30 ; CG = 0.41 ± 0.31 ; P = .006 ) . CONCLUSION The resistance exercise program was effective in reducing the number of patients with GDM who required insulin and in improving capillary glycemic control in this population Exercise prescriptions that can be translated into clinical recommendations are clearly needed for women with gestational diabetes mellitus ( GDM ) . A pilot project was developed to document the effectiveness of a structured low-intensity walking protocol on capillary glucose control in GDM women . Ten GDM women followed conventional management of diet and insulin therapy , plus a low-intensity walking program ( W ) from diagnosis to delivery . Capillary glucose concentrations , insulin requirements , and pregnancy outcomes were compared with a matched cohort by body mass index ( BMI ) , age , and insulin usage ( 20 GDM women who followed conventional management alone ( C ) ) . Baseline capillary glucose concentrations were not significantly different between the W and C groups . The W group had an average acute drop in capillary glucose concentration from pre- to post-exercise of 2.0 mmol x L(-1 ) . In addition , the W group had significantly lower mean glucose concentrations in the fasted state and 1 h after meals than the C group in the week prior to delivery . These lower glucose concentrations were achieved while requiring fewer units of insulin per day ( C , 0.50 + /- 0.37 U x kg(-1 ) ; W , 0.16 + /- 0.13 U x kg(-1 ) ; p < 0.05 ) , injected less frequently . These results suggest an effective role in glucose regulation for this structured walking program PROBLEM Gestational diabetes mellitus , defined as any carbohydrate intolerance first diagnosed during pregnancy , is associated with a variety of adverse outcomes , both for the mother and her child . AIM To investigate the impact of a structured exercise programme which consisted of aerobic and resistance exercises on the parameters of glycaemic control and other health-related outcomes in pregnant women diagnosed with gestational diabetes mellitus . METHODS Thirty-eight pregnant women diagnosed with gestational diabetes mellitus were r and omised to two groups . Experimental group was treated with st and ard antenatal care for gestational diabetes mellitus , and regular supervised exercise programme plus daily brisk walks of at least 30min . Control group received only st and ard antenatal care for gestational diabetes mellitus . The exercise programme was started from the time of diagnosis of diabetes until birth . It was performed two times per week and sessions lasted 50 - 55min . FINDINGS The experimental group had lower postpr and ial glucose levels at the end of pregnancy ( P<0.001 ) . There was no significant difference between groups in the level of fasting glucose at the end of pregnancy . Also , there were no significant differences in the rate of complications during pregnancy and birth , need for pharmacological therapy , maternal body mass and body fat percentage gains during pregnancy , and neonatal Apgar scores , body mass and ponderal index . Neonatal body mass index was higher in the experimental group ( P=0.035 ) . CONCLUSION The structured exercise programme had a beneficial effect on postpr and ial glucose levels at the end of pregnancy OBJECTIVE To examine the feasibility of an individualized exercise program to prevent gestational diabetes mellitus ( GDM ) in obese pregnant women . RESEARCH DESIGN AND METHODS The study was a pilot r and omized controlled trial with obese pregnant women ( intervention group , individualized exercise program [ n = 25 ] ; control group , usual care [ n = 25 ] ) . Average weekly energy expenditure ( MET hours per week and kilocalories per week ) of exercise-specific activity was assessed during pregnancy using the Pregnancy Physical Activity Question naire . Fasting glucose and insulin and homeostasis model assessment of insulin resistance ( HOMA-IR ) were assessed at baseline and 20 , 28 , and 36 weeks ' gestation . RESULTS Of the women in the intervention group , 16 of 22 ( 73 % ) achieved more than 900 kcal/week of exercise-based activity at 28 weeks compared with 8 of 19 women in the control group ( 42 % ) , P = 0.047 . However , insulin resistance ( HOMA-IR ) did not differ between the groups . CONCLUSION This intervention was feasible and prompted a modest increase in physical activity . However , we are not confident that this intervention would be sufficient to prevent GDM CONTEXT Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus ; however , the contributions of peripheral and hepatic tissues to these improvements are not known . OBJECTIVE Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions . DESIGN Subjects were r and omly assigned to one of two groups . The energy balance group consumed an isocaloric diet consisting of 50 % carbohydrate , 30 % fat , and 20 % protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70 % of maximum oxygen consumption maximum during the second 7 d of the 15-d study period . Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study . SETTING The study was performed at Ohio State University 's General Clinical Research Center . PARTICIPANTS There were 18 obese , mildly diabetic humans included in the study . INTERVENTION Aerobic exercise training was performed for 7 d. MAIN OUTCOME MEASURES Whole-body , peripheral , and hepatic insulin sensitivity were measured . RESULTS Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin . Likewise , it did not alter endogenous glucose production during high-dose insulin . However , 1-wk of exercise training increased both whole-body ( P<0.05 ) and peripheral insulin sensitivity ( P<0.0001 ) during high-dose insulin . CONCLUSION Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral , not heptic insulin sensitivity Aims Gestational diabetes mellitus ( GDM ) is associated with adverse maternal and fetal outcome . Screening for GDM is therefore recommended but the best screening method remains controversial . This prospect i ve , r and omized study compared a risk factor‐based screening programme with a universally based one Colado , JC and Triplett , NT . Effects of a short-term resistance program using elastic b and s versus weight machines for sedentary middle-aged women . J Strength Cond Res 22(5 ) : 1441 - 1448 , 2008-This study was design ed to determine whether different effects on functional capacity and body composition were produced by using different devices ( elastic b and s ( EBs ) versus weight machines ( WMs ) ) with the same resistance training program . Forty-five healthy sedentary middle-aged women volunteers were chosen and r and omly assigned to 1 of 3 groups : 21 subjects trained using EBs ( EBG ) , 14 in trained using WMs ( WMG ) , and 10 were controls ( CG ) . Both exercise groups trained with a periodized muscular endurance program twice a week for 10 weeks , with a total of 6 exercises per session for the major muscle groups . Exercise intensity was equalized by jointly monitoring the same targeted number of repetitions ( TNRs ) and rate of perceived exertion in active muscles ( RPE-AM ) . Functional capacity was assessed by using knee push-up ( KPU ) and 60-second squat ( S ) tests . Body composition was measured using an 8-polar bioelectrical impedance analyzer . The results for both the EBG and WMG show a decrease in fat mass ( p = 0.05 and p < 0.01 , respectively ) and an increase in both the fat-free mass ( p < 0.05 and p < 0.01 , respectively ) and the number of repetitions in the KPU ( p < 0.05 and p < 0.01 , respectively ) and S tests ( p < 0.01 in both ) . None of the variables measured for the CG varied significantly . It can be concluded that , independently of the device used , the combined monitoring of TNRs and RPE-AM can be a valid tool for controlling the resistance exercise intensity and can lead to healthy adaptations . EBs can thus offer significant physiological benefits that are comparable to those obtained from WMs in the early phase of strength training of sedentary middle-aged women Please cite this paper as : Oostdam N , van Poppel M , Wouters M , Eekhoff E , Bekedam D , Kuchenbecker W , Quartero H , Heres M , van Mechelen W. No effect of the FitFor2 exercise programme on blood glucose , insulin sensitivity , and birthweight in pregnant women who were overweight and at risk for gestational diabetes : results of a r and omised controlled trial . BJOG 2012;119:1098–1107 Lipid accumulation in muscle is associated with diminished insulin sensitivity . It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 ( RBP4 ) , which is linked to adipose tissue and insulin sensitivity in diabetics . Forty-four women with type 2 diabetes were r and omly assigned to three groups for a period of 12 weeks : control ( asked to maintain a sedentary lifestyle ) ; resistance exercise ( elastic b and exercise at moderate intensity five times per week ) ; and aerobic exercise ( walking for 60 min at moderate intensity five times per week ) . Subcutaneous ( SCAT ) , subfascial ( SFAT ) and intramuscular ( IMAT ) adipose tissues at mid-thigh level were assessed using computed tomography , and RBP4 level and insulin sensitivity ( fractional disappearance rate of insulin , k ITT ) were assessed before and after intervention . Changes in SCAT , SFAT , IMAT , RBP4 and k ITT were similar among the three groups . Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups , but RBP4 decreased significantly only with resistance exercise . Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity |
13,921 | 31,151,198 | Most of the selected studies showed a significant correlation between biofeedback usage and reduction of masticatory muscle activity .
By analyzing qualified studies , it can be concluded that biofeedback can be an effective tool in masticatory muscle activity management | Temporom and ibular disorders ( TMD ) have multifactorial and complex etiology .
Regardless of their etiology , all those conditions may result in central ly mediated chronic muscle pain , myalgia , myofascial pain , myofibrotic contracture , myosistis , myospasm , headache and a variety of neck , shoulder , upper back and lower back pain .
Biofeedback ( BF ) is one of methods that has been used for more than 50 years in rehabilitation to facilitate normal movement patterns after injuries .
Some studies suggest that biofeedback may be an effective treatment option for patients with different muscle disorders .
The aim of this study was to evaluate the efficiency of biofeedback in masticatory muscle activity management in the light of current medical literature . | Objective The aim of this exploratory study was to investigate changes in pain , disability , and muscle activation patterns in patients with chronic whiplash-associated disorder ( WAD ) after 4 weeks of myofeedback training . Methods Eleven WAD patients received ambulatory myofeedback training , during which upper trapezius muscle activation and relaxation were continuously recorded and processed for 4 weeks . Feedback was provided when muscle relaxation was insufficient . Pain in neck , shoulders , and upper back ( Visual Analogue Scale ) , disability ( Neck Disability Index ) , and muscle activation patterns during rest , typing , and stress tasks ( surface electromyography ) were assessed before and after the 4 weeks of training . Results Pain intensity decreased after 4 weeks of training . Clinical ly relevant changes were found with regard to pain in the neck and upper back region ( 55 % of the patients ) , right shoulder ( 64 % ) , and left shoulder ( 18 % ) . A trend for decreased disability was found which was clinical ly relevant in 36 % of the patients . A remarkable reduction was found in the Neck Disability Index items concerning headache and lifting weights . Overall , muscle activation was lower and muscle relaxation was higher after the training period with the largest differences during rest . Clinical ly relevant changes in surface electromyography parameters were found in a minority of patients . Conclusion Four weeks of ambulant training may be beneficial in reducing pain and disability levels and normalizing muscle activation patterns in chronic WAD patients . A r and omized-controlled study is recommended to further explore the effects of myofeedback training PURPOSE Although daytime clenching is believed to be one of the oral parafunctions leading to dental problems , a treatment strategy has not yet been devised . Electromyogram ( EMG ) biofeedback training was performed to ascertain its effect on the regulation of daytime clenching behavior . MATERIAL S AND METHODS Twenty subjects ( mean age , 30.9±5.6 years ) who had mild to moderate masticatory muscle pain with daytime clenching behavior were r and omly divided into either a biofeedback group ( BF ) or control group ( CO ) . Subjects were fitted with a hearing-aid-shaped EMG recording and biofeedback apparatus which was used to record EMG data under natural conditions from the temporal muscle , continuously for five hours on four consecutive days . EMG data on Days 1 and 4 were recorded without biofeedback as pre-test and post-test , respectively , and on Days 2 and 3 , subjects in the BF group noticed their clenching behaviors via an alert sound from the EMG biofeedback apparatus . No alert sound was given for the CO group throughout the recording sessions . RESULTS There was no significant difference in the number of clenching events for five hours between the BF group ( 4.6±2.5 ) and CO group ( 4.6±0.9 ) on Day 1 , however a significant decrease was found in the BF group between Day 1 ( 4.6±2.5 ) and Day 4 ( 2.4±1.7 ; P<0.05 ) . CONCLUSION Daytime clenching was reduced in the short-term with the help of an EMG biofeedback system under natural circumstances . Further research is needed to confirm a long-lasting effect There is emerging evidence that feedback techniques based on contingent electrical stimulation ( CES ) have an inhibitory effect on the electromyogram ( EMG ) activity of jaw-closing muscles and therefore could be useful in the management of sleep bruxism . This polysomnographic ( PSG ) study was design ed to investigate the effect of CES on PSG parameters in subjects with self-reported bruxism . Fourteen subjects underwent a full PSG investigation in the laboratory for three consecutive nights - one night of adaptation , one night without CES , and one night with CES - in a r and omized order . During all sessions the EMG activity was recorded by a portable feedback device from the temporalis muscle . An electrical pulse , which was adjusted to a moderate , but non-painful , intensity , was applied to subjects during the session with CES , if jaw-muscle activity was detected . The total sleep time , the number of micro-arousals per hour of sleep , the time spent in sleep stages 3 and 4 and in rapid eye movement ( REM ) sleep , and the number of periodic limb movements , were not influenced by CES . The number of EMG episodes per hour of sleep during the nights with and without CES was not significantly different . The present study suggests that CES at non-painful intensities does not cause major arousal responses in any of the sleep parameters assessed in this study & NA ; Temporom and ibular disorders ( TMD ) represent a group of chronic painful conditions involving the muscles of mastication and the temporom and ibular joint . Several studies have reported that TMD is associated with enhanced sensitivity to experimental pain . Twenty‐three TMD subjects and 24 pain‐free matched control subjects participated in a set of studies which were design ed to evaluate whether the temporal integrative aspects of thermal pain perception are altered in TMD patients compared with control subjects . Specifically , we have examined in both TMD patients and in age‐ and gender‐matched control subjects : ( 1 ) the time‐course and magnitude of perceived pain evoked by the application of sustained 7‐s noxious thermal stimuli ( 45–48 ° C ) to the face and forearm , ( 2 ) the central summation of C‐fiber‐mediated pain produced by applying brief trains of noxious heat pulses to the skin overlying the ventral aspect of the right palm and ( 3 ) the ability to discriminate small increments in noxious heat applied to facial and volar forearm skin . Data collected from these studies indicate that TMD patients show enhanced temporal integration of thermal pain compared with control subjects . TMD patients show greater thermal C‐fiber‐mediated temporal summation than pain‐free subjects and they report a greater magnitude of sustained noxious heat pulses applied to either the face or the forearm than control subjects . In contrast to these findings , TMD and pain‐free subjects are equally able to discriminate and detect small increments of heat applied to noxious adapting temperatures . These findings suggest that the augmented temporal integration of noxious stimuli may result from alterations in central nervous system processes which contribute to the enhanced pain sensitivity observed in TMD patients & NA ; The pathophysiological mechanisms of myofascial temporom and ibular disorders ( TMD ) are still under investigation . The hypothesis that TMD pain is caused by a generalized sensitization of higher order neurons in the nociceptive pathways combined with a decreased efficacy of endogenous inhibitory systems has recently gained support in the literature . This study was design ed to further investigate the somatosensory sensibility within and outside the craniofacial region . Twenty‐two patients fulfilled the research diagnostic criteria for TMD for myofascial pain ( Dworkin and LeResche , J Craniom and ib Disord Facial Oral Pain 6 ( 1992 ) 301 ) and 21 age‐ and sex‐matched subjects served as a control group . The somatosensory sensibility to a deep tonic input was tested by st and ardized infusions of hypertonic saline into the masseter and anterior tibialis muscle . Furthermore , pressure pain thresholds ( PPTs ) and heat pain thresholds ( HPTs ) were assessed with phasic stimuli at the same sites before and following the infusions . Myofascial TMD patients reported infusion of hypertonic saline to be more painful on 10 cm visual analogue scales ( peak pain 8.8±0.4 cm ) than control subjects ( 6.8±0.5 cm , t‐test : P=0.003 ) in the masseter but not in the anterior tibialis ( 7.4±0.5 vs. 6.6±0.5 cm , P=0.181 ) . The perceived area of experimental masseter pain measured on drawings was marginally larger in TMD patients ( 2.6±0.5 arbitrary units ( a.u . ) ) than in control subjects ( 1.4±0.2 a.u . , Mann – Whitney : P=0.048 ) but no differences were observed for the anterior tibialis ( P=0.771 ) . The PPTs were lower in the myofascial TMD patients compared to the control group , both in the masseter ( analysis of variance ( ANOVA ) : P=0.002 ) and in the anterior tibialis ( P=0.005 ) , whereas there were no significant differences in HPT ( ANOVAs : P=0.357 , P=0.101 ) . There were no significant correlations between measures of somatosensory sensibility and measures of clinical pain intensity , pain duration , grade d chronic pain scores or somatization or depression scores ( Pearson : R<0.304 , P>0.172 ) . The present study in a well‐defined group of myofascial TMD patients found that the responsiveness to both tonic and phasic deep stimuli , but not to phasic superficial inputs at the pain threshold level , in the craniofacial region was higher compared with a control group . These findings suggest that myofascial TMD pain is associated with a facilitation of stimulus‐evoked pain primarily , but not exclusively related to the painful region AIMS To determine whether an intervention reduces oromotor activity and masticatory muscle pain in myofascial temporom and ibular disorder ( M/TMD ) patients with high levels of masticatory muscle activity associated with sleep bruxism . METHODS Fourteen women with M/TMD and prior polysomnographic evidence consistent with sleep bruxism participated in a 10-week single-group pre-test/ post-test mechanistic clinical trial . A 2-week period of baseline monitoring of individually biocalibrated electromyographic ( EMG ) events associated with sleep bruxism was followed by 6 weeks of EMG-event-contingent treatment via an innocuous electrical pulse to the skin overlying the temporalis muscle . Treatment was discontinued during 2-week follow-up monitoring . Each night before sleep , subjects recorded their average daily pain . RESULTS Mixed-model analysis of variance showed a reliable reduction of EMG events during contingent stimulation treatment periods , but frequency of EMG events returned to baseline levels during follow-up ( linear term , P = .002 ; quadratic term , P = .001 ) . In contrast , nightly pain reports failed to show any systematic changes during treatment ( linear and quadratic trends , both P > .10 ) . CONCLUSION Spontaneous pain severity and nighttime oromotor activity vary independently over nights , even in M/TMD patients selected for relatively high levels of both characteristics 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 This study investigated effects of electromyographic ( EMG ) biofeedback ( BFB ) and transcutaneous electrical neuromuscular stimulation ( TENS ) on the EMG activity of the masticatory muscles and skin conductance level ( SCL ) of patients , suffering from myofacial pain syndrome . In the course of the investigation , EMG activity as well as the SCL was measured after a 20 min BFB or , respectively , after a myomonitor session in 20 patients and pre- and post-treatment values were compared . Results showed tendencies of decreased mean-EMG levels for both groups after the treatment sessions , with higher EMG values for the myomonitor group . There was no indication of a significant decrease in mean EMG levels over the sessions . Furthermore , an increase of the SCL during the period of treatment was observed for both groups in session I and II , while session III produced nearly stable values . No existing correlations for changes in SCL and EMG-activity could be established Bruxism contributes to the development of temporom and ibular disorders as well as causes dental problems . Although it is an important issue in clinical dentistry , no treatment approaches have been proven effective . This study aim ed to use electromyogram ( EMG ) biofeedback ( BF ) training to improve awake bruxism ( AB ) and examine its effect on sleep bruxism ( SB ) . Twelve male participants ( mean age , 26·8 ± 2·5 years ) with subjective symptoms of AB or a diagnosis of SB were r and omly divided into BF ( n = 7 ) and control ( CO , n = 5 ) groups to undergo 5-h daytime and night-time EMG measurements for three consecutive weeks . EMG electrodes were placed over the temporalis muscle on the habitual masticatory side . Those in the BF group underwent BF training to remind them of the occurrence of undesirable clenching activity when excessive EMG activity of certain burst duration was generated in week 2 . Then , EMGs were recorded at week 3 as the post-BF test . Those in the CO group underwent EMG measurement without any EMG BF training throughout the study period . Although the number of tonic EMG events did not show statistically significant differences among weeks 1 - 3 in the CO group , events in weeks 2 and 3 decreased significantly compared with those in week 1 , both daytime and night-time , in the BF group ( P < 0·05 , Scheffé 's test ) . This study results suggest that EMG BF to improve AB tonic EMG events can also provide an effective approach to regulate SB tonic EMG events |
13,922 | 31,662,859 | Overall , this systematic review indicates that an increase in Bifidobacterium , Staphylococcus , Enterococcus , Lactobacillus , Pseudomonas , Klebsiella and Proteus genera , as well as a decrease in Faecalibacterium , Roseburia genera and species belonging to Verrucomicrobia and Fusobacteria phyla are common features in IBD and CRD patients , whereas dozens of bacterial species are specific features of CRD and IBD . | Introduction Inflammatory bowel diseases ( IBDs ) and chronic rheumatic diseases ( CRDs ) are systemic chronic disorders sharing common genetic , immune and environmental factors .
About half of patients with IBD develop rheumatic ailments and microscopic intestinal inflammation is present in up to half of CRD patients .
IBD and CRD patients also share a common therapeutic armamentarium .
Disequilibrium in the complex realm of microbes ( known as dysbiosis ) that closely interact with the gut mucosal immune system has been associated with both IBD and CRD ( spondyloarthritis and rheumatoid arthritis ) .
Whether dysbiosis represents an epiphenomenon or a prodromal feature remains to be determined . | We have genotyped 14,436 nonsynonymous SNPs ( nsSNPs ) and 897 major histocompatibility complex ( MHC ) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS ) , autoimmune thyroid disease ( AITD ) , multiple sclerosis ( MS ) and breast cancer ( BC ) . Comparing these data against a common control data set derived from 1,500 r and omly selected healthy British individuals , we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis , ARTS1 and IL23R , and confirmation of the previously reported association of AITD with TSHR and FCRL3 . These findings , enabled in part by increased statistical power result ing from the expansion of the control reference group to include individuals from the other disease groups , highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major ' seronegative ' diseases OBJECTIVE To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha ( TNFalpha ) monoclonal antibody ( infliximab ) in the treatment of spondyloarthropathy ( SpA ) associated with active and inactive Crohn 's disease ( CD ) . METHODS Twenty four patients with SpA associated with active or inactive CD ( 16 active , 8 quiescent ) were treated with anti-TNFalpha monoclonal antibody ( infliximab ) with repeated infusions for a period of 12 - 18 months . The treatment aim ed at ameliorating the general musculoskeletal and spinal pain , controlling peripheral arthritis and enthesitis , decreasing the BASDAI score , modifying acute phase reactants , and reducing CD activity . RESULTS Infliximab improved both gastrointestinal ( p<0.01 ) and overall articular symptoms ( BASDAI , p<0.01 ; general musculoskeletal and spinal pain , p<0.01 ; peripheral arthritis , p<0.01 ) in patients with active CD . Additionally , infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis ( p<0.01 ) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers . Amelioration of gut and musculoskeletal involvement persisted for up to 12 months . CONCLUSION Infliximab may act on the inflammation of entheses and of periarticular structures , which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA , suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD Background The adaptive immune response in rheumatoid arthritis ( RA ) is influenced by an interaction between host genetics and environment , particularly the host microbiome . Association of the gut microbiota with various diseases has been reported , though the specific components of the microbiota that affect the host response leading to disease remain unknown . However , there is limited information on the role of gut microbiota in RA . In this study we aim ed to define a microbial and metabolite profile that could predict disease status . In addition , we aim ed to generate a humanized model of arthritis to confirm the RA-associated microbe . Methods To identify an RA biomarker profile , the 16S ribosomal DNA of fecal sample s from RA patients , first-degree relatives ( to rule out environment/ background as confounding factors ) , and r and om healthy non-RA controls were sequenced . Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link . The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis . Results Patients with RA exhibited decreased gut microbial diversity compared with controls , which correlated with disease duration and autoantibody levels . A taxon-level analysis suggested an expansion of rare taxa , Actinobacteria , with a decrease in abundant taxa in patients with RA compared with controls . Prediction models based on the r and om forests algorithm suggested that three genera , Collinsella , Eggerthella , and Faecalibacterium , segregated with RA . The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A . A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis . Conclusions These observations suggest dysbiosis in RA patients result ing from the abundance of certain rare bacterial lineages . A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression Background Patients with ankylosing spondylitis ( AS ) are at increased risk of developing inflammatory bowel disease ( IBD ) . We aim ed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD . Methods Fecal calprotectin was assessed at baseline ( n = 204 ) and at 5-year follow-up ( n = 164 ) . The patients answered question naires and underwent clinical evaluations . At baseline and at 5-year follow-up , ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg , respectively . The medical records were checked for diagnoses of IBD during the follow-up period . Results Fecal calprotectin > 50 mg/kg was found in two-thirds of the patients at both study visits . In 80 % of the patients , fecal calprotectin changed by < 200 mg/kg between the two measuring points . Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , C-reactive protein , erythrocyte sedimentation rate , and fecal calprotectin at 5-year follow-up . The use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) was associated with higher fecal calprotectin , and 3-week cessation of NSAIDs result ed in a drop of a median 116 mg/kg in fecal calprotectin . The use of tumor necrosis factor ( TNF ) blockers was associated with lower fecal calprotectin at both visits , but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up . The 5-year incidence of Crohn ’s disease ( CD ) was 1.5 % and was predicted by high fecal calprotectin . Conclusions Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits . CD developed in 1.5 % of the patients with AS , and a high fecal calprotectin was the main predictor thereof . The results support a link between inflammation in the gut and the musculoskeletal system in AS . We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD.Trial registration Clinical Trials.gov identifier : NCT00858819 . Registered 9 March 2009 . Last up date d 28 May 2015 A semi-quantitative bacteriological method was used to study faecal flora in 42 patients with Crohn 's disease , 37 with ulcerative colitis and 21 healthy controls . Faecal homogenates were plated on primary isolation plates by a technique that allowed the growth of various microbial isolates to be assessed on a visual 1(+)-5 + score . This method was first calibrated against a st and ard quantitative bacteriological technique , which confirmed the reliability and reproducibility of the results obtained by the simpler method . Patients with clinical ly active Crohn 's disease ( 22 ) had significantly higher total aerobe scores than patients with quiescent disease ( 20 ) ( p less than or equal to 0.006 ) or ulcerative colitis ( p less than or equal to 0.04 ) or normal controls ( p less than or equal to 0.02 ) . The scores of Escherichia coli were parallel to those of total aerobes . Lactobacillus and bifidobacteria scores were significantly reduced in patients with Crohn 's disease compared to those with ulcerative colitis and controls . The anaerobic flora in both Crohn 's disease and ulcerative colitis was indistinguishable from that of controls . Bacteroides vulgatus and B. fragilis were the predominant bacteroides in all groups . Patients with ulcerative colitis , regardless of disease activity , harboured faecal flora that did not differ from that of normal controls . The abnormal faecal flora in Crohn 's disease did not correlate with established clinical and laboratory indicators of disease activity Background : Although the role of microbes in disease pathogenesis is well established , data describing the variability of the vast microbiome in children diagnosed with ulcerative colitis ( UC ) are lacking . This study characterizes the gut microbiome in hospitalized children with severe UC and determines the relationship between microbiota and response to steroid therapy . Methods : Fecal sample s were collected from 26 healthy controls and 27 children hospitalized with severe UC as part of a prospect i ve multicenter study . DNA extraction , polymerase chain reaction ( PCR ) amplification of bacterial 16S rRNA , and microarray hybridization were performed . Results were analyzed in GeneSpring GX 11.0 comparing healthy controls with children with UC , and steroid responsive ( n = 17 ) with nonresponsive patients ( n = 10 ) . Results : Bacterial signal strength and distribution showed differences between UC and healthy controls ( adjusted P < 0.05 ) for Phylum , Class , Order , Family , Genus , and Phylospecies levels with reduction in Clostridia and an increase in Gamma‐proteobacteria . The number of microbial phylospecies was reduced in UC ( 266 ± 69 ) vs. controls ( 758 ± 3 , P < 0.001 ) , as was the Shannon Diversity Index ( 6.1 ± 0.23 vs. 6.49 ± 0.04 , respectively ; P < 0.0001 ) . Steroid nonresponders harbored fewer phylospecies than responders ( 142 ± 49 vs. 338 ± 62 , P = 0.013 ) . Conclusions : Richness , evenness , and biodiversity of the gut microbiome were remarkably reduced in children with UC compared with healthy controls . Children who did not respond to steroids harbored a microbiome that was even less rich than steroid responders . This study is the first to characterize the gut microbiome in a large cohort of pediatric patients with severe UC and describes changes in the gut microbiome as a potential prognostic feature . ( Inflamm Bowel Dis 2012 OBJECTIVE To determine whether sulfasalazine ( SSZ ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis ( PsA ) resistant to nonsteroidal antiinflammatory drug therapy . METHODS Two hundred twenty-one patients with PsA were recruited from 15 clinics , r and omized ( double-blind ) to SSZ or placebo treatment , and followed up for 36 weeks . Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessment s. RESULTS Longitudinal analysis revealed a trend favoring SSZ treatment ( P = 0.13 ) . At the end of treatment , response rates were 57.8 % for SSZ compared with 44.6 % for placebo ( P = 0.05 ) . The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo ( P < 0.0001 ) . Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints , including dyspepsia , nausea , vomiting , and diarrhea . CONCLUSION SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with Over the past years , mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases . Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn 's disease . Mucosal healing may also prevent the development of long-term disease complications , such as bowel damage in Crohn 's disease and colorectal cancer in ulcerative colitis . Histologic healing may be the ultimate therapeutic goal in ulcerative colitis , whereas its impact on the course of Crohn 's disease is unknown . Complete mucosal healing may be required before considering drug withdrawal . Targeting early Crohn 's disease is more effective than approaches aim ed at healing mucosa in longst and ing disease . Several questions remain to be answered : should mucosal healing be systematic ally used in clinical practice ? Should we optimize therapies to achieve mucosal healing ? What is the degree of intestinal healing that is required to change the disease course ? Large prospect i ve studies addressing these issues are needed |
13,923 | 32,020,403 | CEUS is highly efficient in differentiating TIV from PVT and is an alternative or a substitute for CT and /or MRI .
PROSPERO registration number : CRD42019138847 • Characterization of portal vein thrombosis ( PVT ) vs tumor-in-vein ( TIV ) is critical for HCC staging . •
CEUS has an excellent safety profile , provides a real-time analysis without any loss in accuracy compared with CT and MRI . •
This meta- analysis demonstrates that contrast-enhanced ultrasound ( CEUS ) is a suitable method for the detection of PVT and distinction with TIV | Portal vein thrombosis ( PVT ) is a common complication of liver cirrhosis .
However , differentiation of thrombosis and tumor-in-vein ( TIV ) may be challenging .
Contrast-enhanced ultrasound ( CEUS ) is an excellent method for detection of vascularization and could help in the distinction .
We performed a systematic review and meta- analysis for evaluating the diagnostic value of CEUS in differentiating between PVT and TIV in hepatocellular carcinoma ( HCC ) patients . | This document , on the diagnosis and treatment of patients with hepatocellular carcinoma ( HCC ) , was commissioned by the British Society of Gastroenterology as part of a wider initiative to develop guidelines for clinicians in several areas of clinical practice . Cancer care has been the subject of increased scrutiny , with the development of care guidelines forming a major part of the strategy to reduce cancer related mortality in the UK . There is a strong suggestion that HCC is a disease which will be seen more frequently over the next few years , mainly as a result of the hepatitis C virus ( HCV ) epidemic . Previously , HCC has been a relatively rare tumour in the UK and much of the data pertaining to its diagnosis and therapy are derived from studies outside of the UK . Because of the lack of screening programmes and the fact that a significant proportion of HCC presents as symptomatic disease in individuals not known to have liver disease , most non-surgical therapies have been used in patients with advanced disease . There are a significant number of variables known to influence prognosis , with stage of underlying liver disease and tumour size at presentation being the most important . Controlling for these variables is difficult and these factors have contributed to a dearth of r and omised controlled trials of treatment for this tumour . There is however a substantial amount of evidence available which can form the basis of a framework for diagnosis and management . Guidelines are not rigid protocol s and they should not be construed as interfering with local clinical judgement . Hence they do not represent a directive of proscribed routes but a basis on which clinicians can consider the options available more clearly . These guidelines cover two areas of clinical practice relating to HCC : firstly , its diagnosis , including surveillance of high risk individuals ; and AIMS We assessed the role of contrast-enhanced ultrasound ( CEUS ) in the differential diagnosis between benign and malignant portal vein thrombosis ( PVT ) in patients who had liver tumors . METHODS Seventeen consecutive patients who had cirrhosis , liver tumors , and PVT were prospect ively studied with CEUS . CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent ( SonoVue , Bracco , Milan , Italy ) . Presence or absence of thrombus enhancement on CEUS were considered diagnostic for malignant or benign PVT . Five patients also underwent percutaneous portal vein fine-needle biopsy under US guidance . All patients were followed-up . Shrinkage of the thrombus and /or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis , whereas the enlargement of the thrombus , disruption of the vessel wall , and parenchymal infiltration over follow-up were considered consistent with malignancy . RESULTS Follow-up showed signs of malignant thrombosis in 14 of 17 patients . CEUS showed early arterial enhancement of the PVT in 14 patients of 14 malignant PVT , 1 patient of 3 benign PVT and the absence of thrombus enhancement in 2 patients of 3 benign PVT . FNB confirmed the results for malignant PVT in four of five patients , for benign granulomatous inflammation PVT in one of five patients in which CEUS showed early arterial enhancement of the PVT . The sensitivity , specificity and accuracy is 100 % , 66.7 % and 93.3 % at diagnosis of malignant PVT using CEUS . In one patient with intrahepatic bile duct stone , CEUS were positive for malignant PVT , whereas FNB was negative ( benign granulomatous inflammation PVT ) ; follow-up examination confirmed benign PVT . CONCLUSION CEUS seems to be the pretty sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis and tumors Background We assessed the role of contrast-enhanced ultrasound ( CEUS ) in the differential diagnosis between benign and malignant portal vein thrombosis in patients who had cirrhosis with hepatocellular carcinoma ( HCC ) . Methods Fifty-four consecutive patients who had cirrhosis , biopsy-proved HCC , and thrombosis of the main portal vein and /or left/right portal vein on US were prospect ively studied with color Doppler US ( CDUS ) and CEUS . CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent ( SonoVue , Bracco , Milan , Italy ) . Presence or absence of CDUS signals or thrombus enhancement on CEUS were considered diagnostic for malignant or benign portal vein thrombosis . Twenty-eight patients also underwent percutaneous portal vein fine-needle biopsy ( FNB ) under US guidance . All patients were followed-up bimonthly by CDUS . Shrinkage of the thrombus and /or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis , whereas enlargement of the thrombus , disruption of the vessel wall , and parenchymal infiltration over follow-up were considered consistent with malignancy . CDUS , CEUS , and FNB results were compared with those at follow-up . Results Follow-up ( 4 to 21 months ) showed signs of malignant thrombosis in 34 of 54 patients . FNB produced a true-positive result for malignancy in 19 of 25 patients , a false-negative result in six of 25 patients , and a true-negative result in three of three patients . CDUS was positive in seven of 54 patients . CEUS showed enhancement of the thrombus in 30 of 54 patients . No false-positive result was observed at CDUS , CEUS , and FNB . Sensitivities of CDUS , CEUS , and FNB in detecting malignant thrombi were 20 % , 88 % , and 76 % respectively . Three patients showed negative CDUS and CEUS and positive FNB results ; follow-up confirmed malignant thrombosis in these patients . One patient showed negative CDUS , CEUS , and FNB findings . Howewer , follow-up of the thrombus showed US signs of malignancy . Another FNB confirmed HCC infiltration of the portal vein . Conclusion CEUS seems to be the most sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis OBJECTIVES To select an appropriate treatment regimen , it is essential to accurately characterize the nature of a thrombus . This study prospect ively assessed the ability of contrast-enhanced sonography to differentiate between benign and malignant portal vein thrombosis in a population of high-risk patients . METHODS Fifty-five patients ( 43 men and 12 women ; mean age , 66 years ; range , 55 - 83 years ) with thrombi of the portal venous system were examined by power Doppler sonography and contrast-enhanced sonography with the intravenous contrast agent SH U 508A ( Levovist ; Schering AG , Berlin , Germany ) . Of the thrombi , 40 were characterized as malignant and 15 as benign . Pulsatile flow in the thrombus on power Doppler sonography and positive enhancement of the thrombus on contrast-enhanced sonography were judged as indications of a malignant thrombus . The sensitivity and specificity of both methods in differentiating the nature of the thrombus were evaluated . RESULTS The detection of pulsatile flow in a portal vein thrombus as the criterion for diagnosing malignant portal vein thrombus yielded overall sensitivity of 82.5 % and specificity of 100 % , whereas positive enhancement of the portal vein thrombus itself as a criterion for diagnosing malignancy yielded overall sensitivity and specificity of 100 % for each . CONCLUSIONS Contrast-enhanced sonography can be helpful in discriminating between benign and malignant portal vein thrombi OBJECTIVE The objective of our study was to determine if the detection by Doppler sonography of blood flow in portal vein thrombi occurring in patients with cirrhosis could be used to distinguish benign from malignant portal vein thrombi . SUBJECTS AND METHODS Color and duplex Doppler sonographic examinations were performed in 47 patients with proven cirrhosis and portal vein thrombi . The examinations were directed at the detection of continuous or pulsatile flow within the portal vein thrombi . The nature of the portal vein thrombi was proven histologically in 27 patients and by CT findings and clinical history in 20 patients . The frequency , type , and direction of portal vein thrombus flow was evaluated to determine if there was any correlation with the benign or malignant nature of the portal vein thrombi . RESULTS Of the 47 patients , 26 had malignant portal vein thrombi and 21 had benign portal vein thrombi . Blood flow was detected in 22 of the malignant and in 15 of the benign portal vein thrombi . The blood flow was pulsatile in 16 malignant and three benign portal vein thrombi and continuous in six malignant and 12 benign portal vein thrombi . The direction of the pulsatile flow in the malignant portal vein thrombi was predominantly ( 13/16 ) hepatofugal . All continuous flow in both benign and malignant portal vein thrombi was hepatopetal . The detection of pulsatile flow in portal vein thrombi yielded a 62 % sensitivity and 95 % specificity for the diagnosis of malignant portal vein thrombus . CONCLUSION The detection by Doppler sonography of pulsatile flow in portal vein thrombi occurring in patients with cirrhosis is a moderately sensitive but highly specific sign for the diagnosis of malignant portal vein thrombus . However , continuous flow can be detected in benign and malignant portal vein thrombus and is thus not useful in differentiating between the two 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 Malignant portal vein thrombosis is a contraindication for liver transplantation . Patients with cirrhosis and early hepatocellular carcinoma ( HCC ) may have either malignant or benign ( fibrin clot ) portal vein thrombosis . The aim of this study was to assess prospect ively whether well-defined diagnostic criteria would enable the nature of portal vein thrombosis to be established in patients with HCC under consideration for liver transplantation . Benign portal vein thrombosis was diagnosed by the application of the following criteria : lack of vascularization of the thrombus on contrast-enhanced ultrasound and on computed tomography or magnetic resonance imaging , absence of mass-forming features of the thrombus , absence of disruption of the walls of veins , and , if uncertainty persisted , biopsy of the thrombus for histological examination . Patients who did not fulfill the criteria for benign thrombosis were not placed on the transplantation list . In this study , all patients evaluated at our center during 2001 - 2007 with a diagnosis of HCC in whom portal vein thrombosis was concurrently or subsequently diagnosed were discussed by a multidisciplinary group to determine their suitability for liver transplantation . The outcomes for 33 patients who met the entry criteria of the study were as follows : in 14 patients who were placed on the transplantation list and underwent liver transplantation , no malignant thrombosis was detected when liver explants were examined histologically ; 5 patients who were placed on the transplantation list either remained on the list or died from causes unrelated to HCC ; in 9 patients , liver transplantation was contraindicated on account of a strong suspicion , or confirmation , of the presence of malignant portal vein thrombosis ; and 5 patients who were initially placed on the transplantation list were subsequently removed from it on account of progression of HCC in the absence of evidence of neoplastic involvement of thrombosis . In conclusion , for a patient with HCC and portal vein thrombosis , appropriate investigations can establish whether the thrombosis is benign ; patients with HCC and benign portal vein thrombosis are c and i date s for liver transplantation BACKGROUND AND AIM We aim ed to vali date the non-invasive criteria for the characterization of portal vein thrombosis ( PVT ) in patients with cirrhosis and hepatocellular carcinoma ( HCC ) . In a prospect i ve study , we examined the impact of arterial hypervascularity , as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non-invasive diagnosis of HCC , as a criterion for characterizing macroscopic PVT ( EASL/AASLD extension criteria ) . METHODS A total of 96 cases of PVT detected using ultrasonography in patients with cirrhosis and HCC were included in the study . When coincidental arterial hypervascularity was detected by contrast perfusional ultrasonography and helical computed tomography , the thrombus was considered malignant according to our EASL/AASLD extension criteria . In all cases , an ultrasound-guided biopsy examination of the thrombus was performed . RESULTS Coincidental hypervascularity was found in 54 of 96 nodules ( 56.2 % ) , and all were malignant upon biopsy ( 100 % positive predictive value ) . Twenty-four ( 25 % ) had negative results with both techniques ( non-vascular thrombus ) . Biopsies showed HCC in five non-vascular thrombi ( 5.3 % of all thrombi ) and in 13 of 18 thrombi with a hypervascularity result from only one technique . CONCLUSIONS The EASL/AASLD extension criteria for non-invasive diagnosis of malignant thrombosis were satisfied in 75.2 % of malignant thrombi ; thus , a biopsy is frequently required in this setting . However , in the presence of coincidental hypervascularity of a thrombus with both techniques , a biopsy is not required ( absolute positive predictive value for malignancy ) . Relying on imaging techniques in thrombi could miss the diagnosis of malignant portal invasion in up to 24.9 % of cases This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospect i ve r and omized controlled trials ( RCT ) were investigated through uni‐ and multivariate analyses . None of them was suitable for radical therapies ( surgical resection , liver transplantation , or ethanol injection ) or presented end‐stage disease as reflected by an Okuda stage 3 or a Performance Status ≥3 . Sixty‐five patients were Child‐Pugh A , 34 were B , and 3 were C. Most of them exhibited a preserved Performance Status Test ( PST ) ( 0 = 56 ; 1 = 38 ; 2 = 8) . Tumor was solitary in 26 ( ≤5 cm in 16 ) and multinodular/massive in 76 . After a median follow‐up of 17 months , 79 patients died , the 1‐ , 2‐ , and 3‐year survival being 54 % , 40 % , and 28 % . The multivariate study identified PST ( P = .01 ) , constitutional syndrome ( P = .04 ) , vascular invasion ( P = .001 ) , and extrahepatic spread ( P = .04 ) as independent predictors for mortality . The 1‐ , 2‐ , and 3‐year survival for the 48 patients without adverse factors ( Stage 0 ) was 80 % , 65 % , and 50 % , respectively , and 29 % , 16 % , and 8 % in the 54 patients with at least one adverse parameter ( Stage I ) . Therefore , Stage 0 would correspond to an intermediate stage , while Stage I would represent an advanced status , before reaching an end‐stage phase . In conclusion , the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern . Therapeutic trials should be design ed and evaluated considering these characteristics In cirrhosis , portal vein thrombosis ( PVT ) could be a cause or a consequence of the progression of liver disease . We analyzed data from a prospect i ve trial of ultrasound screening for hepatocellular carcinoma in order to identify risk factors for and the impact of PVT in patients with cirrhosis . In all , 1,243 adults with cirrhosis without PVT were enrolled from 43 liver units in France and Belgium between June 2000 and March 2006 . The mean follow‐up was 47 months . Doppler ultrasonography was used to check the portal vein . Progression of liver disease was defined by the development of : ascites , hepatic encephalopathy , variceal bleeding , prothrombin < 45 % , serum bilirubin > 45 μmol/L , albumin < 28 g/L , and /or creatinine > 115 μmol/L. G20210A prothrombin and factor V gene mutations were assessed in sera stored at three large centers . The 5‐year cumulative incidence of PVT was 10.7 % . PVT was mostly partial and varied over time . The development of PVT was independently associated with baseline esophageal varices ( P = 0.01 ) and prothrombin time ( P = 0.002 ) , but not with disease progression before PVT , or prothrombotic mutations . Disease progression was independently associated with baseline age ( hazard ratio [ HR ] 1.55 ; 95 % confidence interval [ CI ] : 1.11‐2.17 ) , body mass index ( HR 1.40 ; 95 % CI : 1.01‐1.95 ) , prothrombin time ( HR 0.79 ; 95 % CI : 0.70‐0.90 ) , serum albumin ( HR 0.97 ; 95 % CI : 0.94‐0.99 ) , and esophageal varices ( HR 1.70 ; 95 % CI : 1.21‐2.38 ) but not with the prior development of PVT ( HR 1.32 ; 95 % CI : 0.68‐2.65 ) . Conclusion : In patients with cirrhosis , the development of PVT is associated with the severity of liver disease at baseline , but does not follow a recent progression of liver disease . There is no evidence that the development of PVT is responsible for further progression of liver disease . ( Hepatology 2015;61:660‐667 |
13,924 | 28,063,195 | The best evidence was found for abiraterone and enzalutamide for effective prolongation of OS and PFS to treat chemotherapy-naive patients with mCRPC . | The aim of this study is to systematic ally evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer ( mCRPC ) . | PURPOSE To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a r and omized controlled trial . PATIENTS AND METHODS We r and omized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone ( 10 mg daily ) . Nonresponding patients on prednisone could receive mitoxantrone subsequently . The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients ( or complete loss of pain if initially 1 + ) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart . Secondary end points were a decrease of > or = 50 % in use of analgesic medication without an increase in pain , duration of response , and survival . Health-related quality of life was evaluated with a series of linear analog self- assessment scales ( LASA and the Prostate Cancer-Specific Quality -of-Life Instrument [ PROSQOLI ] ) , the core question naire of the European Organization for Research and Treatment of Cancer ( EORTC ) , and a disease-specific module . RESULTS Palliative response was observed in 23 of 80 patients ( 29 % ; 95 % confidence interval , 19 % to 40 % ) who received mitoxantrone plus prednisone , and in 10 of 81 patients ( 12 % ; 95 % confidence interval , 6 % to 22 % ) who received prednisone alone ( P = .01 ) . An additional seven patients in each group reduced analgesic medication > or = 50 % without an increase in pain . The duration of palliation was longer in patients who received chemotherapy ( median , 43 and 18 weeks ; P < .0001 , log-rank ) . Eleven of 50 patients r and omized to prednisone treatment responded after addition of mitoxantrone . There was no difference in overall survival . Treatment was well tolerated , except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone . Most responding patients had an improvement in quality -of-life scales and a decrease in serum prostate-specific antigen ( PSA ) level . CONCLUSION Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer Sipuleucel‐T is an investigational active cellular immunotherapy product design ed to stimulate an immune response against prostate cancer . The safety and efficacy of sipuleucel‐T was evaluated in 2 identically design ed , r and omized , double‐blind , placebo‐controlled trials ( D9901 and D9902A ) conducted in men with advanced prostate cancer BACKGROUND Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive and rogen-independent prostate cancer . We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic , hormone-independent prostate cancer . METHODS We r and omly assigned 770 men to one of two treatments , each given in 21-day cycles : 280 mg of estramustine three times daily on days 1 through 5 , 60 mg of docetaxel per square meter of body-surface area on day 2 , and 60 mg of dexamethasone in three divided doses before docetaxel , or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily . The primary end point was overall survival ; secondary end points were progression-free survival , objective response rates , and post-treatment declines of at least 50 percent in serum prostate-specific antigen ( PSA ) levels . RESULTS Of 674 eligible patients , 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone . In an intention-to-treat analysis , the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone ( 17.5 months vs. 15.6 months , P=0.02 by the log-rank test ) , and the corresponding hazard ratio for death was 0.80 ( 95 percent confidence interval , 0.67 to 0.97 ) . The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone ( P<0.001 by the log-rank test ) . PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients , respectively ( P<0.001 ) , and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease , respectively ( P=0.30 ) . Grade 3 or 4 neutropenic fevers ( P=0.01 ) , nausea and vomiting ( P<0.001 ) , and cardiovascular events ( P=0.001 ) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone . Pain relief was similar in both groups . CONCLUSIONS The improvement in median survival of nearly two months with docetaxel and estramustine , as compared with mitoxantrone and prednisone , provides support for this approach in men with metastatic , and rogen-independent prostate cancer BACKGROUND The alpha-emitter radium-223 ( (223)Ra ) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer . We aim ed to study mature outcomes from a r and omised , multicentre , phase II study of (223)Ra . METHODS Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra ( 50 kBq/kg , 33 patients ) or placebo ( 31 patients ) , given every 4 weeks . Primary endpoints were change in bone-alkaline phosphatase ( ALP ) concentration and time to skeletal-related events ( SREs ) . Secondary endpoints included toxic effects , time to prostate-specific-antigen ( PSA ) progression , and overall survival . All tests were done at a 5 % significance level , based on intention to treat . FINDINGS Median relative change in bone-ALP during treatment was -65.6 % ( 95 % CI -69.5 to -57.7 ) and 9.3 % ( 3.8 - 60.9 ) in the (223)Ra group and placebo groups , respectively ( p<0.0001 , Wilcoxon ranked-sums test ) . Hazard ratio for time to first SRE , adjusted for baseline covariates , was 1.75 ( 0.96 - 3.19 , p=0.065 , Cox regression ) . Haematological toxic effects did not differ significantly between two groups . No patient discontinued (223)Ra because of treatment toxicity . Median time to PSA progression was 26 weeks ( 16 - 39 ) versus 8 weeks ( 4 - 12 ; p=0.048 ) for (223)Ra versus placebo , respectively . Median overall survival was 65.3 weeks ( 48.7-infinity ) for (223)Ra and 46.4 weeks ( 32.1 - 77.4 ) for placebo ( p=0.066 , log rank ) . The hazard ratio for overall survival , adjusted for baseline covariates was 2.12 ( 1.13 - 3.98 , p=0.020 , Cox regression ) . INTERPRETATION (223)Ra was well tolerated with minimum myelotoxicity , and had a significant effect on bone-ALP concentrations . Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer . Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist ( LHRH-A ) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer . A total of 205 patients with stage C/D prostate cancer were r and omized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo . Primary study variables have been reported previously . Secondary variables included : time to achieve prostate-specific antigen⩽4 ng/ml , time-to-treatment failure ( TTTF ) , time-to-disease progression ( TTP ) , overall survival ( OS ) , adverse events and adverse drug reactions . Following combination therapy with bicalutamide 80 mg , there were significant ( P<0.001 ) advantages over LHRH-A alone in terms of TTTF and TTP , but the difference in the interim OS was not statistically significant . First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone , with respect to TTTF and TTP . Follow-up for OS continues BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . BACKGROUND Abiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer ( mCRPC ) . Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study . In vitro studies indicate that taxanes may act by disrupting and rogen receptor signalling . We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy . PATIENTS AND METHODS We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone , using Prostate Cancer Working Group and radiological criteria . RESULTS Of the 54 patients treated with abiraterone , 35 subsequently received docetaxel . Docetaxel result ed in a prostate-specific antigen ( PSA ) decline of ≥50 % in nine patients [ 26 % , 95 % confidence interval ( CI ) 13 % to 43 % ] , with a median time to PSA progression of 4.6 months ( 95 % CI 4.2 % to 5.9 % ) . PSA declines ≥30 % were achieved by 13 patients ( 37 % , 95 % CI 22 % to 55 % ) . The median overall survival was 12.5 months ( 95 % CI 10.6 - 19.4 ) . All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory ( N = 8) . In the 24 patients with radiologically evaluable disease , partial responses were reported in four patients ( 11 % ) , none of whom were abiraterone-refractory . CONCLUSION The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients OBJECTIVES To evaluate bicalutamide ( Casodex ) 80 mg as a component of maximum and rogen blockade ( MAB ) in Japanese patients with previously untreated advanced prostate cancer . METHODS 205 patients with previously untreated stage C/D prostate cancer were r and omized ( 1:1 ) to receive once-daily bicalutamide 80 mg or placebo , each combined with a luteinizing hormone-releasing hormone ( LHRH ) agonist . Primary study variables were the 12 week prostate-specific antigen ( PSA ) normalization ( i.e. PSA level < or=4 ng/ml ) rate , the 12 week overall tumor response rate ( proportion with a partial response or better ) and the proportion of withdrawals due to adverse drug reactions ( ADRs ) at follow-up . This interim analysis was undertaken after a minimum of 6 months ' follow-up ( median 15 months ) . RESULTS The 12 week PSA normalization rate was 79.4 % for MAB and 38.6 % for LHRH agonist monotherapy ( P < 0.001 ) . The 12 week overall tumor response rate was 77.5 and 65.3 % , respectively ( P = 0.063 ) . The withdrawal rate due to ADRs was 8.8 % and 10.9 % , respectively . There were differences in favor of MAB over monotherapy with respect to time to treatment failure ( TTTF ) ( P = 0.038 ) and time to progression ( TTP ) ( P = 0.016 ) . There have been too few deaths ( n = 10 ) to analyze survival . The profiles of adverse events and ADRs were broadly similar in the two treatment groups . CONCLUSION In Japanese patients with advanced prostate cancer , first-line treatment with bicalutamide 80 mg in combination with an LHRH agonist is superior to LHRH agonist monotherapy in terms of the antitumor response at 12 weeks , and also time to treatment failure and progression , and does not compromise treatment safety . The study is ongoing OBJECTIVE To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment ( IMPACT ) trial who were r and omized to receive sipuleucel-T or control . METHODS The most powerful of these prognostic factors , baseline prostate-specific antigen ( PSA ) , was subdivided into quartiles to evaluate treatment effect patterns . Cox regression analyses were used to assess predictors of overall survival ( OS ) and sipuleucel-T treatment effect within PSA quartiles . Median OS was estimated by the Kaplan-Meier method . RESULTS PSA was the strongest baseline prognostic factor ( P < .0001 ) . Furthermore , the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA . The OS hazard ratio for patients in the lowest baseline PSA quartile ( ≤22.1 ng/mL ) was 0.51 ( 95 % confidence interval , 0.31 - 0.85 ) compared with 0.84 ( 95 % confidence interval , 0.55 - 1.29 ) for patients in the highest PSA quartile ( > 134 ng/mL ) . Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile . Estimated 3-year survival in the lowest PSA quartile was 62.6 % for sipuleucel-T patients and 41.6 % for control patients , representing a 50 % relative increase . CONCLUSION The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors , particularly those with lower baseline PSA values . These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone Purpose To assess quality of life ( QOL ) data from a double-blind Phase III study evaluating bicalutamide ( Casodex ™ ) 80 mg as part of maximum and rogen blockade ( MAB ) in patients with previously untreated advanced prostate cancer . Methods Patients with untreated stage C/D prostate cancer were r and omized to MAB with bicalutamide plus a luteinizing hormone-releasing hormone agonist ( LHRHa ) or LHRHa monotherapy . QOL was evaluated at baseline and at weeks 1 , 5 , and 24 using the Japanese version of the Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) question naire . Results A total of 203 patients were assessed for QOL . The MAB group had more rapid and greater improvements in “ emotional well-being ” and “ prostate cancer-specific issues ” domain scores than the monotherapy group . Further analysis of “ prostate cancer-specific issues ” revealed that , compared with monotherapy , MAB provided a greater improvement in “ micturition disorder”-related QOL . Complete improvement rates for items related to “ pain and micturition disorder ” were also higher with MAB . Item scores of “ pain and micturition disorder ” did not correlate strongly with prostate-specific antigen levels or tumor size . Fewer patients who had deterioration in their “ pain and micturition disorder ” item scores at week 1 in the MAB group than the monotherapy group . Conclusions Maximum and rogen blockade with bicalutamide plus LHRHa did not reduce the overall QOL of patients with previously untreated advanced prostate cancer . MAB was superior to monotherapy in achieving early improvement of QOL related to micturition disorder and pain To test the hypothesis that maximal and rogen blockade improves the effectiveness of the treatment of prostatic cancer , we conducted a r and omized , double-blind trial in patients with disseminated , previously untreated prostate cancer ( stage D2 ) . All 603 men received leuprolide , an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins , in combination with either placebo or flutamide , a nonsteroidal anti and rogen that inhibits the binding of and rogens to the cell nucleus . As compared with the 300 patients receiving leuprolide and placebo , the 303 patients r and omly assigned to receive leuprolide and flutamide had a longer progression-free survival ( 16.5 vs. 13.9 months ; P = 0.039 ) and an increase in the median length of survival ( 35.6 vs. 28.3 months ; P = 0.035 ) . The differences between the treatments were particularly evident for men with minimal disease and good performance status ; however , further studies should be conducted in this subgroup . Symptomatic improvement was greatest during the first 12 weeks of the combined and rogen blockade , when leuprolide alone often produces a painful flare in the disease . We conclude that in patients with advanced prostate cancer , treatment with leuprolide and flutamide is superior to treatment with leuprolide alone A previously reported , double‐blind , r and omized , multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined and rogen blockade ( CAB ) with luteinizing hormone‐releasing hormone agonist ( LHRH‐A ) plus bicalutamide 80 mg versus LHRH‐A plus bicalutamide‐matching placebo ( LHRH‐A monotherapy ) . The analysis at a median follow‐up of 2.4 years indicated that CAB significantly ( P < .001 ) prolonged the time to progression and the time to treatment failure . In the current report , survival data from a long‐term follow‐up ( median , 5.2 years ) were analyzed In the phase III r and omized ALSYMPCA trial of radium-223 in patients with castration-resistant prostate cancer and bone metastases , improved survival with radium-223 is accompanied by significant quality of life benefits , measured by EQ-5D and FACT-P , including a higher percentage of patients with meaningful improvement in quality of life and a slower decline in quality of life over time |
13,925 | 18,801,830 | In summary , the evidence suggests people with schizophrenia can experience both hyper- and hypo-function of the HPA axis .
It is likely that this contributes to the pattern of poor physical health and premature mortality suffered by people with schizophrenia , in particular the high rates of cardiovascular and metabolic disturbance | There is convincing evidence that environmental stress plays a significant role in modifying both mental and physical health .
The biological mechanisms linking stress to ill health are not fully understood , but significant evidence points to a central role of the stress axes ; the hypothalamic— pituitary — adrenal ( HPA ) axis and the sympathetic nervous system .
Together these two systems link the brain and the body and are crucial in maintaining homeostasis as well as improving an organism ’s survival chances in the face of environmental challenge .
There is evidence of altered HPA axis function in people with a range of mental disorders , and this may in part explain the poor physical health of people with psychotic , mood and anxiety disorders . | The adrenocorticotropic hormone ( ACTH ) and cortisol responses to apomorphine ( APO ) , a direct acting dopamine ( DA ) agonist , have been reported to be significantly blunted in neuroleptic-free patients with schizophrenia ( SCH ) . This study primarily examined the cortisol , but also the prolactin ( PRL ) and growth hormone ( GH ) , response to APO in patients with SCH compared to normal controls , as well as the relationship between endocrine measures and response to antipsychotic drug treatment . APO , 0.01 mg/kg , or placebo was administered to 51–98 patients with SCH and 15–25 normal controls . Psychopathology was assessed at the baseline and six weeks after drug treatment . The plasma cortisol response to APO was markedly blunted in patients with SCH compared to normal controls . Patients who responded to six weeks of treatment with antipsychotic drugs had a higher cortisol response to APO compared to non-responders . The plasma GH , but not PRL , response to APO was blunted in male patients with SCH . Neither plasma GH nor PRL responses to APO were related to treatment response at six weeks . These results provide further evidence of dopaminergic dysfunction in SCH . Furthermore , the APO-stimulated cortisol response may be predictive of subsequent clinical response to antipsychotic drug treatment Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis ( LHPA ) activity . To explore this hypothesis , we prospect ively studied 166 research volunteers ( 19 patients with research diagnostic criteria ( RDC ) major depression , 9 patients with RDC bipolar depression , 45 patients with RDC schizophrenia , and 94 RDC normal controls ) , examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio ( VBR ) and indices of LHPA axis function ( cerebrospinal fluid ( CSF ) corticotropin-releasing factor ( CRF ) , CSF adrenocorticotropic hormone ( ACTH ) , and 24-hour urinary-free cortisol secretion ) . We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers . Of the indices of LHPA activity , only CSF CRF concentrations distinguished the four subject groups , with CSF CRF being significantly elevated in the more severely depressed major depression patients . Indices of LHPA activity were not significantly correlated with VBR in any of the three patient groups or in the normal volunteers . These preliminary results suggest that VBR is not highly associated with alterations in LHPA activity , at least as determined cross-sectionally . Further longitudinal studies with reference to diagnostic subtypes , severity , symptom profiles , and more specific neuroanatomic regions may allow the elucidation of possible relationships between LHPA pathology and structural brain alterations This study examined the prolactin ( PRL ) , adrenocorticotropin ( ACTH ) and cortisol responses to the direct DA receptor agonist apomorphine ( APO ) and the selective 5HT-releasing agent d-fenfluramine ( d-FEN ) in 20 untreated in patients with DSM-IV schizophrenia and without a history of suicide attempt , compared to 23 hospitalized healthy controls . We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters . A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests ( i.e. deltaACTH and deltacortisol ) in the overall population and in schizophrenic patients . Pituitary-adrenal response to APO was lower in patients than in normal controls . Moreover , lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score . Lower pituitary-adrenal responses to APO ( and to a lesser degree to d-FEN ) differentiated paranoid from disorganized schizophrenic patients . Neither PRL suppression to APO , nor PRL stimulation to d-FEN were altered in schizophrenic patients . Our results suggest that decreased hypothalamic DA receptor activity ( possibly secondary to increased presynaptic DA release ) together with relatively decreased 5-HT tone characterize paranoid SCH , while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype In an attempt to define potential immunological dysfunctions in schizophrenia , we determined the production of interleukin-2 ( IL-2 ) , interleukin-4 ( IL-4 ) , interferon-γ ( IFN-γ ) , and soluble IL-2 receptor ( sIL-2R ) in a whole-blood assay after stimulation with phytohemagglutinin ( PHA ) as well as the serum concentrations of sIL-2R . Because CD4+CD45RO+T cells are the main producers of IFN-γ , we determined the percentage of these cells , as well as of pan T , CD4+T , and CD8+T cells , by flow cytometry . A whole-blood count was performed in addition . Two groups of patients were examined , paranoid-type and residual-type schizophrenics . The numbers of both monocytes and neutrophils , but not of lymphocytes , were increased significantly in the schizophrenic sample . The IFN-γ production of the schizophrenics as a whole group , and of the paranoid patients , was reduced significantly in comparison with the control group ( p≤0.05 ) . The residual patients produced less IFN-γ than the controls , but more than the paranoid patients . The latter differences did not reach statistical significance . The production of IL-4 , which physiologically antagonizes the production of IFN-γ , was not significantly higher in the patient group . No changes in the lymphocyte sub population s were observed . The production of IL-2 showed a trend toward reduction in paranoid patients , but not in residual schizophrenics . The serum sIL-2R levels were elevated slightly in schizophrenics when compared with controls . In order to rule out a possible effect of cortisol on cytokine production , 20 schizophrenic were compared with 20 age- and gendermatched controls . However , neither elevated cortisol levels were detected in the schizophrenic sample , nor significant intercorrelations between cortisol levels and cytokine production , or levels of sIL-2R , respectively . In summary , our data reinforce the possibility of immune dysfunction in schizophrenia and point to the possible relevance of disease subgroups in this respect OBJECTIVES Higher rates of dexamethasone test ( DST ) nonsuppression in schizophrenia have been attributed to depressive symptoms , suicidality and negative symptoms . No study concerning first-episode schizophrenia has yet been published . DESIGN In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before , at the end of the acute treatment and after one year . At the same time the clinical evaluation with PANSS was performed . A cortisol value > 5 microgram/dl in either of the postdexamethasone sample s indicated nonsuppression of cortisol . RESULTS A total of 56 males were included . 18 % of pts were DST nonsuppressors at medication-free baseline , 5 % and 16 % after acute treatment and after one year respectively . After 1 year 42/56 of patients fulfilled the criteria of remission . The rate of nonsuppression was 21.4 % , 5 % and 16.4 % in remitters and 7 % , 7 % and 14.3 % in nonremitters . Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one h and and on admission and at the one-year follow-up on the other . Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment . MAIN FINDINGS In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up . CONCLUSIONS Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status . The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness Psychosocial stress is a potent activator of the hypothalamus-pituitary-adrenal ( HPA ) axis . While the physiological mechanisms of HPA axis responses to stress as well as its short and long-term consequences have been extensively examined , less is known why someone elicits an acute neuroendocrine stress response , i.e. what are the psychological processes involved and how are they related to the acute neuroendocrine stress response . To examine this question , a question naire to assess anticipatory cognitive appraisal processes was developed and administered to 81 male healthy subjects in a st and ardized psychosocial stress situation ( Trier social stress test ) . Cortisol stress responses were assessed with repeated measurement of salivary free cortisol . Hierarchical regression analyses show that anticipatory cognitive appraisal , in contrast to general personality factors and retrospective stress appraisal is an important determinant of the cortisol stress response , explaining up to 35 % of the variance of the salivary cortisol response . The reported results emphasize the importance of psychological stress processing for the underst and ing of psychobiological stress responses . Since stress and its biological consequences have been shown to be associated with the onset and the maintenance of somatic illnesses and psychiatric disorders , psychological processes are prime targets for prevention and intervention Summary Psychotic patients underwent a dexamethasone suppression test ( DST ) , careful diagnostic assessment s at baseline and diagnostic reevaluations after 1 year . The predicted associations between baseline DST results and diagnosis were much clearer after prospect i ve observation Most prospect i ve studies of HPA axis have found that non-suppressors in the dexamethasone suppression test ( DST ) are more likely to commit suicide during the follow-up . Attempted suicide is a strong clinical predictor of suicide . The aim of this study was to assess the predictive value of DST for suicide in a group of depressed in patients with and without an index suicide attempt . Historical cohort of 382 psychiatric in patients with mood disorder admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000 were su bmi tted to the DST and followed up for causes of death . During the follow-up ( mean 18 years ) , 36 suicides ( 9.4 % ) occurred , 20 of these were non-suppressors and 16 were suppressors . There was no statistically significant difference in suicide risk between the suppressors and non-suppressors for the sample as a whole . An index suicide attempt predicted suicide . In suicide attempters with mood disorder , the non-suppressor status was significantly associated with suicide indicating that HPA axis hyperactivity is a risk factor for suicide in this group . The dexamethasone suppression test may be a useful predictor within this population BACKGROUND Thyrotropin-releasing hormone ( TRH ) test and Dexamethasone Suppression Test ( DST ) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia . The objectives of this study were to investigate ( 1 ) the relationship between TRH test and DST and various psychiatric symptoms and ( 2 ) the potential value of these tests in prediction of short-term outcome in schizophrenic patients . METHODS TRH test and DST were administered to 58 patients with schizophrenia . All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year . Patients were divided into two groups as remitted ( RP ; n = 30 ) and nonremitted patients ( NRP ; n = 28 ) . Baseline results of these two groups were compared with each other and 30 healthy controls . RESULTS Basal levels of total T3 ( T3 T ) and free T3 ( T3F ) were higher in RP group than controls . Basal prolactin ( PRL ) level was higher in RP group , but not in NRP , compared to controls . Basal growth hormone ( GH ) and thyroid-stimulating hormone ( TSH ) levels of NRP were significantly higher than those of RP . DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group . Blunted TSH response rate in RP group was higher significantly compared to other two groups . CONCLUSIONS The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response , whereas higher total and free T3 levels , a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics Pretreatment measures of hypothalamic-pituitary-adrenocortical ( HYPAC ) function in depressed , manic , and healthy normal subjects showed that nonsuppression on the dexamethasone suppression test ( DST ) had less positive predictive value for major diagnostic category and was more frequent in normals ( 8/77 ) than recently reported , although it was yet more frequent in depressed patients ( 35/111 ) . Nonsuppression was common in manics ( 8/16 ) , was similar in unipolar and bipolar depressed patients ( 35 % and 27 % , respectively ) , and did not segregate with melancholic , endogenous , or psychotic depression subtypes . Patterns of post-DST plasma cortisol concentration other than simple escape or nonescape from suppression were common . Nonsuppression of 9 AM plasma cortisol levels on the DST had as good or better diagnostic specificity as nonsuppression of any of three post-DST sample s. Nonsuppression was not completely synonymous with HYPAC hypersecretion . Means of pre-DST HYPAC measures ( morning plasma cortisol , urine free cortisol , and CSF cortisol levels ) were elevated in depressed patients compared with normals . There were significant differences in HYPAC measures of depressed patients studied at different centers . Age correlated positively and body weight negatively with plasma cortisol level The diurnal variation of plasma beta endorphin was studied in ten schizophrenics , and in age/sex matched control subjects . In the controls beta endorphin was high in the morning ( 21.0±3.5 pmol/l ) and decreased towards evening . In the schizophrenic group the beta endorphin fluctuated r and omly , ranging within 9–40 pmol/l throughout the day . Plasma cortisol showed a normal diurnal pattern in both groups . The mean plasma cortisol levels in the schizophrenics were significantly higher than in the controls throughout the day . The pattern of plasma human growth hormone ( hGH ) level was similar in both groups at the time tested . It is hypothesized that the instability of beta endorphin secretion may contribute to the pathogenesis of schizophrenia There have been limited reports on the effect of the atypical anti-psychotic agent clozapine on sleep measures and hormone secretion . The goal of this study was to determine the type , rate , and extent of changes in sleep measures and nighttime secretion of growth hormone ( GH ) and cortisol during clozapine treatment . Five schizophrenic patients ( age : 32.4+/-7.4 ) and five age- and sex-matched normal subjects ( age : 33.0+/-5.1 ) underwent nocturnal polysomnography ( NPSG ) before clozapine therapy ( S1 ) , and during early and late clozapine therapy ( S2 and S3 ) . Serum GH and cortisol levels were monitored during each NPSG . NPSG findings showed that the mean total sleep time , sleep efficiency , and duration of awakening were increased at S2 , and maintained until S3 . The mean amounts of stage 2 sleep at S2 and S3 increased significantly compared with that of S1 . In unmedicated schizophrenic patients , the mean plasma GH level in rapid eye movement sleep was lower than during the waking stage , and the mean level of plasma cortisol was higher during the waking stage . Plasma cortisol levels did not differ between control subjects and patients at any time , but clozapine treatment decreased plasma cortisol levels at S2 compared with S1 and S3 . Plasma GH levels were unchanged by clozapine treatment . Clozapine improved sleep continuity and increased stage 2 sleep time from the beginning of therapy . These effects were maintained through at least 7 weeks of therapy . However , clozapine did not affect the relationship of plasma GH and cortisol levels with sleep stages in schizophrenic patients We conducted a pilot study in 10 adult male schizophrenics , 5 with predominantly positive symptoms ( group I ) and 5 with predominantly negative symptoms ( group II ) , and 10 healthy matched controls . No significant differences in serum levels of testosterone ( T ) , dehydroepi and rosterone sulfate ( DHEAS ) , estradiol , and cortisol were found between patients as a whole and controls , using radioimmunoassay . However , serum T and DHEAS levels were lower ( P < 0.05 ) in group II patients than in group I. Body hair and aggression scores also were lower ( P < 0.05 ) in group II . In a much larger sample , Shirayama and colleagues also showed that " moderate negative symptoms , but not low negative symptoms " correlated negatively with T ( P < 0.05 ) , but positively with ACTH ( P < 0.05 ) and cortisol ( P < 0.01 ) levels in plasma . Neuroactive steroids , such as DHEAS , and other sex hormones , including their synthetic derivatives , may have an adjunctive role in reversing or slowing the progression of negative symptoms . Indeed , " DHEA augmentation " improved " negative ( P < 0.01 ) , depressive ( P < 0.05 ) , and anxiety ( P < 0.01 ) symptoms . BACKGROUND Hyperactivity of the Hypothalamic-Pituitary-Adrenal ( HPA ) axis is a consistent finding in Major Depressive Disorder ( MDD ) and most prospect i ve studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test ( DST ) are more likely to commit suicide during follow-up . The results of studies on HPA-axis function and attempted suicide are less consistent . Suicide attempts are more common among young people than the elderly , whereas suicide is more common among the elderly . The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance . METHODS The aim of the present study was to investigate the DST results in 36 young adult ( 30 years or younger ) in patients with mood disorder , with ( n=18 ) and without suicide attempt at the index episode . RESULTS The DST non-suppressor rate was 25 % among young mood disorder in patients . DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters . The DST non-suppressor rate was 39 % in young adult suicide attempters compared with 11 % in non-attempters . CONCLUSIONS The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour . The present findings motivate to include HPA axis measures in the assessment of depression in young adults Rationale Increased activity of the hypothalamic – pituitary – adrenal ( HPA ) axis is an important aspect of the pathophysiology of major depression and schizophrenia . Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol , little is known about their effect on HPA axis function . Objective Therefore , this double-blind , placebo-controlled , r and omized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone ( ACTH ) , cortisol , and prolactin levels . Eleven healthy male volunteers were studied during four sessions one week apart , orally receiving placebo , quetiapine ( 50 mg ) , olanzapine ( 5 mg ) , or haloperidol ( 3 mg ) . Blood sample s were taken at hourly intervals from 0900 until 1700 hours . For ACTH , cortisol , and prolactin a significant effect of treatment condition ( p≤0.005 ; p≤0.035 ; p≤0.0001 , respectively ) for area under the curve ( AUC ) was found . In comparison to placebo , quetiapine and olanzapine significantly reduced ACTH ( p≤0.002 ; p≤0.05 , respectively ) and cortisol ( p≤0.005 ; p≤0.03 , respectively ) . No effect of haloperidol on AUC of ACTH or cortisol levels was observed . In comparison with placebo , haloperidol ( p≤0.0001 ) and olanzapine ( p≤0.0001 ) elevated AUC of prolactin plasma levels , whereas no significant effect was observed for quetiapine as a main effect of treatment condition . The atypical antipsychotics ’ strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals ’ blockade of serotonergic receptors , but blockade of adrenergic or histaminergic receptors may play a role as well . The observed HPA-axis down-regulation may be clinical ly important for the atypicals ’ effects on depressive symptomatology and cognitive functioning Objective This study investigated experimentally whether acute stress alters food choice during a meal . The study was design ed to test cl aims of selective effects of stress on appetite for specific sensory and nutritional categories of food and interactions with eating attitudes . Methods Sixty-eight healthy men and women volunteered for a study on “ the effects of hunger on physiology , performance , and mood . ” Eating attitudes and food preferences were measured on entry to the study . The stressed group prepared a 4-minute speech , expecting it to be filmed and assessed after a midday meal , although in fact speeches were not performed . The ad libitum meal included sweet , salty , or bl and high- and low-fat foods . The control group listened to a passage of neutral text before eating the meal . Blood pressure , heart rate , mood , and hunger were measured at baseline and after the 10-minute preparatory period , when appetite for 34 foods and food intake were recorded . Results Increases in blood pressure and changes in mood confirmed the effectiveness of the stressor . Stress did not alter overall intake , nor intake of , or appetite for the six food categories . However , stressed emotional eaters ate more sweet high-fat foods and a more energy-dense meal than unstressed and nonemotional eaters . Dietary restraint did not significantly affect appetitive responses to stress . Conclusions Increased eating of sweet fatty foods by emotional eaters during stress , found here in a laboratory setting , may underlie the previously reported finding that dietary restraint or female gender predicts stress-induced eating . Stress may compromise the health of susceptible individuals through deleterious stress-related changes in food choice BACKGROUND Functional alterations in the central serotonergic system have been reported in schizophrenia but no conclusive data have been provided . In the present study , we investigated the prolactin ( PRL ) response to the selective serotonin ( 5-HT ) releasing agent D-fenfluramine in both patients with schizophrenia and matched healthy subjects . METHODS Sixteen drug-free schizophrenics and 16 healthy subjects were r and omized in a double-blind neuroendocrine test to D-fenfluramine ( 30 mg p.o . ) or placebo . Blood PRL and cortisol concentrations were determined by radioimmunoassay , while plasma levels of D-fenfluramine were measured by mass spectrometry . RESULTS In schizophrenic patients , baseline plasma PRL levels were not different from controls , whereas plasma cortisol concentrations were significantly increased ( p < .03 ) . The PRL response to D-fenfluramine was significantly enhanced in patients as compared to matched control subjects ( p < .005 ) . Schizophrenics meeting Kane 's criteria for previous nonresponse to typical neuroleptics exhibited a PRL response to D-fenfluramine significantly higher than non-drug-resistant patients ( p < .04 ) . No significant difference in plasma D-fenfluramine concentrations was observed between schizophrenic and healthy subjects . CONCLUSIONS These findings suggest a serotonergic hypersensitivity in chronic schizophrenia . This alteration seems to be peculiar to those patients refractory to typical neuroleptics OBJECTIVE This study evaluated whether alterations in serotonin function in schizophrenic patients could be demonstrated by comparing the reactivity to a serotonin partial agonist , m-chlorophenylpiperazine ( MCPP ) in patients and healthy subjects . This study also assessed whether stimulation of serotonin receptors influenced the symptoms of schizophrenia . DESIGN Double-blind r and omized comparison of MCPP ( 0.1 mg/kg , intravenously , administered over 20 minutes ) and placebo effects in patients and healthy subjects . SETTING Department of Veterans Affairs Medical Center , West Haven , Conn. PATIENTS AND HEALTHY SUBJECTS : Fifteen healthy subjects recruited by public advertisement and 12 schizophrenic in patients who had been neuroleptic free for at least 2 weeks prior to entry into the study . MAIN OUTCOME MEASURES The principal outcome variable was the positive symptoms of schizophrenia operationally defined as the sum of scores on the four key items for schizophrenia on the Brief Psychiatric Rating Scale and the Brief Psychiatric Rating Scale thought disorder factor . Anxiety was assessed with a clinician-rated visual analog scale and plasma hormone levels were measured . RESULTS m-Chlorophenylpiperazine significantly increased the positive symptoms of schizophrenia in patients but not healthy subjects . Patients and healthy subjects exhibited anxiety increases of comparable magnitude following MCPP . However , patients had higher baseline levels of anxiety and exhibited more prolonged anxiogenic responses to MCPP . Anxiety elevations did not correlate with increases in the four key symptoms in patients . Patients exhibited lower baseline prolactin levels compared with healthy subjects , but the two groups did not differ in their prolactin , growth hormone , and cortisol responses to MCPP . CONCLUSIONS Schizophrenics , the only psychotic patient group studied to date , are the first patient group to exhibit propsychotic responses to MCPP . These data provide further evidence that serotonin systems modulate positive symptoms in some schizophrenic patients The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic – pituitary – adrenal ( HPA ) axis to the stimulatory influence of cytokines and stress-related mediators . Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia . We determined the relationship between cortisol , cytokines interleukin-2 ( IL-2 ) and interleukin-6 ( IL-6 ) , and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs . Subjects included 30 healthy controls ( HC ) and 78 schizophrenic ( SCH ) in- patients . SCH were r and omly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design . Clinical efficacy was determined using the Positive and Negative Syndrome Scale ( PANSS ) . Serum cortisol and IL-2 levels were assayed by radioimmunometric assay , and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay . Following a 2-week washout period , serum levels of cortisol , IL-2 , and IL-6 were increased in patients with schizophrenia compared to HC . Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH . Moreover , elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms . In all , 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms , but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol . The improvement of negative symptoms was related to the change in cortisol . Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms , and is improved with atypical antipsychotic treatment Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results , which may be related to patient selection and previous exposure to psychotropic medication . The objective of this study was to determine the pattern of corticotropin ( ACTH ) and cortisol release in response to metoclopramide ( a dopamine antagonist ) , which appears to be unique in its ability to release vasopressin ( AVP ) , in drug naive patients with schizophrenia experiencing their first episode of psychosis . In this study , we examined AVP , ACTH and cortisol release in response to metoclopramide in 10 drug-naive , first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age , sex and smoking status . Patients , as compared to controls had higher levels of baseline plasma cortisol ( 375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l , respectively ; t=2.48 , df=9 , p < 0.02 ) and plasma ACTH ( 14.9+/-0.85 vs. 11.3+/-0.57 pg/ml , respectively ; t=4.29 , df=9 , p<0.001 ) . AVP levels were lower in patients though this did not reach statistical significance ( 0.89+/-0.09 vs. 1.3+/-0.08 pmol/l , respectively ; t=1.97 , df=9 , p<0.07 ) . A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol ( F=11.3 , df=6 , 108 , p<0.001 ) and ACTH ( F=15.65 , df=6 , 108 , p<0.002 ) . Post hoc Tukey 's test revealed significant differences between the two groups at + 30 , + 45 , + 60 , + 90 and + 120 min for cortisol ( p<0.01 ) and at + 30 , + 45 , + 60 and + 90 min for ACTH ( p<0.01 ) . The group by time interactions continued to remain significant when cortisol ( F=10.9 , df=6 , 107 , p<0.001 ) and ACTH ( F=13.04 , df=6 , 108 , p<0.002 ) were entered as co-variates . There was a significant positive correlation between AVP and cortisol responses in patients ( r=0.65 , df=8 , p<0.01 ) . Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects BACKGROUND Evidence for basal hypothalamic-pituitary-adrenal ( HPA ) axis dysfunction in schizophrenia is less consistent than that seen in major depression . Potential reasons include sampling procedures and the use of patients on antipsychotic medications which may suppress the HPA axis . Therefore , the objective of this study was to determine whether first episode , drug naïve patients with schizophrenia have evidence of basal HPA axis dysfunction by measuring plasma levels of AVP , ACTH and cortisol from 13:00 to 16:00 h , a time frame which is believed to reflect 24 h concentrations of HPA axis activity . METHOD In this cross-sectional study , plasma levels of AVP , ACTH and cortisol were measured in 12 ( 7 males and 5 females ) ( mean age + /-SD=33.6+/-12.6 years ) patients with DSM-IV schizophrenia and compared with those found in age- and sex-matched healthy controls . RESULTS Patients and controls did not differ in terms of their 13:00 h cortisol and AVP . However , patients with schizophrenia had higher levels of ACTH as compared to control subjects at 13:00 h ( 41.3+/-14.6 vs. 12.4+/-1.1 pg/ml respectively ; t=1.99 , df=11 , p < 0.05 ) . In comparison to controls subjects , patients with schizophrenia , had higher mean ( + /-SE ) AUC of ACTH ( 26.3+/-6.2 vs. 13.9 nmol/l , respectively ; t=2.86 , df=11 , p < 0.02 ) and cortisol ( 279.4+/-26.0 vs. 213.1+/-18.4 nmol/l , respectively ; t=3.72 , df=11 , p < 0.01 ) . Though , patients with schizophrenia , in comparison to control subjects , had lower mean ( + /-SE ) AUC of AVP ( 0.87+/-0.24 vs. 1.42+/-0.34 pmol/l , respectively ; t=2.29 , df=11 , p < 0.02 ) . CONCLUSIONS First episode , drug naïve patients with schizophrenia show evidence of basal overactivity of the pituitary-adrenal axis BACKGROUND Patients with schizophrenia may differ from healthy controls by having dysregulated physiological responses to stress . Our objective was to determine the extent to which cortisol reaction can discriminate between controls and schizophrenia patients while controlling for symptom severity , personality , body mass index ( BMI ) and smoking . METHOD 30 chronic schizophrenia patients and 30 matched controls underwent a modified version of the Trier Social Stress Test ( TSST ) , consisting of public speaking and mental arithmetic . Heart rate , blood pressure , and salivary cortisol were measured repeatedly throughout the TSST . In addition , participants completed the NEO Personality Inventory ( NEO-FFI ) , and were interviewed with the Brief Psychiatric Rating Scale ( BPRS ) . RESULTS Both groups had a significant increase in heart rate and mean arterial pressure following the TSST . Results of a logistic regression suggests that patients can be discriminated from controls with a smaller change in cortisol between baseline and 15 min post-TSST , controlling for BMI and severity of positive symptoms . There was a trend for lower overall cortisol secretion in patients . CONCLUSIONS Despite demonstrable effects of the stressor on cardiac measures , schizophrenia patients tend to have smaller acute cortisol reaction to psychosocial stress . The significance of this conclusion for vulnerability-stress models of schizophrenia is discussed In a neuroendocrine challenge paradigm , the present study investigated responses of schizophrenic patients to m-chlorophenylpiperazine ( MCPP ) , a serotonin ( 5-hydroxytryptamine , 5HT ) agonist . In an oral dose of 0.25 mg/kg , MCPP was administered in a placebo-controlled double-blind design to male schizophrenic patients ( n = 7 ) and normal male controls ( n = 8) . Behavioral ( Positive and Negative Syndrome Scale ; PANSS ) and hormonal ( cortisol , prolactin ) variables were measured over the subsequent 210 min . The schizophrenic patients experienced an overall exacerbation of psychopathology on MCPP as compared with placebo ( p less than 0.05 ) , with specific worsening of PANSS-positive symptoms ( p less than 0.025 ) and PANSS activation ( p less than 0.001 ) . In addition , the schizophrenic patients showed significantly lower cortisol ( p less than 0.05 ) and prolactin ( p less than 0.05 ) responses than the normal subjects . The schizophrenic patients had lower peak MCPP blood levels than the normal subjects , although this difference was not statistically significant . The findings are discussed in terms of 5HT receptor(s ) sensitivity and the pharmacokinetics of MCPP in schizophrenia We studied the relationship between parasympathetic , sympathetic and pituitary-adrenal functions in chronic schizophrenic patients with complications such as postoperative paralytic ileus and hypotension during anaesthesia . Plasma epinephrine , norepinephrine ( NE ) , adrenocorticotropin ( ACTH ) , cortisol and the coefficient of variation ( CV ) of the R-R intervals on the electrocardiogram ( ECG ) as parasympathetic parameter were measured in schizophrenic and control patients . The CV value of the R-R interval on the ECG before the start of anaesthesia was significantly decreased to 2.3 ± 0.2 in the schizophrenic patients as compared with 3.5 ± 0.3 of the control patients . The CV value of the R-R interval on the ECG in schizophrenic patients with postoperative paralytic ileus was more diminished to 1.6 ± 0.2 . The CV values in schizophrenic patients with and without hypotension during anaesthesia were similar and we could not find any significant difference . Chronic schizophrenic patients developed a decrease in NE , ACTH and cortisol responses to surgical stress , while there were no significant differences in these hormonal changes between those patients with and without paralytic ileus and hypotension during anaesthesia . In conclusion , the CV value of the ECG R-R interval may be correlated inversely with the expectancy of postoperative ileus in chronic schizophrenic patients . Their suppressed pituitary-adrenal function and sympathetic system may be indirectly associated with the paralytic ileus and hypotension The aim of this study was to determine the location of antipsychotic-induced weight gain in drug naïve , first episode patients with schizophrenia . Various fatness and fat distribution parameters ( by Computerized Tomography scanning and anthropometry ) and 1600 hr plasma cortisol were measured in 19 ( 15 men and 4 women ) subjects with schizophrenia ( mean age = 31.0 years ; mean body mass index [ BMI ] = 24.6 kg/m2 ) and an equal number of age- and sex- matched controls ( mean age = 32.6 yr ; mean BMI = 23.0 kg/m2 ) . Patients were then given either olanzapine or risperidone . Sixteen patients were re-tested following a treatment period lasting approximately 6 months . Patients with schizophrenia , had significantly more intra-abdominal fat [ IAF ] ( 116.8 + /- 20.2 cm2 vs. 38.0 + /- 4.8 cm2 , respectively ; t = 3.80 , df = 18 , p < 0.0001 ) and had higher levels of plasma cortisol ( 360.2 + /- 49.6 nmol/L vs. 192.7 + /- 19.7 nmol/L , respectively ; t = 3.13 , df = 18 , p < 0.003 ) than appropriately matched control subjects . Treatment with atypical antipsychotics did not result in a significant increase in IAF ( 116.8 + /- 20.2 cm2 vs. 131.7 + /- 20.9 cm2 ; p = NS ) though visceral fat stores still remained significantly higher than those seen in controls ( 38.0 + /- 4.8 cm2 ) ( F = 9.34 ; df = 2 , 51 ; p < 0.0003 ) . However , plasma levels of cortisol did significantly decrease ( 360.2 + /- 49.6 nmol/L + /- vs. 316.2 + /- 48.4 nmol/L ; p < 0.05 ) . Pre-treatment levels of IAF did not differ between those who received risperidone and those who were given olanzapine ( 123.0 + /- 35.9 cm2 vs. 113.1 + /- 15.7 cm2 , respectively ; t = 0.20 , df = 16 , p < 0.84 ) . The increase in IAF did not differ between those given risperidone and those who received olanzapine ( 26.9 + /- 12.1 cm2 vs. 18.24 + /- 11.44 cm2 , respectively ; t = 0.50 , df = 16 , p < 0.63 ) . Patients with drug naïve , first episode , schizophrenia have higher levels of visceral fats stores as compared to matched control subjects . Treatment with atypical antipsychotics does not result in a significant increase in IAF distribution We studied the effects of a short-term hypertonic stimulus on plasma levels of the stress hormones adrenocorticotropin ( ACTH ) , cortisol , prolactin , and the blood volume- and electrolyte-controlling hormones arginine vasopressin ( AVP ) and atrial natriuretic peptide ( ANP ) . Seven patients suffering from chronic schizophrenia with negative symptoms and ten healthy control subjects were investigated by a 20-minute infusion of 10 ml/kg body weight of hypertonic ( 2.5 % ) versus isotonic ( 0.9 % ) saline . All patients , who were medication-free for at least one week prior to the study , and all control subjects participated in two investigations in r and omized order according to a single-blind cross-over design . During hypertonic infusion , plasma osmolarity and sodium levels were increased similarly in both groups and significantly more than during isotonic saline . Hypertonic saline caused a significant increase of plasma ACTH , cortisol and prolactin in patients in contrast to controls . AVP and ANP plasma concentrations were elevated after infusion of hypertonic saline , however , only patients showed a significant rise in plasma ANP . These results show that a dysregulation of the hypothalamic-pituitary-adrenal ( HPA ) system in a subset of patients with chronic schizophrenia may become overt during an osmotic stimulation , indicating an increased sensitivity of patients with schizophrenia to osmotic stress BACKGROUND One of the most dem and ing tasks in psychiatry is to protect patients from suicidal attempts . Preventive strategies could be improved by increasing our knowledge on the pathophysiologic disturbances underlying this behavior . More than 70 - 80 % of suicides occur in the context of depressive disorders , in which dysregulation of the hypothalamus-pituitary-adrenal ( HPA ) axis is one of the most prominent neurobiological findings . So far data on the involvement of the HPA axis in the pathophysiology of suicidal behavior in depressed patients are controversial . METHODS In this retrospective study , we administered the combined dexamethasone-suppression/CRH stimulation ( Dex/CRH ) test to 310 patients with a depressive syndrome characterized at admission for acute and past suicidal behavior within the first 10 days after hospitalization . RESULTS Suicidal behavior in depressed patients , including past and recent suicide attempts as well as suicidal ideation , was associated with a lower adrenocorticotropin and cortisol response in the combined Dex/CRH test , with lowest hormone levels observed in patients with a recent suicide attempt . DISCUSSION The findings suggest that suicidal behavior may alter HPA axis regulation in depressed patients . Large-scale prospect i ve studies assessing neuroendocrine changes may help to develop predictors for an early identification of patients at risk for committing suicide |
13,926 | 10,434,820 | Omitting neostigmine may have a clinical ly relevant antiemetic effect when high doses are used .
Omitting antagonism , however , introduces a non-negligent risk of residual paralysis even with short-acting neuromuscular blocking agents | We have estimated the effect of omitting antagonism of neuromuscular block on postoperative nausea and vomiting . | We studied the influence of mivacurium on the recovery profile following outpatient laparoscopic tubal ligation in 60 healthy , nonpregnant women . After administration of midazolam 2 mg intravenously ( IV ) , anesthesia was induced with fentanyl , 2 micrograms/kg , and thiopental , 4 mg/kg , IV . When the patient became unresponsive ( loss of eyelid reflex ) , either succinylcholine 1 mg/kg , IV ( Group I ) , or mivacurium 0.2 mg/kg , IV ( Groups II and III ) , was administered to facilitate tracheal intubation . Anesthesia was maintained with isoflurane ( 0.5%-2 % inspired concentration ) in combination with 67 % N2O in oxygen . Muscle relaxation was maintained in all three groups with intermittent bolus doses of mivacurium , 2 - 4 mg , IV . In Group III , residual neuromuscular block was reversed with a combination of neostigmine , 2.5 mg , and glycopyrrolate , 0.5 mg , IV , at the end of the operation . In the postanesthesia care unit ( PACU ) , patients in Group III had a significantly increased incidence of postoperative nausea and vomiting compared to Group II . The use of succinylcholine ( versus mivacurium ) was also associated with more frequent postoperative nausea and vomiting . However , these emetic sequelae did not delay postoperative recovery times . In addition , a comparable number of patients in each treatment group required analgesic medication for postoperative pain . Although patients who received succinylcholine complained of significantly more neck pain during the 24-h period after discharge , nausea , vomiting , and shoulder pain were similar in all three groups during this period . We conclude that neostigmine and glycopyrrolate may contribute to the development of postoperative emesis when used for reversal of residual neuromuscular block . ( ABSTRACT TRUNCATED AT 250 WORDS Intrathecal ( IT ) neostigmine produces analgesia in animals and humans and enhances systemic opioid analgesia . To examine the safety of IT neostigmine for eventual use in obstetrics , we studied 24 healthy , term pregnant patients scheduled to receive elective cesarean section using a combined spinal-epidural anesthetic . Using an open-label , dose-ranging design , patients received either IT placebo or neostigmine 10 , 30 , or 100 microg in a 1-mL solution of 5 % glucose in normal saline followed in 15 min by 2 % epidural lidocaine for cesarean section . Neostigmine did not affect fetal heart rate tracings or Apgar scores . The women received patient-controlled analgesia intravenous morphine postoperatively . Compared with the glucose control , neostigmine produced a dose-independent reduction in postoperative morphine use . Cumulative average 24-h morphine use was 82 + /- 7 mg for women receiving IT placebo and 50 + /- 8 mg for women receiving IT neostigmine ( P < 0.003 ) . Hourly morphine use was significantly reduced in the neostigmine groups for 10 h postoperatively . These data indicate that IT neostigmine can produce 10 h of post-cesarean section analgesia without adverse fetal effects and support cautious further prospect i ve study Thirty-eight patients undergoing elective hip or knee surgery were r and omly allocated to two groups . Neuromuscular blockade in group A was antagonized with neostigmine 2.5 mg and atropine 1.2 mg , while group B received no drugs to facilitate antagonism of blockade . The incidence and severity of postoperative nausea and vomiting were assessed 24 h after operation . Nausea and vomiting were significantly reduced in group B. The incidence of nausea in group A was 68 % , compared with 32 % in group B ( P less than 0.01 ) . The incidence of vomiting was 47 % in group A , compared with 11 % in group B ( P less than 0.02 ) . A significant relationship was shown between postoperative emetic symptoms and the antagonism of neuromuscular blockade by neostigmine and atropine Eighty patients undergoing outpatient surgery under general anaesthesia were allocated r and omly to two groups : in group A residual neuromuscular block was antagonized with a mixture of neostigmine 1.5 mg and atropine 0.5 mg ; in group B spontaneous recovery was allowed . The patients were assessed after operation in hospital and 24 h after discharge . We found a significant difference ( P < 0.05 ) in requirements for antiemetic therapy with a smaller need in the group which received neostigmine ( in group A four of 40 patients received an antiemetic compared with 12 in group B ) . There was no significant difference in frequency of nausea or vomiting between the two groups . The incidence of postoperative nausea was 14 in group A and 18 in group B and the number of patients with postoperative vomiting was 10 in group A and 15 in group The study was design ed to compare the frequency and severity of postoperative vomiting in paediatric out- patients receiving controlled ventilation ( IPPV ) or breathing spontaneously ( SV ) during anaesthesia for strabismus repair . One hundred and twenty unpremedicated children ( ages 2 - 12 years ) were studied in a r and omized fashion . After intravenous induction of anaesthesia and tracheal intubation , patients breathed halothane 1 - 1.5 per cent inspired and N2O 66 per cent in O2 spontaneously ( n = 60 ) , or received IPPV , halothane 0.5 - 1 per cent , N2O 66 per cent , and pancuronium 0.05 mg.kg-1 , which was reversed with neostigmine and atropine ( n = 60 ) . The incidence of vomiting with SV was 50 per cent ( 95 per cent confidence limits : 34.5 - 65.5 per cent ) compared with 40 per cent ( 24.5 - 55.5 per cent ) with IPPV ( p > 0.25 ) . Patients in the SV group experiencing emesis had longer operations than those not vomiting ( mean ± SEM = 1.5 ± 0,1 vs 1.2 ± 0.1 hours , p < 0.005 ) . This was not the case with IPPV . There was no correlation between age , sex , duration of surgery , or number of extraocular muscles repaired , and frequency or severity of vomiting or time to discharge . No significant advantage was afforded by IPPV over SV in the present study .RésuméCette étude était conçue afin de comparer la fréquence et sévérité du vomissement post-opératoire chez les patients pédiatriques externes admis pour correction de strabisme sous anesthésie générale en respiration spontanée ( SV ) ou ventilation contrôlée ( IPPV ) . Cent vingt patients non prémédiqués âgés de 2 à 12 ans ont été étudiés ďune façon r and omisée . Après ľinduction intraveineuse de ľanesthésie et ľintubation trachéale les patients ont reçu de ľhalothane 1 - 1.5 pour cent et protoxyde ďazote 66 pour cent avec O2 soit en respiration spontanée ( n = 60 ) , soit en ventilation contrôlée de ľhalothane 0.5 - 1 pour cent , protoxyde ďazote 66 pour cent et pancuronium 0.05 mg-kg-1 , qui a été antagonisé avec la néostigmine et ľatropine ( n = 60 ) . Ľincidence de vomissement en ventilation spontanée était de 50 pour cent ( 95 pour cent limite de confiance : 34.5 - 65.5 pour cent ) comparé à 40 pour cent ( 24.5 - 55.5 pour cent ) avec IPPV ( p > 0.25 ) . Les patients du groupe SV ayant accusé des vomissements ont subi des opérations de plus longue durée que ceux qui n’en ont pas eus ( movenne ± SEM = 1.5 ± 0.1 versus 1.2 ± 0.1 heures , p < 0.005 ) . Ceci n’était pas le cas avec le groupe IPPV . Il n’y avait aucune corrélation avec ľâge , sexe , durée de la chirurgie ou le nombre de muscles extra-oculaires réparés avec la fréquence ou la sévérité des vomissements ou le temps du congé . Aucun avantage significatif n‘a acquis par la ventilation contrôlée comparativement à la ventilation spontanée dans la présente élude 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 In dogs , sheep , and rats , spinal neostigmine produces analgesia alone and enhances analgesia from alpha2 ‐adrenergic agonists . This study assesses side effects and analgesia from intrathecal neostigmine in healthy volunteers . Methods After institutional review board approval and informed consent , 28 healthy volunteers were studied . The first 14 volunteers received neostigmine ( 50–750 micro gram ) through a # 19.5 spinal needle followed by insertion of a spinal catheter . The remaining 14 volunteers received neostigmine through a # 25 or # 27 spinal needle without a catheter . Safety measurements included blood pressure , heart rate , oxyhemoglobin saturation , end‐tidal carbon dioxide , neurologic evaluation , and computer tests of vigilance and memory . Analgesia in response to ice water immersion was measured . Results Neostigmine ( 50 micro gram ) through the # 19.5 needle did not affect any measured variable . Neostigmine ( 150 micro gram ) caused mild nausea , and 500–750 micro gram caused severe nausea and vomiting . Neostigmine ( 150–750 micro gram ) produced subjective leg weakness , decreased deep tendon reflexes , and sedation . The 750‐micro gram dose was associated with anxiety , increased blood pressure and heart rate , and decreased end‐tidal carbon dioxide . Neostigmine ( 100–200 micro gram ) in saline , injected through a # 25 or # 27 needle , caused protracted , severe nausea , and vomiting . This did not occur when dextrose was added to neostigmine . Neostigmine by either method of administration reduced visual analog pain scores to immersion of the foot in ice water . Conclusions The incidence and severity of these adverse events from intrathecal neostigmine appears to be affected by dose , method of administration , and baricity of solution . These effects in humans are consistent with studies in animals . Because no unexpected or dangerous side effects occurred , cautious examination of intrathecal neostigmine alone and in combination with other agents for analgesia is warranted Background : It was hypothesized that non‐depolarizing neuromuscular blocking agents impair hypoxic chemosensitivity in man Magnesium sulphate ( MgSO4 ) is currently used for haemodynamic control during anaesthesia and the early postoperative period . We have investigated the effect of this treatment on residual neuromuscular block after administration of vecuronium . Twenty adult patients were allocated r and omly to one of two groups to receive MgSO4 60 mg kg-1 either at recovery from vecuronium block to a train-of-four ( TOF ) ratio of 0.7 , or 1 h after recovery to a TOF ratio of 0.7 . Neuromuscular transmission was monitored using electromyography and TOF stimulation . MgSO4 caused rapid and profound recurarization in all 20 patients . MgSO4 decreased the amount of acetylcholine released at the motor nerve terminal and thus may lead to recurarization in patients previously exposed to neuromuscular blocking agents This study was design ed to compare the effectiveness of antagonism of mivacurium blockade with either neostigmine , edrophonium , or spontaneous recovery . Thirty ASA physical status I or II patients provided informed consent and were r and omized to one of the following groups : Group 1 , placebo saline ; Group 2 , edrophonium ( 1 mg/kg ) ; and Group 3 , neostigmine ( 70 micro gram/kg ) ( n = 10/group ) . All studied patients had anesthesia induced with propofol and maintained with propofol/N2 O/fentanyl . Mivacurium bolus of 0.2 mg/kg was used for endotracheal intubation and an infusion titrated to maintain deep levels of block ( T1 % = 1%-5 % ) ( T1 % = first response/control response times 100 ) . The antagonist was injected at a deep level of the block ( T1 % = 1%-8 % ) and neuromuscular ( NM ) recovery was evaluated by train-of-four twitches ( TOF ) . T1 % was used during maintenance , whereas both T1 % and TOF% ( fourth response/first response times 100 ) were used during recovery . Investigators were blinded to the antagonist used . Plasma cholinesterase activity was measured prior to antagonist administration ( 0 min ) , as well as 15 , 30 , and 60 min after . Plasma cholinesterase activity was decreased to 29 % of control at 15 min and remained at approximately 60 % of the control after neostigmine administration . Edrophonium did not affect plasma cholinesterase activity . Clinical ly adequate spontaneous recovery ( TOF% > or = to 70 % ) of the mivacurium block with placebo required 15 - 18 min . On average , clinical ly adequate antagonism of mivacurium by edrophonium was 50 % faster than placebo and 30%-40 % faster than with neostigmine . In summary , the speed of antagonism with edrophonium is faster than with neostigmine when antagonizing deep mivacurium NM block . Neostigmine-induced depression of plasma cholinesterase , slower onset of action , or combination of both may explain this observation . ( Anesth Analg 1995;81:1005 - 9 Background : After anaesthesia involving pancuronium a high incidence of both residual neuromuscular block and postoperative pulmonary complications ( POPC ) has been reported . The aim of this study was to compare the incidence of POPC following the use of pancuronium , atracurium , and vecuronium , and to examine the effect of residual neuromuscular block on the incidence of POPC The routine use of cholinesterase inhibitors to antagonize residual neuromuscular block may be associated with increased postoperative emesis . Rapid spontaneous recovery from mivacurium may obviate the need for these drugs . In this r and omized , double-blind , placebo-controlled study of 113 healthy children who had received mivacurium as part of a st and ardized anesthetic regimen , we compared the incidence of postoperative complications after spontaneous recovery and after the use of neostigmine-glycopyrrolate or edrophonium-atropine . The anesthetic regimen consisted of halothane , nitrous oxide , fentanyl , 2 micro gram/kg intravenous ( IV ) , mivacurium in an initial dose of 0.2 mg/kg , followed by an infusion , adjusted to maintain > or = to1 evoked contraction response to a supramaximum train-of-four stimulus . At the end of the procedure , patients received by r and om assignment one of three drug combinations : 1 ) neostigmine 70 micro gram/kg + glycopyrrolate 10 micro gram/kg , IV , 2 ) edrophonium 1 mg/kg + atropine 10 micro gram/kg , IV , and 3 ) saline . The trachea was extubated when evoked responses to peripheral nerve stimulation and clinical signs of adequate neuromuscular recovery were present . Postoperative pain was treated with morphine and emesis with metoclopramide . There were no significant differences between the three groups with respect to age , surgery , intraoperative fentanyl , and mivacurium use , time from the end of surgery to tracheal extubation , postanesthesia care unit ( PACU ) arrival and discharge , or in postoperative oxygen saturation values and analgesic requirements . Compared to the placebo group , emesis occurred more often in the PACU in patients receiving the neostigmine-glycopyrrolate combination , but not after edrophonium-atropine . However , after discharge from the PACU , emesis rates were similar in the three study groups . We conclude that spontaneous recovery or reversal with edrophonium from a moderate degree of mivacurium-induced block may offer advantages over the use of neostigmine , without increasing time to PACU arrival . ( Anesth Analg 1995;80:713 - 17 To investigate the effects of different types of anticholinesterase on the incidence of the postoperative nausea and vomiting , 100 ASA class I-II adult premenopausal female patients undergoing elective lower abdominal surgery were r and omized into two groups . In both groups , anesthesia was induced with thiopental and fentanyl and 50 % nitrous oxide and 0.5 - 1.5 % of isoflurane were used for anesthetic maintenance with succinylcholine 1 approximately 1.5 mg/kg for intubation and atracurium 0.3 mg/kg/hr for maintenance of muscle relaxation . Patients received reversal agents for neuromuscular blockade after operation when the evoked train-of-four ( TOF ) count returned to four visual responses . A mixture of atropine 8 micrograms/kg and edrophonium 0.75 mg/kg was given to the first group of patients while atropine 15 micrograms/kg and neostigmine 40 micrograms/kg was given to another group of patients . All the patients were observed for the occurrence of nausea or vomiting for 2 hours after the operation in the recovery room . The incidence of nausea was not statistically significantly different in both groups ( 20 % in neostigmine group and 26 % in edrophonium group ) . The occurrence of vomiting was also similar in both groups ( 8 % in neostigmine group and 6 % in edrophonium group ) . We concluded that there were no difference in the incidence of postoperative nausea or vomiting with the use of either neostigmine or edrophonium with atropine for antagonizing neuromuscular blockade after the lower abdominal surgery One hundred and twenty-one children were studied in this prospect i ve , r and omized double-blind , placebo-controlled comparison of the effectiveness of anticholinergic prophylaxis for the prevention of emetic symptoms following strabismus surgery . The children were allocated to three groups , to receive placebo ( n = 40 ) , glycopyrrolate ( n = 40 ) or atropine ( n = 41 ) . The incidence of intraoperative oculocardiac reflex ( OCR ) and of postoperative emetic symptoms for 24 h was recorded . The incidence of OCR was 55 % in the placebo group compared with 5 % and 2 % in the glycopyrrolate and atropine groups respectively ( P < 0.05 ) . Thirty percent ( 12/40 ) of patients in the placebo group , 25 % ( 10/40 ) in the glycopyrrolate group , and 22 % ( 9/41 ) in the atropine group experienced nausea and /or vomiting ( difference not significant ) . It is concluded that prophylactic administration of anticholinergic agents during strabismus surgery in children despite being effective against the occurrence of the oculocardiac reflex , does not reduce the incidence of emetic symptoms |
13,927 | 24,661,495 | Conclusions Overall , the studies showed a positive effect of drug reminder packaging on adherence and clinical outcomes . | Evidence mapping was used to reveal the effect of drug reminder packaging on medication adherence , to identify research gaps and to make suggestions for future research . | Although r and omised trials are important for evidence -based medicine , little is known about their overall characteristics . We assessed the epidemiology and reporting of method ological details for all 519 PubMed -indexed r and omised trials published in December , 2000 ( 383 [ 74 % ] parallel-group , 116 [ 22 % ] crossover ) . 482 ( 93 % ) were published in specialty journals . A median of 80 participants ( 10th-90th percentile 25 - 369 ) were recruited for parallel-group trials . 309 ( 60 % ) were blinded . Power calculation , primary outcomes , r and om sequence generation , allocation concealment , and h and ling of attrition were each adequately described in less than half of publications . The small sample sizes are worrying , and poor reporting of method ological characteristics will prevent reliable quality assessment of many published trials Outpatient medication adherence is a major problem , especially for patients repeatedly hospitalized for psychiatric disorders . This study included 39 such patients who were receiving case management services from a community mental health center . Patients were matched and r and omly assigned to receive in a single session either ( 1 ) information regarding medication and its benefits , ( 2 ) guidelines for assuring adherence which encompassed all phases related to pill-taking including filling prescriptions , use of a pill container , transportation , self-reminders , doctor 's appointments and so forth , or ( 3 ) the same guidelines as ( 2 ) above but given in the presence of a family member who was enlisted in support . The results showed that adherence increased to about 94 % after the guidelines were given for both the individual and family guideline procedure , whereas adherence remained unchanged at 73 % after the medication information procedure . These results suggest a practical means for assuring a high level of medication adherence for patients with psychiatric disorders CONTEXT Poor medication adherence diminishes the health benefits of pharmacotherapies . Elderly patients with coronary risk factors frequently require treatment with multiple medications , placing them at increased risk for nonadherence . OBJECTIVE To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PATIENTS A multiphase , prospect i ve study with an observational phase and a r and omized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications . The study was conducted from June 2004 to August 2006 . INTERVENTION After a 2-month run-in phase ( measurement of baseline adherence , BP , and LDL-C ) , patients entered a 6-month intervention phase ( st and ardized medication education , regular follow-up by pharmacists , and medications dispensed in time-specific packs ) . Following the intervention phase , patients were r and omized to continued pharmacy care vs usual care for an additional 6 months . MAIN OUTCOME MEASURES Primary end point of the observation phase was change in the proportion of pills taken vs baseline ; secondary end points were the associated changes in BP and LDL-C. Primary end point of the r and omization phase was the between-group comparison of medication persistence . RESULTS A total of 200 elderly patients ( 77.1 % men ; mean [ SD ] age , 78 [ 8.3 ] years ) , taking a mean ( SD ) of 9 ( 3 ) chronic medications were enrolled . Coronary risk factors included drug-treated hypertension in 184 patients ( 91.5 % ) and drug-treated hyperlipidemia in 162 ( 80.6 % ) . Mean ( SD ) baseline medication adherence was 61.2 % ( 13.5 % ) . After 6 months of intervention , medication adherence increased to 96.9 % ( 5.2 % ; P<.001 ) and was associated with significant improvements in systolic BP ( 133.2 [ 14.9 ] to 129.9 [ 16.0 ] mm Hg ; P = .02 ) and LDL-C ( 91.7 [ 26.1 ] to 86.8 [ 23.4 ] mg/dL ; P = .001 ) . Six months after r and omization , the persistence of medication adherence decreased to 69.1 % ( 16.4 % ) among those patients assigned to usual care , whereas it was sustained at 95.5 % ( 7.7 % ) in pharmacy care ( P<.001 ) . This was associated with significant reductions in systolic BP in the pharmacy care group ( -6.9 mm Hg ; 95 % CI , -10.7 to -3.1 mm Hg ) vs the usual care group ( -1.0 mm Hg ; 95 % CI , -5.9 to 3.9 mm Hg ; P = .04 ) , but no significant between-group differences in LDL-C levels or reductions . CONCLUSIONS A pharmacy care program led to increases in medication adherence , medication persistence , and clinical ly meaningful reductions in BP , whereas discontinuation of the program was associated with decreased medication adherence and persistence . TRIAL REGISTRATION clinical trials.gov Identifier : Background : Poor adherence to warfarin therapy is a major contributor to subtherapeutic anticoagulation . Objective : To determine whether use of a monthly medication organizer , filled at each clinic visit , improves anticoagulation control among warfarin-treated patients . Methods : Patients who had a history of nonadherence to warfarin and were attending an inner-city anticoagulation clinic were enrolled in this prospect i ve cohort study and provided with a 28-day medication organizer . Patients were instructed to bring their organizers and warfarin tablets to each anticoagulation clinic visit over the following 3 months . At each visit , the international normalized ratio ( INR ) was measured , warfarin adherence was assessed , and the organizer was filled with the prescribed warfarin regimen until the next scheduled visit . Data on warfarin adherence and INR values during the 3 months prior to enrollment were collected from medical records and compared with postenrollment data . Results : Thirteen patients were enrolled and completed at least one postenrollment clinic visit . Adherence to warfarin therapy improved with use of the medication organizer ( mean ± SD preenrollment 55 ± 25 % , postenrollment 67 ± 21 % ; p = 0.06 ) . There was a significant decrease in the proportion of subtherapeutic INR values ( 60 ± 25 % to 35 ± 29 % ; p = 0.04 ) and a significant improvement in the percent of time spent within the therapeutic INR range ( 32 ± 22 % to 56 ± 28 % ; p = 0.03 ) after enrollment . Conclusions : Use of a monthly medication organizer significantly reduced the percent of subtherapeutic INR values and improved the time spent within the therapeutic anticoagulation range among previously nonadherent patients managed in an inner-city anticoagulation clinic A study was design ed for practitioners wishing to provide comprehensive educational services to the elderly . The effectiveness of four methods ( i.e. , oral instructions alone or in combination with written information , a medication reminder calendar , or a medication reminder package ) of changing patient attitudes , drug knowledge , and compliance behavior was measured in 158 ambulatory cardiovascular patients using a r and omized , controlled , single-blind design . The results indicate that drug knowledge will most likely be improved by a strategy that provides small amounts of specific information , thereby reducing the possibility of overwhelming the patient . Noncompliance behavior caused by forgetfulness can be best improved by combining a reminder aid with oral reinforcement . The high levels of motivation present in these patients indicate that improving patient attitudes toward medication taking may be unnecessary An estimated 20 million Americans suffer from diabetes . Patients with non-insulin-dependent diabetes mellitus ( NIDDM ) comprise approximately 90 % of the diabetic population . An estimated 10 - 30 % of patients with NIDDM withdraw from their prescribed regimen within 1 year of diagnosis , and of the remainder , nearly 20 % administer insufficient medication to facilitate an adequate reduction in blood glucose . A r and omized trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription-refill compliance with sulfonylurea therapy and health service utilization . The subjects were 258 Medicaid beneficiaries from the state of South Carolina , previously untreated for NIDDM , prescribed 5 mg of the second-generation sulfonylurea glyburide twice daily , and monitored with regard to prescription-refill compliance and health service utilization for 1 year . Subjects provided informed consent and were r and omly assigned to one of four experimental groups : ( i ) the control cohort received st and ard pharmaceutical care with each dispensing of glyburide ; ( ii ) the second cohort received st and ard pharmaceutical care and was mailed a medication-refill reminder 10 days prior to each sequential refill date ; ( iii ) the third cohort received st and ard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request ; ( iv ) the fourth cohort received st and ard pharmaceutical care , mailed medication-refill reminders , and unit-of-use packaging . Analysis of variance ( ANOVA ) procedures revealed that patients receiving mailed prescription-refill reminders , unit-of-use packaging , or a combination of both interventions achieved a significant ( P < or = 0.05 ) increase in the Medication Possession Ratio ( MPR ) for sulfonylurea therapy relative to controls . ( ABSTRACT TRUNCATED AT 250 WORDS 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 OBJECTIVES To determine whether an enhanced compliance program ( ECP ) improves patient compliance with bismuth subsalicylate , metronidazole , and tetracycline hydrochloride ( BMT ) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy . DESIGN A r and omized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts . PATIENTS AND METHODS A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were r and omized to a control group or to the ECP group . The ECP group received medication counseling ( written and oral ) from a pharmacist , along with a medication calendar and a minipillbox , as well as a follow-up telephone call after initiation of therapy . Compliance was assessed by a pill count , and factors affecting adherence to the regimen were identified by patients ' reports . RESULTS There was no statistically significant difference between the 2 groups in the number of patients taking more than 60 % of the medications ( 89 % of the control group vs 95 % of the ECP group ; P>.30 ) . However , there was a statistically significant difference in the number of patients taking more than 90 % of the medications ( 67 % of the control group vs 89 % of the ECP group ; P<.01 ) . An intention-to-treat analysis confirmed these results . The most frequently reported adverse effect was gastrointestinal intolerance . Other factors reported to affect compliance included the frequency of dosing and the number of pills . CONCLUSIONS These findings suggest that although adverse effects were common , most patients were able to complete 60 % or more of the 2-week regimen . An ECP further improved the percentage of medications taken Background : Similar to patients with other chronic disorders , patients with serious mental illness ( SMI ) are often poorly adherent with prescribed medications . Objective : We conducted a r and omized controlled trial examining the effectiveness of a pharmacy-based intervention ( Meds-Help ) in increasing antipsychotic medication adherence among Department of Veterans Affairs ( VA ) patients with SMI . We also examined the impact of Meds-Help on psychiatric symptoms , quality of life , and satisfaction with care . Methods : We enrolled 118 patients from 4 VA facilities with schizophrenia , schizoaffective , or bipolar disorder who were on long-term antipsychotics but had antipsychotic medication possession ratios ( MPRs ) < 0.8 in the prior year . Patients were r and omized to usual care ( UC ; n = 60 ) or the pharmacy-based intervention ( Meds-Help ; n = 58 ) . We reassessed adherence at 6 and 12 months , at which time patients completed Positive and Negative Symptom Scales ( PANSS ) , Quality of Well-being Scales ( QWB ) , and Client Satisfaction Question naires ( CSQ-8 ) . Results : Prior to enrollment , Meds-Help and UC patients had mean antipsychotic MPRs of 0.54 and 0.55 , respectively . At 6 months , mean MPRs were 0.91 for Meds-Help and 0.64 for UC patients ; at 12 months , they were 0.86 for Meds-Help and 0.62 for UC patients . In multivariate analyses adjusting for patient factors , Meds-Help patients had significantly higher MPRs at 6 and 12 months ( P < .0001 ) . There were no significant differences between groups in PANSS , QWB , or CSQ-8 scores , but power to detect small effects was limited . Conclusions : Congruent with prior studies of patients with other disorders , a practical pharmacy-based intervention increased antipsychotic adherence among patients with SMI . However , SMI patients may require additional care management components to improve outcomes Objectives To examine the reporting characteristics and method ological details of r and omised trials indexed in PubMed in 2000 and 2006 and assess whether the quality of reporting has improved after publication of the Consoli date d St and ards of Reporting Trials ( CONSORT ) Statement in 2001 . Design Comparison of two cross sectional investigations . Study sample All primary reports of r and omised trials indexed in PubMed in December 2000 ( n=519 ) and December 2006 ( n=616 ) , including parallel group , crossover , cluster , factorial , and split body study design s. Main outcome measures The proportion of general and method ological items reported , stratified by year and study design . Risk ratios with 95 % confidence intervals were calculated to represent changes in reporting between 2000 and 2006 . Results The majority of trials were two arm ( 379/519 ( 73 % ) in 2000 v 468/616 ( 76 % ) in 2006 ) parallel group studies ( 383/519 ( 74 % ) v 477/616 ( 78 % ) ) published in specialty journals ( 482/519 ( 93 % ) v 555/616 ( 90 % ) ) . In both 2000 and 2006 , a median of 80 participants were recruited per trial for parallel group trials . The proportion of articles that reported drug trials decreased between 2000 and 2006 ( from 393/519 ( 76 % ) to 356/616 ( 58 % ) ) , whereas the proportion of surgery trials increased ( 51/519 ( 10 % ) v 128/616 ( 21 % ) ) . There was an increase between 2000 and 2006 in the proportion of trial reports that included details of the primary outcome ( risk ratio ( RR ) 1.18 , 95 % CI 1.04 to 1.33 ) , sample size calculation ( RR 1.66 , 95 % CI 1.40 to 1.95 ) , and the methods of r and om sequence generation ( RR 1.62 , 95 % CI 1.32 to 1.97 ) and allocation concealment ( RR 1.40 , 95 % CI 1.11 to 1.76 ) . There was no difference in the proportion of trials that provided specific details on who was blinded ( RR 0.91 , 95 % CI 0.75 to 1.10 ) . Conclusions Reporting of several important aspects of trial methods improved between 2000 and 2006 ; however , the quality of reporting remains well below an acceptable level . Without complete and transparent reporting of how a trial was design ed and conducted , it is difficult for readers to assess its conduct and validity This article reports a r and omized controlled trial design ed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control . One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice . After completing preenrollment interviews and blood pressure measurements , subjects were r and omly assigned to receive their antihypertensive medications either in the usual vials or in special unit dose-reminder packaging . Follow-up interviews , pill counts , and blood pressure measurements were performed at three-month intervals . There were no statistically significant differences between the control and experimental groups with regard to age , sex , race , employment , education , marital status , insurance coverage , or blood pressure regimens . Prior to the intervention , the experimental group had slightly lower diastolic blood pressure and reported better compliance than the control group . Analyses performed on 165 subjects completing the first follow-up visit revealed no significant improvements in blood pressure control or compliance for patients receiving special medication packaging . While some patients found it easy to remember to take pills packaged using this format , they also found the packages somewhat more difficult and inconvenient to use . In contrast to previously reported work , this study did not demonstrate any significant improvement in compliance with special packaging of antihypertensive medications OBJECTIVE : The aim of this study was to compare cure rates of Helicobacter pylori ( H. pylori ) infection , compliance , and side effects in patients given 10 days of omeprazole 20 mg b.d . , amoxycillin 500 mg t.d.s . , and metronidazole 400 mg t.d.s . ( OAM ) or 10 days OAM plus compliance enhancing measures . METHODS : A total of 119 H. pylori-positive patients were prospect ively r and omized to receive either 10 days OAM or 10 days OAM plus compliance enhancing measures ( medication in a dose dispensing unit , medication chart , an information sheet about H. pylori treatment , and phone call 2 days after starting therapy ) . H. pylori eradication was assessed by 13C-UBT at least 4 wk after cessation of therapy , compliance by phone interview on the last day of therapy and returned pill count , and side effects by phone interview and returned side effects form . RESULTS : In 113 patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients ( 89.5 % ) after 10 days OAM and in 48 of 56 ( 85.7 % ) after 10 days OAM plus compliance enhancing measures ( p= 0.54 ) . In both groups 97 % of medications were taken . Side effects were common ( 82 % of patients ) . Both side effects ( p= 0.001 ) and ulcer versus nonulcer at endoscopy ( p= 0.016 ) were independent predictors of treatment failure ; side effects also predicted noncompliance ( p= 0.02 ) . CONCLUSIONS : Ten days of OAM was effective for H. pylori eradication in our clinical population . Patient compliance was excellent and attempts to increase compliance had no impact on outcome or compliance . Side effects were very common and were significantly associated with treatment failure and decreased compliance CONTEXT The evaluation of the method ologic quality of r and omized controlled trials ( RCTs ) is central to evidence -based health care . Important method ologic detail may , however , be omitted from published reports , and the quality of reporting is therefore often used as a proxy measure for method ologic quality . We examined the relationship between reporting quality and method ologic quality of published RCTs . METHODS Study of 60 reports of placebo-controlled trials published in English- language journals from 1985 to 1997 . Reporting quality was measured using a 25-item scale based on the 1996 issue of the Consoli date d St and ards of Reporting Trials ( CONSORT ) . Concealment of allocation , appropriate blinding , and analysis according to the intention-to-treat principle were indicators of method ologic quality . Method ologic quality was compared between groups of trials defined by reporting quality scores of low , intermediate , and high . Reporting quality scores were compared between groups defined by high and low method ologic quality . RESULTS Among 23 trials of low reporting quality ( median score , 9 [ range , 3.5 - 10.5 ] ) , allocation concealment was unclear for all but 1 trial , but there were 16 trials ( 70 % ) with adequate blinding and 9 trials ( 39 % ) that had been analyzed according to the intention-to-treat principle . Among 18 trials of high reporting quality ( median score , 18 [ range 16.5 - 22.0 ] ) , there were 8 trials ( 44 % ) with adequate allocation concealment , 16 trials ( 89 % ) with adequate blinding , and 13 trials ( 72 % ) analyzed according to the intention-to-treat principle . The median reporting score was 15.0 for the 33 trials that were analyzed according to intention-to-treat principle and 14.5 for the 14 trials with on-treatment analyses ( P = .67 ) . CONCLUSIONS Similar quality of reporting may hide important differences in method ologic quality , and well-conducted trials may be reported badly . A clear distinction should be made between these 2 dimensions of the quality of RCTs The r and omized allocation format remains an exceedingly powerful tool for clinical research . Because humans are the subjects in clinical research , this area of scientific study must operate within the limits dictated by such basic principles as individual autonomy , justice , and beneficence . As r and omized studies have become more common in clinical research , it has become apparent that there is often need for modification of the basic r and omized format or for alternatives . The most widespread modification is the use of sequential analyses to monitor the progress of a trial and ensure early identification of either unanticipated adverse effects or more pronounced differences than expected . Although this modification does not affect the basic r and omized allocation format , it does provide a protection that is lacking in the conventional trial and should be utilized whenever feasible . Modifications that do affect the basic structure of the r and omized trial include adaptive allocation and pre-r and omization . The former is attractive and useful but limited to studies in which results from early enrollees are known before late enrollees are allocated . The greater the linkage between preceding subject results and subsequent assignments , the greater is the protection afforded by such a format . Pre-r and omization , more universally applicable than adaptive allocation , suffers from pronounced cross-over potential and has been criticized on ethical grounds , a combination of weaknesses that raises questions of whether pre-r and omization truly offers advantages to conventional r and omized formats . True alternatives to the r and omized format include the self-controlled study and the historical control design . Both possess significant ethical advantages over the simple r and omized study . Unfortunately , both are at some method ological disadvantage when the same comparison is made . The self-controlled study is limited to the study of conditions sufficiently stable or recurrent that they permit two or more treatment courses in a single patient . In emergency medicine and critical care , this description fits only a small proportion of the illness spectrum . This design is underutilized in clinical research focused on less severe problems of the type seen in ambulatory and primary -care setting s. Such problems can be suitable topics for research by emergency medicine specialists . Historical control studies are eminently applicable in the emergency and critical-care setting . ( ABSTRACT TRUNCATED AT 400 WORDS AIM To evaluate whether a pocket-size tablet-dispensing device would improve adherence to therapy as judged by reduction of HbA(1c ) levels in a large population of Type 2 diabetic patients . METHODS The study design was prospect i ve , r and omized , open label with two parallel groups . Patients ( 2296 ) were recruited from general practitioners and internists and r and omized to either receive a tablet dispenser ( TD ) or no intervention ( control group , CO ) . Patients ' characteristics and current oral therapy ( including dosage ) were recorded at baseline . HbA(1c ) was compared between groups at baseline and after 6 months ' intervention . RESULTS Data were available in 2081 patients . Baseline characterisitcs , including age , body mass index ( BMI ) , blood pressure and gender distribution were comparable between the two groups , as was HbA(1c)[7.9 ( 7.9 - 8.0 ) , TD vs. 8.0 (7.9 - 8.0)% , CO , means ( 95 % CI ) ] . After 6 months , HbA(1c ) improved in both groups , but improvement was significantly greater in TD than in controls [ -0.74 ( 0.67 - 0.80 ) vs. -0.53 (0.47 - 0.59)% , P < 0.0001 ] . Possession of a dispenser remained an independent predictor of improved control in a multiple regression model . In the subgroup analysis , the effect was significantly more pronounced ( i ) in patients receiving more medications and ( ii ) more diabetes medications per day ( iii ) in younger patients . CONCLUSION In this large study population in a ' realistic ' setting , a simple tablet-dispensing device led to a significant and clinical ly relevant improvement in HbA(1c ) levels . Because patients with a more complex therapy regimen benefited more , we suggest that TD might have improved adherence to therapy A r and omised trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription refill compliance with antihypertensive therapy and subsequent health care expenditures . The subjects were 304 Medicaid beneficiaries from the state of Florida , previously untreated for mild to moderate hypertension , prescribed 240 mg of calcium channel antagonist verapamil once daily and monitored regarding prescription refill compliance and health service utilisation for one year . Subjects provided informed consent and were r and omly assigned to one of four experimental groups : ( 1 ) the control cohort received st and ard pharmaceutical care with each dispensing of antihypertensive therapy , ( 2 ) the second cohort received st and ard pharmaceutical care and was mailed a medication-refill reminder ten days prior to each sequential refill date , ( 3 ) the third cohort received st and ard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request and ( 4 ) the fourth cohort received st and ard pharmaceutical care , mailed medication-refill reminders and unit-of-use packaging . Analysis of variance ( ANOVA ) procedures revealed that patients receiving mailed prescription-refill reminders , unit-of-use packaging or a combination of both interventions achieved a significant ( P < or = 0.05 ) increase in the Medication Possession Ratio ( MPR ) for antihypertensive therapy relative to controls . Receipt of both interventions result ed in a significant ( P < or = 0.05 ) improvement in the MPR for antihypertensive therapy relative to all other groups no significant difference was discerned between groups receiving either mailed prescription-refill reminders or unit-of-use packaging . ( ABSTRACT TRUNCATED AT 250 WORDS Summary : Fifty‐three hospital out patients with epilepsy were r and omly allocated to either a control or an intervention group . Patients in the intervention group were subjected to a combination of compliance‐improving strategies : patient counselling , a special medication container , self‐recording of medication intake and seizures , and mailed reminders to collect prescription refills and attend clinic appointments . Compliance with anticonvulsant therapy ( as measured by plasma anticonvulsant levels and prescription refill frequencies ) , and seizure frequency , were evaluated in each patient prior to intervention and 6 months afterwards . Patient compliance and clinical control improved significantly in the intervention group patients . Seizure frequency was , on average , halved following intervention . Compliance and seizure frequency were unaltered in the control group . Intervention failed to improve clinic appointment keeping . Poor compliance with drug therapy commonly confounds the treatment of epilepsy . This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients Background : Medication-related visits to the emergency department are an important but poorly understood phenomenon . We sought to evaluate the frequency , severity and preventability of drug-related visits to the emergency department . Methods : We performed a prospect i ve observational study of r and omly selected adults presenting to the emergency department over a 12-week period . Emergency department visits were identified as drug-related on the basis of assessment by a pharmacist research assistant and an emergency physician ; discrepancies were adjudicated by 2 independent review ers . Results : Among the 1017 patients included in the study , the emergency department visit was identified as drug-related for 122 patients ( 12.0 % , 95 % confidence interval [ CI ] 10.1%–14.2 % ) ; of these , 83 visits ( 68.0 % , 95 % CI 59.0%–76.2 % ) were deemed preventable . Severity was classified as mild in 15.6 % of the 122 cases , moderate in 74.6 % and severe in 9.8 % . The most common reasons for drug-related visits were adverse drug reactions ( 39.3 % ) , nonadherence ( 27.9 % ) and use of the wrong or suboptimal drug ( 11.5 % ) . The probability of admission was significantly higher among patients who had a drug-related visit than among those whose visit was not drug-related ( OR 2.18 , 95 % CI 1.46–3.27 , p < 0.001 ) , and among those admitted , the median length of stay was longer ( 8.0 [ interquartile range 23.5 ] v. 5.5 [ interquartile range 10.0 ] days , p = 0.06 ) . Interpretation : More than 1 in 9 emergency department visits are due to drug-related adverse events , a potentially preventable problem in our health care system Four compliance strategies were compared with education alone to investigate their impact on the control of high blood pressure . One hundred twelve subjects with documented high blood pressure were r and omly assigned to receive education alone , home blood pressure monitoring , contracts , pill packs , or a combination of techniques . Groups were similar in terms of age , sex , race , initial blood pressure , and medications . At the end of the year , there was no significant change in blood pressure for the group that received education alone ( -3/-1 mm Hg ) . There was a statistically significant change in both systolic and diastolic blood pressure for all compliance groups ( -17/-10 mm Hg ) . Information from compliance question naires adds further support to the observation that education alone does not influence compliance while the specific techniques studied did improve compliance . The study was too small to show any difference among techniques A controlled trial of the effect of a unit dose system of tablet/capsule calendar packaging ( Webster-Pak ) on the rate of successful self medication both in hospital and after discharge to the community has been completed in a geriatric assessment and rehabilitation unit . Eighty-four elderly patients , 45 using calendar packs ( study ) , and 39 using conventional bottles or packs ( control ) , were followed for three months after discharge . There was a significant improvement in patient compliance in the study group over controls on discharge ( 86.7 % vs 66.7 % ) , 10 days ( 68.8 % vs 41.0 % ) , one month ( 64.4 % vs 38.5 % ) and three months ( 48.9 % vs 23.1 % ) after discharge . Unit dose packaging is a cost effective method of improving the delivery of medicine in elderly patients , and should be available as part of the health budget OBJECTIVE To evaluate medication adherence and treatment outcomes in elderly out patients using daily-dose blister packaging ( Pill Calendar ) compared with medications packaged in bottles of loose tablets . DESIGN R and omized controlled trial . SETTING Ambulatory care clinics at Ohio State University Medical Center , Columbus ; University of Arizona Health Science Center , Tucson ; and Riverside Method ist Hospital Family Medicine Clinic , Columbus , Ohio , from July 1 , 2002 , to December 31 , 2004 . PATIENTS 85 individuals 65 years of age or older being treated with lisinopril for hypertension . INTERVENTION Patients were r and omly assigned to receive lisinopril in either daily-dose blister packaging ( Pill Calendar ) or traditional bottles of loose tablets . MAIN OUTCOME MEASURES Adherence was assessed by prescription refill regularity and medication possession ratio ( MPR ) . Treatment outcome and use of medical services were assessed by medical record review of blood pressure and morbidity associated with poorly controlled hypertension . RESULTS Patients receiving lisinopril in the daily-dose blister packaging ( Pill Calendar ) refilled their prescriptions on time more often ( P = 0.01 ) , had higher MPRs ( P = 0.04 ) , and had lower diastolic blood pressure ( P = 0.01 ) than patients who had their medications packaged in traditional bottles of loose tablets . CONCLUSION Providing medications in a package that identifies the day each dose is intended to be taken and provides information on proper self-administration can improve treatment regimen adherence and treatment outcomes in elderly patients 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 BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application This pilot study investigated the effects of three different medication management approaches on medication adherence and re source utilization . Sixty-one participants living in an independent elder community in South Florida were r and omly assigned to one of the three medication management approaches : ( 1 ) a pillbox method , ( 2 ) a voice-activated method , and ( 3 ) self-administration of medications as they had in the past . One outcome was measured by recording the number of doses of medications ingested over a 1- , 3- , and 6-month period . Adherence to medications also was measured by the impact on the medical diagnosis . For example , the hypertensive group was defined adherent by a sustained normotensive pressure . Participants ' medical records were examined as to the number of physician office visits , hospitalizations , and home health visits . There were significant differences in the mean number of doses missed , with the fewest in the voice-activated group to the highest in the self-administration ( control ) group . Additionally , the group that self-administered their own medications had more frequent physician office visits and increased hospitalizations . Because the elder population is prone to medication mismanagement for a variety of reasons , nurses are in a unique position to identify population s at risk and suggest interventions that may improve medication adherence PURPOSE This r and omized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with st and ard care in decreasing pain intensity scores , increasing appropriate analgesic prescriptions , and increasing analgesic intake in oncology out patients with pain from bone metastasis . PATIENTS AND METHODS Patients were r and omly assigned to the PRO-SELF intervention ( n = 93 ) or st and ard care ( n = 81 ) . Patients in the st and ard care arm were seen by a research nurse three times and were called three times by phone between the home visits . PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention , were taught how to use a pillbox , and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions . Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management . RESULTS Pain intensity scores decreased significantly from baseline ( all P < .0001 ) in the PRO-SELF group ( ie , least pain , 28.4 % ; average pain , 32.5 % ; and worst pain , 27.0 % ) compared with the st and ard care group ( ie , least increased by 14.6 % , average increased by 1.9 % , and worst decreased by 1.2 % ) . The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3 % to 37.0 % ( P = .008 ) compared with a change from 29.6 % to 32.5 % in the st and ard care group . CONCLUSION The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain The impact of pill organizers on pill taking was determined in the Trial of Antioxidant Vitamins C and E ( TRACE ) Study , a factorial trial of vitamin C and vitamin E supplementation in 184 individuals . Participants were recruited in 1996 - 1997 and r and omized to one of two groups ( pill organizer or no organizer ) and to one of four supplement groups for 2 months . The pill count ( observed/expected X 100 % ) distribution was similar in the organizer and no organizer group for both vitamins . Mean differences in changes in serum vitamin levels between active and placebo groups did not differ by pill organizer use . The impact of pill organizers and blister packs was compared in another trial , the Vitamins , Teachers , and Longevity ( VITAL ) Study , in 297 individuals r and omized in 1993 - 1994 to receive study pills either in blister packs or in pill organizers and to take one of two supplements . Among those with lower adherence , the pill count distribution in the blister-pack group exceeded that in the organizer group . Mean differences in serum vitamin E levels between active and placebo groups did not differ by types of pill packaging . In summary , use of blister packs , but not pill organizers , improved adherence as measured by pill counts among those with lower adherence . Neither pill delivery system improved adherence as measured by serum vitamin levels OBJECTIVE : To determine the effect of unit-of-use drug packaging of medications on compliance among elderly out patients treated with complex medication regimens . DESIGN : Nonblind , r and omized , clinical trial . SETTING : Geriatric outreach health centers in urban public housing units for independent-living elderly people . PATIENTS : Thirty-one patients ( aged ≥60 y ) , each taking three or more prescribed medications . Patients were r and omly assigned to one of three study groups : Group 1 ( n=12 ) , no change in dosing or packaging ; group 2 ( n=10 ) , conventional packaging with twice-daily dosing ; group 3 ( n=9 ) , unit-of-use packaging with twice-daily dosing . INTERVENTION : A unit-of-use package consisting of a two-ounce plastic cup with a snap-on lid containing all medications to be taken at the time of dosing . MAIN OUTCOME MEASURES : Medication compliance was assessed monthly for six months using tablet counts . RESULTS : Medication compliance was significantly better in group 3 ( 92.6 percent ) using unit-of-use packaging compared with either group 1 ( 79 percent ) or group 2 ( 82.6 percent ) ( p=0.017 ) . Compliance did not differ between groups 1 and 2 . CONCLUSIONS : In this small study of elderly out patients taking three or more medications , unit-of-use packaging and twice-daily dosing improved medication compliance compared with conventional packaging OBJECTIVE To assess the impact of calendar blister pack ( CBP ) use on glycemic and blood pressure control . RESEARCH DESIGN AND METHODS We conducted an 8-month r and omized controlled double-blind study among diabetic patients with poor glucose control ( HbA1c > 9.0 % ) in an urban area of South Auckl and , New Zeal and , with a high proportion of Maori and Pacific Isl and s people . Subjects included 68 consecutive patients , of whom 50 % were prescribed three or more medications per day RESULTS HbA1c was reduced by 0.95+/-0.22 % in the CBP group and 0.15+/-0.25 % in the control group ( P = 0.026 ) . Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group ( P = 0.0041 ) . Systolic blood pressure did not change significantly CONCLUSIONS CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications The impact of a ten-minute , soap opera-style videotape on knowledge and treatment behavior of black men with gonorrhea was tested in r and omized clinical trials . The videotape , shown to individual patients after diagnosis , produced a sizeable increase in the percentage of patients who returned for their test-of-cure examination : while only 43.3 % of control group patients returned , 53.5 % of those in the videotape group did so ; chi 2(1 ) = 9.0 ; P less than 0.003 . In a follow-up study , similar results were found : videotape group ( 59.0 % ) , control group ( 39.1 % ) ; chi 2(1 ) = 6.2 ; P less than 0.015 . The videotape also produced large , significant increases in patient knowledge , as measured by a test administered during patients ' clinic visit ( P less than 0.0001 ) . No measureable effect of the videotape was detected on patients ' willingness to refer sexual contacts for treatment . The findings suggest that clinic-based educational material s , particularly soap opera-style videotapes that engender audience identification , create emotional significance for the viewer , and model requisite communication skills , may have a significant role to play in control of sexually transmitted diseases Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy . The adherence package included an education programme , individualized planning of regimens , and the opportunity for a patient to choose from a number of adherence aids and reminder devices . A r and omized step wedge design was used . Forty-three individuals were r and omized to begin the intervention over a five-month period . There was a substantial fall in the number of missed doses reported for the last four days ( 0.76 to 0.38 , P = 0.03 ) and last seven days ( 1.5 to 0.74 , P = 0.005 ) but not for the last 28 days ( 2.5 to 2.5 , P = 0.63 ) . There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention . The Morisky score during the pre and post intervention periods was significantly different ( P = 0.006 ) , 2.9 ( SD 0.9 ) and 3.3 ( SD 0.8 ) respectively . This adherence package improved self reported adherence during the last four and seven days |
13,928 | 26,626,157 | Conclusions This systematic review suggested that frail older adults seemed to benefit from exercise interventions , although the optimal program remains unclear . | Background Low physical activity has been shown to be one of the most common components of frailty , and interventions have been considered to prevent or reverse this syndrome .
The purpose of this systematic review of r and omized , controlled trials is to examine the exercise interventions to manage frailty in older people . | OBJECTIVES To determine whether obesity is associated with the frailty phenotype and , if so , whether comorbid conditions or inflammatory markers explain this association . DESIGN Cross-sectional analysis of baseline data from the Women 's Health and Aging Studies I ( 1992 ) and II ( 1994 ) , complementary population -based studies . SETTING Twelve contiguous ZIP code areas in Baltimore , Maryl and . PARTICIPANTS Five hundred ninety-nine community-dwelling women aged 70 to 79 with a body mass index ( BMI ) greater than 18.5 kg/m(2 ) . MEASUREMENTS The dependent variables were the frailty syndrome , including prefrailty , defined as presence of one or two of five frailty indicators ( weakness , slowness , weight loss , low physical activity , exhaustion ) , and frailty , defined as three or more indicators . Independent variables included BMI , categorized using World Health Organization criteria as normal ( 18.5 to < 25 kg/m(2 ) ) , overweight ( 25 to < 30 kg/m(2 ) ) , and obese ( > /=30 kg/m(2 ) ) ; chronic diseases ; C-reactive protein ; and serum carotenoids . RESULTS Being overweight was significantly associated with prefrailty , and obesity was associated with prefrailty and frailty . In all frail women , regardless of BMI group , a similar pattern of three defining frailty indicators was found : slowness , weakness , and low activity ( with the addition of weight loss in the normal weight group . ) In multinomial regression models , obesity was significantly associated with prefrailty ( odds ratio (OR)=2.23 , 95 % confidence interval (CI)=1.29 - 3.84 ) and frailty ( OR=3.52 , 95 % CI=1.34 - 9.13 ) , even when controlling for covariates . CONCLUSION Obesity is associated with the frailty syndrome in older women in cross-sectional data . This association remains significant even when multiple conditions associated with frailty are considered . Prospect i ve studies are needed to confirm this finding Body composition and the components of energy metabolism were examined in 12 men and women , aged 56 - 80 y , before and after 12 wk of resistance training . Subjects were r and omly assigned to groups that consumed diets that providing either 0.8 or 1.6 g protein.kg-1.d-1 and adequate total energy to maintain baseline body weight . Fat mass decreased 1.8 + /- 0.4 kg ( P < 0.001 ) and fat-free mass ( FFM ) increased 1.4 + /- 0.4 kg ( P < 0.01 ) in these weight-stable subjects . The increase in FFM was associated with a 1.6 + /- 0.4 kg increase in total body water ( P < 0.01 ) but no significant change in either protein plus mineral mass or body cell mass . With resistance training , the mean energy intake required for body weight maintenance increased by approximately 15 % . Increased energy expenditure included increased resting metabolic rate ( P < 0.02 ) and the energy cost of resistance exercise . Dietary protein intake did not influence these results . Resistance training is an effective way to increase energy requirements , decrease body-fat mass , and maintain metabolically active tissue mass in healthy older people and may be useful as an adjunct to weight-control programs for older adults Background and aim Physical frailty has been regarded as a precursor state to disability and dependence on others for daily activities . Frail individuals are considered to be the group of patients that presents the most complex and challenging problems to health care professionals . The purpose of this study was to evaluate whether a 12-week functional circuit training program ( FCT ) could reduce self-reported fear of falling and improve health status in a group of physically frail community-dwelling older individuals . Methods Fifty-one individuals ( 31 F , 20 M ) , mean age ( SD ) 84 ( 2.9 ) years old , were considered frail and tested at week 0 and r and omly assigned into two groups ( intervention group , FCT = 26 ; control group , CG = 25 ) . FCT underwent a structured 12-week FCT program , which focused on a combination of functional balance and lower-body strength-based exercises . CG met once a week for health education meetings . Measures of self-reported fear of falling ( Activities-specific Balance Confidence scale ) and health status ( SF-12 ) were assessed at week 0 , 12 and 36 . All longitudinal analyses for continuous variables that were measured at the three time points ( week 0 , 12 and 36 ) were performed using linear mixed modeling . Results FCT participants had greater improvements than those in the CG in fear of falling and self-reported physical function , physical composite score and mental composite score ; these improvements were maintained in the week 36 follow-up , with significant group-by-time interactions by the end of the study . Conclusions These data indicate that a FCT program is effective in improving self-reported measures of fear of falling and health status in a group of physically frail individuals BACKGROUND AND PURPOSE Systematic review s and meta-analyses often include an evaluation of the method ological quality of the individual studies that have been included , and are usually conducted by at least 2 individuals . The objective of this study was to assess the method ological quality and reliability of a series of r and omized controlled trials ( RCTs ) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence -Based Data base ( PEDro ) Scale . METHODS Two abstract ors independently review ed 81 RCTs assessing a variety of interventions . The Cohen kappa statistic and the intraclass correlation coefficient ( ICC ) were used to assess agreement between abstract ors . RESULTS The average total PEDro scores were 5.94 ( SD=1.43 ) for all studies combined , 6.88 ( SD=1.2 ) for pharmacological studies , and 5.29 ( SD=1.26 ) for nonpharmacological studies . The median score for pharmacological studies was significantly higher than that for nonpharmacological studies ( 7 versus 5 ) . Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement ( 1.00 ) for r and omization and reporting of results from between-group comparisons . The ICCs associated with the cumulative PEDro score were .91 ( 95 % confidence interval [CI]=.83-.94 ) for all studies , .89 ( 95 % CI=.78-.95 ) for pharmacological studies , and .91 ( 95 % CI=.84-.952 ) for nonpharmacological studies . DISCUSSION AND CONCLUSION The method ological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions . There was good agreement between raters at an individual item level and in total PEDro scores . A lack of reporting clarity , poor organization of the report , or the failure to include salient details contributed to less-than-perfect agreement between raters BACKGROUND frail older people have a high risk of falling . OBJECTIVE assess the effect of a frailty intervention on risk factors for falls and fall rates in frail older people . DESIGN r and omised controlled trial . PARTICIPANTS 241 community-dwelling people aged 70 + without severe cognitive impairment who met the Cardiovascular Health Study frailty definition . INTERVENTION multifactorial , interdisciplinary intervention targeting frailty characteristics with an individualised home exercise programme prescribed in 10 home visits from a physiotherapist and interdisciplinary management of medical , psychological and social problems . MEASUREMENTS risk factors for falls were measured using the Physiological Profile Assessment ( PPA ) and mobility measures at 12 months by a blinded assessor . Falls were monitored with calendars . RESULTS participants had a mean ( SD ) age of 83.3 ( 5.9 ) years , 68 % were women and 216 ( 90 % ) completed the study . After 12 months the intervention group had significantly better performance than the control group , after controlling for baseline values , in the PPA components of quadriceps strength ( between-group difference 1.84 kg , 95 % CI 0.17 - 3.51 , P = 0.03 ) and body sway ( -90.63 mm , 95 % CI -168.6 to -12.6 , P = 0.02 ) , short physical performance battery ( 1.58 , 95 % CI 1.02 - 2.14 , P ≤ 0.001 ) and 4 m walk ( 0.06 m/s 95 % CI 0.01 - 0.10 , P = 0.02 ) with a trend toward a better total PPA score ( -0.40 , 95 % CI -0.83 - 0.04 , P = 0.07 ) but no difference in fall rates ( incidence rate ratio 1.12 , 95 % CI 0.78 - 1.63 , P = 0.53 ) . CONCLUSION the intervention improved performance on risk factors for falls but did not reduce the rate of falls . TRIAL REGISTRATION ACTRN12608000250336 OBJECTIVES To determine the effects of moderate intensity group-exercise programs on falls , functional performance , and disability in older adults ; and to investigate the influence of frailty on these effects . DESIGN A 20-week , multicenter r and omized controlled trial , with 52-week follow-up . SETTING Fifteen homes for the elderly . PARTICIPANTS Two hundred seventy-eight men and women ( mean age + /- st and ard deviation , 85+/-6y ) . INTERVENTIONS Two exercise programs were r and omly distributed across 15 homes . The first program , functional walking ( FW ) , consisted of exercises related to daily mobility activities . In the second program , in balance ( IB ) , exercises were inspired by the principles of Tai Chi . Within each home participants were r and omly assigned to an intervention or a control group . Participants in the control groups were asked not to change their usual pattern of activities . The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks . MAIN OUTCOME MEASURES Falls , Performance Oriented Mobility Assessment ( POMA ) , physical performance score , and the Groningen Activity Restriction Scale ( GARS ) ( measuring self-reported disability ) . RESULTS Fall incidence rate was higher in the FW group ( 3.3 falls/y ) compared with the IB ( 2.4 falls/y ) and control ( 2.5 falls/y ) groups , but this difference was not statistically significant . The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail ( hazard ratio [ HR ] = 2.95 ; 95 % confidence interval [ CI ] , 1.64 - 5.32 ) . For participants who were classified as being pre-frail , the risk of becoming a faller decreased ; this effect became significant after 11 weeks of training ( HR = .39 ; 95 % CI , .18-.88 ) . Participants in both exercise groups showed a small , but significant improvement in their POMA and physical performance scores . In the FW group , this held true for the GARS score as well . Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores . CONCLUSIONS Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail , but not in frail elderly BACKGROUND Little is known about the natural course of frailty . We performed a prospect i ve study to determine the transition rates between frailty states and to evaluate the effect of the preceding frailty state on subsequent frailty transitions . METHODS We studied 754 community-living persons , aged 70 years or older , who were nondisabled in 4 essential activities of daily living . Frailty , assessed every 18 months for 54 months , was defined on the basis of weight loss , exhaustion , low physical activity , muscle weakness , and slow walking speed . Participants were classified as frail if they met 3 or more of these criteria , as prefrail if they met 1 or 2 of the criteria , and as nonfrail if they met none of the criteria . RESULTS Of the 754 participants , 434 ( 57.6 % ) had at least 1 transition between any 2 of the 3 frailty states during 54 months . The rates were 36.8 % , 21.5 % , and 9.2 % for 1 , 2 , and 3 transitions , respectively . During the 18-month intervals , transitions to states of greater frailty were more common ( rates up to 43.3 % ) than transitions to states of lesser frailty ( rates up to 23.0 % ) , and the probability of transitioning from being frail to nonfrail was very low ( rates , 0%-0.9 % ) , even during an extended period . The likelihood of transitioning between frailty states was highly dependent on one 's preceding frailty state . CONCLUSIONS Frailty among older persons is a dynamic process , characterized by frequent transitions between frailty states over time . Our findings suggest ample opportunity for the prevention and remediation of frailty Low-intensity ( ~50 % of a single repetition maximum—1 RM ) resistance training combined with vascular occlusion results in increases in muscle strength and cross-sectional area [ Takarada et al. ( 2002 ) Eur J Appl Physiol 86:308–331 ] . The mechanisms responsible for this hypertrophy and strength gain remain elusive and no study has assessed the contribution of neuromuscular adaptations to these strength gains . We examined the effect of low-intensity training ( 8 weeks of unilateral elbow flexion at 50 % 1 RM ) both with ( OCC ) and without vascular occlusion ( CON ) on neuromuscular changes in the elbow flexors of eight previously untrained men [ 19.5 ( 0.4 ) years ] . Following training , maximal voluntary dynamic strength increased ( P<0.05 ) in OCC ( 22 % ) and CON ( 23 % ) ; however , isometric maximal voluntary contraction ( MVC ) strength increased in OCC only ( 8.3 % , P<0.05 ) . Motor unit activation , assessed by interpolated twitch , was high ( ~98 % ) in OCC and CON both pre- and post-training . Evoked resting twitch torque decreased 21 % in OCC ( P<0.05 ) but was not altered in CON . Training result ed in a reduction in the twitch : MVC ratio in OCC only ( 29 % , P<0.01 ) . Post-activation potentiation ( PAP ) significantly increased by 51 % in OCC ( P<0.05 ) and was not changed in CON . We conclude that low-intensity resistance training in combination with vascular occlusion produces an adequate stimulus for increasing muscle strength and causes changes in indices of neuromuscular function , such as depressed resting twitch torque and enhanced PAP OBJECTIVES To determine the effect of static and dynamic frailty on mortality in older men and women . DESIGN A prospect i ve cohort study with three 3-year measurement cycles . SETTING Population based . PARTICIPANTS The sample was derived from the Longitudinal Aging Study Amsterdam and consisted of respondents who participated in two cycles ( T1 : 1992/1993 and T2 : 1995/1996 ) and for whom there was complete data on disability and chronic diseases ( N=2,257 ) . MEASUREMENTS Nine frailty markers were assessed at T1 and T2 . The frailty markers were defined in two ways : low functioning at T2 ( static frailty ) and change in functioning between T1 and T2 ( dynamic frailty ) . Survival time , calculated in days from T2 to January 1 , 2000 , was used as the outcome variable . Predictive ability was examined using Cox proportional hazards analyses separately for men and women . RESULTS Women were frailer than men . Static frailty was significantly associated with mortality in men ( relative risk (RR)=2.4 ) and in women ( RR=2.6 ) . Dynamic frailty was also associated with mortality in women ( RR=2.6 ) , but it was not significantly associated with mortality in men ( RR=1.3 ) . When disability and chronic diseases were included in the model as possible mediators , these RRs dropped to 1.6 , 2.0 , 2.1 , and 1.2 , respectively , of which the first three were still significant . CONCLUSION Frailty was associated with mortality to a greater extent in women than in men , and this effect was independent of disability and chronic disease . In men , the static definition of frailty was more predictive of mortality than the dynamic definition This r and omized controlled trial examined the effects of multicomponent training on muscle power output , muscle mass , and muscle tissue attenuation ; the risk of falls ; and functional outcomes in frail nonagenarians . Twenty-four elderly ( 91.9 ± 4.1 years old ) were r and omized into intervention or control group . The intervention group performed a twice-weekly , 12-week multicomponent exercise program composed of muscle power training ( 8–10 repetitions , 40–60 % of the one-repetition maximum ) combined with balance and gait retraining . Strength and power tests were performed on the upper and lower limbs . Gait velocity was assessed using the 5-m habitual gait and the time-up- and -go ( TUG ) tests with and without dual-task performance . Balance was assessed using the FICSIT-4 tests . The ability to rise from a chair test was assessed , and data on the incidence and risk of falls were assessed using question naires . Functional status was assessed before measurements with the Barthel Index . Midthigh lower extremity muscle mass and muscle fat infiltration were assessed using computed tomography . The intervention group showed significantly improved TUG with single and dual tasks , rise from a chair and balance performance ( P < 0.01 ) , and a reduced incidence of falls . In addition , the intervention group showed enhanced muscle power and strength ( P < 0.01 ) . Moreover , there were significant increases in the total and high-density muscle cross-sectional area in the intervention group . The control group significantly reduced strength and functional outcomes . Routine multicomponent exercise intervention should be prescribed to nonagenarians because overall physical outcomes are improved in this population BACKGROUND Progressive resistance exercise training ( PRT ) has been shown to increase muscle strength and fat-free mass ( FFM ) in elderly persons . Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons . METHODS Ninety-one community-dwelling sedentary men and women , 78 years and older with physical frailty ( defined using st and ardized objective criteria ) were enrolled in a 9-month trial of exercise training ( ET ) . Physical frailty was defined as having 2 of the 3 following criteria : modified Physical Performance Test score between 18 and 32 , peak aerobic power between 10 and 18 ml/kg/min , or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living . Participants were r and omly assigned to either a control ( CTL ) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT . RESULTS After completion of PRT , ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension ( mean Delta + 5.3 + /- 13 ft/lb vs + 1.1 + /- 11 ft/lb , p = .05 ) , measured using isokinetic dynamometry . Total body FFM ( measured using dual energy x-ray absorptiometry ) increased in the ET group , but not in the CTL group ( mean Delta + 0.84 + /- 1.4 kg vs + 0.01 + /- 1.5 kg , p = .005 ) . Total , trunk , intra-abdominal , and subcutaneous fat mass ( measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging ) did not change in response to PRT . CONCLUSIONS Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail , community-dwelling elderly women and men . This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population Objective To investigate the combined and separate effects of exercise and milk fat globule membrane ( MFGM ) supplementation on frailty , physical function , physical activity level , and hematological parameters in community-dwelling elderly Japanese women . Methods A total of 131 frail , elderly women over 75 years were r and omly assigned to one of four groups : exercise and MFGM supplementation ( Ex+MFGM ) , exercise and placebo ( Ex+Plac ) , MFGM supplementation , or the placebo group . The exercise group attended a 60-minute training program twice a week for three months , and the MFGM group ingested 1 g of the MFGM supplement in pill form , daily for 3 months . The primary outcome measure was change in frailty status based on Fried ’s frailty phenotype . Secondary outcome measures included body composition , physical function and hematological parameters , and interview survey components assessing lifestyle factors . Participants were followed for 4 months post-intervention . Results Significant group × time interactions were observed for usual walking speed ( P = 0.005 ) , timed up & go ( P<0.001 ) , and insulin-like growth factor-binding protein 3 / insulin-like growth factor 1 ratio ( P = 0.013 ) . The frailty components revealed that weight loss , exhaustion , low physical activity , and slow walking speed were reversed , but low muscle strength did not significantly changed . Frailty reversal rate was significantly higher in the Ex+MFGM ( 57.6 % ) than in the MFGM ( 28.1 % ) or placebo ( 30.3 % ) groups at post-intervention ( χ2 = 8.827 , P = 0.032 ) , and at the follow-up was also significantly greater in the Ex+MFGM ( 45.5 % ) and Ex+Plac ( 39.4 % ) groups compared with the placebo ( 15.2 % ) group ( χ2 = 8.607 , P = 0.035 ) . The exercise+MFGM group had the highest odds ratio ( OR ) for frailty reversal at post-intervention and follow-up ( OR = 3.12 , 95 % confidence interval ( CI ) = 1.13–8.60 ; and OR = 4.67 , 95 % CI = 1.45–15.08 , respectively ) . Conclusion This study suggests that interventions including exercise and nutrition can improve frailty status . Statistically significant additive effects of MFGM with exercise could not be confirmed in this population , and further investigation in larger sample s is necessary . Trial Registration The Japan Medical Association Clinical Trial Registry Introduction The purpose of this study was to investigate the effect of a 12-month Balance Training Program on balance , mobility and falling frequency in women with osteoporosis . Methods Sixty-six consecutive elderly women were selected from the Osteometabolic Disease Outpatient Clinic and r and omized into 2 groups : the ‘ Intervention ’ , su bmi tted for balance training ; and the ‘ Control ’ , without intervention . Balance , mobility and falling frequency were evaluated before and at the end of the trial , using the Berg Balance Scale ( BBS ) , the Clinical Test Sensory Interaction Balance ( CTSIB ) and the Timed “ Up & Go ” Test ( TUGT ) . Intervention used techniques to improve balance consisting of a 1-hour session each week and a home-based exercise program . Results Sixty women completed the study and were analyzed . The BBS difference was significant higher in the Intervention group compared to Control ( 5.5 ± 5.67 vs −0.5 ± 4.88 score , p < 0.001 ) . Similarly , the number of patients in the Intervention group presented improvement in two conditions of CTSIB compared to Control ( eyes closed and unstable surface condition : 13 vs one patient , p < 0.001 and eyes open , visual conflict and unstable surface condition : 12 vs one patient , p < 0.001 ) . Additionally , the differences between the TUGT were reduced in the Intervention group compared to Control ( −3.65 ± 3.61 vs 2.27 ± 7.18 seconds , p < 0.001 ) . Notably , this improvement was paralleled by a reduction in the number of falls/patient in the Intervention group compared to Control ( −0.77 ± 1.76 vs 0.33 ± 0.96 , p = 0.018 ) . Conclusion This longitudinal prospect i ve study demonstrated that an intervention using balance training is effective in improving functional and static balance , mobility and falling frequency in elderly women with osteoporosis Objective : To evaluate the specific effects of balance and gait exercises among frail elderly individuals . Design : A r and omized three-group parallel controlled study . Setting : Geriatric health services facility in Japan . Subjects : Thirty-four frail elderly subjects attending the care facility were r and omized into a control group , an exercise group with emphasis on balance or an exercise group with emphasis on gait re-education . Interventions : The two exercise groups received balance or gait exercise for 40 minutes , 2–3 times weekly , for 12 weeks . Main outcome measures : One Leg St and ing Test , Functional Reach Test , Manual Perturbation Test , Functional Balance Scale , Performance-Oriented Mobility Assessment , Timed ‘ Up and Go ’ Test and Stair Climbing/Descending Test . These assessment s were performed before and after 12-week intervention . Results : Comparison of the performance before and after intervention demonstrated significant improvement in One Leg St and ing Test , Functional Reach Test and Functional Balance Scale in the balance exercise group , and Functional Balance Scale , Timed ‘ Up and Go ’ Test and Stair Descending Test showed improvement in the gait exercise group . All test items showed no significant differences in the control groups . Among the three groups , the balance exercise group showed more significant improvement in Functional Balance Scale , and the gait exercise group showed more significant improvement in Performance-Oriented Mobility Assessment than the control group . The balance exercise group showed greater improvement in performance in Functional Reach Test than the gait exercise group . Conclusions : Balance exercises led to improvements in static balance function , and gait exercises result ed in improvements to dynamic balance and gait functions in the very frail elderly OBJECTIVE To determine the reliability of rapid screening by clinical ly derived geriatric criteria in predicting outcomes of elderly hospitalized patients . DESIGN Prospect i ve cohort study of 985 patients screened at the time of hospital admission and followed for 1 year with respect to the outcomes of mortality , hospital readmission , and nursing home utilization . SETTING Palo Alto Veterans Affairs Medical Center , a tertiary care teaching hospital . SUBJECTS Male patients 65 years of age and older admitted to the Medical and Surgical services during the period from October 1 , 1985 through September 30 , 1986 . RESULTS Patients were grouped by specific screening criteria into three groups of increasing frailty : Independent , Frail , and Severely Impaired . Each criterion focused on a geriatric condition and was design ed to serve as a marker for frailty . Increasing frailty was significantly correlated with increasing length of hospital stay ( P less than 0.0001 ) , nursing home utilization ( P less than 0.0001 ) , and mortality ( P less than 0.0001 ) . Multivariate analyses revealed that the clinical groups were more predictive of mortality and nursing home utilization than were age or Diagnosis-Related Groups ( DRGs ) . Rehospitalization was unrelated to age , clinical group , or DRG , suggesting that utilization may not be driven by the clinical factors measured in this study . CONCLUSIONS Rapid clinical screening using specific geriatric criteria is effective in identifying frail older subjects at risk for mortality and nursing home utilization . Our findings suggest that geriatric syndromes are more predictive of adverse outcomes than diagnosis per se . This well operationalized screening process is inexpensive as well as effective and could easily be introduced into other hospital setting 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 OBJECTIVE To determine whether an exercise programme provided by public health nurses is effective in improving physical function and psychological status in elderly people , in reducing falls and risk factors for falls in elderly people , and whether the intervention is a feasible programme within the community . DESIGN Controlled intervention trial . SUBJECTS Participants included 144 persons in the intervention group and 124 persons in the control group , who were living at home , aged over 65 years , and with 5 or more risk factors for falls identified using the question naire for fall assessment ( Suzuki ) . METHODS For participants in the intervention group , an exercise programme was provided by public health nurses . This comprised a weekly exercise class of 2 hours for 17 weeks , supplemented by daily home exercises . Number of risk factors , physical function and psychological status were compared between the intervention and control groups before and after intervention . The number of further falls during the intervention was also compared between the 2 groups . RESULTS The programme significantly improved physical function and emotional status , and reduced the number of falls and risk factors for falls . The excellent adherence rate represented broad acceptance of the intervention . CONCLUSION The intervention programme was effective and feasible to operate in the community OBJECTIVES Although deficits in skeletal muscle strength , gait , balance , and oxygen uptake are potentially reversible causes of frailty , the efficacy of exercise in reversing frailty in community-dwelling older adults has not been proven . The aim of this study was to determine the effects of intensive exercise training ( ET ) on measures of physical frailty in older community-dwelling men and women . DESIGN R and omized controlled trial . SETTING Medical school research center . PARTICIPANTS One hundred fifteen sedentary men and women ( mean age + /- st and ard deviation = 83 + /- 4 ) with mild to moderate physical frailty , as defined by two of the following three criteria : Modified Physical Performance Test ( modified PPT ) score between 18 and 32 , peak oxygen uptake ( VO2 peak ) between 10 and 18 mL/kg/min , and self-report of difficulty or assistance with one basic activity of daily living ( ADL ) , or two instrumental ADLs . INTERVENTION Participants were r and omly assigned to a control group that performed a 9-month low-intensity home exercise program ( control ) or an exercise-training program ( ET ) . The control intervention primarily consisted of flexibility exercises . ET began with 3 months of flexibility , light-resistance , and balance training . During the next 3 months , resistance training was added , and , during the next 3 months , endurance training was added . MEASUREMENTS Modified PPT score , VO2 peak , performance of ADLs as measured by the Older Americans Re sources and Services instrument , and the Functional Status Question naire ( FSQ ) . RESULTS ET result ed in significantly greater improvements than home exercise in three of the four primary outcome measures . Adjusted 95 % confidence bounds on the magnitude of improvement in the ET group compared with the control group were 1.0 to 5.2 points for the modified PPT score , 0.9 to 3.6 mL/kg/min for VO2 peak , and 1.6 to 4.9 points for the FSQ score . CONCLUSIONS Our results show that intensive ET can improve measures of physical function and pre clinical disability in older adults who have impairments in physical performance and oxygen uptake and are not taking hormone replacement therapy better than a low-intensity home exercise program To study risk factors for falling , we conducted a one-year prospect i ve investigation , using a sample of 336 persons at least 75 years of age who were living in the community . All subjects underwent detailed clinical evaluation , including st and ardized measures of mental status , strength , reflexes , balance , and gait ; in addition , we inspected their homes for environmental hazards . Falls and their circumstances were identified during bimonthly telephone calls . During one year of follow-up , 108 subjects ( 32 percent ) fell at least once ; 24 percent of those who fell had serious injuries and 6 percent had fractures . Predisposing factors for falls were identified in linear-logistic models . The adjusted odds ratio for sedative use was 28.3 ; for cognitive impairment , 5.0 ; for disability of the lower extremities , 3.8 ; for palmomental reflex , 3.0 ; for abnormalities of balance and gait , 1.9 ; and for foot problems , 1.8 ; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables . The risk of falling increased linearly with the number of risk factors , from 8 percent with none to 78 percent with four or more risk factors ( P less than 0.0001 ) . About 10 percent of the falls occurred during acute illness , 5 percent during hazardous activity , and 44 percent in the presence of environmental hazards . We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling 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 . OBJECTIVES to determine whether a repetitive activities of daily living ( ADL ) activity programme improves health status , life satisfaction and mobility for older people living in residential care . DESIGN cluster r and omised controlled trial . SETTING five low-level dependency residential care homes in Auckl and , New Zeal and . PARTICIPANTS one hundred and forty-nine older residents ( mean age 84.7 years ) . INTERVENTION trained research staff worked with residents in intervention wards to set a goal and complete a functional assessment for each resident . They then design ed an individualised activity programme based on ADL and worked with residential care home staff to implement the programme into daily activities of residents . MEASUREMENTS mobility : timed-up- and -go ( TUG ) ; life satisfaction : late life satisfaction index ( LSI-Z ) ; and health status : SF-36 were assessed at baseline , 3- and 6-months follow-up . RESULTS in the intervention group the SF-36 total physical component summary ( PCS ) score improved at 3 months in comparison with the control group . There was no difference between groups on mobility measures at any time , nor any measures at 6-months follow-up . Significant contamination is likely to have affected the 6-month follow-up measures . CONCLUSIONS a repetitive ADL exercise programme may improve health status in the short term in a group of frail older people living in residential care . Further research is needed to establish sustainability of change OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( < 12 ng/mL ) at baseline . CONCLUSION Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people The purpose of this study was to determine the influence of simple , progressive lower body exercise training , focusing on strength and power , on functional abilities in frail older adults . Twenty-five residents of a long-term care facility ( 75 - 94 yrs ) participated in this r and omized controlled trial of 10-wks duration . The exercise group ( Ex , n = 18 ) underwent simple , progressive lower body resistance exercises , specifically aim ed at improving muscle power , 3 times/wk ; the control subjects ( Con , n = 7 ) maintained their usual daily activities . Knee extensor strength and power were measured on an isokinetic dynamometer ( 180 degrees/s ) , and functional performance was assessed from a 6-m walk timed test , a 30-s chair st and , and an 8-ft up- and -go timed test , before and after the 10-wk intervention period . Significant increases were found in the Ex group for eccentric ( 44 % ) and concentric ( 60 % ) average power ( p < 0.05 ) , and improvements were seen on each functional test : the 8-foot up- and -go , chair st and , and walk time improved by 31 % , 66 % , and 33 % , respectively ( p < 0.05 ) . No significant change occurred in the Con group . In conclusion , simple progressive exercise training , even in the 10th decade , increases muscle power and is associated with an improved performance of functional activities using the trained muscles BACKGROUND AND PURPOSE There is limited research on the effects of the number of exercises a person is told to perform on compliance and performance , as defined by cueing requirements , correct alignment , and quality of movement . Some studies of medication suggest that compliance decreases as the number of medications increases . The purpose of this study was to determine whether older adults comply and perform better ( ie , requiring less cueing , exhibiting correct alignment , and exhibiting controlled , coordinated , and continuous movements ) when they are asked to do 2 , 5 , or 8 exercises . SUBJECTS Subjects were 11 women and 4 men , aged 67 to 82 years ( X=72.8 ) , who were living independently in their communities . METHODS Subjects were r and omly prescribed 2 , 5 , or 8 general strengthening home exercises . They were instructed on their exercises at an initial session and asked to record the number of repetitions performed each day in a self-report exercise log . At a return session 7 to 10 days later , subjects were scored on their performance of the prescribed exercises using a newly design ed assessment tool . RESULTS The group that was prescribed 2 exercises performed better , as defined by their performance tool score , than the group that was prescribed 8 exercises . The group that was prescribed 5 exercises was not different from the groups that performed 2 or 8 exercises . No differences were found among groups regarding the self-report measurement of compliance . There was a moderate correlation between performance scores and the self-report percentage rates . CONCLUSION AND DISCUSSION Subjects who were prescribed 2 exercises performed better than subjects who were prescribed 8 exercises . The question of an optimal number of exercises to prescribe to elderly people warrants further study BACKGROUND Functional decline in physically frail , elderly persons is associated with substantial morbidity . It is uncertain whether such functional decline can be prevented . METHODS We r and omly assigned 188 persons 75 years of age or older who were physically frail and living at home to undergo a six-month , home-based intervention program that included physical therapy and that focused primarily on improving underlying impairments in physical abilities , including balance , muscle strength , ability to transfer from one position to another , and mobility , or to undergo an educational program ( as a control ) . The primary outcome was the change between base line and 3 , 7 , and 12 months in the score on a disability scale based on eight activities of daily living : walking , bathing , upper- and lower-body dressing , transferring from a chair , using the toilet , eating , and grooming . Scores on the scale ranged from 0 to 16 , with higher scores indicating more severe disability . RESULTS Participants in the intervention group had less functional decline over time , according to their disability scores , than participants in the control group . The disability scores in the intervention and control groups were 2.3 and 2.8 , respectively , at base line ; 2.0 and 3.6 at 7 months ( P=0.008 for the comparison between the groups in the change from base line ) ; and 2.7 and 4.2 at 12 months ( P=0.02 ) . The benefit of the intervention was observed among participants with moderate frailty but not those with severe frailty . The frequency of admission to a nursing home did not differ significantly between the intervention group and the control group ( 14 percent and 19 percent , respectively ; P=0.37 ) . CONCLUSIONS A home-based program targeting underlying impairments in physical abilities can reduce the progression of functional decline among physically frail , elderly persons who live at home The purpose of this study was to evaluate whether a 12-wk functional circuit-training program ( FCT ) could alter markers of physical frailty in a group of frail community-dwelling adults . Fifty-one individuals ( 31 women , 20 men ) , mean age ( ± SD ) 84 ( ± 2.9 ) yr , met frailty criteria and were r and omly assigned into groups ( FCT = 26 , control group [ CG ] = 25 ) . FCT underwent a 12-wk exercise program . CG met once a week for health education meetings . Measures of physical frailty , function , strength , balance , and gait speed were assessed at Weeks 0 , 12 , and 36 . Physical-frailty measures in FCT showed significant ( p < .05 ) improvements relative to those in CG ( Barthel Index at Weeks 0 and 36 : 73.41 ( ± 2.35 ) and 77.0 ( ± 2.38 ) for the FCT and 70.79 ( ± 2.53 ) and 66.73 ( ± 2.73 ) for the CG . These data indicate that an FCT program is effective in improving measures of function and reducing physical frailty among frail older adults |
13,929 | 22,099,531 | XOI improves endothelial function and circulating markers of oxidative stress in patients with , or at risk of , cardiovascular disease . | BACKGROUND Xanthine oxidase inhibition ( XOI ) reduces oxidative stress in the vasculature .
Moreover it reduces uric acid levels , a risk factor for the development of cardiovascular disease .
As such , XOI holds a potentially dual mechanism for the treatment of cardiovascular disease .
AIMS Through systematic review , we sought to clarify the extent of available evidence that has evaluated the effect of XOI upon clinical or surrogate markers of cardiovascular disease and function in humans . | Background —Cigarette smoking causes endothelial dysfunction , possibly through increased oxidant stress . The enzyme xanthine oxidase produces oxidative free radicals . We tested the hypothesis that xanthine oxidase contributes to endothelial dysfunction in cigarette smokers by administering the inhibitor allopurinol . Methods and Results —Fourteen cigarette smokers ( 31±4 pack years ) and 14 age- and sex-matched healthy non-smoking control subjects participated in a single-blinded , r and omized , 2-phase crossover study . All subjects had no other risk factors for atherosclerosis . Inhibition of xanthine oxidase was achieved by a single oral dose of 600 mg of allopurinol on the day of the study . Stimulated nitric oxide endothelial responses were assessed by forearm blood flow responses to intraarterial administration of acetylcholine and bradykinin 4 to 7 hours later ; basal nitric oxide was assessed using the nitric oxide synthase inhibitor NG-monomethyl-l-arginine ( L-NMMA ) ; and nitroprusside was used to assess sensitivity to nitric oxide . Dilatation produced by acetylcholine was significantly less in smokers ( 254±57 % ) than healthy controls ( 390±55 % ) ( P = 0.009 ) . Allopurinol reversed endothelial dysfunction in smokers ( acetylcholine , 463±78 % , P = 0.001 ) without affecting responses in non-smokers ( 401±80 % ) . Bradykinin responses were also impaired in smokers ( P = 0.003 ) , and improved with allopurinol , though not significantly ( P = 0.06 ) . Responses to nitroprusside and L-NMMA were not significantly different between smokers and controls and were not altered by allopurinol . Conclusions —Smoking-induced endothelial dysfunction of resistance vessels is rapidly reversed with oral allopurinol . These data suggest that xanthine oxidase contributes importantly to endothelial dysfunction caused by cigarette smoking Background —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients . Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity Background —Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption . Experimental models suggest that oxidative stress result ing from increased xanthine oxidase ( XO ) activity contributes to this imbalance . Accordingly , we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy . Methods and Results — Patients ( n=9 ; ejection fraction , 29±3 % ) were instrumented to assess myocardial oxygen consumption ( M&OV0312;o2 ) , peak rate of rise of left ventricular pressure ( dP/dtmax ) , stroke work ( SW ) , and efficiency ( dP/dtmax/M&OV0312 ; o2 and SW/M&OV0312;o2 ) at baseline and after sequential infusions of intracoronary allopurinol ( 0.5 , 1.0 , and 1.5 mg/min , each for 15 minutes ) . Allopurinol caused a significant decrease in M&OV0312;o2 ( peak effect , −16±5%;P < 0.01 ; n=9 ) with no parallel decrease in dP/dtmax or SW and no change in ventricular load . The net result was a substantial improvement in myocardial efficiency ( peak effects : dP/dtmax/M&OV0312 ; o2 , 22±9 % , n=9 ; SW/M&OV0312 ; o2 , 40±17 % , n=6 ; both P < 0.05 ) . These effects were apparent despite concomitant treatment with st and ard heart failure therapy , including ACE inhibitors and & bgr;-blockers . XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot . Conclusions —These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy . By reversing the energetic inefficiency of the failing heart , pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure Background and Purpose — Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke . The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models , reduces oxidative stress in the vasculature , and improves endothelial function . We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke . Methods — We performed a r and omized , double-blind , placebo-controlled trial to investigate the safety , tolerability , and effect of 6 weeks ' treatment with high- ( 300 mg once a day ) or low- ( 100 mg once a day ) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke . Results — We enrolled 50 patients with acute ischemic stroke ( 17 , 17 , and 16 in the high , low , and placebo groups , respectively ) . Mean ( ±SD ) age was 70 ( ±13 ) years . Groups had similar characteristics at baseline . There were no serious adverse events . Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group ( by 0.14 mmol/L at 6 weeks , P=0.002 ) . Intercellular adhesion molecule-1 concentration ( ng/mL ) rose by 51.2 in the placebo group , rose slightly ( by 10.6 ) in the low-dose allopurinol group , but fell in the high-dose group ( by 2.6 ; difference between groups P=0.012 , Kruskal-Wallis test ) . Conclusion — Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke . Uric acid levels were lowered with high doses . These findings support further evaluation of allopurinol as a preventive measure after stroke Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction . The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea . A r and omised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea , comparing 300 mg allopurinol daily for 2 weeks with placebo . Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation ( FMD ) at baseline and following treatment . Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress . Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of < 90 % . Allopurinol caused a significant increase in FMD compared to placebo ( 10.4±3.2 versus 7.4±2.8 % , respectively ) . Plasma malondialdehyde levels were significantly reduced with allopurinol treatment ( 1.5±0.3 versus 1.2±0.3 μmol·L−1 ) , consistent with reduced oxidative stress . Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea . These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment AIMS Allopurinol improves endothelial function in chronic heart failure by reducing oxidative stress . We wished to explore if such an effect would attenuate autonomic dysfunction in CHF in line with many other effective therapies in CHF . METHODS We performed a prospect i ve , r and omized , double-blind cross-over study in 16 patients with NYHA Class II-IV chronic heart failure ( mean age 67 + /- 10 years , 13 male , comparing allopurinol ( 2 months ) at a daily dose of 300 mg ( if creatinine < 150 micromol l-1 ) or 100 mg ( if creatinine > 150 micromol l-1 ) with matched placebo . Mean heart rate and dysrhythmia counts were recorded from 24 h Holter tapes at monthly intervals for 6 months . We assessed autonomic function using st and ard time domain heart rate variability parameters ( HRV ) : SDNN , SDANN , SDNN index , rMSSD and TI . RESULTS Allopurinol had no significant effect on heart rate variability compared with placebo ; the results are expressed as a difference in means + /- s.d . with 95 % confidence interval ( CI ) between allopurinol and placebo : SDNN mean = 6.5 + /- 4.8 ms , P = 0.18 and 95 % CI ( -3.7 , 17 ) ; TI mean = -2.1 + /- 1.4 , P = 0.16 and 95 % CI ( -5.2 , 0.8 ) ; SDANN mean = -2.8 + /- 7 ms , P = 0.68 and 95 % CI ( -18 , 12 ) ; SDNNi mean = 2 + /- 6.6 , P = 0.7 and 95 % CI ( -12 , 16 ) ; RMSSD mean = -0.9 + /- 2 , P = 0.68 and 95 % CI ( -5.6 , 3.7 ) . For mean heart rate the corresponding results were 0.9 + /- 1.4 , P = 0.5 and 95 % CI ( -2 , 3.8 ) . Log 24 h ventricular ectopic counts ( VEC ) were 0.032 + /- 0.37 , P = 0.7 and 95 % CI ( -0.1 , 0.2 ) . Patient compliance with study medication was good since allopurinol showed its expected effect of reducing plasma uric acid ( P < 0.001 ) . CONCLUSIONS Allopurinol at doses , which are known to reduce oxidative stress appear to have no significant effect on resting autonomic tone , as indicated by time domain heart rate variability or on dysrhythmia count in stable heart failure patients Background —In patients with chronic heart failure ( CHF ) , hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow . It has been suggested that the causal link of this association is increased xanthine oxidase (XO)–derived oxygen free radical production and endothelial dysfunction . We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies . Methods and Results —In 10 CHF patients with normal serum uric acid ( UA ) levels ( 315±42 & mgr;mol/L ) and 9 patients with elevated UA ( 535±54 & mgr;mol/L ) , endothelium-dependent ( acetylcholine infusion ) and endothelium-independent ( nitroglycerin infusion ) vasodilation of the radial artery was determined . Coinfusion of allopurinol ( 600 & mgr;g/min ) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients ( P < 0.05 ) . In a double-blind , crossover design , hyperuricemic CHF patients were r and omly allocated to allopurinol 300 mg/d or placebo for 1 week . In 14 patients ( UA 558±21 & mgr;mol/L , range 455 to 743 & mgr;mol/L ) , treatment reduced UA by > 120 & mgr;mol/L in all patients ( mean reduction 217±15 & mgr;mol/L , P < 0.0001 ) . Compared with placebo , allopurinol improved peak blood flow ( venous occlusion plethysmography ) in arms ( + 24 % , P = 0.027 ) and legs ( + 23 % , P = 0.029 ) . Flow-dependent flow improved by 58 % in arms ( P = 0.011 ) . Allantoin , a marker of oxygen free radical generation , decreased by 20 % after allopurinol treatment ( P < 0.001 ) . There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment ( r = 0.63 , P < 0.05 ) . Conclusions —In hyperuricemic CHF patients , XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease ( CAD ) that is central ly related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling . Xanthine oxidase ( XO ) , which both binds to and is expressed by endothelial cells , generates superoxide and hydrogen peroxide upon oxidation of purines . Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD , however , remains unknown . We assessed coronary and peripheral ( brachial artery ) endothelial function in 18 patients ( pts ; 65+/-8 years , 86 % male ) with angiographically documented CAD , preserved left ventricular function , and non-elevated uric acid levels ( 233+/-10 microM ) . Patients received incremental doses of intracoronary acetylcholine ( ACh ; 10(-7 ) to 10(-5 ) microM ) , and minimal lumen diameter ( MLD ) and coronary blood flow ( CBF ) were assessed before and after intravenous administration of oxypurinol ( 200 mg ) . Oxypurinol inhibited plasma XO activity 63 % ( 0.051+/- 0.001 vs 0.019+/- 0.005 microU/mg protein ; p<0.01 ) . In pts who displayed endothelial dysfunction as evidence d by coronary vasoconstriction in response to ACh ( n=13 ) , oxypurinol markedly attenuated ACh-induced vasoconstriction ( -23+/- 4 vs -15+/- 4 % at ACh 10(-5 ) microM , p<0.05 ) and significantly increased CBF ( 16+/-17 vs 62+/-18 % at ACh 10(-5 ) microM , p<0.05 ) , whereas in patients with preserved coronary endothelial function , oxypurinol had no effect on ACh-dependent changes in MLD ( + 2.8+/- 4.2 vs 5.2+/- 0.7 % , p>0.05 ) or CBF ( 135+/-75 vs 154+/-61 % , p>0.05 ) . Flow-mediated dilation of the brachial artery , assessed in eight consecutive patients , increased from 5.1+/-1.5 before to 7.6+/-1.5 % after oxypurinol administration ( p < 0.05 ) . Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction , a hallmark of patients with CAD . These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation The objective of this r and omized , double-blind placebo-controlled clinical trial was to evaluate the value of allopurinol treatment on reduction of oxidative stress in patients with diabetes type II patients . Forty-one diabetic type II subjects were r and omly assigned to two groups . One group ( n = 20 ) received 100 mg allopurinol three times a day for 14 days and the other group ( n = 21 ) received a placebo . Blood and saliva sample s were collected before and after intervention for analysis of lipid peroxidation level and total antioxidant power as indices of oxidative stress . At the beginning of the study , the groups were similar based upon age , duration of diabetes , fasting glucose , and HbA1c . Both allopurinol and placebo were effective in reduction of lipid peroxidation and total antioxidant power whether in saliva or plasma in a similar extent . HbA1c and FBS levels did not change through the study neither in case or placebo group . It is concluded that allopurinol therapy is not more effective than placebo in reduction of oxidative stress in diabetic patients . The same trend of changes in blood and saliva shown for oxidative stress indices was interesting and suggests a chance for saliva to be valuable in diagnosis of oxidative stress . However , to elaborate the exact role of allopurinol in diabetes , further large r and omized clinical trials are needed Background —Impaired flow-dependent , endothelium-mediated vasodilation ( FDD ) in patients with chronic heart failure ( CHF ) results , at least in part , from accelerated degradation of nitric oxide by oxygen radicals . The mechanisms leading to increased vascular radical formation , however , remain unclear . Therefore , we determined endothelium-bound activities of extracellular superoxide dismutase ( ecSOD ) , a major vascular antioxidant enzyme , and xanthine-oxidase , a potent radical producing enzyme , and their relation to FDD in patients with CHF . Methods and Results —ecSOD and xanthine-oxidase activities , released from endothelium into plasma by heparin bolus injection , were determined in 14 patients with CHF and 10 control subjects . FDD of the radial artery was measured using high-resolution ultrasound and was assessed before and after administration of the antioxidant vitamin C ( 25 mg/min ; IA ) . In patients with CHF , endothelium-bound ecSOD activity was substantially reduced ( 5.0±0.7 versus 14.4±2.6 U · mL−1 · min−1;P < 0.01 ) and closely related to FDD ( r = 0.61 ) . Endothelium-bound xanthine-oxidase activity was increased by > 200 % ( 38±10 versus 12±4 nmol O2·− · & mgr;L−1;P < 0.05 ) and inversely related to FDD ( r = −0.35 ) in patients with CHF . In patients with low ecSOD and high xanthine-oxidase activity , a greater benefit of vitamin C on FDD was observed , ie , the portion of FDD inhibited by radicals correlated negatively with ecSOD ( r = −0.71 ) but positively with xanthine-oxidase ( r = 0.75 ) . Conclusions —These results demonstrate that both increased xanthine-oxidase and reduced ecSOD activity are closely associated with increased vascular oxidative stress in patients with CHF . This loss of vascular oxidative balance likely represents a novel mechanism contributing to endothelial dysfunction in CHF Xanthine oxidase contributes to oxidant stress and has been proposed as a risk factor for endothelial dysfunction . We studied the role of xanthine oxidase in conduit artery endothelial dysfunction in 12 smokers and 12 controls . Conduit artery vasodilation was impaired in smokers ( 4.3 % ) compared with controls ( 7.9 % ) ( p = 0.006 ) and improved with xanthine oxidase inhibition in smokers ( 9.2 % , p < 0.001 ) In the present study , we hypothesized that exhaustive exercise in patients with chronic obstructive pulmonary disease ( COPD ) results in glutathione oxidation and lipid peroxidation and that xanthine oxidase ( XO ) contributes to free radical generation during exercise . COPD patients performed incremental cycle ergometry until exhaustion with ( n = 8) or without ( n = 8) prior treatment with allopurinol , an XO inhibitor . Reduced ( GSH ) and oxidized glutathione ( GSSG ) and lipid peroxides [ malondialdehyde ( MDA ) ] were measured in arterial blood . In nontreated COPD patients , maximal exercise ( approximately 75 W ) result ed in a significant increase in the GSSG-to-GSH ratio ( 4 . 6 + /- 0.9 % at rest vs. 9.3 + /- 1.7 % after exercise ) . In nontreated patients , MDA increased from 0.68 + /- 0.08 nmol/ml at rest up to 1 . 32 + /- 0.13 nmol/ml 60 min after cessation of exercise . In contrast , in patients treated with allopurinol , GSSG-to-GSH ratio did not increase in response to exercise ( 5.0 + /- 1.2 % preexercise vs. 4.6 + /- 1.1 % after exercise ) . Plasma lipid peroxide formation was also inhibited by allopurinol pretreatment ( 0.72 + /- 0.15 nmol/ml preexercise vs. 0.64 + /- 0.09 nmol/ml 60 min after exercise ) . We conclude that strenuous exercise in COPD patients results in blood glutathione oxidation and lipid peroxidation . This can be inhibited by treatment with allopurinol , indicating that XO is an important source for free radical generation during exercise in COPD Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses ( eg , vitamins C and E ) . A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase . We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age . We examined 23 subjects ( 11 patients with type 2 diabetes and 12 healthy age-matched control subjects ) in 2 parallel groups . The subjects were administered 300 mg allopurinol in a r and omized , placebo-controlled study in which both therapies were administered for 1 month . Endothelial function was assessed with bilateral venous occlusion plethysmography , in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured . Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30 % ( 3.16+/-1.21 versus 2.54+/-0.76 mL. 100 mL(-1 ) . min(-1 ) allopurinol versus placebo ; P=0.012 , 95 % CI 0.14 , 1.30 ) but did not affect the nitroprusside response in patients with type 2 diabetes . There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects . Allopurinol improved endothelial function to near-normal levels . Regarding markers of free radical activity , the level of malondialdehyde was significantly reduced ( 0.30+/-0.04 versus 0 . 34+/-0.05 micromol/L for allopurinol versus placebo , P=0.03 ) in patients with type 2 diabetes but not in control subjects . The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects . In the former group , allopurinol restored endothelial function to near-normal levels BACKGROUND The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction . The present study was performed to determine whether angiotensin-1 ( AT(1 ) ) receptor inhibition improves endothelial dysfunction . METHODS AND RESULTS In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects , we studied microvascular responses to reactive hyperemia , angiotensin II , acetylcholine , and sodium nitroprusside before and after the administration of intra-arterial losartan ( 10 mg ) . Femoral artery flow velocity was measured with a Doppler flow wire , and the femoral vascular resistance index ( FVRI ) was calculated as mean arterial pressure divided by flow velocity . Losartan induced a minor ( 5.9+/-2 % , P=0 . 02 ) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups ( P<0.01 ) . After the administration of losartan , acetylcholine-mediated vasodilation was augmented in patients ( 44+/-5 % to 58+/-4 % reduction in FVRI with infusion at a rate of 150 microgram/min , P<0.001 ) but not control subjects . Vasodilation during reactive hyperemia was also greater after AT(1 ) receptor inhibition ( P=0.03 ) in patients , but the response to sodium nitroprusside remained unchanged . In a separate group of 31 patients with atherosclerosis , we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound . Oral losartan therapy improved flow-mediated brachial artery dilation ( 1.4+/-0.9 % to 3.2+/-0.8 % , P=0.03 ) but had no effect on the nitroglycerin response . Serum nitrogen oxide levels increased from 21.6+/-1.7 to 26.7+/-2.4 micromol/L ( P=0.008 ) . CONCLUSIONS The results of the present study indicate that inhibition of the AT(1 ) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits Background — Allopurinol has been shown to improve endothelial function in chronic heart failure . This study aim ed to establish its mechanism of action and to construct a dose – response curve for the effect of allopurinol . Methods and Results — Two r and omized , placebo-controlled , double-blind , crossover studies were performed for 1 month on patients with New York Heart Association Class II – III chronic heart failure , comparing 300 mg allopurinol , 600 mg allopurinol , and placebo for the first study and 1000 mg probenecid versus placebo in the second study . Endothelial function was assessed by st and ard forearm venous occlusion plethysmography . Allopurinol 600 mg/d significantly increased forearm blood flow response to acetylcholine compared with both allopurinol 300 mg/d and placebo ( % change in forearm blood flow [ mean±SEM ] : 240.31±38.19 % versus 152.10±18.21 % versus 73.96±10.29 % , P<0.001 ) . For similar levels of urate lowering , the uricosuric agent probenecid had no effect on endothelial function . Sodium nitroprusside response was unchanged by all treatments . Vitamin C and acetylcholine coinfusion data showed that 600 mg/d allopurinol completely abolished the oxidative stress that was sensitive to high-dose vitamin C. Conclusions — For the first time , we have shown that a steep dose – response relationship exists between allopurinol and its effect on endothelial function . We also showed that the mechanism of improvement in endothelial function with allopurinol lies in its ability to reduce vascular oxidative stress and not in urate reduction . The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study Summary Background Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume . If such an effect also occurs in man , this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris . We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina . Methods 65 patients ( aged 18–85 years ) with angiographically documented coronary artery disease , a positive exercise tolerance test , and stable chronic angina pectoris ( for at least 2 months ) were recruited into a double-blind , r and omised , placebo-controlled , crossover study in a hospital and two infirmaries in the UK . We used computer-generated r and omisation to assign patients to allopurinol ( 600 mg per day ) or placebo for 6 weeks before crossover . Our primary endpoint was the time to ST depression , and the secondary endpoints were total exercise time and time to chest pain . We did a completed case analysis . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 82040078 . Findings In the first treatment period , 31 patients were allocated to allopurinol and 28 were analysed , and 34 were allocated to placebo and 32 were analysed . In the second period , all 60 patients were analysed . Allopurinol increased the median time to ST depression to 298 s ( IQR 211–408 ) from a baseline of 232 s ( 182–380 ) , and placebo increased it to 249 s ( 200–375 ; p=0·0002 ) . The point estimate ( absolute difference between allopurinol and placebo ) was 43 s ( 95 % CI 31–58 ) . Allopurinol increased median total exercise time to 393 s ( IQR 280–519 ) from a baseline of 301 s ( 251–447 ) , and placebo increased it to 307 s ( 232–430 ; p=0·0003 ) ; the point estimate was 58 s ( 95 % CI 45–77 ) . Allopurinol increased the time to chest pain from a baseline of 234 s ( IQR 189–382 ) to 304 s ( 222–421 ) , and placebo increased it to 272 s ( 200–380 ; p=0·001 ) ; the point estimate was 38 s ( 95 % CI 17–55 ) . No adverse effects of treatment were reported . Interpretation Allopurinol seems to be a useful , inexpensive , well tolerated , and safe anti-ischaemic drug for patients with angina . Funding British Heart Foundation Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis . The urate molecule has antioxidant properties , which could influence endothelial function . The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes , eight healthy regular smokers , and eight age-matched healthy control subjects in a r and omized , four-way , double-blind , placebo-controlled study . Subjects received 1,000 mg uric acid i.v . in vehicle , 1,000 mg vitamin C as a control antioxidant , vehicle alone , or 0.9 % saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography . Responses to acetylcholine , but not sodium nitroprusside , were impaired in patients with diabetes ( P < 0.001 ) and in smokers ( P < 0.005 ) compared with control subjects . Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes ( P < 0.01 ) and in regular smokers ( P < 0.05 ) . Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers , suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk Background Hyperuricemia has been associated with the development of hypertension , cardiovascular , and renal disease . However , there is no data about the effect of lowering uric acid level on hypertension , renal function , and proteinuria in patients with glomerular filtration rate ( GFR ) > 60 ml/min . We therefore conducted a prospect i ve study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function . Material s and methods Forty-eight hyperuricemic and 21 normouricemic patients were included in the study . Hyperuricemic patients received 300 mg/day allopurinol for three months . All patients ’ serum creatinine level , 24-h urine protein level , glomerular filtration rate , and blood pressure levels were measured at baseline and after three months of treatment . Results A total of 59 patients completed the three-month follow-up period of observation . In the allopurinol group , serum uric acid levels , GFR , systolic and diastolic blood pressure , and C-reactive protein ( CRP ) levels significantly improved ( P < 0.05 ) . However , urine protein excretion remained unchanged ( P > 0.05 ) . No correlation was observed between changes in GFR and changes in CRP , or blood pressure in the allopurinol group . No significant changes were observed in the control group ( P > 0.05 ) . Conclusion We bring indirect evidence that hyperuricemia increases blood pressure , and decreases GFR . Hence , management of hyperuricemia may prevent the progression of renal disease , even in patients with normal renal function , suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease ( CKD ) patients . Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension Vascular oxidative stress is the key mechanism involved in the age-related decline in endothelium-dependent dilatation ( EDD ) . We tested the hypothesis that xanthine oxidase ( XO ) , a major vascular source of reactive oxygen species , contributes to the impairment in EDD with ageing . At baseline , brachial artery flow-mediated dilatation ( FMD ) was 55 % lower in older ( n = 9 , 64 + /- 2 years , 8M/1F , mean + /- S.E.M. ) versus young ( n = 9 , 26 + /- 1 years , 8M/1F ) healthy adults ( 3.41 + /- 0.44 versus 7.53 + /- 0.67 % , P < 0.001 ) , whereas endothelium-independent dilatation ( EID ; sublingual nitroglycerin ) did not differ between groups . Plasma oxidized low-density lipoprotein ( oxi-LDL ) , a measure of systemic oxidative stress , was greater at baseline in the older subjects ( 58.3 + /- 5.9 versus 46.8 + /- 2.4 U l(-1 ) , P < 0.05 ) and inversely correlated with baseline FMD ( r = - 0.54 ; P < 0.05 ) . Acute administration of allopurinol , a competitive inhibitor of XO , reduced plasma uric acid concentrations similarly in both groups ( P < 0.001 ) , but did not affect FMD , EID , or oxi-LDL in either group . Vascular endothelial protein expression of XO ( immunofluorescence ) was not different in antecubital venous cells from the young and older subjects ( 0.56 + /- 0.12 versus 0.68 + /- 0.19 XO intensity/human umbilical vein endothelial cell intensity , P = 0.49 ) . We conclude that XO does not contribute to oxidative stress-associated reductions in peripheral conduit artery EDD with ageing in humans , possibly due to an absence of age-associated up-regulation of endothelial XO Objective : To study whether the effect of allopurinol on improvement of endothelial dysfunction in chronic heart failure ( CHF ) translates into improved exercise capacity and to examine whether allopurinol also improves B-type natriuretic peptide ( BNP ) , the other important prognostic marker of CHF . Design : R and omised , double blind , placebo controlled crossover trial . Setting : Teaching hospital . Patients : 50 patients with CHF ( New York Heart Association functional classes II and III ) were recruited . Interventions : 50 patients with CHF were r and omly assigned to three months ’ treatment with allopurinol ( 300 mg/day ) or placebo . At two and three months into treatment , they underwent a modified Bruce exercise protocol and a six minute walk test . Blood was taken for BNP and haemoglobin analysis . Results : Neither exercise test was altered by allopurinol . However , plasma BNP concentrations fell significantly ( p = 0.035 ) with allopurinol ( 11.9 pmol/l ) versus placebo ( 14.4 pmol/l ) . Haemoglobin concentrations also fell highly significantly with allopurinol ( p = 0.001 ) . Conclusions : An important negative finding is that despite high hopes for it , allopurinol had no effect on exercise capacity in CHF . On the other h and , allopurinol did reduce BNP , which is the best available surrogate marker for prognosis in CHF BACKGROUND Cirrhosis is associated with intestinal barrier failure , related in part to enterocytes oxidative damage via xanthine oxidase overactivity . Experimentally , allopurinol , a xanthine oxidase inhibitor , reduces enterocytes ' damage and bacterial translocation . AIM To assess the short-term effects of allopurinol on intestinal permeability , oxidative stress and endotoxin-dependent cytokines in patients with cirrhosis . METHODS Nineteen patients with cirrhosis , in a stable condition ( age : 56 years ; Child A/B/C : 6/7/6 ; ascites : 12 ; alcoholic cirrhosis : 16/19 ; abstinence > 2 weeks ) , were included . At baseline and day 10 of allopurinol 400 mg/day , intestinal permeability [ lactulose/mannitol ( Lac/Man ) ratio test ] , oxidative stress ( serum malondialdehyde ) , as well as TNF-soluble receptor-1 , IL-6 and lipopolysaccharide-binding protein ( which reflects exposition to endotoxin ) were measured . RESULTS Malondialdehyde decreased significantly ( -23 % , P<0.05 ) , whereas no effects were seen on intestinal permeability and the endotoxin-associated systemic inflammatory response . At baseline , portal pressure correlated to the Lac/Man ratio ( r=0.55 , P<0.02 ) . At day 10 , changes in malondialdehyde correlated to changes in the Lac/Man ratio ( r=0.51 , P<0.05 ) . CONCLUSIONS A 10-day course of allopurinol in patients with cirrhosis is associated with a significant reduction in oxidative stress but no effect on intestinal permeability and inflammatory markers . Whether intestinal damage in cirrhosis can be accessible to antioxidant therapy requires further study OBJECTIVE —Type 2 diabetes increases risk of stroke , perhaps because of impaired cerebrovascular basal nitric oxide ( NO ) activity . We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol . RESEARCH DESIGN AND METHODS —We performed a r and omized , double-blind , placebo-controlled crossover study . We measured the response to infusion of NG-monomethyl-L-arginine ( l-NMMA ) in males with type 2 diabetes before and after allopurinol or placebo . The primary end point was the change in internal carotid artery flow following l-NMMA infusion , expressed as the area under the flow-per-time curve . RESULTS —We enrolled 14 participants . Allopurinol improved responses to l-NMMA when compared with responses associated with placebo ( P = 0.032 ; median reduction in internal carotid artery flow following l-NMMA of 3,144 ml [ 95 % CI 375–7,143 ] ) . CONCLUSIONS —Xanthine oxidase inhibition with allopurinol appears to improve cerebral NO bioavailability , as evidence d by a greater response to infusion of l-NMMA BACKGROUND Reactive oxygen species ( ROS ) have been linked to hypertrophy , remodeling and abnormal excitation-contraction coupling . Previous data demonstrated that an increase in oxidative stress is associated to the pathogenesis of congestive heart failure ( CHF ) . We examined whether inhibition of the superoxide anion ( * O2(-))-generating enzyme xanthine oxidase ( XO ) with oxypurinol may improve cardiac function in patients with CHF . METHODS AND RESULTS A r and omized , placebo-controlled , double-blind study on 60 patients ( 30/group ) with New York Heart Association class II-III CHF , comparing 600-mg/day oxypurinol during 1 month with placebo , added to st and ard therapy . Effects on left ventricular ejection fraction ( LVEF ) , serum uric acid ( SUA ) level , and 6-minute walking test were analyzed . SUA decreased by 16.0 + /- 2.8 mg/L from baseline to Week 4 in the oxypurinol group relative to placebo ( P < .01 , n = 30 per group ) . LVEF showed an increase of 4.7 + /- 2.6 % from baseline to Week 4 in the oxypurinol group relative to placebo that did not reach statistical significance ( P < .08 ) . When patients with LVEF > 40 % at baseline were excluded , a statistically significant increase of 6.8 + /- 2.8 % from baseline to Week 4 was seen in the oxypurinol group relative to placebo ( P < .02 , n = 26 placebo , n = 21 oxypurinol ) . No treatment-related adverse effects or increase in walking capacity were detected . CONCLUSION Inhibition of XO by oxypurinol in patients with CHF decreases SUA and improves LVEF in patients with LVEF < or = 40 % after 1 month of treatment Objective : The aim of this study was to determine the implication of xanthine oxidase ( XO ) in the exercise-induced muscle oxidative stress and muscle dysfunction of these patients . Methods : A r and omized , crossover and double-blind study was conducted in nine severe COPD patients , who performed a localized quadriceps endurance test after oral treatment with allopurinol , a XO inhibitor or placebo . Redox status was studied in arterial and venous femoral blood before and after the endurance test . Results : In placebo condition , muscle exercise result ed in a significant increase in AOPP and isoprostanes , with a significant increase in the venoarterial difference ( v-a ) in isoprostanes after exercise as compared with before ( p<0.05 ) . In contrast , allopurinol treatment prevented the elevation in AOPP levels and v-a isoprostanes after exercise . However , no significant improvement in quadriceps muscle endurance was observed , but allopurinol treatment seemed to preserve muscle strength properties . Conclusion : This study demonstrates that XO is implicated in the exercise-induced muscle oxidative stress of COPD patients . Allopurinol administration seemed to improve only some muscle properties . Therefore other sources of muscle oxidative stress should be implicated in muscle dysfunction observed in these patients BACKGROUND Previous studies have not extensively examined the association of hyperuricemia and adverse outcomes in systolic heart failure ( HF ) in relation to xanthine oxidase inhibitor therapy . METHODS The Prospect i ve R and omized Amlodipine Survival Evaluation study included New York Heart Association class IIIB or IV patients with left ventricular ejection fraction < 30 % . For analysis , the population was divided into uric acid quartiles among nonallopurinol users ( 2.2 - 7.1 , > 7.1 - 8.6 , > 8.6 - 10.4 , > 10.4 mg/dL ) and those using allopurinol . Multivariate Cox regression modeling was performed to identify predictors of mortality . Uric acid quartile and allopurinol groups were referenced to the lowest uric acid quartile . RESULTS A total of 1,152 patients were included . In general , patients in the allopurinol group and in the highest uric acid quartile had indicators of more severe HF , including worse renal function and greater proportion of New York Heart Association class IV patients , and greater diuretic use . The allopurinol group and highest uric acid quartile had the highest total mortality ( 41.7 and 42.4 per 100 person-years , respectively ) and combined morbidity/mortality ( 45.6 and 51.0 per 100 person-years , respectively ) . Allopurinol use and highest uric acid quartile were independently associated with mortality ( hazard ratio [ HR ] 1.65 , 95 % CI 1.22 - 2.23 , P = .001 and HR 1.35 , 95 % CI 1.07 - 1.72 , P = .01 , respectively ) and combined morbidity/mortality ( uric acid quartile 4 vs 1 : HR 1.32 , 95 % CI 1.06 - 1.66 , P = .02 ; allopurinol use : HR 1.48 , 95 % CI 1.11 - 1.99 , P = .008 ) . CONCLUSION Elevated uric acid level was independently associated with mortality in patients with severe systolic HF , even when accounting for allopurinol use We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients ( ten men and eight women , aged 20 - 46 years ) in comparison with 12 normal volunteers ( seven men and five women , aged 20 - 45 years ) . The responses of the forearm blood flow ( FBF ) to acetylcholine ( ACh ) ( 7.5 , 15 and 30 microg/min ) , sodium nitroprusside ( SNP ) ( 0.8 , 1.6 , 3.2 microg/min ) and L-NMMA ( 2 , 4 , 8 micromol/min ) were evaluated at baseline and after 1 month of atorvastatin ( 10 mg/day ) treatment . Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography . At baseline , the response to ACh was significantly attenuated in hypercholesterolemics versus controls : at the highest dose ( 30 microg/min ) , FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1 ) respectively ( P<0.0001 ) . No significant differences were found between groups during SNP infusion . The atorvastatin treatment significantly improved ACh-stimulated FBF : at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1 ) . min(-1 ) ( P<0.0001 ) . Similarly , the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment , supporting the improvement of basal nitric oxide . Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment . In conclusion , the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation The aim of this work was to study the mechanism of free radical formation in type 1 diabetes and its possible prevention . We have found oxidation of blood glutathione and an increase in plasma lipoperoxide levels in both human type 1 diabetes and experimental diabetes . Peroxide production by mitochondria does not increase in diabetes . On the contrary , the activity of xanthine oxidase , a superoxide-generating enzyme , increases in liver and plasma of diabetic animals . The increase in plasma xanthine oxidase activity may be explained by the increase in the hepatic release of this enzyme , which is not due to nonspecific membrane damage : release of other hepatic enzymes , such as the amino transferases , does not increase in diabetes . Superoxide formation by aortic rings of rabbits increases significantly in diabetes . This is completely inhibited by allopurinol , an inhibitor of xanthine oxidase . Heparin , which releases xanthine oxidase from the vessel wall , also decreases superoxide formation by aortic rings of diabetic animals . Treatment with allopurinol decreases oxidative stress in type 1 diabetic patients : hemoglobin glycation , glutathione oxidation , and the increase in lipid peroxidation are prevented . These results may have clinical significance in the prevention of late-onset vascular complications of diabetes CONTEXT Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension . Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models . OBJECTIVE To determine whether lowering uric acid lowers blood pressure ( BP ) in hyperuricemic adolescents with newly diagnosed hypertension . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled , crossover trial ( September 2004-March 2007 ) involving 30 adolescents ( aged 11 - 17 years ) who had newly diagnosed , never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children 's Hospital in Houston . Patients were excluded if they had stage 2 hypertension or known renal , cardiovascular , gastrointestinal tract , hepatic , or endocrine disease . INTERVENTION Allopurinol , 200 mg twice daily for 4 weeks , and placebo , twice daily for 4 weeks , with a 2-week washout period between treatments . The order of the treatments was r and omized . MAIN OUTCOME MEASURES Change in casual and ambulatory blood pressure . RESULTS For casual BP , the mean change in systolic BP for allopurinol was -6.9 mm Hg ( 95 % confidence interval [ CI ] , -4.5 to -9.3 mm Hg ) vs -2.0 mm Hg ( 95 % CI , 0.3 to -4.3 mm Hg ; P = .009 ) for placebo , and the mean change in diastolic BP for allopurinol was -5.1 mm Hg ( 95 % CI , -2.5 to -7.8 mm Hg ) vs -2.4 ( 95 % CI , 0.2 to -4.1 ; P = .05 ) for placebo . Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg ( 95 % CI , -3.8 to -8.9 mm Hg ) vs 0.8 mm Hg ( 95 % CI , 3.4 to -2.9 mm Hg ; P = .001 ) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg ( -2.4 to -6.8 mm Hg ) vs -0.3 mm Hg ( 95 % CI , 2.3 to -2.1 mm Hg ; P = .004 ) for placebo . Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo ( P < .001 ) . CONCLUSIONS In this short-term , crossover study of adolescents with newly diagnosed hypertension , treatment with allopurinol result ed in reduction of BP . The results represent a new potential therapeutic approach , although not a fully developed therapeutic strategy due to potential adverse effects . These preliminary findings require confirmation in larger clinical trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288184 BACKGROUND Hyperuricemia is associated with reduced survival among patients with heart failure ( HF ) , but the effect of gout on HF outcomes is unknown . A recent r and omized trial suggested that allopurinol may reduce adverse outcomes among patients with hyperuricemia and HF . Our objective was to determine whether gout and allopurinol use are associated with HF outcomes . METHODS Time-matched , nested case-control analysis of a retrospective cohort of patients with HF who were 66 years or older using health care data bases in Quebec , Canada . The primary outcome measure was a composite measure of HF readmission and all-cause mortality . The secondary outcome measure was all-cause mortality . Rate ratios were calculated using conditional logistic regression and adjusted for known prognostic factors . RESULTS Of the 25,090 patients in this cohort , 14,327 experienced the primary outcome . Both a remote history of gout and an acute episode of gout ( within 60 days of the event date ) were associated with an increased risk of HF readmission or death ( adjusted rate ratio , 1.63 ; 95 % confidence interval , 1.48 - 1.80 ; P<.001 and 2.06 ; 1.39 - 3.06 ; P<.001 , respectively ) . Continuous allopurinol use ( > 30 days of continuous use ) was not associated with the primary outcome among the overall population with HF ( adjusted rate ratio , 1.02 ; 95 % confidence interval , 0.95 - 1.10 ; P=.55 ) but was associated with reduced HF readmissions or death ( 0.69 ; 0.60 - 0.79 ; P<.001 ) and all-cause mortality ( 0.74 ; 0.61 - 0.90 ; P<.001 ) among patients with a history of gout . CONCLUSIONS Patients with HF and a history of gout represent a high-risk population . Among such patients , the use of allopurinol is associated with improved outcomes Allopurinol , an inhibitor of xanthine oxidase , was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models . The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty ( PTCA ) in patients with acute myocardial infa rct ion ( AMI ) and on their clinical outcomes were examined . Thirty-eight AMI patients undergoing primary PTCA were r and omly assigned to control ( group 1 , n = 20 ) and allopurinol treatment groups ( group 2 , n = 18 ) . Allopurinol ( 400 mg ) was administered orally just after the admission ( approximately 60 min before reperfusion ) . Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostagl and in F2&agr ; ( PGF2&agr ; ) after PTCA . Urinary 8-epi-PGF2&agr ; excretion was increased by twofold at 60–90 min after PTCA compared with the baseline value in group 1 . This increase was completely inhibited in group 2 . Plasma allopurinol concentration was 1,146 ± 55 ng/ml in group 2 when reperfusion was achieved . Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1 . Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups . In conclusion , allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans The importance of xanthine oxidase and its products is being increasingly recognized in cardiovascular medicine . Patients who have had a stroke are at high risk of future cardiovascular events and this risk is higher in those with high urate levels . The aim of this pilot study was to see if inhibiting xanthine oxidase altered arterial wave reflection , determined from the augmentation index ( AIx ) . In a double-blind study , 30 patients with high urate ( > or = 0.38 mmol/L ) were r and omized to 300 mg allopurinol or placebo for 8 weeks . AIx measurements were made before and after treatment using the vali date d SphygmoCor pulse waveform analysis system . For patients treated with allopurinol , there was a reduction in AIx from 26.08 + /- 3.31 % to 20.15 + /- 2.23 % compared with an increase in the placebo group from 23.57 + /- 3.13 % to 27.64 + /- 3.44 % ( P = 0.031 , ANOVA ) . The vascular benefits of allopurinol are rapidly emerging . We have demonstrated that allopurinol has beneficial effects on AIx , a vali date d measure of vascular function . A further larger study is warranted to look at whether a therapeutic intervention with allopurinol will impact positively on mortality and morbidity in stroke survivors 1 . Hypercholesterolaemia is associated with abnormal endothelium‐related vasodilator function , possibly due to increased destruction •NO by superoxide anions ( •O2– ) . Oxypurinol , a xanthine oxidase ( XO ) inhibitor with anti‐oxidant properties and the active metabolite of the commonly used drug allopurinol , reduces •NO quenching in vitro and has been reported to acutely improve endothelial function in hypercholesterolaemic subjects AIMS New preventative strategies for stroke are required . One promising strategy is uric acid reduction and xanthine oxidase inhibition with allopurinol . We sought to investigate whether allopurinol improves cerebrovascular reactivity ( CVR ) following subcortical stroke . METHODS We performed a r and omized , double-blind , controlled study to investigate the effect of a 3-month course of 300 mg allopurinol once daily vs. placebo on CVR in individuals with recent ( within 6 months ) subcortical stroke . Participants were r and omized on a 1:1 basis . CVR was defined as the percentage change in middle cerebral artery flow velocity following an intravenous injection of 15 mg kg(-1 ) of acetazolamide . Our primary end-point was the CVR difference between baseline and 3 months . Secondary end-points included measures of peripheral vascular reactivity and blood markers of inflammation and endothelial activation . RESULTS We enrolled 50 participants ; 45 completed the protocol . Baseline serum urate was 0.35 mmol l(-1 ) ( SD 0.1 ) and 0.34 mmol l(-1 ) ( SD 0.1 ) in the allopurinol and placebo groups , respectively . There were no serious adverse events related to treatment . CVR did not change following treatment with allopurinol [ median CVR change 0.89 % after allopurinol ( n = 20 ) and -0.68 % after placebo ( n = 25 ) ; 95 % confidence interval for estimated difference in medians -13.4 , 25.5 , P = 0.64 ] . Urate was significantly lowered by allopurinol but no change in other secondary end-points was seen . CONCLUSION Xanthine oxidase inhibition with allopurinol has previously been shown to improve cerebrovascular function , but no benefit was seen in this study . It may therefore be that previous encouraging findings will not translate into important clinical benefits OBJECTIVES This study evaluated whether a xanthine oxidase ( XO ) inhibitor , oxypurinol , produces clinical benefits in patients with New York Heart Association functional class III to IV heart failure due to systolic dysfunction receiving optimal medical therapy . BACKGROUND Increased XO activity may contribute to heart failure pathophysiology . METHODS Patients ( n = 405 ) were r and omized to oxypurinol ( 600 mg/day ) or placebo . Efficacy at 24 weeks was assessed using a composite end point comprising heart failure morbidity , mortality , and quality of life . RESULTS The percentage of patients characterized as improved , unchanged , or worsened did not differ between those receiving oxypurinol or placebo . Oxypurinol reduced serum uric acid ( SUA ) by approximately 2 mg/dl ( p < 0.001 ) . In a subgroup analysis , patients with elevated SUA ( > 9.5 mg/dl , n = 108 ) responded favorably to oxypurinol ( p = 0.02 for interaction term ) , whereas oxypurinol patients with SUA < 9.5 mg/dl exhibited a trend towards worsening . In addition , SUA reduction to oxypurinol correlated with favorable clinical response . Within the entire oxypurinol patient cohort , those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who worsened ( -2.3 + /- 2.1 mg/dl vs. -1.0 + /- 1.9 mg/dl , p = 0.0006 ) . In placebo patients , lower baseline SUA , but not change in SUA , correlated with improved clinical outcome . CONCLUSIONS Oxypurinol did not produce clinical improvements in unselected patients with moderate-to-severe heart failure . However , post-hoc analysis suggests that benefits occur in patients with elevated SUA in a manner correlating with the degree of SUA reduction . Serum uric acid may serve as a valuable biomarker to target XO inhibition in heart failure . ( Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure ; NCT00063687 ) |
13,930 | 17,426,075 | Findings showed that patients request information about a drug 's indication , expected benefits , duration of therapy , and a thorough list of potential adverse effects .
The evidence about label format supports the use of larger fonts , lists , headers , and white space , using simple language and logical organization to improve readability and comprehension .
Evidence was not sufficient to support the use of pictographic icons .
Little evidence linked label design or content to measurable health outcomes , adherence , or safety .
Conclusions : Evidence suggests that specific content and format of prescription drug labels facilitate communication with and comprehension by patients . | Objective : To evaluate the evidence regarding the optimal content and format of prescription labels that might improve readability , underst and ing , and medication use . | Fifty-five r and omly selected community pharmacy patrons were surveyed regarding their preferences between four different prescription labels . The variables displayed on the four labels were : ( i ) laser printed , ( ii ) dot-matrix printed , ( iii ) glossy surface , and ( iv ) matt surface . The study population was stratified by age and gender . Statistical analysis of the results indicated a clear preference by all groups for the laser printed labels ( P less than 0.001 ) , and the only other statistically significant finding was the preference for the matt surface ( P less than 0.05 ) of females between the ages of 16 and 39 . The implication s for these differences on label readability are discussed , and recommendations are offered for the use of improved laser technology for computer-generated prescription labels Despite the proven benefits of statins , large numbers of patients meeting guideline criteria for therapy are not receiving these drugs . It has been suggested that over-the-counter ( OTC ) availability of statins would allow more consumers to use statins and achieve cardiovascular risk reduction . However , concerns have been raised as to the consumers ' ability to self-manage hyperlipidemia and use statins safely . The Consumer Use Study of OTC Mevacor ( CUSTOM ) was design ed to define consumer behaviors in the setting of OTC statin availability . The study was conducted in a simulated OTC setting and allowed consumers to purchase once-daily lovastatin 20 mg . The CUSTOM data set includes > 3,300 consumers who evaluated OTC lovastatin for potential purchase at study sites and follow-up information on purchasers for up to 6 months of self-managed therapy . These data have been analyzed to address consumers ' knowledge of their cholesterol concentrations as well as their ability to make OTC use decisions based on their cardiovascular risk , avoid drug-drug interactions , self-manage their cholesterol treatment after deciding to use the OTC product , and maintain interactions with physicians while using lovastatin OTC . The results showed that most study participants appropriately self-selected OTC statin therapy and managed their treatment . Use of OTC statins by consumers needing more intensive statin therapy or facing the risk of potential drug-drug interactions remains an area of concern but occurred infrequently in CUSTOM . These data are important for making an informed risk-benefit decision concerning OTC statin availability Background : Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy ( HAART ) . Interventions to ensure a high level of adherence during a relatively long‐term period of therapy are necessary . Methods : This is a prospect i ve , r and omized , two‐arm controlled study including patients starting their first‐ or second‐line HAART who were r and omized to receive psychoeducative intervention to implement adherence ( experimental group [ EG ] ) or a usual medical follow‐up ( control group [ CG ] ) . We aim ed to study the efficacy of a psychoeducative intervention to ensure long‐term adherence to HAART , its relation with the virologic efficacy of treatment , and to determine the variables related to long‐term adherence . Visits were made at weeks 0 , 4 , 24 , and 48 for data collection . Self‐reported adherence was registered at each visit and its veracity was tested by r and omized blood analyses performed without previous warning to 40 % of patients . Appropriate adherence was defined as the consumption of ≥95 % of medication prescribed . Statistical analyses were performed both by the as treated ( AT ) and the intention to treat missing = failure ( ITT ) methods . Results : In all , 116 patients were included . At week 48 , 94 % of patients in the EG versus 69 % controls achieved adherence ≥95 % ( p = .008 ) ; 89 % of patients in the EG versus 66 % controls had HIV‐1 RNA levels < 400 copies/ml ( p = .026 ) . Overall , 85 % of patients with adherence ≥95 % but only 45 % of those with adherence < 95 % had viral load ( VL ) < 400 copies/ml ( p = .008 ) . In multivariate analysis , variables significantly related to adherence were having received a psychoeducative intervention ( odds ratio [ OR ] , 6.58 ; p = .04 ) , poor effort to take medication ( OR , 5.38 ; p = .03 ) , and high self‐perceived capacity to follow the regimen ( OR , 13.76 ; p = .04 ) . Self‐reported adherence and drug plasma levels coincided in 93 % of cases . However , differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG . Conclusions : Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression . There is a clear relation between high adherence levels and virologic success . Assessment of certain specific variables related to adherence may be helpful to monitor patient 's compliance in the clinical setting OBJECTIVES The authors determined patients ' report of prescription drug counseling activities after withdrawal of the pilot program to require patient package inserts in 1980 and implementation of Omnibus Budget Reconciliation Act of 1990 counseling requirements in 1993 . METHODS Four cross-sectional national telephone surveys were conducted in the fall of 1982 , 1984 , 1992 , and 1994 . Telephone households were chosen by r and om-digit dialing . Subjects had obtained a new prescription for themselves or for a family member at a retail pharmacy during the previous 4 weeks . Verbal counseling rates at physician offices and pharmacies for five information categories and the distribution of written information at those locations were determined . RESULTS Spontaneous verbal counseling at the physician 's office has increased slightly , with the largest increases focused on the delivery of side effect and pre caution ary information . Slightly larger increases in pharmacy-delivered information regarding directions for use and pre caution s have occurred . Patient question ing has remained at single digit levels at both sites . The percentage of patients receiving any written information has increased from 5 % to 15 % at the physician 's office and from 16 % to 59 % at the pharmacy . CONCLUSIONS The data indicate small increases in verbal counseling but larger increases in the delivery of written information provided at the pharmacy . In light of Healthy People : 2000 goals for patient counseling and legislation encouraging private-sector initiatives , these data should help to refocus attention on the continuing need for effective patient education interventions Direct-to-consumer ( DTC ) pharmaceutical ads typically describe drug benefits in qualitative terms ; they rarely provide data on how well the drug works . We describe an evaluation of a " prescription drug benefit box"- data from the main r and omized trials on the chances of various outcomes with and without the drug . Most participants rated the information as " very important " or " important " ; almost all found the data easy to underst and . Perceptions of drug effectiveness were much lower for ads that incorporated the benefit box than for ads that did not . Most people we interviewed want benefit data in drug ads , can underst and these data , and are influenced by them Objective To determine how well patients could correctly recognize and comprehend the various information items on patient information leaflets , and to explore the reasons underlying poor comprehensibility . Methods Leaflets from 30 r and omly selected , commonly prescribed medicines were examined by experts using protocol s to evaluate leaflet layout , language and content . The same leaflets were also evaluated by patients who had their medicines dispensed at 24 r and omly selected Swedish pharmacies . A question naire was used for the patients ’ examination . Results The results showed that most information on the leaflets is sound and is well comprehended by the patients . For two information items regarding ’ risks of interactions ’ and ’ contraindications ’ the patient scores were low , indicating poor comprehensibility . Conclusion Leaflets with low scores on warnings of interactions and contraindications were found to deliver more complex messages to older patients as compared to leaflets with high scores for these items The objective was to determine the influence of medicine labels incorporating pictograms on the underst and ing of instructions and on adherence . Eighty-seven Xhosa participants attending an outpatient clinic who had been prescribed a short course of antibiotics were r and omly allocated to either a control group ( 41 participants given text-only labels ) , or an experimental group ( 46 participants given text + pictogram labels ) . All participants had a maximum of 10 years of formal schooling . Follow-up home visits were conducted after 3 - 5 days to assess underst and ing of instructions and to evaluate adherence . A high adherence of greater than 90 % was found for 54 % of the experimental group , compared with only 2 % of the control group . Average percentages for underst and ing in the control and experimental groups were 70 and 95 % , respectively , and average adherence was 72 and 90 % , respectively . The presence of pictograms was found to contribute positively to both underst and ing of instructions and adherence OBJECTIVE : To design , develop , and evaluate a simple , underst and able medicine label and patient information leaflet ( PIL ) for nystatin suspension , and to assess the effect of incorporating pictograms on underst and ing in low-literate participants . METHODS : Patient information material s were design ed and pretested in a pilot study ( n = 20 ) , and were subjected to the Fry 's readability test . The final evaluation was conducted with 60 low-literate participants who had a maximum of 7 years of formal schooling and for whom English was their second language . Demographic data were collected . Participants were r and omly allocated to a control ( text-only information ) or experimental ( text + pictogram information ) group , shown the medicine label and PIL , and asked to read them . A series of questions was asked about the instructions and an underst and ing level was calculated in each case . A second series of questions assessed patient acceptability of the material s. Differences in underst and ing were determined by χ2 tests . RESULTS : Both sets of these simple written material s were generally well understood . However , the presence of pictograms was shown to improve the comprehension of more complex information , result ing in significantly more participants in the experimental group obtaining a score for underst and ing > 80 % for both the medicine label and PIL . A clear preference for the material s incorporating pictograms was expressed . CONCLUSIONS : The presence of pictograms had a positive effect in the acquisition and comprehension of drug information BACKGROUND Patients ' ability to underst and information about medication is crucial for safety and effectiveness . Rates of illiteracy worldwide indicate that written information alone can not meet many patients ' needs . Medication pictograms are an alternative , but may be culturally sensitive . Previous testing has used large pictograms , which are impractical for conventional drug information formats . OBJECTIVE To compare 2 sets of pictograms for instructions or warnings ( from the US and South Africa ) for underst and ability by adults in the UK and examine the effects of pictogram size and repeat presentation on underst and ability among older adults . METHODS In the first part of the study , 160 adults ( aged 17–83 y ) review ed and interpreted 10 pictograms . In the second , 67 older adults ( aged 65–96 y ) were r and omly assigned to review 10 small or large pictograms . After giving their interpretation , they were informed of the correct meaning . One week later , they were shown the same pictograms and gave their interpretation . RESULTS The pictograms for the 10 different instructions and warnings showed great variation in interpretation rates ( 7.5–90 % ) , with few significant differences between the US and South African versions . Only 3 were understood by ≥85 % of the population . Pictograms performed significantly better if they were larger and at the second presentation . CONCLUSIONS Pictograms have the potential to help patients underst and information on drug therapy . This study shows that some existing pictograms are not easily interpreted and that testing is needed before their implementation . A reduction in their size to allow incorporation into conventional written formats may cause additional problems for patients Three thous and four hundred and ten patients recruited at 254 pharmacies took part in a national postal survey of the effect of prescription information leaflets . The patients had been prescribed penicillins , non-steroidal anti-inflammatory drugs ( NSAIDs ) or β-adrenoceptor antagonists . The 1809 patients who received leaflets knew more about their medicines , especially the side effects and were significantly more satisfied than the 1601 patients who were not given additional written information . The leaflets were found to be effective when issued in the north , in the south and in small , medium and large towns . Patients of both sexes , all age groups and social classes were found to benefit from the leaflets and almost everyone ( 97 % ) thought they were a good idea . These results confirm and extend our previous findings and add further support for the routine use of information leaflets with prescribed medicines One hundred and ninety-six patients over the age of 65 years suffering from joint pain were r and omised to receive one of three patient information leaflets describing a hypothetical pain medication , a st and ard textual patient information leaflet ( PIL ) given out by a pharmaceutical chain , and two alternate-forms depicting information with icons and graphs . The results showed that patients r and omised to the traditional PIL were less likely to consider taking the hypothetical medication OBJECTIVES To characterize the degree of disparity between physicians ' perceptions of older patients ' medication regimen and patients ' perceptions of their regimen . DESIGN Prospect i ve observational . Physicians and patients were blinded at index visit ; after , trained medical students made home visits , collecting information about medications that was compared with physician question naires . SETTING Community family medicine residency program . PARTICIPANTS Patients age 65 and older presenting for routine visit , taking at least four prescription medications , and seen by index physician three or more times in the past year . Physicians were family medicine faculty and second- and third-year residents . MEASUREMENTS Fifty physician-patient pairs were analyzed . Average age was 75 ( st and ard deviation ( SD ) + /-5.5 ) ; patients averaged 7.0 prescription medications ( range 3 - 17 , SD + /-2.89 ) . Three hundred seventy-five prescription medications were identified ; the most commonly prescribed were antihypertensives ( 134/375 ; 36 % ) . RESULTS Congruence , defined as agreement between physician and patient regarding all prescription medications , dosages , and frequency , averaged 70 % for faculty ( range 53 - 89 % ) and 58 % for residents ( range 41 - 81 % ) ( P = .08 ) . Fourteen percent ( 7/50 ) demonstrated complete congruence ; 74 % ( 37/50 ) had at least one medication that either the physician was unaware the patient was taking or the physician thought the patient was taking but that was not part of the patient 's regimen ; 12 % ( 6/50 ) had dose and /or frequency discrepancies . CONCLUSIONS This study demonstrates significant disparity in a population where it is crucial for healthcare providers and patients to be in close agreement about intended medication regimens OBJECTIVE This prospect i ve study tested whether implementation intentions increased adherence to short-term antibiotics in a patient sample . Implementation intentions specify exactly when and where an individual will undertake an activity . They may help people achieve health behaviours , such as taking medicines . METHODS A total of 220 patients with an antibiotics prescription were r and omly assigned to four groups ( control , Theory of Planned Behaviour ( TPB ) question naire , TPB question naire+formed own implementation intention for taking the medicine , TPB question naire+ research er formed implementation intention ) . Participants were telephoned at the end of the course to record adherence . Two hundred and seven participants completed the study . RESULTS At follow-up , adherence was high ( 75.8 % reported no tablets left ) . Analysis revealed no significant difference in adherence between groups . CONCLUSION High adherence to antibiotics was achieved , but not improved by implementation intentions . PRACTICE IMPLICATION S Providing information and telephone follow-up may have been the unintended effective intervention in this study Abstract The objective of this study was to evaluate the effects of consumer involvement on information processing from over-the-counter ( OTC ) medication labels . A sample of 256 students evaluated simulated OTC product labels for two product categories ( headache and cold ) in r and om order . Each participant evaluated labels after reading a scenario to simulate high and low involvement respectively . A question naire was used to collect data on variables such as label comprehension , attitude-towards-product label , product evaluation , and purchase intention . The results indicate that when consumers are involved in their purchase of OTC medications they are significantly more likely to underst and information from the label and evaluate it accordingly . However , involvement does not affect attitude-towards-product label nor does it enhance purchase intention |
13,931 | 24,007,269 | Nurse practitioners and medical practitioners have differing views on the essentials of collaboration and on supervision and autonomous nurse practitioner practice .
Medical practitioners who have a working experience with NPs express more positive attitudes towards collaboration .
Both professional groups report concerns and negative experiences with collaborative practice but also value certain advantages of collaboration .
Conclusions The review shows that working in collaboration is a slow progression .
Exposure to working together helps to overcome professional hurdles , dispel concerns and provide clarity around roles and the meaning of collaboration of NPs and MPs . | Background This integrative review synthesis es research studies that have investigated the perceptions of nurse practitioners and medical practitioners working in primary health care .
The aggregation of evidence on barriers and facilitators to working collaboratively and experiences about the processes of collaboration is of value to underst and success factors and factors that impede collaborative working relationships . | Objective : To compare nurse practitioner/physician management of hospital care , multidisciplinary team-based planning , expedited discharge , and assessment after discharge to usual management . Background : In the context of managed care , the goal of academic medical centers is to provide quality care at the lowest cost and minimize length of stay ( LOS ) while not compromising quality . Methods : Comparative , 2-group , quasiexperimental design was used ; 1,207 general medicine patients ( n = 581 in the experimental group and n = 626 in the control group ) were enrolled . The control unit provided usual care . The care management in the experimental unit had 3 different components : an advanced practice nurse who followed the patients during hospitalization and 30 days after discharge , a hospitalist medical director and another hospitalist , and daily multidisciplinary rounds . LOS , hospital costs , mortality , and readmission 4 months after discharge were measured . Results : Average LOS was significantly lower for patients in the experimental group than the control group ( 5 vs. 6 days , P < .0001 ) . The " backfill profit " to the hospital was US$ 1591 per patient in the experimental group ( SE , US$ 639 ) . There were no significant group differences in mortality or readmissions . Conclusions : Collaborative physician/nurse practitioner multidisciplinary care management of hospitalized medical patients reduced LOS and improved hospital profit without altering readmissions or mortality Objective . Hospitals adapt to changing market conditions by exploring new care models that allow them to maintain high quality while containing costs . The authors examined the net cost savings associated with care management by teams of physicians and nurse practitioners , along with daily multidisciplinary rounds and postdischarge patient follow-up . Methods . One thous and two hundred and seven general medicine in patients in an academic medical center were r and omized to the intervention versus usual care . Intervention costs were compared to the difference in nonintervention costs , estimated by comparing changes between preadmission and postadmission in regression-adjusted costs for intervention versus usual care patients . Intervention costs were calculated by assigning hourly costs to the time spent by different providers on the intervention . Patient costs during the index hospital stay were estimated from administrative records and during the 4-month follow-up by weighting selfreported utilization by unit costs . Results . Intervention costs were $ 1187 per patient and associated with a significant $ 3331 reduction in nonintervention costs . About $ 1947 of the savings were realized during the initial hospital stay , with the remainder attributable to reductions in postdischarge service use . After adjustment for possible attrition bias , a reasonable estimate of the cost offset was $ 2165 , for a net cost savings of $ 978 per patient . Because health outcomes were comparable for the 2 groups , the intervention was cost-effective . Conclusions . Wider adoption of multidisciplinary interventions in similar setting s might be considered . The savings previously reported with hospitalist models may also be achievable with other models that focus on efficient inpatient care and appropriate postdischarge care |
13,932 | 29,238,205 | In subgroup analysis , IHP , Deauville criteria , and having no st and ard interpretation groups were factors able to predict PFS ; IHP and having no st and ard interpretation group were able to predict OS .
No significant difference in OS was observed when patients received 3 or fewer cycles of chemotherapy before PET/CT , though OS was significantly lower in patients receiving more than 3 chemotherapy cycles .
Conclusion IHP and Deauville criteria are commonly used for PET/CT visual evaluation at present .
Interim PET/CT analysis after 3 - 4 chemotherapy cycles is capable of predicting disease prognosis . | Objective The objective of the study was to evaluate the prognostic value of positron emission tomography (PET)/computed tomography ( CT ) visual interpretation in patients with aggressive non-Hodgkin 's lymphoma ( NHL ) using a meta- analysis and systematic review . | PET using 18F-FDG has prognostic value when performed at the completion of initial chemotherapy in patients with diffuse large B-cell lymphoma ( DLBCL ) . 18F-FDG PET may also be predictive of outcome when performed during the treatment course of DLBCL , but robust prospect i ve studies and st and ardization of 18F-FDG PET interpretation in this setting are lacking . Methods : In this prospect i ve study , patients with advanced-stage DLBCL were treated with st and ard rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisone chemotherapy , and 18F-FDG PET/CT was performed after cycle 2 or 3 and at the end of therapy . The 18F-FDG PET/CT scans were interpreted according to the International Harmonization Project for Response Criteria in Lymphoma , and the maximum st and ardized uptake value ( SUV ) of the most 18F-FDG – avid lesions was recorded . Results : Fifty patients were enrolled , and all underwent interim 18F-FDG PET/CT . At a median follow-up of 33.9 mo , the positive predictive value ( PPV ) of interim 18F-FDG PET/CT for relapse or progression was 42 % , and the negative predictive value ( NPV ) was 77 % . Interim 18F-FDG PET/CT was significantly associated with event-free survival ( P = 0.017 ) and with progression-free survival ( P = 0.04 ) but not with overall survival ( P = 0.08 ) . End-of-therapy 18F-FDG PET/CT had high PPV and NPV ( 71 % and 80 % , respectively ) and was significantly associated with event-free survival , progression-free survival , and overall survival ( P < 0.001 ) . SUV measurements did not discriminate patients who relapsed or progressed from those who remained in remission . Conclusion : When performed after 2 cycles of immunochemotherapy and interpreted according to International Harmonization Project criteria , early response assessment with PET/CT has a high NPV but low PPV in patients with advanced-stage DLBCL . Prospect i ve trials are required to vali date different criteria for the interpretation of interim 18F-FDG PET/CT and establish the role of interim 18F-FDG PET/CT in the management of patients with DLBCL The International Prognostic Index ( IPI ) is a widely accepted model that is used to predict the prognosis of patients with diffuse large B-cell lymphoma ( DLBCL ) who are treated using chemotherapy . However , the prognostic value of the IPI has been a focal point of debate in the immunochemotherapy era . The aim of this study was to reassess the value of the IPI and revised IPI ( R-IPI ) in a Chinese population . A multicentre retrospective analysis of DLBCL patients who were treated with cyclophosphamide , doxorubicin , vincristine and prednisone (CHOP)-like chemotherapy alone or chemotherapy plus rituximab ( R-CHOP-like ) was performed . The prognostic values of IPI and R-IPI at the time of diagnosis with respect to overall survival ( OS ) and progression-free survival ( PFS ) were evaluated . Among the 438 patients in the study , 241 received a CHOP-like regimen and 197 patients received an R-CHOP-like regimen . Although the IPI remained predictive for the CHOP-like group , it failed to distinguish between the various prognostic categories in the R-CHOP-like group . Notably , redistribution of the IPI factors into R-IPI factors identified three discrete prognostic groups with significantly different outcomes in both the CHOP-like and R-CHOP-like groups . In the R-CHOP-like group , these three risk groups , very good , good and poor , had distinctly different 3-year PFS rates of 96 , 84.3 and 67.5 % ( P=0.001 ) , and 3-year OS rates of 96 , 87.6 and 71.1 % ( P=0.003 ) , respectively . Our study demonstrates the power of the R-IPI as a simplified and more clinical ly relevant predictor of disease outcome than the st and ard IPI in DLBCL population s in the rituximab era . Therefore , the R-IPI merits further study in a larger population -based prospect i ve study The prognostic value of interim positron emission tomography ( PET ) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma ( DLBCL ) . Maximal st and ardized uptake value reduction ( ΔSUVmax ) may better predict outcome . To compare the prognostic value of both methods , we analyzed PET done at baseline ( PET0 ) and after 2 ( PET2 ) and 4 ( PET4 ) cycles in 85 patients with high-risk DLBCL enrolled on a prospect i ve multicenter trial . All images were central ly review ed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 ( ΔSUVmaxPET0 - 2 ) or PET4 ( ΔSUVmaxPET0 - 4 ) . Optimal cutoff to predict progression or death was 66 % for ΔSUVmaxPET0 - 2 and 70 % for ΔSUVmaxPET0 - 4 . Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative . Inversely , ΔSUVmaxPET0 - 2 analysis ( > 66 % vs ≤ 66 % ) identified patients with significantly different 2-year progression-free survival ( 77 % vs 57 % ; P = .0282 ) and overall survival ( 93 % vs 60 % ; P < .0001 ) . ΔSUVmaxPET0 - 4 analysis ( > 70 % vs ≤ 70 % ) seemed even more predictive for 2-year progression-free survival ( 83 vs 40 % ; P < .0001 ) and overall survival ( 94 % vs 50 % ; P < .0001 ) . ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis . The trial was registered at http:// clinical trials.gov as NCT00498043 BACKGROUND Revised response criteria for aggressive lymphomas have been proposed ( Cheson , J Clin Oncol , 2007 ) stressing the role of (18)fluorodeoxyglucose-positron emission tomography ( PET ) in posttreatment evaluation . The value of PET after four cycles compared with the International Workshop Criteria ( IWC ) remains to be established . PATIENTS AND METHODS In all , 103 patients with untreated diffuse large B-cell lymphoma were prospect ively enrolled to evaluate the prognostic impact of PET after two and four cycles . RESULTS Median age was 53 years ( 19 - 79 ) , 68 % male . The International Prognostic Index was low=22 % , low-intermediate=19 % , intermediate-high=33 % and high risk=26 % . Treatment consisted of cyclophosphamide , doxorubicin , vincristine , prednisone ( CHOP ) ( 30 % ) or dose-intensified CHOP ( 70 % ) , with rituximab ( 49 % ) or without ( 51 % ) . Ninety-nine patients were evaluated by PET and IWC at four cycles : 77 ( 78 % ) had a negative PET , while 22 ( 22 % ) remained positive . The 5-year event-free survival ( EFS ) was 36 % for patients with a positive PET versus 80 % with a negative examination , whatever the response [ complete response ( CR ) versus partial response ( PR ) ] according to IWC ( P<0.0001 ) . Positive PET patients had a 5-year EFS of 58 % if in CR/CR unconfirmed by IWC and 0 % if not ( P<0.0001 ) . The same observations could be made in patients treated with and without rituximab . CONCLUSION The integration of PET in treatment evaluation offers a powerful tool to predict outcome PURPOSE (18)F-fluoro-2-dexoy-D-glucose-positron emission tomography (FDG-PET)/computerised tomography ( CT ) has been used for staging and monitoring responses to treatment in patients with diffuse large B cell lymphoma ( DLBCL ) . The sequential interim PET/CT was prospect ively investigated to determine whether it provided additional prognostic information and could be a positive predictable value within patients with the same international prognostic index ( IPI ) after the use of rituximab in DLBCL . METHODS One hundred and sixty-one patients with newly diagnosed DLBCL were enroled ; the assessment of the PET/CT was performed at the time of diagnosis and mid-treatment of rituxibmab , cyclophosphamide , doxorubicin , vincristine and prednisolone ( R-CHOP ) . RESULTS Sixty-seven patients ( 41.6 % ) presented with advanced stage disease and 27 ( 16.8 % ) had bulky lesions . Forty-three patients ( 26.7 % ) continued to have positive metabolic uptakes with a significantly high relapse rate ( 62.8 % ) compared to the patients with a negative interim PET/CT ( 12.1 % ) ( P<0.01 ) . After a median follow-up of 30.8months , the positivity of interim PET/CT was found to be a prognostic factor for both overall survival ( OS ) and progression-free survival ( PFS ) , with a hazard ratio of 4.07 ( 2.62 - 6.32 ) and 5.46 ( 3.49 - 8.52 ) , respectively . In the low-risk IPI group , the 3-year OS and PFS rates were significantly different in the patients with positive ( 53.3 % and 52.5 % ) and negative ( 93.8 % and 88.3 % ) interim PET/CT , respectively ( P<0.01 ) . These significant prognostic differences of interim PET/CT responses were consistent with the results of the patients with high-risk IPI group ( P<0.01 ) . CONCLUSIONS Interim PET/CT scanning had a significant predictive value for disease progression and survival of DLBCL in post-rituximab treatment ; it might be the single most important determinant of clinical outcome in patients with the same IPI risk PURPOSE Our main objective was to prospect ively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography ( PET/CT ) after two cycles of rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone given every 14 days ( R-CHOP-14 ) under st and ardized treatment and PET evaluation criteria . PATIENTS AND METHODS Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab . PET/CT examinations were performed at baseline , after two cycles ( and after four cycles if the patient was PET-positive after two cycles ) , and at the end of treatment . PET/CT examinations were evaluated locally and by central review . The primary end point was event-free survival at 2 years ( 2-year EFS ) . RESULTS Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0 , 1 , or 2 in 56 % , 36 % , or 8 % of the patients , respectively . By local assessment , 83 PET/CT scans ( 60 % ) were reported as positive and 55 ( 40 % ) as negative after two cycles of R-CHOP-14 . Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients ( 48 % v 74 % ; P = .004 ) . Overall survival at 2 years was not significantly different , with 88 % for PET-positive versus 91 % for PET-negative patients ( P = .46 ) . By using central review and the Deauville criteria , 2-year EFS was 41 % versus 76 % ( P < .001 ) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24 % versus 72 % ( P < .001 ) for patients who had PET/CT scans at the end of treatment . CONCLUSION Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospect i ve trial . At this point , interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients Positron emission tomography ( PET ) has been found useful in monitoring response to treatment of malignant lymphoma . We investigated the ability of interim PET to monitor response to st and ard dose R-CHOP chemotherapy in chemotherapy-naïve patients with diffuse large B-cell lymphoma ( DLBCL ) . Between March 2004 and April 2009 , 155 DLBCL patients treated with R-CHOP and available for interim and post-treatment PET/CT were identified and included in this analysis . Response , progression-free survival ( PFS ) , and overall survival ( OS ) were compared between interim PET/CT-negative and positive group , and among three patient groups which were categorized based on their interim and post-treatment PET/CT : those with early metabolic complete response ( mCR ) , delayed mCR , and never mCR . Interim PET/CT-negative patients ( n = 100 ) showed superior CR rates to interim PET/CT-positive patients ( n = 55 ; 93 % vs 62 % , P < 0.001 ) . However , there was no difference in PFS ( P = 0.07 ) and OS ( P = 0.24 ) between interim PET/CT-negative and positive group . We categorized patients into three groups , with 100 ( 64 % ) in the early mCR group , 35 ( 23 % ) in the delayed mCR group , and 20 ( 13 % ) in the never mCR group . Early mCR and delayed mCR group did not differ significantly in PFS ( P = 0.84 ) or OS ( P = 0.20 ) . However , the survival outcome in the never mCR group was significantly inferior to the combined early and delayed mCR group . The result from this study suggests that interim PET/CT might be an inappropriate tool for design ing risk-adaptive therapy in chemotherapy-naïve DLBCL patients treated with R-CHOP . Prospect i ve trials should be performed to clearly determine the role of interim PET/CT This study investigated whether the reference background above which a residual mass is considered positive in the International Harmonization Project criteria should be modified for early 18F-FDG PET evaluation . Methods : In 92 patients with newly diagnosed diffuse large B-cell lymphoma , the maximal st and ardized uptake value ( SUVmax ) was measured on post – cycle 2 PET in the most intense residual mass ( or , in the case of negative PET findings , in the area of most intense tumor uptake before therapy ) , in the mediastinal blood pool ( MBP ) and the liver , as potential reference background tissues . Results : With MBP as a reference ( SUVmax , 2.0 ± 0.6 ) , PET was unable to distinguish early responders from nonresponders . In contrast , with liver as a reference ( SUVmax , 2.5 ± 0.7 ) , 2-y progression-free survival was significantly different between patients with PET-negative findings ( 81.8 % [ 95 % confidence interval , 71%–93 % ] ) and patients with PET-positive findings ( 51.8 % [ 95 % confidence interval , 35%–69 % ] , P = 0.003 ) . Conclusion : When assessing early response , particularly in risk-adapted therapeutic trials , it seems preferable to refer to a background tissue ( liver ) with a higher level of uptake than that of current international criteria ( MBP ) which were design ed for end-of-treatment evaluation Assessment of early therapeutic response using metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma . Between January 2000 and January 2004 , 90 patients with newly diagnosed aggressive lymphoma ( median age 53 years , 94 % diffuse large B-cell ) were prospect ively explored with [18F]fluoro-2-deoxy-D-glucose positron emission tomography ( FDG-PET ) prior to induction chemotherapy , after 2 cycles ( " early PET " ) , and after induction completion . Therapeutic response was evaluated using conventional diagnostic methods at 4 cycles . Induction treatment with an anthracycline-containing regimen was administered to all patients , associated with rituximab in 41 % . According to the International Prognostic Index ( IPI ) , 37 patients and 53 patients belonged to the lower- and higher-risk groups , respectively . At midinduction , " early PET " was considered negative in 54 patients and positive in 36 . After completion of induction , 83 % of PET-negative patients achieved complete remission compared with only 58 % of PET-positive patients . Outcome differed significantly between PET-negative and PET-positive groups ; the 2-year estimates of event-free survival reached 82 % and 43 % , respectively ( P < .001 ) , and the 2-year estimates of overall survival reached 90 % and 61 % , respectively ( P = .006 ) . Predictive value of " early PET " was observed in both the lower-risk and higher-risk groups , indicating prognostic independence from the IPI . Therefore , FDG-PET should be an early guide to first-line strategies in aggressive lymphoma BACKGROUND Although many patients with intermediate- grade or high- grade ( aggressive ) non-Hodgkin 's lymphoma are cured by combination chemotherapy , the remainder are not cured and ultimately die of their disease . The Ann Arbor classification , used to determine the stage of this disease , does not consistently distinguish between patients with different long-term prognoses . This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin 's lymphoma on the basis of the patients ' clinical characteristics before treatment . METHODS Adults with aggressive non-Hodgkin 's lymphoma from 16 institutions and cooperative groups in the United States , Europe , and Canada who were treated between 1982 and 1987 with combination-chemotherapy regimens containing doxorubicin were evaluated for clinical features predictive of overall survival and relapse-free survival . Features that remained independently significant in step-down regression analyses of survival were incorporated into models that identified groups of patients of all ages and groups of patients no more than 60 years old with different risks of death . RESULTS In 2031 patients of all ages , our model , based on age , tumor stage , serum lactate dehydrogenase concentration , performance status , and number of extranodal disease sites , identified four risk groups with predicted five-year survival rates of 73 percent , 51 percent , 43 percent , and 26 percent . In 1274 patients 60 or younger , an age-adjusted model based on tumor stage , lactate dehydrogenase level , and performance status identified four risk groups with predicted five-year survival rates of 83 percent , 69 percent , 46 percent , and 32 percent . In both models , the increased risk of death was due to both a lower rate of complete responses and a higher rate of relapse from complete response . These two indexes , called the international index and the age-adjusted international index , were significantly more accurate than the Ann Arbor classification in predicting long-term survival . CONCLUSIONS The international index and the age-adjusted international index should be used in the design of future therapeutic trials in patients with aggressive non-Hodgkin 's lymphoma and in the selection of appropriate therapeutic approaches for individual patients Abstract Patients with diffuse large B-cell lymphoma ( DLBCL ) with a poor prognosis based upon advanced stage and elevated serum lactate dehydrogenase achieve a 3–4-year progression-free survival ( PFS ) of only 55 % . The role of interim fluoro-2-deoxy-d-glucose ( FDG ) positron emission tomography ( PET ) to guide use of upfront high dose chemotherapy ( HDCT ) and autologous stem cell transplant ( ASCT ) for patients with poor prognosis DLBCL is unproven . A prospect i ve phase II clinical trial was design ed to evaluate the outcomes of HDCT/ASCT for patients with poor prognosis DLBCL aged 18–65 years who had unfavorable interim restaging PET scans . Of the 70 eligible patients , 36 had unfavorable and 34 favorable interim PET responses , with 3-year PFS rates of 65.2 % and 52.7 % , respectively . In conclusion , favorable interim PET response as defined in this study is not associated with improved PFS rates for patients with poor prognosis DLBCL treated with RCHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine , prednisone ) . A phase III trial evaluating this PET-guided approach is not warranted Role of interim-PET ( I-PET ) in diffuse large B-cell Lymphoma ( DLBCL ) is controversial . To determine predictive value of I-PET on progression-free survival ( PFS ) , we enrolled 88 first-line DLBCL patients treated with 6 - 8 R-CHOP courses regardless of I-PET . PET/CT were performed at diagnosis , after 2 to 4 courses and at the end of therapy with central review ing according to visual dichotomous criteria . Results are as follows : I-PET , 72 % negative , 28 % positive ; final-PET ( F-PET ) , 88 % negative , 12 % positive ; clinical complete response 90 % . Concordance between clinical response and F-PET negativity was 97 % because of 2 false positive . With a median follow-up of 26.2 months , 2-year overall survival and PFS were 91 % and 77 % , respectively . Two-year PFS for I-PET and F-PET negative versus positive were as follows : I-PET 85 % versus 72 % ( P = .0475 ) ; F-PET 83 % versus 64 % ( P < .001 ) . Because of a small number of events , 2 independent bivariate Cox models were tested for PFS . In model 1 , F-PET contradicted I-PET ( hazard ratio [ HR ] = 5.03 , P = .015 vs 1.27 , P = 691 ) ; in model 2 , F-PET ( HR = 4.54 ) and International propnostic Index score ( HR = 5.36 , P = .001 ) remained independent prognostic factors . In conclusion , positive I-PET is not predictive of a worse outcome in DLBCL ; larger prospect i ve studies and harmonization of I-PET reading criteria are needed Abstract In diffuse large B-cell lymphoma ( DLBCL ) , the response to first-line immunochemotherapy remains somewhat unpredictable . Interim [18F]fluorodeoxyglucose-positron emission tomography ( FDG-PET ) ( PET-int ) analysis could be an important tool in the prompt shift to intensified regimens . We prospect ively evaluated the effectiveness of PET-int carried out at mid-treatment with st and ard immunochemotherapy in predicting relapse in a series of 85 consecutive patients with DLBCL . PET-int results were dichotomized as positive or negative using the recently vali date d five-point scale scoring system . This examination was also compared with interim computed tomography ( CT-int ) and final PET ( PET-fin ) . End-points were : complete remission ( CR ) , positive predictive value ( PPV ) of refractoriness and relapse , negative predictive value ( NPV ) , overall survival ( OS ) and progression-free survival ( PFS ) . Observation time was fixed to 24 months unless preceded by a DLBCL-related event . The PPV of PET-int was 58 % and the NPV was 77 % . CR was correlated with both PET-int and CT-int ( p < 0.0001 ) , but in multivariate analysis only CT-int was correlated with CR ( p = 0.002 ) . CT-int and PET-fin were predictive of both OS and PFS , whereas PET-int was predictive only of OS ( p = 0.013 ) . In Cox regression only PET-fin was predictive for both OS ( p = 0.004 ) and PFS ( p = 0.005 ) . PET-int was unable to discriminate those chemosensitive patients who would later relapse . We therefore believe that the use of this expensive radioactive tool is not justified as an interim analysis |
13,933 | 11,687,055 | REVIEW ER 'S CONCLUSIONS The results of this review are inconclusive ; the published trials do not provide information on the stimulation parameters which are most likely to provide optimum pain relief , nor do they answer questions about long-term effectiveness . | BACKGROUND Transcutaneous electrical nerve stimulation ( TENS ) is used in a variety of different clinical setting s to treat a range of different acute and chronic pain conditions and has become popular with both patients and health professionals .
OBJECTIVES To evaluate the effectiveness of TENS in chronic pain . | The aim of the present study was to compare the effect of transcutaneous electric nerve stimulation ( TENS ) with the flat occlusal splint in the treatment of temporom and ibular joint ( TMJ ) disk displacement without reduction . Thirty-one patients were included and r and omly selected to be treated 6 weeks with either TENS ( 90 Hz , 30 min , three times/day ) or with a flat occlusal splint ( 24 h/day . Those selected for the TENS group had one electrode placed over the painful TMJ and another electrode over the anterior temporal muscle . The splint group used a conventional flat occlusal splint with cuspid guidance . Both treatment groups visited the clinic once a week . Symptoms and signs were registered before and after treatment . The intensity of pain was recorded with a visual analogue scale ( VAS ) and with an electronic pocket-sized recorder ( Pain-Track ) carried 1 week before and also the last week of treatment for continuous registration of pain . Measured with the VAS , half of the patients treated with splints became pain-free or their TMJ pain improved at least 50 % both at rest and with jaw function compared with only 6 % in the TENS-treated group . With regard to strictly chewing pain , the VAS-registered pain improved in two-thirds of the splint group , compared with 50 % of the TENS group . With the Pain-Track device it was found that in most individuals pain was aggrevated at mealtimes . The conclusion was that flat occlusal splints in several respects are better than TENS in the treatment of symptoms associated with TMJ disk displacement without reduction & NA ; The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double‐blind cross‐over trial using a genuine stimulator and a placebo machine . Placebo analgesic effects occurred in 32 % of trials , as compared with 48 % for actual stimulation . The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double‐blind studies in which medicationms are used & NA ; The effects of transcutaneous electrical nerve stimulation ( TENS ) on myofascial pain and trigger point sensitivity were assessed . Four modes of TENS and a no‐stimulation control were compared in a double‐blind design . Stimulation , carried out for 10 min on 60 subjects ( 12/group ) , showed significant pain reductions with 100 Hz , 250 msec stimulation followed by 100 Hz , 50 msec and then pain suppressor TENS . No pain reductions were found in the 2 Hz , 250 msec TENS or the control . No significant alteration in myofascial trigger point sensitivity , assessed with the pressure algometer , was found between the groups . The results suggest that high frequency , high intensity TENS is effective in reducing myofascial pain , and that these pain reductions do not reflect changes in local trigger point sensitivity Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion 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 OBJECTIVE Our purpose was to compare the effects of high-intensity transcutaneous electrical nerve stimulation and oral naproxen ( 500 mg ) on intrauterine pressure and menstrual pain . STUDY DESIGN An open , r and omized crossover study was performed on 12 women with primary dysmenorrhea . Intrauterine pressure was recorded with a microtransducer catheter , and the pain score was assessed by a visual analog scale . RESULTS Before treatment all patients displayed signs of uterine hyperactivity as judged by a high resting pressure ( 7.5 + /- 0.4 kPa ) , high active pressure ( 24.0 + /- 0.8 kPa ) , and a high frequency of pressure cycles ( 13.3 + /- 0.5 contractions per 0.5 hour ) . Oral administration of naproxen suppressed ( p < 0.01 ) all uterine activity parameters . Treatment with transcutaneous electrical nerve stimulation induced a prompt onset of pain relief in a strictly segmental manner , but there were no significant changes in uterine activity . The pain score was significantly reduced ( p < 0.001 ) from 30 to 60 minutes after treatment with transcutaneous electrical nerve stimulation and from 19 to 120 minutes after naproxen administration . CONCLUSIONS Treatment with transcutaneous electrical nerve stimulation induced a prompt onset of pain relief without any significant changes in uterine activity . Possible mechanisms for the pain relief , decreased uterine ischemia or decreased activity in the pain transmission system at spinal or supraspinal levels , are discussed The purpose of this investigation was to evaluate the long-term course of non-invasively treated chronic headache . A total of 1015 adult patients with primary diagnosis of vascular/migraine or muscle contraction headache participated in the study investigating symptom frequency and severity over a 36 month period after receiving treatment . Treatment consisted of either : relaxation training ( stepwise relaxation/hypnosis/autogenic training/cognitive behavior therapy ) ; biofeedback ( thermal/photoplethysmograph/EMG ) ; micro-electrical therapy ( TENS/Neurotransmitter Modulation ) or multimodal treatment ( combination of any of the above two treatments ) . Seven hundred and ninety-three patients returned sufficient data to be included in the analysis . Patients were r and omly assigned to treatment groups and received either short term intervention ( 15 or less treatments ) or long term intervention ( greater than 15 treatments ) . Results indicate that all treatment conditions significantly reduced frequency and intensity of cephalalgia . Repeated measure analysis of variance indicated that grouping variables of Biofeedback treatment , symptoms being evidence d less than 2 years and receiving over 15 treatment sessions best predicted successful intervention The analgesic efficacy of various pulse patterns of transcutaneous electrical nerve stimulation ( TENS ) were assessed in 84 normal healthy subjects using the cold pressor pain technique . Burst , modulation , r and om and continuous TENS all significantly elevated ice pain threshold . Continuous ( 80 Hz ) TENS produced the greatest mean elevation in threshold but the response to r and om TENS showed the least inter-subject variation . Ice pain tolerance was increased by all modes of TENS , continuous TENS producing the greatest magnitude of response , although these changes did not reach statistical significance . Increasing the size of electrodes reduced the effect of continuous TENS . The clinical implication s of these findings are discussed Acupuncture is one of the oldest healing methods which is used in traditional medicine . In the modern medicine , we are witnessing a renaissance of this ancient treatment applied mainly in the management of chronic pain . A number of modern technological changes are being applied to replace , or modify , the classical needle treatment . Among many modalities used today is the novel addition in Transcutaneous Electrical Nerve Stimulation ( TENS ) called CODETRON which delivers acupuncture-like stimulation in a r and om order . CODETRON was developed by a Canadian Scientist and had been evaluated in a clinical trial in a multidisciplinary pain clinic on patients who came for acupuncture therapy over a period of two years . Indications , effectiveness and experiences with this form of treatment are presented . In addition , results obtained from a six week double-blind r and omized placebo controlled pilot trial of osteoarthritis of the hip/knee with CODETRON which was conducted later . The results were highly suggestive of the beneficial effect of this nonhabituating mode of therapy and confirmed our initial uncontrolled trial results There is currently no established treatment for intermittent claudication with proven long term benefit . Exercise classes have been shown to improve walking distance . Chronic electromyostimulation ( CEMS ) a method of stimulating skeletal muscle has effects on normal muscle which may also benefit claudicants . We investigated the effects of one month of CEMS on claudicants in a single blind placebo controlled study . Patients were r and omised to either CEMS ( treatment ) or transcutaneous nerve stimulation ( TENS ) placebo . The effects of the two modalities were assessed using the conventional measures of claudicating distance ( CD ) , maximum walking distance ( MWD ) , ankle-brachial pressure index ( ABPI ) and pressure recovery time ( PRT ) . Muscle performance was assessed by the fatigue index ( FI ) a technique determining the decrease in ischaemic muscle response to repeated contraction . After 4 weeks treatment the CEMS group showed significant improvements in their median CD ( 88 to 111 ) and MWD ( 118 to 158 ) ; this was not seen in the control group . Muscle performance also increased significantly during the 4 weeks of treatment in the CEMS group but not in the control group . These changes were not maintained after CEMS was stopped . This pilot study suggests that CEMS may well have a role to play in the treatment of intermittent claudication though a number of further studies need to be undertaken Abstract . in this study we describe the use of high‐frequency transcutaneous electrical nerve stimulation ( TENS ) ( 100 Hz ) and low‐frequency TENS ( lf‐TENS ) ( 2 Hz trains ) as compared with placebo‐TENS ( p‐TENS ) in a group of 21 patients suffering from primary dysmenorrhea . Naloxone , a relatively pure opiate antagonist , was an additional test administered to 6 volunteer patients who had experienced an alleviation of pain with TENS . As will be seen , 14 out of 21 patients receiving high‐frequency TENS ( hf‐TENS ) experienced a pain reduction exceeding 50 % of its original intensity . During lf‐TENS or p‐TENS , only 7 and 5 patients , respectively , obtained pain relief exceeding 50 % . in 4 out of 6 volunteer patients , the relief of pain obtained with lf‐TENS was counteracted by naloxone , whereas the relief experienced with hf‐TENS in the same patients was , in general , unaffected by naloxone We compared the effects of four treatment variables on the pain reduction produced by transcutaneous electrical nerve stimulation and attempted to establish indications for TENS based on patient history and pain evaluation items . Treatment variables were the therapist and the three TENS stimulus characteristics -- pulse width , frequency , and amplitude . We r and omly assigned 192 consecutive adult patients suffering from painful conditions to one of four physical therapists and one of 12 stimulus characteristic combinations . We used a st and ard evaluation form that included a visual analog scale ( VAS ) to evaluate pain . Patients were given a 30-minute trial using TENS , followed by reevaluation . The VAS line length change after treatment was the criterion score for comparison of stimulus characteristic effectiveness . Although pain was reduced greatly with TENS ( p = .01 ) , a four-way analysis of variance ( pulse width , frequency , amplitude , and therapist ) attributed little of the treatment effect to the treatment variables or their interactions ( r2 = .101 ) . The amplitude effect , however , was borderline ( p = .056 ) , and subthreshold stimulation proved more effective than stimulation to tolerance ( p = .05 ) . Extensive multiple linear regression analyses failed to provide indications for TENS based on patient information and pain evaluation items . Therefore , pain remains the only indication for TENS , and we recommend subthreshold rather than higher amplitude stimulation on the initial TENS trial Thirty patients with chronic pain due to osteoarthrosis ( OA ) of the knee were enrolled in a r and omised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS . Medication was st and ardised to paracetamol tablets only . As measured on visual analogue scales for pain relief 46 % of patients responded to active therapy and 43 % to placebo . The length of pain relief during active therapy was significantly longer than that during placebo . At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication . Although most of the parameters observed favoured active TENS , it was not possible to establish its clear superiority over placebo , because the response rate to placebo TENS was high and sustained for at least 3 weeks . This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis & NA ; It has recently been shown that ice massage of the web between the thumb and index finger produces significantly greater relief of dental pain than a placebo control procedure . These results indicate that ice massage may be comparable to transcutaneous electrical stimulation ( TES ) and acupuncture , and may be mediated by similar neural mechanisms . The purpose of this study was to examine the relative effectiveness of ice massage and TES for the relief of low‐back pain . Patients suffering chronic low‐back pain were treated with both ice massage and TES . The order of treatments was balanced , and changes in the intensity of pain were measured with the McGill Pain Question naire ( MPQ ) . The results show that both methods are equally effective : based on the Pain Rating Index of the MPQ , 67–69 % of patients obtained pain relief greater than 33 % with each method . The results indicate that ice massage is an effective therapeutic tool , and appears to be more effective than TES for some patients . It may also serve as an additional sensory‐modulation method to alternate with TES to overcome adaptation effects . Evidence that cold signals are transmitted to the spinal cord exclusively by A‐delta fibers and not by C fibers suggests that ice massage provides a potential method for differentiating among the multiple feedback systems that mediate analgesia produced by different forms of intense sensory input Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation ( TENS ) and naproxen , an NSAID . All pre-experiment treatment was withdrawn . Each subject experienced in some order three 3-week treatment phases : NSAID plus placebo TENS ; TENS plus placebo drug ; and double placebo . A broad range of pain measures was used , including daily diary ratings , and four-times-per-day ratings entered into a small electronic data logger ( the PIPER ) worn by the subject . A substantial placebo response occurred across all conditions , which may have masked treatment differences . Broad comparisons across subjects , combining the four main measures of pain , found no significant differences among the three experimental treatments . Analysis of diary and PIPER data for individuals suggested that , in a small minority of subjects , the NSAID plus placebo TENS combination may be more effective than double placebo . The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures , suggesting the value of very frequent pain assessment s , such as those entered by a subject into the PIPER , in the study of chronic pain Patients with acute or chronic low back pain were treated in a double-blind study that compared transcutaneous electrical nerve stimulation at intense levels and gentle , mechanically administered massage . Transcutaneous electrical nerve stimulation produced significantly greater pain relief , based on two measures of the McGill Pain Question naire , and significant improvement in straight leg raising . There were no significant differences between the two groups in backflexion scores . Pain-relief scores and range-of-motion scores were significantly correlated . The results indicate that pain-relief scores provide valuable information and can easily be obtained from patients for whom pain is a major symptom The effects of electrical stimulation by simple pocket size stimulator were evaluated on myofascial trigger points by pain threshold ( PTH ) algometry . The study consisted 14 patients with 76 treated trigger points in r and omly selected double blind cross-over study protocol . The effects of 30 seconds stimulation increased the PTH values 0.58 kg/cm2 in study group , but only 0.13kg/cm2 in controls ( p < 0.01 ) . These results suggested that the stimulation had positive effects on myofascial trigger points , but these effects were seen only on the treated points OBJECTIVE To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Thirty-one patients with symptoms and signs of peripheral neuropathy were r and omized to the electrotherapy or sham treatment ( control ) group . The electrostimulation was given by a portable unit ( H-Wave machine ) than generated a biphasic , exponentially decaying waveform ( pulse width 4 ms , 25–35 V , ≥ 2 Hz ) . Patients treated each of their lower extremities for 30 min daily for 4 weeks at home . Nine patients from the sham-treatment group participated for a second period , during which all of them received the active electrotherapy . Patient 's degree of pain and discomfort was grade d on a scale of 0 to 5 . RESULTS In the sham-treated group ( n = 13 ) , the neuropathic symptoms improved in five ( 38 % ) patients , and the pain score declined from 2.92 ± 0.13 to 2.38 ± 0.26 ( P < 0.04 ) , suggesting a procedure-related placebo effect . In the electrotherapy group ( n = 18 ) , symptomatic improvement was seen in 15 ( 83 % ) cases , 3 of which were completely asymptomatic ; the pain score declined from 3.17 ± 0.12 to 1.44 ± 0.25 ( P < 0.01 ) and the posttreatment pain scores were considerably lower ( P < 0.03 ) , indicating a substantial treatment effect over and above any placebo influence . Patients in the electrotherapy group reported greater reduction in symptoms ( 52 ± 7 % vs. 27 ± 10 % in control subjects , P < 0.05 ) on an analog scale . Moreover , the electrotherapy decreased pain scores ( from 3.0 ± 0.62 to 1.56 ± 0.32 , P < 0.02 ) in nine patients who had received sham treatment earlier . CONCLUSIONS A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy . This novel modality offers a potential non-pharmacological treatment option Although Transcutaneous Electrical Nerve Stimulation ( TENS ) has become a popular modality in pain management over the past 20 yr , there is still debate over its mechanisms of action and the precise relevance of stimulation parameters to its hypoalgesic effects . Thus , confusion still surrounds the selection of optimal stimulation parameters . Two separate studies ( total n=88 ) were carried out to investigate the effect of four combinations of TENS pulse duration s ( 50 ( µ.s & 200 µ.s ) and frequencies ( 4 Hz and 110 Hz ) on nerve conduction in the human superficial radial nerve and on Mechanical Pain Threshold ( MPT ) within the associated sensory distribution of the nerve over the dorsum of the h and . Results showed that application of one combination of TENS parameters ( 110 Hz , 200 µ,s ) directly over the course of the nerve produced a significant increase in both peripheral nerve conduction latency ( P < 0.05 ; analysis of variance ( ANOVA ) ) and MPT ( P < 0.01 ) . In addition , there was a high correlation ( r=0.9 ) between shifts in MPT and negative peak latency for the groups treated with this combination of TENS parameters . The results of this study thus illustrate that combinations of TENS parameters are important to the peripheral neurophysiological effects of this modality and , further , its associated hypoalgesic effects , at least on the model of pain used here A number of treatments are widely prescribed for chronic back pain , but few have been rigorously evaluated . We examined the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , a program of stretching exercises , or a combination of both for low back pain . Patients with chronic low back pain ( median duration , 4.1 years ) were r and omly assigned to receive daily treatment with TENS ( n = 36 ) , sham TENS ( n = 36 ) , TENS plus a program of exercises ( n = 37 ) , or sham TENS plus exercises ( n = 36 ) . After one month no clinical ly or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain , function , and back flexion ; there was no interactive effect of TENS with exercise . Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS ( P not significant ) . The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes . By contrast , after one month patients in the exercise groups had significant improvement in self-rated pain scores , reduction in the frequency of pain , and greater levels of activity as compared with patients in the groups that did not exercise . The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups ( P = 0.02 ) . Two months after the active intervention , however , most patients had discontinued the exercises , and the initial improvements were gone . We conclude that for patients with chronic low back pain , treatment with TENS is no more effective than treatment with a placebo , and TENS adds no apparent benefit to that of exercise alone The object of this study is to determine if the functional motor capacity of the paretic extremity can be improved by stimulation with low intensity low frequency ( 1.7 Hz ) transcutaneous electric nerve stimulation ( Low-TENS ) , started 6 - 12 months after a stroke . Forty-four patients who had a paretic arm as a consequence of their first stroke were included and r and omly assigned to either a treatment group ( n = 26 ) or a control group ( n = 18 ) . Patients in both groups received physiotherapy at a day-care center , usually twice a week . The treatment group received , in addition , Low-TENS for 60 min , five days a week for three months . Results showed that motor function increased significantly in the treatment group , compared to controls . The Low-TENS did not decrease either pain or spasticity . It is concluded that stimulation by means of Low-TENS could be a valuable complement to the usual training of arm and h and function in the rehabilitation of stroke patients Sixty patients aged 60 or over with back pain for at least 6 months were recruited from General Practitioner referrals and r and omized to 4 weeks of treatment with acupuncture or transcutaneous electrical nerve stimulation ( TENS ) . All treatments were administered by the same physiotherapist and both groups had the same contact with him . The following were measured at baseline , completion and at a 3-month follow-up by an independent observer blinded to treatment received : ( 1 ) pain severity on visual analogue scale ( VAS ) ; ( 2 ) pain subscale of Nottingham Health Profile ( NHP ) ; ( 3 ) number of analgesic tablets consumed in previous week ; ( 4 ) spinal flexion from C7 to S1 . Thirty-two patients were r and omized to acupuncture and 28 to TENS ; only three withdrew ( two from acupuncture , one from TENS ) . Significant improvements were shown on VAS ( P < 0.001 ) , NHP ( P < 0.001 ) and tablet count ( P < 0.05 ) between baseline and completion in both groups , these improvements remaining significant comparing baseline with follow-up with a further non-significant improvement in VAS and NHP in the acupuncture group . The acupuncture but not the TENS patients showed a small but statistically significant improvement ( P < 0.05 ) in mean spinal flexion between baseline and completion which was not maintained at follow-up . Thus in these elderly patients with chronic back pain both acupuncture and TENS had demonstrable benefits which outlasted the treatment period . Acupuncture may improve spinal flexion . This trial can not exclude the possibility that both treatments are ' placebos ' The authors report the results of a r and omized controlled trial to examine the effectiveness of transcutaneous electrical nerve stimulation ( TENS/CODETRON ) when added to a st and ard exercise program for industrial workers with acute low back pain ( LBP ) . Fifty-eight work-injured patients with LBP of 3 - 10 weeks duration were r and omized into two groups that received actual or placebo stimulation in combination with the exercise regimen . The groups were compared on the primary outcome measures of disability , pain , and return to work . No significant differences between the experimental and placebo groups were discovered on any of the measured outcomes . Exercise alone , when continued over 4 weeks , reduced disability and pain scores significantly . Under the experimental conditions of this trial , no additional benefits of TENS/CODETRON were detected when added to an active exercise regimen OBJECTIVE A study was conducted to assess a variety of treatment outcomes in long-term users of transcutaneous electrical nerve stimulation ( TENS ) who suffer from chronic pain . Key components of the study examined the effects of long-term TENS therapy on pain-related medications and physical/occupational therapy ( PT/OT ) use . DESIGN From a population of 2,(X)3 chronic pain patients ( CPPs ) who acquired a TENS device ( Epix XL , Empi , Inc. , St. Paul , MN , U.S.A. ) for pain management , a r and omly selected sample of 376 patients who used TENS were interviewed by telephone by an independent research firm . The survey assessed a variety of outcome variables including changes in medication use , number of pain-related medications , and use of PT/OT prior to TENS and after a minimum 6 months of TENS treatment . The data were subjected to a paired t test analysis . A cost simulation model was then applied to the medication and PT/OT data . RESULTS The mean duration of pain , for which TENS was prescribed , was 40 + /- 60 months . As compared with the period prior to TENS use , this long-term TENS user group reported a statistically significant reduction in the following types of pain medications : opiate analgesics , tranquilizers , muscle relaxants , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and steroids . PT/OT use was also significantly reduced . Cost simulations of pain medications and PT/OT are presented . CONCLUSIONS Long-term use of TENS is associated with a significant reduction in the utilization of pain medication and PT/OT . In this study population , cost simulations of medication and PT/OT indicate that with long-term TENS use , costs can be reduced up to 55 % for medications and up to 69 % for PT/OT . The potential for TENS associated improvement , combined with reduced medication-related complications and costs , are important points that clinicians should consider when constructing a treatment plan for chronic pain patients . Finally , cost simulation techniques provide a useful tool for assessing outcomes in pain treatment and research CONTEXT Low back pain ( LBP ) contributes to considerable disability and lost wages in the United States . Commonly used opioid and nonopioid analgesic drugs produce adverse effects and are of limited long-term benefit in the management of this patient population . OBJECTIVE To compare the effectiveness of a novel nonpharmacologic pain therapy , percutaneous electrical nerve stimulation ( PENS ) , with transcutaneous electrical nerve stimulation ( TENS ) and flexion-extension exercise therapies in patients with long-term LBP . DESIGN A r and omized , single-blinded , sham-controlled , crossover study from March 1997 to December 1997 . SETTING An ambulatory pain management center at a university medical center . PATIENTS Twenty-nine men and 31 women with LBP secondary to degenerative disk disease . INTERVENTIONS Four therapeutic modalities ( sham-PENS , PENS , TENS , and exercise therapies ) were each administered for a period of 30 minutes 3 times a week for 3 weeks . MAIN OUTCOME MEASURES Pretreatment and posttreatment visual analog scale ( VAS ) scores for pain , physical activity , and quality of sleep ; daily analgesic medication usage ; a global patient assessment question naire ; and Health Status Survey Short Form ( SF-36 ) . RESULTS PENS was significantly more effective in decreasing VAS pain scores after each treatment than sham-PENS , TENS , and exercise therapies ( after-treatment mean + /- SD VAS for pain , 3.4+/-1.4 cm , 5.5+/-1.9 cm , 5.6+/-1.9 cm , and 6.4+/-1.9 cm , respectively ) . The average + /- SD daily oral intake of nonopioid analgesics ( 2.6+/-1.4 pills per day ) was decreased to 1.3+/-1.0 pills per day with PENS ( P<.008 ) compared with 2.5+/-1.1 , 2.2+/-1.0 , and 2.6+/-1.2 pills per day with sham-PENS , TENS , and exercise , respectively . Compared with the other 3 modalities , 91 % of the patients reported that PENS was the most effective in decreasing their LBP . The PENS therapy was also significantly more effective in improving physical activity , quality of sleep , and sense of well-being ( P<.05 for each ) . The SF-36 survey confirmed that PENS improved posttreatment function more than sham-PENS , TENS , and exercise . CONCLUSIONS In this sham-controlled study , PENS was more effective than TENS or exercise therapy in providing short-term pain relief and improved physical function in patients with long-term LBP OBJECTIVES A preliminary examination of NMES and combined NMES/TENS for the management of chronic back pain . DESIGN Double-blind , placebo-controlled , r and omized repeated measures . SUBJECTS AND SETTING Consecutive sample of 24 chronic back pain patients ( 16 women and 8 men ) attending an outpatient pain clinic ( mean age 51.67 years , mean pain duration 3.83 years ) . All treatments were administered at home . INTERVENTIONS Subjects self-administered NMES , combined NMES/TENS , TENS , and placebo treatments . Each treatment had a duration of 5 consecutive hours per day over 2 consecutive days , with a 2-day hiatus between treatments to minimize carryover effects . MAIN OUTCOME MEASURES Pain reduction was assessed through pretreatment to posttreatment differences on the Present Pain Intensity ( PPI ) scale , and a visual analogue scale of Pain Intensity ( VAS-I ) . Posttreatment pain relief was assessed using a visual analogue scale of Pain Relief ( VAS-R ) . RESULTS Combined treatment , NMES , and TENS each produced significant pretreatment to posttreatment reductions in pain intensity as measured by both the PPI and VAS-I ( p < .05 ) . Combined treatment was superior to placebo on pain reduction ( p = .001 , p = .016 ) as well as pain relief ( p < .001 ) . Combined treatment was also superior to both TENS and NMES for pain reduction and pain relief ( p < .01 ) . NMES and TENS were superior only to placebo for pain relief ( p < .001 ) . CONCLUSIONS Combined NMES/TENS treatment consistently produced greater pain reduction and pain relief than placebo , TENS , or NMES . NMES alone , although less effective , did produce as much pain relief as TENS . Although preliminary , this pattern of results suggests that combined NMES/TENS may be a valuable adjunct in the management of chronic back pain . Further research investigating the effectiveness of both NMES and combined NMES/TENS seems warranted STUDY OBJECTIVES To determine if transcutaneous electrical nerve stimulation ( TENS ) can produce fingertip analgesia . DESIGN R and omized , crossover trial . PARTICIPANTS Fifteen healthy volunteers , naive to the technique of TENS . INTERVENTIONS TENS stimulation was applied to the middle and ring fingers of each subject 's h and s by means of small carbon electrodes placed over the digital nerves . Patients received one fingertip puncture from a mechanically driven sterile lancet device to each digit corresponding to one of four conditions : sham , one minute of TENS , ten minutes of TENS , and 20 minutes of TENS . The TENS unit was operated in the " burst " mode , with two eight-pulse burst groups per second ( pulse width , 225 mu sec ; pulse frequency , 80 Hz ) . The order of the conditions and the finger used for each condition were assigned r and omly . The pain of each puncture was rated on a 10-cm visual-analog scale . Data were analyzed using a repeated- measures analysis of variance with Duncan 's multiple comparisons procedure . MEASUREMENTS AND RESULTS Mean visual-analog scale scores decreased sequentially from sham in each experimental condition : one minute of TENS , 24.4 % ( P < .025 ) ; ten minutes of TENS , 28.2 % ( P < .025 ) ; and 20 minutes of TENS , 55.7 % ( P < 10(-6 ) ) . Two patients had total anesthesia of the fingertip ( visual-analog scale = 0 cm ) in the 20-minute TENS condition . CONCLUSION TENS significantly reduces the pain of lancet-induced trauma to the fingertip . Further studies are warranted to determine if this technique is useful clinical ly as an alternative or adjunct to digital nerve block anesthesia for fingertip surgical procedures Thirty adult fibromyalgia syndrome subjects were r and omly assigned to a massage therapy , a transcutaneous electrical stimulation ( TENS ) , or a transcutaneous electrical stimulation no-current group ( Sham TENS ) for 30-minute treatment sessions two times per week for 5 weeks . The massage therapy subjects reported lower anxiety and depression , and their cortisol levels were lower immediately after the therapy sessions on the first and last days of the study . The TENS group showed similar changes , but only after therapy on the last day of the study . The massage therapy group improved on the dolorimeter measure of pain . They also reported less pain the last week , less stiffness and fatigue , and fewer nights of difficult sleeping . Thus , massage therapy was the most effective therapy with these fibromyalgia patients The purpose of this study was to replicate a previous study to determine the effectiveness of acupuncture-like transcutaneous electrical nerve stimulation in treating primary dysmenorrhea . Twenty-one women with dysmenorrhea received a placebo pill or 30 minutes of acupuncture-like TENS . All subjects completed two pain question naires before treatment ; immediately posttreatment ; 30 , 60 , 120 , and 180 minutes posttreatment ; and the next morning upon awakening . Each woman also participated in a separate study measuring electrical resistance at four auricular acupuncture points before and immediately after treatment . The data were analyzed with a two-factor repeated- measures analysis of variance , which revealed statistical significance over time but not for group or interaction between group and time . Results revealed an average pain relief of at least 50 % immediately posttreatment , indicating that acupuncture-like TENS may be useful for dysmenorrheic pain . This study also suggests that auriculotherapy via acupressure may relieve the pain of primary dysmenorrhea Study Design A r and omized prospect i ve trial of manipulation , massage , corset and transcutaneous muscle stimulation ( TMS ) was conducted in patients with subacute low back pain . Objectives The authors determined the relative efficacy of chiropractic treatment to massage , corset , and TMS . Summary of Background Data Although all of these treatments are used for subacute low back pain treatment , there have been few comparative trials using objective outcome criteria . Patients were enrolled for a period of 3 weeks . They were evaluated once a week by question naires , visual analog scale , range of motion , maximum voluntary extension effort , straight leg raising and Biering-Sorensen fatigue test . The dropout rate was highest in the muscle stimulation and corset groups and lowest in the manipulation group . Rates of full compliance did not differ significantly across treatments . A measure of patient confidence was greatest in the manipulation group . Results After 3 weeks , the manipulation group scored the greatest improvements in flexion and pain while the massage group had the best extension effort and fatigue time , and the muscle stimulation group the best extension . Conclusion None of the changes in physical outcome measures ( range of motion , fatigue , strength or pain ) were significantly different between any of the groups Objective : To evaluate the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS on the level of activities of daily living ( ADL ) of stroke patients . Setting : A university hospital . Patients : Patients who had had a stroke 30–240 days before entry to a university rehabilitation centre . Design : Controlled design with block r and omization and blinded assessment . Intervention : All patients had Todd – Davies exercises . In group 1 ( n = 30 ) TENS with frequency of 100 Hz was used at an intensity that the patient could tolerate ; in group 2 ( n = 30 ) patients were given placebo TENS . The treatment protocol consisted of 40 sessions ( eight weeks ) . Outcomes : The Barthel Index for daily living activities was used to measure functional changes over time , and the Ashworth Scale was used to measure spasticity in the elbow , knee and ankle . These measurements were made prior to and following the treatment by assessors unaware of the patient 's group allocation . Results : There were 30 patients in each group . Patients in group 1 ( active TENS ) were more disabled at entry to the study . Statistically significant improvements were recorded in all parameters such as feeding , transfer , hygiene , toileting , bathing , walking , climbing stairs , dressing , bowel and bladder care for group 1 ( p<0.001 ) but only in some items in group 2 . The change in total score was significant in both groups but the difference in the change score between the two groups was statistically significant ( p<0.001 ) . Spasticity was reduced in the active treatment group . Conclusion : TENS appears to be an effective adjunct in the regaining of motor functions and improving ADL in hemiplegic patients , but the accidental imbalance in severity of disability at entry makes interpretation uncertain Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial , saphenous , popliteal and sciatic nerves , and tender points . Seventy-four percent of patients in the real Codetron ( Group A ) and 28 % of the patients in sham Codetron ( Group B ) improved their pain level more than 25 % as measured by visual analogue scale . The difference in pain improvement in the two groups was statistically significant ( p < 0.02 using Fisher 's exact probability ratio ) Other functional parameters proved to be insensitive to change in this study . This is highly suggestive of beneficial effect of chronic pain conditions such as osteoarthritis A wearable device for transcutaneous electrical tinnitus suppression ( ETS ) has recently been reported to be effective for relief of tinnitus . Twenty patients with sensorineural hearing loss and tinnitus participated in a double-blind crossover study . Both active devices and internally disconnected placebo devices , supplied by the manufacturer , were used . Reduction in severity of tinnitus was reported by 2 of 20 patients ( 10 % ) with the active device and by 4 of 20 ( 20 % ) with the placebo device . Fifteen of 20 ( 75 % ) had no relief with either device . Those who preferred the placebo device , however , reported only minimal relief , while one of the two who preferred the active device stated it had reduced tinnitus severity by 70 % to 80 % . This patient was recalled for a series of one-hour test sessions , during which either an active or placebo device was used , according to a r and om schedule . On each of four on trials , the score for severity of tinnitus for each ear decreased by at least 50 % ( median = 70 % ) , while in three off trials , the severity of tinnitus was unchanged or decreased by up to 30 % ( median = 16 % ) . We conclude that the Therab and headset is effective for a small proportion of patients with sensorineural hearing loss and tinnitus & NA ; In this pilot study , to assess the optimal stimulation parameters , 3 different forms of transcutaneous electrical nerve stimulation were performed in 27 patients . Conventional continuous stimulation with a constant frequency of 70 Hz , burst stimulation ( 90 msec trains of pulses with an internal frequency of 100 Hz repeated at 2 Hz , each train consisting of 10 pulses ) , and frequency‐modulated stimulation ( continuous pulses changed from 90 Hz to 55 Hz over 90 msec ) were r and omly delivered to the patients for half an hour in 3 separate sessions . The patients were blind to the modes of stimulation . This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modulation and burst rather than conventional constant mode The authors carried out a single-blind , r and omized controlled clinical trial of rotational manipulation for low-back pain of recent onset in 81 adults . Control treatments were minimal massage and low-level electrostimulation . Initial status and outcome were measured on scales quantifying symptoms , activities of dally life , mobility , tenderness to palpation , aggravation of pain by coughing or sneezing , limitation of motion on testing , and forward flexion . Both treated and control patients improved rapidly in the 2 - 3-week observation period . On retest there was no statistically significant difference between the improvement scores of the treated or control groups on any of the scales This study is design ed to investigate the immediate effectiveness of electrotherapy on myofascial trigger points of upper trapezius muscle . Sixty patients ( 25 males and 35 females ) who had myofascial trigger points in one side of the upper trapezius muscles were studied . The involved upper trapezius muscles were treated with three different methods according to a r and om assignment : group A muscles ( n = 18 ) were given placebo treatment ( control group ) ; group B muscles ( n = 20 ) were treated with electrical nerve stimulation ( ENS ) therapy ; and group C muscles ( n = 22 ) were given electrical muscle stimulation ( EMS ) therapy . The effectiveness of treatment was assessed by conducting three measurements on each muscle before and immediately after treatment : subjective pain intensity [ ( PI ) with a visual analog scale ] , pressure pain threshold [ ( PT ) with algometry ] , and range of motion [ ( ROM ) with a goniometer ] of upper trapezius muscle ( lateral bending of cervical spine to the opposite side ) . When the effectiveness of treatment was compared with that of the placebo group ( group A ) , there was significant improvement in PI and PT in group B ( P < 0.01 ) but not in group C ( P > 0.05 ) . The improvement of ROM was significantly more in group C ( P < 0.01 ) as compared with that in group A or group B. When each group was divided into two additional subgroups based on the initial PI , it was found that ENS could reduce PI and increase PT significantly ( P < 0.05 ) , but did not significantly ( P > 0.05 ) improve ROM , as compared with the placebo group for both subgroups . EMS could significantly ( P < 0.05 ) improve ROM , but not PT , better than the placebo groups , for either subgroup . It could reduce PI significantly more ( P < 0.05 ) than placebo controls only for the subgroup with mild to moderate pain , but not with severe pain . For pain relief , ENS was significantly better ( P < 0.05 ) than EMS ; but for the improvement of ROM , EMS was significantly better ( P < 0.05 ) than ENS . It is concluded that ENS is more effective for immediate relief of myofascial trigger point pain than EMS , and EMS has a better effect on immediate release of muscle tightness than ENS This research compares different treatment regimes for the management of chronic facial pain associated with the masticatory musculature . Twenty-one females meeting specific criteria were r and omly assigned to one of three treatment conditions : a dental splint and physiotherapy program ; a relaxation program utilizing progressive muscle relaxation , biofeedback , and stress management techniques ; or a minimal treatment program involving transcutaneous electrical nerve stimulation . Improvement was assessed through a dental examination , self-monitoring of pain , and an assessment of EMG activity during resting and task conditions . Significant changes were obtained in response to all treatment programs . The treatment programs differed only in the relative pattern of treatment effects obtained from the self-report monitoring of pain . The data are consistent with the concept of MPD as a psychological response to stress which maintains chronic pain through increased muscle tension in the jaw & 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 We examined the effect of high frequency transcutaneous electrical nerve stimulation on the onset of brachial plexus block . Three groups of patients scheduled for surgery of the h and had a local anaesthetic block performed with 40 ml mepivacaine 1.5 % using the axillary approach . After injection of the local anaesthetic transcutaneous electrical nerve stimulation was applied for 15 min either to the median nerve or the ulnar nerve ; no stimulation was applied in the control group . Before and for 45 min after , the injection of local anaesthetic touch perception , pin prick , motor strength and skin temperature were tested by a blinded investigator in the areas supplied by the median , musculocutaneous , radial and ulnar nerves . There were no differences in the onset of block between the groups . Thus , the frequency‐dependent action of local anaesthetics could not be demonstrated In 20 patients diagnosed with Menière 's disease , transcutaneous nerve stimulation ( TNS ) and applied relaxation ( AR ) were used as a treatment aim ed at reducing tinnitus and dizziness and increasing hearing ability . The main aim of the study was to examine whether TNS could be regarded as a more beneficial treatment regimen than AR . An experimental between-group cross-over design was used . The results from the experimental phase ( group comparisons ) showed a significantly increased ability to hear for the TNS group when measured on visual analogue scales . During the same period , the AR-group showed a significant hearing improvement for the ear not primarily affected by Menière 's disease as measured with pure tone audiometry . The vestibular tests did not reveal any significant changes either after TNS or AR intervention . Tinnitus matching showed changes of pitch and loudness before and after both TNS and AR intervention . However , no statistically significant changes between treatment regimes were found on these measures . The results from this study did not show TNS to be superior to AR in reducing tinnitus , dizziness or increasing hearing ability & NA ; Fifty‐four patients treated in a 3‐week inpatient rehabilitation program were r and omly assigned to and accepted treatment with electroacupuncture ( n = 17 ) , TENS ( low intensity transcutaneous nerve stimulation , n = 18 ) , and TENS dead‐battery ( placebo , n = 18 ) . Outcome measures included estimates of pain ( on a Visual Analogue Scale ) and disability by both physician and patient , physical measures of trunk strength and spine range of motion , as well as the patient 's perceptions of the relative contribution of the education , exercise training , and the electrical stimulation . Analyses of variance were utilized to determine effects of treatment ( electroacupuncture , TENS , placebo ) across time ( admission , discharge , and return ) for the outcome measures . There were no significant differences between treatment groups with respect to their overall rehabilitation . All 3 treatment groups ranked the contribution of the education as being greater than the electrical stimulation . However , the electroacupuncture group consistently demonstrated greater improvement on the outcome measures than the other treatment groups . For the visual analogue scale measure of average pain , there was a statistical trend at the return visit suggesting that the acupuncture group was experiencing less pain A prospect i ve study on the symptomatic effect of traditional Chinese acupuncture treatment and transcutaneous nerve stimulation ( TENS ) of the tibial nerve in patients with interstitial cystitis is presented . There was no difference in voiding frequency , mean voided volume , maximal voided volume or visual analogue scale symptom scores before or after treatment with either TENS or acupuncture . Only one patient became improved both subjectively and objective ly after acupuncture for a short period of time . Even though the present material involves a small group of patients , it seems that the two methods , as applied in this study , have a very limited effect in patients with interstitial cystitis Abstract Ten patients with pain due to osteoarthritis of the knee were treated in a double‐blind cross‐over study with two weeks of transcutaneous electrical nerve stimulation ( TENS ) and placebo . There was statistically significant pain relief by TENS and half of the patients chose to continue using TENS for pain control after the test month . However , at one year 's follow‐up , only two patients had sufficient benefit to continue using the device The professional literature contains relatively few r and omized-control studies that have assessed the efficacy of physical therapy approaches to the management of patients with chronic low back pain ( CLBP ) . The purpose s of this study were : 1 ) to investigate the effects of physical agents , joint manipulation , low-tech exercise , and high-tech exercise on objective measures of CLBP ; 2 ) to track the length of CLBP relief ; and 3 ) to determine treatment cost-effectiveness . Two-hundred-fifty subjects ( 68 females , 182 males ; ages 34 - 51 years ) with CLBP following an L5 laminectomy were r and omly assigned into five separate groups for a treatment period of 8 weeks . Chronic low back pain status was measured by modified-modified Schober , Cybex Liftask , and Oswestry procedures . Results revealed that : 1 ) only low-tech and high-tech exercise produced significant improvements ( p < .05 ) in CLBP , 2 ) the mean period of CLBP relief ranged from 1.6 weeks ( control ) to 91.4 weeks ( low-tech exercise ) , and 3 ) low-tech exercise was most cost-effective . It was concluded that : 1 ) low-tech and high-tech exercise were the only effective treatments for CLBP , 2 ) low-tech exercise produced the longest period of CLBP relief , and 3 ) low-tech exercise was the most cost-effective form of treatment . Clinical ly , low-tech exercise may be the treatment method of choice for the effective management of chronic low back pain & NA ; Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms — frequency modulation and burst — rather than conventional continuous mode . To assess whether long‐term therapeutic effects vali date the immediate test results , this trial was performed in 14 patients with 21 pain conditions . Considering the results of the pilot study , the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were r and omly delivered to each patient who was blind to the modes of stimulation for 20 min . A second observer assessed the pain scores using visual analogue scales . The stimulation modes employed were : ( 1 ) conventional continuous stimulation ( continuous pulses with a constant frequency of 70 Hz ) , ( 2 ) burst stimulation ( 80 msec long trains of pulses , each train consisting of 8 pulses , with an internal frequency of 90 Hz repeated 1.3 times a second ) , ( 3 ) high‐rate frequency modulation , HRFM ( continuous pulses changed from 90 Hz to 55 Hz over 90 msec , 1.3 times a second ) , ( 4 ) low‐rate frequency modulation , LRFM ( continuous pulses changed from 60 Hz to 20 Hz over 90 msec , 1.3 times a second ) . After the test treatment of 4 sessions in the clinic , depending on the pain scores and duration of pain relief recorded , the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home , under our supervision , for 3 months . Fourteen pain conditions out of 21 ( 66 % ) responded well to the therapy ; the majority preferred was the HRFM and burst‐type stimulation . These results vali date the initial testing of different stimulation modes before assessing long‐term stimulation therapy Abstract A single blind r and omised controlled study of auricular and body acupuncture compared with placebo ( mock transcutaneous nerve stimulation ) was performed in 62 patients with post‐herpetic neuralgia . There was no difference in the amount of pain relief recorded in the two groups during or after treatment ; 7 patients in the placebo group and 7 patients in the acupuncture group experienced significant improvement in their pain at the end of treatment . This suggests that acupuncture is of little value as an analgesic therapy for post‐herpetic neuralgia . However the study method and the use of a mock transcutaneous nerve stimulator as a placebo may be of value when assessing the effects of acupuncture in other conditions & NA ; Although high‐frequency low‐intensity transcutaneous electric nerve stimulation ( TENS ) has been extensively used to relieve low back pain , experimental studies of its effectiveness have yielded contradictory findings mainly due to method ological problems in pain evaluation and placebo control . In the present study , separate visual analog scales ( VAS ) were used to measure the sensory‐discriminative and motivational‐affective components of low back pain . Forty‐two subjects were r and omly assigned to 1 of 3 groups : TENS , placebo‐TENS , and no treatment ( control ) . In order to measure the short‐term effect of TENS , VAS pain ratings were taken before and after each treatment session . Also , to measure long‐term effects , patients rated their pain at home every 2 h throughout a 3‐day period before and 1 week , 3 months and 6 months after the treatment sessions . In comparing the pain evaluations made immediately before and after each treatment session , TENS and placebo‐TENS significantly reduced both the intensity and unpleasantness of chronic low back pain . TENS was significantly more efficient than placebo‐TENS in reducing pain intensity but not pain unpleasantness . TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness . This additive effect was not found for placebo‐TENS . When evaluated at home , pain intensity was significantly reduced more by TENS than placebo‐TENS 1 week after the end of treatment , but not 3 months and 6 months later . At home evaluation of pain unpleasantness in the TENS group was never different from the placebo‐TENS group . These results suggest that TENS reduces both the sensory‐discriminative and motivational‐af‐fective components of low back pain in the short term but that much of the reduction in the affective component may be a placebo effect . We conclude that TENS should be used as a short‐term analgesic procedure in a multidisciplinary program for low back pain rather than as an exclusive or long‐term treatment In 23 patients with pancreatitis , daily pain for at least 3 months , and no abuse of alcohol , the pain-relieving effect of electroacupuncture ( 13 patients ) or transcutaneous electric nerve stimulation ( TENS ) ( 16 patients ) was studied . In two prospect i ve studies with a cross-over design , active acupuncture was compared with sham acupuncture , and TENS of the segmental points of the pancreas with sham treatment . Neither electroacupuncture nor TENS brought about pain relief that could substitute for or supplement medical treatment The purpose of this pilot study was to determine the effectiveness of auricular acupuncture-like transcutaneous electrical nerve stimulation on pain . Fifteen subjects ( 6 men , 9 women ) experiencing distal extremity pain received either one placebo pill or a 10-minute treatment of acupuncture-like TENS bilaterally to five acupuncture points on the auricle . Pain levels were measured before treatment and at 0 , 10 , and 30 minutes posttreatment using the visual analogue scale ( VAS ) and the pain rating index ( PRI ) of the McGill Pain Question naire . The VAS showed no statistically significant differences between Experimental Group ( n = 8) and Control Group ( n = 7 ) means at pretreatment or posttreatment ; however , both groups showed a reduction in VAS means over time . The Experimental and Control Group means on the PRI were significantly different ( p less than .05 ) at all three posttreatment measurements , but not at pretreatment baseline measurement . These results suggest that auricular acupuncture-like TENS could be an alternative for relief of distal extremity pain . Additional clinical studies are necessary to vali date the results of this study Transcutaneous electrical nerve stimulation ( TENS ) has been used in a variety of acute and chronic painful conditions , but has not been studied in sickle cell pain crises . We compared TENS versus placebo in a r and omized , double-blind , cross-over study involving 60 trials in 4 crisis severity categories . TENS electrodes were applied to the area of severest pain and patients ' pain ratings and medication usage were evaluated over a 4-hour period . Pain ratings and analgesic requirements at 1 and 4 h from onset of study were similar in the TENS and placebo groups . Patients assessment s of overall treatment efficacy indicated that TENS was more frequently helpful , but there was a substantial placebo effect . Although the value of TENS in this condition was not established in this study , further trials , using varied stimulation parameters , are warranted The effect of transcutaneous nerve stimulation ( TNS ) was evaluated and compared with placebo TNS in 19 patients ( 17 women , mean age 33 years ) with orofacial functional pain and rheumatic disease involving the temporom and ibular joint . In two double-blind noncrossover experiments , high frequency TNS ( 100 Hz ) and low frequency TNS ( 2 Hz ) were evaluated by comparison of the patients ' functional and rest pain , muscle and joint tenderness , and jaw function . A significant treatment effect was obtained for all treatment methods regarding functional and rest pain and muscle and joint tenderness . None of the parameters except functional pain , which improved significantly more after high frequency TNS than placebo TNS , revealed any difference between the methods . Jaw function , however , revealed a few differences between high frequency TNS and placebo TNS |
13,934 | 23,158,845 | The most consistent evidence of effectiveness was for pharmacological interventions for smoking cessation .
This body of work , however , provided scant evidence on the effectiveness of these interventions for ethnic minority groups .
Lastly , given our focus on three health areas and three population s , we have inevitably excluded many studies of adapted interventions for other health topics and other ethnic minority population s. CONCLUSIONS There is currently a lack of evidence on how best to deliver smoking cessation , physical activity and healthy eating-related health promotion interventions to ethnic minority population s. Although culturally adapting interventions can increase salience , acceptability and uptake , there is as yet insufficient evidence on the clinical effectiveness or cost-effectiveness of these adapted approaches . | BACKGROUND There is now a considerable body of evidence revealing that a number of ethnic minority groups in the UK and other economically developed countries experience disproportionate levels of morbidity and mortality compared with the majority white European-origin population .
Across these countries , health-promoting approaches are increasingly viewed as the long-term strategies most likely to prove clinical ly effective and cost-effective for preventing disease and improving health outcomes in those with established disease . | OBJECTIVE To assess the process variables involved in a weight loss program for African-American adolescent girls . Several process variables have been identified as affecting success in in vivo weight loss programs for adults and children , including program adherence , self-efficacy , and social support . The current study sought to broaden the underst and ing of these process variables as they pertain to an intervention program that is presented using the Internet . It was hypothesized that variables such as program adherence , dietary self-efficacy , psychological factors , and family environment factors would mediate the effect of the experimental condition on weight loss . RESEARCH METHODS AND PROCEDURES Participants were 57 adolescent African-American girls who joined the program with one obese parent ; family pairs were r and omized to either a behavioral or control condition in an Internet-based weight loss program . Outcome data ( weight loss ) are reported for the first 6 months of the intervention . RESULTS Results partially supported the hypotheses . For weight loss among adolescents , parent variables pertaining to life and family satisfaction were the strongest mediating variables . For parental weight loss , changes in dietary practice s over the course of 6 months were the strongest mediators . DISCUSSION The identification of factors that enhance or impede weight loss for adolescents is an important step in improving weight loss programs for this group . The current findings suggest that family/parental variables exert a strong influence on weight loss efforts for adolescents and should be considered in developing future programs 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 BACKGROUND The prevalence of obesity in the United States is a significant public health problem . Many obesity-related risk factors are more prevalent in minority population s. Given the recalcitrant nature of weight loss interventions for adults , prevention of overweight and obesity has become a high priority . The present study reports baseline data from an obesity prevention intervention developed for minority preschool children . METHODS Hip-Hop to Health Jr. is a 5-year r and omized controlled intervention that targets 3- to 5-year-old minority children enrolled in 24 Head Start programs . Our primary aim is to test the effect of the intervention on change in body mass index . Data were collected on sociodemographic , anthropometric , behavioral , and cognitive variables for the children and parents at baseline . RESULTS Participants included 416 black children , 337 black parents , 362 Latino children , and 309 Latino parents . Using body mass index for age and sex > or = the 95th percentile as the definition of overweight , 15 % of the black children and 28 % of the Latino children were overweight . More than 75 % of the parents were either overweight or obese . DISCUSSION The development of interventions to effectively prevent or control obesity early in life is crucial . These data highlight the escalating problem of weight control in minority population BACKGROUND Effective clinical weight management approaches are needed to reach African-Americans . METHODS African-Americans recruited through outpatient practice s for a culturally-adapted Healthy Eating and Lifestyle Program were offered 10 weekly weight loss classes ( Phase 1 ) with the option of continuing for another 8 - 18 months ( Phase 2 ) in a r and omized comparison of further group counseling or staff-facilitated self-help vs. follow-up clinic visits only . RESULTS Of 237 enrollees ( 91 % women ; mean age 43.5 years ; mean body mass index 38.0 kg/m(2 ) ) , 70 [ corrected ] attended no classes or only the first Phase 1 class , 134 provided Phase 1 follow-up data , 128 were r and omized in Phase 2 , and 87 provided final follow-up data ( " completers " ) . Mean weight changes for completers were : -1.5 ( P < 0.001 ) , + 0.3 ( P = 0.47 ) , and -1.2 ( P = 0.04 ) kg , respectively , for Phase 1 , Phase 2 , and overall ( baseline to final visit ; average 18 months total duration ) , with no Phase 2 treatment effect ( P = 0.55 ) . Final study weight was > or = 5 % below baseline for 25 % of completers and was strongly predicted by Phase 1 weight loss . CONCLUSIONS Weight loss achieved in Phase 1 was maintained even with relatively minimal follow-up contact . Increasing the percent who achieve clinical ly significant weight loss initially would improve long-term results BACKGROUND Type 2 diabetes is up to four times more common in British Asians , but they know little about its management and complications . AIM To design and evaluate a structured pictorial teaching programme for Pakistani Moslem patients in Manchester with type 2 diabetes . METHOD A r and omized controlled trial of pictorial flashcard one-to-one education in 201 patients attending a hospital outpatient clinic or diabetic clinics in ten general practice s in Manchester . Patients ' knowledge , self-caring skills and attitudes to diabetes were measured on four topics before the structured teaching , and compared with results six months later . RESULTS All parameters of knowledge were increased in the study group ; for example , percentage scores for correctly identifying different food values increased from 57 % to 71 % ( Analysis of Variance ( ANOVA ) adjusted difference + 11.8 % ) and knowledge of one diabetic complication from 18 % to 78 % . Self-caring behaviour improved , with 92 % of patients doing regular glucose tests at six months compared with 63 % at the start . Attitudinal views were more resistant to change , with patients still finding it hard to choose suitable foods at social occasions . Haemoglobin A1c control improved by 0.34 % over six months ( ANOVA adjusted difference , 95 % CI -0.8 % to + 0.1 % ) . CONCLUSION It is concluded that this health education programme can empower Asian diabetics to take control of their diets , learn to monitor and interpret glucose results , and underst and the implication s of poor glycaemic control for diabetic complications OBJECTIVE This study tested the efficacy of an 8-week culturally targeted nutrition and physical activity intervention on body composition . METHODS A r and omized , attention-controlled , two-group trial was conducted in a blackowned commercial gym with a sample of 366 predominantly healthy , obese African American women . A free 1-year membership to the study site gym was provided to participants in both groups . Data were collected at baseline , 2 , 6 , and 12 months . RESULTS Sample retention at 1 year was 71 % . Between-group longitudinal analysis including only participants with complete data revealed a trend toward weight stability in the intervention group at 2 months compared with controls ( + 0.05 kg/m(2 ) , p = 0.75 ; + 0.32 kg/m(2 ) , p = 0.08 , respectively ) , disappearing at 12 months ( + 1.37 kg/m(2 ) , p = 0.0001 ; + 1.02 kg/m(2 ) , p = 0.001 , respectively ) . Within-group analysis demonstrated that intervention and control participants ' fitness ( 1-mile run-walk ) improved by 1.9 minutes ( p = 0.0001 ) and 2.3 minutes ( p = 0.0001 ) , respectively , at 12 months . Mixed model regression analyses demonstrated a significant main effect of the intervention on fitness ( p = 0.0185 ) and a marginally significant effect on body mass index ( BMI ) ( p = 0.057 ) , at 2 months , disappearing by 6 months . By 12 months , however , the controls exhibited a significant advantage in waist circumference stability compared with intervention participants ( + 1.1 cm , p = 0.2763 ; + 2.1 cm , p = 0.0002 , respectively ) . CONCLUSIONS The intervention produced modest short-term improvements in body composition , but the economic incentive of a free 1-year gym membership provided to all participants was a more potent intervention than the education and social support intervention tested . However , longer-term fitness enhancement remains elusive and dem and s research and policy attention . These findings have policy implication s in that employer-/insurer-subsidized gym memberships may require interventions targeting other levels of change ( e.g. , physical or social/environmental ) to foster sustainable fitness improvements A continuing challenge in weight loss treatment is attaining maintenance of weight loss . The goal of this study was to develop a counseling method that would assist African American breast cancer survivors with weight loss maintenance . In this pilot study , 31 obese breast cancer survivors were recruited . Individualized , dietitian-led counseling by telephone and free Weight Watchers coupons were provided to all participants for 18 months . At the 6-month time point , women were r and omized to receive spirituality counseling or not in addition to the st and ard program . The spirituality counseling was delivered via telephone using an 8-step framework . Subjects were asked to utilize daily meditation or prayer , daily readings , and the recording of thoughts in a journal . Mean weight loss from baseline to 6 months was a modest 2.0 % of baseline weight . From 6 to 18 months , there was no further weight change in the spirituality arm and a gain of 0.7 % in the dietitian-only arm . Despite little effect on weight loss , it did appear that spirituality counseling positively affected spiritual well-being ( FACIT-Sp ) scores and dietary quality . The spirituality counseling framework therefore may be further refined and useful for other health promotion studies with African American population Abstract Compared to other racial/ethnic groups , African American ( AA ) women are more likely to be obese but less likely to participate in weight loss interventions or to successfully lose weight . Sustained motivation for weight loss may be especially difficult for AA women due to socioeconomic and cultural factors . The purpose of this study was to examine whether the addition of motivational interviewing ( MI ) to a culturally-targeted behavioral weight loss program for AA women improved adherence to the program , diet and physical activity behaviors , and weight loss outcomes . Forty-four obese ( mean BMI = 39.4 , SD = 7.1 ) AA women were r and omized to receive a 16-week behavioral weight loss program plus four MI sessions , or the same behavioral weight loss program plus four health education ( HE ; attention control ) sessions . Results showed that participants in both MI and HE conditions lost a significant amount of weight , reduced their energy intake and percent calories from fat , and increased their fruit and vegetable consumption ( ps < .05 ) . However , adherence to the behavioral weight loss program and changes in diet , physical activity , and weight did not differ across MI and HE conditions . Future research is warranted to determine the sub population s with which MI is most effective BACKGROUND This article provides a descriptive overview of the implementation process of the Heart , Body , and Soul program . The program objective was to test strategies to reduce the prevalence of cigarette smoking among urban African Americans in East Baltimore . METHOD This study constitutes a prospect i ve r and omized trial among inner-city African Americans design ed to improve quit rates among church attenders . A r and om-digit-dialing survey was conducted to establish baseline levels of self-reported cigarette smoking , examine attendant attitudes , and determine the presence of known cardiovascular risk factors among community residents of the catchment area . A similar survey was conducted among churchgoers to establish a baseline . Twenty-two churches were recruited and r and omly assigned to either intensive or minimal ( self-help ) intervention strategies . Baseline health screenings were held in all participating churches . Innovative culturally specific smoking cessation strategies mediated through lay volunteers from participating churches were implemented in the intensive intervention churches . RESULTS Pastors of all churches were directly involved in all aspects of the planning and implementation process . A total of 29 volunteer lay smoking-cessation specialists were trained and successfully implemented the intensive interventions in churches . An additional 272 church members were trained to conduct their church 's health screenings . CONCLUSION The essential component of this successful implementation process were building trust and acceptance and providing the technical support to encourage smoking-cessation strategies . This description of the project is presented to assist others involved in church-based trials in urban African American communities OBJECTIVES This study tested the efficacy of an 8-week , culturally targeted community-based nutrition and physical activity promotion intervention , Fight Cancer with Fitness ! ( FCF ) . METHODS A r and omized , controlled trial was conducted in a black-owned commercial gym in a sample of 366 predominantly overweight or obese , healthy African-American women . RESULTS Dietary quality as indexed by fruit and vegetable intake improved significantly in the intervention group compared to the control group at 12-month follow-up , and proportion of calories consumed as fat decreased in both groups . CONCLUSIONS This individually targeted cancer prevention intervention produced beneficial effects on dietary quality that were sustained for at least 12 months OBJECTIVES We sought to determine the effects of a community-based , culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes . METHODS One hundred fifty-one African American and Latino adults with diabetes were recruited from 3 health care systems in Detroit , Michigan , to participate in the Racial and Ethnic Approaches to Community Health ( REACH ) Detroit Partnership diabetes lifestyle intervention . The curriculum , delivered by trained community residents , was aim ed at improving dietary , physical activity , and diabetes self-care behaviors . Baseline and postintervention levels of diabetes-specific quality -of-life , diet , physical activity , self-care knowledge and behaviors , and hemoglobin A1C were assessed . RESULTS There were statistically significant improvements in postintervention dietary knowledge and behaviors and physical activity knowledge . A statistically significant improvement in A1C level was achieved among REACH Detroit program participants ( P<.0001 ) compared with a group of patients with diabetes in the same health care system in which no significant changes were observed ( P=.160 ) . CONCLUSIONS A culturally tailored diabetes lifestyle intervention delivered by trained community residents produced significant improvement in dietary and diabetes self-care related knowledge and behaviors as well as important metabolic improvements OBJECTIVE This report examines how sources of fat and patterns of fat-related dietary habits differed between black , Hispanic and white women participating in a r and omized trial of a low-fat diet intervention . DESIGN The intervention consisted of group sessions , which met weekly for 6 weeks , biweekly for 6 weeks and monthly for 9 months , and included didactic nutrition education and activities to provide motivation for sustained dietary change . Outcomes included total fat and fat from nine food groups from a food frequency question naire ( FFQ ) , and a summary scale and five subscales that measure fat-related dietary habits . SETTING /SUBJECTS Data are from 1702 post-menopausal women , recruited from clinical centres in Atlanta , Birmingham and Miami , with dietary assessment s at baseline and 6 months post-r and omization . RESULTS Total fat intake was similar across race/ethnic groups at baseline , yet there were many differences in sources of fat and fat-related dietary habits . For example , blacks consumed less fat from dairy foods and more fat from meats than whites . Effects of the intervention on total fat intake or the summary fat-related dietary habits scale did not differ across race/ethnicity groups . There were , however , many differences in how the intervention affected sources of fat and fat-related dietary habits . For example , the intervention effect for added fats ( e.g. butter and salad dressings ) was -8.9 g for blacks and -12.0 g for whites ( P<0.05 ) . The intervention effect for adopting low-fat meat purchasing and preparation methods was larger for blacks than whites , and the intervention effect for replacing high-fat foods with fruits and vegetables was larger for Hispanics than whites . CONCLUSIONS This study demonstrates that , if properly design ed , a single nutrition intervention programme can work well even in groups with culturally diverse dietary patterns Purpose . This study describes the design , recruitment , and baseline data of the first smoking-cessation clinical trial for African-American light smokers , Kick It at Swope II ( KIS-II ) . Design . KIS-II was a r and omized trial testing the efficacy of nicotine gum ( vs. placebo gum ) in combination with counseling ( motivational interviewing or health education ) . Setting . This study was conducted at an urban community-based clinic serving predominantly lower-income African-Americans . Subjects . African-Americans who smoked 1 to 10 cigarettes per day were eligible . Of 1933 individuals screened , 1012 ( 52 % ) were eligible and 755 ( 75 % ) were enrolled in the study . Measures . Baseline assessment included smoking history and psychometric measures . Analysis . The majority of participants were women ( 67 % ) with a mean age of 45.1 years ( SD = 10.7 ) . Participants smoked on average 7.6 cigarettes ( SD = 3.21 ) per day , had a mean exhaled carbon monoxide level of 13.9 ppm ( SD = 8.9 ) and a mean serum cotinine level of 244.2 ng/mL ( SD = 154.4 ) , and reported high levels of motivation and confidence to quit smoking . Conclusion . African-American light smokers were motivated to stop smoking and to enroll in a smoking-cessation program . Characteristics of our sample suggest African-American light smokers are an appropriate group for inclusion in smoking-cessation interventions Purpose The purpose of this pilot study was to evaluate a culturally tailored intervention for rural African Americans . Social Cognitive Theory provided the framework for the study . Methods Twenty-two participants were recruited and r and omly assigned to either Group or Individual diabetes self-management ( DSME ) . Group DSME included story-telling , h and s-on activities , and problem-solving exercises . Individual DSME sessions focused on goal - setting and problem-solving strategies . Sessions were offered in an accessible community center over a 10-week period . Results Outcomes included glycosylated hemoglobin ( A1C ) , self-care actions , self-efficacy level , goal attainment , and satisfaction with DSME . Participants in both Group and Individual DSME improved slightly over the 3-month period in self-care activities , A1C level , and goal attainment . Although differences were not statistically significant , trends indicate improved scores on dietary actions , foot care , goal attainment , and empowerment for those experiencing Group DSME . Conclusions The culturally tailored approach was well received by all participants . Improvements among those receiving Individual DSME may indicate that brief sessions using a culturally tailored approach could enhance self-care and glycemic control . Additional testing among more participants over a longer time period is recommended PURPOSE this paper describes a clinic and community-based diabetes intervention program design ed to improve dietary , physical activity , and self-care behaviors of older African American women with type 2 diabetes . It also describes the study to evaluate this program and baseline characteristics of participants . METHODS The New Leaf ... Choices for Healthy Living With Diabetes program consists of 4 clinic-based health counselor visits , a community intervention with 12 monthly phone calls from peer counselors , and 3 group sessions . A r and omized , controlled trial to evaluate the effectiveness of this intervention is described . RESULTS Seventeen focus groups of African American women were used to assessed the cultural relevance /acceptability of the intervention and measurement instruments . For the r and omized trial , 200 African American women with type 2 diabetes were recruited from 7 practice s in central North Carolina . Mean age was 59 , mean diabetes duration was 10 years , and participants were markedly overweight and physically inactive . CONCLUSIONS Participants found this program to be culturally relevant and acceptable . Its effects on diet , physical activity , and self-care behaviors will be assessed in a r and omized trial PURPOSE This study was design ed to compare the effects of 2 programs that present diet and exercise components in a different sequence . METHODS At an urban YMCA , African American women with type 2 diabetes , aged 30 to 65 , were r and omly assigned to either 10 weekly sessions about healthy eating followed by 6 weekly sessions about exercise or to the reverse sequence . Sessions consisted of small group discussion s and physical activity or food tasting . Primary outcomes were attendance , percent of calories consumed from fat , fruit and vegetable intake , and minutes of exercise per week . Measures were taken at baseline , and 4 and 12 months after the program . RESULTS The only group difference found at the 12-month follow-up was in diastolic blood pressure . Time effects for both groups combined included an increase in minutes of activity , an increase in vegetable intake , and a decrease in percent of calories consumed from fat . CONCLUSIONS This study does not provide definitive evidence of which sequence may be best to bring about behavior change . The effects of sequencing difficult behavioral changes such as diet modification and establishing an exercise habit deserve further study Objective To develop and vali date version two of the QRISK cardiovascular disease risk algorithm ( QRISK2 ) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in Engl and and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence ( NICE ) . Design Prospect i ve open cohort study with routinely collected data from general practice , 1 January 1993 to 31 March 2008 . Setting 531 practice s in Engl and and Wales contributing to the national Q RESEARCH data base . Participants 2.3 million patients aged 35 - 74 ( over 16 million person years ) with 140 000 cardiovascular events . Overall population ( derivation and validation cohorts ) comprised 2.22 million people who were white or whose ethnic group was not recorded , 22 013 south Asian , 11 595 black African , 10 402 black Caribbean , and 19 792 from Chinese or other Asian or other ethnic groups . Main outcome measures First ( incident ) diagnosis of cardiovascular disease ( coronary heart disease , stroke , and transient ischaemic attack ) recorded in general practice records or linked Office for National Statistics death certificates . Risk factors included self assigned ethnicity , age , sex , smoking status , systolic blood pressure , ratio of total serum cholesterol : high density lipoprotein cholesterol , body mass index , family history of coronary heart disease in first degree relative under 60 years , Townsend deprivation score , treated hypertension , type 2 diabetes , renal disease , atrial fibrillation , and rheumatoid arthritis . Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score . The QRISK2 algorithm explained 43 % of the variation in women and 38 % in men compared with 39 % and 35 % , respectively , by the modified Framingham score . Of the 112 156 patients classified as high risk ( that is , ≥20 % risk over 10 years ) by the modified Framingham score , 46 094 ( 41.1 % ) would be reclassified at low risk with QRISK2 . The 10 year observed risk among these reclassified patients was 16.6 % ( 95 % confidence interval 16.1 % to 17.0%)—that is , below the 20 % treatment threshold . Of the 78 024 patients classified at high risk on QRISK2 , 11 962 ( 15.3 % ) would be reclassified at low risk by the modified Framingham score . The 10 year observed risk among these patients was 23.3 % ( 22.2 % to 24.4%)—that is , above the 20 % threshold . In the validation cohort , the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20 % was 30.6 per 1000 person years ( 29.8 to 31.5 ) for women and 32.5 per 1000 person years ( 31.9 to 33.1 ) for men . The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years ( 25.0 to 26.3 ) for women and 26.4 ( 26.0 to 26.8 ) for men ) . At the 20 % threshold , the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score . Conclusions Incorporating ethnicity , deprivation , and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population . At the 20 % threshold , QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease . As the validation was performed in a similar population to the population from which the algorithm was derived , it potentially has a “ home advantage . ” Further validation in other population s is therefore advised OBJECTIVE Many targeted interventions have been developed and tested with African Americans ( AA ) ; however , AAs are a highly heterogeneous group . One characteristic that varies across AAs is Ethnic Identity ( EI ) . Little research has been conducted on how to incorporate EI into the design of health messages and programs . DESIGN We tested whether tailoring a print-based fruit and vegetable ( F & V ) intervention on EI would enhance program impact . AA adults were recruited from two integrated healthcare delivery systems and then r and omized to receive three newsletters focused on F & V behavior change over three months . One set of newsletters was tailored only on demographic and social cognitive variables ( control condition ) , whereas the other ( experimental condition ) was additionally tailored on EI . MAIN OUTCOME MEASURES The primary outcome for the study was F & V intake , assessed at baseline and three months later using the composite of two brief self-report frequency measures . RESULTS A total of 560 eligible participants were enrolled , of which 468 provided complete 3-month follow-up data . The experimental group increased their daily mean F & V intake by 1.1 servings compared to .8 servings in the control group ( p = .13 ) . Afrocentric experimental group participants showed a 1.4 increase in F & V servings per day compared to a .43 servings per day increase among Afrocentric controls ( p < .05 ) . CONCLUSIONS Although the overall between-group effects were not significant , tailoring dietary messages on ethnic identity may improve intervention impact for some AA subgroups OBJECTIVE This study evaluated changes in smoking-related beliefs and behavior following a brief , culturally adapted smoking cessation intervention for Chinese and Korean smokers . METHOD From May 2002 to March 2003 , 66 smokers residing in or around southeastern Pennsylvania were r and omly assigned to a theory-based smoking cessation intervention or general health counseling . Participants completed assessment s of perceived risks of smoking , pros and cons of quitting , quitting self-efficacy , and distress at baseline and follow-up time points . Sessions were conducted in the participant 's native language ( Korean , Cantonese , or M and arin ) . Both groups received nicotine replacement therapy . RESULTS Overall , 38 % of participants reported quitting smoking at 3-month follow-up . Quit rates were higher ( 52.6 % among Chinese , 60.0 % among Korean ) in the intervention condition compared to the control condition ( 23.5 % among Chinese , 40.0 % among Korean ) at 1-month , but not 3-month , follow-up . There was a main effect of treatment condition for self-efficacy with intervention participants reporting significantly higher levels of self-efficacy compared to control participants . Further , a treatment x time interaction was observed for cons of quitting , reflecting fewer cons in the intervention group than the control group at 1-month and 3-month follow-up . CONCLUSION A culturally adapted intervention for Chinese and Korean Americans can be effective in changing specific smoking-related cognitions and behavior . This study represents a promising first step toward advancing our underst and ing of the associations between smoking-related cognitions and behavior among Asian American smokers BACKGROUND Obesity is associated with many chronic diseases , and weight loss can reduce the risk of developing these diseases . Obesity is highly prevalent among Black women , but weight loss treatment for black women has been understudied until recently . The Obesity Reduction black Intervention Trial ( ORBIT ) is a r and omized controlled trial design ed to assess the efficacy of a culturally proficient weight loss and weight loss maintenance program for black women . This paper describes the design of the trial , the intervention , and baseline characteristics of the participants . METHODS Two hundred thirteen obese black women aged 30 - 65 years were r and omized to the intervention group or a general health control group . The intervention consists of a 6-month weight loss program followed by a 1-year maintenance program . Weight , dietary intake , and energy expenditure are measured at baseline , 6 months , and 18 months . RESULTS More than 40 % of participants had a baseline body mass index ( BMI ) > 40 kg/m(2 ) ( class III obesity ) . Intake of fat and saturated fat was higher and consumption of fruit , vegetables , and fiber was lower than currently recommended guidelines . Self-reported moderate to vigorous physical activity was high ( median 85 min/day ) . However , objective ly measured physical activity among a subgroup of participants was lower ( median 15 min/day ) . CONCLUSIONS Weight loss among obese black women has received inadequate attention in relation to the magnitude of the problem . Factors that contribute to successful weight loss and more importantly , weight loss maintenance need to be identified OBJECTIVE A r and omized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for African-American girls over a 2-year period of intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven overweight ( mean BMI percentile , 98.3 ) African-American girls ( mean age , 13.2 years ) were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . Overweight parents were also participants in the study . Forty adolescent-parent dyads ( 70 % ) completed the 2-year trial . Outcome data including BMI , body weight , body composition , and weight loss behaviors were collected at baseline and at 6-month intervals . A computer server tracked use of the web sites . RESULTS An intention-to-treat statistical approach was used , with the last observation carried forward . In comparison with the control condition , adolescents in the behavioral program lost more mean body fat ( BF ) ( -1.12 + /- 0.47 % vs. 0.43 + /- 0.47 % BF , p < 0.05 ) , and parents in the behavioral program lost significantly more mean body weight ( -2.43 + /- 0.66 vs. -0.35 + /- 0.64 kg , p < 0.05 ) during the first 6 months . This weight loss was regained over the next 18 months . After 2 years , differences in fat for adolescents ( -0.08 + /- 0.71 % vs. 0.84 + /- 0.72 % BF ) and weight for parents ( -1.1 + /- 0.91 vs. -0.60 + /- 0.89 kg ) did not differ between the behavioral and control programs . DISCUSSION An internet-based weight management program for African-American adolescent girls and their parents result ed in weight loss during the first 6 months but did not yield long-term loss due to reduced use of the web site over time Poor adjustment to diabetes in older African American women may result from uncertainty , stemming from a lack of information about self-care activities , a complexity of self-care activities , comorbid conditions , and a lack of re sources . This study evaluated a telephone intervention to reduce uncertainty ( through problem-solving strategies , information , cognitive reframing , and improved patient — provider communication)—namely , to measure its effects on diabetes self-care and psychosocial adjustment . Sixty-eight older African American women were r and omly assigned to an experimental group and a control group . The experimental group received the intervention for 4 weeks , and the control group received usual care . Psychosocial adjustment and self-care were measured in all participants at baseline and 6 weeks postbaseline . The experimental group reported increased participation in exercise ( self-care component ; p < .001 ) and improvement in psychosocial adjustment ( p < .001 ) . Thus , reducing the uncertainty related to diabetes self-care improves self-care exercise , as well as psychosocial adjustment OBJECTIVE To determine whether a culturally appropriate clinic- and community-based intervention for African-American women with type 2 diabetes will increase moderate-intensity physical activity ( PA ) . RESEARCH DESIGN AND METHODS In this r and omized controlled trial conducted at seven practice s in central North Carolina , 200 African-American women , > or = 40 years of age with type 2 diabetes , were r and omized to one of three treatment conditions : clinic and community ( group A ) , clinic only ( group B ) , or minimal intervention ( group C ) . The clinic-based intervention ( groups A and B ) consisted of four monthly visits with a nutritionist who provided counseling to enhance PA and dietary intake that was tailored to baseline practice s and attitudes ; the community-based intervention ( group A ) consisted of three group sessions and 12 monthly phone calls from a peer counselor and was design ed to provide social support and reinforce behavior change goals ; and the minimal intervention ( group C ) consisted of educational pamphlets mailed to participants . The primary study outcome was the comparison of PA levels between groups assessed at 6 and 12 months by accelerometer , which was worn while awake for 7 days . RESULTS Totals of 175 ( 88 % ) and 167 ( 84 % ) participants completed PA assessment at 6 and 12 months , respectively . For comparison of PA , the P value for overall group effect was 0.014 . Comparing group A with C , the difference in the average adjusted mean for PA was 44.1 kcal/day ( 95 % CI 13.1 - 75.1 , P = 0.0055 ) . Comparing group B with C , the difference in the average adjusted mean was 33.1 kcal/day ( 95 % CI 3.3 - 62.8 , P = 0.029 ) . The intervention was acceptable to participants : 88 % were very satisfied with clinic-based counseling to enhance PA , and 86 % indicated that the peer counselor 's role in the program was important . CONCLUSIONS The intervention was associated with a modest enhancement of PA and was acceptable to participants OBJECTIVES Body and Soul was a collaborative effort among two research universities , a national voluntary agency ( American Cancer Society ) , and the National Institutes of Health to disseminate and evaluate under real-world conditions the impact of previously developed dietary interventions for African Americans . METHODS Body and Soul was constructed from two successful research -based interventions conducted in African-American churches . Components deemed essential from the prior interventions were combined , and then tested in a cluster r and omized-effectiveness trial . The primary outcome was fruit and vegetable intake measured with two types of food frequency question naires at baseline and 6-month follow-up . RESULTS At the 6-month follow-up , intervention participants showed significantly greater fruit and vegetable ( F&V ) intake relative to controls . Post-test differences were 0.7 and 1.4 servings for the 2-item and 17-item F&V frequency measures , respectively . Statistically significant positive changes in fat intake , motivation to eat F&V , social support , and efficacy to eat F&V were also observed . CONCLUSIONS The results suggest that research -based interventions , delivered collaboratively by community volunteers and a health-related voluntary agency , can be effectively implemented under real-world conditions OBJECTIVES This study assessed the effects of the Black Churches United for Better Health project on increasing fruit and vegetable consumption among rural African American church members in North Carolina . METHODS Ten counties comprising 50 churches were pair matched and r and omly assigned to either intervention or delayed intervention ( no program until after the follow-up survey ) conditions . A multicomponent intervention was conducted over approximately 20 months . A total of 2519 adults ( 77.3 % response rate ) completed both the baseline and 2-year follow-up interviews . RESULTS The 2 study groups consumed similar amounts of fruits and vegetables at baseline . AT the 2-year follow-up , the intervention group consumed 0.85 ( SE = 0.12 ) servings more than the delayed intervention group ( P < .0001 ) . The largest increases were observed among people 66 years or older ( 1 serving ) , those with education beyond high school ( 0.92 servings ) , those widowed or divorced ( 0.96 servings ) , and those attending church frequently ( 1.3 servings ) . The last improvement occurred among those aged 18 to 37 years and those who were single . CONCLUSIONS The project was a successful model for achieving dietary change among rural African Americans 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 PURPOSE Markers of genetic susceptibility to tobacco-related cancers could personalize harms of smoking and motivate cessation . Our objective was to assess whether a multicomponent intervention that included feedback about genetic susceptibility to lung cancer increased risk perceptions and rates of smoking cessation compared with a st and ard cessation intervention . EXPERIMENTAL DESIGN Our design was a two-arm trial with eligible smokers r and omized in a 1:2 ratio to Enhanced Usual Care or Biomarker Feedback ( BF ) . Surveys were conducted at baseline , 6 , and 12 months later . The setting was an inner city community health clinic . African-American patients who were current smokers ( n = 557 ) were identified by chart abstract ion and provider referral . All smokers received a self-help manual and , if appropriate , nicotine patches . Smokers in the BF arm also were offered a blood test for genotyping the GST(3 ) gene ( GSTM1 ) , sent a test result booklet , and called up to four times by a health educator . Prevalent abstinence was assessed by self-report of having smoked no cigarettes in the prior 7 days at the 6- and 12-month follow-ups and sustained abstinence , i.e. , not smoking at either follow-up or in-between . RESULTS Smoking cessation was greater for the BF arm than the Enhanced Usual Care arm ( 19 % versus 10 % , respectively ; P < 0.006 ) at 6 months but not at 12 months . CONCLUSIONS Smokers agreed to genetic feedback as part of a multicomponent cessation program . Although the program increased short-term cessation rates compared with st and ard intervention , genetic feedback of susceptibility may not benefit smokers with high baseline risk perceptions African-Americans ( AAs ) are significantly less likely to be physically active than other Americans , and , like all Americans , they consume fewer than the recommended five fruit and vegetable ( F & V ) servings per day . This study , titled Healthy Body/Healthy Spirit , has two primary aims : ( 1 ) to test the effectiveness of a culturally tailored self-help dietary ( focusing on F & V intake ) and physical activity ( PA ) intervention compared to st and ard health education material s , and ( 2 ) to test the effectiveness of using Motivational Interviewing ( MI ) , delivered by telephone , to modify PA and dietary habits . The study is a r and omized effectiveness trial with three experimental conditions . Group 1 ( comparison ) will receive st and ard ( existing commercial ) nutrition and PA intervention material s , Group 2 ( TX1 ) will receive a culturally tailored self-help nutrition and PA intervention of similar intensity as Group 1 , and Group 3 ( TX2 ) will receive the same intervention as Group 2 , plus four telephone counseling calls based on MI . Participants will be AA adults recruited through local black churches . Despite the extensive use of MI to modify addictive behaviors , this represents one of the first controlled field trials to employ MI to address diet and PA . Secondly , this is one of the first studies to test the effectiveness of a self-help diet and PA intervention tailored for an African-American church population The effect of message source on message recall and perceived credibility was examined in a r and omized study comparing two different computer-tailored bulletins promoting fruit and vegetable consumption among rural African American church members . An expert oriented ( EXP ) bulletin was compared with a spiritual and pastor-oriented ( SPIR ) bulletin and a control group . Both bulletins had the same format and used an identical set of dietary and psychosocial variables for tailoring . At follow-up , the majority of both intervention groups recalled receiving the bulletin , however message trust was higher in the SPIR group ( P < 0.05 ) . The EXP group reported higher trust of health and nutrition information coming from scientific research ( P < 0.01 ) , and the SPIR group reported higher trust of information coming from the pastor ( P < 0.05 ) . Both bulletin groups increased fruit and vegetable consumption significantly compared to the control group ; however , this difference could not be solely attributed to the tailored intervention which was part of a multi-component program Objective To develop and vali date a new diabetes risk algorithm ( the QDScore ) for estimating 10 year risk of acquiring diagnosed type 2 diabetes over a 10 year time period in an ethnically and socioeconomically diverse population . Design Prospect i ve open cohort study using routinely collected data from 355 general practice s in Engl and and Wales to develop the score and from 176 separate practice s to vali date the score . Participants 2 540 753 patients aged 25 - 79 in the derivation cohort , who contributed 16 436 135 person years of observation and of whom 78 081 had an incident diagnosis of type 2 diabetes ; 1 232 832 patients ( 7 643 037 person years ) in the validation cohort , with 37 535 incident cases of type 2 diabetes . Outcome measures A Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort and to derive a risk equation in men and women . The predictive variables examined and included in the final model were self assigned ethnicity , age , sex , body mass index , smoking status , family history of diabetes , Townsend deprivation score , treated hypertension , cardiovascular disease , and current use of corticosteroids ; the outcome of interest was incident diabetes recorded in general practice records . Measures of calibration and discrimination were calculated in the validation cohort . Results A fourfold to fivefold variation in risk of type 2 diabetes existed between different ethnic groups . Compared with the white reference group , the adjusted hazard ratio was 4.07 ( 95 % confidence interval 3.24 to 5.11 ) for Bangladeshi women , 4.53 ( 3.67 to 5.59 ) for Bangladeshi men , 2.15 ( 1.84 to 2.52 ) for Pakistani women , and 2.54 ( 2.20 to 2.93 ) for Pakistani men . Pakistani and Bangladeshi men had significantly higher hazard ratios than Indian men . Black African men and Chinese women had an increased risk compared with the corresponding white reference group . In the validation data set , the model explained 51.53 % ( 95 % confidence interval 50.90 to 52.16 ) of the variation in women and 48.16 % ( 47.52 to 48.80 ) of that in men . The risk score showed good discrimination , with a D statistic of 2.11 ( 95 % confidence interval 2.08 to 2.14 ) in women and 1.97 ( 1.95 to 2.00 ) in men . The model was well calibrated . Conclusions The QDScore is the first risk prediction algorithm to estimate the 10 year risk of diabetes on the basis of a prospect i ve cohort study and including both social deprivation and ethnicity . The algorithm does not need laboratory tests and can be used in clinical setting s and also by the public through a simple web calculator ( www.qdscore.org ) BACKGROUND Health promotion interventions often contain several , conceptually diverse elements . As a result , it is often difficult to determine why interventions succeed or fail as well as which components should be retained or eliminated . One method to examine the effectiveness of individual intervention elements is process analysis . METHODS Kick It ! is a multicomponent smoking cessation intervention developed for lower socioeconomic African Americans . The intervention includes several components , including a 24-page printed cessation manual , a staged-cessation video , a quit contract , two " Quit and Win " contests , and a single telephone booster call . Using data from a r and omized intervention trial design ed to test the efficacy of the Kick It ! intervention , this article examines the use , impact , and interaction of the intervention 's subcomponents as well as possible mediating variables related to successful quitting among intervention participants ( n = 650 ) . RESULTS In univariate as well as multivariate analyses adjusting for age and stage of change , two of the five elements , watching the video and entering a Quit and Win contest , were significantly associated with 6-month point prevalence abstinence . Su bmi tting a quit contract and receiving the booster call were significantly associated with quitting in univariate analyses , while reading the Kick It ! guide was not significantly associated with quitting in either analysis . CONCLUSIONS Despite the positive effects observed for individual elements , quitting was not significantly greater among intervention relative to comparison subjects . The primary reason for this appears to be the overall lack of intervention use . Additional research examining strategies to increase use of the Kick It ! intervention components as well as the optimal sequencing and combination of components may be warranted PURPOSE To present the development and feasibility testing of a sociocultural environmental change intervention strategy aim ed at integrating physical activity into workplace routine . DESIGN R and omized , controlled , post-test only , intervention trial . Setting . Los Angeles County Department of Health Services ' worksites . PARTICIPANTS Four hundred forty-nine employees , predominantly sedentary , overweight , middle-aged women of color , distributed across 26 meetings . INTERVENTION A single 10-min exercise break during work time involving moderate intensity , low-impact aerobic dance and calisthenic movements to music . MEASURES Primary -level of participation , particularly among sedentary staff ; secondary -self-perceived health status , satisfaction with current fitness level , and mood/affective state . RESULTS More than 90 % of meeting attendees participated in the exercises . Among completely sedentary individuals , intervention participants ' self-perceived health status ratings were significantly lower than controls ' ( OR = 0.17 ; 95 % CI = 0.05 , 0.60 ; P = 0.0003 ) . Among all respondents not regularly physically active , intervention participants ' levels of satisfaction with fitness were more highly correlated with self-ranked physical activity stage of change ( r = 0.588 ) than the control participants ' ( r = 0.376 , z = -2.32 , p = 0.02 ) . Among the completely sedentary , control participants reported significantly higher levels of energy than did intervention participants ( P < 0.01 ) . CONCLUSIONS Captive audiences may be engaged in brief bouts of exercise as a part of the workday , regardless of physical activity level or stage of change . This experience may also appropriately erode sedentary individuals ' self-perception of good health and fitness , providing motivation for adoption of more active lifestyles Although the primary care setting offers an innovative option for weight loss interventions , there is minimal research examining this type of intervention with low-income minority women . Further , there is a lack of research on the long-term effects of these programs . The purpose of this investigation was to examine the weight loss maintenance of low-income African-American women participating in a primary care weight management intervention . A r and omized controlled trial was conducted with overweight and obese women ( N = 144 ) enrolled at two primary care clinics . Women received a 6-month tailored weight loss intervention delivered by their primary care physician and completed follow-up assessment s 9 , 12 , and 18 months following r and omization . The weight loss maintenance of the tailored intervention was compared to a st and ard care comparison group . The weight loss of intervention participants ( -1.52 + /- 3.72 kg ) was significantly greater than that of st and ard care participants ( 0.61 + /- 3.37 kg ) at month 9 ( P = 0.01 ) . However , there was no difference between the groups at the 12-month or 18-month follow-ups . Participants receiving a tailored weight loss intervention from their physician were able to maintain their modest weight loss up to 3 - 6 months following treatment . Women demonstrated weight regain at the 18-month follow-up assessment , suggesting that more intensive follow-up in the primary care setting may be needed to obtain successful long-term weight loss maintenance This study was design ed to increase smoking cessation rates , quit attempts , and cutting down among low-income African Americans using brief clinician advice in conjunction with socioculturally appropriate self-help smoking cessation/relapse prevention material s. Physicians and nurses were instructed in the National Cancer Institute 's smoking intervention at inservice sessions . Smokers interviewed in a Harlem , New York clinic waiting room were recontacted 7 months later by telephone or mail ( 77 % response ) . Residents receiving the intervention reported a 21 % cessation rate at follow-up . An additional 27 % decreased cigarette intake by at least 50 % . Those reporting follow-up abstinence were significantly more likely to design ate a quit date at baseline . They were also more likely to be men , employed , and have a nonsmoking partner . Smokers who decreased their cigarette intake significantly were older , employed , less nicotine-dependent ( eg , delayed their wake-up cigarette ) , and more likely to use project material s. Physician advice had a significant impact both on patients ' cutting down at least 50 % and patients ' watching the project video . Design ation of a quit date and using project material s had a significant impact on making serious quit attempts . Results corroborate large sample , r and omized , controlled trials with noninner-city physicians . We conclude that clinician smoking advice for every patient is warranted This prospect i ve r and omized study examined the impact of three tailored intervention approaches to increase quitting rates among African-American smokers who were clients of a community health center that serves primarily low-income and indigent persons . Smokers were r and omized to one of three groups : ( 1 ) health care provider prompting intervention alone , ( 2 ) health care provider prompting intervention with tailored print communications , and ( 3 ) health care provider prompting intervention with tailored print communications and tailored telephone counseling . Among the 160 smokers who completed the study , 35 ( 21.8 % ) had quit smoking at follow-up . Smokers who received the provider prompting intervention with tailored print material s were more likely to report having quit than smokers who received the provider intervention alone ( 32.7 % vs. 13.2 % , p < 0.05 ) . Smokers who received all three intervention components were not more likely to report having quit at follow-up than those who only received the provider intervention ( 19.2 % vs. 13.2 % ) . Smokers who at baseline were less educated , smoked less than half a pack of cigarettes per day , had a stronger desire to quit , felt more efficacious , and had thought about quitting were more likely to report having quit at follow-up . These results provide support for continued refinement of tailored communications to aid smoking cessation among African-American smokers OBJECTIVE African-American girls and women are at high risk of obesity and its associated morbidities . Few studies have tested obesity prevention strategies specifically design ed for African-American girls . This report describes the design and baseline findings of the Stanford GEMS ( Girls health Enrichment Multi-site Studies ) trial to test the effect of a two-year community- and family-based intervention to reduce weight gain in low-income , pre-adolescent African-American girls . DESIGN R and omized controlled trial with measurements scheduled in girls ' homes at baseline , 6 , 12 , 18 and 24 month post-r and omization . SETTING Low-income areas of Oakl and , CA . PARTICIPANTS Eight , nine and ten year old African-American girls and their parents/caregivers . INTERVENTIONS Girls are r and omized to a culturally-tailored after-school dance program and a home/family-based intervention to reduce screen media use versus an information-based community health education Active-Placebo Comparison intervention . Interventions last for 2 years for each participant . MAIN OUTCOME MEASURE Change in body mass index over the two-year study . RESULTS Recruitment and enrollment successfully produced a predominately low-socioeconomic status sample . Two-hundred sixty one ( 261 ) families were r and omized . One girl per family is r and omly chosen for the analysis sample . R and omization produced comparable experimental groups with only a few statistically significant differences . The sample had a mean body mass index ( BMI ) at the 74 th percentile on the 2000 CDC BMI reference , and one-third of the analysis sample had a BMI at the 95th percentile or above . Average fasting total cholesterol and LDL cholesterol were above NCEP thresholds for borderline high classifications . Girls averaged low levels of moderate to vigorous physical activity , more than 3 h per day of screen media use , and diets high in energy from fat . CONCLUSIONS The Stanford GEMS trial is testing the benefits of culturally-tailored after-school dance and screen-time reduction interventions for obesity prevention in low-income , pre-adolescent African-American girls We design ed , implemented and evaluated an educational intervention to increase fruit and vegetable consumption among urban African-American women . Women aged 20 - 50 years ( n=212 ) from 11 public housing communities participated in seven 90-min classes with a professional nutritionist . Our prospect i ve pre- and post-test design , with 4-month follow-up , assessed the relationship between attendance and dietary change , using three 24-hour recalls per time point . Mean change in average daily dietary values for fruits and vegetables , calories and percent calories from fat ( post-test versus pre-test , follow-up versus pre-test ) was compared by class attendance , to evaluate the impact of class attendance on dietary change . Attendance varied from zero ( 35 % ) to five to seven classes ( 42 % ) . Baseline dietary recalls showed average daily consumption of 3.05 servings of fruits and vegetables , 2416 calories and 35.8 % calories from fat . No improvements in fruit and vegetable consumption , but statistically significant decreases in total calories and percent calories from fat , were seen at both endpoints . Women attending five to seven classes had the greatest dietary improvements , averaging , at post-test and follow-up , respectively , 246.2 and 324.5 fewer calories and 3.08 and 2.97 % fewer calories from fat . Results suggest that , for some residents of low-re source communities , small group interventions are popular , effective vehicles for nutrition education Introduction Breast cancer survival rates are lower for African American women than for white women . Obesity , high-fat diets , and lack of regular physical activity increase risk for breast cancer recurrence , comorbid conditions , and premature death . Eighty-two percent of African American women are overweight or obese , partly because of unhealthy eating and exercise patterns . Although successful weight loss and lifestyle interventions for breast cancer survivors are documented , none has considered the needs of African American breast cancer survivors . This study assessed the feasibility and impact of Moving Forward , a culturally tailored weight loss program for African American breast cancer survivors . Methods The study used a pre-post design with a convenience sample of 23 African American breast cancer survivors . The 6-month intervention was theory-based and incorporated qualitative data from focus groups with the targeted community , urban African American breast cancer survivors . Data on weight , body mass index ( BMI ) , diet , physical activity , social support , and quality of life were collected at baseline and at 6 months . Results After the intervention , we noted significant differences in weight , BMI , dietary fat intake , vegetable consumption , vigorous physical activity , and social support . Conclusion This is the first published report of Moving Forward , a weight loss intervention design ed for African American breast cancer survivors . Although a r and omized trial is needed to establish efficacy , the positive results of this intervention suggest that this weight loss intervention may be feasible for African American breast cancer survivors . Lifestyle interventions may reduce the disparities in breast cancer mortality rates Diet is an important factor in the causation of cancer . Previous systematic review s of one-to-one interventions to encourage dietary change have found that such interventions can achieve modest improvements in diet . However , such interventions are re source intensive and unlikely to be good value for money at a population level . Interventions that address groups , communities or whole population s may be less re source intensive and effect change in a wider population . We report a systematic review of such interventions . We set wide inclusion criteria , including before- and -after studies and studies with a non-r and omized comparison group as well as r and omized trials . We found eighteen studies based in the community , seventeen based on worksites , five based in churches and one based in a supermarket . Interventions which targeted fruit and vegetable intake were most likely to be successful , particularly in worksites and churches . There was also evidence of small positive effects on reducing fat intake in worksites and churches . Overall the community-based interventions showed little effect . The studies included in the present review were generally poorly reported . Dietary changes are reported in the relatively short-term studies review ed here but may not be sustained in the long term . The effects that we have identified are small but the reach is potentially very wide , in some cases as wide as a whole country . The cost effectiveness of such strategies remains to be evaluated Internet-based interventions hold promise as an effective channel for reaching large numbers of youth . However , log-on rates , a measure of program dose , have been highly variable . Methods to enhance log-on rate are needed . Incentives may be an effective method . This paper reports the effect of reinforcement schedule and recruitment method on log-on rates to an 8-week Internet-based obesity prevention program . It also explores trends in log-on rate . Girls were r and omized to receive immediate ( weekly ) or delayed ( program end ) incentives ( $ 5 ) . The study was powered to detect a moderate-to-large effect ( 0.65 ) . Overall log-on rate was 74.5 % . A higher but not statistically different log-on rate was observed in the immediate incentive group ( 79 % ) than in the delayed incentive group ( 70 % ) ( P = 0.118 ) , and among girls recruited via media ( 80 % ) as opposed to non-media methods ( 69 % ) ( P = 0.058 ) . Trend analysis indicated a significant drop in log-on rate between weeks 4 and 5 among all participants ( P = 0.009 ) . Although an acceptable log-on rate was achieved in this program , there was a substantial drop between weeks 4 and 5 . Identifying the reason that this occurred may provide insight into how to further enhance log-on rate . Recruitment method may influence log-on rate Introduction Physical activity participation is low among blacks , and strategies are needed to successfully create immediate and sustained behavior change related to physical activity . Churches can play an important role in health promotion efforts among blacks because of their central role in spiritual guidance , communication , social support , and networking . This pilot study evaluated the feasibility and acceptability of implementing a physical activity program for sedentary black adults in churches . Methods We used a preintervention/postintervention single-group design to evaluate the effect of a 3-month faith-based physical activity intervention on daily walking and moderate- and vigorous-intensity physical activity among sedentary blacks . Eighty-seven black adults participated in eight group sessions that included discussion of physical activity-related topics , an instructor-led physical activity session , and weekly incentives to promote physical activity . We used a question naire to assess moderate and vigorous physical activity in minutes per week at baseline and after 3 months . Walking was assessed weekly in steps per day by using a pedometer . Results Participants ( mean age , 52 yrs ; mean body mass index , 35 kg/m2 ) reported 27 ± 54 and 10 ± 25 minutes per week in moderate-intensity and vigorous-intensity physical activity , respectively , and walked 4822 ± 2351 steps per day at baseline . After 12 weeks , moderate- and vigorous-intensity physical activity increased by 67 ± 78 and 44 ± 66 minutes per week , respectively ( P ≤ .01 ) , and daily walking increased by 1373 ± 728 steps per day ( P < .001 ) . Conclusion These data suggest that a faith-based physical activity intervention may be an appropriate strategy for increasing physical activity among sedentary black adults . Future research will determine the impact of this program in a r and omized , controlled design OBJECTIVE : To determine the efficacy of the transdermal nicotine patch for smoking cessation in inner-city African Americans . DESIGN : Double-blind , placebo-controlled , r and omized trial . SETTING : Outpatient in an inner-city hospital . PATIENTS AND PARTICIPANTS : A computer-generated r and om numbers table with a block size set at 20 was used to r and omize 410 patients to one of two study arms . INTERVENTIONS : The transdermal nicotine patch for 10 weeks as an adjunct to brief counseling . MEASUREMENTS AND MAIN RESULTS : Of the 410 patients r and omized , mean age was 48 years , 65 % were female , 41 % had less than a high school education , 51 % had an annual household income of less than $ 8,000 , and the average number of cigarettes smoked per day was 20 . Quit rates at 10 weeks were 21.5 % ( 44/205 ) with the nicotine patch , and 13.7 % ( 28/205 ) with the placebo patch ( p=.03 ) . At 6 months , quit rates were 17.1 % ( 35/205 ) with the nicotine patch , and 11.7 % ( 24/205 ) with the placebo patch ( p=.08 ) . After adjusting for baseline differences in age and educational attainment , differences remained significant at 10 weeks ( p=.04 ) , but were not significant at 6 months ( p=.14 ) . Compliance rates for return visits were 83 % , 78 % , 55 % , and 52 % , at 1 , 2 , 6 , and 10 weeks , respectively . CONCLUSIONS : The nicotine patch significantly improves short-term quit rates in inner-city African Americans who are interested in trying to quit smoking . Efforts should be made to reach underserved population s through smoking cessation programs , and to assist in maintaining abstinence 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 This study examines the efficacy of targeted versus st and ard care smoking cessation material s among urban African American smokers . Five hundred smokers ( 250 to each group ) are r and omized to receive a culturally targeted or st and ard care videotape and print guide . Both groups receive 8 weeks of nicotine patches and reminder telephone calls at Weeks 1 and 3 . Process outcomes include material use and salience at 1 and 4 weeks postbaseline . Smoking outcomes include 7-day abstinence , smoking reduction , and readiness to quit at 4 weeks and 6 months postbaseline . Despite greater use of the targeted guide ( 68.8 % vs. 59.6 % , p < .05 ) , intervention participants do not perceive the targeted material s as more salient , and no significant differences are found between groups on the smoking outcomes . Findings point to the importance of greater audience segmentation and individual tailoring to better match intervention material s to the needs of the priority population This paper describes ( 1 ) the design , methods and baseline data of the first smoking cessation clinical trial for Chinese Americans with medical conditions - Chinese Community Smoking Cessation Project ( CCSCP ) ; ( 2 ) the collaborative process between research ers and the Chinese community ; and ( 3 ) the barriers and facilitators of implementing the study . CCSCP was a culturally tailored , r and omized , smoking cessation trial testing the efficacy of an intensive ( physician advice , in-person counseling with nicotine replacement therapy , 5 telephone calls ) compared to a minimal ( physician advice and self-help manual ) intervention . The study applied a community-sensitive research method involving community members in all phases of the research process in San Francisco Bay Area during 2001–2007 . CCSCP recruited 464 smokers from health care facilities ( 79 % ) located in Chinese neighborhoods and through Chinese language media ( 21 % ) . Baseline assessment s and interventions were conducted in-person using translated and tested question naire and intervention material s. The majority of the participants were men ( 91 % ) with a mean age of 58.3 years , foreign born ( 98 % ) , with less than high school education ( 58 % ) , spoke no English ( 42 % ) and in non-skilled or semi-skilled occupations ( 60 % ) with < $ 20,000 household income ( 51 % ) . Participants smoked regularly on an average 38.6 ± 17 years , smoked 9.1 ± 8 cigarettes per day and 85 % smoked daily . Cultural tailoring of recruitment methods and intervention design led to successful enrollment and retention of participants , overcoming barriers faced by the participants . Community sensitive collaborative process facilitated implementation of study protocol in community health care setting AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed OBJECTIVE The Girls health Enrichment Multisite Studies ( GEMS ) Fun , Food , and Fitness Project ( FFFP ) was design ed to prevent obesity among 8-year-old African-American girls . DESIGN Twelve-week , two-arm parallel group r and omized controlled pilot study . SETTING Summer day camp and homes in Houston , Texas . PARTICIPANTS Thirty-five girls and their parents or caregivers were r and omly assigned to treatment ( N=19 ) or control groups ( N=16 ) . INTERVENTION Girls in the intervention group attended a special 4-week summer day camp , followed by a special 8-week home Internet intervention for the girls and their parents . Control group girls attended a different 4-week summer day camp , followed by a monthly home Internet intervention , neither of which components included the GEMS-FFFP enhancements . MAIN OUTCOME MEASURES Body mass index ( BMI ) , consumption of fruit , 100 % fruit juice , and vegetables ( FJV ) , physical activity . RESULTS After adjusting for baseline BMI , there were no significant differences in BMI between treatment and control group girls , either at the end of the 4-week summer day camp , or after the full 12-week intervention . By the end of the summer camp , the subgroup of treatment group girls heavier at baseline exhibited a trend ( P<.08 ) toward lower BMI , compared to their heavier counterparts in the control group . Overall results at the end of the 12-week program demonstrated substantial , although not significant , differences between treatment and control groups in the hypothesized directions . On average , less than half the treatment sample logged onto the Website , which limited intervention dose . CONCLUSIONS Summer day camp appears to offer promise for initiating health behavior change . Effective methods must be developed and tested to enhance log-on rates among healthy children and their parents before Internet programs can achieve their potential Dietary and behavioral needs of special population s are rarely considered in traditional weight loss programs . This study assessed the impact of culturally-sensitive modifications to the Duke University Rice Diet weight loss program for African-American dieters . The study was a r and omized modified cross-over study in which volunteers received either early or delayed weight loss intervention . Final outcomes were measured at 8 weeks . At the onset of the study , there were 56 African American participants , however , only 44 ( 79 % ) completed the study . The eight-week intervention was a modified 1000-calorie/day version of the Rice Diet . Modifications to the program included decreased cost , culturally-sensitive recipes , addressing attitudes about exercise , and including family members in weight loss efforts . Average weight loss for subjects completing the program was 14.8 pounds ( SD = 6.8 pounds ) . BMI decreased from 37.8 kg/m2 to 35.3 kg/m2 ( p < 0.01 ) . Total cholesterol levels decreased from 199.2 mg/dL to 185.4 mg/dL ( p < 0.01 ) ; systolic and diastolic blood pressure decreased by 4.3 mmHg ( p < 0.01 ) and 2.4 mmHg ( p < 0.05 ) , respectively . The control group showed no significant change in any outcome measures . We found that diet programs can be successfully tailored to incorporate the needs of African-Americans . Most importantly , these dietary program changes can lead to significant improvement in clinical parameters . Additional studies are necessary to determine the permanence of these short-term changes This study compared the effects of 3 home-based exercise promotion programs for African Americans . Sixty , sedentary African-American adults were r and omly assigned to either a st and ard behavioral counseling group ( N=22 ) , a culturally sensitive counseling group ( N=20 ) , or a physician advice comparison group ( N=10 ) . The key study outcomes measured at baseline and after 6 months included cardiorespiratory fitness and physical activity . Acculturation was examined as a moderating variable . Participants in all 3 groups reported significant increases in walking , but significant improvements in fitness were observed only in the 2 intervention groups . Participants in the culturally sensitive intervention reported significantly higher levels of exercise social support compared to members of the other 2 groups . These findings show that home-based exercise counseling programs are effective for improving fitness , yet the addition of culturally tailored components may not be sufficient to produce better outcomes than st and ard behavioral counseling Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Abstract OBJECTIVE : To examine the predictors of quitting among African American ( AA ) light smokers ( < 10 cigarettes per day ) enrolled in a smoking cessation trial . METHODS : Baseline variables were analyzed as potential predictors from a 2 × 2 cessation trial in which participants were r and omly assigned to 1 of 4 treatment groups : nicotine gum plus health education ( HE ) counseling , nicotine gum plus motivational interviewing ( MI ) counseling , placebo gum plus HE counseling , or placebo gum plus MI counseling . Chi-square tests , 2 sample t-tests , and multiple logistic regression analyses were used to identify predictors of cotinine ( COT ) verified abstinence at month 6 . RESULTS : In the final regression model , HE rather than MI counseling ( odds ratio [OR]=2.26 % , 95 % confidence interval [CI]=1.36 to 3.74 ) , older age ( OR=1.03 % , 95 % CI=1.01 to 1.06 ) , and higher body mass index ( OR=1.04 % , 95 % CI=1.01 to 1.07 ) significantly increased the likelihood of quitting , while female gender ( OR=0.46 % , 95 % CI=0.28 to 0.76 ) , ≤$1,800/month income ( OR=0.60 % , 95 % CI=0.37 to 0.97 ) , higher baseline COT ( OR=0.948 % , 95 % CI=0.946 to 0.950 ) , and not completing all counseling sessions ( OR=0.48 % , 95 % CI=0.27 to 0.84 ) reduced the odds of quitting . CONCLUSIONS : Individual characteristics may decrease the likelihood of quitting ; however , the provision of directive , advice-oriented counseling focused on the addictive nature of nicotine , health consequences of smoking , benefits of quitting , and development of a concrete quit plan may be an important and effective facilitator of quitting among AA light smokers OBJECTIVE This paper describes the development of an after-school obesity-prevention program for African-American girls , and presents findings from a 12-week pilot trial conducted by the University of Minnesota . This study was part of the GEMS project , created to test interventions design ed to reduce excess weight gain in African-American girls . DESIGN Two-arm parallel group , r and omized controlled trial . Measures were taken at baseline and at 12 weeks follow up . SETTING An after-school community program . PARTICIPANTS Fifty-four African-American girls , 8- to 10-years of age , and their parents/caregivers . INTERVENTION The after-school intervention was conducted twice a week for 12 weeks , and focused on increasing physical activity and healthy eating . A family component was also included . Girls in the control group received a program over 12 weeks unrelated to nutrition and physical activity . OUTCOMES Measures included height and weight ( body mass index ) , percent body fat ( DEXA ) , physical activity , assessed using a CSA accelerometer and self-report , two 24-hour dietary recalls , and psycho-social and demographic variables . Parental data included demographic and psycho-social characteristics , and dietary measures . Additionally , process evaluation data on the intervention were collected . RESULTS Recruitment goals were met . After adjustment for baseline level , follow-up BMI did not differ between the treatment groups , an expected finding , given that this was a pilot study . At 12 weeks follow up , differences between the intervention and control groups were in the hypothesized direction of change for most variables , among both the girls and their parents . Process evaluation results demonstrated that the program was well attended , and well received , by girls and parents . CONCLUSIONS An after-school obesity prevention program for low-income African-American girls is a promising model for future efforts Objective . The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies : a st and ard behavioral group intervention , the st and ard intervention supplemented with spiritual strategies , or self-help strategies . Methods . Women were screened at baseline and after one year of participation . The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering . Because spiritual strategies were added to the st and ard intervention by participants themselves , the results from both active groups were similar and , thus , combined for comparisons with the self-help group . Results . A total of 529 women from 16 churches enrolled . Intervention participants exhibited significant improvements in body weight ( −1.1 lbs ) , waist circumference ( −0.66 inches ) , systolic blood pressure ( −1.6 mmHg ) , dietary energy ( −117 kcal ) , dietary total fat ( −8 g ) , and sodium intake ( −145 mg ) . The self-help group did not . In the active intervention group , women in the top decile for weight loss at one year had even larger , clinical ly meaningful changes in risk outcomes ( −19.8 lbs ) . Conclusions . Intervention participants achieved clinical ly important improvements in cardiovascular disease risk profiles one year after program initiation , which did not occur in the self-help group . Church-based interventions can significantly benefit the cardiovascular health of African American women OBJECTIVES This study reports on Eat for Life , a multicomponent intervention to increase fruit and vegetable consumption among African Americans that was delivered through Black churches . METHODS Fourteen churches were r and omly assigned to 3 treatment conditions : ( 1 ) comparison , ( 2 ) self-help intervention with 1 telephone cue call , and ( 3 ) self-help with 1 cue call and 3 counseling calls . The telephone counseling in group 3 was based on motivational interviewing . The primary outcome , assessed at baseline and 1-year follow-up , was fruit and vegetable intake as assessed by 3 food frequency question naires . RESULTS Change in fruit and vegetable intake was significantly greater in the motivational interviewing group than in the comparison and self-help groups . The net difference between the motivational interviewing and comparison groups was 1.38 , 1.03 , and 1.21 servings of fruits and vegetables per day for the 2-item , 7-item , and 36-item food frequency question naires , respectively . The net difference between the motivational interviewing and self-help groups was 1.14 , 1.10 , and 0.97 servings for the 2-item , 7-item , and 36-item food frequency question naires , respectively . CONCLUSIONS Motivational interviewing appears to be a promising strategy for modifying dietary behavior , and Black churches are an excellent setting to implement and evaluate health promotion programs OBJECTIVE The objective of this study was to evaluate the impact of a problem-based empowerment patient education program specifically tailored for urban African Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS The study used a r and omized controlled trial ( RCT ) pretest/post-test design with repeated measures . Patients were r and omly assigned to either a six-week intervention group or a six-week wait-listed control group . After completing the six sessions , patients were invited to participate in one of two follow-up conditions ; attend a monthly support group or receive a monthly phone call from a nurse . Assessment measures included HbA1C , lipids , blood pressure , weight , self-management behavior and psychosocial adaptation . RESULTS Both control and intervention patients showed a broad array of small-to-modest positive changes during the six-week RCT . These gains were maintained or improved upon during the one-year follow-up period . For patients in the two follow-up conditions , a positive correlation was seen between the number of follow-up contacts and their one-year HbA1C values . CONCLUSIONS We believe that results of this study can be attributed to volunteer bias , study effects ( ie , providing study data on several occasions to patients and their physicians during the one-year study period ) , and impact of the interventions . However , the study design does not allow us to examine the relative impact of these three factors on the patient improvements seen over the one-year study period The Obesity Reduction Black Intervention Trial ( ORBIT ) is a r and omized controlled trial design ed to assess the efficacy of a culturally proficient 6-month weight loss intervention followed by a 1-year maintenance intervention . This article describes the results of the 6-month weight loss intervention . Two hundred thirteen obese black women aged 30 - 65 years were r and omized to the intervention group or a general health control group . The intervention consisted of a 6-month culturally adapted weight loss program that targeted changes in diet and physical activity patterns . Weight , dietary intake , and physical activity were measured at baseline and 6 months . A total of 198 women ( 93 % ) completed both the baseline and postintervention assessment s. Women in the intervention group lost significantly more weight than women in the control group ( P < 0.001 ) . However , weight change was variable within the intervention group , with a maximum weight loss of 19.4 % of initial body weight and a maximum weight gain of 6.4 % of initial body weight . Women in the intervention group also showed significant improvements in fruit intake ( P < 0.01 ) , Healthy Eating Index score ( P < 0.001 ) , and moderate ( P = 0.05 ) , and vigorous ( P < 0.001 ) physical activity compared to women in the control group . This study demonstrates that a culturally adapted program can successfully promote weight loss in obese black women . However , average weight loss was relatively modest , and weight change varied widely within the intervention group . Further research is needed in order to develop programs that will allow more black women to achieve their weight loss goals CONTEXT Declines in physical performance are associated with aging and chronic health conditions . Appropriate physical activity interventions can reverse functional limitations and help maintain independent living . Tai chi is a popular form of exercise in China among older adults . OBJECTIVE To determine whether tai chi improves balance , muscular strength and endurance , and flexibility over time . DESIGN Repeated measures intervention ; data collected at baseline , 6 weeks , and 12 weeks . SETTING Community center in the San Francisco Bay Area . PARTICIPANTS Thirty-nine Chinese adults with at least 1 cardiovascular disease ( CVD ) risk factor . INTERVENTIONS A 60-minute tai chi exercise class 3 times per week for 12 weeks . MAIN OUTCOME MEASURES A battery of physical fitness measures specifically developed for older adults assessed balance , muscular strength and endurance , and flexibility . RESULTS Subjects were 65.7 ( + /- 8.3 ) years old , Cantonese-speaking ( 97 % ) immigrants , with 12 years or less of formal education ( 87 % ) and very low income ( 67 % ) . Reported CVD risk factors were hypertension ( 92 % ) , hypercholesteremia ( 49 % ) , diabetes ( 21 % ) , and 1 current smoker . Subjects were below the 50th percentile of fitness at baseline compared to age- and gender-specific normative US data . Statistically significant improvements were observed in all balance , muscular strength and endurance , and flexibility measures after 6 weeks , and they increased further after 12 weeks . CONCLUSIONS Tai chi is a potent intervention that improved balance , upper- and lower-body muscular strength and endurance , and upper- and lower-body flexibility in these older Chinese adults . These findings provide important information for future community-based tai chi exercise programs and support current public health initiatives to reduce disability from chronic health conditions and enhance physical function in older adults A center-based program was design ed and implemented to promote aerobic physical activity among healthy Black-American families with children in the fifth through seventh grade s. Ninety-four Black-American families were actively recruited and r and omly as signed to an experimental or control group . Families in the experimental group were encouraged to participate in a program with the following features : one education and two fitness sessions per week for 14 weeks ; educational sessions that included individual counseling , small group education , aerobic activity , and snack components ; located in a convenient building cherished by the community ; aerobic activity sessions in a fitness center outfitted and staffed according to modern characteristics ; a variety of incentives including free transportation and babysitting and reminders to promote attendance . Per cent participation was low , with about 20 % participating in the desired fitness center sessions by the end of the program . As a result of low participation , no differences were detected beween experimental and control groups on indicators of cardiovascular fitness . In postprogram interviews , conflicts with work and school events were the most commonly reported reasons for nonattendance . We concluded that because of difficulties in at tendance , center-based programs appear to have limited value as the sole modality for intervention in public health programs for promoting physical activity among healthy Ethnic minorities are often underrepresented in clinical trials , and their recruitment can challenge research ers . Developing and communicating effective and efficient recruitment strategies may help research ers enroll more minorities into research studies . Kick It at Swope was a double-blind , r and omized trial that evaluated bupropion for smoking cessation among 600 adult African Americans who smoked 10 or more cigarettes a day . Proactive recruitment strategies ( in-person appeals by study staff and health care providers ) and reactive recruitment strategies ( disseminating information that asked people to call a study hotline ) were implemented sequentially in an additive fashion over 16 months . Result ing patterns of recruitment are described and the two phases are compared based on their relative effectiveness , efficiency , and cost . More enrollees were recruited in the reactive phase ( n=534 ) than in the proactive phase ( n=66 ) . Those recruited in the reactive phase were more likely to be eligible ( OR=4.8 ) and more likely to be enrolled ( OR=4.2 ) than those recruited in the proactive phase . Participants recruited in the reactive phase reported significantly higher levels of education and income , better health , and significantly lower indicators of depression and life hassles , compared with those recruited in the proactive phase . The reactive recruitment phase was less expensive than the proactive recruitment phase ( 22 US Dollars/enrollee vs. 159 US Dollars/enrollee ) . Reactive recruitment strategies added to multiple proactive clinic-based recruitment strategies were more effective , more efficient , and less costly than proactive recruitment alone . Close monitoring combined with the use of multiple recruitment methods and flexible recruitment plans can lead to successful , efficient , and low-cost recruitment of minorities into clinical trials 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 In November 1985 , a television smoking cessation program was broadcast for 20 days on the noon and 9 p.m. news . Smokers in West Garfield Park , an inner-city impoverished area of Chicago , were r and omly assigned either to a comprehensive intervention or to a no-intervention control condition . Although 100,000 self-help manuals had been distributed throughout Chicago , none of the controls in this low-income area had obtained a manual . The intervention consisted of providing the smokers a self-help manual , the televised broadcast , weekly support meetings , and supportive phone calls . At a 4-month follow-up , 20 % of treatment participants were abstinent compared to 9 % of controls . The results indicated that intensive supplementary opportunities enhanced participation by low-income smokers in a media smoking cessation program We examined participation and dietary change among women participants in a community-based nutrition education program , to determine whether intervention results differed by participant body size . Four dietary indicators ( daily servings of fruits and vegetables , total calories , calories from fat , and Healthy Eating Index score ) were assessed from 24-h recalls taken before , immediately after , and 4 months after a seven-session nutritional education program , from 156 African-American women age 20–50 , in Washington , D.C. public housing . Knowledge , attitudes and practice s related to nutritional behavior change were collected at three timepoints as well . R and om effect models were used to examine dietary patterns , and compare change by body size and class attendance . Results showed that obese women ( BMI ≥ 30 ) had more psychosocial barriers to dietary change and poorer baseline diets , but stronger program attendance . Post-intervention , both groups consumed approximately 250 fewer calories and 2.5 % fewer calories from fat . At follow-up , non-obese women consumed significantly fewer calories ; obese women consumed significantly fewer calories from fat , and showed significant improvement in HEI . Given the prevalence of obesity in low re source communities , nutritional interventions should tailor strategies to participant body size and related psychosocial needs Healthy Body Healthy Spirit was a multicomponent intervention to increase fruit and vegetable ( F & V ) consumption and physical activity ( PA ) delivered through Black churches . Sixteen churches were r and omly assigned to 3 intervention conditions . At baseline , 1,056 individuals were recruited across the 16 churches , of which 906 ( 86 % ) were assessed at 1-year follow-up . Group 1 received st and ard educational material s , Group 2 received culturally targeted self-help nutrition and PA material s , and Group 3 received the same intervention as did Group 2 as well as 4 telephone counseling calls based on motivational interviewing ( MI ) delivered over the course of 1 year . At 1-year follow-up , Groups 2 and 3 showed significant changes in both F & V intake and PA . Changes were somewhat larger for F & V. For F & V , but not PA , there was a clear additive effect for the MI intervention OBJECTIVE This study was carried out to test the effectiveness of PATHWAYS , a weight loss program design ed specifically for urban African-American women , when administered in urban churches by trained lay facilitators . RESEARCH DESIGN AND METHODS Thirty-nine obese women were recruited from three urban African-American churches . After r and omization and the collection of baseline data on weight and lifestyle practice s , subjects in the experimental group ( n = 19 ) were assigned to receive a 14-week weight loss program ( PATHWAYS ) conducted by trained lay volunteers ; control group subjects ( n = 20 ) were put on a waiting list to receive the program at the conclusion of the study period . RESULTS Of the 39 women enrolled , 15 experimental group subjects and 18 control group subjects were available for posttreatment data collection . After completing the program , PATHWAYS participants lost an average of 10.0 lb , and the control group subjects gained an average of 1.9 lb . Posttreatment difference in weight loss between the groups was statistically significant ( P < 0.0001 ) . Waist circumference among PATHWAYS participants decreased 2.5 inches , while waist circumference among control group subjects remained relatively the same . This difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS A weight loss program administered by trained lay volunteers was effective in producing significant and clinical ly meaningful weight loss among African-American women who often do not benefit from typical weight loss programs . Ongoing research is focusing on whether the weight loss can be maintained or enhanced through monthly reinforcement sessions Relatively little research has been done to test quitsmoking interventions in African-American population s ? Cigarette smoking is integral to higher rates of cancer and cardiovascular morbidity and mortality for AfricanAmericans compared with their non-African-American counterparts in the United States . 2 African-American women smokers , in particular , may experience increased health risks related to cigarette smoking because they are reported to have higher average levels of cotinine , a nicotine metabolite , than other race or gender groups ? Homogeneity in economic , cultural , and social characteristics between client and provider has been identified as important in increasing the likelihood of success in quitsmoking programs . 2 Because of this , efforts to recruit and train facilitators from the African-American community could improve intervention effectiveness ? The purpose of this study was to evaluate the feasibility and effect of a behavior-change smoking-cessation intervention mailed in four weekly segments supplemented with weekly telephone support calls from an African-American woman ex-smoker , and to compare the effects to an advice-only intervention BACKGROUND It is widely accepted that disease prevention efforts should consider cultural factors when addressing the needs of diverse population s , yet there is surprisingly little evidence that doing so enhances effectiveness . The Institute of Medicine has called for r and omized studies directly comparing approaches that do and do not consider culture . METHODS In a r and omized trial , 1227 lower-income African-American women from 10 urban public health centers were assigned to either a usual care control group , or to receive a series of six women 's health magazines with content tailored to each individual . By r and om assignment , these magazines were generated from either behavioral construct tailoring ( BCT ) , culturally relevant tailoring ( CRT ) or both ( BCT + CRT ) . The CRT magazines were based on four cultural constructs : religiosity , collectivism , racial pride , and time orientation . All tailored magazines sent to women ages 40 - 65 promoted use of mammography ; magazines sent to women ages 18 - 39 promoted fruit and vegetable ( FV ) intake . Analyses examined changes from baseline to 18-month follow-up in use of mammography and servings of FV consumed daily . RESULTS Women receiving BCT + CRT magazines were more likely than those in the BCT , CRT , and control groups to report getting a mammogram ( 76 % vs. 65 % vs. 64 % vs. 55 % , respectively ) , and had greater increases in FV servings consumed daily ( + 0.96 vs. + 0.43 vs. + 0.25 vs. + 0.59 ) . CONCLUSIONS Systematic ally integrating culture into tailored cancer prevention and control interventions may enhance their effectiveness in diverse population BACKGROUND African Americans remain a critically underserved group for smoking cessation interventions . This study tested the effectiveness of a tailored , culturally sensitive intervention for African American smokers who called the NCI Cancer Information Service ( CIS ) for help to quit smoking . METHODS This paper presents results of a 2-year study of tailored counseling strategies among African American smokers ( n = 1,422 ) who called four regional CIS offices in response to a radio-based media campaign in 14 communities . Callers were r and omly assigned to receive either the st and ard CIS quit smoking counseling and guide ( Clearing the Air ) or counseling and a guide ( Pathways to Freedom ) tailored to the quitting needs and barriers of African American smokers . Callers were predominantly female ( 63.6 % ) . ages 20 - 49 ( 88 % ) , with a high school education or more ( 84 % ) . Median smoking history was 17 years ; median smoking rate was 20 cigarettes/day . St and ard ( n = 689 ) and Tailored ( n = 733 ) group subjects did not differ on most baseline measures . RESULTS On most measures , St and ard and Tailored counseling/guides received similar ratings , but the Tailored guide was rated as having more appealing photos ( P = 0.001 ) and as being more appropriate for family members ( P = 0.003 ) . Six-month follow-up with 893 subjects ( response rates were 63 % St and ard , 62 % Tailored , ns ) showed significantly more quit attempts ( P = 0.002 ) and greater use of prequitting strategies ( P < 0.05 ) among Tailored than among St and ard subjects , but no differences in self-reported 1-week abstinence ( 14.4 % St and ard , 16.2 % Tailored ) ( ns ) . An opportunistic 12-month follow-up of subjects recruited in the last year of the study ( n = 445 ) ( response rates were 57 % St and ard , 60 % Tailored , ns ) showed a significantly higher quit rate ( 15.4 % St and ard , 25.0 % Tailored ) for Tailored subjects ( P = 0.034 ) . CONCLUSIONS Results show promise for tailored approaches to boost quit attempts and success rates among African American smokers BACKGROUND African Americans have traditionally made little use of the Cancer Information Service ( CIS ) , an information and education program of the National Cancer Institute , for smoking cessation assistance . This study evaluated whether a targeted communications campaign utilizing strategically placed radio and television advertisements in combination with community outreach could lead more adult African American smokers to call the CIS for smoking cessation information and material s. METHODS Fourteen communities , served by four CIS regional offices , were carefully matched on demographic variables and then r and omly assigned to either an experimental or a control group . Six radio advertisements targeting African American smokers to call the CIS for help in quitting smoking were developed and pretested for three different black-oriented formats . One television spot also was produced and pretested . The audio portion of the television ad was utilized as a seventh radio spot for the general programming formats . These advertisements were placed on selected radio and television stations reaching predominantly African American adult audiences . Also , copies of a videotape design ed to motivate African American smokers to quit and to call the CIS for help in quitting were widely disseminated through community-based organizations in each experimental market . The aim was to increase the number and proportion of quitting-related calls to the CIS from African Americans within experimental communities . RESULTS The call volume from African American smokers was significantly higher in the experimental communities than in the control communities ( P < 0.008 ) . The call rate from African American men was higher than typically observed . Overall , African Americans in the experimental communities reported radio more often than television as the way they heard about the CIS . CONCLUSION The results suggest that paid targeted advertising , using radio as a primary channel , is an effective method of reaching an underserved population at risk . Future research directions are discussed Objective : This r and omized controlled trial tested the efficacy of an internetbased lifestyle behavior modification program for weight management in African-American girls . Design : African-American girls were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . The behavioral intervention included internet counseling and was highly interactive . The control intervention was a passive ( non-interactive ) educational program . Parents were also participants in the study . Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention . Subjects : The study enrolled 57 African-American adolescent girls ( ages 11 to 15 years ) who were overweight or obese and had at least one biological parent who was obese [ body mass index ( BMI ) > 30 kg/m2 ] . Of the 57 participants , 50 ( 88 % ) completed the 6-month trial . Measurements : Outcome data , including BMI , body weight , body composition , dietary intake , and weight loss behaviors were collected at baseline and 6-months later . A computer server tracked utilization of the websites . Participation in the program was measured by number of “ hits ” on the website . Results : Compared to the control condition , adolescents in the behavioral treatment lost more body fat ( group difference = 1.6 % body fat ) and parents lost significantly more body weight ( group difference = 2.1 kg ) . Utilization of the behavioral website by adolescents and parents was associated with positive outcome . Dietary fat intake was lowered for adolescents and parents in the behavioral treatment group . Conclusion : An internet-based behavioral intervention was superior to internet-based health education and yielded decreased body fat for adolescent girls and decreased body weight for parents OBJECTIVE Go Girls was a church-based nutrition and physical activity program design ed for overweight African-American ( AA ) adolescent females . RESEARCH METHODS AND PROCEDURES Ten predominantly middle-socioeconomic churches were r and omized to either a high-intensity ( 20 to 26 sessions ) or moderate-intensity ( six sessions ) culturally tailored behavioral group intervention delivered over 6 months . Each session included an experiential behavioral activity , approximately 30 minutes of physical activity , and preparation and tasting of healthy foods . In the high-intensity group , girls also received four to six telephone counseling calls . From the 10 churches , 123 girls completed baseline and 6-month post-test assessment s. The primary outcome was BMI ; secondary outcomes included waist and hip circumferences , percentage body fat estimated by bioimpedance , serum insulin , glucose , and lipids , and cardiovascular fitness at 6-month follow-up . Selected measures were also collected at 1-year follow-up . RESULTS At 6-month follow-up , the net difference between the high- and moderate-intensity groups was 0.5 BMI units . This difference was not statistically significant ( p = 0.20 ) . There were no significant group differences in secondary outcomes . Girls in the high-intensity condition , however , who attended more than three-quarters of the sessions had significantly lower BMI and percentage body fat relative to girls in the high-intensity group who attended fewer sessions . Findings at 1-year follow-up mirrored those at 6 months . DISCUSSION We concluded that the intervention was not effective in reducing adiposity , although there were some positive findings among high attenders . Despite the null result , the intervention was generally well received by participants . Future interventions may require greater dose and a more structured dietary change program Obesity prevalence is increasing in the U.S. , especially among children and minority population s. This report describes the design and baseline data of the ongoing Girls health Enrichment Multi-site Studies ( GEMS ) trial ( Memphis site ) , which is testing the efficacy of a 2-year family-based intervention to reduce excessive increase in body mass index ( BMI ) . This r and omized , controlled trial conducted at community centers in Memphis , Tennessee requires major measurements at baseline and at 12 and 24 months post-r and omization . The participants are healthy African-American girls and one parent/caregiver of each girl . Participating girls are of ages 8 - 10 years , with BMI > or=25th percentile of the CDC 2000 growth charts or with one overweight or obese parent/caregiver ( BMI > or=25 kg/m(2 ) ) . The active intervention is design ed to prevent excessive weight gain by promoting healthy eating habits and increasing physical activity . An alternative intervention ( comparison group ) promotes general self-esteem and social efficacy . The main outcome measure is the difference between the two treatment groups in the change in BMI at 2 years . Three hundred and three girls have been r and omly assigned to receive the test intervention ( n=153 ) or the alternative intervention ( n=150 ) . The two groups do not differ in baseline characteristics . At the time of enrollment , the mean age was 9 years , the mean BMI was 22 kg/m(2 ) ( mean BMI percentile=77 th ) , and 41 % were overweight ( BMI > /=95th percentile using CDC 2000 growth charts ) . Participants ' intake of fruits and vegetables ( 1.3 serving/day ) and fats ( 36 % kcal ) , and their participation in moderate-to-vigorous physical activity ( 20 min/day ) , did not meet national recommendations . The GEMS obesity prevention intervention targets improved diet and increased physical activity to reduce excessive weight gain in healthy African-American girls of ages 8 - 10 Obesity is a risk factor for a variety of chronic diseases . Although weight loss may reduce these risks , weight loss programs design ed for black women have yielded mixed results . Studies suggest that religion/spirituality is a prominent component of black culture . Given this , the inclusion of religion/spirituality as an active component of a weight loss program may enhance the benefits of the program . The role of religion/spirituality , however , has not been specifically tested as a mechanism that enhances the weight loss process . This paper presents the results of " Faith on the Move , " a r and omized pilot study of a faith-based weight loss program for black women . The goals of the study were to estimate the effects of a 12-week culturally tailored , faith-based weight loss intervention on weight loss , dietary fat consumption and physical activity . The culturally tailored , faith-based weight loss intervention was compared to a culturally tailored weight loss intervention with no active faith component . Fifty-nine overweight/obese black women were r and omized to one of the two interventions . Although the results were not statistically significant , the effect size suggests that the addition of the faith component improved results . These promising preliminary results will need to be tested in an adequately powered trial OBJECTIVES The purpose of this study was to determine the feasibility of implementing a diabetes prevention program ( DPP ) in a rural African-American church . METHODS A six-session DPP , modeled after the successful National Institutes of Health ( NIH ) DPP , was implemented in a rural African-American church . Adult members of the church identified as high risk for diabetes , based on results of a risk question naire , were screened with a fasting glucose . Persons with prediabetes , a fasting glucose of 100 - 125 mg/dL , participated in the six-session , Lifestyle Balance Church DPP . The primary outcomes were attendance rates and changes in fasting glucose , weight and body mass index measured at baseline , six- and 12-month follow-up . RESULTS Ninety-nine adult church members were screened for diabetes risk . Eleven had impaired fasting glucose . Ten of 11 participated in the six-session intervention , for an attendance rate of 78 % . After the intervention and 12-month follow-up , there was a mean weight loss of 7.9 lbs and 10.6 lbs , respectively . CONCLUSIONS This pilot project suggests that a modified six-session DPP can be translated to a group format and successfully implemented in a church setting . Further r and omized studies are needed to determine the effectiveness of such an intervention This article reports on the development and pilot feasibility testing of a culturally competent intervention of education and care for black women with type 2 diabetes mellitus ( T2DM ) . Using a one group , pretest posttest quasi-experimental design , the intervention was tested with a convenience sample of 25 community black women with T2DM . The conceptual basis , process , and content of the intervention as well as the feasibility and acceptability of study material s and methods are described . Significant improvements from baseline to 3 months were observed in measures of glycemic control , weight , body mass index , and diabetes-related emotional distress . The findings suggest that a culturally sensitive intervention of nurse practitioner diabetes care and education is beneficial for black women with T2DM , result ing in program attendance , kept appointments , improved glycemic control and weight , and decreased diabetes-related emotional distress In this study the authors examined psychosocial variables as mediators for fruit and vegetable ( FV ) intake in a clustered , r and omized effectiveness trial conducted in African American churches . The study sample included 14 churches ( 8 intervention and 6 control ) with 470 participants from the intervention churches and 285 participants from the control churches . The outcome of FV intake and the proposed mediators were measured at baseline and at 6-month follow-up . Structural equation modeling indicated that the intervention had direct effects on social support , self-efficacy , and autonomous motivation ; these variables also had direct effects on FV intake . Applying the M. E. Sobel ( 1982 ) formula to test significant mediated effects , the authors confirmed that social support and self-efficacy were significant mediators but that autonomous motivation was not . Social support and self-efficacy partially mediated 20.9 % of the total effect of the intervention on changes in FV intake . The results support the use of strategies to increase social support and self-efficacy in dietary intervention programs OBJECTIVE To assess patterns of recruitment into a community-based NCI-funded physical activity and dietary lifestyle change program targeting African-American women . DESIGN Acquisition of a convenience sample to be screened for participation in a r and omized , controlled prevention intervention . SETTING African-American-owned and -operated health club located in an area of Los Angeles in which African Americans are concentrated . PARTICIPANTS 893 African-American women . RECRUITMENT STRATEGIES : Social networking/word-of-mouth , staff presentations , mass and targeted media , and physician referral . MAIN OUTCOME MEASURE Completion of screening question naire indicating a desire to enroll in the study . Screening question naire domains included self-reported height and weight , recent participation in organized weight loss programs , ability to walk one mile unassisted , current medication use , smoking status , personal medical history of cancer , sociodemographic variables , and recruitment source . RESULTS Sociodemographic and anthropometric characteristics distinguished between respondents obtained through different recruitment strategies . In particular , women with a higher body mass index ( BMI ) were more likely than those with lower BMI s ( P = .014 ) to be recruited through more personalized methods ( eg , social networking ) . CONCLUSIONS Culturally tailored recruitment strategies are critical in securing the participation of members of " hard-to-reach " population s , who are both under-represented in health promotion research and at high risk for chronic diseases The purpose of this study was to provide a culturally specific intervention program for African-American women to alter selected behavioral risk factors , psychosocial responses , and breast self-care variables . Two primary directional hypotheses were tested with an alpha set at 0.05 . These hypotheses were : ( 1 ) a Culturally Appropriate Breast Educational Intervention Program ( CABHEIP ) will lower selected behavioral risk factors ( high fat intake , inadequate amount of physical activity , inadequate fiber intake ) and selected psychosocial responses ( perceived stress , negative coping , low self-efficacy , perceived barriers to Breast Self Examination [ BSE ] and Clinical Breast Examination [ CBE ] ) in African-American women , 20 to 40 years of age , who participate in the program as compared to whose who do not participate ; and ( 2 ) a CABHEIP will raise compliance with BSE , proficiency of BSE , and perceived benefits of BSE and CBE in African-American women , 20 to 40 years of age , who participate in the program as compared to those who do not participate . A sample of 120 ( N = 120 ) African-American women was r and omly assigned to the control and treatment groups ( 60 women per group ; ( n = 60 intervention group ; n = 60 attention control group ) . The sample was obtained from a population of African-American women from four southern and three central Mississippi counties . The intervention group , in clusters of 3 to 9 women , received education on breast cancer , breast self-exams , healthy eating , exercise , and stress management ; and heard stories from breast cancer survivors . The attention control group , in clusters of 3 to 8 women , received education on poison control in the home environment . Data was collected and analyzed using descriptive statistics , correlation coefficients , and repeated measures of analysis of covariance ( ANCOVA ) controlling for covariates . Significant differences between groups for BSE proficiency I ( p < 0.0001 ) , BSE proficiency II ( p = 0.013 ) , and benefit BSE ( p = 0.053 ) were found . Compliance for BSE approached significance between groups ( p = 0.053 ) . Significance to nursing is that education can change outcomes in health promotion for breast cancer in African-American women . Further studies with similar interventions and larger sample sizes are needed to determine other avenues to decrease modifiable risk factors for breast cancer in African-American women BACKGROUND Despite the increased health risks for obese Black women , relatively little research has explored physical activity and nutrition interventions for these women . This article describes the recruitment strategies used in a program design ed specifically for obese Black women . METHODS Recruitment of Black women age 30 to 65 years with body mass indices between 30 kg/m2 and 50 kg/m2was completed using in-person recruitment and flyers within 2 miles of the intervention site along with mass e-mails within the sponsoring university system . Medical clearance from a physician was an eligibility requirement because of Institutional Review Board safety concerns . RESULTS Of the 690 women who were screened , 213 ( 31 % ) were eligible and r and omized . The most common reason for exclusion was failure to return a medical clearance form ( n = 167 , 39 % of ineligible ) . Different rates of efficiency were noted across recruitment approaches . CONCLUSIONS Black women were successfully recruited using in-person community recruitment , e-mail , and community flyers within close proximity to the intervention site . Careful consideration should be given to the advantages and disadvantages of various recruitment strategies that might not generalize across studies The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline . Thirdly , guideline users are often not clear about the implication s of the grading system . They misinterpret the grade of recommendation as relating to its importance , rather than to the strength of the supporting evidence , and may therefore fail to give due weight to low grade recommendations . # # # # Summary points A revised system of determining levels of evidence and grade s Despite multidisciplinary efforts to control the nation 's obesity epidemic , obesity has persisted as one of the U.S. 's top public health problems , particularly among African Americans . Innovative approaches to address obesity that are sensitive to the unique issues of African Americans are needed . Thus , a faith-based weight-loss intervention using a community-based participatory research approach was developed , implemented , and evaluated with a rural African American faith community . A two-group , quasi-experimental , delayed intervention design was used , with church as the unit of assignment ( treatment n = 2 , control n = 2 ) and individual as the unit of observation ( treatment n = 36 , control n = 37 ) . Weekly small groups led by trained community members met for 8 weeks and emphasized healthy nutrition , physical activity , and faith 's connection with health . The mean weight loss of the treatment group was 3.60 ± 0.64 lbs . compared to the 0.59 ± 0.59-lb loss of the control group BACKGROUND Given the relatively low spontaneous quit rates and poor treatment outcomes among African American smokers , this study was design ed to evaluate the effects of a multimodal culturally relevant intervention for smoking behavior change compared with a self-help strategy among urban African Americans in Baltimore churches . METHOD This r and omized controlled trial in urban African American churches used the stages of change model to compare the effectiveness of two interventions in moving smokers along a continuum toward smoking cessation . Twenty-two churches were r and omly assigned to either an intensive culturally specific intervention or a minimal self-help intervention . Smokers were interviewed at baseline church health fairs and at a 1-year follow-up . Self-reported quitters at follow-up were evaluated using saliva cotinine and exhaled carbon monoxide levels ( CO ) . Stages of change were measured by applying a st and ardized stages of change instrument to individual interview response sequences . Analysis compared the two intervention groups at 1-year follow-up with baseline stages . Outcomes included quit rates and positive progress along the stages of change . RESULTS Multiple logistic regression results , controlling for intrachurch correlation and demographic and baseline smoking characteristics , showed that the multimodal cultural intervention group was more likely to make positive progress along the stages of change continuum , compared with self-help intervention group ( OR = 1.68 ; P = 0.04 ) . Church denomination and intervention status interacted in the multivariate model ; Baptists in the intensive intervention were three times ( OR = 3.23 ; P = 0.010 ) more likely to make progress than all the other denomination groups . CONCLUSION The multimodal culturally relevant intervention was more likely than a self-help intervention to positively influence smoking behavior . This is the first community-based intervention study to report progress along the stages of change as a process-oriented measure of success . It is notable that a spiritually based model focusing on environmental sanctions was more likely than a st and ard church disseminated self-help intervention to positively influence smoking behavior in an urban African American population This trial evaluated a 6-month , church-based aerobic exercise intervention to increase physical activity among African American women relative to a health lecture and stretching condition . Participants were 196 women from 11 churches . Churches were r and omized to an Aerobic Exercise or Health N Stretch intervention . Results indicated that physical activity was not different in Aerobic Exercise and Stretch N Health , although attendance in both interventions was low . Both groups reduced physical inactivity prevalence from baseline ( 26 % and 18 % decline , respectively ) . Higher baseline social support predicted change in physical activity , regardless of treatment assignment . Research ers must continue to work to identify successful intervention strategies to increase physical activity in African American women who are at disproportionate risk of chronic diseases associated with physical inactivity The overwhelming evidence about the role lifestyle plays in mortality , morbidity , and quality of life has pushed the young field of modern health promotion to center stage . The field is beset with intense debate about appropriate evaluation method ologies . Increasingly , r and omized design s are considered inappropriate for health promotion research . We have review ed criticisms against r and omized trials that raise philosophical and practical issues , and we will show how most of these criticisms can be overcome with minor design modifications . By providing rebuttal to arguments against r and omized trials , our work contributes to building a sound method ological base for health promotion research The WATCH ( Wellness for African Americans Through Churches ) Project was a r and omized trial comparing the effectiveness of 2 strategies to promote colorectal cancer preventive behaviors among 587 African American members of 12 rural North Carolina churches . Using a 2 X 2 factorial research design , the authors compared a tailored print and video ( TPV ) intervention , consisting of 4 individually tailored newsletters and targeted videotapes , with a lay health advisor ( LHA ) intervention . Results showed that the TPV intervention significantly improved ( p < .05 ) fruit and vegetable consumption ( 0.6 servings ) and recreational physical activity ( 2.5 metabolic task equivalents per hour ) and , among those 50 and older ( n = 287 ) , achieved a 15 % increase in fecal occult blood testing screening ( p = .08 ) . The LHA intervention did not prove effective , possibly because of suboptimal reach and diffusion Objective . To determine the effects of a mass media campaign on the levels of physical activity among children 9 to 13 years of age . Design . A prospect i ve , longitudinal , quasi-experimental design was used . A baseline survey was conducted in April to June 2002 , before the launch of VERB advertising . R and om-digit-dialing methods were used to survey a nationally representative sample of children and parents . The follow-up survey was repeated with the same cohort of children and parents in April to June 2003 . Propensity scoring was used to determine the campaign ’s effects on awareness and physical activity behaviors . Setting . United States . Participants . A total of 3120 parent-child dyads . Intervention . The VERB campaign is a multiethnic campaign that combines paid advertisements with school and community promotions and Internet activities to encourage children 9 to 13 years of age to be physically active every day . Launched in 2002 by the Centers for Disease Control and Prevention , VERB uses commercial marketing methods to advertise being physically active as cool , fun , and a chance to have a good time with friends . Using the VERB br and , paid advertising ran nationally from June 2002 through June 2003 , targeting 9- to 13-year-old youths . Main Outcome Measures . Children ’s awareness of the campaign and self-reported estimates of free-time and organized physical activity sessions during nonschool hours in the week before the interview . Results . After 1 year , 74 % of children surveyed were aware of the VERB campaign . Levels of reported sessions of free-time physical activity increased for subgroups of children 9 to 13 years of age . A pattern of effects across 2 measures was observed for younger children ( 9–10 years of age ) , girls , children whose parents had less than a high school education , children from urban areas that were densely populated , and children who were low active at baseline . These subgroups engaged in more median weekly sessions of free-time physical activity than did children who were unaware of VERB and , as the children ’s level of VERB awareness was incrementally higher , the children engaged in incrementally more free-time physical activity sessions . The average 9- to 10-year-old youth engaged in 34 % more free-time physical activity sessions per week than did 9- to 10-year-old youths who were unaware of the campaign . A pattern of effects for organized activity was found only for children classified as low active at baseline . Conclusions . The VERB campaign achieved high levels of awareness in 1 year . Higher levels of physical activity were reported for subgroups of US children . Promoting physical activity with child-focused commercial advertising shows promise BACKGROUND Eat for Life , a multicomponent intervention to increase fruit and vegetable ( F & V ) consumption among African Americans , is delivered through African American churches . METHODS Fourteen churches were r and omly assigned to one of three treatment conditions : 1 ) comparison ; 2 ) culturally-sensitive multicomponent intervention with one phone call ; and 3 ) culturally-sensitive multicomponent intervention with four phone calls . The intervention included an 18-minute video , a project cookbook , printed health education material s , and several " cues " imprinted with the project logo and a 5 A Day message . A key element of the telephone intervention was the use of motivational interviewing , a counseling technique originally developed for addictive behaviors . Major outcomes for the trial included total F & V intake , assessed by food-frequency question naires ( FFQs ) and 24-hour recalls , and serum carotenoids . Psychosocial variables assessed included outcome expectations , barriers to F & V intake , preference for meat meals , neophobia , social support to eat more F & V , self-efficacy to eat more F & V , and nutrition knowledge . RESULTS Baseline mean F & V intakes across the three FFQs ranged from 3.45 to 4.28 servings per day . Intake based on a single 24-hour recall was 3.0 servings . Variables positively correlated with F & V intake included self-efficacy , outcome expectations , and a belief that F & V contain vitamins . Factors negatively correlated with intake include perceived barriers , meat preference , neophobia , and high-fat cooking practice s. The completion rate for the first telephone counseling call was 90 % . Completion rates for the remaining three calls ranged from 79 % to 86 % . CONCLUSION The recruitment and intervention methods of the Eat for Life study appear promising . The telephone intervention based on motivational interviewing is potentially useful for delivering dietary counseling BACKGROUND Overall incidence of breast cancer is slightly lower , but mortality rates are higher , for Black women compared to White women . Higher body mass index ( BMI ) , sedentary lifestyles , and lower compliance with recommended breast health behaviors may contribute to higher risk and mortality . METHODS A r and omized pilot intervention trial was conducted to assess feasibility and efficacy of a combined breast health/weight loss intervention for 64 overweight or obese Black women , ages 35 - 65 . The primary objectives were to determine whether a 20-week ( twice weekly ) intervention could decrease weight and dietary fat intake and increase physical activity and breast self-exam ( BSE ) proficiency . RESULTS The project was implemented in two cohorts and retention was high for both ( 96 % and 89 % , respectively ) . Both cohorts showed increased proficiency in BSE in the intervention versus the control group ( 2.4 vs. -0.4 , P<0.05 ; 3.3 vs. -0.2 , P<0.001 , respectively ) , but only cohort 2 showed decreased percent body weight ( 4.0 % decrease vs. 0.9 % increase , P<0.01 ) , increased physical activity frequency ( 2.4 vs. 0.1 times/week , P<0.05 ) , and a trend for decreased dietary fat ( -2.6 % kcal vs. 0.0 % kcal , P=0.07 ) in the intervention compared to the control group . CONCLUSION Few studies have documented weight loss among Black women , and no combined breast health/weight loss intervention has been conducted . This study documents the feasibility of recruiting , r and omizing , and retaining women in a combined intervention and demonstrated weight loss and associated lifestyle changes BACKGROUND Khush Dil was set up in Edinburgh in 2002 to manage cardiovascular risk factors in South Asians . We assessed its impact in an in-service evaluation . METHODS Between June 2002 and July 2004 , 304 South Asians attended health visitor led screening clinics . Measurements included self-report , anthropometry , blood pressure and blood tests . A total 140 subjects attended follow-up screening ( henceforth returnees ) . The outcomes relate to them . RESULTS In most respects , including ethnicity , family history , medical history and motivational stage , returnees were similar to the non-returnees , but were a little older and were more likely to be women . Between baseline and return visits , returnees reported an increased motivational status ( those in the action stage of change increased from 12 to 28 % ) and increased physical activity ( e.g. 45 % of women reported improvement at follow-up ) . Returnees had reduced their risk factor profiles at follow-up in a range of risk factors , e.g. reduction in cholesterol ( 0.19 mmol/l ; 95 % CL , 0.1 - 0.37 ) , in diastolic and systolic blood pressures ( 3.15 and 3.7 mmHg , respectively ) and in weight ( 0.61 kg ; 95 % CL , 0.22 - 1.02 ) . CONCLUSIONS The Khush Dil Project had an impact as indicated by self-report , physical measures and laboratory tests . Such initiatives now need evaluation for cost-effectiveness . Cluster r and omized controlled trials warrant consideration 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 The authors develop and test a culturally sensitive , low-intensity smoking cessation intervention for low-socioeconomic African Americans . African American adult smokers were r and omly assigned to receive either a multicomponent smoking cessation intervention comprising a printed guide , a video , and a telephone booster call or health education material s not directly addressing tobacco use . The results of the study were mixed . Although no significant effects were observed for the entire treatment cohort , the results of post hoc analyses suggest that culturally sensitive self-help smoking cessation material s plus a single phone contact can produce short-term cessation rates similar to those reported for majority population s. This conclusion should be tempered by the low completion rate for the booster call and several design limitations of the study This study examined a culturally-specific dance intervention on functional capacity in African American women at three time points . The intervention was two times per week for 8 weeks using two African American churches r and omly assigned to either the experimental or comparison group , had 126 participants , ages 36 - 82 years . Analysis of covariance revealed that both groups improved over time and the only significant difference between groups was at 18 weeks . The increase at 18 weeks in the experimental group remained when controlling for baseline covariates . This study supported culturally-specific dance as an intervention to improve functional capacity in African American women This study examined the relationship between stress and the likelihood of quitting among 300 urban African American smokers enrolled in the placebo arm of a controlled r and omized trial assessing the efficacy of bupropion for smoking cessation . Participants were predominantly female , middle-aged , and of lower income . Participants received 7 weeks of placebo treatment and counseling as well as a self-help guide . Quit status and stress , measured with the Perceived Stress Scale and an adapted Hassles Index , were assessed at baseline , end of treatment , and 6 month follow-up . Results indicated that although baseline stress did not predict quitting at later visits , higher concurrent stress levels were associated with not being abstinent . Furthermore , changes ( reductions ) in perceived stress from baseline also predicted abstinence at the end of treatment . Results suggest that methods to help African Americans cope with stress as they attempt to quit smoking may prevent relapse to smoking Cardiovascular disease ( CVD ) is the number one cause of death in the United States . Obesity is highly related to CVD risk , especially in African American women . This study explored the efficacy of a culturally specific obesity prevention program . Design ed for low-income , inner-city African American girls and their mothers , the program addressed the importance of eating a low-fat , low-cholesterol diet and increasing activity . Mother-daughter dyads were r and omly assigned to a 12-week treatment or an attention placebo group . Participants were assessed at pre- and posttreatment on dietary intake , including daily fat intake , daily saturated fat intake , percentage of daily calories from fat , and daily cholesterol intake . Results showed significant differences between the treatment and control mothers for daily saturated fat intake and percentage of calories from fat . Differences among treatment and control groups were also noted for the daughters on percentage of daily calories from fat . Implication s of the findings for developing culturally specific health risk reduction programs are discussed UNLABELLED BACKGROUND ; The increasing prevalence of overweight among children in the United States presents a national health priority . Higher rates of overweight/obesity among minority women place their children at increased risk . Although increased rates of overweight are observed in 4- to 5-year-old children , they are not observed in 2- to 3-year-old children . Therefore , early prevention efforts incorporating families are critical . METHODS The primary aim of Hip-Hop to Health Jr. is to alter the trajectory toward overweight/obesity among preschool African-American and Latino children . This 5-year r and omized intervention is conducted in 24 Head Start programs , where each site is r and omized to either a 14-week dietary/physical activity intervention or a general health intervention . RESULTS This paper presents the rationale and design of the study . Efficacy of the intervention will be determined by weight change for the children and parent/caretaker . Secondary measures include reductions in dietary fat and increases in fiber , fruit/vegetable intake , and physical activity . Baseline data will be presented in future papers . CONCLUSIONS The problem of overweight/obesity is epidemic in the United States . Behaviors related to diet and physical activity are established early in life and modeled by family members . Early intervention efforts addressing the child and family are needed to prevent obesity later in life . This paper describes a comprehensive , family-oriented obesity prevention program for minority preschool children OBJECTIVE To determine knowledge about smoking , reasons for smoking , and reasons for wishing to quit and the association of these variables with abstinence at ten weeks and six months . DESIGN Descriptive study and longitudinal intervention . SETTING Inner-city public hospital clinics . PARTICIPANTS 410 African-American cigarette smokers interested in quitting were surveyed at baseline and subsequently enrolled into a double-blind , placebo-controlled , r and omized trial of the transdermal nicotine patch . MAIN OUTCOME MEASURES Descriptive information about smoking knowledge , reasons for smoking , and reasons for wishing to quit , and association of these variables with abstinence at 10 weeks and 6 months . RESULTS Among the 410 patients r and omized , mean age was 48 years , 61 % were female , 41 % had less than a high school education , 51 % had an annual household income less than $ 8,000 , and the average number of cigarettes smoked a day was twenty . The average number of questions answered correctly was nine out of eleven ( 84 % ) . The most cited reason for smoking was relaxation/tension reduction and the least cited were stimulation and h and ling of the cigarette . Ninety-nine percent of patients stated they wished to quit for health reasons . Knowledge , reasons for smoking , and reasons for wishing to quit were not significantly associated with 10-week or 6-month abstinence . CONCLUSIONS In this group of inner-city African-American smokers , knowledge about cigarette smoking was high . Reasons for smoking were related to relaxation , craving , and pleasure , and reasons for wishing to quit were largely health-related . Knowledge , reasons for smoking , and reasons for wishing to quit were not associated with 10 week or 6 month abstinence . Since knowledge about smoking is already high , future efforts should be directed at promoting cessation through proven behavioral and pharmacological approaches , rather than didactic patient education BACKGROUND The Alliance of Black Churches Health Project was begun in an effort to address the health problems of the African-American residents of two rural Virginia counties . Smoking cessation was chosen as the principal target behavior in one county . Church coalitions were chosen as the principal organizations through which to implement the interventions . METHOD A smoking cessation program was design ed that combined one-on-one counseling with self-help material s and community-wide activities . To provide these services , up to two smoking cessation counselors were trained from participating churches . To evaluate the impact , population -based cohorts of smokers were assembled in each county using a door-to-door survey . Respondents were recontacted after 18 months . Smoking cessation ( 1-month continuous abstinence ) , stages of change , and exposure to the interventions were assessed . RESULTS The overall smoking prevalence at baseline was 25.8 % . At follow-up , the smoking cessation rate in the intervention county was 9.6 % and in the control county 5.4 % ( P = 0.18 ) . Among those attending church once a month or more , the respective quit rates were 10.5 % and 5.9 % ( P = 0.20 ) . There was significantly more progress along the stages of change in the intervention than in the control county . There was also higher awareness of and contact with smoking cessation programs in the former compared with the latter . CONCLUSION Smoking cessation interventions for African Americans can be successfully implemented through a church coalition . The interventions were associated with significant progress along the stages of cessation . Although the quit rate was higher in the intervention community , the difference was not significant BACKGROUND The High 5 , Low Fat Program ( H5LF ) for African American parents was developed in partnership with the Parents As Teachers program , and was design ed to test a dietary intervention appropriate for national adoption . METHODS H5LF used a group r and omized , nested cohort design with 738 parents . Consistent with organizational goals and methods , parent educators delivered a dietary change program via personal visits , newsletters , and group meetings . Primary outcomes were reducing percentage calories from fat and increasing fruit and vegetable consumption among participating parents ; intermediate aims included improving in nutrition-related skills and parental modeling of dietary behaviors . RESULTS H5LF parents achieved a 0.53 increase in fruit and vegetable consumption ( P = 0.03 ) , and a higher proportion of H5LF parents reduced their intake to less than 30 % calories from fat ( chi(2 ) = 4.8 , P < 0.03 ; -1.7 % calories from fat , p = 0.07 ) and improved performance of dietary behaviors ( F = 14.2 , P = 0.004 ) . Improvements in parental modeling were not statistically significant . CONCLUSIONS H5LF is an effective intervention that is appropriate for national adoption by over 2000 Parents As Teachers sites with the potential to impact dietary intake of African American parents nationwide |
13,935 | 29,790,638 | The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with antidiabetic agents compared with placebo .
Pioglitazone 15 to 30 mg demonstrated the greatest efficacy compared to placebo in network meta- analysis .
No significant differences in acceptability were identified when comparing agents with each other and with placebo .
The current findings indicate a pro-cognitive class effect of antidiabetic agents in AD/MCI . | This study ( registered with PROSPERO , CRD42018085967 ) compares the efficacy ( i.e. pro-cognitive effects ) and acceptability of antidiabetic agents for Alzheimer 's disease ( AD ) and mild cognitive impairment ( MCI ) . | OBJECTIVE To investigate the associations of metformin , serum vitamin B12 , calcium supplements , and cognitive impairment in patients with diabetes . RESEARCH DESIGN AND METHODS Participants were recruited from the Primary Research in Memory ( PRIME ) clinics study , the Australian Imaging , Biomarkers and Lifestyle ( AIBL ) study of aging , and the Barwon region of southeastern Australia . Patients with Alzheimer disease ( AD ) ( n = 480 ) or mild cognitive impairment ( n = 187 ) and those who were cognitively intact ( n = 687 ) were included ; patients with stroke or with neurodegenerative diseases other than AD were excluded . Subgroup analyses were performed for participants who had either type 2 diabetes ( n = 104 ) or impaired glucose tolerance ( n = 22 ) . RESULTS Participants with diabetes ( n = 126 ) had worse cognitive performance than participants who did not have diabetes ( n = 1,228 ; adjusted odds ratio 1.51 [ 95 % CI 1.03–2.21 ] ) . Among participants with diabetes , worse cognitive performance was associated with metformin use ( 2.23 [ 1.05–4.75 ] ) . After adjusting for age , sex , level of education , history of depression , serum vitamin B12 , and metformin use , participants with diabetes who were taking calcium supplements had better cognitive performance ( 0.41 [ 0.19–0.92 ] ) . CONCLUSIONS Metformin use was associated with impaired cognitive performance . Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes . Prospect i ve trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease ( AD ) , and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD . Given this association , we hypothesized that the central nervous system – penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and /or symptomatic therapy for AD , and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid ( CSF ) , neuroimaging , and cognitive biomarkers . Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were r and omized to receive metformin then placebo for 8 weeks each or vice versa . CSF and neuroimaging ( Arterial Spin Label MRI ) data were collected for biomarker analyses , and cognitive testing was performed . Metformin was found to be safe , well-tolerated , and measureable in CSF at an average steady-state concentration of 95.6 ng/mL. Metformin was associated with improved executive functioning , and trends suggested improvement in learning/memory and attention . No significant changes in cerebral blood flow were observed , though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure . Further study of these findings is warranted INTRODUCTION Type 2 diabetes ( DM-2 ) increases the risk of developing Alzheimer´s disease ( AD ) , and patients with AD are more likely to develop DM-2 . DM-2 and AD share some pathophysiological features . In AD , amyloid-β ( Aβ ) is accumulated as extracellular plaques in the gray matter of the brain , while in DM-2 islet amyloid polypeptide ( IAPP ) is accumulated in the pancreas . Premature cellular degeneration is seen in both diseases . Glucagon-like peptide-1 ( GLP-1 ) reduces the amount of Aβ and improves cognition in animal studies . The present study tests the hypothesis that treatment with the long-acting GLP-1 receptor agonist liraglutide affects the accumulation of Aβ in patients with AD . MATERIAL AND METHODS This is a r and omized , controlled , double-blinded intervention study with AD patients treated for six months with liraglutide ( n = 20 ) or placebo ( n = 20 ) . The primary outcome is change in deposition of Aβ in the central nervous system ( CNS ) by Pittsburgh compound B positron emission tomography ( PET ) . The secondary outcome is evaluation of cognition using a neuro-psychological test battery , and examination of changes in glucose uptake in the CNS by 18F-fluoro-deoxy-glucose PET . Finally , a perfusion-weighted magnetic resonance imaging with contrast will be performed to evaluate blood flow . CONCLUSION No registered drug affects the deposition of Aβ in the brain of AD patients . Our goal is to find a new therapeutic agent that alters the pathophysiology in AD patients by decreasing the formation of Aβ plaques and thereby presumably improves the cognitive function . FUNDING The trial is investigator-initiated and investigator-driven and is supported by Novo Nordisk Sc and inavia . TRIAL REGISTRATION Clinical Trials.gov : NCT01469351 OBJECTIVE To examine the effects of intranasal insulin administration on cognition , function , cerebral glucose metabolism , and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease ( AD ) . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Clinical research unit of a Veterans Affairs medical center . PARTICIPANTS The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment ( n = 64 ) or mild to moderate AD ( n = 40 ) . Intervention Participants received placebo ( n = 30 ) , 20 IU of insulin ( n = 36 ) , or 40 IU of insulin ( n = 38 ) for 4 months , administered with a nasal drug delivery device ( Kurve Technology , Bothell , Washington ) . MAIN OUTCOME MEASURES Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score , and secondary measures included the Alzheimer Disease 's Assessment Scale-cognitive subscale ( ADAS-cog ) score and the Alzheimer 's Disease Cooperative Study -activities of daily living ( ADCS-ADL ) scale . A subset of participants underwent lumbar puncture ( n = 23 ) and positron emission tomography with fludeoxyglucose F 18 ( n = 40 ) before and after treatment . RESULTS Outcome measures were analyzed using repeated- measures analysis of covariance . Treatment with 20 IU of insulin improved delayed memory ( P < .05 ) , and both doses of insulin ( 20 and 40 IU ) preserved caregiver-rated functional ability ( P < .01 ) . Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD ( P < .05 ) . Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group , but , in exploratory analyses , changes in memory and function were associated with changes in the Aβ42 level and in the tau protein-to-Aβ42 ratio in cerebrospinal fluid . Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal , frontal , precuneus , and cuneus regions and insulin-minimized progression . No treatment-related severe adverse events occurred . CONCLUSIONS These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD . Trial Registration clinical trials.gov Identifier : NCT00438568 |
13,936 | 30,256,829 | Some studies reported that biomarkers were cost-effective , while their corresponding therapies were not cost-effective .
Conclusion Cancer biomarkers for targeted therapies in mCRC were mostly found to be cost-effective ; otherwise , they at least improved the cost-effectiveness of targeted therapies by saving some costs .
However , this did not necessarily make their corresponding therapies cost-effective .
While companion biomarkers reduced therapy costs , the savings were not sufficient to make the corresponding agents cost-effective . | Background Recent advances in targeted therapies have raised expectations that the clinical application of biomarkers would improve patient ’s health outcomes and potentially save costs .
However , the cost-effectiveness of biomarkers remains unclear irrespective of the cost-effectiveness of corresponding therapies .
It is thus important to determine whether biomarkers for targeted therapies provide good value for money .
This study systematic ally review s economic evaluations of biomarkers for targeted therapies in metastatic colorectal cancer ( mCRC ) and assesses the cost-effectiveness of predictive biomarkers in mCRC . | Purpose .To provide a practical quantitative tool for appraising the quality of cost-effectiveness ( CE ) studies . Methods .A committee comprised of health economists selected a set of criteria for the instrument from an item pool . Data collected with a conjoint analysis survey on 120 international health economists were used to estimate weights for each criterion with a r and om effects regression model . To vali date the grading system , a survey was sent to 60 individuals with health economics expertise . Participants first rated the quality of three CE studies on a visual analogue scale , and then evaluated each study using the grading system . Spearman rho and Wilcoxon tests were used to detect convergent validity and analysis of covariance ( ANCOVA ) for discriminant validity . Agreement between the global rating by experts and the grading system was also examined . Results .Sixteen criteria were selected . Their coefficient estimates ranged from 1.2 to 8.9 , with a sum of 93.5 on a 100-point scale . The only insignificant criterion was “ use of subgroup analyses . ” Both convergent validity and discriminant validity of the grading system were shown by the results of the Spearman rho ( correlation coefficient = 0.78 , P < 0.0001 ) , Wilcoxon test ( P = 0.53 ) , and ANCOVA ( F3,146 = 5.97 , P = 0.001 ) . The grading system had good agreement with global rating by experts . Conclusions . The instrument appears to be simple , internally consistent , and valid for measuring the perceived quality of CE studies . Applicability for use in clinical and re source allocation decision-making deserves further study UNLABELLED In February 2010 , the Medical Advisory Secretariat ( MAS ) began work on evidence -based review s of the literature surrounding three pharmacogenomic tests . This project came about when Cancer Care Ontario ( CCO ) asked MAS to provide evidence -based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario . Evidence -based analyses have been prepared for each of these technologies . These have been completed in conjunction with internal and external stakeholders , including a Provincial Expert Panel on Pharmacogenomics ( PEPP ) . Within the PEPP , subgroup committees were developed for each disease area . For each technology , an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative ( THETA ) and is summarized within the reports . THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT : www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER : An Evidence -Based and Economic Analysis Epidermal Growth Factor Receptor Mutation ( EGFR ) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor ( TKI ) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer : an Evidence -Based and Economic Analysis K-RAS testing in Treatment Decisions for Advanced Colorectal Cancer : an Evidence -Based and Economic Analysis . OBJECTIVE The objective of this systematic review is to determine the predictive value of KRAS testing in the treatment of metastatic colorectal cancer ( mCRC ) with two anti-EGFR agents , cetuximab and panitumumab . Economic analyses are also being conducted to evaluate the cost-effectiveness of KRAS testing . CLINICAL NEED CONDITION AND TARGET POPULATION Metastatic colorectal cancer ( mCRC ) is usually defined as stage IV disease according to the American Joint Committee on Cancer tumour node metastasis ( TNM ) system or stage D in the Duke 's classification system . Patients with advanced colorectal cancer ( mCRC ) either present with metastatic disease or develop it through disease progression . KRAS ( Kristen-RAS , a member of the rat sarcoma virus ( ras ) gene family of oncogenes ) is frequently mutated in epithelial cancers such as colorectal cancer , with mutations occurring in mutational hotspots ( codons 12 and 13 ) of the KRAS protein . Involved in EGFR-mediated signalling of cellular processes such as cell proliferation , resistance to apoptosis , enhanced cell motility and neoangiogenesis , a mutation in the KRAS gene is believed to be involved in cancer pathogenesis . Such a mutation is also hypothesized to be involved in resistance to targeted anti-EGFR ( epidermal growth factor receptor with tyrosine kinase activity ) treatments such as cetuximab and panitumumab , hence , the important in evaluating the evidence on the predictive value of KRAS testing in this context . KRAS MUTATION TESTING IN ADVANCED COLORECTAL CANCER : Both cetuximab and panitumumab are indicated by Health Canada in the treatment of patients with metastatic colorectal cancer whose tumours are WT for the KRAS gene . Cetuximab may be offered as monotherapy in patients intolerant to irinotecan-based chemotherapy or in patients who have failed both irinotecan and oxaliplatin-based regimens and who received a fluoropyrimidine . It can also be administered in combination with irinotecan in patients refractory to other irinotecan-based chemotherapy regimens . Panitumumab is only indicated as a single agent after failure of fluoropyrimidine- , oxaliplatin- , and irinotecan-containing chemotherapy regimens . In Ontario , patients with advanced colorectal cancer who are refractory to chemotherapy may be offered the targeted anti-EGFR treatments cetuximab or panitumumab . Eligibility for these treatments is based on the KRAS status of their tumour , derived from tissue collected from surgical or biopsy specimens . It is believed that KRAS status is not affected by treatments , therefore , for patients for whom surgical tissue is available for KRAS testing , additional biopsies prior to treatment with these targeted agents is not necessary . For patients that have not undergone surgery or for whom surgical tissue is not available , a biopsy of either the primary or metastatic site is required to determine their KRAS status . This is possible as status at the metastatic and primary tumour sites is considered to be similar . RESEARCH QUESTION To determine if there is predictive value of KRAS testing in guiding treatment decisions with anti-EGFR targeted therapies in advanced colorectal cancer patients refractory to chemotherapy . RESEARCH METHODS LITERATURE SEARCH The Medical Advisory Secretariat followed its st and ard procedures and on May 18 , 2010 , search ed the following electronic data bases : Ovid MEDLINE , EMBASE , Ovid MEDLINE In-Process & Other Non-Indexed Citations , Cochrane Central Register of Controlled Trials , Cochrane Data base of Systematic Review s and The International Network of Agencies for Health Technology Assessment data base . The subject headings and keywords search ed included colorectal cancer , cetuximab , panitumumab , and KRAS testing . The search was further restricted to English- language articles published between January 1 , 2009 and May 18 , 2010 result ing in 1335 articles for review . Excluded were case reports , comments , editorials , non systematic review s , and letters . Studies published from January 1 , 2005 to December 31 , 2008 were identified in a health technology assessment conducted by the Agency for Healthcare Research and Quality ( AHRQ ) , published in 2010 . In total , 14 observational studies were identified for inclusion in this EBA : 4 for cetuximab monotherapy , 7 for the cetuximab-irinotecan combination therapy , and 3 to be included in the review for panitumumab monotherapy INCLUSION CRITERIA English- language articles , and English or French- language HTAs published from January 2005 to May 2010 , inclusive . R and omized controlled trials ( RCTs ) or observational studies , including single arm treatment studies that include KRAS testing . Studies with data on main outcomes of interest , overall and progression-free survival . Studies of third line treatment with cetuximab or panitumumab in patients with advanced colorectal cancer refractory to chemotherapy . For the cetuximab-irinotecan evaluation , studies in which at least 70 % of patients in the study received this combination therapy . EXCLUSION CRITERIA Studies whose entire sample was included in subsequent publications which have been included in this EBA . Studies in pediatric population s . Case reports , comments , editorials , or letters . OUTCOMES OF INTEREST Overall survival ( OS ) , medianProgression-free-survival ( PFS ) , median . Response rates . Adverse event rates . Quality of life ( QOL ) . SUMMARY OF FINDINGS OF SYSTEMATIC REVIEW : CETUXIMAB OR PANITUMUMAB MONOTHERAPY : Based on moderate GRADE observational evidence , there is improvement in PFS and OS favouring patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation . CETUXIMAB-IRINOTECAN COMBINATION THERAPY : There is low GRADE evidence that testing for KRAS may optimize survival benefits in patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation . However , cetuximab-irinotecan combination treatments based on KRAS status discount any effect of cetuximab in possibly reversing resistance to irinotecan in patients with the mutation , as observed effects were lower than for patients without the mutation . Clinical experts have raised concerns about the biological plausibility of this observation and this conclusion would , therefore , be regarded as hypothesis generating . ECONOMIC ANALYSIS Cost-effectiveness and budget impact analyses were conducted incorporating estimates of effectiveness from this systematic review . Evaluation of relative cost-effectiveness , based on a decision-analytic cost-utility analysis , assessed testing for KRAS genetic mutations versus no testing in the context of treatment with cetuximab monotherapy , panitumumab monotherapy , cetuximab in combination with irinotecan , and best supportive care . Of importance to note is that the cost-effectiveness analysis focused on the impact of testing for KRAS mutations compared to no testing in the context of different treatment options , and does not assess the cost-effectiveness of the drug treatments alone . CONCLUSIONS KRAS status is predictive of outcomes in cetuximab and panitumumab monotherapy , and in cetuximab-irinotecan combination therapy . While KRAS testing is cost-effective for all strategies considered , it is not equally cost-effective for all treatment options |
13,937 | 30,681,967 | The ABACUS is a reliable tool that can be used to determine the behavior change potential of apps .
This instrument fills a gap by allowing the evaluation of a large number of apps to be st and ardized across a range of health categories | BACKGROUND Using mobile phone apps to promote behavior change is becoming increasingly common .
However , there is no clear way to rate apps against their behavior change potential .
OBJECTIVE This study aim ed to develop a reliable , theory-based scale that can be used to assess the behavior change potential of smartphone apps . | Background Smoking is one of the top preventable causes of mortality in people with psychotic disorders such as schizophrenia . Cessation treatment improves abstinence outcomes , but access is a barrier . Mobile phone apps are one way to increase access to cessation treatment ; however , whether they are usable by people with psychotic disorders , who often have special learning needs , is not known . Objective Research ers review ed 100 r and omly selected apps for smoking cessation to rate them based on US guidelines for nicotine addiction treatment and to categorize them based on app functions . We aim ed to test the usability and usefulness of the top-rated apps in 21 smokers with psychotic disorders . Methods We identified 766 smoking cessation apps and r and omly selected 100 for review . Two independent review ers rated each app with the Adherence Index to US Clinical Practice Guideline for Treating Tobacco Use and Dependence . Then , smokers with psychotic disorders evaluated the top 9 apps within a usability testing protocol . We analyzed quantitative results using descriptive statistics and t tests . Qualitative data were open-coded and analyzed for themes . Results Regarding adherence to practice guidelines , most of the r and omly sample d smoking cessation apps scored poorly—66 % rated lower than 10 out of 100 on the Adherence Index ( Mean 11.47 , SD 11.8 ) . Regarding usability , three common usability problems emerged : text-dense content , abstract symbols on the homepage , and subtle directions to edit features . Conclusions In order for apps to be effective and usable for this population , developers should utilize a balance of text and simple design that facilitate ease of navigation and content comprehension that will help people learn quit smoking skills Background The use of mobile apps for health and well being promotion has grown exponentially in recent years . Yet , there is currently no app- quality assessment tool beyond “ star”-ratings . Objective The objective of this study was to develop a reliable , multidimensional measure for trialling , classifying , and rating the quality of mobile health apps . Methods A literature search was conducted to identify articles containing explicit Web or app quality rating criteria published between January 2000 and January 2013 . Existing criteria for the assessment of app quality were categorized by an expert panel to develop the new Mobile App Rating Scale ( MARS ) subscales , items , descriptors , and anchors . There were sixty well being apps that were r and omly selected using an iTunes search for MARS rating . There were ten that were used to pilot the rating procedure , and the remaining 50 provided data on interrater reliability . Results There were 372 explicit criteria for assessing Web or app quality that were extracted from 25 published papers , conference proceedings , and Internet re sources . There were five broad categories of criteria that were identified including four objective quality scales : engagement , functionality , aesthetics , and information quality ; and one subjective quality scale ; which were refined into the 23-item MARS . The MARS demonstrated excellent internal consistency ( alpha = .90 ) and interrater reliability intraclass correlation coefficient ( ICC = .79 ) . Conclusions The MARS is a simple , objective , and reliable tool for classifying and assessing the quality of mobile health apps . It can also be used to provide a checklist for the design and development of new high quality health apps Background Smartphones are increasingly receiving attention from public health scholars and practitioners as a means to assist individuals ’ health management . A number of smartphone apps for smoking cessation are also available ; however , little effort has been made to evaluate the content and functions of these apps employing a theoretical framework . Objective The present study aims to analyze and evaluate the contents of smoking cessation apps available in South Korea employing the self-determination theory ( SDT ) as a theoretical framework for analysis . This study analyzes the extent to which smoking cessation apps have features that satisfy the basic needs identified in the SDT , which stimulate autonomous motivation . The type of motivational goal content manifested in the apps and how the goal content was framed are also explored . By assessing the features of smoking cessation apps based on the SDT , this study aims to offer direction for improvement for these apps . Methods Out of 309 apps identified from the iTunes store and Google Play ( excluding 27 duplications ) , 175 apps were r and omly drawn and analyzed . The coding scheme was drafted by the authors based on the SDT and gain/loss framing theory and was further finely tuned through the process of coder training and by establishing intercoder reliability . Once the intercoder reliability was established , the coders divided up the rest of the sample and coded them independently . Results The analysis revealed that most apps ( 94.3 % , 165/175 ) had at least one feature that tapped at least 1 of the 3 basic needs . Only 18 of 175 apps ( 10.3 % ) addressed all 3 basic needs . For goal content , money ( 53.7 % , 94/175 ) showed the highest frequency , followed by health ( 32.0 % , 56/175 ) , time ( 7.4 % , 13/175 ) , and appearance ( 1.1 % , 2/175 ) , suggesting that extrinsic goals are more dominantly presented in smoking cessation apps . For the framing of goal content , gain framing appeared more frequently ( 41.7 % , 73/175 ) . Conclusions The results suggest that these smoking cessation apps may not sufficiently stimulate autonomous motivation ; a small number of apps addressed all 3 basic needs suggested by the SDT ( ie , autonomy , competence , and relatedness ) . The apps also tended to present extrinsic goal content ( primarily in terms of money ) over intrinsic ones ( ie , health ) by primarily adopting gain framing . Implication s of these findings for public health practitioners and consumers are discussed Mobile health ( m-health ) apps can bring health prevention and promotion to the general population . The main purpose of this article is to analyze different m-health apps for a broad spectrum of consumers by means of three different experiences . This goal was defined following the strategic documents generated by the main prospect i ve observatories of Information and Communications Technology for health . After a general exploration of the app markets , we analyze the entries of three specific themes focused in this article : type 2 diabetes , obesity , and breast-feeding . The user experiences reported in this study mostly cover the segments of ( 1 ) chronically monitored consumers through a Web mobile app for predicting type 2 diabetes ( Diab_Alert app ) , ( 2 ) information seekers through a mobile app for maternity ( Lactation app ) and partially ( 3 ) the motivated healthy consumers through a mobile app for a dietetic monitoring and assessment ( SapoFit app ) . These apps were developed by the authors of this work Background Regular physical activity is known to help prevent and treat numerous non-communicable diseases . Smartphone applications ( apps ) have been shown to increase physical activity in primary care but little is known regarding the views of patients using such technology or how such technology may change behaviour . Aim To explore patients ’ views and experiences of using smartphones to promote physical activity in primary care . Design and setting This qualitative study was embedded within the SMART MOVE r and omised controlled trial , which used an app ( Accupedo-Pro Pedometer ) to promote physical activity in three primary care centres in the west of Irel and . Method Taped and transcribed semi-structured interviews with a purpose ful sample of 12 participants formed the basis of the investigation . Framework analysis was used to analyse the data . Results Four themes emerged from the analysis : transforming relationships with exercise ; persuasive technology tools ; usability ; and the cascade effect . The app appeared to facilitate a sequential and synergistic process of positive change , which occurred in the relationship between the participants and their exercise behaviour ; the study has termed this the ‘ Know-Check-Move ’ effect . Usability challenges included increased battery consumption and adjusting to carrying the smartphone on their person . There was also evidence of a cascade effect involving the families and communities of participants . Conclusion Notwithst and ing technological challenges , an app has the potential to positively transform , in a unique way , participants ’ relationships with exercise . Such interventions can also have an associated cascade effect within their wider families and communities Objective To carry out a r and omised controlled trial on the effect of a new method of health promotion — email and mobile phone text messages ( short messaging service (SMS))—on young people 's sexual health . Methods 994 people aged 16–29 were recruited at a music festival to a non-blinded r and omised controlled trial . Participants were r and omised to either receive sexual health promotion messages ( n=507 ) or the control group ( n=487 ) . The 12-month intervention included SMS ( catchy sexually transmissible infections prevention slogans ) and emails . Participants completed question naires at the festival at baseline and online after 3 , 6 and 12 months . Outcomes were differences between the control and intervention groups in health-seeking behaviour , condom use with risky partners ( new or casual partners or two or more partners within 12 months ) and STI knowledge . Results 337 ( 34 % ) completed all three follow-up question naires and 387 ( 39 % ) completed the final question naire . At 12 months , STI knowledge was higher in the intervention group for both male ( OR=3.19 95 % CI 1.52 to 6.69 ) and female subjects ( OR=2.36 95 % CI 1.27 to 4.37 ) . Women ( but not men ) in the intervention group were more likely to have had an STI test ( OR=2.51 , 95 % CI 1.11 to 5.69 ) , or discuss sexual health with a clinician ( OR=2.92 , 95 % CI 1.66 to 5.15 ) than their control counterparts . There was no significant impact on condom use . Opinions of the messages were favourable . Conclusion This simple intervention improved STI knowledge in both sexes and STI testing in women , but had no impact on condom use . SMS and email are low cost , popular and convenient , and have considerable potential for health promotion . Clinical trial registration number Australian Clinical Trials Registry - ACTRN12605000760673 OBJECTIVE To evaluate smartphone apps intended for self-management of pain using quality assessment criteria and usability testing with prospect i ve users . DESIGN 1 ) Survey and content analysis of available apps ; and 2 ) individual usability study of two apps . SETTING University of Leeds , United Kingdom . PARTICIPANTS Forty-one participants ( aged 19 - 59 years ) with experience of chronic or recurrent pain episodes . METHODS We undertook a survey , content analysis , and quality appraisal of all currently available mobile phone apps for self-management of pain . Two apps were then selected and assessed with usability testing . RESULTS Twelve apps met the inclusion criteria . The quality assessment revealed wide variation in their clinical content , interface design , and usability to support self-management of pain . Very little user or clinician involvement was identified in the development of the apps . From the usability testing , participants stated a preference for an interface design employing a lighter color scheme and particular text font . Although very few participants were aware of pain-reporting apps prior to participation , many would consider use in the future . CONCLUSIONS Variation in app quality and a lack of user and clinician engagement in development were found across the pain apps in this research . Usability testing identified a range of user preferences . Although useful information was obtained , it would be beneficial to involve users earlier in the process of development , as well as establishing ways to merge end user requirements with evidence -based content , to provide high- quality and usable apps for self-management of pain Many smartphone applications ( apps ) for mental health ( MHapps ) are available to the public . However , few have been the subject of a r and omized controlled trial ( RCT ) , and the change processes that are hypothesized to mediate cl aim ed effects have not been previously studied . This RCT compared the efficacy of three publicly available MHapps to a waitlist control condition in a community sample , in which no MHapp was provided . The three MHapps included cognitive behavioural therapy ( CBT ) toolkit app MoodKit , mood tracking app MoodPrism , and CBT strategy app MoodMission . Participants were r and omly allocated to each condition , completed a baseline assessment , downloaded their allocated MHapp , and completed a second assessment 30 days later , with n = 226 included in final analyses ( 81 % female ; M age = 34 years ) . Compared to the control condition , all MHapp groups experienced increases in mental wellbeing , MoodKit and MoodMission groups experienced decreases in depression , and no groups experienced effects on anxiety . Mediated regressions revealed that increasing coping self-efficacy , rather than emotional self-awareness or mental health literacy , was the underlying process contributing to effects on mental health for all three MHapps . MHapps appear to be an effective solution for improving public mental health , notably by improving users ' confidence in their ability to cope |
13,938 | 30,778,352 | There was no significant difference in any grade pneumonitis and pneumonia in cytotoxic T lymphocyte-associated protein 4 ( CTLA4 ) inhibitors subgroup .
Conclusions : PD-1/PD-L1 inhibitors treatment could increase the risk of all- grade pneumonitis .
CTLA4 inhibitor ipilimumab treatment alone could not increase the risk of pneumonitis but could augment the risk of pneumonitis in PD-1/PD-L1 inhibitor treated patients .
There was no significant increase in the risk of pneumonia after either PD-1/PDL-1inhibitor or CTLA4 inhibitor treatment alone or in combination | Background : We performed a systematic review and meta- analysis to evaluate the risk of pneumonitis and pneumonia associated with immune checkpoint inhibitors ( ICIs ) for solid tumors . | BACKGROUND Treatments for small-cell lung cancer ( SCLC ) after failure of platinum-based chemotherapy are limited . We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens . METHODS The SCLC cohort of this phase 1/2 multicentre , multi-arm , open-label trial was conducted at 23 sites ( academic centres and hospitals ) in six countries . Eligible patients were 18 years of age or older , had limited-stage or extensive-stage SCLC , and had disease progression after at least one previous platinum-containing regimen . Patients received nivolumab ( 3 mg/kg bodyweight intravenously ) every 2 weeks ( given until disease progression or unacceptable toxicity ) , or nivolumab plus ipilimumab ( 1 mg/kg plus 1 mg/kg , 1 mg/kg plus 3 mg/kg , or 3 mg/kg plus 1 mg/kg , intravenously ) every 3 weeks for four cycles , followed by nivolumab 3 mg/kg every 2 weeks . Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg . Depending on tolerability , patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . The primary endpoint was objective response by investigator assessment . All analyses included patients who were enrolled at least 90 days before data base lock . This trial is ongoing ; here , we report an interim analysis of the SCLC cohort . This study is registered with Clinical Trials.gov , number NCT01928394 . FINDINGS Between Nov 18 , 2013 , and July 28 , 2015 , 216 patients were enrolled and treated ( 98 with nivolumab 3 mg/kg , three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg ) . At data base lock on Nov 6 , 2015 , median follow-up for patients continuing in the study ( including those who had died or discontinued treatment ) was 198·5 days ( IQR 163·0 - 464·0 ) for nivolumab 3 mg/kg , 302 days ( IQR not calculable ) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 361·0 days ( 273·0 - 470·0 ) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 260·5 days ( 248·0 - 288·0 ) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . An objective response was achieved in ten ( 10 % ) of 98 patients receiving nivolumab 3 mg/kg , one ( 33 % ) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 14 ( 23 % ) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and ten ( 19 % ) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . Grade 3 or 4 treatment-related adverse events occurred in 13 ( 13 % ) patients in the nivolumab 3 mg/kg cohort , 18 ( 30 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort , and ten ( 19 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( none vs 5 [ 8 % ] vs none ) and diarrhoea ( none vs 3 [ 5 % ] vs 1 [ 2 % ] ) . No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event . Six ( 6 % ) patients in the nivolumab 3 mg/kg group , seven ( 11 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group , and four ( 7 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events . Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events ( myasthenia gravis and worsening of renal failure ) , and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis . INTERPRETATION Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC . These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 r and omised controlled trials in SCLC . FUNDING Bristol-Myers Squibb BACKGROUND Ipilimumab is an approved treatment for patients with advanced melanoma . We aim ed to assess ipilimumab as adjuvant therapy for patients with completely resected stage III melanoma at high risk of recurrence . METHODS We did a double-blind , phase 3 trial in patients with stage III cutaneous melanoma ( excluding lymph node metastasis ≤1 mm or in-transit metastasis ) with adequate resection of lymph nodes ( ie , the primary cutaneous melanoma must have been completely excised with adequate surgical margins ) who had not received previous systemic therapy for melanoma from 91 hospitals located in 19 countries . Patients were r and omly assigned ( 1:1 ) , central ly by an interactive voice response system , to receive intravenous infusions of 10 mg/kg ipilimumab or placebo every 3 weeks for four doses , then every 3 months for up to 3 years . Using a minimisation technique , r and omisation was stratified by disease stage and geographical region . The primary endpoint was recurrence-free survival , assessed by an independent review committee , and analysed by intention to treat . Enrollment is complete but the study is ongoing for follow-up for analysis of secondary endpoints . This trial is registered with EudraCT , number 2007 - 001974 - 10 , and Clinical Trials.gov , number NCT00636168 . FINDINGS Between July 10 , 2008 , and Aug 1 , 2011 , 951 patients were r and omly assigned to ipilimumab ( n=475 ) or placebo ( n=476 ) , all of whom were included in the intention-to-treat analyses . At a median follow-up of 2·74 years ( IQR 2·28 - 3·22 ) , there were 528 recurrence-free survival events ( 234 in the ipilimumab group vs 294 in the placebo group ) . Median recurrence-free survival was 26·1 months ( 95 % CI 19·3 - 39·3 ) in the ipilimumab group versus 17·1 months ( 95 % CI 13·4 - 21·6 ) in the placebo group ( hazard ratio 0·75 ; 95 % CI 0·64 - 0·90 ; p=0·0013 ) ; 3-year recurrence-free survival was 46·5 % ( 95 % CI 41·5 - 51·3 ) in the ipilimumab group versus 34·8 % ( 30·1 - 39·5 ) in the placebo group . The most common grade 3 - 4 immune-related adverse events in the ipilimumab group were gastrointestinal ( 75 [ 16 % ] vs four [ < 1 % ] in the placebo group ) , hepatic ( 50 [ 11 % ] vs one [ < 1 % ] ) , and endocrine ( 40 [ 8 % ] vs none ) . Adverse events led to discontinuation of treatment in 245 ( 52 % ) of 471 patients who started ipilimumab ( 182 [ 39 % ] during the initial treatment period of four doses ) . Five patients ( 1 % ) died due to drug-related adverse events . Five ( 1 % ) participants died because of drug-related adverse events in the ipilimumab group ; three patients died because of colitis ( two with gastrointestinal perforation ) , one patient because of myocarditis , and one patient because of multiorgan failure with Guillain-Barré syndrome . INTERPRETATION Adjuvant ipilimumab significantly improved recurrence-free survival for patients with completely resected high-risk stage III melanoma . The adverse event profile was consistent with that observed in advanced melanoma , but at higher incidences in particular for endocrinopathies . The risk-benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasis-free survival and overall survival endpoints to define its definitive value . FUNDING Bristol-Myers Squibb 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 & Purpose Patients with squamous non-small-cell lung cancer ( NSCLC ) have poor prognosis and limited treatment options . This r and omized , double-blind , phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC . Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were r and omly assigned ( 1:1 ) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles , with ipilimumab or placebo from cycles 3 to 6 and then , after induction treatment , ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better . The primary end point was overall survival ( OS ) in patients receiving at least one dose of blinded study therapy . Results Of 956 r and omly assigned patients , 749 received at least one dose of blinded study therapy ( chemotherapy plus ipilimumab , n = 388 ; chemotherapy plus placebo , n = 361 ) . Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo ( hazard ratio , 0.91 ; 95 % CI , 0.77 to 1.07 ; P = .25 ) . Median progression-free survival was 5.6 months for both groups ( hazard ratio , 0.87 ; 95 % CI , 0.75 to 1.01 ) . Rates of grade 3 or 4 treatment-related adverse events ( TRAEs ) , any- grade serious TRAEs , and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab ( 51 % , 33 % , and 28 % , respectively ) than with chemotherapy plus placebo ( 35 % , 10 % , and 7 % , respectively ) . Seven treatment-related deaths occurred with chemotherapy plus ipilimumab , and one occurred with chemotherapy plus placebo . Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC . The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies . Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors . We assessed the efficacy and safety of nivolumab compared with investigator 's choice of chemotherapy ( ICC ) as a second-line or later-line treatment in patients with advanced melanoma . METHODS In this r and omised , controlled , open-label , phase 3 trial , we recruited patients at 90 sites in 14 countries . Eligible patients were 18 years or older , had unresectable or metastatic melanoma , and progressed after ipilimumab , or ipilimumab and a BRAF inhibitor if they were BRAF(V 600 ) mutation-positive . Participating investigators r and omly assigned ( with an interactive voice response system ) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC ( dacarbazine 1000 mg/m(2 ) every 3 weeks or paclitaxel 175 mg/m(2 ) combined with carboplatin area under the curve 6 every 3 weeks ) until progression or unacceptable toxic effects . We stratified r and omisation by BRAF mutation status , tumour expression of PD-L1 , and previous best overall response to ipilimumab . We used permuted blocks ( block size of six ) within each stratum . Primary endpoints were the proportion of patients who had an objective response and overall survival . Treatment was given open-label , but those doing tumour assessment s were masked to treatment assignment . We assessed objective responses per- protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks , and safety in all patients who had had at least one dose of treatment . The trial is closed and this is the first interim analysis , reporting the objective response primary endpoint . This study is registered with Clinical Trials.gov , number NCT01721746 . FINDINGS Between Dec 21 , 2012 , and Jan 10 , 2014 , we screened 631 patients , r and omly allocating 272 patients to nivolumab and 133 to ICC . Confirmed objective responses were reported in 38 ( 31·7 % , 95 % CI 23·5 - 40·8 ) of the first 120 patients in the nivolumab group versus five ( 10·6 % , 3·5 - 23·1 ) of 47 patients in the ICC group . Grade 3 - 4 adverse events related to nivolumab included increased lipase ( three [ 1 % ] of 268 patients ) , increased alanine aminotransferase , anaemia , and fatigue ( two [ 1 % ] each ) ; for ICC , these included neutropenia ( 14 [ 14 % ] of 102 ) , thrombocytopenia ( six [ 6 % ] ) , and anaemia ( five [ 5 % ] ) . We noted grade 3 - 4 drug-related serious adverse events in 12 ( 5 % ) nivolumab-treated patients and nine ( 9 % ) patients in the ICC group . No treatment-related deaths occurred . INTERPRETATION Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor . Nivolumab represents a new treatment option with clinical ly meaningful durable objective responses in a population of high unmet need . FUNDING Bristol-Myers Squibb BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 ( PD-1 ) that has antitumor activity in advanced non-small-cell lung cancer ( NSCLC ) , with increased activity in tumors that express programmed death lig and 1 ( PD-L1 ) . METHODS In this open-label , phase 3 trial , we r and omly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50 % of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab ( at a fixed dose of 200 mg every 3 weeks ) or the investigator 's choice of platinum-based chemotherapy . Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression . The primary end point , progression-free survival , was assessed by means of blinded , independent , central radiologic review . Secondary end points were overall survival , objective response rate , and safety . RESULTS Median progression-free survival was 10.3 months ( 95 % confidence interval [ CI ] , 6.7 to not reached ) in the pembrolizumab group versus 6.0 months ( 95 % CI , 4.2 to 6.2 ) in the chemotherapy group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.37 to 0.68 ; P<0.001 ) . The estimated rate of overall survival at 6 months was 80.2 % in the pembrolizumab group versus 72.4 % in the chemotherapy group ( hazard ratio for death , 0.60 ; 95 % CI , 0.41 to 0.89 ; P=0.005 ) . The response rate was higher in the pembrolizumab group than in the chemotherapy group ( 44.8 % vs. 27.8 % ) , the median duration of response was longer ( not reached [ range , 1.9 + to 14.5 + months ] vs. 6.3 months [ range , 2.1 + to 12.6 + ] ) , and treatment-related adverse events of any grade were less frequent ( occurring in 73.4 % vs. 90.0 % of patients ) , as were grade 3 , 4 , or 5 treatment-related adverse events ( 26.6 % vs. 53.3 % ) . CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50 % of tumor cells , pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy . ( Funded by Merck ; KEYNOTE-024 Clinical Trials.gov number , NCT02142738 . ) Background : We performed a meta- analysis to evaluate the risk of immune-related colitis associated with PD1/PD-L1 inhibitors as compared to chemotherapy in solid tumor patients . Methods : Eligible studies were identified through a comprehensive search of multiple data bases and included solid tumor patients in r and omized controlled trials ( RCTs ) with PD-1/PD-L1 inhibitors . The data was analyzed by Stata version 12.0 software . Results : After exclusion of ineligible studies , 11 clinical trials were considered eligible for the meta- analysis , including 5751 patients . Compared with chemotherapy , the risk ratios ( RRs ) of all- grade colitis were significant for the PD-1 inhibitor subgroup ( RR 2.69 , 95 % confidence interval ( CI ) : 1.15 - 6.29 , p=0.023 ) , and for pembrolizumab subgroup ( RR 3.17 , 95 % CI : 1.08 - 9.37 , p=0.037 ) , but not for nivolumab treatment and PD-L1 inhibitor ( atezolizumab ) treatment ( RR 2.05 , 95 % CI : 0.52 - 8.13 , p=0.305 ; RR 4.75,95 % CI : 0.56 - 40.50 , p=0.154 , respectively ) . The RR of all- grade colitis was significant for PD-1/PD-L1 inhibitor in NSCLC ( RR 4.34 , 95 % CI : 1.37 - 13.82 , p=0.013 ) , and not significant in melanoma ( RR 2.11 , 95 % CI : 0.54 - 8.34 , p=0.285 ) . Moreover , the RRs of all- grade diarrhea were significant for the PD-1 inhibitor subgroup ( RR 0.61 , 95 % CI : 0.44 - 0.83 , p=0.002 ) , for the nivolumab subgroup ( RR 0.54 , 95 % CI : 0.34 - 0.87 , p=0.012 ) , and for atezolizumab subgroup ( RR 0.48 , 95 % CI : 0.25 - 0.89 , p=0.021 ) . The RR of high- grade diarrhea was significant for atezolizumab subgroup ( RR 0.34 , 95 % CI : 0.12 - 0.94 , p=0.037 ) . Conclusions : Our meta- analysis demonstrates that compared with chemotherapy , pembrolizumab may result in a higher risk of all- grade immune-mediated colitis . PD-1/PD-L1 inhibitor treatment in NSCLC patients , but not in melanoma patients , increases the risk of all- grade colitis incidence 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 The immune checkpoint inhibitor ipilimumab is the st and ard-of-care treatment for patients with advanced melanoma . Pembrolizumab inhibits the programmed cell death 1 ( PD-1 ) immune checkpoint and has antitumor activity in patients with advanced melanoma . METHODS In this r and omized , controlled , phase 3 study , we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab ( at a dose of 10 mg per kilogram of body weight ) every 2 weeks or every 3 weeks or four doses of ipilimumab ( at 3 mg per kilogram ) every 3 weeks . Primary end points were progression-free and overall survival . RESULTS The estimated 6-month progression-free-survival rates were 47.3 % for pembrolizumab every 2 weeks , 46.4 % for pembrolizumab every 3 weeks , and 26.5 % for ipilimumab ( hazard ratio for disease progression , 0.58 ; P<0.001 for both pembrolizumab regimens versus ipilimumab ; 95 % confidence intervals [ CIs ] , 0.46 to 0.72 and 0.47 to 0.72 , respectively ) . Estimated 12-month survival rates were 74.1 % , 68.4 % , and 58.2 % , respectively ( hazard ratio for death for pembrolizumab every 2 weeks , 0.63 ; 95 % CI , 0.47 to 0.83 ; P=0.0005 ; hazard ratio for pembrolizumab every 3 weeks , 0.69 ; 95 % CI , 0.52 to 0.90 ; P=0.0036 ) . The response rate was improved with pembrolizumab administered every 2 weeks ( 33.7 % ) and every 3 weeks ( 32.9 % ) , as compared with ipilimumab ( 11.9 % ) ( P<0.001 for both comparisons ) . Responses were ongoing in 89.4 % , 96.7 % , and 87.9 % of patients , respectively , after a median follow-up of 7.9 months . Efficacy was similar in the two pembrolizumab groups . Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups ( 13.3 % and 10.1 % ) than in the ipilimumab group ( 19.9 % ) . CONCLUSIONS The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high- grade toxicity than did ipilimumab in patients with advanced melanoma . ( Funded by Merck Sharp & Dohme ; KEYNOTE-006 Clinical Trials.gov number , NCT01866319 . ) BACKGROUND In a phase 1 dose-escalation study , combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response , including complete responses , among patients with advanced melanoma . METHODS In this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment , we r and omly assigned patients in a 2:1 ratio to receive ipilimumab ( 3 mg per kilogram of body weight ) combined with either nivolumab ( 1 mg per kilogram ) or placebo once every 3 weeks for four doses , followed by nivolumab ( 3 mg per kilogram ) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects . The primary end point was the rate of investigator-assessed , confirmed objective response among patients with BRAF V600 wild-type tumors . RESULTS Among patients with BRAF wild-type tumors , the rate of confirmed objective response was 61 % ( 44 of 72 patients ) in the group that received both ipilimumab and nivolumab ( combination group ) versus 11 % ( 4 of 37 patients ) in the group that received ipilimumab and placebo ( ipilimumab-monotherapy group ) ( P<0.001 ) , with complete responses reported in 16 patients ( 22 % ) in the combination group and no patients in the ipilimumab-monotherapy group . The median duration of response was not reached in either group . The median progression-free survival was not reached with the combination therapy and was 4.4 months with ipilimumab monotherapy ( hazard ratio associated with combination therapy as compared with ipilimumab monotherapy for disease progression or death , 0.40 ; 95 % confidence interval , 0.23 to 0.68 ; P<0.001 ) . Similar results for response rate and progression-free survival were observed in 33 patients with BRAF mutation-positive tumors . Drug-related adverse events of grade 3 or 4 were reported in 54 % of the patients who received the combination therapy as compared with 24 % of the patients who received ipilimumab monotherapy . Select adverse events with potential immunologic causes were consistent with those in a phase 1 study , and most of these events resolved with immune-modulating medication . CONCLUSIONS The objective -response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy . Combination therapy had an acceptable safety profile . ( Funded by Bristol-Myers Squibb ; Clinical Trials.gov number , NCT01927419 . ) 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 Nivolumab combined with ipilimumab result ed in longer progression‐free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma . We now report 3‐year overall survival outcomes in this trial . METHODS We r and omly assigned , in a 1:1:1 ratio , patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses , followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks ; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo ; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo , until progression , the occurrence of unacceptable toxic effects , or withdrawal of consent . R and omization was stratified according to programmed death lig and 1 ( PD‐L1 ) status , BRAF mutation status , and metastasis stage . The two primary end points were progression‐free survival and overall survival in the nivolumab‐plus‐ipilimumab group and in the nivolumab group versus the ipilimumab group . RESULTS At a minimum follow‐up of 36 months , the median overall survival had not been reached in the nivolumab‐plus‐ipilimumab group and was 37.6 months in the nivolumab group , as compared with 19.9 months in the ipilimumab group ( hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab , 0.55 [ P<0.001 ] ; hazard ratio for death with nivolumab vs. ipilimumab , 0.65 [ P<0.001 ] ) . The overall survival rate at 3 years was 58 % in the nivolumab‐plus‐ipilimumab group and 52 % in the nivolumab group , as compared with 34 % in the ipilimumab group . The safety profile was unchanged from the initial report . Treatment‐related adverse events of grade 3 or 4 occurred in 59 % of the patients in the nivolumab‐plus‐ipilimumab group , in 21 % of those in the nivolumab group , and in 28 % of those in the ipilimumab group . CONCLUSIONS Among patients with advanced melanoma , significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone . ( Funded by Bristol‐Myers Squibb and others ; CheckMate 067 Clinical Trials.gov number , NCT01844505 . BACKGROUND New therapeutic strategies for malignant mesothelioma are urgently needed . In the DETERMINE study , we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 ( CTLA-4 ) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma . METHODS DETERMINE was a double-blind , placebo-controlled , phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease . Eligible patients were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and measurable disease as defined in the modified Response Evaluation Criteria In Solid Tumors ( RECIST ) version 1.0 for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma . Patients were r and omly assigned ( 2:1 ) in blocks of three , stratified by European Organisation for Research and Treatment of Cancer status ( low risk vs high risk ) , line of therapy ( second line vs third line ) , and anatomic site ( pleural vs peritoneal ) , by use of an interactive voice or web system , to receive intravenous tremelimumab ( 10 mg/kg ) or placebo every 4 weeks for 7 doses and every 12 weeks thereafter until a treatment discontinuation criterion was met . The primary endpoint was overall survival in the intention-to-treat population . Safety was assessed in all patients who received at least one dose of study drug . The trial is ongoing but no longer recruiting participants , and is registered with Clinical Trials.gov , number NCT01843374 . FINDINGS Between May 17 , 2013 , and Dec 4 , 2014 , 571 patients were r and omly assigned to receive tremelimumab ( n=382 ) or placebo ( n=189 ) , of whom 569 patients received treatment ( two patients in the tremelimumab group were excluded from the safety population because they did not receive treatment ) . At the data cutoff date ( Jan 24 , 2016 ) , 307 ( 80 % ) of 382 patients had died in the tremelimumab group and 154 ( 81 % ) of 189 patients had died in the placebo group . Median overall survival in the intention-to-treat population did not differ between the treatment groups : 7·7 months ( 95 % CI 6·8 - 8·9 ) in the tremelimumab group and 7·3 months ( 5·9 - 8·7 ) in the placebo group ( hazard ratio 0·92 [ 95 % CI 0·76 - 1·12 ] , p=0·41 ) . Treatment-emergent adverse events of grade 3 or worse occurred in 246 ( 65 % ) of 380 patients in the tremelimumab group and 91 ( 48 % ) of 189 patients in the placebo group ; the most common were dyspnoea ( 34 [ 9 % ] patients in the tremelimumab group vs 27 [ 14 % ] patients in the placebo group ) , diarrhoea ( 58 [ 15 % ] vs one [ < 1 % ] ) , and colitis ( 26 [ 7 % ] vs none ) . The most common serious adverse events were diarrhoea ( 69 [ 18 % ] patients in the tremelimumab group vs one [ < 1 % ] patient in the placebo group ) , dyspnoea ( 29 [ 8 % ] vs 24 [ 13 % ] ) , and colitis ( 24 [ 6 % ] vs none ) . Treatment-emergent events leading to death occurred in 36 ( 9 % ) of 380 patients in the tremelimumab group and 12 ( 6 % ) of 189 in the placebo group ; those leading to the death of more than one patient were mesothelioma ( three [ 1 % ] patients in the tremelimumab group vs two [ 1 % ] in the placebo group ) , dyspnoea ( three [ 1 % ] vs two [ 1 % ] ) ; respiratory failure ( one [ < 1 % ] vs three [ 2 % ] ) , myocardial infa rct ion ( three [ 1 % ] vs none ) , lung infection ( three [ 1 % ] patients vs none ) , cardiac failure ( one [ < 1 % ] vs one [ < 1 % ] ) , and colitis ( two [ < 1 % ] vs none ) . Treatment-related adverse events leading to death occurred in five ( 1 % ) patients in the tremelimumab group and none in the placebo group . The causes of death were lung infection in one patient , intestinal perforation and small intestinal obstruction in one patient ; colitis in two patients , and neuritis and skin ulcer in one patient . INTERPRETATION Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma . The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors . Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing . FUNDING AstraZeneca |
13,939 | 31,508,698 | Our results showed that the impact of MP are mixed when it comes to physical and physical/sexual violence .
Even so , the review suggests that the effect of MP on sexual violence is trivial or nonexistent .
Regarding the impact of CTPs , the present study showed that the effects on physical , physical/sexual , psychological , and sexual violence were also heterogeneous .
Women more empowered and with some autonomy could be at risk . | Intimate partner violence ( IPV ) is a worldwide public health problem .
Many proposals aim ing to eliminate its occurrence include the empowerment of women through their socio-economic development .
In this context , some studies suggested that microcredit programs ( MP ) and cash transfer programs ( CTP ) are initiatives that can also reduce the risk of IPV .
Others pointed to an opposite effect .
The objective of this study was to investigate the influence of women 's economic empowerment in MP and CTP on the risk of physical , psychological and sexual violence through a systematic review . | OBJECTIVE To explore whether adding a gender and HIV training programme to microfinance initiatives can lead to health and social benefits beyond those achieved by microfinance alone . METHODS Cross-sectional data were derived from three r and omly selected matched clusters in rural South Africa : ( i ) four villages with 2-year exposure to the Intervention with Microfinance for AIDS and Gender Equity ( IMAGE ) , a combined microfinance-health training intervention ; ( ii ) four villages with 2-year exposure to microfinance services alone ; and ( iii ) four control villages not targeted by any intervention . Adjusted risk ratios ( aRRs ) employing village-level summaries compared associations between groups in relation to indicators of economic well-being , empowerment , intimate partner violence ( IPV ) and HIV risk behaviour . The magnitude and consistency of aRRs allowed for an estimate of incremental effects . FINDINGS A total of 1409 participants were enrolled , all female , with a median age of 45 . After 2 years , both the microfinance-only group and the IMAGE group showed economic improvements relative to the control group . However , only the IMAGE group demonstrated consistent associations across all domains with regard to women 's empowerment , intimate partner violence and HIV risk behaviour . CONCLUSION The addition of a training component to group-based microfinance programmes may be critical for achieving broader health benefits . Donor agencies should encourage intersectoral partnerships that can foster synergy and broaden the health and social effects of economic interventions such as microfinance Background Women who engage in sex work are at risk for experiencing violence from numerous perpetrators , including paying partners . Empirical evidence has shown mixed results regarding the impact of participation in microfinance interventions on women ’s experiences of violence , with some studies demonstrating reductions in intimate partner violence ( IPV ) and others showing heightened risk for IPV . The current study reports on the impact of participation in a microsavings intervention on experiences of paying partner violence among women engaged in sex work in Mongolia . Methods Between 2011 and 2013 , we conducted a two-arm , non-blinded r and omized controlled trial ( RCT ) comparing an HIV/STI risk reduction intervention ( HIVSRR ) ( control condition ) to a combined microsavings and HIVSRR intervention ( treatment condition ) . Eligible women ( aged 18 or older , reported having engaged in unprotected sex with paying partner in past 90 days , expressed interest in microsavings intervention ) were invited to participate . One hundred seven were r and omized , including 50 in the control and 57 in the treatment condition . Participants completed assessment s at baseline , immediate post-test following HIVSRR , and at 3-months and 6-months after completion of the treatment group intervention . Outcomes for the current study include any violence ( physical and /or sexual ) , sexual violence , and physical violence from paying partners in the past 90 days . Results An intention-to-treat approach was utilized . Linear growth models revealed significant reductions over time in both conditions for any violence ( β = −0.867 , p < 0.001 ) , physical violence ( β = −0.0923 , p < 0.001 ) , and sexual violence ( β = −1.639 , p = 0.001 ) from paying partners . No significant differences between groups were found for any violence ( β = 0.118 , p = 0.389 ) , physical violence ( β = 0.091 , p = 0.792 ) , or sexual violence ( β = 0.379 , p = 0.114 ) from paying partners . Conclusions Microsavings participation did not significantly impact women ’s risk for paying partner violence . Qualitative research is recommended to underst and the cause for reductions in paying partner violence in both study conditions . Trial registration Evaluating a Microfinance Intervention for High Risk Women in Mongolia ; NCT01861431 ; May 20 , 2013 Intimate partner violence is widespread and represents an obstacle to human freedom and a significant public health concern . Poverty alleviation programs and efforts to economically " empower " women have become popular policy options , but theory and empirical evidence are mixed on the relationship between women 's empowerment and the experience of violence . We study the effects of a successful poverty alleviation program on women 's empowerment and intimate partner relations and violence from 2009 to 2011 . In the first experiment , a cluster-r and omized superiority trial , 15 marginalized people ( 86 % women ) were identified in each of 120 villages ( n = 1800 ) in Gulu and Kitgum districts in Ug and a. Half of villages were r and omly assigned via public lottery to immediate treatment : five days of business training , $ 150 , and supervision and advising . We examine intent-to-treat estimates of program impact and heterogeneity in treatment effects by initial quality of partner relations . 16 months after the initial grants , the program doubled business ownership and incomes ( p < 0.01 ) ; we show that the effect on monthly income , however , is moderated by initial quality of intimate partner relations . We also find small increases in marital control ( p < 0.05 ) , self-reported autonomy ( p < 0.10 ) , and quality of partner relations ( p < 0.01 ) , but essentially no change in intimate partner violence . In a second experiment , we study the impact of a low-cost attempt to include household partners ( often husb and s ) in the process . Participants from the 60 waitlist villages ( n = 904 ) were r and omly assigned to participate in the program as individuals or with a household partner . We observe small , non-significant decreases in abuse and marital control and large increases in the quality of relationships ( p < 0.05 ) , but no effects on women 's attitudes toward gender norms and a non-significant reduction in autonomy . Involving men and changing framing to promote more inclusive programming can improve relationships , but may not change gender attitudes or increase business success . Increasing women 's earnings has no effect on intimate partner violence BACKGROUND HIV infection and intimate-partner violence share a common risk environment in much of southern Africa . The aim of the Intervention with Microfinance for AIDS and Gender Equity ( IMAGE ) study was to assess a structural intervention that combined a microfinance programme with a gender and HIV training curriculum . METHODS Villages in the rural Limpopo province of South Africa were pair-matched and r and omly allocated to receive the intervention at study onset ( intervention group , n=4 ) or 3 years later ( comparison group , n=4 ) . Loans were provided to poor women who enrolled in the intervention group . A participatory learning and action curriculum was integrated into loan meetings , which took place every 2 weeks . Both arms of the trial were divided into three groups : direct programme participants or matched controls ( cohort one ) , r and omly selected 14 - 35-year-old household co-residents ( cohort two ) , and r and omly selected community members ( cohort three ) . Primary outcomes were experience of intimate-partner violence -- either physical or sexual -- in the past 12 months by a spouse or other sexual intimate ( cohort one ) , unprotected sexual intercourse at last occurrence with a non-spousal partner in the past 12 months ( cohorts two and three ) , and HIV incidence ( cohort three ) . Analyses were done on a per- protocol basis . This trial is registered with Clinical Trials.gov , number NCT00242957 . FINDINGS In cohort one , experience of intimate-partner violence was reduced by 55 % ( adjusted risk ratio [ aRR ] 0.45 , 95 % CI 0.23 - 0.91 ; adjusted risk difference -7.3 % , -16.2 to 1.5 ) . The intervention did not affect the rate of unprotected sexual intercourse with a non-spousal partner in cohort two ( aRR 1.02 , 0.85 - 1.23 ) , and there was no effect on the rate of unprotected sexual intercourse at last occurrence with a non-spousal partner ( 0.89 , 0.66 - 1.19 ) or HIV incidence ( 1.06 , 0.66 - 1.69 ) in cohort three . INTERPRETATION A combined microfinance and training intervention can lead to reductions in levels of intimate-partner violence in programme participants . Social and economic development interventions have the potential to alter risk environments for HIV and intimate-partner violence in southern Africa OBJECTIVES We sought to obtain evidence about the scope of women 's empowerment and the mechanisms underlying the significant reduction in intimate partner violence documented by the Intervention With Microfinance for AIDS and Gender Equity ( IMAGE ) cluster-r and omized trial in rural South Africa . METHODS The IMAGE intervention combined a microfinance program with participatory training on underst and ing HIV infection , gender norms , domestic violence , and sexuality . Outcome measures included past year 's experience of intimate partner violence and 9 indicators of women 's empowerment . Qualitative data about changes occurring within intimate relationships , loan groups , and the community were also collected . RESULTS After 2 years , the risk of past-year physical or sexual violence by an intimate partner was reduced by more than half ( adjusted risk ratio=0.45 ; 95 % confidence interval=0.23 , 0.91 ) . Improvements in all 9 indicators of empowerment were observed . Reductions in violence result ed from a range of responses enabling women to challenge the acceptability of violence , expect and receive better treatment from partners , leave abusive relationships , and raise public awareness about intimate partner violence . CONCLUSIONS Our findings , both qualitative and quantitative , indicate that economic and social empowerment of women can contribute to reductions in intimate partner violence BACKGROUND Cash transfers have been proposed as an intervention to reduce HIV-infection risk for young women in sub-Saharan Africa . However , scarce evidence is available about their effect on reducing HIV acquisition . We aim ed to assess the effect of a conditional cash transfer on HIV incidence among young women in rural South Africa . METHODS We did a phase 3 , r and omised controlled trial ( HPTN 068 ) in the rural Bushbuckridge subdistrict in Mpumalanga province , South Africa . We included girls aged 13 - 20 years if they were enrolled in school grade s 8 - 11 , not married or pregnant , able to read , they and their parent or guardian both had the necessary documentation necessary to open a bank account , and were residing in the study area and intending to remain until trial completion . Young women ( and their parents or guardians ) were r and omly assigned ( 1:1 ) , by use of numbered sealed envelopes containing a r and omisation assignment card which were numerically ordered with block r and omisation , to receive a monthly cash transfer conditional on school attendance ( ≥80 % of school days per month ) versus no cash transfer . Participants completed an Audio Computer-Assisted Self-Interview ( ACASI ) , before test HIV counselling , HIV and herpes simplex virus (HSV)-2 testing , and post-test counselling at baseline , then at annual follow-up visits at 12 , 24 , and 36 months . Parents or guardians completed a Computer-Assisted Personal Interview at baseline and each follow-up visit . A stratified proportional hazards model was used in an intention-to-treat analysis of the primary outcome , HIV incidence , to compare the intervention and control groups . This study is registered at Clinical Trials.gov ( NCT01233531 ) . FINDINGS Between March 5 , 2011 , and Dec 17 , 2012 , we recruited 10 134 young women and enrolled 2537 and their parents or guardians to receive a cash transfer programme ( n=1225 ) or not ( control group ; n=1223 ) . At baseline , the median age of girls was 15 years ( IQR 14 - 17 ) and 672 ( 27 % ) had reported to have ever had sex . 107 incident HIV infections were recorded during the study : 59 cases in 3048 person-years in the intervention group and 48 cases in 2830 person-years in the control group . HIV incidence was not significantly different between those who received a cash transfer ( 1·94 % per person-years ) and those who did not ( 1·70 % per person-years ; hazard ratio 1·17 , 95 % CI 0·80 - 1·72 , p=0·42 ) . INTERPRETATION Cash transfers conditional on school attendance did not reduce HIV incidence in young women . School attendance significantly reduced risk of HIV acquisition , irrespective of study group . Keeping girls in school is important to reduce their HIV-infection risk . FUNDING National Institute of Allergy and Infectious Diseases , National Institute of Mental Health of the National Institutes of Health Violence against women is a major health and human rights problem yet there is little rigorous evidence as to how to reduce it . We take advantage of the r and omized roll-out of Ecuador 's cash transfer program to mothers to investigate how an exogenous increase in a woman 's income affects domestic violence . We find that the effect of a cash transfer depends on a woman 's education and on her education relative to her partner 's . Our results show that for women with greater than primary school education a cash transfer significantly decreases psychological violence from her partner . For women with primary school education or less , however , the effect of a cash transfer depends on her education relative to her partner 's . Specifically , the cash transfer significantly increases emotional violence in households where the woman 's education is equal to or more than her partner 's |
13,940 | 26,697,988 | Despite the availability of numerous treatment options , CINV was found to have a strong impact on HRQoL of patients .
Direct costs are particularly affected , but this result could be due to scarcity of studies assessing indirect costs .
Evidence supports the notion that CINV continues to have a negative impact on HRQoL of patients , even for those receiving moderately emetic chemotherapy . | BACKGROUND Chemotherapy-induced nausea and vomiting ( CINV ) is a particularly distressing event for oncology patients .
This review aims at analyzing the impact of CINV on Health-Related Quality of Life ( QoL ) and on the use of healthcare re sources . | CONTEXT AND OBJECTIVE Nausea and vomiting are major inconveniences for patients undergoing chemotherapy . Despite st and ard preventive treatment , chemotherapy-induced nausea and vomiting ( CINV ) still occurs in approximately 50 % of these patients . In an attempt to optimize this treatment , we evaluated the possible effects of carbamazepine for prevention of CINV . DESIGN AND LOCATION Prospect i ve nonr and omized open-label phase II study carried out at a Brazilian public oncology service . METHODS Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited . In addition to st and ard antiemetic protocol that was made available , they received carbamazepine orally , with staggered doses , from the third day before until the fifth day after chemotherapy . Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention , we used Simon 's two-stage design , in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries . The Functional Living Index-Emesis question naire was used to measure the impact on quality of life . RESULTS None of the ten patients ( 0 % ) presented overall complete prevention . In three cases , carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy . Seven were able to take the medication for the entire period and none were responsive , so the study was closed . There was no impact on the patients ' quality of life . CONCLUSION Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population BACKGROUND Delayed chemotherapy-induced nausea and vomiting ( CINV ) remains a major adverse effect of cancer chemotherapy . We assessed , under current practice patterns , the occurrence and impact on healthcare re source utilization of CINV in patients receiving emetogenic chemotherapy . An additional aim of this study was to estimate costs imputable to CINV in the German healthcare environment . MATERIAL S AND METHODS This prospect i ve , multi-center , cross-sectional cost-of-illness study was conducted in three hospitals and in three office-based facilities in Germany . Consecutive patients undergoing emetogenic chemotherapy ( levels 4 or 5 according to Hesketh classification of emetogenicity ) were enrolled . Data were obtained from preplanned chart review s and from self-administered patient question naires . Analysis of direct costs was performed from the perspectives of third party payer ( statutory sick fund ) , provider ( hospital ) and patients . Indirect costs were assessed on the basis of paid workdays lost . RESULTS During the 5-day observation period , 134 of 208 chemotherapy cycles observed ( 64.4 % ) were associated with at least one episode of nausea or vomiting . More patients experienced delayed than acute CINV ( 60.7 % versus 32.8 % ) , and more patients reported nausea than vomiting ( 62.5 % versus 26.0 % ) . A total of 68 patients ( 32.6 % ) utilized healthcare re sources due to CINV . The most frequently used re sources were rescue medications and outpatient hospital and office physician visits . Only one patient required hospitalization and only three patients lost workdays due to CINV . Average costs imputable to CINV per patient ( with or without CINV ) per treatment cycle incurred by third party payers and hospital providers were Euro 49 and Euro 48 , respectively . Patient or treatment characteristics that were associated with high costs imputable to CINV were as follows : cisplatin-containing regimen ; experience of emesis ; and presence of delayed CINV . CONCLUSIONS A substantial proportion of patients continue to experience CINV . This entails not only clinical but also economic consequences , and highlights a continuing need for improved utilization of existing antiemetic agents and for new , more efficacious treatments . The greatest improvements in patient care and potential for cost offset may be realized by preventing delayed CINV INTRODUCTION Chemotherapy-induced nausea and vomiting ( CINV ) is one of the most important worries of cancer patients . Although not life-threatening , it has a great negative impact on quality of life ( QOL ) . OBJECTIVE The aim of this study was to determine the impact of CINV ( i.e. , acute and delayed ) on breast cancer patients QOL and to discern opinions related with antiemetic guidelines used dependent on the three main races in Malaysia ( Malay , Chinese , Indian ) . METHODS In this longitudinal prospect i ve observational study , 158 breast cancer patients treated with chemotherapy were interviewed and valid question naires ( MANE and ONEM ) were used to report the impact of CINV on their QOL within the first 24 hours and after 3 to 5 days of chemotherapy treatment . RESULTS The main result was that delayed CINV has an impact on QOL greater than acute CINV . The impact of nausea was reportedly higher than that of vomiting . Also differences in race i.e. , genetic polymorphisms ( pharmacogenomics ) influenced the utility of antiemetic treatments and patients opinions . CONCLUSION Based on the results of our study a new guideline for antiemetic treatment should be used to reduce the impact of CINV on QOL , taking into account variation in genetic polymorphisms among the three races in Malaysia This study compared the efficacy and tolerability of oral ondansetron ( 8 mg twice daily [ BID ] for up to 3 days ) with those of phenothiazine prochlorperazine ( 10 mg BID for up to 3 days ) in 133 cancer patients receiving cyclophosphamide-based chemotherapy . In addition , the study evaluated the impact of these treatments on patients ' health-related quality of life , measured with both the Functional Living Index -- Cancer and the Functional Living Index -- Emesis question naires . The first dose of study drug was administered 30 minutes before initiation of chemotherapy . Patients received a rescue antiemetic at their request or if the investigator deemed it necessary . There was a statistically significant difference in the number of patients with no emetic episodes over the 3-day study period : 60 % in the ondansetron group compared with 21 % in the prochlorperazine group . Twenty-five percent of ondansetron-treated patients compared with 68 % of prochlorperazine-treated patients experienced three or more emetic episodes , rescue medication use , or withdrawal from the study due to adverse events or lack of efficacy of the study drug . Among patients with at least one emetic episode , the mean time to emesis was significantly longer ( 13 hours and 37 minutes ) in the ondansetron group compared with the prochlorperazine group ( 9 hours and 30 minutes ) . Nausea and appetite scores did not differ significantly between groups . The score on the vomiting subscale of the Functional Living Index -- Emesis was significantly more favorable in the ondansetron group compared with the prochlorperazine group , indicating better maintenance of health-related quality of life in ondansetron-treated patients . Both treatments were well tolerated . The most common potentially drug-related adverse event was headache , which occurred in significantly more ( 16 % ) ondansetron-treated patients compared with prochlorperazine-treated patients ( 3 % ) . The results of this study demonstrate that oral ondansetron 8 mg BID for up to 3 days is more effective than prochlorperazine 10 mg BID for up to 3 days in the prevention of emesis associated with moderately emetogenic chemotherapy Objectives Chemotherapy-induced nausea and vomiting ( CINV ) remains a major adverse effect of cancer chemotherapy which may increase morbidity , reduce quality of life and threaten the success of cancer therapy . Aprepitant is effective in preventing CINV , achieving higher complete response ( no emesis and no rescue therapy ) compared to st and ard prevention , in patients receiving either highly ( HEC ) or moderately emetogenic chemotherapy ( MEC ; absolute reduction = 11 and 13 % , respectively ) . We assessed the cost effectiveness of aprepitant-based vs st and ard prevention in these indications in Belgium . Material s and methods A decision analytical model was developed in MS Excel ( Fig. 1 ) . To estimate re source use , two approaches were used . The first is based on the preventive regimens applied in r and omized controlled trials comparing aprepitant-based CINV prevention ( for HEC : aprepitant days 1–3 , ondansetron 32 mg i.v . day 1 , oral placebo twice daily days 2–4 , oral dexamethasone days 1–4 ; for MEC : aprepitant days 1–3 , ondansetron 16 mg p.o . day 1 , placebo on days 2–3 , oral dexamethasone day 1 ) , vs a st and ard regimen ( for HEC : oral placebo days 1–3 , ondansetron 32 mg i.v . day 1 and 16 mg p.o . days 2–4 , oral dexamethasone days 1–4 ; for MEC : oral placebo , ondansetron 16 mg p.o . days 1–3 , dexamethasone day 1 ) The second analysis is based on current real-world re source use in the Belgian setting in the prevention of CINV using a longitudinal Hospital Data base . CINV-specific utility values were used to calculate quality -adjusted life years ( QALYs ) . Drug costs were obtained from official reimbursement listings . Treatment costs for CINV were obtained from a German study and adapted to Belgium . Results The aprepitant-based regimen is associated with 0.003 and 0.014 more QALYs in HEC and MEC , respectively and with per patient savings of € 66.84 ( trial based ) and € 74.62 ( real-life based ) for HEC and € 17.95 ( trial based ) and € 21.70 ( real-life based ) for MEC . Hence , aprepitant is both more effective and less expensive ( = dominant ) . One-way sensitivity analyses were performed on treatment cost of emesis , the clinical benefit of aprepitant and the cost of ondansetron and showed that the results were robust on the first two parameters but sensitive on the decrease in cost of ondansetron for the moderately emetogenic chemotherapy regimens . Conclusions In both approaches , the aprepitant-based strategy is more effective and less expensive compared to st and ard care Purpose Nausea is a troublesome and distressing symptom for patients receiving chemotherapy . While vomiting is well controlled with current antiemetics , nausea is a more difficult symptom to manage . The aim of this study was to assess the impact of nausea on nutritional status , quality of life and psychological distress . Methods This was a prospect i ve observational study over two cycles of chemotherapy . Patients completed the Multinational Association of Supportive Care in Cancer Antiemesis Tool , a measure of nutritional status ( Patient-Generated Subjective Global Assessment ) , the Functional Assessment of Cancer Therapy-General ( FACT-G ) quality of life scale and the Hospital Anxiety and Depression Scale at the end of each chemotherapy cycle ( around day 10 post-chemotherapy ) . Results The sample consisted of 104 patients , primarily female , receiving anthracycline-based chemotherapy . While vomiting was minimal ( 5.2–14.6 % of the patients ) , high levels of nausea were observed ( 55.2–72.9 % ) , and severe nausea ( > 6 on a 0–10 scale ) was reported by 20.5–29.2 % of the participants . Severe nausea had a borderline significant impact in relation to physical functioning ( p = 0.025 ) and a significant impact on nutritional status ( severe acute nausea , p = 0.003 ; severe delayed nausea , p = 0.017 ) . Clinical ly meaningful changes were observed in relation to the FACT-G total score . Conclusion Chemotherapy-induced nausea does have an impact on nutritional status and physical functioning and can impair anxiety and quality of life . As a key symptom associated with other symptoms , it is imperative that greater attention is given to managing treatment-related nausea through innovative non-pharmacological and nutritional interventions Purpose Addition of rolapitant to st and ard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting ( CINV ) in phase 3 trials of patients receiving highly emetogenic chemotherapy ( HEC ) or moderately emetogenic chemotherapy ( MEC ) . Here , we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis ( FLIE ) . Methods In three double-blind phase 3 studies , patients receiving HEC or MEC were r and omized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy . Patients completed the FLIE question naire on day 6 of cycle 1 . Endpoints included FLIE total score , nausea and vomiting domain scores , and the proportion of patients with no impact on daily life ( total score > 108 [ range 18–126 ] ) . We performed a prespecified analysis of the MEC/anthracycline-cyclophosphamide ( AC ) study and a post hoc analysis of two pooled cisplatin-based HEC studies . Results In the pooled HEC studies , rolapitant significantly improved the FLIE total score ( 114.5 vs 109.3 , p < 0.001 ) , nausea score ( 55.3 vs 53.5 , p < 0.05 ) , and vomiting score ( 59.2 vs 55.8 , p < 0.001 ) versus control ; similar results were observed in the MEC/AC study for FLIE total score ( 112.7 vs 108.6 , p < 0.001 ) , nausea score ( 54.1 vs 52.3 , p < 0.05 ) , and vomiting score ( 58.6 vs 56.3 , p < 0.001 ) . A higher proportion of patients reported no impact on daily life with rolapitant than with control in the MEC/AC study ( 73.2 vs 67.4 , p = 0.027 ) . Conclusions Compared with control , rolapitant improved quality of life in patients receiving HEC or MEC Background This study was design ed to mainly evaluate the activity and safety of olanzapine compared with 5-hydroxytryptamine3(5-HT3 ) receptor antagonists for prevention of chemotherapy-induced nausea and vomiting(CINV ) in patients receiving highly or moderately emetogenic chemotherapy ( HEC or MEC ) . The second goal was to evaluate the impact of olanzapine on quality of life ( QoL ) of cancer patients during the period of chemotherapy . Methods 229 patients receiving highly or moderately emetogenic chemotherapy were r and omly assigned to the test group [ olanzapine(O ) 10 mg p.o . plus azasetron ( A ) 10 mg i.v . and dexamethasone ( D ) 10 mg i.v . on day 1 ; O 10 mg once a day on days 2 - 5 ] or the control group ( A 10 mg i.v . and D 10 mg i.v . on day 1 ; D 10 mg i.v . once a day on days 2 - 5 ) . All the patients filled the observation table of CINV once a day on days 1 - 5 , patients were instructed to fill the EORTC QLQ-C30 QoL observation table on day 0 and day 6 . The primary endpoint was the complete response ( CR ) ( without nausea and vomiting , no rescue therapy ) for the acute period ( 24 h postchemotherapy ) , delayed period ( days 2 - 5 poschemotherapy ) , the whole period ( days 1 - 5 postchemotherapy ) . The second endpoint was QoL during chemotherapy administration , drug safety and toxicity . Results 229 patients were evaluable for efficacy . Compared with control group , complete response for acute nausea and vomiting in test group had no difference ( p > 0.05 ) , complete response for delayed nausea and vomiting in patients with highly emetogenic chemotherapy respectively improved 39.21 % ( 69.64 % versus 30.43 % , p < 0.05 ) , 22.05 % ( 78.57 % versus 56.52 % , p < 0.05 ) , complete response for delayed nausea and vomiting in patients with moderately emetogenic chemotherapy respectively improved 25.01 % ( 83.07 % versus 58.06 % , p < 0.05 ) , 13.43 % ( 89.23 % versus 75.80 % , p < 0.05 ) , complete response for the whole period of nausea and vomiting in patients with highly emetogenic chemotherapy respectively improved 41.38 % ( 69.64 % versus 28.26 % , p < 0.05 ) , 22.05 % ( 78.57 % versus 56.52 % , p < 0.05 ) , complete response for the whole period of nausea and vomiting in patients with moderately emetogenic chemotherapy respectively improved 26.62 % ( 83.07 % versus 56.45 % , p < 0.05 ) , 13.43 % ( 89.23 % versus 75.80 % , p < 0.05 ) . 214 of 299 patients were evaluable for QoL. Comparing test group with control group in QoL evolution , significant differences were seen in global health status , emotional functioning , social functioning , fatigue , nausea and vomiting , insomnia and appetite loss evolution in favour of the test group ( p < 0.01 ) . Both treatments were well tolerated . Conclusion Olanzapine can improve the complete response of delayed nausea and vomiting in patients receiving the highly or moderately emetogenic chemotherapy comparing with the st and ard therapy of antiemesis , as well as improve the QoL of the cancer patients during chemotherapy administration . Olanzapine is a safe and efficient drug for prevention of CINV BACKGROUND 5-HT3 antagonists are effective in reducing the acute nausea and vomiting caused by cancer chemotherapy . However , it is not clear whether continuing these agents beyond twenty four hours is useful in controlling emesis on days two to seven after chemotherapy . PATIENTS AND METHODS Four hundred seven patients receiving moderately emetogenic chemotherapy who had been given dexamethasone 8 mg i.v . and either ondansetron 32 mg i.v . or dolasetron 2.4 mg/kg i.v . were r and omized to continue either an oral form of their 5-HT3 antagonist ( ondansetron 8 mg b.i.d . or dolasetron 200 mg daily ) plus dexamethasone 8 mg p.o . daily or dexamethasone alone for days two to seven . Endpoints assessed by self-report were : 1 ) complete control ( no vomiting , no rescue medications , no missing data ) of emesis ; 2 ) nausea severity ; and 3 ) quality -of-life as measured by the EORTC QLQ-C30 . RESULTS Continuation of 5-HT3 antagonists improved slightly , but not significantly , the complete control rate ( 47 % vs. 41 % : P = 0.24 one-sided ) after chemotherapy . However , mean nausea severity was significantly ( P = 0.015 one sided ) reduced ( by 3 mm on a 10 cm scale ) on the combined arm . Minimal differences in quality of life were observed . CONCLUSION The benefit of continuing 5-HT3 antagonists beyond 24 hours is modest and the merits of routine use in these circumstances debatable PURPOSE / OBJECTIVES To determine the feasibility of administering a flavonoid-rich adjunctive treatment ( Concord grape juice ) for the management of chemotherapy-induced nausea and vomiting ( CINV ) ; to evaluate the usefulness of existing measures for assessing CINV frequency and severity , quality of life , control over life events , and psychological state ; to identify any actual or potential adverse events associated with frequent grape juice intake ; and to provide preliminary data concerning the effect of Concord grape juice on CINV , quality of life , perceived control over life events , and psychological state . DESIGN Double-blind , r and omized clinical trial . SETTING A cancer center in an academic health science center in the northeastern United States . SAMPLE 77 adult patients with cancer receiving moderately or highly emetogenic chemotherapy agents . METHODS Participants drank 4 oz . of grape juice or placebo prior to meals for one week following each of four chemotherapy treatment cycles . They recorded frequency , duration , and distress of nausea , vomiting , and retching daily , beginning the evening of chemotherapy administration and continuing for seven days . Data were analyzed with generalized estimating equations methodology to model differences between groups over time . MAIN RESEARCH VARIABLES Nausea and vomiting frequency , duration , and distress ; quality of life ; control over decision making ; and psychological state . FINDINGS Nausea and vomiting frequency , duration , and distress were lower for experimental group members , although a high attrition rate ( 50 % ) result ed in insufficient power to detect statistically significant differences over time . Greater levels of anxiety , depression , and hostility at baseline were related to nausea and vomiting , quality of life , and perceived control over decision making . CONCLUSIONS The effect of grape juice flavonoids on CINV should be investigated further with a larger sample to determine whether preliminary findings are supported . Alterations to the study protocol will be necessary to decrease attrition . IMPLICATION S FOR NURSING Flavonoid-rich fruits and vegetables may provide additional protection against CINV . If the compounds work , they would offer a low-cost , readily available adjunctive treatment for the management of CINV The purpose of the study was to assess the impact of postchemotherapy nausea and vomiting ( PCNV ) after moderately emetogenic chemotherapy on health-related quality of life ( HRQOL ) in patients with cancer being treated in a routine clinical practice setting . The European Organization for Research and Treatment in Cancer ( EORTC ) Quality of Life Question naire ( QLQ-C30 ) was administered on day 2 and day 6 following moderately emetogenic chemotherapy to 119 patients with a variety of cancers . Patients kept daily diaries to record the occurrence and severity of nausea and vomiting . The QLQ-C30 questions were modified , for this study only , to assess the impact of nausea and vomiting on HRQOL in patients who experienced nausea and /or vomiting during the six days following chemotherapy . Those patients who experienced either nausea or vomiting experienced a decrease in HRQOL from prechemotherapy levels on six functioning and five symptom scales at day 2 , and on four functioning and four symptom scales on day 6 . Comparison of mean scores between the unmodified QLQ-C30 and the nausea and vomiting versions demonstrated that the HRQOL rating attributed to nausea and vomiting accounted for much , but not all , of the deterioration in HRQOL scores in patients who experienced these symptoms . It can be concluded that patients who experience PCNV experience a significant negative impact on their HRQOL and that this impact can be attributed in large part to their experience of nausea and vomiting . However , since not all of the deterioration is attributable to these symptoms , other reasons for some of the decrease in HRQOL must also be identified in future studies Ondansetron has had a major impact on the prevention of emesis in patients receiving chemotherapy . However , the high cost and potential for inappropriate prescribing of this agent warranted a closer examination of its utilization . Hospital guidelines regarding the use of ondansetron were prepared by the Pharmacy and Therapeutics Committee and approved by the Medical Advisory Committee . The guidelines were then distributed to all physicians . Physicians were r and omized into an intervention or non-intervention group . A prospect i ve drug use evaluation was then conducted for a 10-week period where pharmacists monitored ondansetron prescribing and compared each order against hospital guidelines . For orders deemed inappropriate , only the intervetion-group physicians were contacted for therapy modification . The control of nausea and vomiting was then assessed for all patients 24 h and 72 h after chemotherapy via a simple patient question naire . There were no significant differences with respect to the control of nausea and vomiting between patients who received ondansetron according to guidelines and those who did not . A total of 76 % ( 48/63 ) of the prescriptions met hospital guidelines in the intervention group compared to 51.6 % ( 33/64 ) in the control ( P=0.007 ) . During the study period , physicians in the intervention group prescribed $ Can 757 worth of ondansetron inappropriately compared to $ 1814 in the control . Drug use evaluation with pharmacist intervention was an effective method of controlling unnecessary hospital costs and contributed towards the appropriate use of on-dansetron without compromising patient care Purpose Chemotherapy-induced nausea and vomiting ( CINV ) is a debilitating side effect of chemotherapy , but it may be prevented or mitigated with medications . Uncontrolled CINV can lead to reduced quality of life and can result in increased costs ( due to health care utilization and missed work ) . We prospect ively assessed the prevalence and burden of CINV in a US population . Methods Final analysis was performed on 178 patients , beginning chemotherapy during 2007–2008 at oncology specialty setting s. Patients kept a diary recording use of antiemetic medications just before the start of chemotherapy and use of antiemetic medications , health care re sources , and episodes of nausea and vomiting during the 5 days following . In addition , they completed a Functional Living Index — Emesis ( FLIE ) question naire and a Work Productivity and Assessment Inventory – Nausea and Vomiting assessment , to determine the impact of CINV on daily functioning and on work productivity , respectively . Physicians independently recorded prescribed medications and health care utilization . Results Of the patients , 61.2 % reported experiencing CINV ( 34.3 % with acute CINV and 58.4 % with delayed CINV ) . Based on the FLIE assessment , 37.2 % of all patients reported reduced daily functioning , and of those with poorly managed CINV , about 90 % reported a significant impact on daily functioning . Total costs due to CINV were on average $ 778.58 per patient from the day of administration through the 5 days following the first cycle of chemotherapy ; patients with more severe CINV typically had higher costs . Conclusions CINV remains a significant problem among US patients , suggesting a need for more effective prophylaxis use in clinical practice Background Chemotherapy-induced nausea and vomiting ( CINV ) in cancer patients are common symptoms most feared by patients . The aim of this study was to analyze the impact of CINV associated to moderate/highly emetogenous chemotherapy regimens on patients ’ quality of life ( QoL ) . Patients and methods Open , multicenter , prospect i ve observational study was performed . Each patient filled out a patient diary for each cycle from the day before chemotherapy and for the next 5 days that included the number of emetic episodes , the intensity of nausea , and QoL evaluation ( functional living index-emesis question naire ) . Results Data from 202 consecutive patients from nine university hospitals were collected , but only data from 160 were analyzed ( 79.2 % ) . Most of the participants ( 70 % ) were women with a mean age of 50 years ( SD 1.2 years ) . The most frequent cancer site was breast ( 44 % ) followed by lung ( 16 % ) and 76.3 % were receiving highly emetogenous chemotherapy . Despite the use of antiemetic prophylaxis , patients experienced significant nausea and vomiting during 31 % ( 3.2 % during acute , 15.0 % during delayed phase , and 13.2 % during both phases ) and 45.1 % ( 5.1 % only during the acute phase , 23.5 % only during the delayed phase and 16.5 % during both phases ) of the cycles , respectively , having 44.5 % ( nausea ) and 39.3 % ( emesis ) of the cycles an impact on patients ’ QoL. Conclusions The results of the study confirm the detrimental effect of CINV on patients ’ QoL despite the use of antiemetic prophylaxis ( 5HT3 receptor antagonist , steroids , and dopamine receptor antagonists ) . It is m and atory to intensify the detection of CINV in order to improve the management of these important , albeit frequent , side effects of cancer treatments Purpose Prevention of chemotherapy-induced nausea and vomiting ( CINV ) remains an important goal for patients receiving chemotherapy . The objective of this study was to define , from the UK payer perspective , the cost-effectiveness of an antiemetic regimen using aprepitant , a selective neurokinin-1 receptor antagonist , for patients receiving chemotherapy for breast cancer . Methods A decision-analytic model was developed to compare an aprepitant regimen ( aprepitant , ondansetron , and dexamethasone ) with a st and ard UK antiemetic regimen ( ondansetron , dexamethasone , and metoclopramide ) for expected costs and health outcomes after single-day adjuvant chemotherapy for breast cancer . The model was populated with results from patients with breast cancer participating in a r and omized trial of CINV preventative therapy for cycle 1 of single-day chemotherapy . Results During 5 days after chemotherapy , 64 % of patients receiving the aprepitant regimen and 47 % of those receiving the UK comparator regimen had a complete response to antiemetic therapy ( no emesis and no rescue antiemetic therapy ) . A mean of £ 37.11 ( 78 % ) of the cost of aprepitant was offset by reduced health care re source utilization costs . The predicted gain in quality -adjusted lifeyears ( QALYs ) with the aprepitant regimen was 0.0048 . The incremental cost effectiveness ratio ( ICER ) with aprepitant , relative to the UK comparator , was £ 10,847/QALY , which is well below the threshold commonly accepted in the UK of £ 20,000–£30,000/QALY . Conclusion The results of this study suggest that aprepitant is cost-effective for preventing CINV associated with chemotherapy for patients with breast cancer in the UK health care setting This study combines secondary analysis of efficacy and side-effect data from a r and omised controlled trial with estimates of re source use to evaluate the likely economic effects of the new antiemetic agent ondansetron . Costs , effects and cost-effectiveness of ondansetron in the prophylaxis of acute nausea and vomiting induced by chemotherapy are assessed relative to antiemetic therapy with metoclopramide . Superior efficacy of ondansetron is quantified both in terms of significant emesis avoided and emesis management costs avoided . A simple cost analysis , with the metoclopramide dosage priced at 10 pounds , indicates that therapy with ondansetron would give equivalent net treatment costs , at a price ratio ( ondansetron/metoclopramide ) of 2.3 to 1 . If therapeutic success is defined as the avoidance of emesis and antiemetic side-effects , then the two therapies would be equally cost-effective at a drug price ratio of 5 to 1 . We conclude that , ( i ) economic evaluation prior to price setting is feasible and informative ; ( ii ) such models can indicate prospect i ve data collection priorities Background . Chemotherapy‐induced emesis is one of the most disturbing side effects in cancer therapy . Thus , antiemetic treatment is a m and atory adjunct in emetogenic chemotherapy PURPOSE To compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours ; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours ; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy . PATIENTS AND METHODS This was a multicenter , double-blind , r and omized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients . In arm 1 , dolasetron ( 2.4 mg/kg ) was given intravenously ( I.V. ) prechemotherapy , followed 24 hours later by oral dolasetron ( 200 mg once daily ) for 6 days . Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg I.V. , followed 24 hours later by oral dexamethasone ( 8 mg once daily ) in one arm , and oral dexamethasone and dolasetron in the other , also for 6 days . In arms 4 , 5 , and 6 , ondansetron ( 32 mg I.V. or 8 mg orally twice daily ) was administered in a similar manner to arms 1 , 2 , and 3 before and 24 hours after chemotherapy . Mean nausea severity ( MNS ) was assessed on a visual analog scale ( VAS ) in a daily diary . RESULTS Of 703 patients enrolled , 696 were eligible . There were 343 dolasetron- and 353 ondansetron-treated patients ; 57 % of dolasetron-treated patients had complete protection in the first 24 hours versus 67 % of patients who received ondansetron ( P = .013 ) . MNS was also more pronounced on the dolasetron arm ( P = .051 ) . Sixty-seven percent of patients who received added dexamethasone in the first 24 hours had complete protection , compared with 55 % without dexamethasone ( P < .001 ) . MNS was significantly reduced with the addition of dexamethasone ( P < .001 ) . At 7 days , dolasetron and ondansetron had equivalent complete protection rates ( 36 % and 39 % , respectively ) . With the addition of dexamethasone , 48 % of patients compared with 28 % had complete protection ( P < .001 ) . MNS was significantly improved with added dexamethasone ( P < .001 ) . CONCLUSION At the doses used , dolasetron was significantly less effective than ondansetron at controlling nausea and vomiting in the first 24 hours in patients receiving moderately emetogenic chemotherapy , but there was no demonstrable difference between both drugs over 7 days . The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days The optimal management of transplantation preparative regimen-induced nausea and vomiting remains unknown . We conducted a Phase III double-blind study to determine the efficacy and costs of oral ondansetron versus oral granisetron versus IV ondansetron and PRN rescue antiemetics for the prevention/control of nausea and vomiting associated with high-dose chemotherapy or chemoradiotherapy prior to stem cell transplantation . One hundred two patients were r and omized to receive either 8 mg PO ondansetron every 8 hours , 1 mg PO granisetron every 12 hours , or 32 mg IV ondansetron every 24 hours plus 10 mg IV dexamethasone daily during and 1 day after the various preparative regimens . Study arms were compared in terms of emetic episodes , subjective nausea , amount and cost of rescue antiemetics used , and total costs . Response was defined as complete response ( CR ) , no emesis with no or mild nausea and no rescue antiemetics ; major response ( MR ) , 1 episode of emesis or moderate nausea with or without rescue antiemetics ; and major efficacy ( ME ) , CR + MR . Subjective nausea was assessed using a 100-mm visual analog scale ( VAS ) with 0 = no nausea . Ninety-six patients completed the study ; the trial was analyzed according to intention-to-treat . Overall CR rates were : 48 % for oral ondansetron , 47 % for oral granisetron , and 49 % for IV ondansetron . Overall ME rates were 82 % for oral ondansetron , 84 % for oral granisetron , and 81 % for IV ondansetron . Mean VAS scores were 32 for oral ondansetron , 32 for oral granisetron , and 27 for IV ondansetron . None of the differences were statistically significant . A cost analysis revealed significant differences among all arms ( P = .0001 , all comparisons ) . All 3 regimens had similar efficacy in this BMT population ; oral ondansetron was the most cost-effective OBJECTIVE To compare the efficacy between acupuncture and ondansetron in the prevention of delayed chemotherapy induced nausea and vomiting ( CINV ) . METHODS 70 patients were r and omized to receive either 1 ) acupuncture at P6 point before chemotherapy infusion or 2 ) ondansetron 8 mg intravenously 30 min before chemotherapy infusion in their first cycle with cross-over of antiemetic regimen in the consecutive cycle . All patients received dexamethasone 5 mg orally twice a day for 3 days . Patients were given additional does of ondansetron 4 mg orally every 12h if they experienced emesis . Emetic episode , severity of nausea score of 0 - 10 and adverse events were recorded . Complete response was defined as no nausea , no vomiting and no requirement of additional antiemetic drugs . FACT-G scale was used to evaluate quality of life ( QOL ) 7 days after each cycle of chemotherapy . RESULTS The acupuncture group had a significantly higher rate of complete response in the prevention of delayed CINV ( 52.8 % and 35.7 % , P = 0.02 ) . Compared to another group , the acupuncture group reported significantly lower delayed nausea ( 45.7 % and 65.7 % , P = 0.004 ) , nausea score ( P < 0.001 ) and fewer dosages of additional oral ondansetron ( P = 0.002 ) . Adverse effects were also significantly lower in the acupuncture group with less frequent constipation ( P = 0.02 ) and insomnia ( P = 0.01 ) . Overall FACT-G scores were significantly higher in the acupuncture group . CONCLUSION Acupuncture is effective in preventing delayed CINV and in promoting better QOL . With fewer adverse effects , it may be used as an alternative treatment option for CINV In this double-blind , r and omized trial performed at five study centers , the prophylactic , antiemetic effect of two different dosages of tropisetron ( Navoban ; S and oz Pharma Ltd , Basel , Switzerl and ) was investigated in dacarbazine-treated patients with melanoma . Patients received tropisetron 5 mg or 10 mg orally ( as one capsule ) once daily ( minimum 3 days ) on each day of chemotherapy . No significant differences were found in the effects of tropisetron 5 mg and 10 mg . During the first 24 hours , total control of vomiting was seen in 93 % and 98 % of patients receiving tropisetron 5 mg and 10 mg , respectively . Total control of nausea was achieved in 84 % and 80 % of patients receiving tropisetron at these dosages . Over days 2 to 7 of chemotherapy , total control of vomiting and nausea remained high . Patients reported that quality of life remained good throughout chemotherapy , as did mood ; only a small decrease in food intake occurred . Tropisetron was well tolerated . Constipation was the most common adverse event , occurring in 13 % of patients . Headache ( 4 % ) , diarrhea ( 4 % ) , and anorexia ( 2 % ) also were observed A multicentre r and omised , double-blind parallel group study has been carried out in order to confirm the antiemetic efficacy of orally administered ondansetron . A total of 259 chemotherapy-naive breast cancer patients treated with a 5-fluorouracil , doxorubicin , cyclophosphamide ( FAC ) or 5-fluorouracil , epirubicin , cyclophosphamide ( FEC ) regimen were r and omly assigned to ondansetron ( OND ) 8 mg tablet or alizapride ( ALI ) 150 mg intravenous ( i.v . ) injection , prior to chemotherapy . These treatments were then followed by OND 8 mg tablet or ALI 50 mg tablet , respectively , 8 to 12 h later . Oral treatment was then continued twice a day over 3 - 5 days . The number of emetic episodes ( EE = vomits+retches ) and the grade of nausea were recorded ; quality of life was assessed using a specific question naire . Of the 254 patients analysed for efficacy , complete or major control ( success : 0 - 2 EE ) over the 24 h following start of chemotherapy was obtained in 81 % of the OND group compared with 47 % of the ALI group ( P < 0.001 ) . A significant difference in favour of OND was also observed for nausea ( P < 0.0001 ) . For on days 2 to 4 emesis , the arm containing OND was superior to that with ALI ( worst day analysis ): 77 % success versus 63 % ( P < 0.002 ) . The overall control of emesis ( from day 1 to day 4 ) was better with OND ( 64 % patients success in the OND group versus 41 % in the ALI group ; P < 0.0001 ) . At the end of the study the number of patients wishing to receive the same anti-emetic treatment for their next course was 83 % for OND compared with 54 % for ALI ( P < 0.0001 ) . In terms of quality of life in relation to emesis phenomena , OND was significantly superior to ALI ( P = 0.04 ) . Both treatments were well tolerated . In the prevention of the prolonged emesis induced by FAC/FEC-type emetogenic chemotherapy , orally administered OND was superior to ALI , given as an i.v . injection and followed by tablets OBJECTIVE To estimate the effect of chemotherapy-associated nausea and emesis on patients ' functional status and on costs to the health care system , the patients and society before antagonists to the serotonin ( 5-hydroxytryptamine ) receptor subtype 5-HT3 became available . DESIGN A 5-day prospect i ve survey between February and May 1991 of patients receiving chemotherapy for cancer . Data were obtained from question naires completed by nurses and patients . SETTING Five Canadian cancer treatment centres in Ontario ( three ) and Quebec ( two ) . PATIENTS Out patients and in patients 18 years of age and older who were scheduled to receive chemotherapy with a moderate to high potential for emesis as defined by st and ardized criteria . Patients were excluded if they were scheduled to receive an investigational antiemetic or had received chemotherapy within the previous 7 days . Of the 128 who were eligible , 112 agreed to participate ; 107 returned the completed question naire , but the data for 15 were excluded because the patients received multiple-day chemotherapy . MAIN OUTCOME MEASURES The degree of nausea ( on a seven-point scale ) and the frequency of emesis ( vomiting or retching ) were recorded for each day of the survey . Functional status was assessed before and after chemotherapy by means of the Functional Living Index-Emesis ( FLIE ) . The direct health care costs and the indirect costs ( e.g. , of time off work ) associated with nausea and emesis were estimated from the survey responses and secondary data sources . RESULTS On the day of chemotherapy 38 of the 92 patients ( 41 % ) experienced emesis with or without nausea , and over the 5 days of the survey 72 patients ( 78 % ) reported at least one episode of nausea or emesis . The absolute risk of either problem decreased over time , but the risk of nausea relative to emesis increased over time . The FLIE scores indicated significant worsening of functional status after chemotherapy . On the day after treatment the main impact was from emesis , particularly with regard to leisure activities , household tasks and hardship to the family . Nausea had a significantly greater impact than emesis on overall functioning . The additional direct health care cost for managing emesis was estimated to be $ 63 and the indirect cost $ 121 . CONCLUSIONS Despite prophylaxis with antiemetic drugs , nausea and emesis were significant problems in this population receiving chemotherapy . The management of emesis consumed relatively small amounts of health care re sources , but there were costs outside the hospital for patients and others OBJECTIVES Decision analysis is commonly used to perform economic evaluations of new pharmaceuticals . The outcomes of such studies are often reported as an incremental cost per quality -adjusted life year ( QALY ) gained with the new agent . Decision analysis can also be used in the context of estimating drug cost before market entry . The current study used neurokinin-1 ( NK-1 ) receptor antagonists , a new class of antiemetics for cancer patients , as an example to illustrate the process using an incremental cost of dollars Can20,000 per QALY gained as the target threshold . METHODS A decision model was developed to simulate the control of acute and delayed emesis after cisplatin-based chemotherapy . The model compared st and ard therapy with granisetron and dexamethasone to the same protocol with the addition of an NK-1 before chemotherapy and continued twice daily for five days . The rates of complete emesis control were abstract ed from a double-blind r and omized trial . Costs of st and ard antiemetics and therapy for breakthrough vomiting were obtained from hospital sources . Utility estimates characterized as quality -adjusted emesis-free days were determined by interviewing twenty-five oncology nurses and pharmacists by using the Time Trade-Off technique . These data were then used to estimate the unit cost of the new antiemetic using a target threshold of dollars Can20,000 per QALY gained . RESULTS A cost of dollars Can6.60 per NK-1 dose would generate an incremental cost of dollars Can20,000 per QALY . The sensitivity analysis on the unit cost identified a range from dollars Can4.80 to dollars Can10.00 per dose . For the recommended five days of therapy , the total cost should be dollars Can66.00 ( dollars Can48.00-dollars Can100.00 ) for optimal economic efficiency relative to Canada 's publicly funded health-care system . CONCLUSIONS The use of decision modeling for estimating drug cost before product launch is a powerful technique to ensure value for money . Such information can be of value to both drug manufacturers and formulary committees , because it would facilitate negotiations for optimal pricing in a given jurisdiction The cost effectiveness of ondansetron was compared with that of metoclopramide in the prevention of acute emesis due to highly emetogenic chemotherapy in an open , r and omised , parallel group pilot study . Ondansetron was given as three 8 mg intravenous doses ( 0 , 4 and 8 h ) and metoclopramide as an intravenous loading dose ( 3 mg/kg ) followed by a maintenance dose of 0.5 mg/kg/h for 8 h. Therapeutic outcomes and full utilisation costs , that is nursing time , material costs , in addition to drug acquisition prices were recorded for each antiemetic for 24 h following chemotherapy . The cost per successfully treated patient ( < or = 1 emetic episode and no adverse events ) was 95.20 pounds for ondansetron and 92.18 pounds for metoclopramide . The results of the study therefore suggest that for the control of acute emesis due to highly emetogenic chemotherapy ondansetron and metoclopramide are equally cost-effective treatments Goals of workThe aim of this paper is to analyze the costs of chemotherapy-induced nausea and vomiting ( CINV ) in Italy . Material s and methods In this prospect i ve observational study at seven public oncology centers , incidence and intensity of CINV daily for 8 days after chemotherapy in consecutive patients receiving cisplatin-containing chemotherapy were recorded . All costs related to CINV ( direct medical , direct nonmedical , and indirect ) were recorded ( in 2003 euros).Main results A total of 172 patients were enrolled ; cost data were available for 168 patients . Thirty-seven percent of patients experienced acute CINV , and 57 % experienced delayed CINV ; 39 % achieved total control , defined as no nausea , vomiting , or rescue therapy . Mean per-patient costs of acute and delayed CINV were € 30.03 from the hospital perspective , € 4.9 from the patient perspective , and € 26.85 from the National Health Service ( NHS ) perspective . Costs of CINV were highly variable among oncology centers , largely because of differences in procedures for preventing delayed CINV . These costs were four times higher when antiemetic drugs were prescribed and paid for by the NHS than when antiemetic prophylaxis was provided directly from hospital pharmacies . Moreover , in the delayed phase , the NHS incurred a 94 % increase in costs for patients without total control . Overall costs for patients who did not experience total control of CINV were € 35.57 higher than for those who did ( 85 % increase ) . Conclusions Costs of CINV for the Italian NHS could be reduced if hospitals furnished antiemetic prophylaxis directly to patients . Better control of both acute and delayed CINV would improve patient well-being as well as reduce the budgetary impact of CINV in Italy This was a multicentre , r and omised , double-blind , parallel-group study which included female breast cancer patients , receiving their first of 6 scheduled courses of chemotherapy ( cyclophosphamide greater than or equal to 500 mg/m2 ) . Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy , followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days . A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide . On day 1 of their first course of treatment 91 and 60 % of patients in the ondansetron and metoclopramide groups respectively were free of emesis ( p less than 0.001 ) . Over the 5-day treatment period , the corresponding figures were 81 and 48 % ( p less than 0.001 ) . The results for nausea also revealed highly statistically significant treatment differences ( p less than 0.001 ) in favour of ondansetron for both day 1 and day 1 - 5 analyses of the first treatment course . Over the series of courses , 67 % of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day , compared with 28 % of patients receiving metoclopramide ( p less than 0.001 ) . A similar analysis for nausea revealed that 49 % of patients receiving ondansetron completed all 6 courses with ' none ' or ' mild ' nausea compared with 27 % of patients receiving metoclopramide ( p less than 0.001 ) . These differences were reflected in quality of life data ( Rotterdam Symptom Checklist ) . After the first course of treatment , a statistically significant improvement ( p = 0.002 ) in the psychological subscale scores was observed after ondansetron compared with metoclopramide . No differences were observed in the physical or functional activity subscales after the first course . However , the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores ( p less than 0.001 ) as well as trends in favour of ondansetron in the physical ( p = 0.096 ) and functional activity ( p = 0.056 ) subscales . Extrapyramidal symptoms were reported in 19 % of patients in the metoclopramide group and result ed in 15 % of patients withdrawing from their r and omised anti-emetic schedule , either during or between treatment courses . Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment . In conclusion , this study shows that ondansetron is significantly superior to metoclopramide ( each with a single pre-treatment dose of dexamethasone ) in the control of emesis over 6 courses of chemotherapy for breast cancer . ( ABSTRACT TRUNCATED AT 400 WORDS |
13,941 | 32,270,873 | We did not find any studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of clonidine for the prevention or treatment of procedural or postoperative pain , or pain associated with clinical conditions in neonates | BACKGROUND Critically ill newborn infants undergo a variety of painful procedures or experience a variety of painful conditions during their early life in the neonatal unit .
In the critically ill paediatric and neonatal population , clonidine is prescribed as an adjunct to opioids or benzodiazepines aim ing to reduce the doses of these drugs that are required for analgesia or sedation , or to facilitate weaning from mechanical ventilation .
It has been shown that clonidine premedication might have a positive effect on postoperative pain in children .
OBJECTIVES To assess the benefit and harms of clonidine for the prevention or treatment of procedural pain ; postoperative pain ; or pain associated with clinical conditions in non-ventilated neonates . | Objectives To evaluate the ability of the Behavioral Indicators of Infant Pain ( BIIP ) scale to discriminate between skin-breaking and nonskin breaking procedures , and to identify sensitized pain responses in preterm infants in the neonatal intensive care unit ( NICU ) . Methods Sixty-nine infants born between 24 and 32 weeks gestational age were assessed at 32 weeks postconceptional age during blood collection on one day ( procedure A ) , and then on another day during blood collection preceded by a diaper change ( procedure B ) . Procedure order was r and omized . Outcome measures were changes in BIIP coded from continuous bedside video recordings and changes in heart rate ( HR ) . Results During blood collection ( procedure A ) , BIIP scores ( P<0.0001 ) and mean HR ( P<0.0001 ) were higher than during the diaper change and higher when the infants had had a preceding diaper change ( procedure B vs. procedure A ) ( P<0.03 ) . HR changed from baseline to the stressors for each procedure . No differences in mean HR were observed during Lance phase between the procedure A and the B blood collection ; however , HR remained elevated significantly during the Recovery phase when blood collection was preceded by the diaper change ( P<0.03 ) . Discussion The BIIP scale is reliable , accurate , and valid assessment for measuring acute pain in preterm infants in the NICU . This assessment combines the relatively most specific , anatomically based , theoretically derived indicators ; and it allows evaluation of behavioral and physiologic pain responses separately OBJECTIVES To examine the construct validity , inter-rater reliability , and feasibility of the Premature Infant Pain Profile-Revised in infants of varying gestational ages , diagnoses , and procedures . METHODS A prospect i ve cross-over study with infants in three gestational age groups ( 26 - 31 , 32 - 36 , and ≥37 weeks ) at three university-affiliated Neonatal Intensive Care Units in Canada . One hundred and ninety five bedside nurses and expert raters rated 202 hospitalized infants ' pain during scheduled procedures using the measure . An expert rater and a nurse independently assessed infants ' pain scores , using the Premature Infant Pain Profile-Revised , during 246 scheduled pairs of painful and non-painful procedures in the 202 infants . Nurses also completed a feasibility survey on using the measure in a clinical setting . To establish construct validity , pain scores were computed during painful and non-painful procedures . Inter-rater reliability between pain experts and nurses was calculated . A 5-point Likert scale was used to measure feasibility in terms of clarity , ease of use , and time to complete . RESULTS Irrespective of gestational age , Premature Infant Pain Profile-Revised scores were significantly higher during painful procedures ( mean 6.7 [ SD 3.0 ] ) compared to non-painful procedures ( mean 4.8 [ SD 2.9 ] ) . There was a high degree of correlation between nurses ' and experts ' ratings for painful ( all R(2)=0.92 , p<0.001 ) and non-painful ( all R(2)=0.87 , p<0.001 ) procedures . Mean scores on all feasibility indicators were equal to or higher than 3.8 . DISCUSSION The Premature Infant Pain Profile Revised has beginning construct validation , inter-rater reliability , and is considered feasible by clinicians . Concurrent validation studies should be considered CONTEXT Effective strategies to improve pain management in neonates require a clear underst and ing of the epidemiology and management of procedural pain . OBJECTIVE To report epidemiological data on neonatal pain collected from a geographically defined region , based on direct bedside observation of neonates . DESIGN , SETTING , AND PATIENTS Between September 2005 and January 2006 , data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospect ively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France ( 11.3 millions inhabitants ) for the Epidemiology of Procedural Pain in Neonates ( EPIPPAIN ) study . MAIN OUTCOME MEASURE Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy . RESULTS The mean ( SD ) gestational age and intensive care unit stay were 33.0 ( 4.6 ) weeks and 8.4 ( 4.6 ) calendar days , respectively . Neonates experienced 60,969 first-attempt procedures , with 42,413 ( 69.6 % ) painful and 18,556 ( 30.4 % ) stressful procedures ; 11,546 supplemental attempts were performed during procedures including 10,366 ( 89.8 % ) for painful and 1180 ( 10.2 % ) for stressful procedures . Each neonate experienced a median of 115 ( range , 4 - 613 ) procedures during the study period and 16 ( range , 0 - 62 ) procedures per day of hospitalization . Of these , each neonate experienced a median of 75 ( range , 3 - 364 ) painful procedures during the study period and 10 ( range , 0 - 51 ) painful procedures per day of hospitalization . Of the 42,413 painful procedures , 2.1 % were performed with pharmacological-only therapy ; 18.2 % with nonpharmacological-only interventions , 20.8 % with pharmacological , nonpharmacological , or both types of therapy ; and 79.2 % without specific analgesia , and 34.2 % were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons . Prematurity , category of procedure , parental presence , surgery , daytime , and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia , whereas mechanical ventilation , noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia . CONCLUSION During neonatal intensive care in the Paris region , large numbers of painful and stressful procedures were performed , the majority of which were not accompanied by analgesia BACKGROUND Spinal anesthesia ( SA ) remains the ' gold st and ard ' in neonatal anesthesia for inguinal herniorrhaphy but its short duration impedes its usefulness . We previously demonstrated that clonidine prolongs neonatal SA without immediate side effects . METHODS We conducted a prospect i ve observational study of 124 infants undergoing herniorrhaphy under SA with bupivacaine and clonidine . Two cohorts , term ( n = 57 ) and former preterm ( n = 67 ) infants , were evaluated and compared with regard to episodes of apnea , desaturation , and bradycardia within 24 h of SA . RESULTS In both groups , postoperative desaturation episodes were unchanged after SA , compared with the 12 preoperative hours , despite significantly increased apnea ( P < 0.003 and < 0.011 respectively ) . Transient bradycardias occurred in former preterm infants ( P < 0.014 ) : they spontaneously resolved in all cases . Mean arterial pressure did not vary during the study . Upper sensory level of SA , sedation on entering the postanesthesia care unit ( PACU ) and duration of stay in the PACU were similar in both groups . CONCLUSIONS The clinical significance of short apneas , recovering spontaneously without desaturation , remains debatable . It is concluded that addition of clonidine to neonatal SA results in acceptable side effects . Side effects must be compared with the potential advantages before future recommendations Objectives : To assess the influence of an infusion of clonidine 1 & mgr;g/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants . Design : Prospect i ve , double-blind , r and omized controlled multicenter trial . Controlled trials.com/IS RCT N77772144 . Setting : Twenty-eight level 3 German PICUs/neonatal ICUs . Patients : Ventilated newborns and infants : stratum I ( 1–28 d ) , stratum II , ( 29–120 d ) , and stratum III ( 121 d to 2 yr ) . Interventions : Patients received clonidine 1 & mgr;g/kg/hr or placebo on day 4 after intubation . Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score . Measurements and Main Results : Two hundred nineteen infants were r and omized ; 212 received study medication , 69.7 % were ventilated in the postoperative care and 30.3 % for other reasons . Primary endpoint : consumption of fentanyl and midazolam in the 72 hours following the onset of study medication ( main observation period ) in the overall study population . The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam . Explorative age-stratified analysis demonstrated that in stratum I ( n = 112 ) the clonidine group had a significantly lower consumption of fentanyl ( clonidine : 2.1 ± 1.8 & mgr;g/kg/hr , placebo : 3.2 ± 3.1 & mgr;g/kg/hr ; p = 0.032 ) and midazolam ( clonidine : 113.0 ± 100.1 & mgr;g/kg/hr , placebo : 180.2 ± 204.0 & mgr;g/kg/hr ; p = 0.030 ) . Strata II ( n = 43 ) and III ( n = 46 ) showed no statistical difference . Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I ( p < 0.001 ) . Frequency of severe adverse events did not differ between groups . Conclusions : Clonidine 1 & mgr;g/kg/hr in ventilated newborns reduced fentanyl and midazolam dem and with deeper levels of analgesia and sedation without substantial side effects . This was not demonstrated in older infants , possibly due to lower clonidine serum levels OBJECTIVE Inadequate assessment of pain in premature infants is a persistent clinical problem . The objective of this research was to develop and vali date a measure for assessing pain in premature infants that could be used by both clinicians and research ers . DESIGN The Premature Infant Pain Profile ( PIPP ) was developed and vali date d using a prospect i ve and retrospective design . Indicators of pain were identified from clinical experts and the literature . Indicators were retrospectively tested using four existing data sets . PATIENTS AND SETTING S Infants of varying gestational ages undergoing different painful procedures from three different setting s were utilized to develop and vali date the measure . METHODS AND RESULTS The largest data set ( n = 124 ) was used to develop the PIPP . The development process included determining the factor structure of the data , developing indicators and indicator scales and establishing internal consistency . The remaining three data sets were utilized to establish beginning construct validity . CONCLUSIONS The PIPP is a newly developed pain assessment measure for premature infants with beginning content and construct validity . The practicality and feasibility for using the PIPP in clinical practice will be determined in prospect i ve research in the clinical setting Objective The objectives of this study were to : ( 1 ) evaluate the validity of the Neonatal Facial Coding System ( NFCS ) for assessment of postoperative pain and ( 2 ) explore whether the number of NFCS facial actions could be reduced for assessing postoperative pain . Design Prospect i ve , observational study . Patients Thirty-seven children ( 0–18 months old ) undergoing major abdominal or thoracic surgery . Outcome Measures The outcome measures were the NFCS , COMFORT “ behavior ” scale , and a Visual Analog Scale ( VAS ) , as well as heart rate , blood pressure , and catecholamine and morphine plasma concentrations . At 3-hour intervals during the first 24 hours after surgery , nurses recorded the children 's heart rates and blood pressures and assigned COMFORT “ behavior ” and VAS scores . Simultaneously we videotaped the children 's faces for NFCS coding . Plasma concentrations of catecholamine , morphine , and its metabolite M6 G were determined just after surgery , and at 6 , 12 , and 24 hours postoperatively . Results All 10 NFCS items were combined into a single index of pain . This index was significantly associated with COMFORT “ behavior ” and VAS scores , and with heart rate and blood pressure , but not with catecholamine , morphine , or M6 G plasma concentrations . Multidimensional scaling revealed that brow bulge , eye squeeze , nasolabial furrow , horizontal mouth stretch , and taut tongue could be combined into a reduced measure of pain . The remaining items were not interrelated . This reduced NFCS measure was also significantly associated with COMFORT “ behavior ” and VAS scores , and with heart rate and blood pressure , but not with the catecholamine , morphine , or M6 G plasma concentrations . Conclusion This study demonstrates that the NFCS is a reliable , feasible , and valid tool for assessing postoperative pain . The reduction of the NFCS to 5 items increases the specificity for pain assessment without reducing the sensitivity and validity for detecting changes in pain IMPORTANCE Continuous morphine infusion as st and ard postoperative analgesic therapy in young infants is associated with unwanted adverse effects such as respiratory depression . OBJECTIVE To determine whether intravenous paracetamol ( acetaminophen ) would significantly ( > 30 % ) reduce morphine requirements in neonates and infants after major surgery . DESIGN , SETTING , AND PATIENTS Single-center , r and omized , double-blind study conducted in a level 3 pediatric intensive care unit in Rotterdam , The Netherl and s. Patients were 71 neonates or infants younger than 1 year undergoing major thoracic ( noncardiac ) or abdominal surgery between March 2008 and July 2010 , with follow-up of 48 hours . INTERVENTIONS All patients received a loading dose of morphine 30 minutes before the end of surgery , followed by continuous morphine or intermittent intravenous paracetamol up to 48 hours postsurgery . Infants in both study groups received morphine ( boluses and /or continuous infusion ) as rescue medication on the guidance of the vali date d pain assessment instruments . MAIN OUTCOME MEASURES Primary outcome was cumulative morphine dose ( study and rescue dose ) . Secondary outcomes were pain scores and morphine-related adverse effects . RESULTS The cumulative median morphine dose in the first 48 hours postoperatively was 121 ( interquartile range , 99 - 264 ) μg/kg in the paracetamol group ( n = 33 ) and 357 ( interquartile range , 220 - 605 ) μg/kg in the morphine group ( n = 38 ) , P < .001 , with a between-group difference that was 66 % ( 95 % CI , 34%-109 % ) lower in the paracetamol group . Pain scores and adverse effects were not significantly different between groups . CONCLUSION AND RELEVANCE Among infants undergoing major surgery , postoperative use of intermittent intravenous paracetamol compared with continuous morphine result ed in a lower cumulative morphine dose over 48 hours . TRIAL REGISTRATION trialregister.nl Identifier : NTR1438 BACKGROUND Propofol is a popular agent for providing procedural sedation in pediatric population during lumbar puncture and spinal anesthesia . Adjuvants like clonidine and fentanyl are administered intrathecally to prolong the duration of spinal anesthesia and to provide postoperative analgesia . We studied the propofol requirement after intrathecal administration of clonidine or fentanyl in infants undergoing lower abdominal surgeries . METHODS Sixty-five ASA I infants undergoing elective lower abdominal surgery under spinal anesthesia were assigned into four groups in this prospect i ve r and omized double-blinded study . Group B received bupivacaine based on body weight ( < 5 kg = 0.5 mg kg(-1 ) ; 5 - 10 kg = 0.4 mg kg(-1 ) ) . Group BC received 1 microg kg(-1 ) of clonidine with bupivacaine , group BF received 1 microg kg(-1 ) of fentanyl with bupivacaine , and patients in group BCF received 1 microg kg(-1 ) each of clonidine and fentanyl with bupivacaine . A bolus of 2 - 3 mg kg(-1 ) of propofol bolus was administered for lumbar puncture . Sedation was assessed using a six-point sedation score ( 0 - 5 ) and a five-point reactivity score ( 0 - 4 ) which was based on a behavioral score . After achieving a sedation and reactivity score of 3 - 4 , the patients were placed lateral in knee chest position and lumbar puncture performed and test drug administered . Further intraoperative sedation was maintained with an infusion of 25 - 50 microg kg(-1 ) min(-1 ) of propofol infusion . RESULTS The mean + /- SD infusion requirement of propofol decreased from 35.5 + /- 4.5 in group B to 33.4 + /- 5.4 microg kg(-1 ) min(-1 ) in group BF and further decreased to 16.7 + /- 6.2 microg kg(-1 ) min(-1 ) and 14.8 + /- 4.9 microg kg(-1 ) min(-1 ) in group BC and BCF , respectively . There were no statistically significant differences between BC and BCF groups . The mean sedation and reactivity scores were higher in groups BC and BCF when compared to groups B and BF . CONCLUSION Our study show that the requirement of propofol sedation reduces with intrathecal adjuvants . The reduction was significant with the addition of clonidine and clonidine-fentanyl combination as opposed to bupivacaine alone or with fentanyl . There was no significant difference in propofol infusion requirement with the use of bupivacaine alone or with fentanyl OBJECTIVE : Ophthalmologic examination for retinopathy of prematurity is a painful procedure . Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations . This study aims to evaluate the analgesic effect of 25 % glucose using a vali date d pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight ≤1,500 g and /or gestational age ≤32 weeks . METHODS : A masked , r and omized clinical trial for one dose of 1 ml of oral 25 % glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010 . The results were compared to those of a control group that did not receive oral glucose solution . Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups . Clinical trials.gov : NCT00648687 RESULTS : One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included . Seventy were included in the intervention group and 54 in the control group . The number of patients with pain immediately before the procedure was similar in both groups . The number of patients with pain after ophthalmologic examination was 15.7 % in the intervention group and 68.5 % in the control group ( p<0.001 ) . CONCLUSIONS : One ml of oral 25 % glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief OBJECTIVE To develop and vali date a scale suitable for use in clinical practice as a tool for assessing prolonged pain in premature infants . METHODS Pain indicators identified by observation of preterm infants and selected by a panel of experts were used to develop the EDIN scale ( Échelle Douleur Inconfort Nouveau-Né , neonatal pain and discomfort scale ) . A cohort of preterm infants was studied prospect ively to determine construct validity , inter-rater reliability , and internal consistency of the scale . RESULTS The EDIN scale uses five behavioural indicators of prolonged pain : facial activity , body movements , quality of sleep , quality of contact with nurses , and consolability . The validation study included 76 preterm infants with a mean gestational age of 31.5 weeks . Inter-rater reliability was acceptable , with a κ coefficient range of 0.59–0.74 . Internal consistency was high : Cronbach 's α coefficients calculated after deleting each item ranged from 0.86 to 0.94 . To establish construct validity , EDIN scores in two extreme situations ( pain and no pain ) were compared , and a significant difference was observed . CONCLUSIONS The validation data suggest that the EDIN is appropriate for assessing prolonged pain in preterm infants . Further studies are warranted to obtain further evidence of construct validity by comparing scores in less extreme situations In a r and omised controlled trial , preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine , with ( n = 8) or without ( n = 8) the addition of fentanyl ( 10 micrograms/kg intravenously ) to the anaesthetic regimen . Major hormonal responses to surgery , as indicated by changes in plasma adrenaline , noradrenaline , glucagon , aldosterone , corticosterone , 11-deoxycorticosterone , and 11-deoxycortisol levels , in the insulin/glucagon , molar ratio , and in blood glucose , lactate , and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group . The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non-fentanyl group on the second and third postoperative days . Compared with the fentanyl group , the non-fentanyl group had circulatory and metabolic complications postoperatively . The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome & NA ; Assessment of infant pain is a pressing concern , especially within the context of neonatal intensive care where infants may be exposed to prolonged and repeated pain during lengthy hospitalization . In the present study the feasibility of carrying out the complete Neonatal Facial Coding System ( NFCS ) in real time at bedside , specifically reliability , construct and concurrent validity , was evaluated in a tertiary level Neonatal Intensive Care Unit ( NICU ) . Heel lance was used as a model of procedural pain , and observed with n=40 infants at 32 weeks gestational age . Infant sleep/wake state , NFCS facial activity and specific h and movements were coded during baseline , unwrap , swab , heel lance , squeezing and recovery events . Heart rate was recorded continuously and digitally sample d using a custom design ed computer system . Repeated measures analysis of variance ( ANOVA ) showed statistically significant differences across events for facial activity ( P<0.0001 ) and heart rate ( P<0.0001 ) . Planned comparisons showed facial activity unchanged during baseline , swab and unwrap , then increased significantly during heel lance ( P<0.0001 ) , increased further during squeezing ( P<0.003 ) , then decreased during recovery ( P<0.0001 ) . Systematic shifts in sleep/wake state were apparent . Rise in facial activity was consistent with increased heart rate , except that facial activity more closely paralleled initiation of the invasive event . Thus facial display was more specific to tissue damage compared with heart rate . Inter‐observer reliability was high . Construct validity of the NFCS at bedside was demonstrated as invasive procedures were distinguished from tactile . While bedside coding of behavior does not permit raters to be blind to events , mechanical recording of heart rate allowed for an independent source of concurrent validation for bedside application of the NFCS scale We performed the current study in mice lacking individual α2-adrenoceptor subtypes to eluci date the contribution of α2-adrenoceptor subtypes to the neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic brain injury . On postnatal Day 5 , wild-type mice and mice lacking α2A-adrenoceptor ( α2A-KO ) or α2C-adrenoceptor subtypes ( α2C-KO ) were r and omly assigned to receive dexmedetomidine ( 3 & mgr;g/kg ) or phosphate-buffered saline intraperitoneally . Thirty minutes after the intraperitoneal injection , the glutamatergic agonist ibotenate ( 10 & mgr;g ) was intracerebrally injected , producing transcortical necrosis and white matter lesions that mimic perinatal human hypoxic-like lesions . Quantification of the lesions was performed on postnatal Day 10 by histopathologic examination . Dexmedetomidine reduced mean lesion size in the cortex of wild-type mice and α2C-KO mice by 44 % and 49 % , respectively . Ibotenate-induced white matter lesions were reduced by 71 % ( wild-type mice ) and 75 % ( α2C-KO mice ) after pretreatment with dexmedetomidine . In contrast , in α2A-KO mice , dexmedetomidine did not protect against the cortical excitotoxic insult , and white matter lesions were even more pronounced ( 82 % increase of mean lesion size ) . Dexmedetomidine provides potent neuroprotection in a model of perinatal excitotoxic brain damage . This effect was completely abolished in α2A-KO mice , suggesting that the neuroprotective effect is mediated via the α2A-adrenoceptor subtype Objective : To establish evidence of clinical validity and reliability of the Neonatal Pain , Agitation , and Sedation Scale ( N-PASS ) in neonates with acute heelstick pain . Study Design : Prospect i ve psychometric evaluation , r and omized crossover design . Two nurses administered the N-PASS simultaneously and independently during an actual and sham heelstick done in r and omized order . One nurse also administered the Premature Infant Pain Profile ( PIPP ) concurrently with the N-PASS . Heelsticks were videotaped for repeat analysis . Result : Construct ( discriminate ) validity was established through the Wilcoxon Signed-ranks test , comparing the distribution of the heelstick and sham N-PASS scores . The mean pain scores were 3.93 ( 2.30 ) and 0.81 ( 1.21 ) for the heelstick and sham procedures , respectively ( Z=−6.429 , P<0.0001 ) . Convergent validity was demonstrated by correlation with the PIPP scores ( Spearman rank correlation coefficient of 0.75 and 0.72 for raters 1 and 2 , respectively ) . Inter-rater reliability was high , measured by intra-class coefficients ; the ICC estimates ( 95 % CI ) of the pain scale were 0.86 ( 0.78 , 0.92 ) and 0.93 ( 0.88 , 0.96 ) for a single rating and average of two independent ratings , respectively ( P<0.0001 ) . Internal consistency , measured by Cronbach 's alpha , was evident ( 0.84 to 0.89 ) . Test – retest reliability was demonstrated by repeat scoring of videotaped heelsticks , measured by Spearman 's rho correlation ( 0.874 , P<0.0001 ) . Conclusion : This research provides beginning evidence that the N-PASS is a valid and reliable tool for assessing acute heelstick pain in infants 0 to 30 days of age , 23 to 40 weeks gestation CONTEXT Newborns admitted to neonatal intensive care units ( NICUs ) undergo a variety of painful procedures and stressful events . Because the effect of continuous morphine infusion in preterm neonates has not been investigated systematic ally , there is confusion regarding whether morphine should be used routinely in this setting . OBJECTIVE To evaluate the effects of continuous intravenous morphine infusion on pain responses , incidence of intraventricular hemorrhage ( IVH ) , and poor neurologic outcome ( severe IVH , periventricular leukomalacia , or death ) . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled trial conducted between December 2000 and October 2002 in 2 level III NICUs in the Netherl and s of 150 newborns who had received ventilatory support ( inclusion criteria : postnatal age younger than 3 days and ventilation for less than 8 hours ; exclusion criteria : severe asphyxia , severe IVH , major congenital malformations , and administration of neuromuscular blockers ) . INTERVENTIONS Intravenous morphine ( 100 microg/kg and 10 microg/kg per hour ) or placebo infusion was given for 7 days ( or less because of clinical necessity in several cases ) . MAIN OUTCOME MEASURES The analgesic effect of morphine , as assessed using vali date d scales ; the effect of morphine on the incidence of IVH ; and poor neurologic outcome . RESULTS The analgesic effect did not differ between the morphine and placebo groups , judging from the following median ( interquartile range ) pain scores : Premature Infant Pain Profile , 10.1 ( 8.2 - 11.6 ) vs 10.0 ( 8.2 - 12.0 ) ( P = .94 ) ; Neonatal Infant Pain Scale , 4.8 ( 3.7 - 6.0 ) vs 4.8 ( 3.2 - 6.0 ) ( P = .58 ) ; and visual analog scale , 2.8 ( 2.0 - 3.9 ) vs 2.6 ( 1.8 - 4.3 ) ( P = .14 ) , respectively . Routine morphine infusion decreased the incidence of IVH ( 23 % vs 40 % , P = .04 ) but did not influence poor neurologic outcome ( 10 % vs 16 % , P = .66 ) . In addition , analyses were adjusted for the use of additional open-label morphine ( 27 % of morphine group vs 40 % of placebo group , P = .10 ) . CONCLUSIONS Lack of a measurable analgesic effect and absence of a beneficial effect on poor neurologic outcome do not support the routine use of morphine infusions as a st and ard of care in preterm newborns who have received ventilatory support . Follow-up is needed to evaluate the long-term effects of morphine infusions on the neurobehavioral outcomes of prematurity BACKGROUND Opioid analgesia is commonly used during neonatal intensive care . We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates ( NEOPAIN ) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death , severe intraventricular haemorrhage ( IVH ) , and periventricular leucomalacia ( PVL ) in preterm neonates . METHODS Ventilated preterm neonates ( n=898 ) from 16 centres were r and omly assigned masked placebo ( n=449 ) or morphine ( n=449 ) infusions . After a loading dose ( 100 microg/kg ) , morphine infusions ( 23 - 26 weeks of gestation 10 microg kg(-1 ) h(-1 ) ; 27 - 29 weeks 20 microg kg(-1 ) h(-1 ) ; 30 - 32 weeks 30 microg kg(-1 ) h(-1 ) ) were continued as long as clinical ly justified ( maximum 14 days ) . Open-label morphine could be given on clinical judgment ( placebo group 242/443 [ 54.6 % ] , morphine group 202/446 [ 45.3 % ] ) . Analyses were by intention to treat . FINDINGS Baseline variables were similar in the r and omised groups . The placebo and morphine groups had similar rates of the composite outcome ( 105/408 [ 26 % ] vs 115/419 [ 27 % ] ) , neonatal death ( 47/449 [ 11 % ] vs 58/449 [ 13 % ] ) , severe IVH ( 46/429 [ 11 % ] vs 55/411 [ 13 % ] ) , and PVL ( 34/367 [ 9 % ] vs 27/367 [ 7 % ] ) . For neonates who were not given open-label morphine , rates of the composite outcome ( 53/225 [ 24 % ] vs 27/179 [ 15 % ] , p=0.0338 ) and severe IVH ( 19/219 [ 9 % ] vs 6/189 [ 3 % ] , p=0.0209 ) were higher in the morphine group than the placebo group . Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine ( 78/228 [ 34 % ] vs 27/179 [ 15 % ] , p<0.0001 ) . Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH ( 36/190 [ 19 % ] vs 19/219 [ 9 % ] , p=0.0024 ) . INTERPRETATION Pre-emptive morphine infusions did not reduce the frequency of severe IVH , PVL , or death in ventilated preterm neonates , but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome . The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates Objective . Bronchopulmonary dysplasia ( BPD ) is the endpoint of many intervention trials in neonatology , yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians . We previously reported a technique to st and ardize the definition of BPD between sites by using a timed room-air challenge in selected infants . We hypothesized that a physiologic definition of BPD would reduce the variation in observed rates of BPD among different neonatal centers . Methodology . A total of 1598 consecutive inborn premature infants ( 501–1249 g birth weight ) who remained hospitalized at 36 weeks ' postmenstrual age were prospect ively assessed and assigned an outcome with both a clinical definition and physiologic definition of BPD . The clinical definition of BPD was oxygen supplementation at exactly 36 weeks ' postmenstrual age . The physiologic definition of BPD was assigned at 36 ± 1 weeks ' postmenstrual age and included 2 distinct sub population s. First , neonates on positive pressure support or receiving > 30 % supplemental oxygen with saturations between 90 % and 96 % were assigned the outcome BPD and not tested further . Second , those receiving ≤30 % oxygen or effective oxygen > 30 % with saturations > 96 % underwent a room-air challenge with continuous observation and oxygen-saturation monitoring . Outcomes of the room-air challenge were “ no BPD ” ( saturations ≥90 % during weaning and in room air for 30 minutes ) or “ BPD ” ( saturation < 90 % ) . At the conclusion of the room-air challenge , all infants were returned to their baseline oxygen levels . Safety ( apnea , bradycardia , increased oxygen use ) and outcomes of the physiologic definition versus the clinical definition were assessed . Results . A total of 560 ( 35.0 % ) neonates were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks ' postmenstrual age . The physiologic definition diagnosed BPD in 398 ( 25.0 % ) neonates in the cohort . All infants were safely studied . There were marked differences in the impact of the definition on BPD rates between centers ( mean reduction : 10 % ; range : 0–44 % ) . Sixteen centers had a decrease in their BPD rate , and 1 center had no change in their rate . Conclusions . The physiologic definition of BPD reduced the overall rate of BPD and reduced the variation among centers . Significant center differences in the impact of the physiologic definition were seen , and differences remained even with the use of this st and ardized definition . The magnitude of the change in BPD rate is comparable to the magnitude of treatment effects seen in some clinical trials in BPD . The physiologic definition of BPD facilitates the measurement of BPD as an outcome in clinical trials and the comparison between and within centers over time Background Neonatal pain assessment generally requires access to facial expression . Improved neonatology practice s , such as greater protection against bright lights and non-invasive mask ventilation , have made facial observation more difficult . Objective To vali date a ‘ faceless ’ acute neonatal pain scale ( FANS ) , which does not depend on facial expression . Methods In a prospect i ve , multicentre study , 24–40-week-old neonates were videotaped during a painful procedure ( heel prick ) . Three investigators then scored the pain using FANS and a previously vali date d scale : DAN ( Douleur aiguë du Nouveau-né ) . FANS is based on assessment of limb movement , cry and autonomic reaction . Reliability was assessed by inter-rater agreement and internal consistency ( Cronbach 's α ) . Validity was evaluated by agreement between scales ( intraclass correlation coefficient ( ICC ) ) . The Wilcoxon test evaluated the FANS score differences between conditions . Results are expressed as medians ( 25th and 75th percentiles ) . Ranges are presented for outcome parameters . Results From April 2006 to September 2007 , 53 preterms of 32 ( 30–35 ) gestational weeks and 1500 ( 1000–2200 ) g were observed . Cronbach 's α was 0.72 . The ICC was 0.92 ( 0.9–0.98 ) for inter-rater agreement and 0.88 ( 0.76–0.93 ) for agreement between scales . Conclusion FANS , which is reliable and valid , is the first scale to score pain in preterm newborns when facial expression is not accessible Objective : To establish beginning evidence of clinical validity and reliability of the Neonatal Pain , Agitation and Sedation Scale ( N-PASS ) in neonates with prolonged pain postoperatively and during mechanical ventilation . Study Design : Prospect i ve psychometric evaluation . Two nurses administered the N-PASS simultaneously and independently before and after pharmacologic interventions for pain or sedation . One nurse also administered the premature infant pain profile ( PIPP ) concurrently with the N-PASS . The setting consisted of 50-bed level III neonatal intensive care unit . Convenience sample of 72 observations of 46 ventilated and /or postoperative infants , 0 to 100 days of age , gestational age 23 to 40 weeks was used . Outcome measures comprised convergent and construct validity , interrater reliability and internal consistency . Result : Interrater reliability measured by intraclass coefficients of 0.85 to 0.95 was high ( P<0.001 to 0.0001 ) . Convergent validity was demonstrated by correlation with the PIPP scores ( Spearman 's rank correlation coefficient of 0.83 at high pain scores , 0.61 at low pain scores ) . Internal consistency , measured by Cronbach 's α , was evident with pain scores ( 0.82 ) , and with sedation scores ( 0.87 ) . Construct validity was established via the Wilcoxon signed-rank test , comparing the distribution of N-PASS scores before and after pharmacologic intervention showing pain scores of 4.86 ( 3.38 ) and 1.81 ( 1.53 ) ( mean ( s.d . ) , P<0.0001 ) and sedation scores of 0.85 ( 1.66 ) and −2.78 ( 2.81 ) ( P<0.0001 ) for pre- and postintervention assessment s , respectively . Conclusions : This research provides beginning evidence that the N-PASS is a valid and reliable tool for assessing pain/agitation and sedation in ventilated and /or postoperative infants 0 to 100 days of age , and 23 weeks gestation and above Spinal anesthesia may reduce the incidence of morbidity that follows general anesthesia in neonates and in former preterm infants . However , bupivacaine alone provides a block too short for complete surgery in up to 40 % of the patients . Clonidine lengthens spinal anesthesia in adults and caudal block in children without significant side effects . We conducted a controlled , prospect i ve , dose-ranging study of clonidine in spinal anesthesia in 75 neonates , including 50 % of former preterm infants , undergoing elective inguinal herniorrhaphy . Patients were given a spinal anesthetic with either 0.5 % plain isobaric bupivacaine ( 1 mg/kg ) , or bupivacaine plus 0.25 , 0.5 , 1 , or 2 & mgr;g/kg clonidine . Mean arterial blood pressure , heart rate , Spo2 , sensory block extension and duration were the main data recorded . Mean arterial blood pressure , heart rate , Spo2 , and block extension were similar in the five groups . Duration of spinal block increased from 67 ( 58–82 ) min in the control group up to 111 ( 93–125 ) min in the group receiving 1 & mgr;g/kg clonidine ( P < 0.003 ) . Transient hypotension occurred more often ( P < 0.05 ) , and caffeine was given more often , when 2 & mgr;g/kg clonidine was given . We conclude that 1 & mgr;g/kg clonidine provides a significant improvement in spinal anesthesia duration in newborns without significant side effects Purpose Our previous study demonstrated that dexmedetomidine drastically reduced mortality and inhibited the inflammatory response during endotoxemia in rats . The aim of this study was to clarify the dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxemia in rats . Methods Male Wistar rats ( n = 96 ) were anesthetized intraperitoneally with pentobarbital sodium and assigned to one of two protocol s : one representing the dose-related effects of dexmedetomidine , and the other , the time-related effects of dexmedetomidine . To evaluate the dose-related effects , the animals were r and omly assigned to one of four groups ( n = 15 each ) : endotoxemic group ( group E ) , receiving intravenous Escherichia coli endotoxin ( 15 mg·kg−1 over 2 min ) ; small-dose group ( group S ) , treated with a small dose of dexmedetomidine ( 2.5 μg·kg−1·h−1 , IV ) ; medium-dose group ( group M ) , treated with a medium dose ( 5 μg·kg−1·h−1 , IV ) ; and large-dose group ( group L ) , treated with a large dose ( 10 μg·kg−1·h−1 , IV ) . To evaluate the time-related effects , the animals were r and omly assigned to one of three groups ( n = 12 per group ) : endotoxemic group ; early posttreatment group , treated with 10 μg·kg−1·h−1 dexmedetomidine at 1 h after endotoxin injection ; and late posttreatment group , treated with 10 μg·kg−1·h−1 at 2 h after endotoxin injection . Hemodynamics and arterial blood gases were recorded and plasma cytokine concentrations were measured throughout the observation period . The mortality rate was assessed up to 8 h after endotoxin injection . Results In the dose-related study , the mortality rates at 8 h after endotoxin injection were 81 % , 26 % , 32 % , and 20 % for groups E , S , M , and L , respectively . Plasma tumor necrosis factor-alpha ( TNF ) concentrations were lower in groups M and L than in group E at 2 h after endotoxin injection . Plasma interleukin-6 ( IL-6 ) concentrations were lower in groups M and L than in group E at 4 and 5 h after endotoxin injection . In the time-related study , the mortality rates at 8 h after the endotoxin injection were 83 % , 33 % , and 58 % for the endotoxemic , early posttreatment , and late posttreatment groups , respectively . The TNF concentration was lower in the early posttreatment group than in the endotoxemic group at 2 h after endotoxin injection , and the IL-6 concentration was lower in the early posttreatment group than in the endotoxemic group at 5 h after endotoxin injection . Conclusion Dexmedetomidine dose-dependently attenuated extremely high mortality rates and increases in plasma cytokine concentrations after endotoxin injection . Moreover , the early administration of dexmedetomidine drastically reduced the high mortality rate and inhibited cytokine responses in endotoxin-exposed rats . These findings suggest that dexmedetomidine administration may be effective during sepsis ABSTRACT This study determined the effects of cumulative exposure to painful needle procedures and sucrose analgesia on the development of remote hyperalgesia in newborn infants , defined as an increase in response to a normally painful stimulus at a site distal from the site of injury . One‐hundred and twenty healthy newborns and 120 healthy newborn infants of diabetic mothers equally r and omized to sucrose analgesia or placebo prior to all needle procedures in the first two days after birth were divided into two exposure groups according to number of needle procedures they had undergone [ high ( ⩾5 ) or low ( ⩽4 ) ] using the median cut‐off technique . Compared to the low exposure group , infants in the high exposure group had a higher pain response during a subsequent venipuncture distal to the site of previous injury , assessed by the Premature Infant Pain Profile ( PIPP ) [ 7.1 vs. 8.4 ; p = 0.012 ] and Visual Analog Scale ( VAS ) [ 2.5 cm vs. 3.2 cm ; p = 0.047 ] , and a trend for longer cry duration [ 25.7 s vs. 33.8 s ; p = 0.171 ] . PIPP scores did not differ during a routine diaper change , suggesting a nociceptive specific mechanism for the remote hyperalgesia to venipuncture . Sucrose reduced PIPP , VAS , and cry duration scores during venipuncture , but did not prevent hyperalgesia ( p > 0.05 ) . There was a preponderance of infants of diabetic mothers in the high exposure group ; however , the analysis did not demonstrate this to be a confounding factor . In conclusion , sucrose analgesia for repeated painful procedures in the first day of life does not prevent development of remote hyperalgesia in newborns OBJECTIVE The aim of this study was to vali date a clinician-friendly pain assessment tool for all groups of critically ill infants cared for in the specific neonatal intensive care units ( NICUs ) studied . DESIGN A prospect i ve study was undertaken to test the Pain Assessment Tool ( PAT ) . Interrater reliability of the PAT score was assessed by two nurses who simultaneously determined an infant 's PAT score . The PAT was vali date d against the CRIES score -- crying , requires increased oxygen administration , increased vital signs , expression , sleeplessness-- and the mother 's assessment of her infant 's discomfort using the Visual Analogue Scale ( VAS ) . SETTING The NICUs at two children 's hospitals . PATIENTS Participants were 144 preterm and term infants . Infants on a ventilator and those who had undergone surgery were included . RESULTS The interrater reliability of the PAT was .85 with a mean difference of 0.17 ( st and ard deviation : 1.73 ) . There was a strong correlation between the PAT and CRIES scores ( r = 0.76 ) and a moderate correlation ( .38 ) between the PAT score and the VAS scores of the infant 's mother . The correlation coefficient between the PAT score and CRIES score was significant for all groups ( p < .01 ) . CONCLUSIONS The PAT score was shown in this study to be a valid , reliable , and clinician-friendly pain assessment measurement tool for all infants nursed in the NICU OBJECTIVE To describe the long-term outcome of very preterm infants receiving prolonged sedation and /or analgesia and examine the relationship between prolonged sedation and /or analgesia and this long-term outcome . DESIGN A prospect i ve population -based study ( Etude EPIdémiologique sur les Petits Ages GEstationnels [ EPIPAGE ] ) . To reduce bias , the propensity score method was used . SETTING Nine regions of France . PARTICIPANTS The study population included very preterm infants of fewer than 33 weeks ' gestational age , born in 1997 , who received mechanical ventilation and /or surgery . Main Exposure Prolonged exposure to sedative and /or analgesic drugs in the neonatal period , defined as exposure of more than 7 days to sedative and /or opioid drugs . MAIN OUTCOME MEASURE Presence of moderate or severe disability at 5 years of age . RESULTS The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and /or analgesia in the neonatal period was available . A total of 115 were exposed and 1457 were not exposed . There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and /or analgesia and the group who were not . Exposed very preterm infants had severe or moderate disability at 5 years ( 41/97 ; 42 % ) more often than those who were not exposed ( 324/1248 ; 26 % ) . After adjustment for gestational age and propensity score , this association was no longer statistically significant ( adjusted relative risk , 1.0 ; 95 % confidence interval , 0.8 - 1.2 ) . CONCLUSION Prolonged sedation and /or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score Clonidine is effective in treating sevoflurane-induced postanesthesia agitation in children . We conducted a study on 169 children to quantify the risk reduction of clonidine agitation in patients admitted to our day-surgery pediatric clinic . Children were r and omly allocated to receive clonidine 2 & mgr;g/kg or placebo before general anesthesia with sevoflurane that was also supplemented with a regional or central block . An observer blinded to the anesthetic technique assessed recovery variables and the presence of agitation . Pain and discomfort scores were significantly decreased in the clonidine group ; the incidence of agitation was reduced by 57 % ( P = 0.029 ) and the incidence of severe agitation by 67 % ( P = 0.064 ) . Relative risks for developing agitation and severe agitation were 0.43 ( 95 % confidence interval , 0.24–0.78 ) and 0.32 ( 0.09–1.17 ) , respectively . Clonidine produces a substantial reduction in the risk of postsevoflurane agitation in children Objectives : The aim of this study was to document the effects of a new sedative agent , dexmedetomidine , on the mortality rate and inflammatory responses to endotoxin-induced shock in rats . Design : R and omized laboratory study . Setting : University experimental laboratory . Subjects : Fifty-seven male rats . Interventions : The animals were r and omly assigned to one of four groups . The endotoxemic group ( n = 16 ) received intravenous Escherichia coli endotoxin ( 15 mg/kg over 2 mins ) . The saline control group ( n = 10 ) was given saline alone . The dexmedetomidine alone group ( n = 15 ) was treated identically to the control group but also received dexmedetomidine ( infusion at 5 μg·kg−1·hr−1 ) immediately after the injection of 0.9 % saline . The dexmedetomidine-endotoxin group ( n = 16 ) was treated identically to the endotoxemic group with the additional administration of dexmedetomidine ( infusion at 5 μg·kg−1·hr−1 ) immediately after endotoxin injection . Measurements and Main Results : Hemodynamics and arterial blood gases were recorded and plasma cytokine concentrations measured during the observation . The mortality rate was assessed up to 8 hrs after endotoxin or saline injection . In addition , microscopic findings of lung tissue for each group were obtained at necropsy . Mortality rates 8 hrs after endotoxin injection were 94 % , 10 % , 0 % , and 44 % for the endotoxemic , saline control , dexmedetomidine alone , and dexmedetomidine-endotoxin groups , respectively . Hypotension and increases in plasma cytokine ( tumor necrosis factor-&agr ; and interleukin-6 ) concentrations and infiltration of neutrophils in the airspace or vessel walls of the lungs were less in the dexme-detomidine-endotoxin group than in the endotoxemic group . Conclusions : Dexmedetomidine reduced mortality rate and had an inhibitory effect on inflammatory response during endotoxemia . These findings suggest that dexmedetomidine administration may inhibit the inflammatory response Background A growing number of children have severe neurologic impairment related to very premature birth . Experimental data suggest that overstimulation of cerebral N-methyl-d-aspartate ( NMDA ) receptors caused by excessive glutamate release may be involved in the genesis of perinatal hypoxic – ischemic brain injury . & agr;2-Adrenoceptor agonists are protective in models of brain ischemia in adults . The authors sought to determine whether they prevent perinatal excitotoxic neuronal damage . Methods Five-day-old mice were allocated at r and om to clonidine ( 4–400 & mgr;g/kg ) , dexmedetomidine ( 1–30 & mgr;g/kg ) , or saline injected intraperitoneally before an intracerebral stereotactic injection of the NMDA receptor agonist ibotenate ; cortical and white matter lesions were quantified 5 days later by histopathologic examination . Cortical neuron cultures exposed to 300 & mgr;m NMDA were used to evaluate the effects of clonidine or dexmedetomidine on neuronal death assessed by counting the number of pycnotic nuclei after fluorescent chromatin staining . Results In vivo , both clonidine and dexmedetomidine induced significant concentration-dependent reductions in the size of ibotenate-induced lesions in the cortex and white matter . In vitro , the number of neurons damaged by NMDA exposure was significantly decreased by both dexmedetomidine ( −28 ± 12 % at 10 & mgr;m;P < 0.01 ) and clonidine ( −37 ± 19 % at 100 & mgr;m;P < 0.01 ) as compared with controls . In both models , the selective & agr;2-adrenoceptor antagonist yohimbine abolished the neuroprotective effect of clonidine and dexmedetomidine . Conclusions Clonidine and dexmedetomidine are potent neuroprotectors that act by stimulating the & agr;2 adrenoceptors . These results obtained in a murine model of perinatal excitotoxic injury may be relevant to some forms of neonatal brain damage in humans |
13,942 | 20,091,526 | No significant difference was noted for the majority of secondary outcomes for any of the planned comparisons . | BACKGROUND A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolemia .
However , a consensus has yet to be reached on the most appropriate dietary treatment .
OBJECTIVES To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia .
Further , to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids , soya proteins , plant sterols or plant stanols . | The effect on serum high density lipoprotein subfractions of a low fat diet with a high ratio of polyunsaturated-to-saturated fatty acids was studied in 38 middle-aged volunteers ( 19 men and 19 women ) in North Karelia , Finl and . The mean serum HDL2 cholesterol decreased from 32 + /- 2 mg/dl ( mean + /- SE ) to 28 + /- 2 mg/dl ( p less than 0.001 ) during the experimental diet and returned to 33 + /- 2 mg/dl ( p less than 0.001 ) after a return to the original diet . No changes were observed in the concentration of HDL3 cholesterol . A highly significant decrease was observed in serum apoprotein A-I concentration , but not in apoprotein A-II concentration during the experimental diet . It is concluded that a low-fat , high-P/S ratio diet lowers LDL and HDL2 cholesterol in healthy volunteers , but does not influence the level of HDL3 subfraction The Minnesota Coronary Survey was a 4.5-year , open enrollment , single end-time , double-blind , r and omized clinical trial that was conducted In six Minnesota state mental hospitals and one nursing home . It Involved 4393 Institutionalized men and 4664 Institutionalized women . The trial compared the effects of a 39 % fat control diet ( 18 % saturated fat , 5 % polyunsaturated fat , 16 % monounsaturated fat , 446 mg dietary cholesterol per day ) with a 38 % fat treatment diet ( 9 % saturated fat , 15 % polyunsaturated fat , 14 % monounsaturated fat , 166 mg dietary cholesterol per day ) on serum cholesterol levels and the Incidence of myocardlal Infa rct ions , sudden deaths , and all-cause mortality . The mean duration of time on the diets was 384 days , with 1568 subjects consuming the diet for over 2 years . The mean serum cholesterol level In the pre-admission period was 207 mg/dl , falling to 175 mg/dl in the treatment group and 203 mg/dl In the control group . For the entire study population , no differences between the treatment and control groups were observed for cardiovascular events , cardiovascular deaths , or total mortality . A favorable trend for all these end-points occurred In some younger age groups It has been suggested that alpha-tocopherol , a safe and effective antioxidant , be used in clinical trials to evaluate the ability of antioxidant therapy to inhibit atherosclerosis . Recent reports , however , have raised the possibility that there may be greater enrichment of plasma low density lipoprotein ( LDL ) in alpha-tocopherol result ing from the use of the naturally occurring RRR-alpha-tocopherol isomer compared with the other isomers present in the synthetic racemic form of alpha-tocopherol . Therefore , we fed equal dosages ( 1,600 mg/day ) of the two forms of vitamin E to 16 men and women for 8 weeks and compared the effects of this supplementation on the susceptibility of isolated lipoproteins to oxidation . Neither form of vitamin E had appreciable effects on lipid or lipoprotein levels . alpha-Tocopherol levels in LDL increased at a similar rate in both groups and were nearly twofold higher than baseline levels by the end of the study . The susceptibility of LDL to oxidation was measured by formation of conjugated dienes , lipid peroxides , and thiobarbituric acid-reactive substances , as well as by macrophage degradation of LDL exposed to oxidizing conditions in vitro . The susceptibility of LDL to oxidation was decreased in both vitamin E groups compared with the baseline value , and this reduction occurred to a similar extent in both vitamin E-supplemented groups . alpha-Tocopherol levels in LDL also strongly correlated with all measures of LDL oxidation . This study demonstrates that , at this dosage , supplementation with either the natural or synthetic form of alpha-tocopherol provided equal antioxidant protection to LDL The effects of high oleic acid rapeseed oil compared with polyunsaturated fats on serum lipoprotein levels are largely unknown . Therefore , we fed 30 women and 29 men a baseline diet rich in saturated fat , which was followed by a diet rich in high oleic and low erucic acid rapeseed oil ( total energy content of fat , 38 % ; saturates , 12.4 % ; monounsaturates , 16 % ; n-6 polyunsaturates , 6 % ; and n-3 polyunsaturates , 2 % ) and one rich in sunflower oil ( total energy content of fat , 38 % ; saturates , 12.7 % ; monounsaturates , 10 % ; n-6 polyunsaturates , 13 % ; and n-3 polyunsaturates , 0 % ) . The oils were incorporated into mixed natural diets that were dispensed in a r and om order for 3.5 weeks each in a blinded crossover design . The diet composition was confirmed by analysis of duplicate diets . Both test diets reduced serum total cholesterol ( TC ) and low density lipoprotein ( LDL ) cholesterol levels from baseline , the monounsaturated rapeseed oil diet more than the polyunsaturated sunflower oil diet ( TC : -15 % versus -12 % , p less than 0.01 ; LDL cholesterol : -23 % versus -17 % , p less than 0.01 ) . Very low density lipoprotein ( VLDL ) cholesterol and total , VLDL , and LDL triglyceride levels were lower during the sunflower oil diet compared with the rapeseed oil diet . Total high density lipoprotein ( HDL ) cholesterol levels remained unchanged by both diets . The consumption of rapeseed oil result ed in a more favorable HDL2 to LDL cholesterol ratio ( 0.43 + /- 0.19 versus 0.39 + /- 0.18 , p less than 0.01 ) and an apolipoprotein A-I to B ratio ( 3.0 + /- 1.4 versus 2.4 + /- 1.6 , p less than 0.001 ) than did the sunflower oil . ( ABSTRACT TRUNCATED AT 250 WORDS This report describes the effects of feeding linoleate- or oleate-enriched diets to subjects who were concurrently taking 1200 mg/d of alpha-tocopherol on the susceptibility of low-density lipoprotein ( LDL ) and buoyant and dense LDL subfractions to oxidation . LDL isolated from subjects who consumed linoleate-enriched diets was more susceptible to copper-mediated oxidation , as measured by formation of conjugated dienes and lipid peroxides and loss of unsaturated fatty acids , compared with LDL isolated from subjects who consumed their usual or oleate-enriched diets . In all subjects , buoyant LDL had a higher content of alpha-tocopherol per particle and a lower 18:2 to 18:1 ratio and was considerably more resistant to oxidation than dense LDL . Although dense LDL from all groups had comparable alpha-tocopherol levels , dense LDL from the linoleate group was most susceptible to oxidation , followed by that from the st and ard diet , whereas dense LDL isolated from the oleate diet group was most resistant . In summary , high dosages of alpha-tocopherol did not prevent enhanced susceptibility to oxidation of LDL isolated from subjects fed linoleate-enriched diets . Furthermore , dense LDL was more susceptible to oxidation than was buoyant LDL , and this effect was greatly exaggerated in the dense LDL isolated from subjects fed linoleate-enriched diets . Conversely , dense LDL isolated from subjects fed oleate-enriched diets was the most protected . If oxidation of LDL is important in the pathogenesis of atherosclerosis , then these data suggest that in people with increased amounts of small , dense LDL , dietary enrichment in oleic acid may decrease the susceptibility of their LDL to oxidation Effects of small amounts of sitosterol , sitostanol and sitostanol esters ( < 1 g/day of free sterols ) dissolved in rapeseed oil ( RSO ) were studied on serum lipids and cholesterol metabolism in patients with primary hypercholesterolemia and different apolipoprotein E phenotypes on an RSO diet . One of the four groups was an RSO-fed control . Serum total and LDL cholesterol reductions were small in different plant sterol-fed groups , tended to be highest in the sitostanol ester group ( -7 % ) , but were significantly reduced by about 5 % in the combined plant sterol groups . The reductions were -8 % in the subjects with epsilon 4 allele and insignificant in those with apo E3/3 phenotype . Cholesterol precursor sterols in serum , markers of cholesterol synthesis , were increased only in the subjects with epsilon 4 allele . Cholesterol absorption was reduced by 7 % , being 31 % in the subjects with epsilon 4 allele , and fecal elimination of cholesterol was increased , a finding also indicating increased cholesterol synthesis . The changes in cholesterol absorption were related to those in fecal plant sterols ( change in dietary intake ) and serum total and LDL cholesterol ( P = 0.04 , 0.01 and 0.05 , respectively ) . Thus , small amounts of dietary plant sterols ( < 1 g/day ) , especially sitostanol esters dissolved in dietary fats , decrease serum total and LDL cholesterol by a proportional decrease in cholesterol absorption which , in turn , is associated with a compensatory increase in cholesterol synthesis . The effects are most consistent in subjects with epsilon 4 allele , but for effective hypocholesterolemic treatment dietary amount of sitostanol ester should exceed 1 g/day Background Do the benefits of intensive lipid-lowering therapy seen in symptomatic patients extend to high-risk subjects who have never had symptoms ? Methods and ResulsOf 120 men completing the FATS trial , 91 were symptomatic and 29 asymptomatic . All had apolipoprotein B 2125 mg/dL , a positive family history , and coronary atherosclerosis . All were counseled in diet and r and omized to intensive therapy : colestipol 10 g TID plus either niacin 1 g QID or lovastatin 20 mg BID or to conventional therapy : placebos , or colestipol if low-density lipoprotein cholesterol was elevated . End points included quantitative arteriographic disease change and clinical events over a 2.5-year interval . At baseline , symptomatic and asymptomatic patients had comparable risk profiles , but proximal stenosis severity averaged 36 % for symptomatic and 23 % for asymptomatic patients ( P<.001 ) . Among the 91 symptomatic patients , those in the intensive group experienced definite ( .101%S ) proximal lesion progression less frequently than conventional ( 24 % of intensive versus 48 % of conventional ) and definite regression more frequently ( 36 % of intensive versus 15 % of conventional ) ( P=.009 ) . Similarly , among the 29 asymptomatic patients , 19 % of intensive versus 38 % of conventional had progression and 31 % of intensive versus 0%1 of conventional , regression ( P=.04 ) . Ischemia on baseline exercise tolerance testing was associated with significantly greater proximal disease progression among the asymptomatic patients . Clinical cardiovascular events ( death , infa rct ion , or revascularization ) occurred in 10 of 38 symptomatic patients originally assigned to conventional therapy , compared with 5 of 76 symptomatic patients assigned to intensive ( P<.01 ) ; no asymptomatic patient had an event . ConcluionsAsymptomatic subjects with this high-risk profile have less coronary disease at baseline than comparable symptomatic patients , and they have an excellent short-term clinical prognosis . However , asymptomatic subjects are indistinguishable from symptomatic patients in terms of their arterial disease progression with conventional therapy and their regression with intensive . These findings may justify an active treatment strategy in such subjects , particularly those with provokable ischemia The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease ( CHD ) incidence . Secondarily , the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality , presence of CHD at baseline , or the simultaneous introduction of other interventions was explored . All r and omized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence ; analysis was performed with weighted linear regression . The trials include those that used primary and secondary intervention , diet and drugs , and single or multifactor design . Nineteen trials were analyzed for total mortality , and of the 19 , 16 were analyzed for CHD incidence rate . Net difference in cholesterol change between study groups was used as the independent variable , and the three previously mentioned dichotomous design characteristics were used as additional independent variables . For every 1 % reduction in cholesterol , an estimated 2.5 % reduction in CHD incidence is indicated ( 95 % CL : 1.1 , 3.9 ) . With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials . With regard to total mortality , this efficiency was higher in secondary than in primary preventive trials . The efficiency was also somewhat dependent on the baseline cholesterol level . This study shows that cholesterol reduction is effective in lowering CHD incidence , but cholesterol reduction must be at least 8 - 9 % to be effective in lowering total mortality This study was aim ed at determining the effect of fish oil supplementation on copper-catalyzed oxidation of low density lipoproteins ( LDL ) from nine hypertriglyceridemic human subjects . A rapid headspace gas chromatographic method was used to measure the volatile oxidation products from LDL . Propanal and hexanal were the major volatile products formed in the oxidation of n−3 and n−6 polyunsaturated fatty acids ( PUFA ) , respectively . Fish oil supplementation result ed in a significant increase in propanal formation from 3.7 to 13.4 nmol/mL LDL ( P<0.01 ) ; it also result ed in small decreases in pentanal formation from 14.7 to 11.4 nmol/mL LDL and in hexanal formation from 138 to 108 nmol/mL LDL ( P<0.05 ) . The changes in peroxidation products paralleled the changes in LDL composition , which showed a significant increase in n−3 PUFA from 3.2 to 14.6 % ( P<0.01 ) and a decrease in n−6 PUFA from 43.7 to 35.0 % ( P<0.05 ) . Propanal formation was highly and significantly correlated with n−3 PUFA content ( r=0.950,P<0.001 ) . Since total volatiles remained unchanged , this indicated that the two groups of LDL sample s did not differ in overall oxidative susceptibility . Although fish oil intake did not alter the oxidative susceptibility of LDL , the chemically modified LDL particles generated a distinct pattern of volatile oxidation products that reflected changes in their fatty acid composition We compared observed and predicted changes in serum cholesterol in women with mammographic dysplasia who participated for 12 mo in a r and omized , controlled trial of a low-fat , high-carbohydrate diet , in which total fat intake was reduced from an average of 37 % of calories to 21 % and carbohydrate intake increased from 44 % to 52 % of calories . Changes observed in serum cholesterol were greater than those predicted ( by the formulas of Hegsted and Keys ) for subjects with initial serum cholesterol values in the upper tertile of the population , were not significantly different from those predicted for subjects with baseline values in the middle tertile , and were significantly less than those predicted for subjects with initial values in the lower tertile . These results show that the usefulness of serum cholesterol as a marker of change in dietary fat intake in women depends on the distribution of serum cholesterol values in the population studied The effects of dietary fats on plasma cholesterol , serum lipoproteins , and apoproteins ( Apo ) , A-1 , B , and CIII were studied . Twelve men consumed three different cholesterol-free formula diets in which polyunsaturated and saturated fats were partially substituted ( 20 % of calories ) for monoenoic fats with a constant of 40 % of calories from fat . Total cholesterol and low-density lipoprotein cholesterol dropped from base-line values of 166 and 103 to 133 and 81 mg/dl ( sat ) , 127 and 71 mg/dl ( mono ) , and 123 and 65 mg/dl ( poly ) , respectively . High-density lipoprotein cholesterol changed very little from base-line values of 46 to 40 mg/dl ( sat ) , 45 mg/dl ( poly ) , and 43 mg/dl ( mono ) . The plasma concentrations of ApoB declined from base-line values of 80.3 mg/dl to 54.6 mg ( mono ) , 51.8 mg ( poly ) , and 59.6 mg ( sat ) while Apo CIII and Apo AI did not show any changes . This study demonstrates that : 1 ) changes in dietary fat affect serum lipids , lipoproteins , and apoproteins even when consumed on a cholesterol-free diet , and 2 ) omega-6 polyunsaturated fat lowers low-density lipoprotein cholesterol , total cholesterol , and ApoB to a greater extent than monounsaturated or saturated fat , 3 ) consumption of a cholesterol-free formula diet results in significant decreases in the concentrations of total and low-density lipoprotein cholesterol in plasma when compared to values obtained on a mixed food home diet containing approximately 300 mg cholesterol/day Obesity and dietary plant sterols were negatively associated with fractional absorption of dietary cholesterol in a r and om population of 63 middle-aged men . Absorbed dietary cholesterol increased linearly with the increase of dietary cholesterol intake . The higher the fractional and absolute absorption of dietary cholesterol the lower the rates of biliary secretion , fecal elimination , and cholesterol synthesis . The findings also revealed that high serum levels of total , LDL , and HDL cholesterol were associated with high cholesterol absorption and that of HDL cholesterol was associated also with low synthesis and fecal elimination of cholesterol . Thus , cholesterol absorption efficiency and absorbed dietary cholesterol significantly regulate cholesterol synthesis and elimination and are important determinants of within- population variation in the serum levels of total , LDL , and HDL cholesterol Twenty-three young adult males were fed diets containing either 400 or 1400 mg of cholesterol per day under controlled conditions for 4 wk . There were minimal differences between the two diets in total protein , carbohydrate , fat , and the P/S fatty acid ratio . In both diets 400 mg of cholesterol was supplied from nonegg food sources ; the additional 1000 mg of cholesterol was from four whole eggs . Blood sample s were collected after a 12- to 14-h fast at the beginning of the study , weekly throughout the experimental period , and 1 wk after completion of the study . Plasma total cholesterol and triglycerides and high-density , low-density , and very low-density lipoprotein cholesterol levels were measured . No significant differences in plasma total cholesterol , triglycerides , and lipoprotein cholesterol levels were observed between groups at any time . However , plasma cholesterol and cholesterol content of individual lipoproteins varied considerably among the individual subjects fed the high cholesterol diet . The importance of changes in the properties and metabolic activity of individual lipoproteins induced by dietary cholesterol with or without gross changes in the cholesterol levels remains to be determined A r and omized trial was conducted to compare effects of a diet high in monounsaturated fatty acids , enriched with avocado ( AE ) , and a high-complex-carbohydrate diet ( AHA-III ) on blood lipid concentrations . Fifteen females between 37 and 58 y of age were allocated either to AE followed by AHA-III , or vice versa . Each dietary phase lasted 3 wk . Both diets were found to lower total cholesterol compared with baseline values . AE was more effective , with an 8.2 % decrease ( P less than 0.05 ) whereas AHA-III was associated with a 4.9 % decrease ( NS ) . Low-density-lipoprotein cholesterol and apolipoprotein B decreased significantly on AE but not on AHA-III ( P less than 0.05 ) . The high-density-lipoprotein ( HDL ) concentration did not change on AE but decreased 13.9 % on AHA-III ( P less than 0.01 ) . It is concluded that AE is more effective than is AHA-III in decreasing total cholesterol , and , unlike AHA-III , it does not decrease HDL concentrations In this experiment the effect of dietary cholesterol in a hinoheic acid-rich diet on serum cholesterol was tested . In a cross-over design 41 young healthy students received a hinoleic acid-rich diet for 4 weeks at two levels of dietary cholesterol . The diet contained 14 to 15 energy% linoleic acid . The high cholesterol diet was obtained by adding two egg yolks a day to the rations . Supplementation of the linoheic acid-rich diet with the egg yolk cholesterol caused a significant rise of serum cholesterol of about 11 mg/lOO ml ( 0.29 mmole/liter ) . The dietary cholesterol did not influence serum triglyceride levels . The influence on serum cholesterol was much less than expected , based on several predictive formulas . It is concluded that the presence of a high content of linoheic acid in the diet reduces the effect of dietary cholesterol on serum cholesterol if the cholesterol is provided as egg yolk . Am . J. Clin . Nutr . 33 : 2183 - 2187 , 1979 . Since the 1950 's numerous studies The effect of fatty fish consumption on plasma lipid and lipoprotein concentrations was studied in 118 healthy men in a cross-over controlled trial . Subjects ate 100 g or more of fatty fish at least twice a week for 3 months , and little or no fatty fish for another 3 months . The mean plasma triglyceride concentration decreased significantly by 6.7 % on the fish diet ; there were no significant changes in plasma total cholesterol , high-density lipoprotein cholesterol , or low-density lipoprotein cholesterol . A realistic intake of fatty fish has a detectable effect on blood lipids One half of a group of 129 men and women ( 74 men and 55 women ) , in a cross-over design at , within a self-selected diet , one egg and at least 5 oz of beef daily for 3 months while the other half at one egg and at least 5 oz of poultry and fish daily . Then they reversed their diets for 3 months . Blood sample s were drawn by venipuncture before the study started and at the end of the 3 and 6 months , for analyses of serum total cholesterol , triglycerides , and high density lipoprotein cholesterol . No statistically significant changes were found in serum lipids in men . In women serum triglycerides but not other serum lipids were significantly higher when poultry and fish had been ingested The effect on the fasting serum lipid levels of adding daily 291 mg of cholesterol to diets containing 3 mg of cholesterol and equal fat content , but different fatty acid composition , was tested on 12 young men . The saturated diet provided 97 g/day of a staurated oil made up of 2 parts of palm oil and 1 part of coconut oil . The polyunsatured diet provided 97 g/day of safflower oil . The cholesterol was dissolved in 40 g of either oil incorporated into a spread . A similar spread , devoid of cholesterol , was fed during the cholesterol free periods . Duration of dietary periods was 14 days . Addition of cholesterol produced a mean elevation of serum cholesterol of 9 mg/dl ( SE + /- 2.1 ) in the presence of the saturated diet , and of 8 mg/dl ( SE + /- 1.6 ) in the presence of the polyunsaturated diet . Both cholesterol elevations were significant ( P less than 0.01 ) but not significantly different from each other . Substitution of the saturated diet for the polyunsatured diet caused a significant elevation of serum cholesterol which was the same when the substitution was made in the presence or in the absence of added dietary cholesterol The efficacy of the total substitution of animal proteins with a textured soybean protein in hypercholesterolemic individuals was assayed in 42 in- patients and 18 out- patients . The in- patients studied followed one of three different crossover protocol s : in protocol A , the soybean diet was compared with a st and ard low lipid diet ; protocol B compared two soybean diets , one with added cholesterol , one without ; and protocol C compared a soybean diet containing a high P/S fatty acid ratio to one with a low P/S ratio . In all three protocol s , the soybean regimen provided valid and reproducible hypocholesterolemic effects that were not modified by the addition of cholesterol . P/S variations appeared , however , to modify the final effect : soybean definitely had a decreased effectiveness with a low P/S ( 0.1 ) regimen . The overall plasma cholesterol changes in the 42 in- patients after 3 weeks on the different soybean diet protocol s was -20 % . Patients with type IIA and IIB hypercholesterolemia provided almost equivalent results , whereas patients with mixed phenotypes ( IIB-III ) appeared somewhat more sensitive to the dietary effect . Cholesterol decreased mostly in the low density lipoprotein fraction , but some very low density lipoprotein changes were also noted upon variation of the P/S ratio . The out- patients studied provided less satisfactory results . possibly due to the difficulty of adequately complying with the diet . These studies indicate that treatment with the soybean diet is an effective regimen for inducing a significant cholesterol reduction in type II patients refractory to st and ard low lipid regimens The effect of guar gum in capsule form on serum total cholesterol , triglycerides , and lipoprotein cholesterol ( very low-density lipoproteins , low-density lipoproteins , and high-density lipoproteins ) was studied in healthy volunteers in this double-blind study . Twenty-four subjects equally divided into treatment and placebo groups , received 9.0 g/day of guar and glucose in 600 mg identical capsules , respectively , for 4 wk under conditions of constant body weight and dietary stability . Guar significantly lowered serum total cholesterol ( 16.6 % p less than 0.05 ) and low-density lipoprotein cholesterol ( 25.6 % p less than 0.05 ) but had no significant effect ( p less than 0.05 ) on serum triglycerides , high-density lipoproteins and very low-density-lipoprotein cholesterol . No significant changes ( p greater than 0.05 ) were seen in blood lipids in the placebo group We tested semihardened blends of edible oils , suitable for commercial food manufacture , with a lower-than-conventional saturated fatty acid content , for their effects on plasma cholesterol . Twenty-six mildly hypercholesterolemic men took part in a double-blind crossover experiment in which two test blends were compared with two control dietary periods [ which resembled the Australian fat intake : proportions of polyunsaturated , monounsaturated , and saturated fatty acids ( PMS ) 0.4:0.9:1 ] . PMS in the test diets was approximately 0.8:1.3:1 and result ed in significantly lower LDL-cholesterol concentrations ( reductions of less than or equal to 7.7 % ) . HDL cholesterol and plasma triglyceride were unchanged . The trans fatty acid ( mainly elaidic ) content of the blends was 16 % , raising its contribution to energy by 4 % but without apparent effect on LDL and HDL concentrations . Provided the overall ratio of linoleic acid to palmitic acid in commercial edible-oil blends exceeds that in the prevailing national diet , partial hydrogenation will not negate the LDL-lowering potential BACKGROUND Naturally occurring plant sterol esters ( SEs ) favorably affect serum cholesterol concentrations in humans and could aid in the treatment of children with familial hypercholesterolemia ( FH ) . OBJECTIVE We studied the effect of SE-enriched spread on serum lipids , lipoproteins , carotenoids , fat-soluble vitamins , and physiologic variables in children with FH aged 7 - 12 y. DESIGN In a r and omized , double-blind crossover study comprising two 8-wk interventions , 38 children with FH consumed 18.2 + /- 1.5 g SE spread/d , corresponding to 1.60 + /- 0.13 g SEs , or a control spread . Blood sample s were analyzed at the start and end of each diet period . RESULTS Plasma LDL-cholesterol concentrations decreased by 10.2 % ( P = 0.003 ) during the SE period compared with the control period . Total cholesterol and apolipoprotein B concentrations were reduced by 7.4 % ( P = 0.007 and P = 0.020 , respectively ) during the SE period . No changes were observed in HDL cholesterol , triacylglycerol , or apolipoprotein A-I. Serum concentration of lipid-adjusted lycopene decreased by 8.1 % ( P = 0.015 ) in the SE period , with no changes in the other carotenoids . Lipid-adjusted retinol and alpha-tocopherol concentrations increased by 15.6 % ( P < 0.001 ) and 7.1 % ( P = 0.027 ) , respectively . There was an increase ( 16.8 % , P = 0.04 ) in alanine transaminase in the SE period , but this was explained by a significantly lower starting concentration in the SE period than in the control period . The children consumed a recommended American Heart Association Step I diet during both intervention periods . CONCLUSION A daily intake of 1.6 g SEs induces an additional reduction in LDL-cholesterol concentrations in children with FH consuming a recommended diet The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol , 218 to 307 mg/dl . The diets were low in cholesterol , 200 mg/day , with 13 to 16 % of energy as protein , 30 to 35 % as fat , and a polyunsaturated to saturated fat ratio of 0.5 . Of protein 65 % was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats . Fresh egg yolk was added to balance the cholesterol content of the diets . Proteins from grains and vegetables were identical in both menus and contributed about 35 % of dietary protein . Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol . Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups . Mean decreases in plasma cholesterol , 16 and 13 % , for responders in the animal and soy groups were significant , p less than 0.01 and 0.05 , respectively . Responders in both groups had higher initial plasma cholesterol values than nonresponders . Although plasma high-density lipoprotein cholesterol decreased slightly , the high-density lipoprotein cholesterol to cholesterol ratio ( high-density lipoprotein cholesterol/total cholesterol ) remained constant for most individuals . The hypocholesterolemic effects were similar for both animal and soy protein ( p less than 0.05 ) and fat ( p less than 0.05 ) while on the experimental diet . All groups significantly decreased dietary cholesterol ( p less than 0.001 ) To evaluate selected metabolic effects of plant fibers , we fed control and oat-bran diets in an alternating sequence to eight men with previously documented hypercholesterolemia . The two solid diets differed only in the inclusion of 100 g of oat bran in the test diet . We r and omized diet sequences and the measured intakes of carbohydrate , protein , fat , and cholesterol were virtually identical on the two diets . Serum total cholesterol concentrations were stable on control diets whereas a progressive reduction was observed in seven men on oat-bran diets . On oat-bran diets , average reductions in serum total cholesterol concentrations were 13 % ( p less than 0.01 , N = 8) ; plasma low-density lipoprotein cholesterol concentrations were 14 % lower ( p less than 0.05 ) while high-density lipoprotein cholesterol concentrations were not changed . Fasting and postpr and ial serum glucose , insulin , and triglyceride concentrations were similar on the two diets . Fecal excretion of total bile acids was 54 % higher ( p less than 0.001 ) on oat-bran diets than on control diets but neutral steroid excretion was slightly lower while on oat bran . Palatable and inexpensive high-fiber foods such as oat bran may have a role in the treatment of certain patients with hypercholesterolemia Plant sterols have been shown to reduce dietary cholesterol absorption and hence , total and low-density-lipoprotein (LDL)-cholesterol concentrations in humans . In this study the cholesterol-lowering effects of dietary supplementation with the hydrogenated plant sterol sitostanol ( 3 g/d ) were tested in 33 men with moderate hypercholesterolemia who were consuming an outpatient diet in which dietary cholesterol was restricted to < 200 mg/d . Sitostanol therapy did not significantly lower LDL cholesterol compared with the diet alone . Similarly , sitostanol therapy in conjunction with a cholesterol-lowering regimen of diet and 8 g cholestyramine did not significantly lower LDL-cholesterol concentrations . Hence , although previous reports have suggested that low-dose sitostanol therapy is an effective means of reducing LDL-cholesterol concentrations , its effectiveness may be attenuated when the diet is low in cholesterol This study 's purpose was to evaluate the fasting human plasma lipid and lipoprotein responses to dietary beef fat ( BF ) by comparison with coconut oil ( CO ) and safflower oil ( SO ) , fats customarily classified as saturated and polyunsaturated . Nineteen free-living normolipidemic men aged 25.6 + /- 3.5 yr consumed central ly-prepared lunches and dinners of common foods having 35 % fat calories , 60 % of which was the test fat . The test fats were isocalorically substituted , and each fed for five weeks in r and om sequences with intervening five weeks of habitual diets . Plasma total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) concentrations among individuals follows the same relative rank regardless of diet . Triglycerides ( TG ) concentrations among individuals also maintain their relative rank regardless of diet but in a different order from that of the cholesterols . Plasma TC , HDL-C , and LDL-C responses to BF were significantly lower and TG higher than to CO . As compared to SO , BF produced equivalent levels of TG , HDL-C , and LDL-C and marginally higher TC . Thus , the customary consideration of BF as " saturated " and grouping it with CO appears unwarranted Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk . The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet . Plasma total cholesterol was reduced with corn oil , but high-density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive . Plasma apolipoprotein B levels were equally reduced by both diets ; apolipoprotein AI and the apo AI : B ratio rose only with olive oil . Plasma-glucose levels were lowered significantly with olive oil . Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid ( particularly with corn oil ) and to collagen ( particularly with olive ) . An olive oil diet with a moderate fat intake ( about 30 % of total calories ) leads to favorable plasma lipoprotein and platelet changes Fully refined , bleached , deodorized corn oil and soy oil , and lightly hydrogenated , winterized soy oil were compared for effectiveness in lowering plasma cholesterol . Twenty-four , healthy , young college students were the subjects for the 10-wk studies . At the 300 cal level , the corn oil and unhydrogenated soy oil diets contained approximately 53 g of polyunsaturated and 26 g of saturated fat . The hydrogenated soy oil diet contained 42 and 25 g , respectively . All diets contained approximately 700 mg of cholesterol . Corn oil and unhydrogenated soy oil were equally effective in lowering both total and low density lipoprotein cholesterol . Lightly hydrogenated soy oil was also quite effective , but less so that the more unsaturated oils . Triglycerides were also lowered , but very low density and high density lipoprotein cholesterol concentrations , as well as total high density lipoproteins , were scarcely affected . All of the polyunsaturated fat diets produced small but statistically significant reductions in the cholesterol to protein ratio of all three lipoproteins The effects of various cholesterol-lowering diets on plasma lipid and lipoprotein cholesterol levels were assessed in normal and hypercholesterolemic subjects . The base-line diet was an ad libitum hospital diet of normal composition . Diet A was a 20 % protein , 40 % carbohydrate , 40 % fat , polyunsaturated : saturated fat ratio 0.1 to 0.3 , 250 to 300 mg cholesterol diet , diet B was identical to diet A except that the polyunsaturated/saturated fat ratio was 1.8 to 2.2 , and diet C was a 20 % protein , 80 % carbohydrate , very low fat ( 5 to 10 g ) , polyunsaturated/saturated fat ratio 0.1 to 0.3 , 150 to 200 mg cholesterol diet . Diet A ( low cholesterol ) caused mean reductions in plasma , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol of 5.9 , 5.6 , and 6.3 % , respectively , in 11 normal subjects . Diet B ( low cholesterol , high polyunsaturated fat ) caused significant decreases in plasma cholesterol , LDL cholesterol and HDL cholesterol of 17.0 , 16.2 , and 17.4 % , respectively , in 12 normal subjects ; and reductions of 11.0 , 10.8 , and 17.1 % , respectively , in 19 hypercholesterolemic subjects . Diet C ( low cholesterol , very low fat ) produced significant mean decreases in plasma , LDL , and HDL cholesterol of 26.7 , 29.9 , and 27.9 % , respectively , in 11 normal subjects , and in nine hypercholesterolemic patients of 22.6 , 27.2 , and 28.6 % , respectively . The reductions in plasma cholesterol caused by these diets were therefore due to decreases in both LDL and HDL cholesterol with no significant changes in the LDL cholesterol : HDL cholesterol ratio Low-fat , natural diets were fed to 11 middle-aged , healthy male subjects for two 40-d periods to determine effects on plasma lipoproteins . The diets were design ed to maintain saturated and monounsaturated fatty acids at 10 en% and linoleic acid ( LA ) at 3.8 and 10.8 en% . When compared with baseline concentrations , total cholesterol decreased 10 % at the end of the lower LA diet and 15 % at the end of the higher LA diet . Low-density-lipoprotein cholesterol ( LDL-C ) decreased 18 % and 22 % , respectively , during the same periods . Plasma high-density-lipoprotein cholesterol ( HDL-C ) at the end of each dietary period was not significantly different but the midpoint values were lower by 12.5 % on the lower LA diet and 7.3 % on the higher LA diet . Apolipoprotein B decreased 27 % at the end of the lower LA diet and 37 % at the end of the higher LA diet whereas apolipoprotein A-I increased 18 % and 24 % , respectively . HDL-C was not reduced by dietary LA over a 6-wk period An image input apparatus receives image data from a scanner having a reading surface on which an original image is placed , the image data being generated through reading the reading surface . An image outline determination apparatus determines an outline of an original image placed on the reading surface of the scanner in accordance with the image data obtained by the scanner . An area design ation section design ates a rectangular proposed area of which at least portion enters into an area of the original image placed on the reading surface . An outline determination section determines the outline of the original image by repeating a plurality of number of times an area alteration processing in which a movement of sides defining an outline of the proposed area outside or inside the proposed area is determined in accordance with differential or difference of image data for vicinity of the sides , and the proposed area is altered in accordance with a decision of the movement , wherein the area alteration processing is repeated taking an area after the proposed area is altered as a new proposed area The effect of dietary protein source on the kinetics of plasma very low-density lipoprotein ( VLDL ) ( Sf 60 to 400 ) in hypercholesterolemic men was investigated . Using a crossover design , five subjects received sequentially either 1 ) a high polyunsaturated fat , low cholesterol control diet containing mixed protein from meat , dairy products , and plant sources or 2 ) an all-plant protein experimental diet in which the meat and dairy protein of the former diet was replaced by soybean protein and soy milk . There was no significant change in the mean values for fasting serum cholesterol and triglycerides over the 6-wk period of administration of the control versus experimental diets . The kinetics of VLDL ( Sf 60 to 400 ) apolipoprotein B were studied at the end of each dietary period after reinjection of 125I-labeled autologous VLDL ( Sf 60 to 400 ) . The VLDL apolipoprotein B pool size was similar during the experimental and control protocol s ; however , the fractional catabolic rate was consistently higher during the experimental protocol ( 8.5 + /- 1.3 versus 6.5 + /- 1.2 day-1 , p less than 0.01 ) and the production rate of apoprotein B was higher than control in four of five subjects ( mean values 18.6 + /- 3 versus 12.6 + /- 1 mg/day/kg , respectively ) . Administration of an all-plant protein diet significantly increased the fractional turnover rate of VLDL apolipoprotein B , even when no changes in VLDL ago B pool size or VLDL lipid concentrations were observed This r and omized blind crossover study compared serum lipid and apolipoprotein concentrations in 20 men consuming 37 - 43 % of energy as fat from diets based on corn oil , high-oleic acid sunflower oil , and butter . Each phase of the crossover design included 2 wk of butter-based diet followed by 5 wk of design ated vegetable-oil-based diet with a 7-wk washout period between phases . Compared with values for the butter-based diet , the vegetable-oil-based diets reduced serum total cholesterol by 16 - 21 % ( p less than 0.001 ) , LDL cholesterol by 21 - 26 % ( p less than 0.001 ) , triglycerides by 10 - 21 % ( p less than 0.01 for the higher figure ) , and apolipoprotein B-100 by 22 - 29 % ( p less than 0.001 ) . When values fell , they fell further on the corn-oil-based diet . There were no significant changes in serum HDL cholesterol or apolipoprotein A-1 . These data suggest that when men on diets high in saturated fatty acids reduce their saturated fatty acid intake but not their total fat intake , many can still experience a significant lowering in serum total cholesterol To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells , 12 type II patients were r and omly allocated to three different diets , which provided polyunsaturated fatty acids ( corn oil ) , monounsaturated fatty acids ( olive oil ) , and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet . Olive oil and , more significantly , n-3 ethyl esters lowered total cholesterol best ( -2.2 % and -5.8 % , respectively ) ; the latter diet , as expected , also significantly lowered triglyceridemia ( -21.4 % ) . The corn-oil diet exerted a small , statistically significant reduction of high-density-lipoprotein cholesterol ( HDL ) ( -4.3 % ) , and it also lowered plasma total apo B concentrations ( -3.8 % ) . n-3 ethyl esters significantly raised both total ( + 3.1 % ) and particularly HDL2 cholesterol ( + 24 % ) . Platelet reactivity was insignificantly reduced by the three regimens , but all three significantly reduced thrombin-stimulated formation of thromboxane B2 . Finally , only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes . Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients , but significant differences may be found between the three tested regimens Low-density-lipoprotein ( LDL ) oxidation was examined in 22 subjects ( 10 men , 12 women ) after a daily dose of 18 mg beta-carotene , 900 mg vitamin C , and 200 mg alpha-tocopherol for 6 mo . Control subjects ( 12 men , 11 women ) took no vitamin supplements . After 3-mo supplementation plasma concentrations of beta-carotene , alpha-tocopherol , and ascorbic acid increased fivefold ( P < 0.001 ) , 55 % ( P < 0.01 ) , and 27 % ( P < 0.05 ) , respectively . There was no difference from baseline in rate of oxidation or total amount of conjugated diene produced between subjects taking or not taking vitamins . Malondialdehyde in LDL before and after oxidation was not different between the two groups . Lag time before the onset of oxidation was significantly lengthened after antioxidant supplementation ( 28 % and 35 % after 3 and 6 mo , respectively , P < 0.001 ) . There was a significant independent correlation between percent change in lag time and percent change in plasma alpha-tocopherol ( r = 0.47 , P < 0.01 ) In general , vegetarians have lower serum lipids and blood pressures than omnivores have . We tested the blood pressure and serum lipid lowering effects of two fat-modified diets differing primarily in their source of protein . Twenty-six men were r and omized in an incomplete block design to two of three diets : a high-fat diet , a fat-modified lactoovovegetarian diet ( LOV ) and a diet in which 60 % of plant protein in the LOV was replaced with lean meat ( LM ) . Compared with the high-fat diet both prudent diets significantly lowered blood pressure , serum total cholesterol ( TC ) , and LDL cholesterol but significantly increased serum triglycerides . The LOV diet had a significantly greater cholesterol-lowering effect than did the LM diet ( 10 % vs 5 % decrease ) but blood pressure reductions were similar . The partial substitution of lean meat for plant protein in a fat-modified diet did not negate the overall cardiovascular-risk lowering of the lactoovovegetarian diet The efficacy , safety , acceptability , and cholesterol lowering potential of sucrose polyester ( SPE ) , a liquid , nonabsorbable , fat-like material were assessed in normolipidemic men . In the first phase of the study , the subjects consumed for 10 days a basal diet that contained 800 mg of cholesterol per day ( P/S = 0.4 ) , or 300 mg ofcholesterol ( P/S = 1.0 ) , or for 21 days a basal diet that contained less than 50 mg of cholesterol ( P/S = 1.5 ) . Subsequently over three consecutive periods of 10 days each 8 , 16 , or 25 g of liquid SPE or 19 , 38 , or 62 g of an 80/20 mixture of SPE and completely hydrogenated palm oil ( HPO ) was added daily to these same diets . Every treatment group but one showed at least a nominal decrease in plasma total and low density lipoprotein cholesterol . Though not all of these decreases were statistically significant , all 24 of the subjects showed a decrease in both of these plasma components on at least one of the dosages of SPE . The lowering was observed whether the daily diet ofthe subjects contained 800 , 300 , or less than 50 mg ofcholesterol , and whether the SPE was added as such or together with HPO . Using 25 g of liquid SPE or 62 g ofthe SPE/HPO mixture , mean group low density lipoprotein cholesterol was lowered by 10 to 19 % with significant reductions on all three levels of cholesterol intake . A similar pattern of change was seen in the levels of plasma vitamin A and E. Plasma high density lipoprotein cholesterol and triglycerides were not changed . These responses of the plasma lipids are like those seen earlier with SPE that was a semisolid . Neither preparation result ed in any untoward effects , although the subjects preferred the mouth-feel of the liquid material that was used in this study . The vegetable oil-like culinary properties of liquid SPE should facilitate adherence to a regimen that includes this apparently safe and effective cholesterol-lowering agent . Am . J. C/in . Nutr . 32 : 1636 - 1644 , 1979 . Sucrose polyester ( SPE ) is a fat like matena ! consisting of a mixture of the hexa- , hepta- , and octa-esters formed by the reaction of sucrose with long-chain fatty acids ( 1 - 3 ) . This material is not hydrolyzed by the enzymes in the gastrointestinal tract ( 1 ) , and as a consequence it is not absorbed ( 2 ) . The addition of SPE to the diets of rats has been shown to result in a decreased absorption of dietary cholesterol ( 4 ) . The same effect has been observed for enterohepatic circulating cholesterol in rats ( F. H. Mattson and R. J. J and acek , unpublished observations ) . The mechanism proposed ( 4 ) for this action was the distribution of the cholesterol in the lumen of the intestinal tract between the usual micellar phase and the unabsorbable fat phase of SPE . The cholesterol that was dissolved in this fat phase was then egested in the feces . The effects of the daily ingestion by humans of 50 g of SPE for 10 days have been reported ( 3 ) . The addition or substitution of I From the General Clinical Research Center and Lipid Research Division , University of Cincinnati , College of Medicine , and from the Miami Valley Laboratories of the Procter and Gamble Company , Cincinnati , Ohio 45247 . 2 Supported in part by the General Clinical Research Center Grant , RR 0006815 , and by a grant from the Procter and Gamble Company . A portion of this work was done during Dr. Glueck ’s tenure as an Established Investigator of the American Heart Association , 19711976 . 3Address reprint requests to : Fred H. Mattson , Procter and Gamble Company , Miami Valley Laboratories , P.O. Box 39175 , Cincinnati , Ohio 45247 . by gest on S etem er 4 , 2012 ajcn.trition.org D ow nladed fom SUCROSE POLYESTER AND PLASMA CHOLESTEROL 1637 the SPE for culinary fats in the diets produced significant reductions oftotal and low density lipoprotein cholesterol of 14 and 17 % , respeclively , despite the diet containing 800 mg of cholesterol and the dietary fat having a P/S ratio of 0.4 . There was an increased loss of fecal neutral steroids during the period of SPE consumption ( 5 ) . Thus the lowering of plasma cholesterol in man is likely by the same mechanism as that proposed earlier for the rat ( 4 ) , namely reduced cholesterol absorption . In the study ( 3 ) with human subjects it was observed also that plasma vitamin A and E levels were lowered , although both were still within ranges that are considered normal . Despite the presence of some 50 g of unhydrolyzed SPE in the stools , there was no clinical or chemical steatorrhea . The subjects had few or no complaints of gastrointestinal discomfort . Although the particular SPE preparation used in the initial study was easily incorporated into routine food stuffs , the material had at room temperature an appearance and consistency similar to that of lard or tallow , and the subjects indicated that many of the food items containing SPE had a waxy or greasy feel or taste . In the study reported here , a new preparation of SPE was used . Since this material was a liquid at room temperature , it was believed that it would be more acceptable . In addition , the effects elicited by various levels of the SPE when it was incorporated into diets supplying approximately 800 , 300 , or less than 50 mg of cholesterol per day were determined . Our preliminary studies with the liquid SPE indicated the daily intake of more than 25 g would result in occasional anal leakage . However , studies with rats had shown that this phenomenon could be prevented by the presence in the diet of palmitic , or longer chain saturated fatty acids , if these were introduced in a form that made the saturated acids unabsorbable ( R. J. J and acek and R. A. Volenphein , unpublished observations ) . Completely hydrogenated palm oil ( HPO ) is one material fulfilling these requirements . In pilot studies , we found that as much as 50 g/ day of liquid SPE could be ingested without anal leakage ensuing , if the diet also contained 12 g of HPO . The diet of half of the subjects in the present study contained this 80/20 by weight combination of SPE and HPO . Material s and methods As described earlier in greater detail ( 1 , 2 , 6 ) , SPE is produced by esterifying six to eight of the hydroxyl groups of sucrose with long-chain fatty acids . For use in this study , sucrose was esterified with the fatty acids of safflower seed oil so as to obtain a product that was a liquid at and below room temperature . The ester composition was 43 % octaester , 43 % heptaester , and 14 % hexaester . The appearance and consistency of this preparation of SPE was similar to that of corn oil . A portion of this material was used as such in the study ; it is referred to as SPE Liquid . Another portion of the same preparation was introduced into the diet as an 80/20 mixture of SPE and HPO . This is referred to as SPE/ HPO mix . Its consistency was a semisolid somewhat similar to shortenings Adding 36 g of wheat fiber for 3 weeks to the metabolically controlled diets of six subjects produced a significant increase in daily fecal weight from 70.8 g + /- 6.2 SEM to 217 g + /- 12.1 ; serum iron also fell by 21 micrograms/100 ml + /- 2.1 SEM ( P less than 0.001 ) during the added fiber period ( measured in five subjects ) as did mean corpuscular volume and mean corpuscular hemoglobin . Fecal neutral steroid concentration ( measured in four subjects ) fell from 31 to 17.3 mg/g dry weight ( P less than 0.05 ) but the change in neutral steroid output and in acid steroid concentration and output was not significant . No change was seen in the serum levels of cholesterol and triglyceride The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet . Ninety-five subjects with moderate hyperlipoproteinemia were r and omly assigned to one of the two well-controlled diets prepared at the hospital kitchen . Total serum , low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15 % , 16 % , and 11 % ( P < 0.001 ) , respectively , on the rapeseed oil diet and by 16 % , 14 % , and 13 % ( P < 0.001 ) on the sunflower oil diet . Serum triglycerides decreased more markedly ( by 29 % , P < 0.001 ) on the sunflower oil than on the rapeseed oil diet ( 14 % , P < 0.01 ) . The n-3 fatty acids ( 20:5 and 22:5 ) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet . There was an increase in the alpha-tocopherol concentrations after both diets . The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet The effects of the American Association of Cereal Chemists coarse wheat bran fiber and exercise were evaluated in 20 males , aged 24 to 35 yr , and at least 10 % above ideal weight . Thirteen of the subjects participated in a 4 mile walk-jog run program 3 times weekly . In a cross-over design with diets switched midway through the experiment , both the exercising and sedentary groups consumed isocaloric amounts of either white bread or white bread containing wheat bran ( 0.5 g/kg body weight ) . Plasma total and lipoprotein cholesterol and triglycerides , body weights , and percentage body fats were determined at 0 , 6 , and 12 wk . No consistent effects were observed as a result of the wheat bran feeding on any of the parameters measured . Exercise training tended to decrease body weights and percentage body fats , and was associated with significantly increased ( p less than 0.05 ) plasma high-density lipoprotein cholesterol levels and high-density lipoprotein cholesterol to low-density lipoprotein cholesterol ratios . After a rise in triglycerides at wk 6 , a significant decline ( p less than 0.05 ) back to base-line values was observed at wk 12 for the exercised subjects Twenty-six Yeshiva students were r and omly assigned to a 24-wk crossover study of monounsaturated fatty acid ( MUFA ) vs polyunsaturated fatty acid ( PUFA ) diets ( 50 % carbohydrate , 32 % fat , 18 % protein ) fed alternately during two 12-wk periods . Total plasma cholesterol ( TC ) decreased significantly by approximately 10 % and approximately 16 % on the MUFA and PUFA diets , respectively . Plasma triglyceride response was variable . Low-density-lipoprotein cholesterol ( LDL-C ) decreased in both groups with an additional significant effect between periods . Concentrations of high-density-lipoprotein cholesterol did not change significantly . LDL-receptor status in fresh monocytes , affinity of LDL towards the LDL receptor in cultured fibroblasts , zonal-centrifugation profiles , and lipoprotein composition were not significantly different between the diets . There was a significantly higher tendency toward lipid peroxidation on the PUFA diet , as ascertained by more thiobarbituric acid-reactive-substances formation on that diet . Dietary PUFA results in somewhat lower TC and LDL-C concentrations whereas with MUFA the susceptibility of LDL to oxidative stress is lower Sucrose polyester ( SPE ) was studied in a double-blind , placebo-controlled trial in 91 out patients with primary hypercholesterolemia . All patients maintained an isocaloric diet with cholesterol intake of 400 mg/day and a polyunsaturated to saturated fat ratio of 0.8 to 1.2 for the duration of the study . The study sequence consisted of a diet lead-in period , a first 8-wk treatment period , a 4-wk washout period , and a second 8-wk treatment period . Subjects were r and omly assigned to six groups that differed by SPE dose ( 8 , 16 , and 32 g/day ) and by the treatment period in which either SPE or an olive oil placebo was given in a bread spread formulation . Compared to placebo , the 8 , 16 , and 32 g/day doses of SPE decreased low-density lipoprotein cholesterol by 2 % , 4 % ( p less than 0.05 ) , and 5 % ( p less than 0.05 ) respectively , without changing high-density lipoprotein cholesterol . On SPE , 14/91 ( 15 % ) of the subjects experienced a decrease in low-density lipoprotein cholesterol greater than or equal to 10 % , while only 2/91 ( 2 % ) showed this decrease with placebo The association between low serum selenium , vitamin A , and vitamin E levels and mortality from cardiovascular disease ( CVD ) was investigated in a case-control study nested in a 9-yr prospect i ve study in the Netherl and s. For 10,532 persons aged greater than or equal to 5 yr who participated in a 1975 - 1978 medical survey , serum was stored at -20 degrees C. For the 84 of 106 subjects aged 37 - 87 yr who died of CVD after the baseline exam , 168 cohort members alive at the end of 1983 and matched for age and gender were selected as controls . No significant associations between serum selenium . vitamin A , vitamin E , and CVD mortality were observed before and after multivariate analyses . The adjusted risk of death from CVD for subjects in the lowest selenium quintile ( less than 105.0 micrograms/L ) was 1.6 ( 95 % CI , 0.8 - 3.2 ) . For coronary and stroke death risk , estimates were 1.1 ( 95 % CI , 0.5 - 2.6 ) and 3.2 ( 95 % CI , 0.8 - 12.1 ) . Our findings do not show a clear CVD risk from low selenium and vitamin levels . Although some of the risk estimates were strong , larger studies are required for definitive conclusions Background : Familial hypercholesterolemia ( FH ) is associated with a high risk of coronary heart disease . Pharmacological treatment and diet are both essential for the management of FH . Foods rich in plant sterols ( PS ) may play an important role in the treatment of patients with these disorders . Objective : To test the effect of the intake of PS on low-density lipoprotein ( LDL ) concentration , endothelial function ( EF ) and LDL particle size in 30 patients with FH . Design : R and omized and crossover dietary intervention study . Setting : Tertiary outpatient care . Subjects : Thirty-eight were recruited , but only 30 were subjected to four low-fat dietary intervention periods , each of 4 weeks . Methods : Each intervention had a different content of cholesterol ( < 150 or 300 mg/day ) and sitosterol ( < 1 or 2 g/day ) . Lipid response , EF and LDL particle size were analysed after the intervention . Results : Plasma sitosterol/cholesterol ratio was higher during both plant sterol-rich periods than during the low plant sterols periods . Basal sitosterol concentrations predicted the LDL-cholesterol response during the intake of plant sterol-enriched diets . The change in LDL-cholesterol was significantly greater in subjects in the upper and intermediate tertiles of basal plasma sitosterol concentrations ( −21±8 mg/dl , P=0.03 ; −19±7 mg/dl , P=0.04 , respectively ) than in subjects in the lower tertile ( 8±5 mg/dl ) when they changed from a low cholesterol diet to a low cholesterol plus plant sterol diet . Conclusion : Our study demonstrates that basal sitosterol values can predict hypolipidemic response in patients with FH The effects of a low-fat , low-cholesterol diet ( LFD ) or a higher-fat , higher-cholesterol diet ( HFD ) on plasma concentrations of lipids , lipoproteins , lathosterol ( an index of cholesterol synthesis rate ) , and plant sterols were determined in 19 patients with familial hypercholesterolemia ( FH ) treated with simvastatin . The study followed a r and omized crossover design including two 8-week diet periods . The LFD significantly decreased plasma lathosterol ( -22 % ) , cholesterol ( -6 % ) , low-density lipoprotein ( LDL ) cholesterol ( -6 % ) , and high-density lipoprotein ( HDL ) cholesterol ( -7 % ) levels compared with the HFD . Decreases in plasma lathosterol and LDL cholesterol concentrations in patients during the LFD were significantly correlated ( r = .522 , n = 19 , P < .05 ) . These results suggest that a LFD may enhance the decrease in cholesterol synthesis induced by simvastatin treatment , and in this way might contribute to the decrease in plasma cholesterol levels when the fat content of the diet is reduced in simvastatin-treated FH patients Abstract Objective : To determine the relative efficacy in general practice of dietary advice given by a dietitian , a practice nurse , or a diet leaflet alone in reducing total and low density lipoprotein cholesterol concentration . Design : R and omised six month parallel trial . Setting : A general practice in Oxfordshire . Subjects : 2004 subjects aged 35 - 64 years were screened for hypercholesterolaemia ; 163 men and 146 women with a repeat total cholesterol concentration of 6.0 - 8.5 mmol/l entered the trial . Interventions : Individual advice provided by a dietitian using a diet history , a practice nurse using a structured food frequency question naire , or a detailed diet leaflet sent by post . All three groups were advised to limit the energy provided by fat to 30 % or less and to increase carbohydrate and dietary fibre . Main outcome measures : Concentrations of total cholesterol and low density and high density lipoprotein cholesterol after six months ; antioxidant concentration and body mass index . Results : No significant differences were found at the end of the trial between groups in mean concentrations of lipids , lipoproteins , and antioxidants or body mass index . After data were pooled from the three groups , the mean total cholesterol concentration fell by 1.9 % ( 0.13 mmol/l , 95 % confidence interval 0.06 to 0.22 , P<0.001 ) to 7.00 mmol/l , and low density lipoprotein cholesterol also fell . The total carotenoid concentration increased by 53 nmol/l ( 95 % confidence interval 3.0 to 103 , P=0.039 ) . Conclusions : Dietary advice is equally effective when given by a dietitian , a practice nurse , or a diet leaflet alone but results in only a small reduction in total and low density lipoprotein cholesterol . To obtain a better response more intensive intervention than is normally available in primary care is probably necessary . Key messages Key messages In this study dietary advice had only a modest effect on lipid and lipoprotein concentrations Personalised advice from a nurse or dietitian was no more effective than a detailed diet leaflet Antioxidant concentrations increased slightly , but this requires further study A mass approach to dietary change is needed to produce significant The effect of oral calcium carbonate on serum lipoprotein concentrations was tested in 50 children with familial hypercholesterolemia ( type II-A ) consuming a low cholesterol high polyunsaturated fat diet , using a cross-over design versus a placebo . Cholesterol was measured in serum and in the individual lipoprotein density classes . Serum apolipoprotein B ( the protein moiety of low density lipoprotein ) and apolipoprotein A-I ( the main protein of high density lipoprotein ) were measured by specific immunoassays . Calcium carbonate treatment induced only a slight increase in serum apolipoprotein A-I ( + 4 % ) and a slight decrease in low density lipoprotein cholesterol ( -4 % ) , both changes being significant at the P=0.05 level A multicentre , double blind , r and omised between-group study comparing the triglyceride lowering effect of MaxEPA , a natural marine oil , and a placebo control is described . Eighty-six patients with hypertriglyceridaemia ( fasting serum triglyceride greater than or equal to 2 mmol/l ) were studied for three months . There were no significant differences between the groups ( 48 active , 38 control ) in respect of age , sex , height or weight , smoking habits or alcohol consumption . After one month triglyceride levels were reduced significantly from baseline in the treatment group and there was also a highly significant difference between the groups in favour of the marine oil . There was no significant change in serum total cholesterol in either group but there were fluctuations in high density lipoprotein ( HDL ) in both groups . Minor gastrointestinal side effects were reported by patients in both groups . St and ard haematological and biochemical tests were done and there were no significant changes from baseline The oral administration of neomycin or niacin as single-drug therapy can significantly lower total and low-density lipoprotein cholesterol concentrations in patients with type II hyperlipoproteinemia . However , in the majority of patients treated with one of these drugs as sole therapy plasma lipid and lipoprotein concentrations do not normalize . The effect of combined neomycin ( 2 g/day ) and niacin ( 3 g/day ) treatment on the plasma lipoprotein concentrations was determined in 25 type II hyperlipoproteinemic patients in a double-blind , r and omized , placebo-controlled , crossover clinical trial . Treatment with neomycin was well tolerated by all 25 study patients and significantly reduced total and low-density lipoprotein cholesterol concentrations by 23 % and 29 % , respectively ( p less than .05 ) . In contrast to the well-tolerated neomycin regimen , 11 patients ( 44 % ) were unable to continue niacin treatment because of adverse side effects . In the 14 patients treated with both neomycin and niacin , niacin further lowered the concentrations of total and low-density lipoprotein cholesterol by 18 % and 25 % , respectively , and increased high-density lipoprotein cholesterol by 32 % ( p less than .05 ) compared with that in the patients receiving neomycin plus niacin placebo . Compared with diet-only therapy , combined treatment with neomycin plus niacin reduced the total plasma cholesterol concentration by 36 % , low-density lipoprotein cholesterol by 45 % , and the low-density lipoprotein/high-density lipoprotein ratio by 46 % and it increased plasma high-density lipoprotein concentrations by 24 % ( p less than .001 ) . During the study , 80 % of all the study patients and 92 % of the patients who complied with the combined regimen normalized their total and low-density lipoprotein concentrations . ( ABSTRACT TRUNCATED AT 250 WORDS In the National Heart , Lung and Blood Institute Type II Coronary Intervention Study , patients with Type II hyperlipoproteinemia and coronary artery disease ( CAD ) were placed on a low-fat , low-cholesterol diet and then were r and omly allocated to receive either 6 g cholestyramine four times daily or placebo . This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography . Diet alone reduced the low-density lipoprotein cholesterol 6 % in both groups . After r and omization , low-density lipoprotein cholesterol decreased another 5 % in the placebo group and 26 % in the cholestyramine-treated group . Coronary angiography was performed in 116 patients before and after 5 years of treatment . CAD progressed in 49 % ( 28 of 57 ) of the placebo-treated patients vs 32 % ( 19 of 59 ) of the cholestyramine-treated patients ( p less than .05 ) . When only definite progression was considered , 35 % ( 20 of 57 ) of the placebo-treated patients vs 25 % ( 15 of 59 ) of the cholestyramine-treated patients exhibited definite progression ; the difference was not statistically significant . However , when this analysis was performed with adjustment for baseline inequalities of risk factors , effect of treatment was more pronounced . Of lesions causing 50 % or greater stenosis at baseline , 33 % of placebo-treated and 12 % of cholestyramine-treated patients manifested lesion progression ( p less than .05 ) . Similar analyses with other end points ( percent of baseline lesions that progressed , lesions that progressed to occlusion , lesions that regressed , size of lesion change , and all cardiovascular end points ) all favored the cholestyramine-treated group , but were not statistically significant . Thus , although the sample size does not allow a definitive conclusion to be drawn , this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia Fourteen women and five men participated in a 20-week controlled , cross-over trial of the interaction of simvastatin , an HMGCoA reductase inhibitor , with high and low fat diets . Simvastatin was found to be just as effective at lowering LDL cholesterol whether the subjects were on a 22 % fat diet or a 38 % fat diet ( 25 % and 29 % falls , respectively ) . Nevertheless , the lowest cholesterol levels were achieved by combining simvastatin with a low fat diet , the latter adding a further 5 % reduction in plasma cholesterol . Simvastatin plus a low or high fat diet increased HDL cholesterol by 10.0 % and 2.9 % respectively ( P = 0.003 overall ) and reduced triglyceride concentration by 15.9 % and 19 % respectively ( P less than 0.001 ) . Significant diet-drug interactions were seen in LDL and HDL3 cholesterol . Simvastatin blunted the effect of dietary fat change so that the difference in LDL cholesterol , which was 0.71 mmol/l between high and low fat in the absence of simvastatin , was only 0.22 mmol/l with simvastatin . On a high fat diet , simvastatin produced almost no rise in HDL3 cholesterol whereas on a low fat diet HDL3 cholesterol was increased by 8.8 % with simvastatin . The cholesterol content of VLDL and LDL were significantly reduced by simvastatin . The effects of diet and drug on apoproteins A-I and B resembles those on HDL and LDL cholesterol . The findings show interactions between simvastatin and dietary fat which have a bearing on the treatment of hypercholesterolemia BACKGROUND Data continue to accumulate supporting a proatherogenic role for oxidized low-density lipoprotein ( Ox-LDL ) . Antioxidant micronutrients such as ascorbate , alpha-tocopherol , and beta carotene , levels of which can be favorably manipulated by dietary measures without side effects , could be a safe approach in inhibiting LDL oxidation . In fact , in vitro studies have shown that all three antioxidants can inhibit LDL oxidation . The present study was undertaken to ascertain both the safety and antioxidant effect of combined supplementation with alpha-tocopherol , ascorbate , and beta carotene on LDL oxidation . METHODS AND RESULTS The effect of combined supplementation with alpha-tocopherol ( 800 IU/d ) plus ascorbate ( 1.0 g/d ) and beta carotene ( 30 mg/d ) on copper-catalyzed LDL oxidation was tested in a r and omized , placebo-controlled study in two groups of 12 male subjects over a 3-month period . Blood sample s for the lipoprotein profile , antioxidant levels , and LDL isolation were obtained at baseline and at 3 months . Neither placebo nor combined antioxidant therapy result ed in any side effects or exerted an adverse effect on the plasma lipoprotein profile . Compared with placebo , combined antioxidant therapy result ed in a significant increase in plasma ascorbate and lipid st and ardized alpha-tocopherol and beta carotene levels ( 2.6- , 4.1- , and 16.3-fold , respectively ) . At baseline , there were no significant differences in the time course curves and kinetics of LDL oxidation as evidence d by the thiobarbituric acid reacting substances ( TBARS ) assay and the formation of conjugated dienes . However , at 3 months , combined supplementation result ed in a twofold prolongation of the lag phase and a 40 % decrease in the oxidation rate . The combined antioxidant group was also compared with a group that received 800 IU of alpha-tocopherol only . Although the combined antioxidant group had significantly higher ascorbate and beta carotene levels than the group supplemented with alpha-tocopherol alone , there were no significant differences between the two groups with respect to LDL oxidation kinetics . CONCLUSIONS Combined supplementation with ascorbate , beta carotene , and alpha-tocopherol is not superior to high-dose alpha-tocopherol alone in inhibiting LDL oxidation . Hence , alpha-tocopherol therapy should be favored in future coronary prevention trials involving antioxidants STUDY OBJECTIVE To compare the efficacy of gemfibrozil and colestipol with gemfibrozil and lovastatin in patients with familial combined hyperlipidemia . DESIGN A prospect i ve , r and omized trial . SETTING An outpatient clinical research center in a tertiary care center . PATIENTS Seventeen patients with familial combined hyperlipidemia documented by studies of first-degree relatives ; nine patients with type 2b hyperlipoproteinemia , and eight patients with type 4 hyperlipoproteinemia . INTERVENTIONS Baseline lipid , lipoprotein , and apolipoprotein levels were obtained during control periods on diet alone and on gemfibrozil therapy . Patients then received gemfibrozil and colestipol or gemfibrozil and lovastatin in a r and omized order . MEASUREMENTS AND MAIN RESULTS In patients with type 2b hyperlipoproteinemia , gemfibrozil alone significantly reduced total cholesterol by 11 % , and low density lipoprotein (LDL)-apolipoprotein B by 18 % , did not change LDL-cholesterol , and raised high density lipoprotein (HDL)-cholesterol levels by 26 % . Addition of either colestipol or lovastatin reduced LDL-cholesterol levels by 17 % and 25 % , respectively , compared to gemfibrozil alone . However , colestipol mitigated the HDL-cholesterol raising effect of gemfibrozil and did not further reduce LDL-apolipoprotein B levels . In contrast , addition of lovastatin caused an additional reduction of LDL-apolipoprotein B 19 % compared with gemfibrozil alone . In patients with type 4 hyperlipoproteinemia , gemfibrozil alone reduced triglycerides by 40 % , raised HDL-cholesterol by 26 % , and increased LDL-cholesterol levels by 29 % . The addition of either colestipol or lovastatin reduced LDL-cholesterol levels by 34 % and 33 % , respectively ( compared with gemfibrozil alone ) , but greater reductions of LDL-apolipoprotein B ( 30 % with lovastatin compared with 15 % with colestipol , compared with gemfibrozil alone ) , and increases in HDL-cholesterol levels ( 8 % increase with lovastatin compared with 10 % decrease with colestipol , compared to gemfibrozil alone ) were seen with the lovastatin combination . CONCLUSIONS Although gemfibrozil with either colestipol or lovastatin favorably altered lipoprotein levels in patients with hypertriglyceridemia and familial combined hyperlipidemia , the combination of gemfibrozil and lovastatin appeared superior overall BACKGROUND A diet low in saturated fat and cholesterol is the st and ard initial treatment for hypercholesterolemia . However , little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined effects of diet and drug therapy . METHODS One hundred eleven out patients with moderate hypercholesterolemia were treated at five lipid clinics with the National Cholesterol Education Program Step 2 diet ( which is low in fat and cholesterol ) and lovastatin ( 20 mg once daily ) , both alone and together . A diet high in fat and cholesterol and a placebo identical in appearance to the lovastatin were used as the respective controls . Each of the 97 patients completing the study ( 58 men and 39 women ) underwent four consecutive nine-week periods of treatment according to a r and omized , balanced design : a high-fat diet-placebo period , a low-fat diet-placebo period , a high-fat diet-lovastatin period , and a low-fat diet-lovastatin period . RESULTS The level of low-density lipoprotein ( LDL ) cholesterol was a mean of 5 percent ( 95 percent confidence interval , 3 to 7 percent ) lower during the low-fat diet than during the high-fat diet ( P < 0.001 ) . With lovastatin therapy as compared with placebo , the reduction was 27 percent . Together , the low-fat diet and lovastatin led to a mean reduction of 32 percent in the level of LDL cholesterol . The level of high-density lipoprotein ( HDL ) cholesterol fell by 6 percent ( 95 percent confidence interval , 4 to 8 percent ) during the low-fat diet ( P < 0.001 ) and rose by 4 percent during treatment with lovastatin ( P < 0.001 ) . The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin ( P < 0.001 ) , but not by the low-fat diet . CONCLUSIONS The effects of the low-fat-low-cholesterol diet and lovastatin on lipoprotein levels were independent and additive . However , the reduction in LDL cholesterol produced by the diet was small , and its benefit was possibly offset by the accompanying reduction in the level of HDL cholesterol A group of 33 mildly hypercholesterolemic men were stratified into three groups on diets closely matched except for the polyunsaturated fatty acid supplement . The first group received 14 g/day of linoleic acid ( safflower oil ) ; the second group , 9 g of alpha-linolenic acid ( linseed oil ) ; and the third group , 3.8 g of n-3 fatty acids ( fish oil ) . Only fish oil lowered plasma triglycerides ( by 24 % at 6 weeks , p less than 0.05 compared to safflower oil ) . Very low density lipoprotein ( VLDL ) apoprotein ( apo ) B , triglyceride , and cholesterol all fell significantly with the fish-oil diet ( p less than 0.01 ) . Low density lipoprotein ( LDL ) cholesterol fell by 0.18 and 0.10 mmol/l , respectively , with the safflower-oil and linseed-oil diets , but rose by 0.24 mmol/l with the fish-oil diet ( p less than 0.05 ) . There was a strong correlation between the changes in VLDL triglyceride and LDL cholesterol with the fish-oil diet ( r = -0.84 , p less than 0.002 ) . High density lipoprotein ( HDL ) cholesterol fell slightly in all three groups ( p less than 0.02 with the linseed-oil diet only ) . However , the apo A-I/A-II ratio rose by 5 % ( p less than 0.05 ) , and the HDL2/HDL3 protein ratio increased by 28 % with the fish-oil diet ( p less than 0.005 ) . Fish oil reduced the capacity for transfer of cholesteryl ester between LDL and HDL by 23 % ( p less than 0.02 compared to baseline ) , reduced plasma lecithin : cholesterol acyltransferase activity by 21 % ( p less than 0.05 ) , and reduced maximal stimulated thromboxane production by 9 % ( p less than 0.05 ) . Thus fish oil produced three potentially beneficial changes : significant decreases in VLDL concentration and in thromboxane production and an increase in the HDL2/HDL3 ratio . The increase in the average HDL particle size probably reflected reduced cholesteryl ester acceptor capacity within the smaller pool of VLDL , as well as the decline in lipid transfer activity in plasma involving transfer protein itself , LDL , and HDL OBJECTIVE To examine the effect of supplementation with vitamin E ( alpha tocopherol ) , beta carotene , or both on the incidence of angina pectoris in men without known previous coronary heart disease . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING AND PARTICIPANTS Participants in the Alpha Tocopherol , Beta Carotene Cancer Prevention Study ( N=29133 ) were male smokers aged 50 through 69 years who were living in southern and western Finl and . Of these men , 22269 were considered free of coronary heart disease at baseline and were followed up for the incidence of angina pectoris . INTERVENTION Participants were r and omized to receive 50 mg/d of alpha tocopherol , 20 mg/d of beta carotene , both , or placebo in a 2x2 design . OUTCOME MEASURES An incident case was defined as the first occurrence of typical angina pectoris identified in administering the annually repeated World Health Organization ( Rose ) Chest Pain Question naire . RESULTS During a median follow-up time of 4.7 years ( 96427 person-years ) , 1983 new cases of angina pectoris were detected . Comparing alpha tocopherol-supplemented subjects with non-alpha tocopherol-supplemented subjects showed a relative risk ( RR ) of angina pectoris incidence of 0.91 ( 95 % confidence interval[CI ] , 0.83 to 0.99 ; P=.04 ) . The RR for incidence of angina pectoris for the beta carotene- supplemented subjects compared with those not receiving beta carotene was 1.06 ( 95 % CI , 0.97 to 1.16 ; P=.19 ) . Compared with those receiving placebo , the RRs for incidence of angina pectoris were 0.97 ( 95 % CI , 0.85 to 1.10 ) and 0.96 ( 95 % CI , 0.85 to 1.09 ) in the alpha tocopherol and alpha tocopherol plus beta carotene groups , respectively , and 1.13 ( 95 % CI , 1.00 to 1.27 ) in the beta carotene group ( P=.06 ) . Baseline dietary intakes and serum levels of alpha tocopherol and beta carotene did not predict incidence of angina pectoris . CONCLUSIONS Supplementation with alpha tocopherol was associated with only a minor decrease in the incidence of angina pectoris . Beta carotene had no preventive effect and was associated with a slight increase of angina The effects of colestipol ( 30 grams/day ) , niacin ( 7.3 grams/day ) , and diet on blood lipids and apolipoproteins after one year of therapy are reported . Men selected on the basis of previous coronary artery bypass surgery were r and omly assigned to drug or control treatments in an angiographic study of atherosclerosis progression and regression . In 14 men , drugs and diet produced the following changes : Baseline total cholesterol 245 mg/dl , triglyceride 189 mg/dl , and LDL cholesterol 164 mg/dl were decreased by 73 mg/dl ( 29 % ) , 83 mg/dl ( 41 % ) and 69 mg/dl ( 40 % ) respectively . Baseline HDL cholesterol , 44 mg/dl was increased 13 mg/dl ( 33 % ) . Baseline apolipoprotein B , 124 mg/dl and apolipoprotein C-lll ( heparin precipitate ) 5.6 mg/dl were decreased 40 mg/dl ( 31 % ) and 2.4 mg/dl ( 41 % ) respectively . All these changes are significant , p < 0.01 . Apolipoprotein A-l and apolipoprotein C-lll ( heparin supernate ) were not significantly changed . In the controls , placebo and diet produced no significant decrease in blood lipid or lipoproteins , with the exception that baseline apolipoprotein B , 111 mg/dl increased 18 mg/dl ( 12 % ) , p < 0.05 BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes We have studied whether a low-fat diet is as effective in lowering some risk factors for atherosclerosis as a diet rich in polyunsaturated fat ( PUFA ) . During a 2.5 week control period , 60 volunteers were given a moderate-fat diet ( MOD ) providing 30 % of the daily energy intake ( energy % ) in the form of fat , one-third of which was PUFA . For the next 5 weeks subjects were divided into 4 groups and received diets providing varying amounts of total fat and of PUFA : for group LO , 20 energy % PUFA ; group HIPUF , 40 energy % fat and 19 energy % PUFA ; and group HISAT , 40 energy % fat and 3 energy % PUFA . The diets contained the same amounts of cholesterol , phytosterols , oligosaccharides and other nutrients , known to affect serum lipid levels . All food was prepared daily and weighed out for each individual appropriate to his energy needs . Nutrient intakes were checked by 7-day records and by chemical analysis of double portions . On diet LO , total serum cholesterol concentration increased by 0.25 mmol/l while HDL cholesterol concentration did not change significantly . The HDL cholesterol/apoprotein-A1 ratio fell , and VLDL and LDL triglyceride centrations were elevated . On the HIPUF diet , total serum cholesterol concentration was not significantly lower , but HDL cholesterol concentration increased by 0.10 mmol/l . On the HISAT diet , total serum cholesterol concentration went up by 0.38 mmol/l ; 0.12 mmol/l of this was due to HDL . LDL cholesterol/serum apoprotein-B ratios were unaffected by any of the diets . It was concluded that after 5 weeks , the influence of a low-fat , high-carbohydrate diet on the concentrations of serum lipoproteins was less favourable than that of moderate- or high-fat diets rich in polyunsaturated fatty acids In heterozygous familial hypercholesterolemia ( FH ) , serum low density lipoprotein ( LDL ) cholesterol levels are already elevated at birth . Premature coronary heart disease occurs in approximately 30 % of heterozygous untreated adult patients . Accordingly , to retard development of atherosclerosis , preventive measures for lowering cholesterol should be started even in childhood . To this end , 19 FH families consumed dietary stanol ester for 3 months . Stanol ester margarine lowers the serum cholesterol level by inhibiting cholesterol absorption . Each individual in the study replaced part of his or her daily dietary fat with 25 g of 80 % rapeseed oil margarine containing stanol esters ( 2.24 g/d stanols , mainly sitostanol ) . The families who consumed this margarine for 12 weeks included 24 children , aged 3 to 13 years , with the North Karelia variant of FH ( FH-NK ) , 4 FH-NK parents , and 16 healthy family members , and a separate group of 12 FH-NK adults who consumed the margarine for 6 weeks and who were on simvastatin therapy ( 20 or 40 mg/d ) . Fat-soluble vitamins were measured by high-pressure liquid chromatography , and cholesterol precursor sterols ( indexes of cholesterol synthesis ) and cholestanol and plant sterols ( indexes of cholesterol absorption efficiency ) were assayed by gas-liquid chromatography . No side effects occurred . Serum LDL cholesterol levels were reduced by 18 % ( P<0.001 ) , 11 % , 12 % ( P<0.001 ) , and 20 % ( P<0.001 ) in the 4 groups , respectively . The serum campesterol-to-cholesterol ratios fell by 31 % ( P<0.001 ) , 29 % , 23 % ( P<0.001 ) , and 36 % ( P<0.001 ) , respectively , suggesting that cholesterol absorption efficiency was inhibited . Serum lathosterol ratios were elevated by 38 % ( P<0.001 ) , 11 % , 15 % ( P<0.001 ) , and 19 % ( P<0.001 ) , respectively , suggesting that cholesterol synthesis was compensatorily upregulated . The FH-NK children increased their serum lathosterol ratio more than did the FH-NK adults treated with stanol ester margarine and simvastatin ( P<0.01 ) . In the FH-NK children , serum retinol concentration and alpha-tocopherol-to-cholesterol ratios were unchanged by stanol ester margarine , but alpha- and beta-carotene concentrations and ratios were decreased . As assayed in a genetically defined population of FH patients , a dietary regimen with stanol ester margarine proved to be a safe and effective hypolipidemic treatment for children and adults . In FH-NK adults on simvastatin therapy , serum LDL cholesterol levels could be reduced even further by including a stanol ester margarine in the regimen 1 . Serum cholesterol reduction and changes in cholesterol metabolism were studied during rapeseed oil feeding without and with increasing amounts of sitostanol trans-esterified with rapeseed oil fatty acids and dissolved in rapeseed oil mayonnaise . Fifteen mildly hypercholesterolaemic subjects replaced 50 g of their usual dietary fat by 50 g of rapeseed oil fat mayonnaise for 6 weeks followed by r and omization so that eight subjects continued on rapeseed oil mayonnaise alone ( control group ) for 15 weeks and seven on rapeseed oil mayonnaise with a small dose of sitostanol ester ( 800 mg/day of sitostanol ) for 9 weeks followed by 6 weeks with higher dose of sitostanol ester ( 2000 mg/day of sitostanol ) . 2 . During the rapeseed oil period the reduction in serum low-density lipoprotein cholesterol was 14 % from the home diet . The control-adjusted reduction by the low sitostanol ester dose was 7.4 % ( not significant ) and by the higher dose it was 15.7 % . 3 . The low dose of sitostanol ester had no consistent effect on cholesterol precursors or cholestanol in serum , reduced serum levels of campesterol and sitosterol by 28.2 % and 23.6 % , respectively , and reduced cholesterol absorption efficiency significantly from 28.7 % to 23.4 % . In accordance , faecal excretion of neutral and particularly endogenous neutral sterols increased ( 16.7 % and 19.7 % , respectively ) , but faecal cholesterol elimination and cholesterol synthesis were only insignificantly increased . 4 . During the high dose of sitostanol ester the high-density lipoprotein-to low-density lipoprotein-cholesterol ratio increased . ( ABSTRACT TRUNCATED AT 250 WORDS Plasma lipid response to dietary fat and cholesterol is , in part , genetically controlled . The apolipoprotein A-IV ( apoA-IV protein ; APOA4 , gene ) has been shown to influence the response to dietary changes in normolipidemic individuals . The response to diet in subjects with familial hypercholesterolemia ( FH ) is also variable , and no studies are available on the influence of APOA4 mutations on dietary response in these subjects . We studied the effect of 2 common apoA-IV genetic variants ( Gln360 - ->His and Thr347 - ->Ser ) on the lipid response to the National Cholesterol Education Program type I ( NCEP-I ) diet in 67 FH heterozygotes ( 43 women and 24 men ) . Subjects were studied at baseline ( after consuming for 1 month a diet with 35 % fat [ 10 % saturated ] and 300 mg/d cholesterol ) and after 3 months of consuming a low-fat diet . No sex-related differences were found , and results were combined for men and women . The APOA4 - 360 mutation was assessed in 67 subjects , 51 with genotype 1/1 and 16 with genotype 1/2 . The APOA4 - 2 allele was associated with marginally significantly lower ( P=0.049 ) low density lipoprotein ( LDL ) cholesterol levels and significantly lower ( P=0.027 ) apoB levels independent of diet effects . After consuming an NCEP-I diet , carriers of the APOA4 - 2 allele showed a significantly lower reduction in apoB concentration ( 6.2 % ) than 1/1 subjects ( 14.1 % ; P=0.036 ) ; however , no significant differences in response were noted for LDL cholesterol . The APOA4 - 347 mutation was assessed in 63 individuals , 44 with the A/A allele and 19 with the A/T and T/T alleles . No significant differences were observed in baseline or post-NCEP-I diet values for these 2 groups in total , LDL , and high density lipoprotein cholesterol and plasma apoB levels . After dietary intervention , A/A individuals showed significant reductions in plasma triglyceride and very low density lipoprotein cholesterol levels ; no changes were found in carriers of the T allele . Haplotype analysis suggested that in these FH subjects , the APOA4 - 360 - 2 allele was associated with lower plasma lipid levels during the NCEP-I diet period , whereas no significant effects were observed for the APOA4 - 347-T allele In a placebo-controlled trial healthy volunteers and patients with hyperlipoproteinemias types II and IV received orally vitamin E at doses of 300 mg and 600 mg daily for 2 weeks . Serum tocopherol levels increased two-fold , but serum concentrations of total lipids , cholesterol , triglycerides , ceruloplasmin and transferrin remained unchanged . Dietary supplementation with vitamin E suppressed elevated concentrations of plasma lipid peroxides and this effect was correlated with an increase in serum antioxidant activity . In patients a mild platelet suppressant effect of vitamin E ( 600 mg daily ) was observed . Feeding an atherogenic diet to rabbits for a week result ed in elevation of plasma lipid peroxides and a 90 % decrease in arterial generation of prostacyclin . Enrichment of the atherogenic diet with 100 mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries . Thus , in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis In a controlled trial 40 healthy persons ( 20 men and 20 women ) were tested before and after a daily supplement with 25 ml cod liver oil for 8 weeks . The diet increased the eicosapentaenoic acid ( 20:5 n-3 ) content in serum and monocytes four- to five-fold whereas the arachidonic acid ( 20:4 n-6 ) content decreased 10 - 20 % in both serum and monocytes . Stimulation of blood with a low concentration of lipopolysaccharides ( LPS ) revealed a 40 % suppression of LPS-induced thromboplastin synthesis in the monocytes after 8 weeks of CLO intake . In the same LPS stimulation system , men were found to generate significantly more thromboxane B2 than women ( 4.9 ng ml-1 versus 3.4 ng ml-1 ) . After the CLO supplementation for 8 weeks the thromboxane B2 was reduced by a mean of 70 % in women and 60 % in men . Factor VII and fibrinogen appeared to be unaltered by CLO intake . Determination of whole blood clot lysis time and tissue plasminogen activator ( t-PA ) did not indicate any significant influence of n-3 fatty acids on fibrinolysis Summary CI-924 ( CI ) , 5,5′-[[1,1′-biphenyl]-2,5-diylbis(oxy)]bis[2,2-dimethylpentanoic acid ] is chemically similar to gemfibrozil . Patients with Type II ( n=13 ) and Type IV ( n=22 ) hyperlipoproteinaemia ( HLP ) were maintained 12 weeks on a baseline diet containing 55 % sugar , 15 % protein 30 % fat and < 300 mg cholesterol daily to stabilize weight and lipids . They were then entered in a parallel group double-blinded protocol and received 0 , 300 , 600 , or 1200 mg CI p.o . daily for 12 weeks . CI consistently elevated anti-atherogenic HDL and lowered VLDL at 600 mg/day in both Type II and Type IV HPL at 8 weeks . In Type II patients , CI lowered cholesterol , decreased LDL/HDL and increased ApoA-I. In Type IV patients , CI also lowered TC while elevating LDL and ApoA-II . CI had no effect on Apo-B , LDL-ApoB , or Patients with familial hypercholesterolemia ( type IIa ) were given 30 ml cod liver oil ( CLO ) as dietary supplement daily for 6 weeks . The effects on platelets , bleeding time , coagulation and blood and platelet lipids were examined . The major findings were a reduced collagen-induced platelet aggregation and a decrease in thrombin-stimulated thromboxane B2 generation in platelets in vitro . The primary bleeding time was not significantly prolonged . Statistically significant increase in eicosapentaenoic acid/arachidonic acid ratios in the main platelet phospholipids were also observed . These changes did not correlate with any of the changes in platelet behavior observed after CLO intake . The serum total and HDL cholesterol and triglycerides were not altered during the trial The present article summarizes the effects of diets containing either cow 's milk or soy protein beverage on plasma lipids and lipoproteins in children with familial hypercholesterolemia . After a stabilization period of 6 weeks without any hypolipemic medication , 10 subjects aged 6 - 12 years were r and omly assigned to either cow 's milk or soy protein beverage with subsequent crossover after a washout period , each of 4 weeks duration . During the experimental periods , subjects were fed diets containing 20 % of energy as protein , of which 35 % was from cow 's milk protein or soy protein isolate , 28 % of energy as fat with a polyunsaturated : monounsaturated : saturated fat ratio of 1:3:3 , and less than 200 mg/day of cholesterol . The soy protein beverage , compared to cow 's milk , induced significant reductions in plasma triglycerides and very-low-density lipoprotein cholesterol , as well as a significant increase in high-density lipoprotein cholesterol , indicating that consumption of soy protein beverage may be beneficial for the prevention of coronary heart disease in children with familial hypercholesterolemia Ten healthy male subjects on an ordinary diet were given daily dietary supplement of 25 ml cod liver oil ( CLO ) or corn oil ( CO ) for periods of 6 weeks in a crossover study . Significant changes were observed in the plasma total fatty acid composition . The main platelet phospholipids fractions were also significantly altered , particularly by CLO with an increase of the eicosapentaenoic acid ( EPA ) : arachidonic acid ( AA ) ratio . Both supplements reduced collagen induced platelet aggregation and TXB2 production , with CLO as the most potent one . No spontaneous release of an antiaggregatory substance or 6-keto-PGF1 alpha from vein tissues were found , and the total urinary excretion of prostagl and in metabolites ( E and F series ) remained unchanged Lipid-lowering diets enriched in polyunsaturated fat decrease the serum cholesterol in hyperlipoproteinaemia , usually by reducing both the low-density-lipoprotein ( LDL ) and high-density-lipoprotein ( HDL ) cholesterol concentrations . The aim of the present study was to investigate whether the effects on LDL could be maintained but those on HDL cholesterol be diminished by reducing the ratio , polyunsaturated : saturated fat ( P : S ) of the diet . Twenty hyperlipoproteinaemic patients ( six with type IIa , eight with type IIb and six with type IV ) in a metabolic ward were given two fat-modified diets during two consecutive 3-week periods in a r and omized order . The diets were identical with regard to nutrient composition but differed with regard to the P : S values , which were 2.0 and 1.3 respectively . The lipoprotein-lipid composition and serum apolipoprotein concentrations were similar at the end of the two dietary periods in type IIa and type IV patients but in type IIb patients a more pronounced reduction of the LDL-cholesterol concentration by 9 % ( P less than 0.05 ) was achieved on the diet with the higher P : S value . The HDL-cholesterol did not differ significantly . The results indicate that increasing the P : S value of lipid-lowering diets from 1.3 to 2.0 does not offer a great advantage with regard to the lipoprotein-lipid reductions achieved in moderate hyperlipoproteinaemia Because marine oil capsules may vary widely in their content of omega-3 fatty acids , saturated fat , and cholesterol composition and , therefore , their biologic potency , we compared the lipid-lowering effects of three representative preparations in patients with different forms of hyperlipidemia . The ester and triglyceride forms of marine oil both effectively lowered triglyceride , but the response of low-density lipoprotein cholesterol was variable ; it declined modestly in patients with hypercholesterolemia and was either unchanged or increased in those with hypertriglyceridemia . The saturated fat and cholesterol content of the marine oil preparation appeared to influence the low-density lipoprotein cholesterol response . Therefore , marine oil capsules are useful for lowering levels of very-low-density lipoprotein cholesterol , but the large dose required to achieve and sustain this effect ( 4.5 g of omega-3 fatty acids , or nine to 18 capsules daily ) may limit long-term compliance Abstract . 25 children with familial hypercholesterolemia ( type II A ) were treated with cholestyramine or placebo in a cross over study during 2 periods of each 10 weeks . The medication was added to a high linoleic acid diet , which had been started at least 1 year earlier . Serum lipids and platelet aggregation were investigated at the end of the 2 periods . On cholestyramine , serum cholesterol levels decreased significantly , whereas the linoleate and oleate content of cholesterylesters and serum triglycerides did not change systematic ally . Platelet aggregation time , measured with a filtragometer , did not systematic ally change either Abstract The effect on serum lipids of oral administration of 2 g calcium daily during 8 weeks was studied in 16 Hyperlipidemic patients . The study was preceded by a 4 week placebo period . Five patients were classified as having type IIA hyperlipidemia according to Fredrickson et al. ( as modified ) , 10 patients as having type IIB and 1 patient as having type IV . Body weight before the study and mean values during placebo and calcium therapy were 70.2 ± 2.49 kg , 70.0 ± 2.54 kg and 69.4 ± 2.55 kg respectively . The difference between placebo mean value and calcium mean value was significant at the 5 % level . The average serum triglyceride value before treatment was 2.89 ± 0.383 mmol/1 , during treatment with placebo 2.45 ± 0.266 mmol/l and during calcium treatment 2.70 ± 0.286 mmol/l . The decrease during placebo therapy when compared to the mean value before treatment was significant at the 5 % level . No decrease in serum triglycerides could be ascribed to calcium therapy . The average serum cholesterol value before treatment was 337 ± 13.5 mg/ 100 ml and decreased to 321 ± 12.8 mg/ 100 ml during placebo treatment and to 303 ± 12.0 mg/ 100 ml during treatment with calcium . The decrease was significant at the 1 % level when the mean value before treatment was compared to the average value during placebo therapy , and was significant at the 0.1 % level when the mean value during placebo treatment was compared to the mean value during calcium therapy . No correlation was noted between either total or low density lipoprotein cholesterol levels before treatment and decrease in total cholesterol levels Plant sterols may be a useful additive therapy in the treatment of hypercholesterolaemic patients . The purpose of this study was to determine the effect of a fat spread enriched with vegetable oil sterols on plasma lipid , lipoprotein and apolipoprotein concentrations . A r and omised double blind placebo-controlled crossover trial with two consecutive periods of 8 weeks was conducted . 30 patients with heterozygous familial hypercholesterolaemia treated concurrently with an HMG-CoA reductase inhibitor ( statin ) and 32 patients with type IIa primary hypercholesterolaemia with a total cholesterol concentration > 6.5 mmol/l not taking lipid-lowering drug therapy were recruited from a hospital lipid clinic . The active treatment was a fortified fat spread ( 25 g/day ) providing 2.5 g of plant sterols . The control spread was indistinguishable in taste and appearance . Comparison at the end of the two 8-week trial periods showed a statistically significant reduction in total and LDL-cholesterol with use of the fortified spread but the results were confounded by a carry-over effect , which was partly explained by changes in the background diet . Because a carry-over effect was present , further analyses were restricted to the parallel arms of the first treatment period and were conducted on an intention to treat basis . After 4 weeks , LDL-cholesterol had decreased by 0.04 mmol/l ( [ 0.8 % ] 95 % confidence interval -0.44 - 0.37 NS ) in the placebo group and decreased by -0.76 mmol/l ( [ 15.0 % ] 95 % CI -1.03 - -0.48 , P<0.0001 ) in the active treatment group . After 8 weeks , the corresponding results were 0.0 mmol/l ( [ 0.0 % ] 95 % CI -0.26 - 0.24 NS ) and -0.51 mmol/l ( [ 10.0 % ] 95 % CI -0.73 - -0.29 P<0.0001 ) . There were no significant changes in apolipoprotein AI or B concentrations in the placebo group , but there was a small but statistically significant increase in apolipoprotein AI and a decrease in apolipoprotein B in the active treatment group . HDL cholesterol and triglyceride concentrations were unchanged . There was no difference in response between patients with statin-treated familial hypercholesterolaemia and patients with type IIa hyperlipoproteinaemia . We conclude that a fortified fat spread enriched with vegetable oil sterols reduces LDL-cholesterol by 10 - 15 % with no difference in response between hypercholesterolaemic patients prescribed statins and those not taking lipid-lowering drug therapy Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia . The effects of a 6-week intervention with fish oil capsules ( daily intake : 216 mg eicosapentaenoic acid , 140 mg docosahexaenoic acid , 390 mg gamma-linolenic acid , and 3480 mg linoleic acid ) on in vivo platelet survival ( 111 In-oxine labeled platelets ) and on ex vivo markers of platelet activation were investigated in a placebo-controlled , double-blind study with 26 hypercholesterolemic patients . In vivo platelet survival increased in the fish oil group ( T ) from a mean of 159+/-14 hours to a mean of 164+/-12 hours ( p=0.025 ) , whereas it remained unchanged in the placebo ( P ) group ( T vs. P ; p=0.055 ) . Ex vivo , thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL ( p=0.003 ) in T but did not change in P ( T vs. P : p=0.002 ) . Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9 ) platelets , p=0.005 , as compared with P ( T vs. P ; p=0.018 ) . The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostagl and in I2 by fish oil . Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either . The changes in platelet activation parameters in T were associated with significant reductions in cholesterol ( -2.9 % ) , low density lipoprotein cholesterol ( -3.5 % ) , and triglycerides ( -12.4 % ) . Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids , which might be beneficial in reducing atherothrombotic risk , in patients with hyperlipoproteinemia type IIa and IIb OBJECTIVE To show whether the ratios of squalene and cholesterol precursor sterols to cholesterol and cholestanol and plant sterols to cholesterol change differently in plasma and especially in the red cells of hypercholesterolemic children during consumption of plant stanol and sterol ester spreads . STUDY DESIGN In a r and omized , double-blind , crossover study , hypercholesterolemic children ( n = 23 ) consumed low-fat plant stanol and sterol ester spreads for 5-week periods separated by a 5-week washout period . Plasma and red cell lipids , squalene , and noncholesterol sterols were measured before and at the end of each period . RESULTS The plant stanol and sterol ester spreads lowered plasma total ( -9 % and -6 % , respectively ) and low-density lipoprotein ( -12 % and -9 % ) cholesterol but had no effect on red cell cholesterol , high-density lipoprotein cholesterol , or plasma triglycerides . The ratios of plasma and red cell sitosterol and campesterol to cholesterol decreased by 32 % to 36 % ( P < .001 ) with the plant stanol ester and increased by 40 % to 52 % ( P < .001 ) with the sterol ester spread . CONCLUSIONS Consumption of plant sterols increases and consumption of plant stanols decreases the ratios of plant sterols to cholesterol in red cells of hypercholesterolemic children proportionately to the respective changes in plasma The effects of marine omega-3 polyunsaturated fatty acids ( FAs ) and antioxidants on the oxidative modification of LDL were studied in a r and omized , double-blind , placebo-controlled trial . Male smokers ( n = 41 ) with combined hyperlipidemia were allocated to one of four groups receiving supplementation with omega-3 FAs ( 5 g eicosapentaenoic acid and docosahexaenoic acid per day ) , antioxidants ( 75 mg vitamin E , 150 mg vitamin C , 15 mg beta-carotene , and 30 mg coenzyme Q10 per day ) , both omega-3 FAs and antioxidants , or control oils . LDL and human mononuclear cells were isolated from the patients at baseline and after 6 weeks of supplementation . LDL was subjected to cell-mediated oxidation by the patients ' own mononuclear cells , as well as to Cu(2+)-catalyzed and 2,2'-azobis-(2-amidinopropane hydrochloride ) (AAPH)-initiated oxidation . Extent of LDL modification was measured as lag time , the formation rate of conjugated dienes ( CDs ) , the maximum amount of CDs formed , formation of lipid peroxides , and the relative electrophoretic mobility of LDL on agarose gels . Dietary supplementation with omega-3 FAs increased the concentration of total omega-3 FAs in LDL and reduced the concentration of vitamin E in serum . The omega-3 FA-enriched LDL particles were not more susceptible to Cu(2+)-catalyzed , AAPH-initiated , or autologous cell-mediated oxidation than control LDL . In fact , enrichment with omega-3 FAs significantly reduced the formation rate of CDs when LDL was subjected to AAPH-induced oxidation . Supplementation with moderate amounts of antioxidants significantly increased the concentration of vitamin E in serum and increased the resistance of LDL to undergo Cu(2+)-catalyzed oxidation , measured as increased lag time , reduced formation of lipid peroxides , and reduced relative electrophoretic mobility compared with control LDL . Supplementation with omega-3 FAs/antioxidants showed oxidizability of LDL similar to that of control LDL and omega-3 FA-enriched LDL . In conclusion , omega-3 FAs neither rendered the LDL particles more susceptible to undergo in vitro oxidation nor influenced mononuclear cells ' ability to oxidize autologous LDL , whereas moderate amounts of antioxidants protected LDL against oxidative modification Functional and immunological Antithrombin III ( AT III ) levels were studied in normal and hyperlipoproteinemic subjects undergoing crossover therapeutic trials of either diets or hypocholesterolemic drugs . The diet trial subjects , 7 hyperlipoproteinemics and 15 normals , were r and omly assigned to crossover between a high saturated fat diet ( P/S ratio 1:8 ) and a high polyunsaturated fat diet ( P/S ratio 4:1 ) for periods of 6 - 8 weeks , preceded by a baseline period on regular American diet ( P/S ratio 1:1 ) . For the drug trials , 33 type II A or B hyperlipoproteinemics were treated in r and om and double-blind fashion with Colestipol ( 20 gm/day ) or both , for periods of 3 months , preceded by a double placebo period . Mean low density lipoprotein cholesterol levels were significantly different ( p less than 0.001 ) between high saturated and high polyunsaturated fat diets ( 157 + /- 37 mg/dl vs 137 + /- 31 mg/dl respectively , mean + /- S.D. ) and between placebo and drug treatment periods ( 226 + /- 51 mg/dl vs 183 + /- 44 mg/dl respectively , mean + S.D. ) . There was no difference in basal functional or immunological AT III levels between normal and hyperlipoproteinemics . AT III levels did not correlate significantly with cholesterol or triglyceride levels and remained unchanged despite significant reductions in serum cholesterol related to the diet and drug therapy . There appears to be no significant association between baseline or post treatment serum cholesterol levels and functional or immunological AT III . Thus , changes in AT III are unlikely to play a role in the link between hypercholesterolemia and thrombosis BACKGROUND & AIM The optimal diet for type III hyperlipoproteinemia is unknown . We examined blood lipids and body weight following low or high glycemic index diets in comparison with a lipid-lowering diet . MATERIAL S AND METHODS Sixteen overweight/obese men completed a cross-over study where they followed a st and ard lipid-lowering diet , a high and a low glycemic index diet , each lasting 4 weeks . Measurements were obtained at the end of each diet intervention . RESULTS The lipid-lowering diet reduced significantly LDL cholesterol , and apolipoprotein B by 24 % , and 17 % , whereas high glycemic index increased LDL cholesterol with 21 % . The low glycemic index diet reduced ( p<0.05 ) total and LDL cholesterol and apolipoprotein B compared with the lipid-lowering diet . A moderate weight loss ( p<0.05 ) was achieved after the lipid-lowering diet compared with baseline : 1.4 ( -3.6 - 0.2 ; median , 95 % CI ) kg and similar to that after high glycemic index diet . A low glycemic index diet result ed in 2.4 ( -3.9 - 1.4 ) kg weight loss compared with the high glycemic index diet ( p<0.05 ) . CONCLUSION A low glycemic index diet may be superior to that of a st and ard lipid-lowering diet in type III hyperlipoproteinemia STUDY OBJECTIVE To determine the effects of fish oil supplementation on plasma cholesterol in middle-aged men with isolated hypercholesterolemia . DESIGN R and omized double-blind placebo-controlled ( safflower oil ) two-period crossover trial with 12-week treatment periods . SETTING Outpatient general medicine clinic at a university-affiliated Veterans Affairs hospital . PATIENTS Thirty-eight men with plasma cholesterol between 5.68 and 7.76 mmol/L ( 220 to 300 mg/dL ) , triglyceride levels less than 3.39 mmol/L ( 300 mg/dL ) , and free of coexisting diseases . INTERVENTIONS Fish oil and placebo ( safflower oil ) supplementation . After basal measurements and a 4-week lead-in period , twenty 1-g capsules of either fish oil or placebo oil were provided for 12 weeks ( period 1 ) . After a 4-week washout phase participants then received the other oil for an additional 12 weeks ( period 2 ) . MEASUREMENTS AND MAIN RESULTS Blood was drawn at the beginning and end of each study period and analyzed for levels of total cholesterol , high-density lipoprotein ( HDL ) cholesterol , triglycerides , apolipoprotein A1 , and apolipoprotein B. Low-density lipoprotein ( LDL ) cholesterol was calculated using the Friedewald equation . Total and LDL cholesterol increased from the before treatment values by 4.8 % and 9.1 % , respectively , after ingestion of fish oil . Compared with placebo , LDL cholesterol was significantly higher ( 4.5 compared with 4.1 mmol/L , P = 0.01 ) and triglycerides lower ( 1.3 compared with 1.8 mmol/L , P = 0.01 ) after fish oil . Total and HDL cholesterol and apolipoprotein A1 and B levels did not differ . CONCLUSIONS Fish oil supplements do not lower plasma cholesterol levels in middle-aged men with hypercholesterolemia without elevated triglycerides . They should not be recommended as a method to lower plasma cholesterol in these patients We have investigated the relationship of diet to plasma lipid and lipoprotein levels in 6494 hypercholesterolemic ( Type MA ) men who were instructed in an isocaloric , 400 mg cholesterol , 0.8 polyunsaturated-to-saturated fat ratio diet in the course of recruitment for the Lipid Research Clinics Coronary Primary Prevention Trial . Single 24-hour dietary recalls , plasma total and high density lipoprotein cholesterol , and total triglyceride determinations were obtained approximately 1 month before and after dietary instruction . Cross-sectional correlation analysis disclosed no significant association between diet and plasma cholesterol at entry . However , when diet-associated changes were similarly analyzed , weight loss , decreased intakes of saturated fat and cholesterol , and increased intake of polyunsaturated fat were all significantly and independently predictive of falls in plasma cholesterol , mainly in its low density lipoprotein fraction . The multiple correlation coefficient for the result ant four-variable regression model was 0.29 . Diet-associated changes in plasma very low density lipoprotein cholesterol were less marked but in the same direction . These dietary changes were also weakly associated with a lowering of plasma high density lipoprotein cholesterol , while weight loss had an opposite effect of similar strength . When one takes into account the variability of dietary recall data , the observed diet-associated changes in plasma cholesterol were compatible with the findings of metabolic ward studies Background Because of the inverse relation between dietary fish consumption and coronary heart disease and because of the importance of serum homocysteine as an independent risk factor for atherosclerosis , the effect of fish oil on serum homocysteine was studied in hyperlipemic men . Methods Fifteen men with either type IIa or llb lipoproteinemia or hypertriglyceridemia were maintained on a controlled , balanced diet and given either fish oil or olive oil supplements , 12 g/d for 3 weeks , followed by a cross-over period of 3 weeks during which the olive oil or fish oil supplements were given in reverse order . Serum homocysteine was determined by liquid chromatography of acid hydrolyzates of whole serum . Results Fish oil was found to diminish serum homocysteine levels in 14 of 17 subjects ( P<0.01 ) . Serum homocysteine was 48 % ±33 % less than control values in seven of nine patients and 36 % ± 22 % less than values in seven of eight subjects who had first received olive oil . There was no effect of olive oil supplements on serum homocysteine , compared with control values , but olive oil produced an increase in serum homocysteine in those who had first received fish oil . Serum triglycerides and very low-density lipoprotein were decreased by fish oil in patients who were first given olive oil , in agreement with previous studies . There was no effect of either fish oil or olive oil on total cholesterol , apolipoprotein B , low-density lipoprotein , or high-density lipoprotein . Conclusions The protection against coronary heart disease afforded by a diet rich in fish may be attributed to the lowering of serum homocysteine levels by the n-3 polyunsaturated fatty acids of fish oils OBJECTIVE The primary objective of this study was to determine whether the National Cholesterol Education Program Step II ( NCEP-II ) diet or supplementation with docosahexaenoic acid ( DHA ) with the diet , affects endothelial function in children with familial hypercholesterolemia ( FH ) or the phenotype of familial combined hyperlipidemia ( FCH ) . As secondary endpoints , the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation , and asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of nitric oxide synthase , were all evaluated . METHODS In a double-blind , placebo-controlled , r and omized , crossover study design , 20 children ( ages 9 - 19 years ) with FH ( n = 12 ) and FCH ( n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II ( NCEP-II ) and food guide pyramid dietary guidelines for 6 weeks . They were then r and omly assigned to supplementation with docosahexaenoic acid ( DHA 1.2 g/d ) or placebo for 6 weeks , followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet . Endothelium-dependent flow-mediated dilation ( FMD ) of the brachial artery was determined by high-resolution ultrasound . Plasma levels of total cholesterol , triglycerides and lipoprotein classes ( LDL , HDL , VLDL ) were measured by ultracentrifugation and enzymatic methods , plasma F2 isoprostanes by gas chromatography/mass spectrometry , urinary 8-OH-2 ' deoxyguanosine by liquid chromatography , high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography . RESULTS FMD increased significantly after DHA supplementation compared to baseline ( p < 0.001 ) , diet alone ( p < 0.002 ) , placebo ( p < 0.012 ) and washout ( p < 0.001 ) phases of the study without affecting biomarkers for oxidative stress , inflammation or ADMA . DHA supplementation was associated with increased levels of total cholesterol ( p < 0.01 ) , LDL- and HDL cholesterol concentrations ( p < 0.001 ) compared to the NCEP-II diet . CONCLUSION This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children . The endothelium may thus be a therapeutic target for DHA . This is consistent with a hypothesis of increasing NO bioavailability , with the potential for preventing the progression of early coronary heart disease in high-risk children Oat or bean products , rich in water-soluble fiber , have distinct hypocholesterolemic effects in humans . After a control diet , 20 hypercholesterolemic men were r and omly allocated to oat-bran or bean supplemented diets for 21 days on a metabolic ward . Control and test diets provided equivalent energy , fat , and cholesterol but test diets had twice more total and 3-fold more soluble fiber . Oat-bran diets decreased serum cholesterol concentrations by 19 % ( p less than 0.0005 ) and calculated low-density lipoprotein cholesterol by 23 % ( p less than 0.0025 ) . Bean diets decreased serum cholesterol concentrations by 19 % ( p less than 0.0005 ) and low-density lipoprotein cholesterol by 24 % ( p less than 0.0005 ) . Oat-bran increased fecal weight by 43 % but beans did not . While oat-bran increased fecal bile acid excretion , beans had the opposite effect . Oat-bran or bean supplements may have an important role in nutritional management of selected hypercholesterolemic patients In a secondary prevention trial conducted by the National Heart , Lung , and Blood Institute , the effect of lipid lowering by drug intervention on the progression of existing coronary artery disease ( CAD ) was evaluated in type II hyperlipidemic patients . This first r and omized , secondary prevention trial compared the effect of cholestyramine and diet with that of placebo and diet in 143 patients over a 5-year period . End points evaluated were progression or regression of CAD , as demonstrated by angiographic changes compared with baseline angiograms . The cholestyramine-treated group demonstrated a significant reduction in total cholesterol and in low-density lipoprotein cholesterol ( LDL ) levels as compared with placebo , and an 8 % increase in high-density lipoprotein cholesterol ( HDL ) . A statistically significant result supporting the use of cholestyramine treatment was found in one category of CAD progression We studied the effects of dietary supplementation with an encapsulated fish oil concentrate ( Maxepa ) on platelet function , fibrinolysis , and plasma lipids and lipoproteins in 9 normal subjects , 10 patients with type IV hyperlipoproteinemia , and 6 with type IIB hyperlipoproteinemia . After a baseline period , the subjects crossed over r and omly between treatment periods with Maxepa ( providing 3.24 g eicosapentaenoic acid and 2.16 g docosahexaenoic acid per day ) and safflower oil ( used as a control ) , given for 6 weeks each . Administration of Maxepa led to a slight prolongation of the bleeding time in all groups and to modest inhibition of platelet aggregation in the type IV hyperlipoproteinemics and normal subjects , with partial ( 41 % ) inhibition of thromboxane synthesis from baseline levels noted in the normal group . Plasma total fibrinolytic actively did not change significantly in any group . Maxepa treatment result ed in a marked decrease in triglyceride and VLDL-cholesterol and a slight increase in HDL-cholesterol was noted after Maxepa in the type IV hyperlipoproteinemics ( 4.11 + /- 0.13 mmol/l vs. 3.10 + /- 0.16 mmol/l , Maxepa vs. safflower oil ) . We conclude that dietary supplementation with fish oil results in a relatively minor degree of inhibition of platelet function in normal and hyperlipoproteinemic subjects , and a potentially adverse increase in LDL-cholesterol in type IV hyperlipoproteinemics The Cholesterol Lowering Atherosclerosis Study , a r and omized , placebo-controlled trial of blood lipid lowering , demonstrated significant benefit in 2-year coronary angiograms . Using angiograms of subjects in the Cholesterol Lowering Atherosclerosis Study who received a placebo and 24-hour dietary recall data , we performed an epidemiologic study of risk factors for formation of new atherosclerotic lesions . Age and baseline plus on-trial lipid levels , blood pressure levels , and diet variables were included . Significant dietary energy sources were protein , carbohydrate , alcohol , total fat , and polyunsaturated fat . Each quartile of increased consumption of total fat and polyunsaturated fat was associated with a significant increase in risk of new lesions . Increased intake of lauric , oleic , and linoleic acids significantly increased risk . Subjects in the Cholesterol Lowering Atherosclerosis Study in whom new lesions did not develop increased dietary protein to compensate for reduced intake of fat by substituting low-fat meats and dairy products for high-fat meats and dairy products . These results indicate that when total and saturated fat intakes are reduced to levels recommended by the National Cholesterol Education Program , protein and carbohydrate are preferred substitutes for fat calories , rather than monounsaturated or polyunsaturated fat To find out whether the variable response of serum cholesterol levels to changes in cholesterol intake in man is due to constitutional differences in responsiveness , we have reinvestigated in 1982 34 healthy men and women , who habitually consumed at least 1 egg/day and had participated in a trial in 1976 . Serum cholesterol was measured on the habitual diet ( about 800 mg cholesterol/day ) , and after 3 weeks during which no eggs or egg-containing products were consumed ( about 300 mg cholesterol/day ) . Serum cholesterol decreased by 0.16 + /- 0.42 mmol/1 ( 6 + /- 16 mg/dl ) in 1976 and by 0.31 + /- 0.35 mmol/l ( 12 + /- 14 mg/dl ) in 1982 ( mean + /- SD ) . Individual responses varied from -1.0 to + 0.5 mmol/l ( -39 to + 19 mg/dl ) . The correlation between the responses in 1976 and 1982 was r = 0.32 ( P less than 0.05 ) . The decrease in serum cholesterol was most pronounced for subjects with a low body mass index and a high level of HDL-cholesterol . In men , the increase in serum cholesterol with age was correlated with the mean decrease in the trials ( r = 0.42 , n = 16 , P = 0.11 ) . In a controlled trial , 4 hypo- and 2 hyperresponders were given 11 mg cholesterol/MJ ( 11 mg/240 kcal ; 116 mg/day ) for 4 weeks followed by 72 mg/MJ for another 4 weeks ; all other nutrients were kept constant . Almost all food was supplied and intakes were rigidly controlled . The 2 hyperresponders and 3 of the 4 hyporesponders were also hyper- and hyporesponsive under the controlled conditions . We conclude that part of the cholesterolemic response to dietary cholesterol in man is individually determined and stable for at least 6 years Probucol [ 4,4-(isopropylidendithio bis)(2,6-di-t-butylphenol ) ] , as as an adjunct to diet , was evaluated for its effect on lowering the plasma cholesterol level in patients with familial hypercholesterolemia ( type II ) . The trial had a double-blind , placebo-controlled , crossover design . About half of the 30 patients responded to a low-cholesterol modified-fat diet with a decrease in the plasma cholesterol level of approximately 13 % . When probucol was added to the diet of the responders , their plasma cholesterol level was lowered a further 13 % . Patients who did not respond to the diet did show reduced plasma cholesterol concentrations when receiving probucol plus the diet . Analysis of the cholesterol content of the various lipoprotein fractions showed that the low-density lipoproteins accounted for most of the total plasma cholesterol level decrease . There was , as expected , no effect on plasma triglyceride concentrations . Neither the 7-dehydrocholesterol nor the desmosterol level was increased in the plasma of patients treated with probucol for three months . Probucol is useful as an adjunct to diet in lowering plasma cholesterol levels in patients with familial hypercholesterolemia . The drug was well tolerated by all patients Twenty patients accepted for coronary bypass surgery were r and omized to receive either a concentrated ethylester compound of n-3 fatty acids , with a daily dose of 3.15 g of eicosapentaenoic acid ( EPA ) and 1.89 g of docosahexaenoic acid ( DHA ) , or corn oil ( controls ) in a double blind study , to evaluate the effect on lipids , platelets and coagulation during the pre- and postoperative phase . Only patients with fasting triglyceride ( TG ) levels greater than or equal to 1.6 mmol/l at recruitment were eligible . The study was continued for 5 to 6 months . Surgery was usually performed at mid-intervention . Blood sample s were collected during morning hours in fasting subjects , just prior to intervention , preoperatively and at final postoperative follow-up . Moreover , blood loss was accurately accounted for postoperatively . A threefold increase ( p = 0.0001 ) of EPA was noted at pre- and postoperative follow-up . TG-levels were reduced 20 and 39 % , respectively , in patients on n-3 fatty acids , reaching statistical significance at end of intervention ( p = 0.034 ) . TG-levels in controls remained largely unchanged . In patients on n-3 fatty acids , there was a statistically significant increase in serum total cholesterol preoperatively , but this change was no longer present at completion of the study . No significant changes were noted in platelet function , as judged by bleeding time , collagen induced platelet aggregation and release of TxB2 during aggregation . Parameters of extrinsic coagulation , including phospholipase C-sensitive factor VII ( PLC-VII ) and extrinsic pathway inhibitor ( EPI ) , also remained essentially unchanged in both groups of patients . However , fibrinogen was significantly reduced in controls ( p less than 0.05 ) at end of intervention . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Lung cancer and cardiovascular disease are major causes of death in the United States . It has been proposed that carotenoids and retinoids are agents that may prevent these disorders . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers , former smokers , and workers exposed to asbestos . The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol ( vitamin A ) in the form of retinyl palmitate per day on the primary end point , the incidence of lung cancer , were compared with those of placebo . RESULTS A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up ( mean length of follow-up , 4.0 years ) . The active-treatment group had a relative risk of lung cancer of 1.28 ( 95 percent confidence interval , 1.04 to 1.57 ; P=0.02 ) , as compared with the placebo group . There were no statistically significant differences in the risks of other types of cancer . In the active-treatment group , the relative risk of death from any cause was 1.17 ( 95 percent confidence interval , 1.03 to 1.33 ) ; of death from lung cancer , 1.46 ( 95 percent confidence interval , 1.07 to 2.00 ) ; and of death from cardiovascular disease , 1.26 ( 95 percent confidence interval , 0.99 to 1.61 ) . On the basis of these findings , the r and omized trial was stopped 21 months earlier than planned ; follow-up will continue for another 5 years . CONCLUSIONS After an average of four years of supplementation , the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer , cardiovascular disease , and any cause in smokers and workers exposed to asbestos Twelve volunteers ( mean age , 60.7 + /- 4.2 years ) were treated with placebo for the first week and then given partially purified eicosapentaenoic acid ( EPA , 67 % purity ) at 2 g per day for 4 weeks . Significant decreases in ADP- , collagen- and adrenalin-induced platelet aggregation were observed at 2 and 4 weeks after EPA treatment , together with an increase in the plasma ratio of EPA to arachidonic acid and in platelet phospholipids . It was concluded that the administration of partially purified EPA was effective in decreasing platelet aggregation , possibly by changing the platelet ratio of EPA to arachidonic acid The effects of a fish oil supplement on lipid and lipoprotein levels , platelet function , and vital signs were investigated in 31 hypercholesterolemic patients . Thirteen patients took 5 g of encapsulated fish oil per day and 18 patients took 5 g of encapsulated safflower oil " placebo " per day for 28 days . Diet and exercise patterns were kept as constant as possible during the study . The fish oil group had significant increases in several lipid/lipoprotein values at the end of the treatment , including an increase of total cholesterol of 14 % ( P = 0.0001 ) , LDL of 16 % ( P = 0.003 ) , HDL of 13 % ( P = 0.015 ) and HDL2 of 36 % ( P = 0.009 ) . The triglyceride level fell 24 % , a nonsignificant change ( P = 0.217 ) . The ratios of total cholesterol/HDL and LDL/HDL were increased at the end of fish oil treatment , and returned to baseline 30 days after fish oil was stopped . The placebo group had no significant changes in any of the lipid/lipoprotein values . Neither the fish oil nor the placebo group had significant changes in vital signs or platelet function tests ( bleeding time , thromboxane B2 , platelet factor 4 and beta-thromboglobulin ) during the study . These results suggest that fish oil supplements may have an adverse effect on lipid/lipoprotein values in hypercholesterolemic patients Abstract 1 . 1 . Ninety-nine male patients between the ages of 20 yr and 50 yr with documented myocardial infa rct ions were r and omly divided into two diet therapy groups . The comparability of these two groups was defined with regard to age , age at time of infa rct ion , family history of coronary heart disease , prevalence of hypertension , degree of angina , height , weight , long-term anti-coagulant therapy , electrocardiographic severity and blood cholesterol level . 2 . 2 . The diet plans for two 30 per cent fat diets , one high in polyunsaturated fatty acid to saturated fatty acid and the second with reciprocal ratio , were outlined . 3 . 3 . Forty-eight subjects who were in the study for one year and maintained or achieved ideal weight were followed on these diet patterns . In the two groups studied , there was no significant difference in cholesterol response . 4 . 4 . Weight loss was comparable prior to beginning either assigned diet . 5 . 5 . The diets utilized in the entire group reduced blood cholesterol levels by 23 mg per 100 ml or 9 per cent over the 12-month period . 6 . 6 . A 30 per cent fat diet , with or without an unsaturated fat supplement , appears to be a satisfactory and palatable regimen for free-living adult males for as prolonged a period as one year . This fact is corroborated by a less than 5 per cent drop-out rate during this period of study . 7 . 7 . There appears to be a relationship between weight reduction and cholesterol change in the group studied The effect of colestipol on plasma lipids and lipoproteins was studied in children , adolescents and young adults with familial hypercholesterolemia . O.125 g or 0.25 g/kg body weight were given in r and omized sequence for period of 4 weeks . Total cholesterol was lowered by 13 and 18 % with the smaller and larger dose , respectively , and LDL cholesterol lowered by 15 % with the smaller and 12 % with the larger dose . HDL cholesterol rose by 18 an 32 % . LDL composition before and during the study was abnormal due to a markedly reduced triglyceride content . " Low-dose " colestipol is less effective lowering total plasma and LDL cholesterol than conventional doses but may , due to very few side effects , by advantageously used in cases of familial hypercholesterolemia when plasma cholesterol levels after dietary management are only 15 - 20 % above normal The extended use of diet and cholestyramine therapy in familial type II hyperlipoproteinemia was examined in patients who previously participated in a short-term , double-blind trial . A striking secondary failure in therapeutic response during 4 yr of use of this therapy was noted with plasma cholesterol rising an average of 15 % . A 3 mo , out-patient , follow-up study design ed to reinforce patient motivation and dietary and drug adherence result ed in a prompt but partial reversal of this therapeutic deterioration in 16 patients . Additional inpatient studies confirmed that patient noncompliance with the dietary regimen was the major factor responsible for the secondary failure . Cholestyramine together with a low cholesterol diet can be an effective agent in familial type II hyperlipoproteinemia , given a comprehensive program of out-patient follow-up with continued emphasis on dietary principles and drug adherence 36 G of wheat fibre , pectin , or guar gum was given over 2-week periods to healthy volunteers taking normal diet . Mean serum-cholesterol levels fell significantly while the volunteers were taking guar and pectin by 36 - 3 and 29 - 2 mg , per 100 . respectively , but rose slightly after wheat fibre by 6 - 7 , mg per 100 . , Attention should be focused on fruit and vegetable gels rather than wheat fibre in the search of natural hypocholesterolaemic agents Pharmacological treatment of hyperlipidemia may be associated with deterioration of glucose tolerance . We r and omized 20 nonobese patients with primary familial hypercholesterolemia ( serum total cholesterol 7.8 + /- 0.4 mM , triglycerides 1.4 + /- 0.2 mM ) to an isocaloric , reduced fat ( < 30 % ) low-cholesterol ( 200 mg/day ) diet with placebo or pravastatin ( 40 mg/day ) . Oral glucose tolerance , endogenous insulin response to glucose , insulin sensitivity ( determined by the euglycemic insulin clamp technique ) , hepatic glucose production ( by the tritiated glucose technique ) , and substrate utilization ( by indirect calorimetry ) were measured at baseline and after 8 weeks of treatment . Ten normocholesterolemic healthy subjects , matched to the patients by age , sex , and body weight , served as the control group . Diet alone ( with no change in body weight ) was associated with a significant 15 % decrease in both serum low density lipoprotein (LDL)-cholesterol and triglycerides ( p < 0.001 for both ) , and a slight decrease in high density lipoprotein (HDL)-cholesterol concentrations , paralleled by reductions in Apo B , C2 , C3 , and E levels ( p < 0.05 or less ) . The addition of pravastatin led to a significantly larger reduction in LDL-cholesterol ( 30 % , p < 0.05 ) and an 8 % increase ( p < 0.02 ) in total HDL-cholesterol concentrations . Accordingly , the ratio of LDL : HDL cholesterol ( which was 60 % higher than in controls at baseline ) remained unchanged in the placebo-diet group whereas it was restored to normal in the pravastatin-diet group . Glucose tolerance , insulin response , insulin-induced inhibition of hepatic glucose production and lipolysis , and insulin-mediated glucose uptake and oxidation were all slightly but not significantly improved after treatment , with no significant differences between pravastatin and placebo . In nonobese patients with primary hypercholesterolemia , pravastatin treatment in combination with an isocaloric , reduced-fat diet leads to a marked reduction in LDL-cholesterol and triglycerides levels and a normalization of the LDL : HDL ratio without affecting glucose tolerance or insulin sensitivity During three experimental periods , nine adults were hospitalized on a metabolic ward and fed a meal containing 500 mg of cholesterol as a component of scrambled eggs . In addition , the meal contained : 1 ) no additive , 2 ) 1 g beta-sitosterol , or 3 ) 2 g beta-sitosteryl oleate . Stools for the succeeding 5 days were analyzed to determine the percentage of the cholesterol in the test meal that was absorbed . The addition of beta-sitosterol result ed in a 42 % decrease in cholesterol absorption ; the beta-sitosteryl oleate caused a 33 % reduction . These results indicate that the judicious addition of beta-sitosterol or beta-sitosteryl oleate to meals containing cholesterol-rich foods will result in a significant decrease in cholesterol absorption , with a consequent decrease in plasma cholesterol The effects of orange flavoured colestipol granules , 10 g/day , in 37 boys and 29 girls aged 10 - 16 years with familial hypercholesterolaemia were examined first in an eight week double blind , placebo controlled protocol , then in open treatment for 44 - 52 weeks . All patients were on a low fat diet . Low density lipoprotein cholesterol levels were reduced by 19.5 % by colestipol v 1.0 % by placebo . Levels of serum folate , vitamin E , and carotenoids were reduced in the colestipol group , but not the vitamin E/cholesterol and carotenoid/cholesterol ratios or serum concentrations of vitamins A and D. After one year of colestipol , two thirds of the participants remained in the study , of whom half took > or = 80 % of the prescribed dose . Those who took > or = 80 % of the dose had a greater decrease in serum 25-hydroxyvitamin D levels than those who took < 80 % . No adverse effects on weight gain or linear growth velocity were observed . Although low dose colestipol effectively reduces low density lipoprotein cholesterol levels , only a minority of adolescents adhered to the new formulation for one year . Folate and possibly vitamin D supplementation is recommended Though the data in the first three weeks of oestrogen therapy would be consistent with an effect of oestrogen on testicular function mediated through the pituitary , the later observations showing discrepancies between luteinizing hormone and testosterone levels would suggest that the effects are complex and that oestrogens may have a direct effect on the testes independently of the pituitary . Such effects have been demonstrated in experimental animals-for example , by Samuels et al. ( 1964 ) . It is also conceivable that failure of complete suppression could be accounted for by protein-binding phenomena , though these have not been shown to be significant for luteinizing hormone or for testosterone . The investigation also demonstrates that oestrogen therapy does not suppress pituitary production of growth hormone or of A.C.T.H. ; it thus gives further support to the belief that the place of early hypophysectomy in the treatment of metastatic cancer of the prostate warrants further study Objective : To study the compliance and changes in plasma lipids , plant sterols , fat-soluble vitamins and carotenoids in children and parents with familial hypercholesterolemia ( FH ) consuming a plant sterol ester-enriched ( PSE ) spread . Design : A 26-week open-label follow-up of children who had previously been studied in a controlled cross-over design . The parents were also included in the open-label arm of the study . Setting : Outpatient clinic for treatment of hyperlipidemia . Subjects : A total of 37 children ( 7–13 y ) and 20 parents ( 32–51 y ) diagnosed with ‘ definite ’ or ‘ possible ’ heterozygous FH . In all , 19 of the parents , but no children , used statins . All were patients at the Lipid Clinic , National Hospital in Oslo . Interventions : Subjects were recommended to eat 20 g/day of PSE spread as part of their lipid-lowering diet . Results : The mean intake of PSE spread was 13.7 and 16.5 g/days in the children and parents , respectively , corresponding to 1.2 and 1.5 g of plant sterols . Plasma total cholesterol decreased by 9.1 % in both children ( P<0.001 ) and parents ( P=0.002 ) . The corresponding decreases in LDL cholesterol were 11.4 % ( P<0.001 ) and 11.0 % ( P=0.012 ) . Increases in serum lathosterol , campesterol and sitosterol , adjusted for total cholesterol , were observed in the children ( 31 , 96 , 48 % , respectively , P<0.001 ) at the end of the controlled cross-over period . In the parents , serum campesterol and sitosterol , adjusted for total cholesterol , increased by 92 and 39 % , respectively ( P < 0.001 ) . Lipid-adjusted serum α- and β-carotene decreased by 17.4 % ( P=0.008 ) and 10.9 % ( P=0.018 ) , respectively , in the children at the end of the controlled PSE period , but increased again during the follow-up . In the parents , serum α- and β-carotene concentrations were unchanged , while serum lutein and lycopene decreased by 7.3 % ( P=0.037 ) and 14.6 % ( P=0.044 ) , respectively . Conclusions : Sustained efficacy of cholesterol reduction and long-term compliance of PSE intake were demonstrated in this study .Sponsorship : Unilever Research and Development , Vlaardingen , The Netherl and A soybean textured protein induced a 14 % decrease of plasma-cholesterol levels after two weeks and 21 % after three when substituted for animal proteins in a group of 20 patients with type-II hyperlipoproteinaemia . Comparison of soybean diet with a st and ard low-lipid diet in the same patients , according to a cross-over protocol , indicated that this hypocholesterolaemic effect was not due to differences in the lipid composition of the two diets . The hypothesis that a soy protein has a hypocholesterolaemic action per se is supported by the results of a subsequent experiment in 8 type-II patients in whom the addition of cholesterol ( 500 mg/day ) to soy protein did not modify the hypocholesterolaemic response Abstract The effects of the isocaloric substitution of soy for animal protein on plasma lipoprotein lipid and apoprotein levels was examined in 12 out patients with primary hypercholesterolemia and 4 normals . After stabilization on either a st and ard NIH-Type IIA low-cholesterol diet ( Type II patients ) , or a regular diet ( normals ) for 6 weeks , the animal and soy protein diets were administered in r and om sequence ( forward studies : animal → soy , reverse studies : soy → animal ) for 6 weeks . The nutrient content and composition of the two experimental diets were the same in all respects except for the type of protein . Body weights remained constant , and the results of both forward ( n = 6 ) and reverse ( n = 10 ) studies were similar . The soy and animal protein diets both lowered plasma cholesterol , low density lipoprotein ( LDL ) cholesterol and apoprotein B levels in the hypercholesterolemic patients significantly below levels achieved on the basal diets . Since the two experimental diets differed only in their protein constituents , the independent effects of soy protein on plasma lipid and apoprotein concentrations could be determined . The isocaloric substitution of soy for animal protein result ed in additional reductions in the plasma concentrations of total cholesterol by −3.5 ± 5 % ( P = 0.05 ) , LDL cholesterol by −6.0 ± 7.2 % ( P Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid ( GLA , 18:3 n-6 ) ( n = 13 ) or a marine oil concentrate containing n-3 fatty acids ( n = 14 ) in a double-blind cross-over design during 8 + 8 weeks with olive oil as placebo . During GLA supplementation , increases in GLA and dihomogammalinolenic acid ( 20:3 n-6 ) were found in plasma lipid esters and platelet phospholipids , whereas platelet function and serum lipoproteins were unaffected . During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol . A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets , mainly at the expense of the n-6 fatty acids . No pronounced effects on platelet reactivity could be demonstrated . Our results confirm a triglyceride-lowering effect of n-3 fatty acids , whereas no such effect of GLA could be demonstrated STUDY OBJECTIVE To determine the effects of fish oil supplements low in saturated fat and cholesterol on plasma lipid and lipoprotein levels in hypertriglyceridemic patients . DESIGN Single-blind , placebo-controlled ( safflower oil ) , crossover trial with 6-week treatment periods . SETTING Outpatient lipid clinic in a university medical center . PATIENTS Eleven adult patients had isolated hypertriglyceridemia ( type IV ) and seven had concomitant hypercholesterolemia ( Type IIb ) . INTERVENTION Twelve 1-g capsules of either fish oil or placebo ( safflower oil ) were taken daily during each treatment period . MEASUREMENTS AND MAIN RESULTS Blood was drawn at the fifth and sixth week of each period and analyzed for total lipids ; cholesterol in very low , low ( LDL ) , and high density ( HDL ) lipoproteins ( mmol/L ) ; and apoprotein B ( mg/dL ) . Compared with the placebo , fish oil lowered plasma triglyceride levels ( 4.0 + /- 1.8 to 2.5 + /- 1.0 ) , and raised LDL cholesterol levels ( 3.7 + /- 1.75 to 4.25 + /- 0.85 ) , apolipoprotein B levels ( 122 + /- 29 to 140 + /- 34 ) , and the ratio of LDL cholesterol to HDL cholesterol ( 4.0 + /- 0.9 to 4.7 + /- 1.4 ) ( P less than 0.05 ; mean + /- SD ) . No significant changes were seen in levels of HDL or HDL cholesterol subfractions . Similar responses were seen in patients with both type IIb and IV lipoprotein phenotypes . CONCLUSIONS Because the fish oil supplement contributed negligible amounts of cholesterol and saturated fat to the diet , the n-3 fatty acids most likely caused the observed effects . These findings indicate that relatively small amounts of fish oil can have beneficial effects on plasma triglyceride levels in hypertriglyceridemic patients , but the increase in LDL cholesterol and apoprotein B levels , and in the LDL cholesterol to HDL cholesterol ratio suggests the need for careful monitoring of plasma lipoprotein changes during fish oil supplementation , and for a careful evaluation of their long-term benefits A r and omised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infa rct ion ( MI ) . 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors : a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat , an increase in fatty fish intake , and an increase in cereal fibre intake . The advice on fat was not associated with any difference in mortality , perhaps because it produced only a small reduction ( 3 - 4 % ) in serum cholesterol . The subjects advised to eat fatty fish had a 29 % reduction in 2 year all-cause mortality compared with those not so advised . This effect , which was significant , was not altered by adjusting for ten potential confounding factors . Subjects given fibre advice had a slightly higher mortality than other subjects ( not significant ) . The 2 year incidence of reinfa rct ion plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens . A modest intake of fatty fish ( two or three portions per week ) may reduce mortality in men who have recovered from MI An encapsulated preparation of fish oil ( Maxepa ) was administered to hyperlipidaemic patients in order to establish the responsiveness of the common lipid phenotypes to dietary supplementation with n-3 fatty acids . 13 patients took 6 g/day of fish oil and 12 patients took 16 g/day in a r and omized , double-blind crossover study , whereby each subject took fish oil for 3 months and matching placebo for 3 months . The study was conducted against a background diet restricted in saturated fat and cholesterol . In Types IIa and IIb hyperlipoproteinaemia there was no substantial fall in plasma cholesterol concentration . Plasma triglyceride concentrations were reduced significantly in Types IIb and IV ( 28 % and 41 % respective reductions ) . In a separate study using 16 g/day of fish oil in patients with Type V hyperlipoproteinaemia , plasma triglycerides were reduced by 58 % and plasma cholesterol concentration by 34 % . The change in plasma triglyceride concentration was significantly correlated with the basal triglyceride level ( r = -0.94 ) , and was dose-related ( 33 % fall on 6 g/day and 58 % fall on 16 g/day ) . The fall in plasma triglyceride concentration was accompanied by a significant reduction in the concentration of very low-density lipoprotein cholesterol ( -42 % ) , a significant rise in low density lipoprotein cholesterol ( + 7 % ) , and a significant rise in high-density lipoprotein cholesterol concentration ( + 6 % ) , there being no significant change in the ratio of low density to high density lipoprotein cholesterol . There were changes in the fatty acid composition of plasma and platelet lipids which reflected dietary supplementation with n-3 fatty acids , notably an increase in the proportion of eicosapentaenoic and docosahexaenoic acids which occurred in a dose-dependent fashion . Despite these changes there was no significant variation in the bleeding time , platelet count or blood viscosity during the treatment The short-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of 10 free-living moderately hypercholesterolemic human subjects ( four men , six women ) were studied under closely supervised dietary control during the consumption of constant , low intakes of fat and cholesterol and the maintenance of stable body weight as well as constant fiber consumption . Subjects were r and omly allocated to either the high or low protein diets ( mean , 23 % v 11 % of energy as protein , 24 % as fat , and 53 % v 65 % as carbohydrate ) and then switched to the other diet for another 4 to 5 weeks . Mean fasting plasma high-density lipoprotein cholesterol ( HDL-C ) was significantly higher by 12 % + /- 4 % ( 0.97 + /- 0.08 v 0.89 + /- 0.08 mmol/L , P less than .01 ) , whereas mean total cholesterol ( TC ) was lower by 6.5 % + /- 1.3 % ( 5.7 + /- 0.3 v 6.1 + /- 0.3 mmol/L , P less than .001 ) , mean low-density lipoprotein-cholesterol ( LDL-C ) lower by 6.4 % + /- 2.0 % ( 4.5 + /- 0.2 v 4.8 + /- 0.2 mmol/L , P less than .02 ) , mean total triglycerides ( TG ) lower by 23 % + /- 5 % ( 1.7 + /- 0.1 v 2.4 + /- 0.3 mmol/L , P less than .02 ) , and mean high versus low protein diet . Mean values for LDL-C were significantly lower during weeks 3 to 5 of the high protein diet than during either weeks 1 to 5 or weeks 1 to 2 of the high protein diet ( 4.3 + /- 0.3 , 4.5 + /- 0.2 , and 4.7 + /- 0.3 mmol/L , respectively , P less than .05 ) and 11 % + /- 3 % lower than on low protein diet , P less than .005 . The ratio of plasma LDL-C to HDL-C was consistently lower by 17 % + /- 3 % during the high versus low protein diet ( 4.9 + /- 0.5 v 5.8 + /- 0.5 , P less than .001 ) . Lowering plasma TC and LDL-C and total TG and VLDL-TG and increasing HDL-C by chronic isocaloric substitution of dietary for carbohydrate may enhance the cardiovascular risk reduction obtained by restriction of dietary fat and cholesterol The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid . In study no. 1 , normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter ( CB ) ; oleic acid provided by olive oil ( OO ) ; linoleic acid provided by soybean oil ( SO ) ; and myristic acid ( and lauric acid ) provided by dairy butter ( B ) . In study no. 2 , different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate ( C ) , CB , CB+B ( 4:1 , MIX ) , and myristic ( and lauric ) acid provided by B. Both studies used a r and omized , crossover , double-blind experimental design , and experimental subjects ( n = 18 for study no. 1 and n = 15 for study no. 2 ) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period . The diets provided 37 % of calories from fat , of which 81 % was provided by the test fat . Ten ounces ( 280 g ) C was provided daily by the C diet . In study no. 1 , the B diet was hypercholesterolemic , whereas the SO diet was hypocholesterolemic , compared with the other diets . The OO and SO diets were hypocholesterolemic compared with the CB diet . Low-density lipoprotein ( LDL ) cholesterol levels , in general , paralleled the changes in plasma total cholesterol levels . SO significantly decreased apolipoprotein ( apo ) B levels compared with the other diets . Plasma very-low density lipoprotein ( VLDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , and apo A-I levels were unaffected by the experimental diets . ( ABSTRACT TRUNCATED AT 250 WORDS The mechanisms by which dietary fat influences fasting plasma lipid concentrations have been investigated in hyperlipidaemic subjects . The synthetic and fractional catabolic ( FCR ) rates of the apoprotein B ( apo B ) of very-low density ( VLDL ) and low-density ( LDL ) lipoproteins were measured using radioiodinated autologous lipoproteins . Reductions of LDL concentration in eight subjects during low-fat ( 25 % of energy ) diets were largely explained by diminished synthesis ( -20 % , P less than 0.02 ) , and possibly also by an increased FCR ( + 15 % , P = 0.05 ) of LDL , compared with observations made during a high-fat ( 45 % of energy ) diet of similar fatty acid composition . VLDL apo B synthesis and FCR were not significantly altered . When a diet rich in polyunsaturated fatty acids was exchanged for one high in saturated fatty acids ( fat providing 45 % of energy on both occasions ) in four subjects , the synthetic rates of both VLDL apo B ( -31 % , P less than 0.02 ) and LDL apo B ( -23 % , P less than 0.10 ) were reduced while their FCRs were unchanged Abstract Thirteen children with the heterozygous form of familial hypercholesterolaemia were treated by a diet low in ordinary fat ( largely saturated ) and supplemented with cornoil foods ( rich in polyunsaturated fatty acids ) . A mean reduction in serum-cholesterol of 24 % was achieved : the greater the amount of ordinary fat in the diet the smaller was the reduction in serum-cholesterol , but there was no correlation between the amount of corn oil and the reduction in serum-cholesterol . It seems that corn oil has no specific hypocholesterolaemic action in familial hypercholesterolaemia , but it is still important in treatment since it greatly improves the palatability of a diet low in ordinary fat . It also avoids the need for a high-carbohydrate intake which may lead to hypertriglyceridaemia . Clofibrate , given in addition to diet , decreased the serum-cholesterol further , and result ed in a mean total reduction of 33 % . One child with the homozygous form has been treated for 2 years with diet , clofibrate , and cholestyramine . Serum-cholesterol fell by 32 % and her xanthomas decreased both in size and number Fish oils containing n-3 fatty acids have been shown in humans to decrease platelet aggregation in vitro , lower plasma triglycerides , and to increase bleeding time . The in vivo effects of fish oils on microcirculatory blood flow in humans has not been studied to date . Twenty-one male subjects were r and omly assigned to either olive oil ( n = 10 ) or fish oil ( n = 11 ) supplemented groups to determine the effects of these oils on capillary blood flow velocity ( CBV ) in the nailfold area . The subjects were given the oils for three weeks ( 1.5 g oil/10 kg b.wt./day ) in a single blind study design . In addition to CBV plasma lipid profiles , blood viscosity , blood pressure and platelet and erythrocyte fatty acids were also determined prior to and after the dietary intervention . Fish oil supplementation significantly increased CBV , by 1.75-fold ( 0.144 + /- 0.069 to 0.253 + /- 0.147 mm/s ) . The olive oil group remained unchanged . Increased levels of n-3 fatty acids were noted in platelets and erythrocytes of the fish compared to olive oil-supplemented groups . Blood viscosity was unaltered in both groups , however , blood pressure in the olive oil supplemented group was significantly decreased . Plasma triglycerides were significantly decreased in the fish oil supplemented group . These observations suggest that increases in CBV after fish oil supplementation are due to changes in vascular tone and not to alterations in blood pressure or blood viscosity Low‐density lipoprotein ( LDL ) subclass pattern B is a common genetically influenced lipoprotein profile characterized by a predominance of small , dense LDL particles , and associated with increased levels of triglyceride‐rich lipoproteins , reductions in high‐density lipoprotein cholesterol ( HDL‐C ) , and increased risk of coronary artery disease compared to individuals with a predominance of larger LDL ( pattern A ) . We sought to determine whether LDL subclass patterns are associated with response of plasma lipoprotein levels to changes in dietary fat and carbohydrate content . In a r and omized cross‐over study , 105 men consumed , for six weeks each , high‐fat ( 46 % ) and low‐fat ( 24 % ) solid food diets , with replacement of fat by carbohydrate . Diet‐induced changes in subjects who exhibited pattern B ( n = 18 ) following the high‐fat diet differed significantly from those in subjects with pattern A ( n = 87 ) : in pattern B subjects LDL cholesterol ( LDL‐C ) reductions were two‐fold greater and plasma apolipoprotein ( apo ) B levels decreased significantly . These differences remained significant after adjustment for levels of plasma LDL‐C , apo B , HDL‐C , and body mass index . Thus , LDL subclass pattern is a factor that contributes significantly to interindividual variation of plasma lipoprotein response to a low‐fat , high‐carbohydrate diet.— Dreon , D. M. , Fernstrom , H. A. , Miller , B. , Krauss , R. M. Low‐density lipoprotein subclass patterns and lipoprotein response to a reduced‐fat diet in men . FASEB J. 8 : 121‐126 ; 1994 The effect on serum lipid and lipoprotein levels of a st and ard low fat , low cholesterol diet was compared with that of a soy protein-substituted low fat , low cholesterol diet in 23 children with familial or polygenic hypercholesterolemia : 12 boys and 11 girls ( mean age , 9.3 + /- 4.5 years ) were included in this outpatient program . Group 1 received the soy protein diet for 8 weeks ; group 2 received the low fat , low cholesterol diet . After an interruption of 8 weeks , each group was placed on the alternate regimen . Fasting blood sample s were collected at the beginning of each dietary period . During the soy protein diet , the levels of total cholesterol decreased by 16 % in group 1 and 18 % in group 2 , and low-density lipoprotein cholesterol ( LDL-C ) levels decreased about 22 % in group 1 and 25 % in group 2 . During the st and ard low fat , low cholesterol diet , total cholesterol and LDL-C levels were reduced by 8 % and 7 % in group 1 and by 12 % and 13 % , respectively , in group 2 . The effect on LDL-C was significantly greater ( p < 0.05 ) in the soy protein group than in the low fat , low cholesterol group . We conclude that a diet substituting soy protein for animal protein has a more beneficial short-term effect on total cholesterol and LDL-C levels in children with hypercholesterolemia than a st and ard low fat diet It has been reported that lipid-lowering diets may reduce high density lipoprotein as well as low density lipoprotein cholesterol but that the reduction of the high density lipoproteins is less pronounced with diets of lower P/S ratios . The aim of the present study was therefore to investigate whether the effects on the low density lipoproteins could be maintained , but those on the high density lipoproteins diminished , by reducing the P/S ratio from 1.3 to 0.7 . Fourteen hyperlipoproteinaemic patients in a metabolic ward were given two fat-modified diets during two consecutive 3-week periods in a r and omized order . The diets were identical with regard to nutrient composition but differed with regard to the P/S ratios , which were 1.3 and 0.7 , respectively . The average serum lipoprotein lipid composition and the apolipoprotein concentrations were similar at the end of the two periods . However , in the group of patients ( n = 7 ) who started on the diet with P/S ratio 1.3 the low density lipoprotein cholesterol increased significantly ( p less than 0.05 ) by 7 % and the apolipoprotein B concentration by 10 % ( p less than 0.001 ) when shifting to the diet with P/S ratio 0.7 . No changes of the high density lipoprotein concentrations were seen . The relative content of saturated fatty acids , of oleic acid , and of arachidonic acid in the plasma lipid esters decreased , but the content of linoleic acid increased , when shifting from the diet with a P/S ratio of 0.7 to that of 1.3 . ( ABSTRACT TRUNCATED AT 250 WORDS Long-term effects of diet and colestipol ( a bile acid sequestrant ) were studied in 25 patients with familial type II hyperlipoproteinemia . Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then r and omized into placebo and drug-treatment groups . After explaining that the drug is nontoxic and effective in lowering serum lipids , total cholesterol ( C ) and low-density lipoprotein cholesterol ( LDL-C ) , colestipol ( 30 g/day ) and diet were given to the 25 patients who remained in the long-term follow-up program . The treatment result ed in highly significant lowering of serum lipids ( mg/dl , mean + /- SEM ) : C and LDL-C from 412.7 + /- 24.4 and 331.1 + /- 22.8 to 270 + /- 11.0 and 188.1 + /- 13.8 , respectively ( p less than 0.001 in each instance ) over 7 - -7 1/2 years . Although we observed no absolute increase in high density lipoprotein ( HDL ) , the HDL/LDL ratio was elevated . Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response . It did not cause nutritional or metabolic disturbances In normal , hypertensive and hyperlipemic subjects , diets supplemented with linoleic acid ( LA ) or alpha-linolenic acid ( LNA ) result ed in an increase of the corresponding fatty acids in serum lipids . However , their C20-derivatives , the prostagl and in precursors arachidonic acid ( AA ) and eicosapentaenoic acid ( EPA ) , respectively , were not or only slightly augmented . On the other h and , an EPA-rich diet produced a marked increase of this fatty acid , especially in cholesterol esters . After this diet the decreases of blood pressure and serum lipids were more pronounced when compared with LA- and LNA-rich diets containing a 20-fold higher dose of the polyunsaturated fatty acids . The slow formation of AA and EPA from LA and LNA seems to be a characteristic finding in humans , being different from preferred laboratory animals , for instance , rats . This observation was independent of the presence of risk factors , like arterial hypertension or hyperlipoproteinemia ( HLP ) We studied the metabolic effects of stearic acid ( 18:0 ) on plasma lipoprotein levels in 11 subjects during three dietary periods of three weeks each . The three liquid-formula diets , which were used in r and om order , were high in palmitic acid ( 16:0 ) , stearic acid , and oleic acid ( 18:1 ) , respectively . Caloric intakes were the same during the three periods . As compared with the values observed when the subjects were on the high-palmitic-acid diet , plasma total cholesterol decreased by an average of 14 percent during consumption of the high-stearic-acid diet ( P less than 0.005 ) and by 10 percent during consumption of the high-oleic-acid diet ( P less than 0.02 ) . Low-density lipoprotein cholesterol levels fell by 21 percent in subjects on the high-stearic-acid diet ( P less than 0.005 ) and by 15 percent in subjects on the high-oleic-acid diet ( P less than 0.005 ) . No significant differences were observed in the plasma levels of triglycerides or high-density lipoprotein cholesterol among the three diets . Measurements of the intestinal absorption of palmitic , stearic , and oleic acids revealed essentially complete absorption of each during the three dietary periods . The oleic acid content of plasma triglycerides and cholesteryl esters increased significantly during the high-stearic-acid period , suggesting that stearic acid is rapidly converted to oleic acid . We conclude that stearic acid appears to be as effective as oleic acid in lowering plasma cholesterol levels when either replaces palmitic acid in the diet Abstract Objectives : To determine the extent to which plasma antioxidant concentrations in people with habitual low intake of fruit and vegetables respond to increased intakes of these foods . To examine whether advice to increase fruit and vegetables will result in reduction of concentrations of total and low density lipoprotein cholesterol . Design : R and omised controlled trial in which intervention and control groups were followed up for eight weeks . The intervention group was asked to consume eight servings of fruit and vegetables a day . Setting : Dunedin , New Zeal and . Subjects : Eighty seven subjects with normal lipid concentrations who ate three or fewer servings of fruit and vegetables daily . Main outcome measures : Plasma concentrations of vitamin C , retinol , α and ß carotene , α tocopherol , lipids , and lipoproteins . Dietary intake assessed with diet records over four days . Results : The mean plasma vitamin C , α carotene , and ß carotene concentrations increased in parallel with increased dietary intake of fruit and vegetables in the intervention group . Concentrations of retinol , α tocopherol , lipids , and lipoproteins remained unchanged despite some increase in dietary vitamin E and a small reduction in saturated fat intake . Conclusions : Following a recommendation to increase fruit and vegetable consumption produces change in plasma concentrations of vitamin C , α carotene , and ß carotene likely to reduce incidence of cancer . More specific dietary advice to modify fat intake may be necessary to reduce the risk of cardiovascular disease mediated by lipoprotein and vitamin E. Key messages Increasing intake of fruit and vegetables raises plasma concentrations of vitamin C and α and ß carotene These changes in plasma concentrations of antioxidants are probably associated with reduced risk of cancer A simple recommendation to increase fruit and vegetable intake has little effect on plasma concentrations of α tocopherol , lipids , and lipoproteins More specific dietary advice to modify fat intake may be necessary to reduce risk of cardiovascular disease associated with lipoproteins and vitamin Background The enzyme lecithin-cholesterol acyl transferase ( LCAT ) esterifies free cholesterol on highdensity lipoprotein ( HDL ) and the cholesteryl ester transfer protein ( CETP ) transfers cholesteryl esters to very-low-density lipoproteins ( VLDL ) and low-density lipoproteins ( LDL ) . Using statins , contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetatlipoproteinemia . In contrast , LCAT activity appears to be unaffected by simvastatin . Antioxidants have also been proposed for use in anti-atherosclerotic treatment , because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis . Objective To investigate , in hypercholesterolemic patients , whether a combination of pravastatin with the antioxidant , vitamin E , has greater effects on the activity of CETP and of LCAT than does pravastatin alone . Methods This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned r and omly to groups to receive : diet and 20–40 mg pravastatin ( n = 52 ) , diet and pravastatin in combination with 100 mg/day vitamin E ( 100 IU ) as DL-α-tocopherol ( n = 56 ) , diet and α-tocopherol ( n = 60 ) , or diet associated with placebo ( n = 52 ) . Plasma LCAT activity was determined using excess exogenous substrate , containing [3H]cholesterol . Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2 + . The exchange of cholesteryl esters between [14C]cholesteryl esterlabeled LDL and unlabeled HDL was measured during a 16-h incubation , while LCAT was inhibited . Results The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity ( P < 0.05 ) ; this effect was less evident in the group cotreated with vitamin E. For the first time , it was shown that CETP concentrations increased significantly after vitamin E alone ( P < 0.05 ) . No significant differences in the plasma activity of LCAT were observed among the groups . Conclusions Pravastatin reduced CETP activity , but not that of LCAT . Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity . The mechanism responsible for these effects is unknown , but could involve the prevention of radical-induced damage to CETP by vitamin E. Coronary Artery Dis The effectiveness of lovastatin was compared with both a high-fat vs low-fat diet . Hypercholesterolemic subjects were studied under metabolic ward conditions for diet periods of 3 weeks while receiving lovastatin ( 40 mg/d ) or placebo . Multiple lipoprotein levels were measured during the final week of each diet period . Nineteen subjects completed the study on the high-fat ( 43 % of kilojoules ) diet and 16 on the low-fat ( 25 % of kilojoules ) diet . Lovastatin reduced total cholesterol by 23 % and low-density lipoprotein cholesterol by 30 % , compared with placebo on both diets , with no significant diet-drug interaction . High-density lipoprotein cholesterol was raised by 7 % to 8 % on the diet regimens . Addition of lovastatin to the low-fat diet permitted 80 % of subjects on this diet , but less than 50 % of those on the high-fat diet , to achieve current guidelines . Although lovastatin produces a comparable percentage reduction in lipoprotein profiles on either diet , the accompanying low-fat diet remains advisable for additional reduction of low-density lipoprotein cholesterol levels to specified goals We studied the effect of th bite acid sequestrant colestipol , alone and in combination with clofibrate or niacin , in patients with heterozygous familial hypercholesterolemia who were given a diet low in cholesterol and saturated fat . With colestipol alone , mean cholesterol levels in serum decreased 16 to 25 per cent . The addition of clofibrate produced a total mean decrement of only 28 per cent . In contrast , serum cholesterol levels fell 45 per cent when colestipol as combined with niacin . Low-density-lipoprotein ( LDL ) cholesterol decreased 55 per cent with colestipol and niacin , whereas high-density-lipoprotein ( HDL ) cholesterol increased . Mean LDL cholesterol was lower in patients given this regimen than in matched normal controls eating an unrestricted diet . Tendinous xanthomas , measured by quantitative xeroradiography , were significantly reduced ( P < 0.01 ) , indicating that this regimen mobilized cholesterol from tissue pools with slow turnover . Colestipol plus niacin promises to be useful in the treatment of patients at high risk from elevated levels of LDL To identify diets that are more effective than existing ones in reducing lipoprotein-mediated risk of atherosclerotic heart disease , the serum lipids and lipoprotein response to three modified diets was studied in twelve normal men living in an institution . The " Western " reference diet ( 40 % energy from fat , P/S ratio 0.27 ) was compared in Latin square design with a fat-modified diet ( diet B , 27 % energy from fat , P/S 1.0 , reduced cholesterol content ) ; with a fat-modified diet supplemented with fruit , vegetable , and cereal fibre ( diet C ) ; and with a diet providing 40 % energy from fat , having P/S ratio 1.0 and supplemented by fibre ( diet D ) . The effects of fat modification and fibre-supplementation ( diets C and D ) were strongly additive-a fall serum cholesterol by 24 - 29 % , in low-density-lipoprotein ( LDL ) cholesterol by 31 - 34 % , and in serum triglyceride by 21 - 26 % ; and the reduction , by diet C , of the ratio of serum cholesterol to high-density-lipoprotein (HDL)-cholesterol by 21 % , and that of LDL-cholesterol to HDL2-cholesterol by 26 % . The additive effects of multiple changes in nutrient intake , each moderate in extent , permits the design of diets which are remarkably effective in reducing serum-cholesterol level We conducted a r and omized , controlled trial in 72 patients with heterozygous familial hypercholesterolemia to test whether reducing plasma low-density lipoprotein levels by diet and combined drug regimens can induce regression of coronary lesions . Four hundred fifty-seven lesions were measured before and after a 26-month interval by computer-based quantitative angiography . The primary outcome variable was within-patient mean change in percent area stenosis . Mean low-density lipoprotein cholesterol levels decreased from 7.32 + /- 1.5 to 4.45 + /- 1.6 mmol/L. The mean change in percent area stenosis among controls was + 0.80 , indicating progression , while the mean change for the treatment group was -1.53 , indicating regression ( P = .039 by two-tailed t test for the difference between groups ) . Regression among women , analyzed separately , was also significant . The change in percent area stenosis was correlated with low-density lipoprotein levels on trial . We conclude that reduction of low-density lipoprotein cholesterol levels can induce regression of atherosclerotic lesions of the coronary arteries in patients with familial hypercholesterolemia . The anticipation of benefit from treatment applies to women and men alike The nonabsorbable bile acid sequestrant resin , colestipol , was administered to 16 patients with primary hypercholesterolemia , and its effect on serum lipids , lipoprotein fractions , and circulating platelet aggregate ratio and platelet aggregation in response to adenosine diphosphate ( ADP ) was compared with that of sitosterol . Cholesterol absorption and sterol balance studies were done in four of the subjects during the following treatment periods : diet alone , colestipol , and sitosterol . Total serum cholesterol was significantly reduced by colestipol but only slightly decreased by sitosterol . Combination treatment with colestipol and sitosterol was associated with a smaller decrease in serum cholesterol than was demonstrated with colestipol alone . Serum triglycerides tended to increase during colestipol therapy ( this increase was not clinical ly significant ) but showed a minimal nonsignificant decrease with sitosterol treatment . Colestipol decreased cholesterol absorption , whereas sitosterol slightly increased it . Fecal sterol excretion was increased with colestipol treatment but was minimally affected by administration of sitosterol . Low-density lipoprotein and high-density lipoprotein cholesterol significantly decreased with colestipol treatment . The circulating platelet aggregate ratio was significantly lower in the group of patients with hypercholesterolemia who received colestipol initially than in control subjects , but platelet aggregation in response to ADP was not significantly different between these two groups . No significant change in platelet aggregation was noted during colestipol or sitosterol treatment despite a significant decrease in total serum cholesterol with colestipol therapy , a suggestion that the platelet and lipid abnormalities are not interrelated Abstract The mortality from coronary heart-disease ( C.H.D. ) and other causes was studied in two mental hospitals during a long-term ( twelve-year ) controlled preventive trial . The trial was cross-over in design . In one of the hospitals a serum-cholesterol-lowering diet was introduced and the other hospital using a normal diet served as the control . After six years the diets were reversed , and the trial was continued for six more years . In men , the use of the cholesterol-lowering diet was associated with considerably and significantly reduced mortality from C.H.D. Total mortality also was consistently lower on this diet , although the differences were too small for statistical significance . In women , the mortality from C.H.D. also appeared to be lower during the diet period , but the differences were small and not significant . In female total mortality no appreciable differences were found The effects of soy protein ( 35 % of protein energy ) given as a beverage and those of cow-milk proteins were investigated on plasma lipoprotein concentrations in children with familial hypercholesterolemia ( FH ) . Subjects were r and omly assigned to either the soy-protein or cow-milk-protein experimental period , with subsequent crossover after a washout period , each period lasting 4 wk . Diets were planned to provide 20 % energy as protein , 28 % as fat ( polyunsaturated : monounsaturated : saturated fatty acids , 1:3:3 ) and less than 200 mg cholesterol/d . No changes were observed in either plasma cholesterol , low-density-lipoprotein cholesterol , or apolipoprotein concentrations . However , the soy beverage significantly reduced the concentrations of triglyceride and very-low-density-lipoprotein cholesterol ( P less than 0.05 ) and significantly increased the concentrations of high-density-lipoprotein cholesterol ( HDL-C ) and HDL3-C ( P less than 0.04 and P less than 0.03 , respectively ) . These results indicate that the administration of soy protein may induce clinical ly beneficial effects in children with FH It has previously been shown that fish oil supplementation , compared to olive oil , reduces plasma fibrinogen . Presented here are the results of a r and omized , double-blind , crossover controlled trail that compared the effects of dietary n-3 and n-6 fatty acid supplementation on plasma fibrinogen levels in 10 patients with hyperlipoproteinemia types IIb or IV . Plasma fibrinogen levels showed statistically significant reductions during both the fish oil and corn oil treatment periods . Other variables related to hemostasis which showed no significant changes from baseline included tissue plasminogen activator activity and inhibitor , protein C antigen , antithrombin III activity , bleeding time , and platelet counts . These data confirm the two previous reports that fish oil supplementation is associated with reductions in plasma fibrinogen levels , thereby modifying a potential nonlipid risk factor for cardiovascular disease . Unlike previous reports , however , n-6 polyunsaturated fatty acids were also associated with significant reductions in fibrinogen levels . Therefore , it is premature to conclude that the fibrinogen-lowering effects of dietary fish oil are unique to n-3 polyunsaturated fatty acids The Type II Coronary Intervention Study ( Type II Study ) is a double-blind , r and omized , placebo-controlled clinical trial conducted by the Division of Intramural Research of the National Heart , Lung , and Blood Institute of Bethesda , Maryl and . The study was design ed to evaluate the 5-year treatment effect of cholestyramine on low density lipoprotein ( LDL ) cholesterol and on lesions in the coronary arteries . One hundred forty-three patients with Type II hyperlipoproteinemia ( elevated LDL cholesterol ) and coronary artery disease ( CAD ) were entered into the study between 1972 and 1976 . Patients were stratified by sex and extent of coronary disease as defined angiographically and were r and omly allocated to a daily dosage of 24 g cholestyramine and diet ( treatment group ) or placebo and diet ( control group ) . Changes in the coronary arteries were evaluated by sequential coronary angiography carried out before and after five years of treatment . This report describes the trial design and baseline characteristics of the study patients BACKGROUND Vitamin E ( alpha-tocopherol ) is thought to have a role in prevention of atherosclerosis , through inhibition of oxidation of low-density lipoprotein . Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of alpha-tocopherol and lower rates of ischaemic heart disease . We tested the hypothesis that treatment with a high dose of alpha-tocopherol would reduce subsequent risk of myocardial infa rct ion ( MI ) and cardiovascular death in patients with established ischaemic heart disease . METHODS In this double-blind , placebo-controlled study with stratified r and omisation , 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days ( range 3 - 981 ) . 1035 patients were assigned alpha-tocopherol ( capsules containing 800 IU daily for first 546 patients ; 400 IU daily for remainder ) ; 967 received identical placebo capsules . The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as non-fatal MI alone . FINDINGS Plasma alpha-tocopherol concentrations ( measured in subsets of patients ) rose in the actively treated group ( from baseline mean 34.2 micromol/L to 51.1 micromol/L with 400 IU daily and 64.5 micromol/L with 800 IU daily ) but did not change in the placebo group . Alpha-tocopherol treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal MI ( 41 vs 64 events ; relative risk 0.53 [ 95 % Cl 0.34 - 0.83 ; p=0.005 ) . The beneficial effects on this composite endpoint were due to a significant reduction in the risk of non-fatal MI ( 14 vs 41 ; 0.23 [ 0.11 - 0.47 ] ; p=0.005 ) ; however , there was a non-significant excess of cardiovascular deaths in the alpha-tocopherol group ( 27 vs 23 ; 1.18 [ 0.62 - 2.27 ] ; p=0.61 ) . All-cause mortality was 36 of 1035 alpha-tocopherol-treated patients and 27 of 967 placebo recipients . INTERPRETATION We conclude that in patients with angiographically proven symptomatic coronary atherosclerosis , alpha-tocopherol treatment substantially reduces the rate of non-fatal MI , with beneficial effects apparent after 1 year of treatment . The effect of alpha-tocopherol treatment on cardiovascular deaths requires further study |
13,943 | 17,991,265 | Remifentanil does not seem to offer any advantage for lengthy , major interventions , but may be useful for selected patients , e.g. when postoperative respiratory depression is a concern | null | null |
13,944 | 27,431,504 | The selected studies reported promising results for LLLT ; elevated acceleration of tooth movement and lower pain scores , than controls .
With respect to method , there were wide variations in type of laser techniques .
The results highlight the need for high quality research , with consistency in study design , to determine whether LLLT can enhance fixed appliance treatment in children and young adults | Background Recently low-level laser therapy ( LLLT ) has been proposed to improve orthodontic treatment .
The aims of this systematic review were to investigate the scientific evidence to support applications of LLLT : ( a ) to accelerate tooth movement , ( b ) to prevent orthodontic relapse and ( c ) to modulate acute pain , during treatment with fixed appliances in children and young adults . | OBJECTIVE The aim of this study was to investigate the effect of low-level laser therapy ( LLLT ) on reducing post-adjustment orthodontic pain via evaluation of gingival crevicular fluid ( GCF ) composition changes at the level of prostagl and in-E(2 ) ( PGE(2 ) ) and visual analogue scale ( VAS ) . BACKGROUND DATA LLLT has been found to be effective in pain relief . PGE(2 ) has the greatest impact on the process of pain signals and can be detected in GCF in order to investigate the response of dental and periodontal tissues in a biochemical manner . MATERIAL S AND METHODS Nineteen patients ( 11 females and 8 males ; mean age 13.9 years ) were included in this study . Maxillary first molars were b and ed and then a r and omly selected first molar at one side was irradiated ( λ820 nm ; continuous wave ; output power : 50 mW ; focal spot : 0.0314 cm(2 ) ; exposure duration : 5 sec ; power density : 1.59 W/cm(2 ) ; energy dose : 0.25 J ; energy density : 7.96 J/cm(2 ) for each shot ) , while the molar at the other side was served as placebo control . The GCF was collected from the gingival crevice of each molar to evaluate PGE(2 ) levels , before b and placement , 1 and 24 h after laser irradiation . Pain intensity was analyzed at 5 min , 1 h , and 24 h after b and placement by using VAS . RESULTS Although no difference was found in pain perception at 5 min and 1 h , significant reduction was observed with laser treatment 24 h after application ( p<0.05 ) . The mean PGE(2 ) levels were significantly elevated in control group , whereas a gradual decrease occurred in laser group . The difference in PGE(2 ) levels at both 1 and 24 h were statistically significant between two groups ( p<0.05 ) . CONCLUSIONS The significant reductions in both pain intensity and PGE(2 ) levels revealed that LLLT was efficient in reducing orthodontic post-adjustment pain Background : Low level laser therapy ( LLLT ) has gained increasing popularity in the management of tendinopathy and arthritis . Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action . Objective : To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon . Subjects : Seven patients with bilateral Achilles tendinitis ( 14 tendons ) who had aggravated symptoms produced by pain inducing activity immediately before the study . Method : Infrared ( 904 nm wavelength ) LLLT ( 5.4 J per point , power density 20 mW/cm2 ) and placebo LLLT ( 0 J ) were administered to both Achilles tendons in r and om blinded order . Results : Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 ( 95 % confidence interval 0.87 to 0.95 ) . Prostagl and in E2 concentrations were significantly reduced 75 , 90 , and 105 minutes after active LLLT compared with concentrations before treatment ( p = 0.026 ) and after placebo LLLT ( p = 0.009 ) . Pressure pain threshold had increased significantly ( p = 0.012 ) after active LLLT compared with placebo LLLT : the mean difference in the change between the groups was 0.40 kg/cm2 ( 95 % confidence interval 0.10 to 0.70 ) . Conclusion : LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis . LLLT may therefore have potential in the management of diseases with an inflammatory component OBJECTIVE To analyze the effect of low-level laser therapy ( LLLT ) on perception of pain after separator placement and compare it with perceptions of control and placebo groups using a frequent irradiation protocol . MATERIAL S AND METHODS Eighty-eight patients were r and omly allocated to a laser group , a light-emitting diode ( LED ) placebo group , or a control group . Elastomeric separators were placed on the first molars . In the laser and LED groups , first molars were irradiated for 30 seconds every 12 hours for 1 week using a portable device . Pain was marked on a visual analog scale at predetermined intervals . Repeated measure analysis of variance was performed for statistical analysis . RESULTS The pain scores of the laser group were significantly lower than those of the control group up to 1 day . The pain scores in the LED group were not significantly different from those of the laser group during the first 6 hours . After that point , the pain scores of the LED group were not significantly different from those of the control . CONCLUSIONS Frequent LLLT decreased the perception of pain to a nonsignificant level throughout the week after separator placement , compared with pain perception in the placebo and control groups . Therefore , LLLT might be an effective method of reducing orthodontic pain INTRODUCTION The purpose of this study was to clinical ly evaluate the effect of low-level laser therapy ( LLLT ) as a method of reducing pain reported by patients after placement of their first orthodontic archwires . METHODS The sample comprised 60 orthodontic patients ( ages , 12 - 18 years ; mean , 15.9 years ) . All patients had fixed orthodontic appliances placed in 1 dental arch ( maxillary or m and ibular ) , received the first archwire , and were then r and omly assigned to the experimental ( laser ) , placebo , or control group . This was a double-blind study . LLLT was started in the experimental group immediately after placement of the first archwire . Each tooth received a dose of 2.5 J per square centimeter on each side ( buccal and lingual ) . The placebo group had the laser probe positioned into the mouth at the same areas overlying the dental root and could hear a sound every 10 seconds . The control group had no laser intervention . All patients received a survey to be filled out at home describing their pain during the next 7 days . RESULTS The patients in the LLLT group had lower mean scores for oral pain and intensity of pain on the most painful day . Also , their pain ended sooner . LLLT did not affect the start of pain perception or alter the most painful day . There was no significant difference in pain symptomatology in the maxillary or m and ibular arches in an evaluated parameter . CONCLUSIONS Based on these findings , we concluded that LLLT efficiently controls pain caused by the first archwire OBJECTIVE To test the hypothesis that there is no difference in the pain associated with orthodontic force application after the application of local CO(2 ) laser irradiation to the teeth involved . MATERIAL S AND METHODS Separation modules were placed at the distal contacts of the maxillary first molars in 90 patients in this single-blinded study . In 60 of these patients ( 42 females and 18 males ; mean age = 19.22 years ) this was immediately followed by laser therapy . The other 30 patients ( 18 females and 12 males ; mean age = 18.8 years ) did not receive active laser irradiation . Patients were then instructed to rate their levels of pain on a visual analog scale over time , and the amount of tooth movement was analyzed . RESULTS Significant pain reductions were observed with laser treatment from immediately after insertion of separators through day 4 , but no differences from the nonirradiated control side were noted thereafter . No significant difference was noted in the amount of tooth movement between the irradiated and nonirradiated group . CONCLUSIONS The hypothesis was rejected . The results suggest that local CO(2 ) laser irradiation will reduce pain associated with orthodontic force application without interfering with the tooth movement The aim of this study was to evaluate the pain sensation that orthodontic patients experience when elastic separators are placed between molars and premolars and to determine the degree of analgesic efficacy of low-level laser therapy ( LLLT ) compared to a placebo treatment . The study was conducted with 20 volunteers who were fitted with elastic separators between the maxillary molars and premolars . One quadrant was r and omly chosen to be irradiated with an 830-nm laser , 100 mW , beam diameter of 7 mm , 250 mW/cm2 applied for 20 s per point ( 5 J/cm2 ) . Three points were irradiated in the buccal face and three were irradiated in the palate . The same procedure was applied in the contralateral quadrant with a placebo light . A visual analogue scale was used to assess pain 5 min , 6 h , 24 h , 48 h , and 72 h after placement of the separators . Maximum pain occurred 6–24 h after placement of the elastic separators . Pain intensity was significantly lower in the laser-treated quadrant ( mean , 7.7 mm ) than in the placebo-treated quadrant ( mean , 14.14 mm ; p = 0.0001 ) . LLLT at these parameters can reduce pain in patients following placement of orthodontic rubber separators Phototherapy with low-level coherent light ( laser ) has been reported as an analgesic and anti-inflammatory as well as having a positive effect in tissue repair in orthodontics . However , there are few clinical studies using low-level LED therapy ( non-coherent light ) . The aim of the present study was to analyze the pain symptoms after orthodontic tooth movement associated with and not associated with coherent and non-coherent phototherapy . Fifty-five volunteers ( mean age = 24.1 ± 8.1 years ) were r and omly divided into four groups : G1 ( control ) , G2 ( placebo ) , G3 ( protocol 1 : laser , InGaAlP , 660 nm , 4 J/cm2 , 0.03 W , 25 s ) , G4 ( protocol 2 : LED , GaAlAs , 640 nm with 40 nm full-b and width at half-maximum , 4 J/cm2 , 0.10 W , 70 s ) . Separators were used to induce orthodontic pain and the volunteers pain levels were scored with the visual analog scale ( VAS ) after the separator placement , after the therapy ( placebo , laser , or LED ) , and after 2 , 24 , 48 , 72 , 96 , and 120 h. The laser group did not have statistically significant results in the reduction of pain level compared to the LED group . The LED group had a significant reduction in pain levels between 2 and 120 h compared to the control and the laser groups . The LED therapy showed a significant reduction in pain sensitivity ( an average of 56 % ) , after the orthodontic tooth movement when compared to the control group OBJECTIVE The purpose of this study was to evaluate the efficacy of GaAlAs laser light to reduce pain induced by post-adjustment orthodontic final archwire , compared with a placebo control group , and also to evaluate if there are differences in pain gradient when conventional brackets or self-ligating brackets are used for orthodontic treatment . BACKGROUND DATA Previous reports indicate that laser therapy is a safe and efficient alternative to alleviate pain caused in the initial stages of treatment , but there are no studies about its efficacy during the last stages of orthodontic treatment . METHODS The initial sample was 60 orthodontic patients from a private practice , treated by straight wire technique , 30 of them with mini brackets Equilibrium ( ® ) ( Dentaurum , Ispringen , Germany ) and 30 with self-ligation In-Ovation C ( ® ) ( GAC/Dentsply , Tokyo , Japan ) slot 0.022 inch brackets . The archwires used in the final stage of orthodontic treatment were stainless steel 0.019 × 0.025 inch , slot 0.022 inch in both groups . In a design of divided mouth , the dental arches were r and omly assigned to receive one dental arch irradiation with 830 nm 100mW therapeutic laser ( Photon Lase II ) , for 22 sec ( 2.2 J , 80 J/cm(2 ) ) along the vestibular surface and 22 sec ( 2.2 J , 80 J/cm(2 ) ) along the palatal surface of the root in the r and omly selected arch . The opposite dental arch received placebo treatment , with the laser light off . Pain was evaluated using a visual analog scale ( VAS ) after 2 , 6 , and 24 h , and 2 , 3 , and 7 days of application . RESULTS The time course of pain showed the same tendency in both groups , reaching a peak 24 h after the archwire activation . The application of laser therapy reduced pain for any period of time up to 7 days ( p<0.00001 ) and for any kind of bracket . CONCLUSIONS Low intensity laser application reduces pain induced by archwires used during the final stage of orthodontic treatment , without any interference regarding the kind of bracket , as reported by patients OBJECTIVE The objective of this study was to evaluate the effectiveness of the use of irradiation with a low-level laser therapy ( LLLT ) , wavelength 830 nm , for treating pain inherent to tooth movement caused by orthodontic devices , simulated by positioning interdental elastomeric separators . METHODS Sixty orthodontic patients were r and omly assigned to two groups : GA ( ages 12 - 25 years ; mean 17.1 years ) was the control , and GB ( ages 12 - 26 years ; mean 17.9 years ) the intervention group . All patients received elastomeric separators on the mesial and distal surfaces of one of the lower first molars , and immediately after insertion of the separators received irradiation as r and omly indicated . The intervention group ( GB ) received irradiation with LLLT ( aluminum gallium arsenide diode ) , by a single spot in the region of the radicular apex at a dose of 2 J/cm(2 ) and application along the radicular axis of the buccal surface with three spots of 1 J/cm(2 ) ( wavelength 830 nm ; infrared ) . Control group ( GA ) received irradiation with a placebo light in the same way . This was a double-blind study . All the patients received a question naire to be filled out at home describing their levels of pain 2 , 6 , and 24 h and 3 and 5 days after orthodontic separator placement , in situations of relaxed and occluded mouth . RESULTS The patients in the intervention group ( LLLT ) had lower mean pain scores in all the measures . The incidence of complete absence of pain ( score=0 ) was significantly higher the intervention group . CONCLUSIONS Based on this study , authors concluded that single irradiation with LLLT of wavelength 830 nm efficiently controlled the pain originating from positioning interdental elastomeric separators , to reproduce the painful sensation experienced by patients when fixed orthodontic devices are used OBJECTIVES To test the hypothesis that mechanical forces combined with low-level laser therapy stimulate the rate of orthodontic tooth movement . STUDY DESIGN This study was a double blind , r and omized placebo/control matched pairs clinical trial to test the efficacy of GaAlAs low-level laser therapy ( LLLT ) on 12 young adult patients who required retraction of maxillary canines into first premolar extraction spaces using tension coil springs with fixed edgewise appliance . LLLT was applied on the mucosa buccally , distally and palatally to the canine on the test side and using a pseudo-application on the placebo side . Dental impressions and casts were made at the commencement of the trial and at the end of the first , second and third months after starting the trial . Measurement of tooth movements was made on each stage model using a stereo microscope . RESULTS There was no significant difference of means of the canine distal movement between the LLLT side and the placebo side for any time periods ( p-value = 0.77 ) . CONCLUSION The energy density of LLLT ( GaAlAs ) at the surface level in this study ( 25 J/cm(2 ) ) was probably too low to express either stimulatory effect or inhibitory effect on the rate of orthodontic tooth movement INTRODUCTION The long duration of orthodontic treatment is a major concern for patients . A noninvasive method of accelerating tooth movement in a physiologic manner is needed . The aim of this study was to evaluate of the efficacy of low-intensity laser therapy in reducing orthodontic treatment duration and pain . METHODS Twenty patients requiring extraction of first premolars were selected for this study . We used a r and omly assigned incomplete block split-mouth design . Individual canine retraction by a nickel-titanium closed-coil spring was studied . The experimental side received infrared radiation from a semiconductor ( aluminium gallium arsenide ) diode laser with a wavelength of 810 nm . The laser regimen was applied on days 0 , 3 , 7 , and 14 in the first month , and thereafter on every 15th day until complete canine retraction was achieved on the experimental side . Tooth movement was measured on progress models . Each patient 's pain response was ranked according to a visual analog scale . RESULTS An average increase of 30 % in the rate of tooth movement was observed with the low-intensity laser therapy . Pain scores on the experimental sides were significantly lower compared with the control sides . CONCLUSIONS Low-intensity laser therapy is a good option to reduce treatment duration and pain The purpose of this study was to assess the effect of 810-nm ( DMC Equipamentos , Sao Carlos , Brazil ) continuous wave low-level laser therapy ( LLLT ) on the pain caused by orthodontic elastomeric separators . Thirty-seven orthodontic patients ( 12 male and 25 female , aged 11–32 years , mean age = 24.97 years ) participated in the study , including 20 subjects aged 18 years or more , and 17 under 18 years of age . Four elastomeric separators ( Dentarum , Springen , Germany ) were placed for the first permanent molars ( distal and mesial ) , either for maxillary ( 22 patients ) or m and ibular ( 15 patients ) arches ; one quadrant was r and omly selected and used as a placebo group ( received no laser irradiation ) . After separator placement for each quadrant , patients received 10 doses ( 2 J/cm2 , 100 mW , 20 s ) of laser irradiation on the buccal side ( at the cervical third of the roots ) , for distal and mesial of the second premolars and first permanent molars , as well as distal of second permanent molars ( five doses ) . The same procedure was repeated for the lingual or palatal side ( five doses ) . After 24 h , patients returned to the clinic and received another 10 doses of laser irradiation on the same quadrant . Postseparation pain level recorded on a 10-cm visual analog scale for both jaws immediately ( hour 0 ) , and after 6 , 24 , 30 h , as well as on days 3 , 4 , 5 , 6 , and 7 . Significant differences in the pain perception ( PP ) were found between the laser and placebo groups at 6 , 24 , 30 h , and day 3 of the experiment ( P < 0.05 ) . Friedman ’s test of multiple comparisons revealed significant differences in the PP among various time intervals for laser ( chi-square = 173.407 , P = 0.000 ) and placebo ( chi-square = 184.712 , P = 0.000 ) groups . In both groups , pain was highest at 6 and 30 h after placing elastomeric separators . No gender differences were observed in both groups . More pain was recorded in the m and ible ( P < 0.05 ) at 24 ( laser group ) and 30 h ( both groups ) after starting the experiment . The PP was significantly higher ( P < 0.05 ) for the group aged 18 years or more , only at days 3 [ both groups ] and 4 [ laser group only ] of the experiment . The 810-nm continuous wave LLLT significantly reduced the PP in the first 3 days after orthodontic separation . However , the mean postseparation PP in both groups was low and wide ranges of PP scores were observed The effects of soft laser ( low reactive level laser ) on reduction of pain while undergoing orthodontic treatment was examined in this study . These patients were r and omly separated into 3 groups : non-treated control group ( CG ) , blind irradiation group ( BG ) , and laser irradiated group ( LG ) . The effect of laser irradiation on reduction in pain was analyzed by a question naire given to patients who had been wired with an edgewise appliance of a multi-bracket system for orthodontic therapy . Just after application of the initial wire , LG patients were irradiated with the soft laser from the labial and lingual sites for a total of one minute . Reduction in pain was found in some patients who had been irradiated . In particularly , delay in the pain appearance was noted as compared to the other two control groups Low level laser therapy ( LLLT ) has been shown to produce analgesic effects in many clinical applications . The aim of this clinical study was to test the efficacy of LLLT in controlling orthodontic postadjustment pain . Thirty-nine volunteers were selected for this study that used a double-blind design with placebo control . Elastomeric separators were placed at the proximal contacts of one premolar in each quadrant of the dentition to induce orthodontic pain . The tip of a 30 mW gallium-arsenide-aluminium ( 830 nm ) diode laser probe was then placed at the buccal gingiva and directed at the middle third of the root . Three different treatment duration s of 15 , 30 , and 60 seconds and one placebo treatment of 30 seconds were tested within each subject . The study was conducted over 5 days , and the visual analogue scale ( VAS ) was used to quantify the pain experienced by the subjects before and after laser applications for each day . Analysis of the VAS median scores showed that teeth exposed to laser treatment had lower levels of pain as compared with those with the placebo treatment . However , nonparametric statistical analysis of the data showed that the differences between treatments and placebo within each subject were not statistically significant |
13,945 | 29,548,932 | HIGHLIGHTSThe prefrontal cortex , cingulate cortex , and basal ganglia are modified after MBI in depression .
MBIs have modulatory effects on several brain regions implicated in the pathophysiology of MDD , such as the prefrontal cortex , the basal ganglia , the anterior and posterior cingulate cortices , and the parietal cortex .
These regions have been implicated in self‐awareness , attention and emotion regulation .
Some of these findings were consistent with the effects of MBIs observed in healthy subjects and patients with other psychiatric disorders , especially enhanced activity in the frontal and subcortical regions related to the improved somatosensory awareness . | Attentional processes and self‐awareness are key aspects of the effects of MBI on depression .
The MBI‐induced neural changes are correlated with clinical improvements .
ABSTRACT Growing evidence has suggested that mindfulness‐based interventions ( MBIs ) could have beneficial effects on the acute phase of depression and on the prevention of depressive relapse or recurrence .
Despite growing clinical interest , the effects of MBIs on brain functioning in patients with MDD remain unclear .
The aim of this systematic review was to assess the changes in brain functioning associated with MBIs in patients with MDD . | CONTEXT : Although cognitive aspects of meditation underlie much of its clinical application , very little research has examined meditation 's cognitive consequences . This investigation provides experimental support for the idea that meditation leads to a reduction in habitual responding using r and omly selected subjects , a secular form of meditation , and a full experimental design . OBJECTIVE : To test the hypothesis that meditation leads to a reduction in habitual responding . DESIGN : Studies 1 and 2 each incorporated pre-test and post-test design s with a 20-minute intervening attention task ( meditation , rest , or a cognitive control ) . SETTING : Yale University in New Haven , Conn , and the University of California , Berkeley . PARTICIPANTS : One hundred and twenty and 90 undergraduates participated in Studies 1 and 2 , respectively . MAIN OUTCOME MEASURES : Stroop and Word Production ( category generation and stem-completion ) tasks assessed habitual responding in Study 1 . Galvanic Skin response measured arousal in Study 1 . The category generation task assessed habitual responding in Study 2 . Tellegen 's Absorption Scale ( TAS ) measured attention ability . RESULTS : In Study 1 , meditation participants showed a reduction in habitual responding on the Stroop task as compared to controls . Study 1 revealed no statistically significant effects in the word production task . Stroop task performance was not mediated by arousal reduction . In Study 2 , meditation participants showed a reduction in habitual responding on the category production task . Specifically , when participants generated either typical or atypical items , on average , meditation participants produced more atypical items than controls . Category production performance was not mediated by Tellegen 's Absorption Scale ( TAS ) scores . Overall , high TAS scores were related to atypical responding . CONCLUSION : Across cognitive tasks , when participants understood that the goal was to respond non-habitually , meditation reduced habitual responding BACKGROUND Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence . Maintenance antidepressants for at least 2 years is the current recommended treatment , but many individuals are interested in alternatives to medication . Mindfulness-based cognitive therapy ( MBCT ) has been shown to reduce risk of relapse or recurrence compared with usual care , but has not yet been compared with maintenance antidepressant treatment in a definitive trial . We aim ed to see whether MBCT with support to taper or discontinue antidepressant treatment ( MBCT-TS ) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months . METHODS In this single-blind , parallel , group r and omised controlled trial ( PREVENT ) , we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants , from primary care general practice s in urban and rural setting s in the UK . Participants were r and omly assigned to either MBCT-TS or maintenance antidepressants ( in a 1:1 ratio ) with a computer-generated r and om number sequence with stratification by centre and symptomatic status . Participants were aware of treatment allocation and research assessors were masked to treatment allocation . The primary outcome was time to relapse or recurrence of depression , with patients followed up at five separate intervals during the 24-month study period . The primary analysis was based on the principle of intention to treat . The trial is registered with Current Controlled Trials , IS RCT N26666654 . FINDINGS Between March 23 , 2010 , and Oct 21 , 2011 , we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practice s. 212 patients were r and omly assigned to MBCT-TS and 212 to maintenance antidepressants . The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months ( hazard ratio 0·89 , 95 % CI 0·67 - 1·18 ; p=0·43 ) , nor did the number of serious adverse events . Five adverse events were reported , including two deaths , in each of the MBCT-TS and maintenance antidepressants groups . No adverse events were attributable to the interventions or the trial . INTERPRETATION We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence . Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence , residual depressive symptoms , and quality of life . FUNDING National Institute for Health Research ( NIHR ) Health Technology Assessment ( HTA ) programme , and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula Rationale An involvement of 5-HT1A receptors is postulated in the pathophysiology of affective disorders and mechanism of action of antidepressants . Methods for study ing their functional integrity in humans are , however , limited . Preliminary data suggests that activation of somatodendritic 5-HT1A receptors cause a negative shift in the EEG frequency spectrum . Animal research suggests that pindolol is an agonist at these receptors but an antagonist at postsynaptic 5-HT1A receptors . Objective We postulated that while pindolol would antagonise known postsynaptic mediated neuroendocrine responses to the 5-HT1A agonist buspirone , both drugs would have a similar effect on the EEG frequency spectrum . Methods Fourteen healthy men were administered placebo or pindolol ( 20 mg orally ) 90 min before placebo or buspirone ( 30 mg orally ) in a double blind cross-over study . Plasma prolactin and growth hormone were assayed and EEGs recorded before and after drug administration . Results A significant negative shift in the EEG frequency spectrum was found for both buspirone and pindolol , with the combination producing a similar effect to each drug alone . In contrast , the neuroendocrine response to buspirone was significantly attenuated by pindolol . Conclusions The data obtained are consistent with the EEG effects of buspirone and pindolol being mediated by somatodendritic 5-HT1A receptors , in contrast to the neuroendocrine response , which is known to be mediated by postsynaptic receptors . The development of this novel method of assessing somatodendritic 5-HT1A receptors in humans is a potentially important advance which may allow the testing of hypotheses of its involvement in depression and response to antidepressants Meditation-based interventions reduce the relapse risk in recurrently depressed patients . R and omized trials utilizing neurophysiologic outcome measures , however , have yielded inconsistent results with regard to a prophylactic effect . Although frontal brain asymmetry , assessed through electroencephalographic ( EEG ) alpha activity ( 8 - 13 Hz ) , is indicative of approach vs. withdrawal-related response dispositions and represents a vulnerability marker of depression , clinical trials have provided mixed results as to whether meditation has beneficial effects on alpha asymmetry . Inconsistencies might have arisen since such trials relied on resting-state recordings , instead of active paradigms under challenge , as suggested by contemporary notions of alpha asymmetry . We examined two groups of remitted , recurrently depressed females . In a " mindfulness support group " , EEG was recorded during neutral rest , and rest following a negative mood induction . Subsequently , participants received initial meditation instructions . EEG was then obtained during an active period of guided mindfulness meditation and rest following the active period . In a " rumination challenge group " , EEG was obtained during the same resting conditions , whereas in the active period , initial meditation instructions were followed by a rumination challenge . A significant shift in mid-frontal asymmetry , yielding a pattern indicative of approach motivation , was observed in the mindfulness support group , specifically during the meditation period . This indicates that mindfulness meditation may have a transient beneficial effect , which enables patients to take an approach-related motivational stance , particularly under circumstances of risk The human brain spontaneously generates neural oscillations with a large variability in frequency , amplitude , duration , and recurrence . Little , however , is known about the long-term spatiotemporal structure of the complex patterns of ongoing activity . A central unresolved issue is whether fluctuations in oscillatory activity reflect a memory of the dynamics of the system for more than a few seconds . We investigated the temporal correlations of network oscillations in the normal human brain at time scales ranging from a few seconds to several minutes . Ongoing activity during eyes-open and eyes-closed conditions was recorded with simultaneous magnetoencephalography and electroencephalography . Here we show that amplitude fluctuations of 10 and 20 Hz oscillations are correlated over thous and s of oscillation cycles . Our analyses also indicated that these amplitude fluctuations obey power-law scaling behavior . The scaling exponents were highly invariant across subjects . We propose that the large variability , the long-range correlations , and the power-law scaling behavior of spontaneous oscillations find a unifying explanation within the theory of self-organized criticality , which offers a general mechanism for the emergence of correlations and complex dynamics in stochastic multiunit systems . The demonstrated scaling laws pose novel quantitative constraints on computational models of network oscillations . We argue that critical-state dynamics of spontaneous oscillations may lend neural networks capable of quick reorganization during processing dem and OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results Mindfulness-based stress reduction ( MBSR ) is an established program shown to reduce symptoms of stress , anxiety , and depression . MBSR is believed to alter emotional responding by modifying cognitive-affective processes . Given that social anxiety disorder ( SAD ) is characterized by emotional and attentional biases as well as distorted negative self-beliefs , we examined MBSR-related changes in the brain-behavior indices of emotional reactivity and regulation of negative self-beliefs in patients with SAD . Sixteen patients underwent functional MRI while reacting to negative self-beliefs and while regulating negative emotions using 2 types of attention deployment emotion regulation-breath-focused attention and distraction-focused attention . Post-MBSR , 14 patients completed neuroimaging assessment s. Compared with baseline , MBSR completers showed improvement in anxiety and depression symptoms and self-esteem . During the breath-focused attention task ( but not the distraction-focused attention task ) , they also showed ( a ) decreased negative emotion experience , ( b ) reduced amygdala activity , and ( c ) increased activity in brain regions implicated in attentional deployment . MBSR training in patients with SAD may reduce emotional reactivity while enhancing emotion regulation . These changes might facilitate reduction in SAD-related avoidance behaviors , clinical symptoms , and automatic emotional reactivity to negative self-beliefs in adults with SAD Mindfulness-based cognitive therapy ( MBCT ) effectively prevents relapse/recurrence in major depression . The ability to deploy and maintain attention on a particular focus is considered as a prerequisite for ' mindful ' , ' metacognitive ' awareness , and hence crucial for therapy success . Accordingly , sustained concentration is the skill most extensively taught in MBCT . The goal of the present study was to test whether this ability increases after MBCT , as assumed . The late component of the contingent negative variation ( CNV ) , an event-related brain potential ( ERP ) , known to reflect the allocation of attentional re sources , was used as the measure of concentration ability . In the main phase of the study , 91 recurrently depressed patients in remission were r and omly assigned to eight-week treatment by either MBCT or waiting ( WAIT for delayed MBCT ) . The CNV response to an auditory test stimulus was measured pre- and post-treatment in a ' mindfulness task ' , in which patients were instructed to focus on their breath , as taught in MBCT . The late CNV ( LCNV ) was increased only after MBCT ( and not after WAIT ) . This result reflects patients ' improved ability to shift their attention toward current moment experience and away from potentially depressogenic thinking or rumination during mild dysphoric states-a known risk factor for depressive relapse/recurrence The present investigation examined the contributions of specific attentional networks to long-term trait effects of meditation . It was hypothesized that meditation could improve the efficiency of executive processing ( inhibits prepotent/incorrect responses ) or orientational processing ( orients to specific objects in the attentional field ) . Participants ( 50 meditators and 10 controls ) were given the Stroop ( measures executive attention ) and Global-Local Letters ( measures orientational attention ) tasks . Results showed that meditation experience was associated with reduced interference on the Stroop task ( p < 0.03 ) , in contrast with a lack of effect on interference in the Global-Local Letters task . This suggests that meditation produces long-term increases in the efficiency of the executive attentional network ( anterior cingulate/prefrontal cortex ) but no effect on the orientation network ( parietal systems ) . The amount of time participants spent meditating each day , rather than the total number of hours of meditative practice over their lifetime , was negatively correlated with interference on the Stroop task ( r = -0.31 , p < 0.005 ) This study investigated the effects of a meditation-based treatment for preventing relapse to depression , mindfulness-based cognitive therapy ( MBCT ) , on prefrontal & agr;-asymmetry in resting electroencephalogram ( EEG ) , a biological indicator of affective style . Twenty-two individuals with a previous history of suicidal depression were r and omly assigned to either MBCT ( N=10 ) or treatment-as-usual ( TAU , N=12 ) . Resting electroencephalogram was measured before and after an 8-week course of treatment . The TAU group showed a significant deterioration toward decreased relative left-frontal activation , indexing decreases in positive affective style , while there was no significant change in the MBCT group . The findings suggest that MBCT can help individuals at high risk for suicidal depression to retain a balanced pattern of baseline emotion-related brain activation |
13,946 | 25,162,713 | The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference .
There was also no statistically significant difference in DFS and OS of stage I NSCLC patients .
The systematic review with meta- analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer . | BACKGROUND The prognostic value of epidermal growth factor receptor ( EGFR ) mutations in resected non-small cell lung cancer ( NSCLC ) remains controversial .
We performed a systematic review with meta- analysis to assess its role . | BACKGROUND Previous , uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer . METHODS In this phase 3 , open-label study , we r and omly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib ( 250 mg per day ) ( 609 patients ) or carboplatin ( at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute ) plus paclitaxel ( 200 mg per square meter of body-surface area ) ( 608 patients ) . The primary end point was progression-free survival . RESULTS The 12-month rates of progression-free survival were 24.9 % with gefitinib and 6.7 % with carboplatin-paclitaxel . The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority , as compared with carboplatin-paclitaxel , with respect to progression-free survival in the intention-to-treat population ( hazard ratio for progression or death , 0.74 ; 95 % confidence interval [ CI ] , 0.65 to 0.85 ; P<0.001 ) . In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene ( EGFR ) mutation , progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel ( hazard ratio for progression or death , 0.48 ; 95 % CI , 0.36 to 0.64 ; P<0.001 ) , whereas in the subgroup of 176 patients who were negative for the mutation , progression-free survival was significantly longer among those who received carboplatin-paclitaxel ( hazard ratio for progression or death with gefitinib , 2.85 ; 95 % CI , 2.05 to 3.98 ; P<0.001 ) . The most common adverse events were rash or acne ( in 66.2 % of patients ) and diarrhea ( 46.6 % ) in the gefitinib group and neurotoxic effects ( 69.9 % ) , neutropenia ( 67.1 % ) , and alopecia ( 58.4 % ) in the carboplatin-paclitaxel group . CONCLUSIONS Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia . The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib . ( Clinical Trials.gov number , NCT00322452 . PURPOSE Epidermal growth factor receptor ( EGFR ) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer ( NSCLC ) . The implication s of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown . KRAS is frequently activated in NSCLC . The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described . PATIENTS AND METHODS Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were r and omly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival , response , and time to progression ( TTP ) . EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients . Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses . RESULTS EGFR mutations were detected in 13 % of tumors and were associated with longer survival , irrespective of treatment ( P < .001 ) . Among erlotinib-treated patients , EGFR mutations were associated with improved response rate ( P < .05 ) and there was a trend toward an erlotinib benefit on TTP ( P = .092 ) , but not improved survival ( P = .96 ) . KRAS mutations ( 21 % of tumors ) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients . CONCLUSION EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib , and may predict greater likelihood of response . Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy . Further studies are needed to confirm the findings of this retrospective subset analysis PURPOSE This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group . PATIENTS AND METHODS We included in the analysis all eligible patients ( N = 1,052 ) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party ( ELCWP ) during one decade . The patients were treated by chemotherapy regimens based on platinum derivatives . We prospect ively collected 23 variables and analyzed them by univariate and multivariate methods . RESULTS The global estimated median survival time was 29 weeks , with a 95 % confidence interval of 27 to 30 weeks . After univariate analysis , we applied two multivariate statistical techniques . In a Cox regression model , the selected explanatory variables were disease extent , Karnofsky performance status , WBC and neutrophil counts , metastatic involvement of skin , serum calcium level , age , and sex . These results were confirmed by application of recursive partitioning and amalgamation algorithms ( RECPAM ) , which led to classification of the patients into four homogeneous subgroups . CONCLUSION We confirmed by our analysis the role of well-known independent prognostic factors for survival , but also identified the effect of the neutrophil count , rarely studied , with the use of two methods : a classical Cox regression model and a RECPAM analysis . The classification of patients into the four subgroups we obtained needs to be vali date d in other series BACKGROUND This study prospect ively assessed the efficacy of gefitinib and the survival benefit for non-small cell lung cancer ( NSCLC ) patients with epidermal growth factor receptor ( EGFR ) mutations . METHOD Patients with either recurrent disease after undergoing surgery or advanced NSCLC disease ( IIIB or IV ) which demonstrated EGFR mutations were eligible for this study . EGFR mutations in exons 19 - 21 were examined . The patients with EGFR mutations were enrolled in this study after obtaining their informed consent a second time , and they were thereafter treated with gefitinib . RESULTS EGFR mutations were detected in 20 of 48 patients with NSCLC , and 19 patients were enrolled onto this study and treated with gefitinib . Seven patients had an exon 19 deletion , 10 had L858R , 1 had both , and 1 had an exon 19 deletion and G796A . The overall response rate was 63.2 % , and the disease control rate was 89.5 % . In patients with an exon 19 del and L858R , the response rates were 71.4 % and 60.0 % , respectively . The median progression-free survival time was 7.1 months , and the median survival time was 20.0 months . No life-threatening toxicity was observed . Four of five acquired resistant tumors showed an acquired T790 M mutation . CONCLUSIONS EGFR mutations in exons 19 or 21 are considered to be a good predictor of the efficacy of gefitinib |
13,947 | 25,511,932 | Conclusion The results show that antibiotic use could be improved by educational interventions , being mostly used multifaceted interventions | Background Excessive and inappropriate antibiotic use contributes to growing antibiotic resistance , an important public-health problem .
Strategies must be developed to improve antibiotic-prescribing . | OBJECTIVES to evaluate the effect of two interventions on reducing antibiotic prescription in pharyngitis . METHODS a prospect i ve , non-r and omized , before-after controlled study was carried out in primary care centres throughout Spain . General practitioners ( GPs ) registered all cases of pharyngitis during a 3 week period before and after two types of intervention in 2008 and 2009 , respectively . Full intervention consisted of discussion sessions of the results of the first registry , courses for GPs , guidelines , patient information leaflets , workshops on rapid tests and the use of rapid antigen detection tests ( RADTs ) in their consulting offices . The physicians in the partial intervention group underwent all the above intervention except for the workshop , and RADTs were not provided . A control group was also included in 2009 . Multilevel logistic regression was performed considering the prescription of antibiotics as the dependent variable . RESULTS a total of 280 GPs registered cases with pharyngitis ( 70 partial intervention and 210 full intervention ) . Fifty-nine new physicians were included as a control group . A total of 6849 episodes of pharyngitis were registered . Antibiotic prescription was significantly lower after intervention for the full intervention group , but not for the partial intervention group . According to the multivariate model , in comparison with the control group , the odds ratio of antibiotic prescription after the intervention was 0.52 [ 95 % confidence interval ( 95 % CI ) 0.23 - 1.18 ] in the partial intervention group and 0.23 ( 95 % CI 0.11 - 0.47 ) in the full intervention group . CONCLUSIONS intervention was beneficial for reducing the prescription of antibiotics , but was only statistically significant when the GPs were provided with RADTs BACKGROUND A multiple intervention targeted to reduce antibiotic prescribing with an educational outreach programme had proven to be effective in a r and omized controlled trial in 12 peer review groups , demonstrating 12 % less prescriptions for respiratory tract infections . OBJECTIVE To assess the effectiveness of a multiple intervention in primary care at a large scale . METHODS A controlled before and after study in 2006 and 2007 was design ed . Participants were from general practice s within a geographically defined area in the middle region of The Netherl and s. Participants were GPs in 141 practice s in 25 peer review groups . A control group of GP practice s from the same region , matched for type of practice and mean volume of antibiotic prescribing . The multiple intervention consisted of the following elements : ( i ) group education meeting and communication training ; ( ii ) monitoring and feedback on prescribing behaviour ; ( iii ) group education for GPs and pharmacists assistants and ( iv ) patient education material . The main outcome measures are as follows : ( i ) number of antibiotic prescriptions per 1000 patients per GP and ( ii ) number of second-choice antibiotics , obtained from cl aims data from the regional health insurance company . The associations between predictors and outcome measurements were assessed by means of a multiple regression analyses . RESULTS At baseline , the number of antibiotic prescriptions per 1000 patients was slightly higher in the intervention group than in the control group ( 184 versus 176 ) . In 2007 , the number of prescriptions had increased to 232 and 227 , respectively , and not differed between intervention and control group . CONCLUSIONS The implementation of an already proven effective multiple intervention strategy at a larger scale showed no reduction of antibiotic prescription rates . The failure might be attributed to a less tight monitoring of intervention and audit . Inserting practical tools in the intervention might be more successful and should be studied OBJECTIVE This study assessed the effect of a h and held computer-based decision support system ( DSS ) on antibiotic use and patient outcomes in a critical care unit . DESIGN A DSS containing four types of evidence ( patient microbiology reports , local antibiotic guidelines , unit-specific antibiotic susceptibility data for common bacterial pathogens , and a clinical pulmonary infection score calculator ) was developed and implemented on a h and held computer for use in the intensive care unit at a tertiary referral hospital . System impact was assessed in a prospect i ve " before/after " cohort trial lasting 12 months . Outcome measures were defined daily doses ( DDDs ) of antibiotics per 1,000 patient-days , patient length of stay , and mortality . RESULTS The number of admissions , APACHE ( Acute Physiology , Age , and Chronic Health Evaluation ) II and SAPS ( Simplified Acute Physiology Score ) II for patients in preintervention , and intervention ( DSS use ) periods were statistically comparable . The mean patient length of stay and the use of antibiotics in the unit during six months of the DSS use decreased from 7.15 to 6.22 bed-days ( p = 0.02 ) and from 1,767 DDD to 1,458 DDD per 1,000 patient-days ( p = 0.04 ) , respectively , with no change in mortality . The DSS was accessed 674 times during 168 days of the trial . Microbiology reports and antibiotic guidelines were the two most commonly used ( 53 % and 22.5 % , respectively ) types of evidence . The greatest reduction was observed in the use of beta-lactamase-resistant penicillins and vancomycin . CONCLUSION H and held computer-based decision support contributed to a significant reduction in patient length of stay and antibiotic prescribing in a critical care unit Background Acute respiratory tract infections ( ARTI ) are among the most frequent reasons for consultations in primary care . Although predominantly viral in origin , ARTI often lead to the prescription of antibiotics for ambulatory patients , mainly because it is difficult to distinguish between viral and bacterial infections . Unnecessary antibiotic use , however , is associated with increased drug expenditure , side effects and antibiotic resistance . A novel approach is to guide antibiotic therapy by procalcitonin ( ProCT ) , since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases . The aim of this trial is to compare a ProCT-guided antibiotic therapy with a st and ard approach based on evidence -based guidelines for patients with ARTI in primary care . Methods / Design This is a r and omised controlled trial in primary care with an open intervention . Adult patients judged by their general practitioner ( GP ) to need antibiotics for ARTI are r and omised in equal numbers either to st and ard antibiotic therapy or to ProCT-guided antibiotic therapy . Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial . Exclusion criteria for patients are antibiotic use in the previous 28 days , psychiatric disorders or inability to give written informed consent , not being fluent in German , severe immunosuppression , intravenous drug use , cystic fibrosis , active tuberculosis , or need for immediate hospitalisation . The primary endpoint is days with restrictions from ARTI within 14 days after r and omisation . Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days , days off work and days with side-effects from medication within 14 days , and relapse rate from the infection within 28 days after r and omisation . Discussion We aim to include 600 patients from 50 general practice s in the Northwest of Switzerl and . Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age , proportion of female physicians , specialisation , years of postgraduate training and years in private practice OBJECTIVE Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors . We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit ( PICU ) . METHODS We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients . Process and outcomes measures were monitored prospect ively during a 6-month control and a 6-month intervention period . M and atory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period . Clinician opinions of the decision support tool were surveyed via question naire . RESULTS The rate of pharmacy interventions for erroneous drug doses declined by 59 % . The rate of anti-infective subtherapeutic patient days decreased by 36 % , and the rate of excessive-dose days declined by 28 % . The number of orders placed per antiinfective course decreased 11.5 % , and the robust estimate of the antiinfective costs per patient decreased 9 % . The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar , as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches . The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events . CONCLUSIONS Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders , improved therapeutic dosage targets , and was associated with a decreased robust estimate of antiinfective costs per patient . antiinfective agents , decision support systems , drug therapy , medication errors , child , infant BACKGROUND Antibiotic misuse is common and costly and may promote antibiotic resistance . We tested the efficacy of a targeted one-on-one educational program ( " academic detailing " ) design ed to improve the appropriateness of broad-spectrum antibiotic use . METHODS A r and omized controlled trial was conducted in a large US teaching hospital . During an 18-week study period , 17 general medical , oncology , and cardiology services either received academic detailing or did not . The intervention was prompted by an order for either levofloxacin or ceftazidime that led to a computer-based review of data for that patient . Orders for the 2 target antibiotics deemed unnecessary by a priori criteria were included in the study . The primary outcome examined was the number of days that unnecessary levofloxacin or ceftazidime was administered in intervention and control groups . RESULTS Before the trial , intervention and control services had similar prescribing patterns for the target antibiotics ; the drugs were used for similar indications throughout the study period . During the intervention , there was a reduction of 37 % in days of unnecessary levofloxacin or ceftazidime use per 2-week interval on services r and omized to the educational intervention vs control services ( P < .001 ) . In multivariable analyses controlling for baseline prescribing and study interval , the rate of unnecessary use of the 2 target antibiotics was reduced by 41 % on the intervention services compared with controls ( 95 % confidence interval , 44%-78 % ; P < .001 ) . Length of stay , intensive care unit transfers , readmission rates , and in-hospital death rates were similar in both groups ( P > or = .10 for all ) . CONCLUSION Targeted one-on-one education is a practical , effective , and safe method for reducing excessive broad-spectrum antibiotic use From 1998 to 2000 , 13 rural Alaskan villages ( population , 3326 ) were surveyed annually by nasopharyngeal cultures for Streptococcus pneumoniae carriage . Data regarding antibiotic use for the entire population was abstract ed from clinic records . In 1999 , education of medical providers and the community about appropriate antibiotic use began in 4 villages ; this program was exp and ed to include all villages in 2000 . Antibiotic courses per person decreased by 31 % in the initial intervention villages and by 35 % in the remaining villages after education ( P<.01 for each ) . Sample s were obtained for culture from a mean of 31 % of the population each year ; 31 % carried pneumococcus . No sustained decrease in carriage of penicillin-nonsusceptible strains was observed . When linear regression was used , serotype accounted for 81 % of the variance in pneumococcal minimum inhibitory concentrations after the intervention , compared with 7 % for antibiotic use . This suggests that reducing the carriage of serotypes associated with antibiotic resistance by use of pneumococcal conjugate vaccines may have a greater short-term impact than does decreasing antibiotic use Objective The study objective was to evaluate the effectiveness of an operational multidisciplinary antibiotic team , including an infectious disease physician and a clinical pharmacist , in reducing the hospital antimicrobial consumption and costs . Setting The 1800-bed University Hospitals of Nancy ( France ) . Method A cluster controlled ‘ before-after ’ study was performed . The intervention group comprised 11 medical and surgical wards in setting s where the operational antibiotic team was implemented , and the control group comprised 6 wards without this operational team . The ‘ before ’ period ( 2005 ) preceded the implementation of the operational team in the intervention group and ‘ after ’ ( July 2007 to June 2008 ) followed its full implementation . Main outcome measure We compared consumption of antibiotics overall and by therapeutic class ( in defined daily doses per 1,000 patient days ) and cost savings ( in € ) between ‘ before ’ and ‘ after ’ in both groups ( control and intervention ) , using a mixed effect linear model . Results The overall consumption of antibiotics decreased after implementation of the operational team by 33.6 % in the intervention group and by 3.3 % in the control group ( P = 0.003 ) . Compared with the control group , the decrease in antibiotic use in the intervention group was significantly higher for various therapeutic classes ( broad-spectrum penicillins , injectable fluoroquinolones , glycopeptides ) and specific drugs ( imipenem , ciprofloxacin , teicoplanin ) . For the same activity , the total cost savings were 14-fold higher in the intervention group . Conclusion Establishment of an operational multidisciplinary team may be an effective way to reduce hospital antibiotic use and cost , with a good acceptance rate among prescribers Background Psychological theories of behaviour may provide a framework to guide the design of interventions to change professional behaviour . Behaviour change interventions , design ed using psychological theory and targeting important motivational beliefs , were experimentally evaluated for effects on the behavioural intention and simulated behaviour of GPs in the management of uncomplicated upper respiratory tract infection ( URTI ) . Methods The design was a 2 × 2 factorial r and omised controlled trial . A postal question naire was developed based on three theories of human behaviour : Theory of Planned Behaviour ; Social Cognitive Theory and Operant Learning Theory . The beliefs and attitudes of GPs regarding the management of URTI without antibiotics and rates of prescribing on eight patient scenarios were measured at baseline and post-intervention . Two theory-based interventions , a " grade d task " with " action planning " and a " persuasive communication " , were incorporated into the post-intervention question naire . Trial groups were compared using co-variate analyses . Results Post-intervention question naires were returned for 340/397 ( 86 % ) GPs who responded to the baseline survey . Each intervention had a significant effect on its targeted behavioural belief : compared to those not receiving the intervention GPs completing Intervention 1 reported stronger self-efficacy scores ( Beta = 1.41 , 95 % CI : 0.64 to 2.25 ) and GPs completing Intervention 2 had more positive anticipated consequences scores ( Beta = 0.98 , 95 % CI = 0.46 to 1.98 ) . Intervention 2 had a significant effect on intention ( Beta = 0.90 , 95 % CI = 0.41 to 1.38 ) and simulated behaviour ( Beta = 0.47 , 95 % CI = 0.19 to 0.74 ) . Conclusion GPs ' intended management of URTI was significantly influenced by their confidence in their ability to manage URTI without antibiotics and the consequences they anticipated as a result of doing so . Two targeted behaviour change interventions differentially affected these beliefs . One intervention also significantly enhanced GPs ' intentions not to prescribe antibiotics for URTI and result ed in lower rates of prescribing on patient scenarios compared to a control group . The theoretical frameworks utilised provide a scientific rationale for underst and ing how and why the interventions had these effects , improving the reproducibility and generalisability of these findings and offering a sound basis for an intervention in a " real world " trial . Trial registration Clinical trials.gov UNLABELLED The inappropriate use of antibiotics for the treatment of infections is a worldwide problem that has implication s for the cost of treatment and the development of resistant strains of bacteria . The use of antibiotics should follow specific criteria ; they are on top of the list of self-medication drugs in countries that do not control their commercialization . OBJECTIVES To determine the percentage of pharmacies that attend the public and sell antibiotics without medical prescription in a medium-sized city in Brazil , and analyze the variables involved in this procedure . MATERIAL S AND METHODS 107 of the 136 pharmacies registered in our city were evaluated . These pharmacies were visited by actresses who simulated having a sister with symptoms of a non-complicated rhino-sinusitis , so that they could obtain antibiotics without a medical prescription . Each pharmacy was visited only once ; the only variable in the simulated clinical setting was the report of fever temperature , which was r and omly assigned between 38.5 and 40 degrees Celsius . RESULTS Antibiotics were offered in 58 % of the pharmacies , and this offer was increased to 74 % after the actresses insisted on having them . In 65.4 % of the pharmacies , the actresses were attended by a pharmacist , and 84.2 % of them said they would sell antibiotics . When the request for antibiotics was denied ( 26 % ) , only 7.5 % was due to absence of prescription . The most frequent reason for refusal to sell antibiotics , was because the attendant deemed it unnecessary ( 46.6 % ) CONCLUSION Antibiotics can be easily bought in the great majority of the pharmacies in our town without a medical prescription and a clear indication . Fever temperature did not modify the attendant 's indication of the drug OBJECTIVES . To determine whether we could increase adherence to the Centers for Disease Control and Prevention ( CDC ) recommendations with well-accepted approaches to improving quality of care and adherence to the CDC recommendations result ed in improved outcomes for acute otitis media ( AOM ) . METHODS . A cluster r and omization study was conducted in 12 pediatric practice s ( 6 intervention and 6 control sites ) . The main outcome measures were adherence to the CDC recommendations ( modified to include 2 additional antimicrobial agents ) and a subsequent antibiotic prescription for AOM within 30 days after diagnosis . RESULTS . Of 3152 patients referred to research assistants , 2584 ( 82 % ) were eligible . Of those eligible , 1368 ( 99 % ) of 1382 at the intervention sites and 1138 ( 99 % ) of 1146 at the control sites consented to participate . Rates of adherence to the CDC recommendations were not significantly higher at the intervention sites than at the control sites , for initial enrollment episodes ( 78.2 % vs 70.6 % ) or second episodes ( 62.6 % vs 59.9 % ) . After controlling for clustering according to site and covariates , children who were not treated in adherence to the CDC recommendations for both episodes had 1.60 times the odds of a subsequent prescription within 12 days , compared with those treated in adherence at both episodes . CONCLUSIONS . Despite using evidence -based approaches that are known to influence physician behavior , we were unable to increase adherence to the CDC recommendations for treatment of AOM . However , we did establish that prescription of antimicrobial therapy consistent with the CDC recommendations for a second episode of AOM was associated with improved outcomes , measured as the need for subsequent antibiotic prescription . Because of the selection of resistant otopathogens , adherence to the CDC recommendations is likely more important in subsequent episodes of AOM than in the initial episode OBJECTIVE To implement and evaluate the effect of a computerized decision support tool on antibiotic use in an intensive care unit ( ICU ) . DESIGN Prospect i ve before- and -after cohort study . SETTING Twenty-four bed tertiary hospital adult medical/surgical ICU . PARTICIPANTS All consecutive patients from May 2001 to November 2001 ( N = 524 ) and March 2002 to September 2002 ( N = 536 ) . INTERVENTION A real-time microbiology browser and computerized decision support system for isolate directed antibiotic prescription . MAIN OUTCOME MEASURES Number of courses of antibiotic prescribed , antibiotic utilization ( defined daily doses (DDDs)/100 ICU bed-days ) , antibiotic susceptibility mismatches , and system uptake . RESULTS There was a significant reduction in the proportion of patients prescribed carbapenems [ odds ratio ( OR ) = 0.61 , 95 % confidence interval ( CI ) = 0.39 - 0.97 , P = 0.04 ] , third-generation cephalosporins ( OR = 0.58 , 95 % CI = 0.42 - 0.79 , P = 0.001 ) , and vancomycin ( OR = 0.67 , 95 % CI = 0.45 - 1.00 , P = 0.05 ) after adjustment for risk factors including Apache II score , suspected infection , positive microbiology , intubation , and length of stay . The decision support tool was associated with a 10.5 % reduction in both total antibiotic utilization ( 166 - 149 DDDs/100 ICU bed days ) and the highest volume broad-spectrum antibiotics . There were fewer susceptibility mismatches for initial antibiotic therapy ( OR = 0.63 , 95 % CI = 0.39 - 0.98 , P = 0.02 ) and increased de-escalation to narrower spectrum antibiotics . Uptake of the program was high with 6028 access episodes during the 6-month evaluation period . CONCLUSIONS This tool streamlined collation and clinical use of microbiology results and integrated into the daily ICU workflow . Its introduction was accompanied by a reduction in both total and broad-spectrum antibiotic use and an increase in the number of switches to narrower spectrum antibiotics BACKGROUND The association between antibiotic use in the community and antimicrobial resistance is known . Attention has recently focused on the type of agents being prescribed . OBJECTIVES To implement , evaluate and compare the efficacy of two community intervention programs -- continuous versus seasonal medical education -- oriented to primary care physicians with emphasis on the appropriate use of antimicrobial drugs . METHODS From October 2000 to April 2003 we conducted two interventions : a ) a monthly educational campaign in selected clinics promoting appropriate diagnosis of common infectious diseases and prudent antibiotic use ( continuous intervention group ) ; and b ) a massive educational campaign , conducted before two consecutive winters , promoting the judicious use of antibiotics for treating respiratory infections ( continuous intervention group and seasonal intervention group ) . Sixteen similar clinics were r and omized ( 8 to each group ) . The total antibiotic use was measured as defined daily dose/1000 patients /day , and compared between the groups . RESULTS The total use of antibiotics decreased between 1999 - 2000 and 2002 - 2003 in both groups , but slightly more significantly in the continuous intervention group . The DDD/1000 patients /day for the seasonal group in 1999 - 2000 was 27.8 vs. 23.2 in 2002 - 2003 ; and for the continuous group 28.7 in 1999 - 2000 vs. 22.9 in 2002 - 2003 , a reduction of 16.5 % and 20.0 % respectively ( P < 0.0001 ) . The main change in antibiotic use was noted for broad-spectrum antibiotics . CONCLUSIONS We present a successful community intervention program aim ed to reduce unnecessary antibiotic use . Amplification of this type of intervention is imperative to stop the increase in antimicrobial resistance OBJECTIVES Infections with group A streptococcus ( GAS ) occur in 10 % to 20 % of patients with sore throats , whereas antibiotics are prescribed 50 % of the time . Clinical scoring rules can more accurately predict the likelihood of GAS infection , but whether family physicians will adopt such approaches is unclear . This study sought to determine whether repeated clinical prompts to use a scoring approach could help family physicians lower antibiotic use in patients with a sore throat . STUDY DESIGN R and omized trial in which physicians were assigned to use either ( 1 ) chart stickers that prompted them to calculate a score based on clinical findings and provided management recommendations linked to score totals or ( 2 ) a clinical checklist . POPULATION Ninety-seven family physicians in Ontario , Canada , assessed 621 children and adults with sore throat and obtained a throat swab for culture . OUTCOMES MEASURED ( 1 ) Unnecessary antibiotic prescriptions given to patients with a negative throat culture and ( 2 ) overall antibiotic use . RESULTS There were no differences between the control and intervention group in unnecessary antibiotic prescriptions ( 16.1 % vs 20.4 % , respectively , P = .29 ) or overall antibiotic use ( 27.9 % vs 28.1 % , P = .97 ) . However , a number of physicians dropped out of the study ; as a result , the characteristics of the physicians in the 2 groups were dissimilar in factors related to prescribing . After adjusting for these differences and patient clustering by physician , the odds ratio for the effect of the intervention on unnecessary antibiotic prescriptions was 0.76 ( 95 % confidence interval [ CI ] = 0.42 , 1.40 ) and 0.57 for overall antibiotic use ( 95 % CI = 0.27 , 1.17 ) . CONCLUSIONS Chart prompts during clinical encounters to use a clinical score in the assessment of patients with a sore throat did not reduce unnecessary antibiotic prescribing by family physicians . The problems encountered in conducting this community-based intervention trial are discussed in relation to the negative result OBJECTIVES To investigate the effect of reinforcing a narrow-spectrum antibiotic policy on antibiotic prescription and Clostridium difficile infection ( CDI ) rates by feedback of antibiotic use to doctors , as part of a departmental audit and feedback programme . DESIGN A prospect i ve controlled interrupted time-series ( ITS ) study , with pre-defined pre- and post-intervention periods , each of 21 months . SETTING Three acute medical wards for elderly people in a teaching hospital . PARTICIPANTS Six thous and one hundred and twenty-nine consecutive unselected acute medical admissions aged > or=80 years . INTERVENTIONS A ' narrow-spectrum ' antibiotic policy ( reinforced by an established programme of audit and feedback of antibiotic usage and CDI rates ) was introduced , following an unplanned rise in amoxicillin/clavulanate ( Augmentin ) use . It targeted broad-spectrum antibiotics for reduction ( cephalosporins and amoxicillin/clavulanate ) and narrow-spectrum antibiotics for increase ( benzyl penicillin , amoxicillin and trimethoprim ) . Changes in the use of targeted antibiotics ( intervention group ) were compared with those of untargeted antibiotics ( control group ) using segmented regression analysis . Changes in CDI rates were examined by the Poisson regression model . Methicillin-resistant Staphylococcus aureus ( MRSA ) acquisition rates acted as an additional control . RESULTS There was a reduction in the use of all targeted broad-spectrum antibiotics and an increase in all targeted narrow-spectrum antibiotics , statistically significant for sudden change and /or linear trend . All other antibiotic use remained unchanged . CDI rates fell with incidence rate ratios of 0.35 ( 0.17 , 0.73 ) ( P=0.009 ) . MRSA incidence did not change [ 0.79 ( 0.49 , 1.28 ) ; P=0.32 ] . CONCLUSIONS This is the first controlled prospect i ve ITS study to use feedback to reinforce antibiotic policy and reduce CDI . Multicentre ITS or cluster r and omized trials of this and other methods need to be undertaken to establish the most effective means of optimizing antibiotic use and reducing CDI Objective The study evaluates the short term impacts of an intensive control program for the appropriate us of antimicrobials , and to provide a novel strategy for antimicrobial control in inpatient wards in Taiwan . Method In September 2002 , a dual intensive antimicrobial control program was implemented within a 921-bed medical center in Taiwan . The study sample included all patients admitted to the medical center during the basal period ( October – December 2001 ) and the intervention period ( October – December 2002 ) , where at least one type of parenteral antimicrobial was administered . The sample comprised of 5046 patients during the basal period and 5054 patients during the intervention period . Main outcome measure Analysis of the impact of the intensive antimicrobial control program was undertaken by comparing clinical outcomes , parenteral antimicrobial consumption and bacterial susceptibilities , before and after the establishment of the intensive antimicrobial control program . Results No statistical differences were found between the basal and intervention periods with regard to either the demographic variables , such as age and gender , or the incidence of nosocomial infections . The clinical outcomes , including length of stay in the medical center , mortality and readmission rates , were also similar for both periods . As compared to the basal period , the consumption of parenteral antimicrobials — in defined daily doses ( DDDs ) per 100 patient days (PDs)—declined by 13.2 % during the intervention period ( 71.2 vs. 61.8 ) . There were significant increases in the susceptibilities of Pseudomonas aeruginosa to both amikacin and ciprofloxacin , and Serratia spp . to ciprofloxacin ( P < 0.05 ) , while all others remained stable . Conclusion This study reports positive responses to intensive antimicrobial control measures among health professionals within a Taiwanese medical center . Following the implementation of the intensive control program , both prescriptions and consumption levels of parenteral antimicrobials were reduced without compromising the clinical outcomes of patients , while the susceptibility patterns of bacterial organisms mostly remained stable . Long-term control of parenteral antimicrobials under such a program may well produce significant benefits for in patients through the overall rationalization of antimicrobial usage , leading to potential reductions in both the ␣ incidence of adverse effects and the burden of resistant organisms . A method of incorporating this intensive control program into a computerized prescription order system is currently under construction ABSTRACT Studies have shown benefits to patients from improved interventions involving antimicrobial therapy . The purpose of the present study was to evaluate prospect ively the impact of improved interventions by ( i ) the use of TheraTrac 2 , a computer software program which electronically links susceptibility testing results immediately to the pharmacy and alerts pharmacists of potential interventions , and ( ii ) the education of pharmacists involving microbiologic topics . The study group had the new intervention program . The control group had interventions performed the way that they had previously been done by manually review ing hard copies of susceptibility testing data . In a 5-month period , all in patients whose last names began with A to K were the study group ; in patients whose last names began with L to Z were controls . Three analyses were done ; one analysis ( analysis A ) involved only patients with interventions , one analysis ( analysis B ) involved all patients for whom antimicrobial testing was done and who were matched for diagnosis-related groups ( DRGs ) , regardless of whether an intervention occurred , and one analysis ( analysis C ) involved these DRG-matched patients by using severity-adjusted data . In analysis A , the study group had a 4.8 % decreased rate of mortality , an average of a 16.5-day decreased length of stay per patient , and $ 20,886 decreased variable direct costs per patient . None of these differences was statistically significant . In analysis B , the study patients had a 1.2 % higher mortality rate ( P = 0.741 ) , an average of a 2.7-day decreased length of stay per patient ( P = 0.035 ) , and $ 2,626 decreased variable direct costs per patient ( P = 0.008 ) . In analysis C , the study patients had a 1.4 % lower mortality rate , a 1.2-day decreased length of stay per patient , and $ 1,466 decreased variable direct costs per patient . In conclusion , the institution of this program caused substantial cost savings We tested a low-cost , multifaceted intervention program comprising formulary restriction measures , continued comprehensive education , and guidelines to improve in-hospital use of antibiotics and related costs . In a short-term analysis , total antibiotic consumption per patient admitted , which was expressed as defined daily doses ( DDD ) , decreased by 36 % ( P < .001 ) , and intravenous DDDs decreased by 46 % ( P < .01 ) . Overall expenditures for antibiotic treatment decreased by 53 % ( 100 US dollars per patient admitted ) . The 2 main cost-lowering factors were a reduction in prescription of antibiotics ( 35 % fewer treatments ; P < .0001 ) and more diligent use of 5 broad-spectrum antibiotics ( 23 % vs. 10 % of treatments ; P = .001 ) . Quality of care was not compromised . A pharmacy-based , prospect i ve , long-term surveillance of DDDs and costs over 4 years showed an ongoing effect . This comprehensive intervention program , which aim ed to reduce antibiotic consumption and costs , was highly successful and had long-lasting effects CONTEXT Prescribing practice s for otitis media are not consistent with current evidence -based recommendations . OBJECTIVE To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN R and omized , controlled trial . SETTING Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence -based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES Proportion of prescriptions for otitis media that were for < 10 days and frequency with which antibiotics were prescribed . RESULTS Intervention providers had a 34 % greater reduction in the proportion of time they prescribed antibiotics for < 10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition OBJECTIVES To assess the impact of a multifaceted educational intervention concerning treatment of infections in the nursing home setting . METHODS We used a cluster r and omized controlled trial . Fifty-eight nursing homes in Sweden were r and omly assigned either to educational intervention or control . The intervention consisted of small educational group sessions with nurses and physicians , feedback on prescribing , presentation of guidelines and written material s. The primary outcome was the proportion of quinolones prescribed for lower urinary tract infection ( UTI ) in women . Secondary outcomes were for all infections : number of UTIs per resident , proportion of recorded infections treated with an antibiotic , proportion of infections h and led by physicians as ' wait and see ' , and for lower UTI in women , proportion of nitrofurantoin . RESULTS Of the 58 nursing homes , 46 completed the study . A total of 702 and 540 infections were recorded pre- and post-intervention . The proportion of quinolones decreased significantly in the intervention and control groups , by -0.196 ( 9/93 to 36/123 ) and -0.224 ( 4/66 to 31/109 ) , respectively [ 95 % confidence interval ( CI ) -0.338 , -0.054 and -0.394 , -0.054 ] , but the difference between intervention and control groups was not significant , with an absolute risk reduction of 0.028 ( 95 % CI -0.193 , 0.249 ) . The changes in proportion of infections treated with antibiotics and proportion of infections h and led by physicians as ' wait and see ' was significant in comparison with controls : -0.124 ( 95 % CI -0.228 , -0.019 ) and 0.143 ( 95 % CI 0.047 , 0.240 ) . No intervention effect could be seen for the other outcomes . CONCLUSIONS The educational intervention had no effect on the primary outcome , but decreased the overall prescribing of antibiotics BACKGROUND Multidisciplinary antimicrobial utilization teams ( AUTs ) have been proposed as a mechanism for improving antimicrobial use , but data on their efficacy remain limited . OBJECTIVE To determine the impact of an AUT on antimicrobial use at a teaching hospital . DESIGN R and omized controlled intervention trial . SETTING A 953-bed , public , university-affiliated , urban teaching hospital . PATIENTS Patients who were given selected antimicrobial agents ( piperacillin-tazobactam , levofloxacin , or vancomycin ) by internal medicine ward teams . INTERVENTION Twelve internal medicine teams were r and omly assigned monthly : 6 teams to an intervention group ( academic detailing by the AUT ) and 6 teams to a control group that was given indication-based guidelines for prescription of broad-spectrum antimicrobials ( st and ard of care ) , during a 10-month study period . MEASUREMENTS Proportion of appropriate empirical , definitive ( therapeutic ) , and end ( overall ) antimicrobial usage . RESULTS A total of 784 new prescriptions of piperacillin-tazobactam , levofloxacin , and vancomycin were review ed . The proportion of antimicrobial prescriptions written by the intervention teams that was considered to be appropriate was significantly higher than the proportion of antimicrobial prescriptions written by the control teams that was considered to be appropriate : 82 % versus 73 % for empirical ( risk ratio [ RR ] , 1.14 ; 95 % confidence interval [ CI ] , 1.04 - 1.24 ) , 82 % versus 43 % for definitive ( RR , 1.89 ; 95 % CI , 1.53 - 2.33 ) , and 94 % versus 70 % for end antimicrobial usage ( RR , 1.34 ; 95 % CI , 1.25 - 1.43 ) . In multivariate analysis , teams that received feedback from the AUT alone ( adjusted RR , 1.37 ; 95 % CI , 1.27 - 1.48 ) or from both the AUT and the infectious diseases consultation service ( adjusted RR , 2.28 ; 95 % CI , 1.64 - 3.19 ) were significantly more likely to prescribe end antimicrobial usage appropriately , compared with control teams . CONCLUSIONS A multidisciplinary AUT that provides feedback to prescribing physicians was an effective method in improving antimicrobial use . Trial registration . Clinical Trials.gov identifier : NCT00552838 Abstract Objectives To assess the effectiveness of a multiple intervention aim ed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care . Design R and omised controlled trial . Subjects Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht , Netherl and s. Intervention The intervention consisted of group education meetings , with a consensus procedure on indication for and type of antibiotics and with training in communication skills ; monitoring and feedback on prescribing behaviour ; group education for assistants of general practitioners and pharmacists ; and educational material for patients . The control group did not receive any of these elements . Main outcome measures Antibiotic prescription rates for acute symptoms of the respiratory tract and patients ' satisfaction . Results 89 general practitioners completed the study ( 89 % ) . At baseline , prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group ( 27 % v 29 % , respectively ) . After nine months , the prescription rates in the intervention group fell to 23 % , whereas the control group 's rose to 37 % ( mean difference in change −12 % , 95 % confidence interval −18.9 % to −4.0 % ) . Multilevel analysis confirmed the results of the unadjusted analysis ( intervention effect −10.7 % , −20.3 % to −1.0 % ) . Patients ' satisfaction was high and did not differ in the two groups at baseline or after the intervention . Conclusions A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients . Further research should focus on the sustainability and cost effectiveness of this intervention The aim of this study was to explore the relationship between pharmacy size and the likelihood of obtaining antibiotics without medical prescription at a pharmacy . In 2008 in Catalonia , two actors presented three different cases in a r and omised sample of pharmacies and asked pharmacists for an antibiotic . Pharmacies were considered as small when having limited space with only one counter and a maximum of two professionals selling medicines , as medium sized with three or four attending professionals , and as large with a large selling space and more than four attending professionals . Of the 197 pharmacies visited , 88 ( 44.7 % ) were considered as small while only 25 ( 12.7 % ) were large . Antibiotics were obtained without a medical prescription in 89 ( 45.2 % ) pharmacies , mainly in small pharmacies ( 63.6 % ) , followed by medium-sized pharmacies ( 35.7 % ) and large pharmacies ( 12 % ) ( p<0.001 ) . Large pharmacies , that probably have a greater income , more closely followed the prevailing legislation of not selling antibiotics to patients without a medical prescription . This observation should now be confirmed in other countries where over-the-counter sales of antibiotics are prevalent and should be taken into account by programmes aim ing at achieving a more prudent use of antibiotics OBJECTIVES Assessing the efficacy of an educational intervention that aim ed to reduce unnecessary antibiotic prescriptions in primary care by motivating GPs to change their attitudes to communication and by empowering patients . METHODS One hundred and four GPs in North-Rhine/Westphalia-Lippe , Germany were cluster-r and omized into intervention and control . GPs r and omized to receive the intervention were visited by peers . The intervention strategy was focused on the communication within the encounter , not on sharing knowledge about antibiotic prescribing . Leaflets and posters were provided that aim ed at patient empowerment , thus enabling patients to raise the topic of antibiotic prescriptions themselves . RESULTS Eighty-six GPs ( 83 % ) remained in the study at 6 weeks and 61 GPs ( 59 % ) at 12 months . Antibiotic prescription rates within the control group were 54.7 % at baseline and 36.4 % within the intervention group at baseline . Generalized estimating equation models were applied . Baseline imbalances and confounding variables were controlled by adjustment . After the intervention , the ORs for the prescription of an antibiotic dropped to 0.58 [ 95 % CI : ( 0.43;0.78 ) , P < 0.001 ] after 6 weeks and were 0.72 [ 95 % CI : ( 0.54;0.97 ) , P = 0.028 ] after 12 months in the intervention group . In the control group , the ORs rose to 1.52 [ 95 % CI : ( 1.19;1.95 ) , P = 0.001 ] after 6 weeks and were 1.31 [ 95 % CI : ( 1.01;1.71 ) , P = 0.044 ] after 12 months ; these ORs correspond to an approximately 60 % relative reduction in antibiotic prescription rates at 6 weeks and a persistent 40 % relative reduction at 12 months . CONCLUSIONS An interventional strategy that focused on doctor-patient communication and patient empowerment is an effective concept to reduce antibiotic prescriptions in primary care BACKGROUND Acute pharyngitis is one of the most frequent reasons for a GP consultation , and in most cases an antibiotic is prescribed . AIM To determine the impact of rapid antigen detection testing ( RADT ) to identify group A beta haemolytic streptococcus in acute pharyngitis on the utilisation of antibiotics and appropriateness of their use . DESIGN AND SETTING Cluster r and omised controlled trial in primary care centres in Catalonia , Spain . METHOD Patients with acute pharyngitis aged 14 years or older with at least one Centor criterion ( fever , tonsillar exu date , tender enlarged anterior cervical lymph nodes , or absence of cough ) were recruited . Participant physicians were r and omly assigned to one of two study arms : an intervention group ( assigned to RADT ) and a control group ( following usual care , without RADT ) . RESULTS Of the 557 adults enrolled , 543 could be evaluated for analysis ( 281 [ 51.7 % ] in the intervention group and 262 [ 48.3 % ] in the control group ) . GPs without access to RADT were more likely to prescribe antibiotics compared with those who performed rapid tests ( 64.1 % versus 43.8 % , P<0.001 ) . The more Centor criteria the patients presented , the greater the number of antibiotics prescribed , regardless of whether RADT was available ( P<0.001 ) . Antibiotics were prescribed in 30.7 % of the cases with negative RADT results . Inappropriate antibiotic prescription was observed in 226 cases ( 43 % ) , and was significantly greater in the control than in the intervention group ( 60 % versus 26.9 % ; P<0.001 ) . CONCLUSION Even though more than 30 % of negative RADT results result ed in antibiotic prescribing , the study findings support the use of RADT in the consultation . This strategy has an important impact on reducing antibiotic prescription among adults with acute pharyngitis BACKGROUND Appropriate antibiotic treatment decreases mortality , while superfluous treatment is associated with antibiotic resistance . We built a computerized decision support system for antibiotic treatment ( TREAT ) targeting these outcomes . METHODS Prospect i ve cohort study comparing TREAT 's advice to physician 's treatment followed by a cluster r and omized trial comparing wards using TREAT ( intervention ) versus antibiotic monitoring without TREAT ( control ) . We included patients suspected of harbouring bacterial infections in three hospitals ( Israel , Germany and Italy ) . The primary outcome , appropriate antibiotic treatment , was assessed among patients with microbiologically documented infections ( MDI ) . Length of hospital stay , adverse events , mortality ( interventional trial ) and antibiotic costs ( both studies ) , including costs related to future antibiotic resistance , were compared among all included patients . RESULTS Among 1203 patients included in the cohort study ( 350 with MDI ) , TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians ( 70 % versus 57 % , P < 0.001 ) using less broad-spectrum antibiotics at half physicians ' antibiotic costs . The r and omized trial included 2326 patients , 570 with MDI . The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [ 73 % versus 64 % , odds ratio ( OR ) : 1.48 , 95 % confidence interval ( CI ) : 0.95 - 2.29 , intention to treat , adjusted for location and clustering ] . For patients treated according to TREAT 's advice in intervention wards , the difference with controls was highly significant ( OR : 3.40 , 95 % CI : 2.25 - 5.14 ) . Length of hospital stay , costs related to future resistance and total antibiotic costs were lower in intervention versus control wards . CONCLUSIONS TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment Abstract Objective To assess whether a multifaceted intervention can reduce the number of prescriptions for antimicrobials for suspected urinary tract infections in residents of nursing homes . Design Cluster r and omised controlled trial . Setting 24 nursing homes in Ontario , Canada , and Idaho , United States . Participants 12 nursing homes allocated to a multifaceted intervention and 12 allocated to usual care . Outcomes were measured in 4217 residents . Interventions Diagnostic and treatment algorithm for urinary tract infections implemented at the nursing home level using a multifaceted approach — small group interactive sessions for nurses , videotapes , written material , outreach visits , and one on one interviews with physicians . Main outcome measures Number of antimicrobials prescribed for suspected urinary tract infections , total use of antimicrobials , admissions to hospital , and deaths . Results Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes ( 1.17 v 1.59 courses ; weighted mean difference −0.49 , 95 % confidence intervals −0.93 to −0.06 ) . Antimicrobials for suspected urinary tract infection represented 28.4 % of all courses of drugs prescribed in the intervention nursing homes compared with 38.6 % prescribed in the usual care homes ( weighted mean difference −9.6 % , −16.9 % to −2.4 % ) . The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different ( 3.52 v 3.93 ; weighted mean difference −0.37 , −1.17 to 0.44 ) . No significant difference was found in admissions to hospital or mortality between the study arms . Conclusion A multifaceted intervention using algorithms can reduce the number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes BACKGROUND Antibiotic overuse is of great public health concern . This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use , specifically in classes known to promote antibiotic resistance among children in a community setting . METHODS We performed a cluster r and omized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practice s. The intervention was led by local leaders and engaged the participating physicians . It included physician focus group meetings , workshops , seminars , and practice campaigns . These activities focused on self-developed guidelines , improving parent and physician knowledge , diagnostic skills , and parent-physician communication skills that promoted awareness of antibiotic resistance . The main outcome measure was the change in annual antibiotic prescription rates ( APRs ) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians . The study comprised a 2-year pre-intervention period , a 3-year intervention period , and a 1-year follow-up period . Mixed-effect models were used to assess risk ratios to account for the clustered study design . RESULTS A decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year ( APR decrease among control physicians , 40 % ; APR decrease among intervention physicians , 22 % ; relative risk [ RR ] , .76 ; 95 % confidence interval [ CI ] , .75-.78 ) . This reduction crossed over all antibiotic classes but was most prominent for macrolides ( macrolide prescription rate among control physicians , 58 % ; macrolide prescription rate among intervention physicians , 27 % ; RR , .58 ; 95 % CI , .55-.62 ) . The effect was sustained during the 4 following years . CONCLUSIONS . Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained . CLINICAL TRIALS REGISTRATION NCT01187758 BACKGROUND Current regulations in Spain state that antibiotics can not be sold without a medical prescription . The objective of this study was to quantify the percentage of pharmacies selling antibiotics without an official medical prescription in Catalonia , Spain , by the simulation of 3 different clinical cases presented by actors . METHODS A prospect i ve study was performed from January through May 2008 . Three different cases were presented at pharmacies : sore throat , acute bronchitis , and a urinary tract infection . Three levels of dem and were used to convince the pharmacists to sell an antibiotic . RESULTS A total of 197 pharmacies were visited . Antibiotics were obtained from 55 ( 79.7 % ) of 69 pharmacies when a urinary tract infection was simulated , 24 ( 34.8 % ) of 69 pharmacies when a sore throat was simulated , and 10 ( 16.9 % ) of 59 pharmacies when acute bronchitis was simulated ( P < .001 ) . Among the pharmacies that sold antibiotics , the pharmacists provided an explanation as to the number of times per day the drug should be taken in 84.3 % , explained the duration of treatment in 68.7 % , and inquired about allergies prior to the sale of the antibiotic in only 16.9 % . Of the 108 pharmacies that did not sell the antibiotics , only 57 ( 52.8 % ) explained that they could not be given over the counter for health care reasons or to avoid antibiotic resistance . CONCLUSIONS These results demonstrate that , although illegal , the sale of antibiotics without a prescription continues in Spain . This should be taken into account by countries that are currently considering the possibility of making some antibiotics available over the counter OBJECTIVE To assess the effect of an educational intervention aim ed at optimizing antibiotic prescribing in long-term care ( LTC ) facilities . DESIGN Cluster r and omized , controlled trial . SETTING Eight public LTC facilities in the Montreal area . PARTICIPANTS Thirty-six physicians . INTERVENTION The educational intervention consisted of mailing an antibiotic guide to physicians along with their antibiotic prescribing profile covering the previous 3 months . Targeted infections were urinary tract , lower respiratory tract , skin and soft tissues , and septicemia of unknown origin . In the prescribing profile , each antibiotic was classified as adherent or nonadherent to the guide . Physicians in the experimental group received the intervention twice , 4 months apart , whereas physicians in the control group provided usual care . MEASUREMENTS Data on antibiotic prescriptions were collected over four 3-month periods : preintervention , postintervention I , postintervention II , and follow-up . A generalized estimating equation ( GEE ) model was used to compare the proportion of nonadherent antibiotic prescriptions of the experimental and control groups . RESULTS By the end of the study , nonadherent antibiotic prescriptions decreased by 20.5 % in the experimental group , compared with 5.1 % in the control group . Based on the GEE model , during postintervention II , physicians in the experimental group were 64 % less likely to prescribe nonadherent antibiotics than those in the control group ( odds ratio=0.36 , 95 % confidence interval=0.18 - 0.73 ) . CONCLUSION An educational intervention combining an antibiotic guide and a prescribing profile was effective in decreasing nonadherent antibiotic prescriptions . Repetition of the intervention at regular intervals may be necessary to maintain its effectiveness OBJECTIVES To study patterns of outpatient antibiotic use in the Great Tehran , in order to develop interventional strategies in rationalizing drug and especially antibiotic use . MATERIAL S AND METHODS Ten-percent r and om sample of all prescription belonging to practitioners in south of Tehran and kept in a data bank was sample d. Drug use indicators were determined in order to develop intervention program to promote rational drug use among practitioners in Tehran . Based on the values of drug use indicators , an interventional program , a program of continuing medical education ( CME ) targeting rational use of drugs , was design ed . Eighty general practitioners ( GPs ) who contributed to the data bank were selected and allocated to two groups , intervention group and control group . Each group contained 40 GPs . Drug use indicators were measured in each group three times ; before and in two intervals after the intervention . The indicators were compared before and after as well as between groups . RESULTS The drug use indicators determined through the data bank showed that 19 % of all prescribed drugs in data bank were antibiotics , which ranked second only after ' analgesics and CNS drugs ' with 24 % . The drug use indicators were improved in the intervention group ( the average number of drugs per encounter lowered from 4.3 + /- 0.5 pre-intervention to 3.6 + /- 0.1 six months thereafter , p value = 0.001 ) . The percentage of encounters with an antibiotic prescribed were lowered in intervention group compared with control group but the difference was not statistically significant . The intervention made a change to all other measured indicators but not all of them were statistically significant . CONCLUSIONS Irrational use of antibiotics can improve by appropriate educational intervention , using CME programs Objective A major problem with inappropriate use of antibiotics is the emergence of resistance . Thus , cost-effective interventional strategies are required to improve their use . This study aim ed to evaluate the effect of multifaceted interventions on prescribing practice s of antibiotics in health centers of Khartoum State , Sudan . Methods Twenty health centers were r and omly assigned to receive : ( 1 ) no intervention ; ( 2 ) audit and feedback ; ( 3 ) audit and feedback + seminar ; or ( 4 ) audit and feedback + academic detailing . A total of 1,800 patient encounters , 30 from each health center , were r and omly collected . The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice , dose and duration of therapy before the study and at 1 and 3 months post-intervention . Results In comparison to the control group , the prescriber targeted interventions involving audit and feedback , together with academic detailing ( 4 ) , reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . In addition , the mean number of encounters with an inappropriate antibiotic with respect to diagnosis , doses and / or duration of therapy was reduced by 5.3 and 5.9 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . For audit and feedback together with seminars ( 3 ) and for audit and feedback alone ( 2 ) , the corresponding reductions were 5.3 , 7.1 , 4.4 and 5.1 ( p<0.001 ) and 1.4 , 2.8 , 1.8 and 1.9 ( p>0.05 ) , respectively . Conclusion Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State , Sudan , are alarmingly high . Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practice s of antibiotics than audit and feedback alone Abstract BACKGROUND : Inappropriate use of antimicrobials to treat acute upper respiratory tract infections ( URIs ) , which usually have a viral etiology , contributes to emergence and spread of antimicrobial resistance in Streptococcus pneumoniae and other human bacterial pathogens . OBJECTIVE : To reduce antimicrobial use for management of acute URIs in adult and pediatric patients . DESIGN : Prospect i ve , nonr and omized , controlled trial . SETTING : Four primary care clinics within a staff model HMO in Detroit , Mich. PARTICIPANTS : Twenty-one primary care physicians at clinics where the educational intervention was implemented , and 9 primary care physicians at control clinics where no educational programs were implemented . MEASUREMENTS : Antibiotic prescribing for acute URIs during the baseline and study years among the intervention and control groups . RESULTS : A generalized linear mixed-effects model was used and showed that antimicrobial prescribing among the intervention group physicians decreased 24.6 % from the baseline to the postintervention period ( P<.0001 ) for both pediatric and adult medicine physicians . From the baseline to the study period , there was no significant decline in rates of antimicrobial prescribing by the control group of physicians ( pediatricians , P=.35 ; internists , P=.42 ) . The rates of decline in antimicrobial prescribing differed significantly between the intervention and control groups ( P<.0003 for pediatricians and P<.01 for Internists ) . CONCLUSIONS : An interactive , case-based educational program for physicians and their staff proved effective for reducing unwarranted prescribing of antibiotics in the treatment of URIs by primary care physicians in a Medicaid HMO setting Abstract Objective . Prescribing of broad spectrum antibiotics and antidepressants in general practice often does not accord with guidelines . The aim was to determine the effectiveness of educational outreach in improving the prescribing of selected antibiotics and antidepressants , and whether the effect is sustained for two years . Design . Single blind r and omized trial . Setting . Twenty-eight general practice s in Leicestershire , Engl and . Intervention . Educational outreach visits were undertaken , tailored to barriers to change , 14 practice s receiving visits for reducing selected antibiotics and 14 for improving antidepressant prescribing . Main outcome measures . Number of items prescribed per 1000 registered patients for amoxicillin with clavulanic acid ( co-amoxiclav ) and quinolone antibiotics , and average daily quantities per 1000 patients for lofepramine and fluoxetine antidepressants , measured at the practice level for six-month periods over two years . Results . There was no effect on the prescribing of co-amoxiclav , quinolones , or fluoxetine , but prescribing of lofepramine increased in accordance with the guidelines . The increase persisted throughout two years of follow-up . Conclusion . A simple , group-level educational outreach intervention , design ed to take account of identified barriers to change , can have a modest but sustained effect on prescribing levels . However , outreach is not always effective . The context in which change in prescribing practice is being sought , the views of prescribers concerning the value of the drug , or other unrecognised barriers to change may influence the effectiveness of outreach Objective To evaluate the impact of pharmacist interventions on antibiotic use in in patients with respiratory tract infections in a tertiary hospital in China . Method Two independent respiratory wards were r and omized into control and intervention group . Between July 2009 and April 2010 , all in patients diagnosed with respiratory tract infections were enrolled . Pharmacist interventions were performed on the physicians in the intervention group . The total cost of hospitalization , cost of antibiotics , length of hospital stay and the scores of 6 items of inappropriate antibiotic use ( including indication , choice , dosage , dosing schedule , duration and conversion ) were analyzed . Results The total costs of hospitalization in the intervention group were significant lower compared to the control group ( $ 1442.3 ± 684.9 vs. $ 1729.6 ± 773.7 , P < 0.001 ) , as well as the cost of antibiotics ( $ 832.0 ± 373.0 vs. $ 943.9 ± 412.0 , P = 0.01 ) , and the patients required shorter length of hospital stay ( 14.2 ± 6.2 vs. 15.8 ± 6.0 days , P = 0.03 ) . The scores with respect to the 6 items of inappropriate antibiotic use were all lower in the intervention group than in the control group . Conclusions Pharmacist interventions , interacted directly with the physicians at ward level , could play an important role in optimizing antibiotic use , thus lead to the reduction in patients ’ length of hospital stay and health care cost BACKGROUND AND OBJECTIVE Judicious use of antibiotics is essential considering the growth of antimicrobial resistance and escalating costs in health care . This intervention study used treatment guidelines to improve antibiotic therapy by changing prescribing practice . METHODS A before-after intervention study was performed in a 550-bed tertiary care teaching hospital in Switzerl and , with an additional follow-up analysis 1 year later . The pre-intervention phase included chart analysis of current antibiotic use in 100 consecutive patients from the representative medical and surgical wards included in the study . Treatment guidelines were defined , taking into account published guidelines , the local antibacterial sensitivity of the pathogens , and the hospital antibiotic formulary defined by the drug and therapeutics committee . The guidelines were presented to the medical residents on a pocket card . They were informed and educated by the pharmacist ( intervention ) . In the post-intervention phase immediately after the instruction , and in the follow-up phase 1 year later , a prospect i ve analysis of antibiotic prescription was performed by chart review of 100 antibacterial treatments in consecutive patients to detect changes in antibiotic prescribing ( treatment ) and to determine whether these changes were sustained . RESULTS The pre-intervention review of antibiotic use showed the need for therapy improvements in urinary tract infections ( UTI ) and hospital-acquired pneumonia ( HAP ) . In the post-intervention phase 100 % of UTI were treated as recommended , compared to 30 % before the intervention ( P < 0.001 ) . The follow-up analysis showed a decrease in guideline adherence to 39 % in patients with UTI . Before implementation of the clinical guidelines , HAP was inappropriately treated like community-acquired pneumonia ( CAP ) . Immediately after the intervention , 50 % of HAP patients were treated as recommended , and 1 year later ( follow-up phase ) 56 % of HAP patients received the recommended antibiotic medication . This change in prescription practice was significant ( P < 0.05 ) . CONCLUSION Antibiotic treatment guidelines for the infections most commonly occurring in hospitalized patients result ed in a significant increase in appropriate antibiotic use . The program was successful in changing prescription practice and achieved a sustained optimization of HAP therapy . Implementing , teaching and monitoring treatment guidelines can have a major impact on patient care OBJECTIVES To assess the effect of a tailored professional intervention , including academic detailing , on antibiotic prescribing for acute cough . METHODS In a cluster-r and omized controlled before and after study 85 Flemish GPs included adult patients with acute cough consulting in the periods February-April 2000 and 2001 . The intervention consisted of a clinical practice guideline for acute cough , an educational outreach visit and a postal reminder to support its implementation in January 2001 . Antibiotic prescribing rates and patients ' symptom resolution were the main outcome measures . RESULTS Thirty-six of 42 GPs received the intervention and 35 of 43 GPs served as controls ; 1503 patients were eligible for analysis . Only in the intervention group were patients less likely to receive antibiotics after the intervention [ OR(adj ) ( 95 % CI)=0.56 ( 0.36 - 0.87 ) ] . Prescribed antibiotics were also more in line with the guideline in the intervention group [ 1.90 ( 0.96 - 3.75 ) ] and less expensive from the perspective of the National Sickness and Invalidity Insurance Institute [ MD(adj ) ( 95 % CI)= Euro -6.89 [ -11.77-(-2.02 ) ] ] . No significant differences were found between the groups for the time to symptom resolution . CONCLUSIONS An (inter)actively delivered tailored intervention implementing a guideline for acute cough is successful in optimizing antibiotic prescribing without affecting patients ' symptom resolution . Further research efforts should be devoted to cost-effectiveness studies of such interventions OBJECTIVES . Reducing unnecessary antibiotic use , particularly among children , continues to be a public health priority . Previous intervention studies have been limited by size or design and have shown mixed results . The objective of this study was to determine the impact of a multifaceted , community-wide intervention on overall antibiotic use for young children and on use of broad-spectrum agents . In addition , we sought to compare the intervention 's impact on commercially and Medicaid-insured children . METHODS . We conducted a controlled , community-level , cluster-r and omized trial in 16 nonoverlapping Massachusetts communities , studied from 1998 to 2003 . During 3 years , we implemented a physician behavior-change strategy that included guideline dissemination , small-group education , frequent up date s and educational material s , and prescribing feedback . Parents received educational material s by mail and in primary care practice s , pharmacies , and child care setting s. Using health-plan data , we measured changes in antibiotics dispensed per person-year of observation among children who were aged 3 to < 72 months , resided in study communities , and were insured by a participating commercial health plan or Medicaid . RESULTS . The data include 223135 person-years of observation . Antibiotic-use rates at baseline were 2.8 , 1.7 , and 1.4 antibiotics per person-year among those aged 3 to < 24 , 24 to < 48 , and 48 to < 72 months , respectively . We observed a substantial downward trend in antibiotic prescribing , even in the absence of intervention . The intervention had no additional effect among children aged 3 to < 24 months but was responsible for a 4.2 % decrease among those aged 24 to < 48 months and a 6.7 % decrease among those aged 48 to < 72 months . The intervention effect was greater among Medicaid-insured children and for broad-spectrum agents . CONCLUSIONS . A sustained , multifaceted , community-level intervention was only modestly successful at decreasing overall antibiotic use beyond substantial secular trends . The more robust impact among Medicaid-insured children and for specific medication classes provides an argument for specific targeting of re sources for patient and physician behavior change OBJECTIVES To compare two strategies for implementing guidelines for nursing home-acquired pneumonia ( NHAP ) and to measure outcomes associated with treatment in accordance with the guidelines . DESIGN R and omized controlled trial . SETTING Ten skilled nursing facilities ( SNFs ) from a single metropolitan area . PARTICIPANTS Patients with an episode of pneumonia acquired more than 3 days after admission to SNF ( N = 350 ) : 226 preintervention episodes of pneumonia and 116 postintervention episodes . INTERVENTIONS Multi-faceted education intervention including small-group consensus process limited to physicians and a similar intervention that included physicians and nurses within r and omly selected SNFs . MEASUREMENTS Antibiotic use at diagnosis compared with the guidelines , hospital admission , severity of pneumonia , and 30-day mortality . RESULTS Data were complete for 344 episodes of NHAP . For the preintervention group ( n = 226 ) , 62.2 % ( 79/127 ) of the episodes were treated with parenteral antibiotics ( PA ) when PA were recommended by the guidelines and 57.6 % ( 57/99 ) of episodes were treated with oral antibiotics ( OA ) when OA were indicated by the guidelines . Postintervention , treatment with PA and OA according to the guidelines was not significantly different between the two groups of r and omized SNFs . A multivariate analysis comparing PA use pre- and postintervention for all SNFs , adjusted for variation in the frequency and severity of pneumonia , found significantly more of the postintervention episodes were treated with PA in accordance with the guidelines ( P < .02 ) . A preintervention significant difference in 30-day mortality observed between episodes with indications for PA ( 37.8 % ( 48/127 ) ) and episodes with indications for OA ( 6.1 % ( 6/99 ) ) ( P < .001 ) was not present postintervention ( 11.5 % ( 6/52 ) ; ( 23.8 % ( 15/64 ) ; P = .06 ) . There was no significant difference in 30-day mortality preintervention and postintervention for episodes with guideline indications for OA ( P = .35 ) or for PA ( P = .05 ) ( P = .16 for multivariate analysis ) . The difference in PA use was not associated with significant differences in hospital admissions for episodes on NHAP . CONCLUSION The increase in the use of PA provides evidence that care within SNFs can be significantly changed using st and ard quality improvement techniques . Use of the guidelines did not significantly affect mortality . The addition of a practical severity of NHAP model or a change in reimbursement structure may enhance the guidelines ' impact on hospitalization for NHAP . The financial benefits available with use of the guidelines will be limited unless the guidelines contribute to a reduction in rates of hospitalization OBJECTIVES : To measure and improve antibiotic use for acute respiratory tract infections ( ARIs ) in the elderly . DESIGN : Prospect i ve , nonr and omized controlled trial . SETTING : Ambulatory office practice s in Denver metropolitan area ( n=4 intervention practice s ; n=51 control practice s ) . PARTICIPANTS : Consecutive patients enrolled in a Medicare managed care program who were diagnosed with ARIs during baseline ( winter 2000/2001 ) and intervention ( winter 2001/2002 ) periods . A total of 4,270 patient visits were analyzed ( including 341 patient visits in intervention practice s ) . INTERVENTION : Appropriate antibiotic use and antibiotic resistance educational material s were mailed to intervention practice households . Waiting and examination room posters were provided to intervention office practice s. MEASUREMENTS : Antibiotic prescription rates , based on administrative office visit and pharmacy data , for total and condition-specific ARIs . RESULTS : There was wide variation in antibiotic prescription rates for ARIs across unique practice s , ranging from 21 % to 88 % ( median=54 % ) . Antibiotic prescription rates varied little by patient age , sex , and underlying chronic lung disease . Prescription rates varied by diagnosis : sinusitis ( 69 % ) , bronchitis ( 59 % ) , pharyngitis ( 50 % ) , and nonspecific upper respiratory tract infection ( 26 % ) . The educational intervention was not associated with greater reduction in antibiotic prescription rates for total or condition-specific ARIs beyond a modest secular trend ( P=.79 ) . CONCLUSION : Wide variation in antibiotic prescription rates suggests that quality improvement efforts are needed to optimize antibiotic use in the elderly . In the setting of an ongoing physician intervention , a patient education intervention had little effect . Factors other than patient expectations and dem and s may play a stronger role in antibiotic treatment decisions in elderly population PURPOSE The aim of this study is to evaluate the effectiveness of academic detailing ( AD ) plus postal prescribing feedback versus postal prescribing feedback alone in reducing : ( i ) the overall rate of antibiotic ; and ( ii ) proportion of second-line antibiotic prescribing . In addition , the cost-effectiveness of an outreach prescriber adviser service versus a postal prescribing feedback service was evaluated . METHODS Volunteer general practitioner practice s ( n = 98 ) were r and omized to receive prescribing feedback via postal bulletin ( PB ) ( n = 50 ) or academic detailing plus postal bulletin ( AD ) ( n = 48 ) . Data analysis was based on the HSE- primary care reimbursement service ( HSE-PCRS ) prescribing data base . Regression ( beta ) coefficients , indicating proportion change in prescribing per month , and 95 % confidence intervals ( CIs ) are presented . The cost-effectiveness ratio was calculated from the total cost of the intervention divided by percentage change in antibiotic prescribing in AD versus PB group . RESULTS Immediately post intervention PB ( beta = -0.02 , 95 % CI -0.04 , -0.001 ) and AD ( beta = -0.02 , 95 % CI -0.03 , -0.001 ) practice s significantly decreased overall antibiotic prescribing . Second-line antibiotic prescribing was also significantly decreased by 2 - 3 % in both groups . However , there were no significant differences in antibiotic prescribing between the r and omized groups in the immediate or long-term post-intervention period . In the cost-effectiveness analysis a postal prescribing feedback service would cost euro 88 per percentage change in prescribing practice compared with euro 778 for a prescriber adviser service . CONCLUSION Prescribing feedback significantly reduced overall and second-line antibiotic prescribing , but academic detailing was not significantly more effective than postal bulletin in changing antibiotic prescribing practice Private pharmacies are the first line of health care in many communities , commonly selling antibiotics in small doses and prescription-only drugs such as steroids without medical supervision . The aim was to study the effectiveness of a multi-faceted intervention on the dispensing practice s of drug sellers in Hanoi and Bangkok . The study was a r and omized , controlled trial with 68 Hanoi and 78 Bangkok pharmacies , r and omly selected and assigned for intervention and control . Behaviour was assessed by five simulated client visits per pharmacy per dispensing practice , at baseline and a month or more after each intervention . Three three-month interventions were implemented sequentially with four months in between : enforcement of regulations with local inspectors visiting to emphasize the importance of prescription-only medicine legislation ; education , performed face-to-face in Hanoi and by a large group in Bangkok ; and peer review , voluntary in Bangkok and compulsory in Hanoi . The intervention result ed in significant improvements in Hanoi , reducing the dispensing of illegal steroids ( 29 % vs. 62 % ) and low dose antibiotics ( 69 % vs. 90 % ) , sustained by means of the peer review ( 17 % vs. 57 % steroids and 71 % vs. 95 % antibiotics ) , and in fewer dispensers asking no questions and giving no advice ( 11 % vs. 30 % steroids and 51 % vs. 81 % antibiotics ) . The only significant improvement in Bangkok was the reduction in illegally dispensing steroids ( 25 % vs. 44 % ) after the regulatory intervention . In Bangkok , fewer of those in the group who volunteered for the peer review asked no questions and gave no advice for low-dose antibiotics requests after the peer review ( 58 % vs. 81 % ) . A multi-component intervention can have a profound effect in changing dispensers ' behaviour , but the effect is dependant on the context and the method of implementation . Possible reasons for differences are discussed OBJECTIVES Emergence of multiresistant Gram-negative organisms in intensive care units ( ICUs ) throughout the world is a concerning problem . Therefore we undertook a study to follow the resistance patterns of the most common clinical ly isolated Gram-negative organisms within our ICU following an antibiotic stewardship intervention to evaluate whether a reduction in broad-spectrum antibiotics improves local antibiotic resistance patterns . METHODS This prospect i ve study was conducted over a 7 year period within an ICU at a tertiary teaching hospital in Melbourne , Australia . All clinical ly isolated Gram-negative organisms were identified and extracted from the hospital pathology system . Three monthly antibiograms were created . The pre-interventional period occurred between January 2000 and June 2002 ( 10 quarters ) and the post-interventional period was defined from July 2002 to December 2006 ( 18 quarters ) . Segmented linear regression was used to analyse for a difference in the rates of change in susceptibility . RESULTS A total of 2838 Gram-negative organisms were isolated from clinical sites from ICU patients during the study period . There was significant improvement in susceptibility of Pseudomonas to imipenem 18.3%/year [ 95 % confidence interval ( CI ) : 4.9 - 31.6 ; P = 0.009 ] and gentamicin 11.6%/year ( 95 % CI : 1.8 - 21.5 ; P = 0.02 ) compared with the pre-intervention trend . Significant changes in the rates of gentamicin and ciprofloxacin susceptibility were also observed in the inducible Enterobacteriaceae group although these were less clinical ly significant . CONCLUSIONS This study demonstrates improved antibiotic susceptibility of ICU Gram-negative isolates including Pseudomonas following an intervention aim ed at reducing broad-spectrum antibiotics BACKGROUND Inappropriate use of antibiotics is a major clinical problem and public health concern . We developed and implemented a pilot hospitalist-delivered academic detailing intervention to improve the patterns of antibiotic prescribing for in patients . OBJECTIVE To improve antibiotic prescribing patterns on the hospitalist service of an academic medical center . DESIGN , SETTING , AND PARTICIPANTS Hospitalist practitioners were recruited to participate in this pre- and postintervention pilot study at Johns Hopkins Bayview Medical Center ( JH BMC ) . Public health principles for creating a conceptual framework based on behavioral change theory were used in developing the intervention . METHODS Antibiotic prescribing patterns of 17 hospitalist practitioners were retrospectively review ed . Antimicrobial prescriptions were classified as appropriate , effective but inappropriate , or inappropriate . A profile was assembled for each hospitalist , and an academic detailing intervention session was arranged . The session review ed inappropriate prescribing practice s as well as current practice guidelines . After the detailing meeting , the prescribing patterns of the hospitalists were followed prospect ively . MAIN OUTCOME MEASURES The main outcome measures were the proportions of antibiotics prescribed inappropriately before the intervention , during the detailing period , and after the intervention . RESULTS Seventeen hospitalist practitioners who participated in the study . A total of 247 prescriptions were review ed in the preintervention and 129 prescriptions in the postintervention period . Prior to academic detailing , 43 % ( 95 % CI 37%-49 % ) of the prescriptions were appropriate and 57 % ( 95 % CI 51%-63 % ) were inappropriate . After the intervention , 74 % ( 95 % CI 65%-81 % ) of the prescriptions were appropriate and 26 % ( 95 % CI 19%-35 % ) were inappropriate ; P < .0001 . CONCLUSIONS A carefully planned and method ically executed intervention can result in behavior change , even among busy hospitalists . The academic detailing intervention , which included a practice -based learning component , improved antibiotic prescribing practice s of hospitalists at JH BMC Sc and J Prim Health Sci 2002;20:000 - 000 . ISSN 0281 - 3432 Objective - To evaluate the impact of feedback on the prescribing of antibiotics supplementary to clinical guidelines in the treatment of respiratory tract infections . Design - R and omised , controlled trial with GPs allocated to one of two groups . The first group received clinical guidelines on the treatment of respiratory tract infections plus postal feedback with aggregated data on their prescribing patterns for antibiotics . The second group served as controls for the first group and received the guidelines only . Setting - 299 GPs representing 181 practice s with 455 843 listed patients in the County of Funen , Denmark . Main outcome measures - Effects on GP prescribing patterns were measured by means of a prescription data base and followed for a period of 2 years with 2 outcome measures : 1 ) the antibiotic prescription rate and 2 ) the fraction of prescriptions for narrow-spectrum antibiotics . Results - The addition of feedback had no impact on GP prescribing patterns . Conclusion - Postal disseminated prescriber feedback in addition to a clinical guideline on the diagnosis and treatment of respiratory tract infections does not influence GP prescribing patterns . Interventions aim ed at improving performance in general practice should go beyond just giving GPs information on whether they are living up to st and ards BACKGROUND Antibiotic prescribing for upper respiratory tract infections ( URTIs ) is widespread , is often inappropriate , and may contribute to antibiotic resistance among community-acquired pathogens , such as Streptococcus pneumoniae . METHODS A multifaceted intervention involving health care professionals and patients was introduced to a small rural Utah community and included the repetitive use of printed diagnostic and treatment algorithms by professionals . Data on the quantity and class of antibiotic prescribing , which were collected from multiple sources , were measured for the intervention period ( from January through June ) in 2001 and compared with data for the baseline period during the same months in 2000 . RESULTS Medicaid cl aims data revealed that the percentage of patients in the community who received antibiotics for URTIs during the intervention period was 15.6 % less than that for the baseline period , whereas the percentage in the rest of rural Utah was relatively stable , with a 1.5 % decrease ( P=.006 ) . The greatest impact of the intervention was on prescribing for acute bronchitis ( decreases of 56.1 % and 1.7 % in the community and rural Utah , respectively ; P=.024 ) and on prescribing of macrolides ( decreases of 13.4 % and 0.2 % in the community and rural Utah , respectively ; P<.001 ) . Community pharmacy data likewise revealed a 17.5 % decrease in the rate of antibiotic prescribing during the intervention period ( P<.001 ) , with the largest decrease observed for macrolide prescribing ( 50.9 % ; P<.001 ) . Chart review data , in contrast , revealed no significant decrease in the percentage of patients with URTI who were prescribed an antibiotic ( 3.8 % ; P=.49 ) , although there was a significant decrease of 11.2 % in macrolide use ( P=.045 ) . CONCLUSIONS A multifaceted intervention involving the repetitive use of printed algorithms result ed in modest improvements in antibiotic prescribing for outpatient URTIs , although one data source did not corroborate this . However , macrolide prescribing decreased sharply , irrespective of the source of data BACKGROUND Excessive and inappropriate use of antibiotics has been identified as a leading cause of the emergence of multiply resistant strains of pneumococci . OBJECTIVE To examine the effects of academic detailing and a parental education program on community pediatricians ' prescription of antibiotics for young children . METHODS Physician leaders in study practice s prepared educational modules and presented the modules to their practice s. The control groups received only practice -specific report cards . Using a time-series analysis , we collected data on office visits and antibiotic prescriptions filled between May 1 , 2000 , and April 30 , 2001 ( baseline period ) , and between May 1 , 2001 , and April 30 , 2002 ( intervention period ) . Antibiotic prescription rate was defined as the ratio of antibiotic prescriptions filled to the number of office visits . RESULTS The antibiotic prescription rate decreased to 0.82 ( 95 % confidence interval , 0.71 - 0.95 ) of the baseline rate for the study group ( 6 practice s ) and to 0.86 ( 95 % confidence interval , 0.77 - 0.95 ) of the baseline for the control group ( 5 practice s ) . Similar patterns for antibiotic prescription rates were seen for study and control groups both before and after the intervention . Wide variations in prescription rates were observed among the practice s , but , in general , the control practice s had lower antibiotic prescribing rates during both the baseline and the intervention periods . Use of amoxicillin increased slightly in the study group and decreased slightly in the control group . The use of cephalosporins increased slightly in both groups . CONCLUSION Overall , academic detailing appeared to be no more effective in reducing antibiotic use than the practice -specific report cards alone OBJECTIVE Inappropriate use of antibiotics is common in primary care , and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance . The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities . METHODS A nonr and omized , controlled , community intervention trial was conducted in northern Wisconsin Clinicians . Clinic staff received educational material s and small-group presentations ; material s were distributed to parents through clinics , child care facilities , and community organizations . Prescribing data were analyzed for 151 clinicians who provided primary pediatric care ; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period ( January-June 1997 ) and for 472 children in the postintervention period ( January-June 1998 ) . RESULTS The median number of solid antibiotic prescriptions per clinician declined 19 % in the intervention region and 8 % in the control region . The median number of liquid antibiotic prescriptions per clinician declined 11 % in the intervention region , compared with an increase of 12 % in the control region . Retail antibiotic sales declined in the intervention region but not in the control region . Among participating children in child care facilities , there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions . CONCLUSIONS A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing , but in child care facilities , there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae . Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility The objective of this study was to assess the effects of a multicomponent intervention on private pharmacy practice . From 641 private pharmacies in Hanoi , 68 pharmacies were r and omly selected and matched into 34 pairs . Each pair consisted of a control and an intervention pharmacy . Three interventions were applied sequentially : Regulatory enforcement , Education , and Peer influence . Four tracer conditions were selected : uncomplicated acute respiratory infection ( ARI ) , sexually transmitted disease ( STD ) , requesting the prescription-only drugs prednisolone , and a short course of cefalexin . Practice was assessed through the Simulated Client Method ( SCM ) . The intervention pharmacies improved significantly compared to the control pharmacies ( P < .05 ) in all tracer conditions . For ARI , antibiotic dispensing decreased ( P < .02 ) and questions regarding breathing increased ( P < .01 ) . For STD , advice to go to the doctor and dispensing the correct syndromic treatment increased ( P < .01 ) . Dispensing of prednisolone and cefalexin decreased ( P < .01 ) and prescription requests increased ( P < .01 ) . Our conclusion is that it is possible to improve private pharmacy practice with a multicomponent intervention Objectives .The objective of the study was to evaluate the effectiveness of 2 educational strategies aim ed at improving prescribing st and ards in primary care . Methods .A pragmatic controlled trial was design ed ; the study population included general and family practitioners in Galicia ( northwestern Spain ) divided into 3 study groups : a one-to-one education group ( n = 98 ) , a by-group education group ( n = 92 ) , and a control group ( n = 405 ) . The educational intervention included explicit recommendations for selecting nonsteroidal anti-inflammatory drugs ( NSAIDs ) for inflammation signs . Some of the subjects were given reminders . Mixed-effect linear models were applied to data analysis . Analyses were done by intention-to-treat . The dependent variable is a rate with a numerator that is the number of prescribed units of the NSAIDs recommended during intervention ; the denominator is the total number of prescribed units of the NSAID total . Results .One-to-one education obtained an average prescribing behavior improvement of 6.5 % ( P < 0.001 ) in the 9 months after intervention . In the education group , the average improvement was 2.4 % ( P < 0.05 ) for the same period . Statistically significant differences were observed between the group intervention and one-to-one groups . The reminder increased significantly the effectiveness of the one-to-one intervention . Conclusions .A single , short educational session to primary care doctors can improve their prescribing st and ards during long periods of ≥9 months . Of the 2 strategies followed in the trial , one-to-one education has shown to be the most effective . Results also show that the effectiveness of these interventions increases when presented together with written material OBJECTIVE To test whether an educational outreach intervention for families and physicians , based on the Centers for Disease Control and Prevention ( CDC ) principles of judicious antibiotic use , decreases antimicrobial drug prescribing for children younger than 6 years old . Setting . Twelve practice s affiliated with 2 managed care organizations ( MCOs ) in eastern Massachusetts and northwest Washington State . Patients . All enrolled children younger than 6 years old . METHODS Practice s stratified by MCO and size were r and omized to intervention or control groups . The intervention included 2 meetings of the practice with a physician peer leader , using CDC-endorsed summaries of judicious prescribing recommendations ; feedback on previous prescribing rates were also provided . Parents were mailed a CDC brochure on antibiotic use , and supporting material s were displayed in waiting rooms . Automated enrollment , ambulatory visit , and pharmacy cl aims were used to determine rates of antibiotic courses dispensed ( antibiotics/person-year ) during baseline ( 1996 - 1997 ) and intervention ( 1997 - 1998 ) years . The primary analysis ( for children 3 to < 36 months and 36 to < 72 months ) assessed the impact of the intervention among children during the intervention year , controlling for covariates including patient age and baseline prescription rate . Confirmatory analyses at the practice level were also performed . RESULTS The practice s cared for 14 468 and 13 460 children in the 2 study years , respectively ; 8815 children contributed data in both years . Sixty-two percent of antibiotic courses were dispensed for otitis media , 6.5 % for pharyngitis , 6.3 % for sinusitis , and 9.2 % for colds and bronchitis . Antibiotic dispensing for children 3 to < 36 months old decreased 0.41 antibiotics per person-year ( 18.6 % ) in intervention compared with 0.33 ( 11.5 % ) in control practice s. Among children 36 to < 72 months old , the rate decreased by 0.21 antibiotics per person-year ( 15 % ) in intervention and 0.17 ( 9.8 % ) in control practice s. Multivariate analysis showed an adjusted intervention effect of 16 % in the younger and 12 % in the older age groups . The direction and approximate magnitude of effect were confirmed in practice -level analyses . CONCLUSIONS A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practice s , even in the setting of substantial secular trends toward decreased prescribing . Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse PURPOSE In an environment of multiple campaigns promoting judicious antibiotic use in children , identification of effective strategies is important . We assessed physician responses to a community-level intervention with respect to antibiotic prescribing , related practice s , and perceived effectiveness . METHODS This study was a mixed qualitative and quantitative evaluation of a r and omized controlled community-wide educational intervention in 16 Massachusetts communities . Physicians in intervention communities received locally endorsed guidelines , group educational sessions , and biweekly newsletters . Parents simultaneously received material s in physicians ’ offices and by mail . After the intervention , we conducted a mailed physician survey and individual interviews to assess the impact of the intervention . We compared survey responses for intervention and control physicians , and we analyzed interview transcripts to provide in-depth information about selected topics . RESULTS Among survey respondents ( n = 168 ) , 91 % of intervention and 4 % of control physicians reported receiving intervention material s. Physicians received information from multiple other sources . More intervention than control physicians reported decreased antibiotic prescribing from 2000–2003 ( 75 % vs 58 % , P = .03 ) , but there were no differences between groups in knowledge , attitudes , or behaviors favoring judicious antibiotic use . Both groups were concerned about antibiotic resistance and reported room to reduce their own prescribing . Interviewed physicians suggested frequent repetition of messages , brief written material s on specific topics for themselves and patients , and promotion in the mass media as the most effective strategies to reduce prescribing . CONCLUSIONS In multiple communities an intervention in physician offices to promote judicious antibiotic prescribing reached its intended audience , but physicians ’ self-reported attitudes and practice s were similar in intervention and control communities . Campaigns that repeat brief , consistent reminders to multiple stakeholder groups may be most effective at assuring judicious antibiotic use |
13,948 | 21,824,383 | Conclusions CCDSSs inconsistently improved process of care measures and seldomly improved patient outcomes .
Lack of clear patient benefit and lack of data on harms and costs preclude a recommendation to adopt CCDSSs for drug therapy management | Background Computerized clinical decision support systems ( CCDSSs ) for drug therapy management are design ed to promote safe and effective medication use .
Evidence documenting the effectiveness of CCDSSs for improving drug therapy is necessary for informed adoption decisions .
The objective of this review was to systematic ally review r and omized controlled trials assessing the effects of CCDSSs for drug therapy management on process of care and patient outcomes .
We also sought to identify system and study characteristics that predicted benefit . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions UNLABELLED What is already known about this subject . Computerized prompts and reminders have been shown to be effective in changing the behaviour of health professionals in a variety of setting s. There is little literature describing or evaluating electronic decision-support for pharmacists . What this study adds . An electronic prompt in dispensing software for a targeted clinical intervention has a significant effect on pharmacists ' behaviour . A markedly increased rate of recording and performing the targeted clinical intervention was found . The effect of the prompt reduces markedly once the prompt is deactivated . AIM To evaluate the effect of an electronic prompt in dispensing software on the frequency of clinical interventions recorded by community pharmacists . METHOD An electronic decision-support prompt identifying patients for a targeted proactive clinical intervention was developed and implemented . Each time an oral antidiabetic agent was dispensed , a prompt was displayed reminding pharmacists to discuss the suitability of aspirin therapy in eligible patients with diabetes . The prompt was r and omly assigned to 31 of 52 metropolitan pharmacies in Melbourne ( Australia ) for 6 weeks , with the remaining pharmacies as controls . RESULTS One hundred and fifty pharmacists in 52 pharmacies recorded a total of 2396 clinical interventions at an intervention rate of 0.92 interventions per 100 patients [ 95 % confidence interval ( CI ) 0.58 , 1.23 ] . Pharmacists recorded a total of 201 target interventions related to aspirin therapy in diabetes at an intervention rate of 2.55 interventions per 100 diabetic patients ( 95 % CI 0.85 , 4.24 ) . All of the targeted clinical interventions were recorded in the prompt arm ; no targeted interventions were recorded in the control group . The effect of the prompt decreased over the study period and was not maintained after prompt deactivation . CONCLUSION An electronic prompt significantly increased pharmacists ' recording of the targeted clinical intervention in diabetic patients . An electronic decision-support prompt has significant potential to promote community pharmacists ' contribution to the quality use of medicines BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions Background — Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system . However , r and omized trials comparing these methods in a clinical setting are lacking . We studied the effect of both alerting and on-dem and decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners . Methods and Results — In a clustered r and omized trial design , 38 Dutch general practice s ( 77 physicians ) and 87 886 of their patients ( 39 433 men 18 to 70 years of age and 48 453 women 18 to 75 years of age ) who used the ELIAS electronic health record participated . Each practice was assigned to receive alerts , on-dem and support , or no intervention . We measured the percentage of patients screened and treated after 12 months of follow-up . In the alerting group , 65 % of the patients requiring screening were screened ( relative risk versus control=1.76 ; 95 % confidence interval , 1.41 to 2.20 ) compared with 35 % of patients in the on-dem and group ( relative risk versus control=1.28 ; 95 % confidence interval , 0.98 to 1.68 ) and 25 % of patients in the control group . In the alerting group , 66 % of patients requiring treatment were treated ( relative risk versus control=1.40 ; 95 % confidence interval , 1.15 to 1.70 ) compared with 40 % of patients ( relative risk versus control=1.19 ; 95 % confidence interval , 0.94 to 1.50 ) in the on-dem and group and 36 % of patients in the control group . Conclusion — The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners BACKGROUND A cluster r and omized trial of tailored interventions to support the implementation of guidelines for sore throat and urinary tract infection found little or no change in the main outcomes , which were antibiotic prescriptions , use of laboratory tests and use of telephone consultations . There was great variation between the practice s in the change in these outcomes . OBJECTIVES Our aim was to evaluate how the interventions were received and to underst and why practice s did or did not change . METHODS The trial was conducted in general practice s in Norway . Data for this process evaluation were collected from the 120 practice s that completed the trial . Multiple methods were used : observations , semi-structured telephone interviews , a postal survey and data extracted from electronic medical records . We investigated factors that might explain a lack of change , including : agreement with the guidelines ; communication within each practice ; degree of participation in the project ; taking time to discuss the guidelines and their implementation ; use of the components of the interventions ; and routines for telephone consultations . Possible explanatory factors were explored in relation to variation in change and the overall extent of change in rates of use of antibiotics , laboratory tests and telephone consultations . RESULTS Sixty-three per cent of practice s agreed with the guidelines . Only 35 % reported having regular meetings , and 33 % discussed the project before its start , although 75 % reported agreement about participating within the practice . Only 33 % reported meeting to discuss the guidelines . Use of the components of the interventions ranged from 11 % for the increased fee for telephone consultations to 48 % for the computerized decision support . Forty-four per cent reported problems with telephone routines . No single factor explained the observed variation in the extent of change across practice s. CONCLUSIONS Inadequate time , re sources and support were the most salient factors that might explain a lack of change . Problems with internal communication and telephone routines were important contributing factors in many practice OBJECTIVES To determine whether a computerized tool that alerted pharmacists when patients aged 65 and older were newly prescribed potentially inappropriate medications was effective in decreasing the proportion of patients dispensed these medications . DESIGN Prospect i ve , r and omized trial . SETTING U.S. health maintenance organization . PARTICIPANTS All 59,680 health plan members aged 65 and older were r and omized to intervention ( n=29,840 ) or usual care ( n=29,840 ) . Pharmacists received alerts on all patients r and omized to intervention who were newly prescribed a targeted medication . INTERVENTION Prescription and age information were linked to alert pharmacists when a patient aged 65 and older was newly prescribed one of 11 medications that are potentially inappropriate in older people . MEASUREMENTS Physicians and pharmacists collaborated to develop the targeted medication list , indications for medication use for which an intervention should occur , intervention guidelines and scripts , and to implement the intervention . RESULTS Over the 1-year study , 543 ( 1.8 % ) intervention group patients aged 65 and older were newly dispensed prescriptions for targeted medications , compared with 644 ( 2.2 % ) usual care group patients ( P=.002 ) . For medication use indications in which an intervention should occur , dispensings of amitriptyline ( P<.001 ) and diazepam ( P=.02 ) were reduced . CONCLUSIONS This study demonstrated the effectiveness of a computerized pharmacy alert system plus collaboration between healthcare professionals in decreasing potentially inappropriate medication dispensings in elderly patients . Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can improve prescribing safety in patients aged 65 and older OBJECTIVE To assess the effects on health care re source utilization of a network of microcomputer workstations for writing all inpatient orders . DESIGN R and omized controlled clinical trial . SETTING Inpatient internal medicine service of an urban public hospital . SUBJECTS A total of 5219 internal medicine patients and the 68 teams of house officers , medical students , and faculty internists who cared for them . INTERVENTION Microcomputer workstations , linked to a comprehensive electronic medical record system , for writing all inpatient orders . MAIN OUTCOME MEASURES Total inpatient charges for each admission and charges for specific categories of orders . A time-motion study of selected interns assessed the ordering system 's time consumption . RESULTS Intervention teams generated charges that were $ 887 ( 12.7 % ) lower per admission than did control teams ( P = .02 ) . Significant reductions ( P < .05 ) were demonstrated separately for bed charges , diagnostic test charges , and drug charges . Reductions of similar proportion and statistical significance were found for hospital costs . The mean length of stay was 0.89 day shorter for intervention resident teams ( P = .11 ) . Interns in the intervention group spent an average of 33 minutes longer ( 5.5 minutes per patient ) during a 10-hour observation period writing orders than did interns in the control group ( P < .0001 ) . CONCLUSIONS A network of microcomputer workstations for writing all inpatient orders significantly lowered patient charges and hospital costs . This would amount to savings of more than $ 3 million in charges annually for this hospital 's medicine service and potentially tens of billions of dollars nationwide . However , the system required more physician time than did the paper charts . Research at other sites and system advances to reduce time requirements are warranted Abstract Objective To test the effectiveness of educational interventions in improving detection rates and management of dementia in primary care . Design Unblinded , cluster r and omised , before and after controlled study . Setting General practice s in the United Kingdom ( central Scotl and and London ) between 1999 and 2002 . Interventions Three educational interventions : an electronic tutorial carried on a CD Rom ; decision support software built into the electronic medical record ; and practice based workshops . Participants 36 practice s participated in the study . Eight practice s were r and omly assigned to the electronic tutorial ; eight to decision support software ; 10 to practice based workshops ; and 10 to control . Electronic and manual search es yielded 450 valid and usable medical records . Main outcome measures Rates of detection of dementia and the extent to which medical records showed evidence of improved concordance with guidelines regarding diagnosis and management . Results Decision support software ( P = 0.01 ) and practice based workshops ( P = 0.01 ) both significantly improved rates of detection compared with control . There were no significant differences by intervention in the measures of concordance with guidelines . Conclusions Decision support systems and practice based workshops are effective educational approaches in improving detection rates in dementia BACKGROUND Medication errors are frequently related to failure to appropriately select medications or adjust for laboratory parameters . Differences between guideline recommendations and actual frequency of therapeutic laboratory monitoring are substantial . This study evaluated interventions to improve laboratory monitoring at initiation of medication therapy . METHODS This cluster-r and omized trial compared 3 interventions to usual care for 10 medications in 15 primary care clinics in a health maintenance organization with an electronic medical record system . Eligible patients , identified from electronic data bases , had not received recommended laboratory monitoring within 5 days after new dispensing of a study medication . Interventions were an electronic medical record reminder to the prescribing health care professional , an automated voice message to the patient , and a pharmacy team outreach to the patient . Primary outcome was completion of all recommended baseline laboratory monitoring . RESULTS A total of 961 patients participated in the study . At 25 days , 95 ( 48.5 % ) of 196 patients in the electronic medical record reminder group , 177 ( 66.3 % ) of 267 in the automated voice message group , 214 ( 82.0 % ) of 261 in the pharmacy team outreach group , and 53 ( 22.4 % ) of 237 in the usual care group had completed all recommended baseline laboratory monitoring ( P<.001 ) . After adjustments , the hazard ratios for completing laboratory monitoring compared with usual care were 2.5 ( 95 % confidence interval , 1.8 - 3.5 ) for electronic medical record reminder , 4.1 ( 95 % confidence interval , 3.0 - 5.6 ) for automated voice message , and 6.7 ( 95 % confidence interval , 4.9 - 9.0 ) for pharmacy team outreach . CONCLUSIONS All 3 interventions were effective in increasing laboratory monitoring when initiating new medications in primary care . Further work is necessary to determine if these interventions improve patient outcomes Guided dosing within a computerized provider order entry ( CPOE ) system is an effective method of individualizing therapy for patients . Physicians ' responses to guided dosing decision support have not been extensively studied . As part of a r and omized trial evaluating efficacy of dosing advice on reducing falls in the elderly , CPOE prompts to physicians for 88 drugs included tailored messages and guided dose lists with recommended initial doses and frequencies . The study captured all prescribing activity electronically . The primary outcome was the ratio between prescribed dose and recommended dose . Over 9 months , 778 providers entered 9111 study -related medication orders on 2981 patients . Physicians using guided orders chose recommended doses more often than controls(28.6 % vs. 24.1 % , p<0.001 ) . Selected doses were significantly lower in the intervention group ( median ratio of actual to recommended 2.5 , interquartile range [ 1.0,4.0 ] ) than the control group ( median 3.0 interquartile range [ 1.5,5.0 ] , p<0.001 ) . While physicians selected the recommended dose less than a third of the time , guided geriatric dosing modestly improved compliance with guidelines Background : To investigate whether intensive treatment with methotrexate ( MTX ) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis . Methods : In a two-year multicentre open label strategy trial , 299 patients with early rheumatoid arthritis were r and omly assigned to the intensive strategy group or the conventional strategy group . Patients in both groups received MTX , the aim of treatment being remission . Patients in the intensive treatment group came to the outpatient clinic once every month ; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria , using a computerised decision program . Patients of the conventional strategy group came to the outpatient clinic once every three months ; they were treated according to common practice . Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses . Results : Seventy six ( 50 % ) patients in the intensive strategy group achieved at least one period of remission during the two year trial , versus 55 patients ( 37 % ) in the conventional strategy group ( p = 0.03 ) . Areas under the curve for nearly all clinical variables were significantly lower — that is , there was a better clinical effect for the intensive treatment group compared with the conventional treatment group . Conclusion : The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX , aim ing for remission , tailored to the individual patient . Furthermore , participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice OBJECTIVE To assess the impact of an automated intraoperative alert to redose prophylactic antibiotics in prolonged cardiac operations . DESIGN R and omized , controlled , evaluator-blinded trial . SETTING University-affiliated hospital . PATIENTS Patients undergoing cardiac surgery that lasted more than 4 hours after the preoperative administration of cefazolin , unless they were receiving therapeutic antibiotics at the time of surgery . INTERVENTION R and omization to an audible and visual reminder on the operating room computer console at 225 minutes after the administration of preoperative antibiotics ( reminder group , n = 137 ) or control ( n = 136 ) . After another 30 minutes , the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered . RESULTS Intraoperative redosing was significantly more frequent in the reminder group ( 93 of 137 ; 68 % ) than in the control group ( 55 of 136 ; 40 % ) ( adjusted odds ratio , 3.31 ; 95 % confidence interval , 1.97 to 5.56 ; P < .0001 ) . The impact of the reminder was even greater when compared with the 6 months preceding the study period ( 129 of 480 ; 27 % ; P < .001 ) , suggesting some spillover effect on the control group . Redosing was formally declined for 19 of the 44 patients in the reminder group without redosing . The rate of surgical-site infection in the reminder group ( 5 of 137 ; 4 % ) was similar to that in the control group ( 8 of 136 ; 6 % ; P = .42 ) , but significantly lower than that in the pre- study period ( 48 of 480 ; 10 % ; P = .02 ) . CONCLUSION The use of an automatic reminder system in the operating room improved compliance with guidelines on perioperative antibiotic prophylaxis Abstract Objective : To underst and the factors influencing the adoption of a computerised clinical decision support system for two chronic diseases in general practice . Design : Practice based , longitudinal , qualitative interview study . Setting : Five general practice s in north east Engl and . Participants : 13 respondents ( two practice managers , three nurses , and eight general practitioners ) gave a total of 19 semistructured interviews . 40 people in practice s included in the r and omised controlled trial ( 34 doctors , three nurses ) and interview study ( three doctors , one previously interviewed ) gave feedback . Results : Negative comments about the decision support system significantly outweighed the positive or neutral comments . Three main areas of concern among clinicians emerged : timing of the guideline trigger , ease of use of the system , and helpfulness of the content . Respondents did not feel that the system fitted well within the general practice context . Experience of “ on-dem and ” information sources , which were generally more positively viewed , informed the comments about the system . Some general practitioners suggested that nurses might find the guideline content more clinical ly useful and might be more prepared to use a computerised decision support system , but lack of feedback from nurses who had experienced the system limited the ability to assess this . Conclusions : Significant barriers exist to the use of complex clinical decision support systems for chronic disease by general practitioners . Key issues include the relevance and accuracy of messages and the flexibility to respond to other factors influencing decision making in primary care . What is already known on this topic R and omised controlled trials of complex computerised decision support systems have found low rates of use and no effects on process and outcomes of care What this study adds Clinicians found a computerised decision support system for chronic disease in general practice to be difficult to use and unhelpful clinical ly It did not fit well into a general practice consultation and compared unfavourably with “ on-dem and ” information “ Active ” decision support can make clinicians aware of gaps between their own practice and “ best ” practice , but computer prompts need to be relevant and OBJECTIVE A research prototype Physician Workstation ( PWS ) incorporating a graphical user interface and a drug ordering module was compared with the existing hospital information system in an academic Veterans Administration General Medical Clinic . Physicians in the intervention group received recommendations for drug substitutions to reduce costs and were alerted to potential drug interactions . The objective was to evaluate the effect of the PWS on user satisfaction , on health-related outcomes , and on costs . DESIGN A one-year , two-period , r and omized controlled trial with 37 subjects . MEASUREMENTS Differences in the reliance on noncomputer sources of information , in user satisfaction , in the cost of prescribed medications , and in the rate of clinical ly relevant drug interactions were assessed . RESULTS The study subjects logged onto the workstation an average of 6.53 times per provider and used it to generate 2.8 % of prescriptions during the intervention period . On a five-point scale ( 5 = very satisfied , 1 = very dissatisfied ) , user satisfaction declined in the PWS group ( 3.44 to 2.98 p = 0.008 ) , and increased in the control group ( 3.23 to 3.72 , p < 0.0001 ) . CONCLUSION The intervention physicians did not use the PWS frequently enough to influence information-seeking behavior , health outcomes , or cost . The study design did not determine whether the poor usage result ed from satisfaction with the control system , problems using the PWS intervention , or the functions provided by the PWS intervention . Evaluative studies should include provisions to improve the chance of successful implementation as well as to yield maximum information if a negative study occurs BACKGROUND Decision-support information technology is often adopted to improve clinical decision making , but it is rarely rigorously evaluated . Congress m and ated the evaluation of Problem-Knowledge Couplers ( PKC Corp , Burlington , Vt ) , a decision-support tool proposed for the Department of Defense 's new health information network . METHODS This was a patient-level r and omized trial conducted at 2 military practice s. A total of 936 patients were allocated to the intervention group and 966 to usual care . Couplers were applied before routine ambulatory clinic visits . The primary outcome was quality of care , which was assessed based on the total percentage of any of 24 health care quality process measures ( opportunities to provide evidence -based care ) that were fulfilled . Secondary outcomes included medical re sources consumed within 60 days of enrollment and patient and provider satisfaction . RESULTS There were 4639 health care opportunities ( 2374 in the Coupler group and 2265 in the usual-care group ) , with no difference in the proportion of opportunities fulfilled ( 33.9 % vs 30.7 % ; P = .12 ) . Although there was a modest improvement in performance on screening/preventive measures , it was offset by poorer performance on some measures of acute care . Coupler patients used more laboratory and pharmacy re sources than usual-care patients ( logarithmic mean difference , 71 dollars ) . No difference in patient satisfaction was observed between groups , and provider satisfaction was mixed . CONCLUSION This study provides no strong evidence to support the utility of this decision-support tool , but it demonstrates the value of rigorous evaluation of decision-support information technology OBJECTIVES To evaluate the effectiveness of computer-assisted decision support in reducing potentially inappropriate prescribing to older adults . DESIGN R and omized , controlled trial . SETTING An academic emergency department ( ED ) in Indianapolis , Indiana , where computerized physician order entry was used to write all medication prescriptions . PARTICIPANTS Sixty-three emergency physicians were r and omized to the intervention ( 32 physicians ) or control ( 31 physicians ) group . INTERVENTION Decision support that advised against use of nine potentially inappropriate medications and recommended safer substitute therapies . MEASUREMENTS The primary outcome was the proportion of ED visits by seniors that result ed in one or more prescriptions for an inappropriate medication . The main secondary outcomes were the proportions of medications prescribed that were inappropriate and intervention physicians ' reasons for rejecting the decision support . RESULTS The average age of the patients was 74 , two-thirds were female , and just over half were African American . Decision support was provided 114 times to intervention physicians , who accepted 49 ( 43 % ) of the recommendations . Intervention physicians prescribed one or more inappropriate medications during 2.6 % of ED visits by seniors , compared with 3.9 % of visits managed by control physicians ( P=.02 ; odds ratio=0.55 , 95 % confidence interval=0.34 - 0.89 ) . The proportion of all prescribed medications that were inappropriate significantly decreased from 5.4 % to 3.4 % . The most common reason for rejecting decision support was that the patient had no prior problems with the medication . CONCLUSION Computerized physician order entry with decision support significantly reduced prescribing of potentially inappropriate medications for seniors . This approach might be used in other efforts to improve ED care . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00297869 OBJECTIVE To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners ( GPs ) . RESEARCH DESIGN AND METHODS A r and omized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Data base . Among these , 150 GPs ( intervention group ) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor ( " high risk " ) , whereas the other 150 GPs ( control group ) received only the letter . The electronic reminder , integrated into a st and ard software system for the management of the daily clinical practice , was displayed when every participating GP opened the medical record of diabetic patients aged > or = 30 years . Only high-risk diabetic patients were included in the analysis . Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up . RESULTS We selected 15,343 high-risk diabetic patients , 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group . Overall , 1,672 patients ( 22.9 % ) of the control group and 1,886 ( 23.5 % ) patients of the intervention group received antiplatelet drugs at baseline ( P = N.S. ) . At the end of the follow-up , the number of treated patients was significantly increased in the intervention group ( odds ratio 1.99 , 95 % CI 1.79 - 2.22 ) versus the control group . The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases ( CVDs ) , compared with those with CVDs . CONCLUSIONS These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs BACKGROUND Although they are effective in outpatient setting s , computerized reminders have not been proved to increase preventive care in inpatient setting s. METHODS We conducted a r and omized , controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for in patients . During an 18-month study period , a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service ( for a total of 10,065 hospitalizations ) , generating preventive care reminders as appropriate . Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for in patients . RESULTS The reminder system identified 3416 patients ( 53.6 percent ) as eligible for preventive measures that had not been ordered by the admitting physician . For patients with at least one indication , computerized reminders result ed in higher adjusted ordering rates for pneumococcal vaccination ( 35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group , P<0.001 ) , influenza vaccination ( 51.4 percent vs. 1.0 percent , P < 0.001 ) , prophylactic heparin ( 32.2 percent vs. 18.9 percent , P<0.001 ) , and prophylactic aspirin at discharge ( 36.4 percent vs. 27.6 percent , P<0.001 ) . CONCLUSIONS A majority of hospitalized patients in this study were eligible for preventive measures , and computerized reminders significantly increased the rate of delivery of such therapies CONTEXT Computerized systems to remind physicians to provide appropriate care have not been widely evaluated in large numbers of patients in multiple clinical setting s. OBJECTIVE To examine whether a computerized reminder system operating in multiple Veterans Affairs ( VA ) ambulatory care clinics improves resident physician compliance with st and ards of ambulatory care . DESIGN , SETTING , AND PARTICIPANTS A total of 275 resident physicians at 12 VA medical centers were r and omly assigned in firms or half-day clinic blocks to either a reminder group ( n = 132 ) or a control group ( n = 143 ) . During a 17-month study period ( January 31 , 1995-June 30 , 1996 ) , the residents cared for 12,989 unique patients for whom at least 1 of the studied st and ards of care ( SOC ) was applicable . MAIN OUTCOME MEASURES Compliance with 13 SOC , tracked using hospital data bases and encounter forms completed by residents , compared between residents in the reminder group vs those in the control group . RESULTS Measuring compliance as the proportion of patients in compliance with all applicable SOC by their last visit during the study period , the reminder group had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 58.8 % vs 53.5 % ; odds ratio [ OR ] , 1.24 ; 95 % confidence interval [ CI ] , 1.08 - 1.42 ; P = .002 ) and for 5 of the 13 st and ards examined individually . Measuring compliance as the proportion of all visits for which care was indicated in which residents provided proper care , the reminder group also had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 17.9 % vs 12.2 % ; OR , 1.57 ; 95 % CI , 1.45 - 1.71 ; P<.001 ) and for 9 of the 13 st and ards examined individually . The benefit of reminders , however , declined throughout the course of the study , even though the reminders remained active . CONCLUSIONS Our data indicate that reminder systems installed at multiple sites can improve residents ' compliance to multiple SOC . The benefits of such systems , however , appear to deteriorate over time . Future research needs to explore methods to better sustain the benefits of reminders . JAMA . 2000;284:1411 - 1416 Objective : To determine the efficacy of a computerised decision aid in patients with atrial fibrillation making decisions on whether to take warfarin or aspirin therapy . Design : Two-armed open exploratory r and omised controlled trial . Setting : Two research clinics deriving participants from general practice s in Northeast Engl and . Participants : 109 patients with atrial fibrillation aged over 60 . Interventions : Computerised decision aid applied in shared decision-making clinic compared to evidence -based paper guidelines applied as direct advice . Main outcome measures : Primary outcome measure was the decision conflict scale . Secondary outcome measures included anxiety , knowledge , decision-making preference , treatment decision , use of primary and secondary care services and health outcomes . Results : Decision conflict was lower in the computerised decision aid group immediately after the clinic ; mean difference −0.18 ( 95 % CI −0.34 to −0.01 ) . Participants in this group not already on warfarin were much less likely to start warfarin than those in the guidelines arm ( 4/16 , 25 % compared to the guidelines group 15/16 , 93.8 % , RR 0.27 , 95 % CI 0.11 to 0.63 ) . Conclusions : Decision conflict was lower immediately following the use of a computerised decision aid in a shared decision-making consultation than immediately following direct doctor-led advice based on paper guidelines . Furthermore , participants in the computerised decision aid group were significantly much less likely to start warfarin than those in the guidelines arm . The results show that such an approach has a positive impact on decision conflict comparable to other studies of decision aids , but also reduces the uptake of a clinical ly effective treatment that may have important implication s for health outcomes OBJECTIVE To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system ( CDSS ) and a specific implementation strategy . Evaluation of patient outcome . DESIGN R and omised study with health centres as units . The intervention group had the CDSS installed and made ready for use , doctors and assistants were trained and received a user-manual , the doctors were offered telephone repetitions , a seminar in risk intervention and , at the same seminar , further demonstration of the CDSS . The doctors received baseline registration s with information of how they treated their own hypertensive patients , and use of the CDSS was checked repeatedly . SETTING General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . PARTICIPANTS Seventeen health centres with 24 doctors and 984 patients in the intervention group . Data from 879 patients used in the final analyses . Twelve health centres with 29 doctors and 1255 patients in the control group . Data from 1119 patients used in the final analyses . MAIN OUTCOME MEASURES After an intervention period of 18 months , group differences in level of systolic and diastolic blood pressure , serum cholesterol , body mass index , and risk score for myocardial infa rct ion were calculated , as well as group differences in fractions of smokers . RESULTS Significant group difference in favour of intervention group : diastolic blood pressure 1 mmHg ( 95 % CI -1.89 , -0.17 ) . However , a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg ( 95 % CI 1.0 , 4.5 ) had been reduced to 1.2 mmHg ( 95 % CI -0.6 , 3.0 ) after intervention . CONCLUSION Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinical ly significant way Objectives : Having shown previously that an electronic prescription writer and decision support system improved pediatric prescribing behavior for otitis media in an academic clinic setting , we assessed whether point-of-care delivery of evidence could demonstrate similar effects for a wide range of other common pediatric conditions . Design : Cluster r and omized controlled trial . Setting : A teaching clinic/ clinical practice site and a primary care pediatric clinic serving a rural and semi-urban patient mix . Participants : A total of 36 providers at the teaching clinic/ practice site and eight providers at the private primary pediatric clinic . Intervention : An evidence -based message system that presented real-time evidence to providers based on prescribing practice s for acute otitis media , allergic rhinitis , sinusitis , constipation , pharyngitis , croup , urticaria , and bronchiolitis . Outcome measures : The proportion of prescriptions dispensed in accordance with evidence . Results : The proportion of prescriptions dispensed in accordance with evidence improved four percentage points , from 38 % at baseline to 42 % following the intervention . The control group improved by one percentage point , from 39 % at baseline to 40 % at trial 's conclusion . The adjusted difference between the intervention and control groups was 8 % ( 95 % confidence interval 1 % , 15 % ) . Intervention effectiveness did not decrease with time . Conclusion : For common pediatric outpatient conditions , a point-of-care evidence -based prescription writer and decision support system was associated with significant improvements in prescribing practice OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care BACKGROUND Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor . METHODS We recruited 68 primary care family and internal medicine practice s ; 66 were r and omly allocated to a study arm ; 5 practice s withdrew , result ing in 29 receiving the Third Adult Treatment Panel ( ATP III ) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC-7 ) . The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III-recommended treatment . All practice s received copies of each clinical practice guideline , an introductory lecture , 1 performance feedback report , and 4 visits for intervention-specific academic detailing . Data were abstract ed at 61 practice s from r and om sample s of medical records of patients treated from June 1 , 2001 , through May 31 , 2003 ( baseline ) , and from May 1 , 2004 , through April 30 , 2006 ( follow-up ) . The proportion screened with subsequent appropriate decision making ( primary outcome ) was calculated . Generalized estimating equations were used to compare results by arm , accounting for clustering of patients within practice s. RESULTS We examined 5057 baseline and 3821 follow-up medical records . The screening rate for lipid levels increased from 43.6 % to 49.0 % ( ATP III practice s ) and from 40.1 % to 50.8 % ( control practice s ) ( net difference , -5.3 % [ P = .22 ] ) . Appropriate management of lipid levels decreased slightly ( 73.4 % to 72.3 % ) in ATP III practice s and more markedly ( 79.7 % to 68.9 % ) in control practice s. The net change in appropriate management favored the intervention ( + 9.7 % ; 95 % confidence interval [ CI ] , 2.8%-16.6 % [ P < .01 ] ) . Appropriate drug prescription within 4 months decreased in both arms ( 38.8 % to 24.8 % in ATP III practice s and 45.3 % to 24.1 % in control practice s ; net change , + 7.2 % [ P = .37 ] ) Overtreatment declined from 6.6 % to 3.9 % in ATP III and rose from 4.2 % to 6.4 % in control practice s ( net change , -4.9 % [ P = .01 ] ) . CONCLUSIONS A multifactor intervention including personal digital assistant-based decision support may improve primary care physician adherence to the ATP III guidelines . Trial Registration clinical trials.gov Identifier : NCT00224848 OBJECTIVE This study sought to determine whether a computerized tool that alerted pharmacists when pregnant patients were prescribed U.S. Food and Drug Administration pregnancy risk category D or X medications was effective in decreasing dispensings of these medications . DESIGN R and omized trial . Pharmacy , diagnostic , and laboratory data were linked to identify pregnant patients prescribed targeted medications . Women ( n = 11,100 ) were r and omized to intervention or usual care . Physicians and pharmacists collaborated on the intervention . MEASUREMENTS The primary outcome was the proportion of pregnant women dispensed a category D or X medication . The secondary outcome was the total number of first dispensings of targeted medications . RESULTS A total of 2.9 % of intervention ( n = 177 ) and 5.5 % of usual care ( n = 276 ) patients were dispensed targeted medications ( p < 0.001 ) : 1.8 % of intervention ( n = 108 ) and 3.9 % of usual care ( n = 198 ) patients were dispensed only category D medication(s ) ; 0.9 % of intervention ( n = 54 ) and 1.2 % of usual care ( n = 58 ) patients were dispensed only category X medication(s ) ; 0.2 % of intervention ( n = 15 ) and 0.4 % of usual care ( n = 20 ) patients were dispensed both category D and X medications ( p = 0.05 ) . This result ed in intervention patients receiving 238 dispensings of unique targeted medications and usual care patients receiving 361 dispensings of unique targeted medications ( p = 0.03 ) . The study was stopped primarily due to 2 false-positive alert types : Mis identification of medications as contraindicated in pregnancy by the pharmacy information system and mis identification of pregnancy related to delayed transfer of diagnosis information . CONCLUSION Coupling data from information systems with knowledge and skills of physicians and pharmacists result ed in improved prescribing safety . Systems limitations contributed to project discontinuation . Linking ambulatory clinical , laboratory , and pharmacy information to provide safety alerts is not sufficient to ensure project success and sustainability OBJECTIVE Errors of omission are a common cause of systems failures . Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments . The authors hypothesized that automated , guideline -based reminders to physicians , provided as they wrote orders , could reduce these omissions . DESIGN The study was performed on the inpatient general medicine ward of a public teaching hospital . Faculty and housestaff from the Indiana University School of Medicine , who used computer workstations to write orders , were r and omized to intervention and control groups . As intervention physicians wrote orders for 1 of 87 selected tests or treatments , the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders . The physicians could accept or reject these suggestions . RESULTS During the 6-month trial , reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians . Intervention physicians ordered the suggested corollary orders in 46.3 % of instances when they received a reminder , compared with 21.9 % compliance by control physicians ( p < 0.0001 ) . Physicians discriminated in their acceptance of suggested orders , readily accepting some while rejecting others . There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups . CONCLUSION This study demonstrates that physician workstations , linked to a comprehensive electronic medical record , can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines CONTEXT Prescribing practice s for otitis media are not consistent with current evidence -based recommendations . OBJECTIVE To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN R and omized , controlled trial . SETTING Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence -based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES Proportion of prescriptions for otitis media that were for < 10 days and frequency with which antibiotics were prescribed . RESULTS Intervention providers had a 34 % greater reduction in the proportion of time they prescribed antibiotics for < 10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake Abstract Objective : To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat Design : Unblinded , cluster r and omised pretest-post-test trial Setting : 142 general practice s in Norway Participants : 72 practice s received interventions to implement guidelines for urinary tract infection and 70 practice s received interventions to implement guidelines for sore throat , serving as controls for each other . 59 practice s in the urinary tract infection group and 61 practice s in the sore throat group completed the study . Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection . Interventions : Interventions were developed to overcome identified barriers to implementing the guidelines . The main components of the tailored interventions were patient educational material , computer based decision support and reminders , an increase in the fee for telephone consultations , and interactive courses for general practitioners and practice assistants Main outcome measures : Changes in rates of use of antibiotics , laboratory tests , and telephone consultations Results : Patients in the sore throat group were 3 % less likely to receive antibiotics after the intervention . Women with symptoms of urinary tract infection in the intervention group were 5.1 % less likely to have a laboratory test ordered . No significant differences were found between the groups for the other outcomes . Large variation was found across the included practice sin the rates of antibiotic prescription , use of laboratory tests and telephone consultations , and in the extent of change for all three outcome measures Conclusions : Passively delivered , complex interventions targeted at identified barriers to change had little effect in changing BACKGROUND Appropriate antibiotic treatment decreases mortality , while superfluous treatment is associated with antibiotic resistance . We built a computerized decision support system for antibiotic treatment ( TREAT ) targeting these outcomes . METHODS Prospect i ve cohort study comparing TREAT 's advice to physician 's treatment followed by a cluster r and omized trial comparing wards using TREAT ( intervention ) versus antibiotic monitoring without TREAT ( control ) . We included patients suspected of harbouring bacterial infections in three hospitals ( Israel , Germany and Italy ) . The primary outcome , appropriate antibiotic treatment , was assessed among patients with microbiologically documented infections ( MDI ) . Length of hospital stay , adverse events , mortality ( interventional trial ) and antibiotic costs ( both studies ) , including costs related to future antibiotic resistance , were compared among all included patients . RESULTS Among 1203 patients included in the cohort study ( 350 with MDI ) , TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians ( 70 % versus 57 % , P < 0.001 ) using less broad-spectrum antibiotics at half physicians ' antibiotic costs . The r and omized trial included 2326 patients , 570 with MDI . The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [ 73 % versus 64 % , odds ratio ( OR ) : 1.48 , 95 % confidence interval ( CI ) : 0.95 - 2.29 , intention to treat , adjusted for location and clustering ] . For patients treated according to TREAT 's advice in intervention wards , the difference with controls was highly significant ( OR : 3.40 , 95 % CI : 2.25 - 5.14 ) . Length of hospital stay , costs related to future resistance and total antibiotic costs were lower in intervention versus control wards . CONCLUSIONS TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment Introduction The object of this study was to examine the effect of population -based disease management and case management on re source use , self-reported health status , and member satisfaction with and retention in a Medicare Plus Choice health maintenance organization ( HMO ) . Methods Study design consisted of a prospect i ve , r and omized controlled open trial of 18 months ' duration . Participants were 8504 Medicare beneficiaries aged 65 and older who had been continuously enrolled for at least 12 months in a network model Medicare Plus Choice HMO serving a contiguous nine-county metropolitan area . Members were care managed with an expert clinical information system and frequent telephone contact . Main outcomes included self-reported health status measured by the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) , re source use measured by admission rates and bed-days per thous and per year , member satisfaction , and costs measured by paid cl aims . Results More favorable outcomes occurred in the intervention group for satisfaction with the health plan ( P < .01 ) and the social function domain as measured by SF-36 ( P = .04 ) . There was no difference in member retention or mortality between groups . Use of skilled nursing home services was significantly lower in the intervention group than in the control ( 616 vs 747 days per thous and members per year , P = .02 ) . This reduction , however , did not lead to lower mean total expenditures in the intervention group compared with the control ( $ 6828 per member for 18 months vs $ 7001 , P = .61 ) . Conclusion Population -based disease management and case management led to improved self-reported satisfaction and social function but not to a global net decrease in re source use or improved member retention We analyze the effect of a decision support tool design ed to help physicians detect and correct medical " missteps " . The data comes from a r and omized trial of the technology on a population of commercial HMO patients . The key findings are that the new information technology lowers average charges by 6 % relative to the control group . This reduction in re source utilization was the result of reduced in-patient charges ( and associated professional charges ) for the most costly patients . The rate at which identified issues were resolved was generally higher in the study group than in the control group , suggesting the possibility of improvements in care quality along measured dimensions and enhanced diffusion of new protocol s based on new clinical evidence BACKGROUND Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease . The Computer-based Clinical Decision Support System provides an opportunity t close these gaps . OBJECTIVES To study the impact of computerized intervention on secondary prevention of CAD . METHODS The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an up date d lipoprotein profile and treatment with lipid-lowering drugs . The program produced automatic computer-generated monitoring and treatment recommendations . Adjusted primary clinics were r and omly assigned to intervention ( n=56 ) or st and ard care arms ( n=56 ) . Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment . Compliance and lipid levels were monitored . The study group comprised all patients with CAD who were alive at least 3 months after hospitalization . RESULTS Follow-up was available for 7448 patients ( median 19.8 months , range 6 - 36 months ) . Overall , 51.7 % of patients were adequately screened , and 55.7 % of patients were compliant with treatment to lower lipid level . In patients with initial low density lipoprotein > 120 mg/dl , a significant decrease in LDL levels was observed in both arms , but was more pronounced in the intervention arm : 121.9 + /- 34.2 vs. 124.3 + /- 34.6 mg/dl ( P < 0.02 ) . A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs , 37 % vs. 40.9 % ( P < 0.001 ) . CONCLUSIONS This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines , presenting a major obstacle to implementing effective secondary prevention . Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation OBJECTIVE Recommendations for routine laboratory monitoring to reduce the risk of adverse medication events are not consistently followed . We evaluated the impact of electronic reminders delivered to primary care physicians on rates of appropriate routine medication laboratory monitoring . DESIGN We enrolled 303 primary care physicians caring for 1,922 patients across 20 ambulatory clinics that had at least one overdue routine laboratory test for a given medication between January and June 2004 . Clinics were r and omized so that physicians received either usual care or electronic reminders at the time of office visits focused on potassium , creatinine , liver function , thyroid function , and therapeutic drug levels . MEASUREMENTS Primary outcomes were the receipt of recommended laboratory monitoring within 14 days following an outpatient clinic visit . The effect of the intervention was assessed for each reminder after adjusting for clustering within clinics , as well as patient and provider characteristics . RESULTS Medication-laboratory monitoring non-compliance ranged from 1.6 % ( potassium monitoring with potassium-supplement use ) to 6.3 % ( liver function monitoring with HMG CoA Reductase Inhibitor use ) . Rates of appropriate laboratory monitoring following an outpatient visit ranged from 14 % ( therapeutic drug levels ) to 64 % ( potassium monitoring with potassium-sparing diuretic use ) . Reminders for appropriate laboratory monitoring had no impact on rates of receiving appropriate testing for creatinine , potassium , liver function , renal function , or therapeutic drug level monitoring . CONCLUSION We identified high rates of appropriate laboratory monitoring , and electronic reminders did not significantly improve these monitoring rates . Future studies should focus on setting s with lower baseline adherence rates and alternate drug-laboratory combinations Context Prescription drug costs are a major component of health care expenditures , yet re sources to support evidence -based prescribing are not widely available . Objective To evaluate the effectiveness of computerized prescribing alerts , with or without physician-led group educational sessions , to reduce the prescribing of heavily marketed hypnotic medications . Design Cluster-r and omized controlled trial . Setting We r and omly allocated 14 internal medicine practice sites to receive usual care , computerized prescribing alerts alone , or alerts plus group educational sessions . Measurements Proportion of heavily marketed hypnotics prescribed before and after the implementation of computerized alerts and educational sessions . Main Results The activation of computerized alerts held the prescribing of heavily marketed hypnotic medications at pre-intervention levels in both the alert-only group ( adjusted risk ratio [ RR ] 0.97 ; 95 % CI 0.82–1.14 ) and the alert-plus-education group ( RR 0.98 ; 95 % CI 0.83–1.17 ) while the usual-care group experienced an increase in prescribing ( RR 1.31 ; 95 % CI 1.08–1.60 ) . Compared to the usual-care group , the relative risk of prescribing heavily marketed medications was less in both the alert-group ( Ratio of risk ratios [ RRR ] 0.74 ; 95 % CI 0.57–0.96 ) and the alert-plus-education group ( RRR 0.74 ; 95 % CI 0.58–0.97 ) . The prescribing of heavily marketed medications was similar in the alert-group and alert-plus-education group ( RRR 1.02 ; 95 % CI 0.80–1.29 ) . Most clinicians reported that the alerts provided useful prescribing information ( 88 % ) and did not interfere with daily workflow ( 70 % ) . Conclusions Computerized decision support is an effective tool to reduce the prescribing of heavily marketed hypnotic medications in ambulatory care setting s . Trial Registration clinical trials.gov Identifier : NCT00788346 OBJECTIVE : Suboptimal treatment of hyperlipidemia in patients with coronary artery disease ( CAD ) is well documented . We report the impact of a computer-assisted physician-directed intervention to improve secondary prevention of hyperlipidemia . DESIGN AND SETTING : Two hundred thirty-five patients under the care of 14 primary care physicians in an academically affiliated practice with an electronic health record were enrolled in this proof-of-concept physician-blinded r and omized , controlled trial . Each patient with CAD or risk equivalent above National Cholesterol Education Program-recommended low-density lipoprotein ( LDL ) treatment goal for greater than 6 months was r and omized , stratified by physician and baseline LDL . Physicians received a single e-mail per intervention patient . E-mails were visit independent , provided decision support , and facilitated “ one-click ” order writing . MEASUREMENTS : The primary outcomes were changes in hyperlipidemia prescriptions , time to prescription change , and changes in LDL levels . The time spent using the system was assessed among intervention patients . RESULTS : A greater proportion of intervention patients had prescription changes at 1 month ( 15.3 % vs 2 % , P=.001 ) and 1 year ( 24.6 % vs 17.1 % , P=.14 ) . The median interval to first medication adjustment occurred earlier among intervention patients ( 0 vs 7.1 months , P=.005 ) . Among patients with baseline LDLs > 130 mg/dL , the first postintervention LDLs were substantially lower in the intervention group ( 119.0 vs 138.0 mg/dL , P=.04 ) . Physician processing time was under 60 seconds per e-mail . CONCLUSION : A visit-independent disease management tool result ed in significant improvement in secondary prevention of hyperlipidemia at 1-month postintervention and showed a trend toward improvement at 1 year A computer was used to prospect ively detect and suggest responses to simple , medication-related events as reflected in a computerized record in a prospect i ve , r and omized study of a diabetes clinic with primary -care responsibility . There were two categories of event/suggestions : when the last observation of a test required for medication control was too old , the computer suggested a repeat ; and when an abnormality with therapeutic implication s was detected , the computer suggested a specific change in therapeutics . Clinicians responded to 36 % of events in the first category with computer reminders and 11 % without ( P less than 0.0001 ) ; they responded to 28 % of events in the second category with computer assistance and 13 % without ( P less than 0.026 ) . For the most clinical ly significant of these second category events , the difference was even greater : 47 % with and 4 % without computer assistance ( P less than 0.0004 ) . I believe that computer detection and response ( in the form of reminders ) to simple clinical events will change clinician behavior CONTEXT . Barriers impede translating recommendations for asthma treatment into practice , particularly in inner cities where asthma morbidity is highest . METHODS . The purpose of this study was to test the effectiveness of timely patient feedback in the form of a letter providing recent patient-specific symptoms , medication , and health service use combined with guideline -based recommendations for changes in therapy on improving the quality of asthma care by inner-city primary care providers and on result ant asthma morbidity . This was a r and omized , controlled clinical trial in 5- to 11-year-old children ( n = 937 ) with moderate to severe asthma receiving health care in hospital- and community-based clinics and private practice s in 7 inner-city urban areas . The caretaker of each child received a bimonthly telephone call to collect clinical information about the child 's asthma . For a full year , the providers of intervention group children received bimonthly computer-generated letters based on these calls summarizing the child 's asthma symptoms , health service use , and medication use with a corresponding recommendation to step up or step down medications . We measured the number and proportion of scheduled visits result ing in stepping up of medications , asthma symptoms ( 2-week recall ) , and health care use ( 2-month recall ) . RESULTS . In this population , only a modest proportion of children whose symptoms warranted a medication increase actually had a scheduled visit to reevaluate their asthma treatment . However , in the 2-month interval after receipt of a step-up letter , 17.1 % of the letters were followed by scheduled visits in the intervention group compared with scheduled visits 12.3 % of the time by the control children with comparable clinical symptoms . Asthma medications were stepped up when indicated after 46.0 % of these visits in the intervention group compared with 35.6 % in the control group , and when asthma symptoms warranted a step up in therapy , medication changes occurred earlier among the intervention children . Among children whose medications were stepped up at any time during the 12-month study period , those in the intervention group experienced 22.1 % fewer symptom days and 37.9 % fewer school days missed . The intention-to-treat analysis showed no difference over the intervention year in the number of symptom days , yet there was a trend toward fewer days of limited activity and a significant decrease in emergency department visits by the intervention group compared with controls . This 24 % drop in emergency department visits result ed in an intervention that was cost saving in its first year . CONCLUSIONS . Patient-specific feedback to inner-city providers increased scheduled asthma visits , increased asthma visits in which medications were stepped up when clinical ly indicated , and reduced emergency department visits BACKGROUND Evidence suggests that preoperative clinics , like other hospital outpatient clinics and inpatient wards , fail to systematic ally provide smoking cessation care to patients having planned surgery . METHODS The aim of the study was to assess the efficacy , acceptability , and cost of a multifaceted intervention to facilitate the provision of comprehensive smoking cessation care to patients attending a preoperative clinic . Two hundred ten smoking patients attending a preoperative clinic at a major teaching hospital in Australia took part in the study . One hundred twenty-four patients were r and omly assigned to an experimental group and 86 patients to a usual cessation care group . A multifaceted intervention was developed that included the use of opinion leaders , consensus processes , computer-delivered cessation care , computer-generated prompts for care provision by clinic staff , staff training , and performance feedback . RESULTS Ninety-six percent of experimental group patients received behavioral counseling and tailored self-help material . Experimental group patients were significantly more likely than usual care patients to report receiving brief advice by nursing ( 79 % vs. 47 % ; P < 0.01 ) and anaesthetic ( 60 % vs. 39 % ; P < 0.01 ) staff . Experimental group patients who were nicotine dependent were also more likely to be offered preoperative nicotine replacement therapy ( NRT ) ( 82 % vs. 8 % ; P < 0.01 ) and be prescribed postoperative NRT ( 86 % vs. 0 % ; P < 0.01 ) . The multifaceted intervention was found to be acceptable by staff . CONCLUSION A multifaceted clinical practice change intervention may be effective in improving the delivery of smoking cessation care to preoperative surgical patients A computerized medical record system was design ed to detect and remind the responsible clinician about clinical events that might need corrective action . These reminders significantly increased the clinician response rate ( in terms of test orders and treatment changes ) to the events in question . The addition of relevant medical literature citations to the reminders did not significantly change the clinician response rate as compared with that with reminders alone , nor did it stimulate the physicians to read any of the cited articles kept in an immediately available " library " of reprints OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits OBJECTIVES To evaluate the implementation of clinical guidelines for diabetes mellitus in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . METHODS R and omized study with health center as unit . General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . Seventeen health centers with 24 doctors and 499 patients with diabetes mellitus were in the intervention group and 12 health centers with 29 doctors and 535 patients were in the control group . Main outcome measures were group differences in fractions of patients without registration s ( process evaluation ) and mean group differences for the same variables ( patient outcome evaluation ) . RESULTS Statistically significant group differences were experienced for fractions of patients without registration of cigarette smoking ( intervention group , 82.6 % ; control group 94.5 % ) , body mass index ( 78.2 % vs. 93.0 % ) , and sufficient registration s for calculation of risk score for myocardial infa rct ion ( 91.1 % vs. 98.3 % ) ; all during 18 months . Large center variations were shown for all variables . The only statistically significant group difference was -2.3 mm Hg ( 95 % CI , -3.8 , -0.8 ) in diastolic blood pressure in favor of the intervention group . Statistically insignificant differences in favor of the intervention group were HbA1c , -0.1 % ( 95 % CI , -0.4 , 0.1 ) , systolic blood pressure , -1.2 mm Hg ( 95 % CI , -4.4 , 2.0 ) . Statistically insignificant differences in favor of the control group were fractions of smokers , + 3.0 % ( 95 % CI , -4.0 , 10.0 ) , body mass index , + 0.3 kg/m2 ( 95 % CI , -0.8 , 1.4 ) , risk score in female + 0.1 ( 95 % CI , -5.1 , 5.2 ) , and risk score in male + 2.6 ( 95 % CI , -14.2 , 19.5 ) . CONCLUSIONS Implementation of clinical guidelines for diabetes mellitus in general practice , by means of a CDSS and several procedures for implementation , did not result in a clinical ly significant change in doctors ' behavior or in patient outcome Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p < 0.001 ) ; 61.7 % ( 156/253 ) of patients in the intervention group , compared with 42.6 % ( 110/258 ) of control patients , showed improvement ( difference 19.1 % , p < 0.001 ) . The clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 . OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice UNLABELLED OBJECTIVE To determine whether a computerized clinical decision support system providing patient-specific recommendations in real-time improves the quality of prescribing for long-term care residents with renal insufficiency . DESIGN R and omized trial within the long-stay units of a large long-term care facility . R and omization was within blocks by unit type . Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units . Measurement The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories : ( 1 ) recommended medication doses ; ( 2 ) recommended administration frequencies ; ( 3 ) recommendations to avoid the drug ; ( 4 ) warnings of missing information . RESULTS The rates of alerts were nearly equal in the intervention and control units : 2.5 per 1,000 resident days in the intervention units and 2.4 in the control units . The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units ( relative risk 0.95 , 95 % confidence interval 0.83 , 1.1 ) for the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units : relative risk 2.4 for maximum frequency ( 1.4 , 4.4 ) ; 2.6 for drugs that should be avoided ( 1.4 , 5.0 ) ; and 1.8 for alerts to acquire missing information ( 1.1 , 3.4 ) . Overall , final drug orders were appropriate significantly more often in the intervention units-relative risk 1.2 ( 1.0 , 1.4 ) . CONCLUSIONS Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions . TRIAL REGISTRATION http:// clinical trials.gov Identifier : NCT00599209 The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested . Sixty family physicians were r and omised to two treatment strategies . " Test " physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing . Computer feedback on management was mailed to the doctors . This encouraged doctors to apply the " stepped care " protocol , supplied charts of diastolic blood pressure v time , and ranked patients ' diastolic blood pressures by percentile . Letters were mailed to patients to remind them of appointments . " Control " doctors filled out the same data collection forms as test physicians , but neither doctors nor patients received computer feedback . Physicians who used the computer saw more patients per practice than control doctors ( test 50 patients , control 40 ) . For all patients the length of follow up was significantly longer in test practice s ( test 199 days , control 167 ) , and a smaller percentage dropped out of active treatment in test practice s ( test 37.5 % , control 42.1 % ) . For patients with " moderate " hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practice s ( 88.5 mm Hg ) , but it failed to reach this goal in control practice s ( 93.3 mm Hg ) . A greater average reduction of diastolic pressure was achieved in test practice s ( test 21.7 mm Hg , control 16.7 mm Hg ) . Though patients with " moderate " hypertension were better controlled in test practice s than in control practice s , the patients in test practice s visited their doctors less often ( test 13.3 visits per patient-year , control 17.4 visits ) . Among patients with newly detected hypertension test practice s achieved a greater reduction in diastolic pressure than control practice s ( test 15.1 mm Hg v control 11.3 mm Hg ) and more sustained control of hypertension ( test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days ) OBJECTIVES To evaluate the efficacy of computerized provider order entry with clinical decision support for preventing adverse drug events in long-term care . DESIGN Cluster-r and omized controlled trial . SETTING Two large long-term care facilities . PATIENTS One thous and one hundred eighteen long-term care residents of 29 resident care units . INTERVENTION The 29 resident care units , each with computerized provider order entry , were r and omized to having a clinical decision support system ( intervention units ) or not ( control units ) . MEASUREMENTS The number of adverse drug events , severity of events , and whether the events were preventable . RESULTS Within intervention units , 411 adverse drug events occurred over 3,803 resident-months of observation time ; 152 ( 37.0 % ) were deemed preventable . Within control units , there were 340 adverse drug events over 3,257 resident-months of observation time ; 126 ( 37.1 % ) were characterized as preventable . There were 10.8 adverse drug events per 100 resident-months and 4.0 preventable events per 100 resident-months on intervention units . There were 10.4 adverse drug events per 100 resident-months and 3.9 preventable events per 100 resident-months on control units . Comparing intervention and control units , the adjusted rate ratios were 1.06 ( 95 % confidence interval (CI)=0.92 - 1.23 ) for all adverse drug events and 1.02 ( 95 % CI=0.81 - 1.30 ) for preventable adverse drug events . CONCLUSION Computerized provider order entry with decision support did not reduce the adverse drug event rate or preventable adverse drug event rate in the long-term care setting . Alert burden , limited scope of the alerts , and a need to more fully integrate clinical and laboratory information may have affected efficacy Background —The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence . This study evaluated interventions for implementing a new practice guideline advocating the use of & bgr;-blockers for heart failure patients . Methods and Results —This was a r and omized controlled trial involving heart failure patients ( n=169 ) with an ejection fraction ≤45 % and no contraindications to & bgr;-blockers . Patients ’ primary providers were r and omized in a stratified design to 1 of 3 interventions : ( 1 ) control : provider education ; ( 2 ) provider and patient notification : computerized provider reminders and patient letters advocating & bgr;-blockers ; and ( 3 ) nurse facilitator : supervised nurse to initiate and titrate & bgr;-blockers . The primary outcome , the proportion of patients who were initiated or uptitrated and maintained on & bgr;-blockers , analyzed by intention to treat , was achieved in 67 % ( 36 of 54 ) of patients in the nurse facilitator group compared with 16 % ( 10 of 64 ) in the provider/patient notification and 27 % ( 14 of 51 ) in the control groups ( P < 0.001 for the comparisons between the nurse facilitator group and both other groups ) . The proportion of patients on target & bgr;-blocker doses at the study end ( median follow-up , 12 months ) was also highest in the nurse facilitator group ( 43 % ) compared with the control ( 10 % ) and provider/patient notification groups ( 2 % ) ( P < 0.001 ) . There were no differences in adverse events among groups . Conclusions —The use of a nurse facilitator was a successful approach for implementing a & bgr;-blocker guideline in heart failure patients . The use of provider education , clinical reminders , and patient education was of limited value in this setting BACKGROUND Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance . AIM To evaluate the influence on prescribing practice of a computer-based decision support system ( CDSS ) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy . DESIGN Cluster-r and omized controlled trial . METHODS We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms , excluding those with a poor prognosis or major contraindication to anticoagulation . After observation of routine prescribing practice ( 6 months ) in each hospital , centres were r and omized for 6 months to either control ( routine practice observed ) or intervention ( practice observed while the CDSS provided patient-specific information ) . We compared , between control and intervention centres , the risk reduction ( estimated by the CDSS ) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy , and the proportions of subjects prescribed the optimal therapy identified by the CDSS . RESULTS Sixteen hospitals recruited 1952 subjects . When the CDSS provided information , the mean relative risk reduction attained by prescribing increased by 2.7 percentage units ( 95%CI -0.3 to 5.7 ) and the odds ratio for the optimal therapy being prescribed was 1.32 ( 0.83 to 1.80 ) . Some 55 % ( 5/9 ) of clinicians believed the CDSS had influenced their prescribing . CONCLUSIONS Cluster-r and omized trials provide excellent frameworks for evaluating novel clinical management methods . Our CDSS was feasible to implement and acceptable to clinicians , but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P<.001 ) . The effect of provider advice combined with patient education was not significantly different from provider advice alone ( P=.88 ) . Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients OBJECTIVE To demonstrate the potential effect of deploying a sentinel system that scans administrative cl aims information and clinical data to detect and mitigate errors in care and deviations from best medical practice s. METHODS Members ( n = 39 462 ; age range , 12 - 64 years ) of a midwestern managed care plan were r and omly assigned to an intervention or a control group . The sentinel system was programmed with more than 1000 decision rules that were capable of generating clinical recommendations . Clinical recommendations triggered for subjects in the intervention group were relayed to treating physicians , and those for the control group were deferred to study end . RESULTS Nine hundred eight clinical recommendations were issued to the intervention group . Among those in both groups who triggered recommendations , there were 19 % fewer hospital admissions in the intervention group compared with the control group ( P < .001 ) . Charges among those whose recommendations were communicated were dollar 77.91 per member per month ( pmpm ) lower and paid cl aims were dollar 68.08 pmpm lower than among controls compared with the baseline values ( P = .003 for both ) . Paid cl aims for the entire intervention group ( with or without recommendations ) were dollar 8.07 pmpm lower than those for the entire control group . In contrast , the intervention cost dollar 1.00 pmpm , suggesting an 8-fold return on investment . CONCLUSION Ongoing use of a sentinel system to prompt clinical ly actionable , patient-specific alerts generated from administratively derived clinical data was associated with a reduction in hospitalization , medical costs , and morbidity We tested whether off-line data analysis , instead of event monitoring , was a viable method for initiating a clinical quality alert . A cohort of patients eligible for an alert was identified by off-line data analysis and a flag was set in their ambulatory Electronic Medical Records . One hundred clinicians were r and omly assigned either to a control group or to a group that received the alert when viewing the electronic medical record of eligible patients . Primarily due to actions of their clinicians , 315 of the 580 patients ( 54.3 % ) seen by alerted clinicians were no longer eligible for the alert at the end of the one month study , compared to 128 of the 496 patients ( 25.8 % ) seen by control clinicians ( p<.001 ) . When not alerted , Allied Health clinicians were less likely than physicians to prescribe aspirin , but they responded similarly to the alert . There were no differences in response by specialty or gender of the clinician . Off-line data analysis proved to be an effective method of initiating a clinical alert We describe the design and implementation of a clinical decision support system for ambulatory hyperlipidemia management . Despite readily available and evidence -based guidelines , cholesterol control remains persistently sub-optimal in clinical practice . " FastTrack " is an integrated , multi-faceted informatics tool to reduce barriers to effective cholesterol management by proactively integrating pertinent clinical information , evidence -based decision support and a simple means to act via a single FastTrack e-mail . We tested the intervention in a r and omized , controlled trial involving 14 physicians and 276 patients . In an interim analysis , we found that physicians on average were able to review and act upon 9 patient e-mails in less than 15 minutes . Significantly more intervention patients were initiated on a statin therapy or had their dose increased ( 15.3 % vs. 2.3 % , p < 0.001 ) . Impact of the intervention on LDL levels will be assessed at trial completion The Personal Digital Assistance for Guideline Adherence ( GLAD Heart ) study was design ed to test a strategy to improve quality of care through increased adherence to ATPIII cholesterol guidelines . This paper describes the overall study design including the multi-faceted intervention and outcome measures . Sixty-one primary care practice s in NC were recruited and r and omized to either a personal digital assistant-based cholesterol management intervention or an intervention similar in intensity and frequency of contact but focused on a hypertension clinical practice guideline . Installation and implementation of the technology intervention was challenging . Over the course of the study , there were 74 technical issues requiring assistance for the palm pilot from 23 participating practice s. The GLAD Heart project was completed successfully with some impact on cholesterol management . Technology has the potential to improve the quality of care provided in the healthcare setting . However , potentially expensive interventions such as that conducted in GLAD Heart should undergo rigorous testing to assure their efficacy before widespread adoption OBJECTIVES To provide physicians with evidence -based recommendations for care at the point of service , using an automated system , and to evaluate its effectiveness in promoting prescriptions to prevent cardiovascular events . STUDY DESIGN R and omized controlled trial . METHODS Patients at risk for cardiovascular events who might benefit from angiotensin-converting enzyme inhibitors or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) were identified from electronic data in a managed care organization and r and omly assigned into 2 groups . Physicians seeing out patients in the intervention group were faxed a sheet with pertinent patient data , including a recommendation to prescribe the indicated medication . In the control group , the data sheet did not include the recommendation . Dispensed prescriptions were compared between groups . RESULTS More than 4000 visits were observed for each medication type . Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were dispensed in 7.1 % of visits in the intervention group versus 5.7 % in the control group ( P = .048 ) following the first patient-physician encounter . No significant difference was observed for statins ( intervention , 8.1 % vs control , 7.7 % ) . Data for all patient-physician encounters and both medications were combined in logistic regression analysis . The odds ratio was 1.19 for a dispensed prescription in the intervention group and 1.54 for 2 or more visits versus 1 visit . CONCLUSIONS An automated system that provides pertinent data and tailored recommendations for care at the point of service modestly increased prescription dispensing rates . Targeting patient-provider encounters to change provider behavior is challenging ; however , even small effects can produce clinical ly important results over time BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior OBJECTIVE To evaluate the effectiveness of a computerized decision support system for ovarian stimulation with gonadotropins . DESIGN Retrospective and prospect i ve r and omized studies . SETTING Private and university teaching hospital . PATIENT(S ) Women undergoing ovarian stimulation to treat infertility . MAIN OUTCOME MEASURE(S ) Pregnancy rate . RESULT ( S ) In the retrospective study , computer-generated decisions were compared with clinicians ' decisions in 118 stimulated cycles in 53 patients . In 90 % of cases , the choice of FSH regimens and adjustments to dosages were identical . In the prospect i ve study , the computer-generated decisions achieved a pregnancy rate per cycle of 18 % ( 15 of 82 cycles ) , compared with 16 % ( 13 of 82 cycles ) achieved by clinicians . CONCLUSION ( S ) A computerized decision making system was as effective as skilled clinicians in achieving pregnancy by using ovarian stimulation with FSH BACKGROUND We conducted a cluster r and omized controlled trial to examine the effectiveness of computerized decision support ( CDS ) design ed to improve hypertension care and outcomes in a racially diverse sample of primary care patients . METHODS We r and omized 2,027 adult patients receiving hypertension care in 14 primary care practice s to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group . We assessed prescribing of guideline -recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients ’ race/ethnicity using interaction terms . MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42 % at baseline and 46 % at the outcome visit with no significant differences between groups . After adjustment for patients ’ demographic and clinical characteristics , number of prior visits , and levels of baseline blood pressure control , there were no differences between intervention groups in the odds of outcome blood pressure control . The use of CDS to providers significantly improved Joint National Committee ( JNC ) guideline adherent medication prescribing compared to usual care ( 7 % versus 5 % , P < 0.001 ) ; the effects of the intervention remained after multivariable adjustment ( odds ratio [ OR ] 1.39 [ CI , 1.13–1.72 ] ) and the effects of the intervention did not differ by patients ’ race and ethnicity . CONCLUSIONS CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control . Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed Background — Although & bgr;-blockers are known to prolong survival for patients with reduced left ventricular ejection fraction , they are often underused . We hypothesized that a reminder attached to the echocardiography report would increase the use of & bgr;-blockers for patients with reduced left ventricular ejection fraction . Methods and Results — We r and omized 1546 consecutive patients with a left ventricular ejection fraction < 45 % found on echocardiography at 1 of 3 laboratories to a reminder for use of & bgr;-blockers or no reminder . Patients were excluded from analysis if they died within 30 days of r and omization ( n=89 ) , did not receive medications through the Veterans Affairs system after 30 days ( n=180 ) , or underwent echocardiography at > 1 laboratory ( n=6 ) . The primary outcome was a prescription for an oral & bgr;-blocker between 1 and 9 months after r and omization . The mean age of the 1271 included patients was 69 years ; 60 % had a history of heart failure , and 51 % were receiving treatment with & bgr;-blockers at the time of echocardiography . More patients r and omized to the reminder had a subsequent & bgr;-blocker prescription ( 74 % , 458 of 621 ) compared with those r and omized to no reminder ( 66 % , 428 of 650 ; P=0.002 ) . The effect of the reminder was not significantly different for subgroups based on patient location ( inpatient versus outpatient ) or prior use of & bgr;-blockers . Conclusions — A reminder attached to the echocardiography report increased the use of & bgr;-blockers in patients with depressed left ventricular systolic function OBJECTIVE To test the efficiency and cost-effectiveness of interventions aim ed at enhancing laboratory monitoring of medication . STUDY DESIGN Cost-effectiveness analysis . METHODS Patients of a not-for-profit , group-model HMO were r and omized to 1 of 4 interventions : an electronic medical record reminder to the clinician , an automated voice message to patients , pharmacy-led outreach , or usual care . Patients were followed for 25 days to determine completion of all recommended baseline laboratory monitoring tests . We measured the rate of laboratory test completion and the cost-effectiveness of each intervention . Direct medical care costs to the HMO ( repeated testing , extra visits , and intervention costs ) were determined using trial data and a mix of other data sources . RESULTS The average cost of patient contact was $ 5.45 in the pharmacy-led intervention , $ 7.00 in the electronic reminder intervention , and $ 4.64 in the automated voice message reminder intervention . The electronic medical record intervention was more costly and less effective than other methods . The automated voice message intervention had an incremental cost-effectiveness ratio ( ICER ) of $ 47 per additional completed case , and the pharmacy intervention had an ICER of $ 64 per additional completed case . CONCLUSIONS Using the data available to compare strategies to enhance baseline monitoring , direct clinician messaging was not an efficient use of re sources . Depending on a decision maker 's willingness to pay , automated voice messaging and pharmacy-led efforts can be efficient choices to prompt therapeutic baseline monitoring , but direct clinician messaging is probably a less efficient use of re sources BACKGROUND Hospitalizations are an opportunity to provide preventive care . OBJECTIVE To determine if computer reminders , which we have shown to be effective in our ambulatory care setting , increasing the provision of inpatient preventive care . METHODS R and omized , controlled trial on the general medicine inpatient service of an urban , university-affiliated public hospital . Study subjects were 78 house staff rotating on the 6 general medicine services . The intervention was reminders to physicians printed on daily rounds reports about preventive care for which their patients were eligible , and suggested orders for preventive care provided through the physicians ' workstations . The preventive care guidelines were derived from the US Preventive Care Task Force recommendations . Compliance with preventive care guidelines and house staff attitudes toward providing preventive care to hospitalized patients were the main outcome measures . RESULTS No significant differences were seen between intervention and control physicians in compliance with preventive care guidelines in the aggregate or when individual preventive care actions individual preventive care actions were analyzed . This was true even though most physicians endorsed providing most kinds of preventive care for hospitalized patients . CONCLUSIONS Despite past success in increasing preventive care in the outpatient setting , we were unable , using a moderately intensive intervention , to increase the provision of preventive care during hospitalizations . The physicians providing care during the hospitalization were not the patients ' primary care physicians , which proved to be an important barrier . More intensive interventions , or more direct linkages between inpatient and outpatient care providers , may be required to overcome this resistance PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma BACKGROUND Errors involving medication use are common . Computerized physician order entry ( CPOE ) can improve prescribing practice s. Few studies have examined the effect of CPOE in combination with decision support tools on prescribing practice s in the outpatient setting . Less is known about prescribers ' adherence to laboratory monitoring recommendations . OBJECTIVE To evaluate if reminders presented during CPOE for medications would increase physicians ' compliance with guidelines for laboratory monitoring at initiation of therapy . STUDY DESIGN R and omized prospect i ve intervention study . METHODS Two hundred seven primary care physicians in a group-model managed care organization were r and omized to receive or not receive drug laboratory monitoring alerts within the CPOE system . Adherence to laboratory monitoring recommendations for patients prescribed selected medications was compared between physician groups . RESULTS There was no significant difference between the control and intervention group physicians in the overall rate of compliance with ordering the recommended laboratory monitoring for patients prescribed study medications . Laboratory monitoring was performed as recommended 56.6 % of the time in the intervention group compared with 57.1 % of the time in the control group ( P = .31 ) . In cases in which a statistically significant difference was demonstrated , improved compliance favored the intervention group ( eg , 71.2 % vs 62.3 % [ P = .003 ] for gemfibrozil and 75.7 % vs 73.9 % [ P = .05 ] for statins ) . CONCLUSIONS As CPOE becomes more prevalent , additional research is needed to determine effective decision support tools . These findings then should be communicated to the developers and users of computerized medical record systems BACKGROUND The importance of laboratory monitoring for drugs is reflected in product labeling and published guidelines , but monitoring recommendations are followed inconsistently . Opportunity exists to improve monitoring , with the potential to decrease therapy complications . METHODS The objective of this r and omized trial was to determine whether computerized alerts were effective at increasing the percentage of ambulatory patients with laboratory monitoring at initiation of drug therapy . Physicians and pharmacists teamed up to develop organization-specific guidelines for monitoring selected drugs . In collaboration with physicians , pharmacists were alerted to missing laboratory test results , ordered missing tests , reminded patients to obtain tests , assessed test completion , review ed test results , and managed abnormal results . Eligible individuals included patients with therapy initiated for any of 15 drugs among 400,000 health plan members . RESULTS In the intervention group , 79.1 % ( n = 4076 ; 95 % confidence interval [ CI ] , 78.0%-80.2 % ) of dispensings were monitored compared with 70.2 % ( n = 3522 ; 95 % CI , 68.9%-71.5 % ) in the usual-care group ( P < .001 ) . For example , 78.6 % of amiodarone ( 95 % CI , 73.1%-83.5 % ) dispensing was monitored in the intervention group vs 51.4 % ( 95 % CI , 44.4%-58.4 % ) in the group receiving usual care ( P < .001 ) . CONCLUSIONS This study demonstrates the effectiveness of a computerized tool plus collaboration among health care professionals at increasing the percentage of patients receiving laboratory monitoring at initiation of therapy . Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can result in improved patient monitoring Context Decision making about thrombolysis in acute myocardial infa rct ion ( AMI ) can be difficult . The Thrombolytic Predictive Instrument ( TPI ) estimates the risk for death and hemorrhage with and without thrombolysis . Its effect on patient care is unknown . Contribution This r and omized trial of the TPI in emergency departments showed that printing TPI predictions on the admission electrocardiogram increased the frequency of reperfusion for inferior AMI but not anterior AMI . The effect of the TPI was greatest for women and for patients who required off-site consultation . Implication s The TPI is a tool to assure all patients the same st and ard of care . The Editors Emergent coronary reperfusion for acute myocardial infa rct ion ( AMI ) can be lifesaving for appropriate patients who are promptly recognized and treated ( 1 - 4 ) . However , in the emergency department setting , this prompt recognition can be difficult , especially for less-obvious c and i date s and when physician decision makers are not all on site . To assist in treatment decisions , the Thrombolytic Predictive Instrument ( TPI ) , incorporated into conventional computerized electrocardiography , prints on the electrocardiogram ( ECG ) text header its predictions of key outcomes of thrombolytic therapy : 30-day mortality , 1-year mortality , cardiac arrest , hemorrhagic stroke , and bleeding requiring transfusion ( 5 , 6 ) . Over the past decade , as a result of intensive efforts by physician leaders , the U.S. National Institutes of Health National Heart Attack Alert Program , organizations interested in quality of medical care , the pharmaceutical industry , and others ( 3 , 7 - 16 ) , more patients with AMI have received thrombolytic therapy and have received it sooner ( 17 ) . However , further improvement is needed ( 17 - 20 ) , especially for patients with AMI other than anterior AMI ( the category of AMI for which thrombolytic therapy was first recognized as effective [ 1 , 2 ] ) and for women ( who have received reperfusion therapy at lower rates than men [ 18 , 20 ] ) . Also needed are ways to support prompt , accurate decisions about reperfusion therapy in hospitals and in prehospital emergency medical service ( EMS ) setting s where consultation with off-site physicians may be required . The need for prompt recognition of potential benefit also applies to acute reperfusion by primary percutaneous transluminal coronary angioplasty ( PTCA ) , which may be equivalent to thrombolytic therapy or even preferable for some patients with AMI ( 21 - 25 ) . Thus , any method of increasing use of thrombolytic therapy should not interfere with the alternative use of PTCA , when indicated . To test whether the TPI addresses these needs , we did a r and omized , controlled , clinical effectiveness trial in the emergency departments of 28 diverse hospitals . We sought to determine whether the TPI would help physicians 1 ) identify patients needing thrombolytic therapy who would not otherwise have been identified ; 2 ) use thrombolytic therapy sooner ; 3 ) identify more c and i date s for overall coronary reperfusion , including medical thrombolysis or primary PTCA ; and 4 ) expedite decisions about reperfusion when physician decision makers are not all on site . Methods Study Sites Our study was done in 28 U.S. hospitals , including public , private , community , and tertiary care hospitals in urban , suburban , and rural areas : Bess Kaiser Medical Center ( Portl and , Oregon ) , Boston City Hospital ( Boston , Massachusetts ) , Box Butte General Hospital ( Alliance , Nebraska ) , Carney Hospital ( Dorchester , Massachusetts ) , Cedars-Sinai Medical Center ( Los Angeles , California ) , Chadron Community Hospital ( Chadron , Nebraska ) , Cooley Dickinson Hospital ( Northampton , Massachusetts ) , Decatur County Hospital ( Oberlin , Kansas ) , Franklin Medical Center ( Greenfield , Massachusetts ) , Huntington Hospital ( Huntington , New York ) , Lincoln Community Hospital ( Hugo , Colorado ) , Mary Lane Hospital ( Ware , Massachusetts ) , Memorial Health Center ( Sidney , Nebraska ) , Memorial Hospital ( Craig , Colorado ) , New Engl and Medical Center ( Boston , Massachusetts ) , Noble Hospital ( Westfield , Massachusetts ) , North Shore University HospitalGlen Cove ( Glen Cove , New York ) , Plains Medical Center ( Limon , Colorado ) , Presbyterian/St . Luke 's Medical Center ( Denver , Colorado ) , Regional West Medical Center ( Scottsbluff , Nebraska ) , Rhode Isl and Hospital ( Providence , Rhode Isl and ) , Silverheels Health Center ( Fairplay , Colorado ) , Southeast Colorado Hospital ( Springfield , Colorado ) , Sunnyside Medical Center ( Clackamas , Oregon ) , Swedish Hospital ( Engelwood , Colorado ) , Timberline Medical Center ( Granby , Colorado ) , University Hospital ( Boston , Massachusetts ) , and University HospitalStony Brook ( Stony Brook , New York ) . Patients and Intervention We included all consenting patients 35 years of age and older who 1 ) presented with AMI to any study hospital during the 22-month period beginning 24 April 1995 and 2 ) had , on presentation to the emergency department , detection of ST-segment elevation characteristic of AMI on an ECG . At study hospitals , software that generated the TPI predictions was installed on conventional computerized electrocardiographs ( Hewlett-Packard , Palo Alto , California ) so that ST-segment elevation characteristic of AMI was automatically detected . When this elevation was detected , the patient was automatically r and omly assigned to the control or the TPI group . R and omization did not delay obtaining an ECG or treatment . ( In accordance with Institutional Review Board approval [ given that usual ECGs and ECGs with TPI predictions both represent st and ard care and that it is necessary not to disrupt initial emergency care ] , we obtained written informed consent as soon as was practical after the initial ECG . ) For patients in the TPI group , the electrocardiograph automatically prompted the user to enter patient information needed to make the TPI predictions : age , sex , history of hypertension , history of diabetes , blood pressure , and time since onset of ischemic symptoms . The remaining variables , based on measurement of ECG waveforms , were automatically acquired by the electrocardiograph . Then the ECG was printed with the TPI predictions on its header . If any variables for the calculations were missing , predictions were not calculated and an alert listing the missing variables was printed . Entry of missing data , if available , was allowed . Predictions were not generated for patients older than 75 years of age ( 5 , 26 , 27 ) . For controls , the ECG was automatically printed with the header text customarily used in that emergency department . Data Collection and Analysis At presentation and during hospitalization , we collected sociodemographic information ; data on clinical features , ECGs , and all cardiac biomarker test results ( at minimum , serial creatine kinase MB tests ) at presentation and follow-up ; the triaging physician 's training level and specialty and whether he or she was emergency departmentbased ; whether on- or off-site ( telephone ) consultations were used in making the reperfusion treatment decision ; whether the patient received thrombolytic therapy and , if so , the time from onset of chest pain to receipt of therapy ; and whether the patient received primary PTCA . The TPI software allowed real-time acquisition of the clinical variables required for the TPI calculations and automatic acquisition of Q-wave , ST-segment , and T-wave measurements . Follow-up data needed to assign confirmed true diagnoses were collected from arrival at the emergency department through the 30-day follow-up visit . The overall 30-day follow-up rate was 100 % . Site physicians , blinded to study group assignments , used World Health Organization criteria ( 28 ) to assign confirmed diagnoses on the basis of presentation , clinical course , initial and follow-up ECGs , and biomarker tests . An AMI was classified as anterior if the patient had at least two contiguous ECG anterior leads with ST-segment elevation , regardless of whether this was accompanied by elevation elsewhere . Any AMI with no significant anterior ST-segment elevation was classified as inferior . Emergency department care was classified by whether consultation with an off-site physician was used in making the treatment decision . Hospital size , hospital type , presence of on-site emergency department staff , and physician type were used as potentially explanatory variables . Statistical Analysis Baseline comparisons of patient characteristics between the control and TPI groups were done by using t-tests for continuous variables and chi-square tests for categorical variables . Because of skewed distributions of times from symptom onset , median times from symptom onset to initial ECG were compared between groups by using the Wilcoxon rank-sum test . Chi-square tests for 2 2 tables were used to compare crude differences between groups in rates of use of thrombolytic therapy ; use of thrombolytic therapy within 1 hour of r and omization ; and overall use of reperfusion , including PTCA . The predictive discrimination of the TPI 's mortality predictions was measured by using the area under the receiver-operating characteristic ( ROC ) curve , estimated by the c statistic from the logistic regression model predicting the outcome with the predicted values as the sole independent variable . Relative risks and P values were derived from the 2 2 tables and chi-square tests . Analyses by AMI location and patient sex were also adjusted for hospital type ( urban teaching hospital , teaching-affiliated hospital , or community or rural hospital ) by using the CochranMantelHaenszel test . Hospital groupings were made before analyses were done and reflect similar characteristics and expected reperfusion rates . Commonality of the relative risk across hospital type was tested by using the BreslowDay chi-square statistic . We used SAS , version 8 ( SAS , Inc. , Cary , North Carolina ) for all analyses . Role of the Funding Source Neither the funding source nor the manufacturers of equipment or software had any role in the STUDY OBJECTIVE To assess the effects of evidence -based treatment suggestions for hypertension made to physicians and pharmacists using a comprehensive electronic medical record system . DESIGN R and omized controlled trial with a 2 x 2 factorial design of physician and pharmacist interventions , which result ed in four groups of patients : physician intervention only , pharmacist intervention only , intervention by physician and pharmacist , and intervention by neither physician nor pharmacist ( control ) . SETTING Academic primary care internal medicine practice . SUBJECTS Seven hundred twelve patients with uncomplicated hypertension . MEASUREMENTS AND MAIN RESULTS Suggestions were displayed to physicians on computer workstations used to write outpatient orders and to pharmacists when filling prescriptions . The primary end point was generic health-related quality of life . Secondary end points were symptom profile and side effects from antihypertensive drugs , number of emergency department visits and hospitalizations , blood pressure measurements , patient satisfaction with physicians and pharmacists , drug therapy compliance , and health care charges . In the control group , implementation of care changes in accordance with treatment suggestions was observed in 26 % of patients . In the intervention groups , compliance with suggestions was poor , with treatment suggestions implemented in 25 % of patients for whom suggestions were displayed only to pharmacists , 29 % of those for whom suggestions were displayed only to physicians , and 35 % of the group for whom both physicians and pharmacists received suggestions ( p=0.13 ) . Intergroup differences were neither statistically significant nor clinical ly relevant for generic health-related quality of life , symptom and side-effect profiles , number of emergency department visits and hospitalizations , blood pressure measurements , charges , or drug therapy compliance . CONCLUSION Computer-based intervention using a sophisticated electronic physician order-entry system failed to improve compliance with treatment suggestions or outcomes of patients with uncomplicated hypertension Discrepancies between clinical guidelines and clinical practice call for practical implementation strategies . This study evaluates the implementation of clinical guidelines for hypertension in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . We carried out a r and omized study of general practice health centres in Sør- and Nord-Trøndelag counties in Norway ( population 380000 ) . A total of 17 health centres were included , with 24 doctors and 984 patients in the intervention group . Data from 887 patients was used in the analyses . There were 12 health centres with 29 doctors and 1255 patients in the control group . Data from 1127 control patients was used in the analyses . The main outcome measures were doctor 's behaviour , measured by adherence to registration of recommended variables in the Norwegian clinical guidelines for hypertension . The aim of the intervention was to lower the fractions of patients without registration s. However , there were no clinical ly significant differences between the intervention group and the control group for fractions of patients without registration of blood pressure ( intervention group 14.3 % , control group 14.2 % ) or serum cholesterol ( 62.3 % vs. 56.8 % ) during 12 months , nor , during 18 months , for fractions of patients without a registration of cigarette smoking ( 82.9 % vs. 87.1 % ) , cardiovascular inheritance ( 79.5 % vs. 73.4 % ) and body mass index ( 81.5 % vs. 89.2 % ) . One or several variables necessary for calculation of risk score for myocardial infa rct ion were missing in 91.7 % of patients in the intervention group and 91.9 % of patients in the control group . Large centre variations were shown for all variables . Implementation of clinical guidelines in the treatment of hypertensive patients in general practice , by means of a CDSS and several procedures for implementation did not result in clinical ly significant changes in the doctors ' behaviour . Of importance are both the lack of user-friendliness of the specific CDSS and problems in performing time-consuming multidimensional procedures Objective To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic . Design A r and omized trial . Setting The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System , Seattle Division . Patients / Participants Clinic providers were r and omized to a control group ( n=35 ) or intervention group ( n=36 ) . We targeted the providers of patients being treated for hypertension with calcium channel blockers , a class of drug not recommended for initial therapy . InterventionAn automated computer query identified eligible patients and their providers . A guideline reminder was placed in the charts of patients of intervention providers ; the charts of patients of control providers received no reminder . Measurements and main results During the 5-month study period , 346 patients were seen by the 36 primary care providers ( staff physicians , nurse practitioners , residents , and fellows ) in the intervention group , and 373 patients were seen by the 35 providers in the control group . Intervention providers changed 39 patients ( 11.3 % ) to other medications during the study period , compared with 1 patient ( < 1.0 % ) of control providers ( p<.0001 ) . For patients whose therapy was unchanged , providers noted angina in 23.1 % , indications other than those for hypertension in 9.5 % , intolerable adverse effects with first-line therapy in 13.9 % , and inadequte control with first-line therapy in 13.9 % . Of those patients without provider-indicated contraindications , 23.6 % were switched from calcium channel blockers to first-line agents during the intervention period . Conclusions The use of a computerized , clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general , and decreased the use of calcium channel blockers for the treatment of hypertension in particular Abstract One hundred and sixteen patients with hypertension were allocated r and omly to treatment by a computer program or by physicians . All were under the care of physicians in one of two hypertension clinics , but for computer treated patients ( C ) the program provided physicians with treatment recommendations which they were free to follow or reject whereas no recommendations were made for physician treated patients ( P ) . The computer program could use thiazide , alphamethyldopa , hydralazine or quanethidine ; physicians used whatever drugs they wished . Blood pressure ( BP ) response was similar for both groups , as were drug side effects and overt non-compliance with treatment . A computer program such as this one could guide allied health workers in setting s where expert physicians are scarce , improving large scale treatment of hypertension i lthough treatment with angiotensin-converting enzyme ACE ) inhibitors is known to improve outcome for patients ith left ventricular dysfunction , their use in the commuity has been suboptimal . Even when ACE inhibitors are rescribed , the dose used is usually below what has been hown to be effective in r and omized clinical trials . The oal of this study was to determine if the addition of a eminder to the echocardiography report for patients with a educed ejection fraction could increase the use of moderate r greater doses of ACE inhibitors or alternative appropriate reatment ( eg , angiotensin receptor blockers ) BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant |
13,949 | 27,207,303 | Although the risk for bias was high across studies , the findings suggest that there is promising but limited evidence that transitional care improves clinical outcomes for SNF patients . | Transitional care may be an effective strategy for preparing older adults for transitions from skilled nursing facilities ( SNF ) to home . | PURPOSE The Providing Assistance to Caregivers in Transition ( PACT ) program offers nursing home discharge planning and case management for individuals in the transitional period following a return to the community . The PACT program targeted individuals newly admitted to nursing homes and worked with a family caregiver to develop and implement a nursing home discharge plan . DESIGN AND METHOD Reported are the results of a r and omized control design evaluating the program 's effectiveness . Those individuals r and omly assigned to the intervention group ( n = 33 ) received PACT case management in addition to their usual medical and nursing home care . The individuals in the control group ( n = 29 ) continued their usual care . RESULT There were no statistical differences in the discharge rate ( 84 % treatment vs 76 % controls ) or in the median length of stay ( 42 days vs 55 days ) between the two groups of individuals . IMPLICATION S Replications or extensions of a PACT-type intervention might consider a broader mix of nursing homes , working directly with the nursing home 's admission Minimum Data Set coordinator in patient selection , or working with Medicare or Medicaid HMO plans The purpose of this pilot study was to test the initial efficacy , feasibility , and safety of a specially design ed postacute care transitional rehabilitation intervention for cardiac patients . Cardiac Transitional Rehabilitation Using Self-Management Techniques ( Cardiac TRUST ) is a family-focused intervention that includes progressive low-intensity walking and education in self-management skills to facilitate recovery following a cardiac event . Using a r and omized two-group design , exercise self-efficacy , steps walked , and participation in an outpatient cardiac rehabilitation ( CR ) program were compared in a sample of 38 older adults ( 17 Cardiac TRUST , 21 usual care ) . At discharge from postacute care , the intervention group trended toward higher levels of self-efficacy for exercise outcomes than the usual care group . During the 6 weeks following discharge , the intervention group had greater attendance in outpatient CR and a trend toward more steps walked during the first week . The feasibility of the intervention was better for the home health care participants than for those in the skilled nursing facility . The provision of CR during postacute care has the potential to bridge the gap in transitional services from hospitalization to outpatient CR for these patients at high risk for future cardiac events . Further evidence of the efficacy of Cardiac TRUST is warranted Context The relationship between factors indicative of personal socioeconomic disadvantage , such as where patients live , and readmission risk is unclear . Contribution The authors linked the ZIP+4 codes for Medicare patients ' residences to census block groups in the 2000 U.S. census . For each census block group ( or neighborhood ) , they calculated an area deprivation index score . Multivariable models assessed the relationship between area deprivation index score rankings and rehospitalization , controlling for patient and hospital characteristics . Caution The study did not assess the quality of care provided by the hospitals . Implication Medicare patients from disadvantaged neighborhoods have an increased risk for rehospitalization . The Editors Thirty-day rehospitalizations affect 1 in 5 hospitalized Medicare patients , cost more than $ 17 billion annually , and result in hospital-based Medicare payment penalties for congestive heart failure , pneumonia , and acute myocardial infa rct ion rehospitalizations ( 1 ) . Most persons believe that all hospitals can prevent at least some rehospitalizations by using a spectrum of programs to better support vulnerable patients during the high-risk period after hospital discharge ( 13 ) . However , the targeting of these programs has proven challenging , potentially because important factors contributing to rehospitalizations , such as socioeconomic disadvantage , are not well-measured ( 4 , 5 ) . Socioeconomic disadvantage is a complex theoretical concept , which describes the state of being challenged by low income , limited education , and subst and ard living conditions for both the person and his or her neighborhood or social network ( 6 , 7 ) . Detailed assessment of an individual patient 's socioeconomic status is a time-consuming and potentially uncomfortable task to add to a clinical encounter , and because such information is rarely available in the patient 's medical record , clinical teams often overlook socioeconomic factors when creating individualized care plans after hospital discharge ( 8) . Measures of neighborhood socioeconomic disadvantage , such as concentration of poverty in the neighborhood surrounding the patient 's residence , could be more easily accessed and assigned as a risk factor at the point of patient admission by using the patient 's address . However , the association between neighborhood disadvantage and rehospitalization risk has not yet been established . It is plausible that neighborhood socioeconomic disadvantage would influence rehospitalization risk because vulnerable patients depend on neighborhood supports for stability generally ( 912 ) , and these needs are likely to be increased in the period after hospital discharge ( 3 ) . Safety-net hospitals in the United States , which serve socioeconomically disadvantaged areas , are more apt to be financially penalized for their rehospitalization rates ( 1316 ) . Living in a socioeconomically disadvantaged neighborhood has been associated with health behaviors ( 17 ) ; access to food ( 18 , 19 ) and safety ( 20 ) ; and outcomes , such as mortality ( 10 , 1217 ) , birthweight ( 21 ) , and rehospitalization risk for heart failure ( 22 ) . In addition , important health indicators improve with moving persons to areas of less concentrated poverty ( 23 , 24 ) . In 2003 , Singh created a composite measure of neighborhood socioeconomic disadvantage for the United States , the area deprivation index ( ADI ) , on the basis of similar measures used in many other countries for re source planning and health policy development ( 2529 ) . The ADI is a factor-based index that uses 17 U.S. census poverty , education , housing , and employment indicators to characterize census-based regions ( 25 , 2729 ) . It has been correlated with many health outcomes , including all-cause , cardiovascular , cancer , and childhood mortality and cervical cancer prevalence ( 25 , 2732 ) . Socioeconomic disadvantage based on neighborhood risk through a ZIP codelinked ADI does not require a potentially lengthy and intrusive discussion with patients and families and could easily be made available to clinical teams and policymakers . Our objective was to determine whether neighborhood socioeconomic disadvantage could be useful to clinical planning by examining its relevance in a population likely to be targeted by clinical improvement activities design ed to reduce readmission risk . We analyzed the association between ADI ( defined at the census block group level ) and 30-day rehospitalizations for patients discharged with congestive heart failure , pneumonia , or acute myocardial infa rct ion , the clinical conditions used for the current calculation of Medicare 's rehospitalization penalties . Methods Data Sources and Study Population We used data from 2004 to 2009 from the Chronic Condition Data Warehouse ( 33 ) , including Medicare cl aims and enrollment files prelinked to annual Medicare provider of service files for a 5 % r and om national sample of Medicare beneficiaries . Beneficiaries who received railroad retirement benefits or were in an HMO were excluded because these groups have incomplete data . We identified 307 827 patients who were older than 65 years hospitalized with congestive heart failure , acute myocardial infa rct ion , or pneumonia using Medicare readmission measure definitions ( 3436 ) . We used the ZIP+4 code listed for the patient 's residence within Medicare data to link to the census block group with the same ZIP+4 area in 2000 U.S. census data for the 50 U.S. states and the District of Columbia . Each census block group covers an area of 600 to 3000 persons , averaging 1500 persons per group ( 37 ) . We excluded 52 083 patients without a ZIP+4 code in their Medicare data ( n = 9741 ) or whose documented ZIP+4 code did not exist in the 2000 census data ( n = 42 342 ) . Patients in this latter category may include those who design ate a post office box as their primary residence or those who reside in new ZIP+4 areas , U.S. territories , or institutions ( such as prisons ) . H and -checking of a small r and om sampling of these patients ' ZIP+4 codes suggests that most were assigned to a post office box . The final sample size was 255 744 patients . These patients originated from 4802 unique hospitals ( mean patients per hospital , 53.3 ; range , 1 to 743 patients ) . The University of Wisconsin Institutional Review Board approved this study . Variables Census Block GroupLevel Variables We calculated ADI scores for each U.S. census block group using the Singh method ( 14 , 1618 ) . This involved summing Singh 's 17 census indicators weighted by Singh 's factor score coefficients for each indicator ( 25 ) ( Table 1 ) . The Appendix contains more detail on constructing the ADI . We examined the distribution of ADI values and sorted neighborhoods into percentiles by increasing ADI . Table 1 . Census Data Block Group Components and Factor Score Coefficients in the Singh ADI Patient-Level Variables We constructed all-cause rehospitalization within 30 days of discharge from Medicare cl aims ( 3436 ) . Other variables drawn from Medicare files included patient age , sex , race , Medicaid status , initial Medicare enrollment due to disability , index hospitalization length of stay , and discharge to a skilled-nursing facility . Race was categorized as white , black , or other based on the beneficiary race code . Each patient 's Centers for Medicare & Medicaid Services hierarchical condition category score , calculated from all outpatient and inpatient cl aims over the 12 months before the index hospitalization , was included as a risk adjustment measure ( 38 ) . Comorbid conditions were identified using Elixhauser methods , incorporating data from the index hospitalization and from all hospitalizations and physician cl aims during the year before the index hospitalization ( 39 ) . Of the comorbid conditions identified using this approach , 17 had frequencies of greater than 5 % in the sample and were included as indicators . Comorbid conditions occurring less often were compiled into an other comorbid condition indicator and included alcohol or drug abuse , rheumatoid arthritis , collagen vascular disease , chronic blood loss anemia , liver disease , lymphoma , metastatic cancer , solid tumor without metastases , paralysis , psychoses , and peptic ulcer disease . We assessed the rurality of each patient 's ZIP code of residence using the U.S. Department of Agriculture 's ruralurban commuting area codes , grouped into categories of urban core areas , suburban areas , large town areas , and small town or isolated rural areas ( 40 , 41 ) . Index hospital characteristics , including Medicare geographic region , for-profit status , and medical school affiliation , were drawn from the Medicare provider of service file corresponding to the patient 's index hospitalization date ( 42 ) . We estimated the annual Medicare discharge volume for each hospital by multiplying the number of cl aims from each hospital in the 5 % national sample by 20 . We then grouped hospitals into low- , middle- , and high-volume tertiles . Approximately 0.1 % of our sample was missing data on race ( n = 291 ) , and less than 0.3 % were missing data on hospital medical school affiliation ( n = 777 ) and for-profit status ( n = 777 ) . There were no missing data for other patient-level variables . Statistical Analysis We examined the unadjusted relationship between ADI percentile and 30-day rehospitalization , overall and by primary disease . On the basis of the empirical ADI data , the most disadvantaged neighborhoods made up the top 15 % of the distribution . To better assess within-group differences , we divided this most disadvantaged 15 % into 3 equally sized 5 % groupings representing the third-most , second-most , and most disadvantaged 5 % of neighborhoods . The remaining neighborhoods ( 85 % ) were grouped into a comparator category . We examined frequencies of patient and index hospital characteristics for each grouping . We used logistic regression to assess the relationship between ADI grouping and 30-day rehospitalization . Next , to assess the full spectrum of ADI effect , we divided STUDY OBJECTIVE To assess the impact of a pilot pharmacist-managed medication reconciliation program on mortality and use of health care services in patients discharged to home from a skilled nursing facility ( SNF ) . DESIGN Quasi-experimental , controlled trial . SETTING Health maintenance organization ( HMO ) . PATIENTS Five hundred twenty-one HMO members . INTERVENTION Patients were assigned to the medication reconciliation program ( 113 patients ) or to the usual care control group ( 408 patients ) after discharge to home from an SNF . Assignment to the medication reconciliation group or to the control group was based on provider su bmi ssion of a discharge summary within 0 - 48 hours of discharge or more than 48 hours after discharge , respectively . MEASUREMENTS AND MAIN RESULTS Integrated electronic medical and pharmacy data and multivariate analyses were used to assess the medication reconciliation program with regard to its impact on postdischarge mortality , rehospitalization , and ambulatory clinic and emergency department visits . Compared with usual care during the 60 days after discharge from the SNF , patients who received the medication reconciliation intervention had an adjusted 78 % reduction in the risk of death ( adjusted hazard ratio 0.22 , 95 % confidence interval [ CI ] 0.06 - 0.88 ) and a trend toward an increased rate of ambulatory care visits ( adjusted incidence risk ratio 1.17 , 95 % CI 0.99 - 1.37 ) . No significant differences were noted in adjusted risks of an emergency department visit and rehospitalization ( p>0.05 ) between the medication reconciliation and usual care groups . CONCLUSION Our data support the hypothesis that a formal medication reconciliation process , with its increased coordination of information between health care providers and patients , can decrease mortality after discharge from an SNF . Our findings support the role of medication reconciliation as an integral step in the transitional care process and interests of health care accrediting agencies , such as the Joint Commission , that have included medication reconciliation as an important initiative |
13,950 | 26,596,716 | This meta- analysis has shown that alvimopan significantly accelerates recovery of gastrointestinal function and reduces the length of stay in patients performed radical cystectomy . | PURPOSE The aim of the study was to evaluate the efficacy of alvimopan on accelerates gastrointestinal recovery after radical cystectomy . | BACKGROUND Radical cystectomy ( RC ) for bladder cancer is frequently associated with delayed gastrointestinal ( GI ) recovery that prolongs hospital length of stay ( LOS ) . OBJECTIVE To assess the efficacy of alvimopan to accelerate GI recovery after RC . DESIGN , SETTING , AND PARTICIPANTS We conducted a r and omized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics . INTERVENTION Oral alvimopan 12 mg ( maximum : 15 inpatient doses ) versus placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The two-component primary end point was time to upper ( first tolerance of solid food ) and lower ( first bowel movement ) GI recovery ( GI-2 ) . Time to discharge order written , postoperative LOS , postoperative ileus (POI)-related morbidity , opioid consumption , and adverse events ( AEs ) were evaluated . An independent adjudication of cardiovascular AEs was performed . RESULTS AND LIMITATIONS Patients were r and omized to alvimopan ( n=143 ) or placebo ( n=137 ) ; 277 patients were included in the modified intention-to-treat population . The alvimopan cohort experienced quicker GI-2 recovery ( 5.5 vs 6.8 d ; hazard ratio : 1.8 ; p<0.0001 ) , shorter mean LOS ( 7.4 vs 10.1 d ; p=0.0051 ) , and fewer episodes of POI-related morbidity ( 8.4 % vs 29.1 % ; p<0.001 ) . The incidence of opioid consumption and AEs or serious AEs ( SAEs ) was comparable except for POI , which was lower in the alvimopan group ( AEs : 7 % vs 26 % ; SAEs : 5 % vs 20 % , respectively ) . Cardiovascular AEs occurred in 8.4 % ( alvimopan ) and 15.3 % ( placebo ) of patients ( p=0.09 ) . Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy . CONCLUSIONS Alvimopan is a useful addition to a st and ardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS , with a safety profile similar to placebo . PATIENT SUMMARY This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer . Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo , with comparable safety . TRIAL REGISTRATION Clinical Trials.gov identifier NCT00708201 BACKGROUND Reporting methodology is highly variable and nonst and ardized , yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance . OBJECTIVE We sought to define the type , incidence , and severity of early postoperative morbidities following radical cystectomy ( RC ) using a st and ardized reporting methodology . DESIGN , SETTING , AND PARTICIPANTS Between 1995 and 2005 , 1142 consecutive RCs were entered into a prospect i ve complication data base and retrospectively review ed for accuracy . All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were analyzed and grade d according to the Memorial Sloan-Kettering Cancer Center complication grading system . Complications were defined and stratified into 11 specific categories . Univariate and multivariate regression models were used to define predictors of complications . RESULTS AND LIMITATIONS Sixty-four percent ( 735/1142 ) of patients experienced a complication within 90 d of surgery . Among patients experiencing a complication , 67 % experienced a complication during the operative hospital admission and 58 % following discharge . Overall , the highest grade of complication was grade 0 in 36 % ( n=407 ) , grade 1 - 2 in 51 % ( n=582 ) , and grade 3 - 5 in 13 % ( n=153 ) . Gastrointestinal complications were most common ( 29 % ) , followed by infectious complications ( 25 % ) and wound-related complications ( 15 % ) . The 30-d mortality rate was 1.5 % . CONCLUSIONS Surgical morbidity following RC is significant and , when strict reporting guidelines are incorporated , higher than previously published . Accurate reporting of postoperative complications after RC is essential for counseling patients , combined modality treatment planning , clinical trial design , and assessment of surgical success Objective Optimizing peri‐operative care using an enhanced recovery programme improves short‐term outcomes following colonic resection . This study compared a prospect i ve group of patients undergoing resection of colorectal cancer within an enhanced recovery programme , with a prospect ively studied historic cohort receiving conventional care OBJECTIVE To investigate the efficacy and safety of alvimopan , 12 mg , administered orally 30 to 90 minutes preoperatively and twice daily postoperatively in conjunction with a st and ardized accelerated postoperative care pathway for managing postoperative ileus after bowel resection . DESIGN , SETTING , AND PATIENTS This multicenter , r and omized , placebo-controlled , double-blind , phase 3 trial enrolled adult patients undergoing partial bowel resection with primary anastomosis by laparotomy and scheduled to receive intravenous , opioid-based , patient-controlled analgesia . A st and ardized accelerated postoperative care pathway including early ambulation , oral feeding , and postoperative nasogastric tube removal was used to facilitate gastrointestinal ( GI ) tract recovery in all of the patients . MAIN OUTCOME MEASURES The primary end point was time to GI-2 recovery ( toleration of solid food and first bowel movement ) . Secondary end points included time to GI-3 recovery ( toleration of solid food and first flatus or bowel movement ) , hospital discharge order written , and actual hospital discharge . Postoperative length of hospital stay based on calendar day of hospital discharge order written , opioid consumption , and overall postoperative ileus-related morbidity were recorded . RESULTS Alvimopan , 12 mg , was well tolerated and significantly accelerated GI-2 recovery , GI-3 recovery , and actual hospital discharge compared with a st and ardized accelerated postoperative care pathway alone ( hazard ratio = 1.5 , 1.5 , and 1.4 , respectively ; P < .001 for all ) . Time to hospital discharge order written as measured by hazard ratio ( 1.4 ) and by postoperative calendar days ( mean for alvimopan , 5.2 days ; mean for placebo , 6.2 days ) was also accelerated . Opioid consumption was comparable between groups , and alvimopan was associated with reduced postoperative ileus-related morbidity compared with placebo . CONCLUSIONS Alvimopan , 12 mg , administered 30 to 90 minutes before and twice daily after bowel resection is well tolerated , accelerates GI tract recovery , and reduces postoperative ileus-related morbidity without compromising opioid analgesia Postoperative ileus ( POI ) is a transient loss of coordinated peristalsis precipitated by surgery and exacerbated by opioid pain medication . Ileus causes a variety of symptoms including bloating , pain , nausea , and vomiting , but particularly delays tolerance of oral diet and liquids . Thus POI is a primary determinant of hospital stay after surgery . ‘ Fast-track ’ recovery protocol s , opioid sparing analgesia , and laparoscopic surgery reduce but do not eliminate postoperative ileus . Alvimopan is a mu opioid receptor antagonist that blocks the effects of opioids on the intestine , while not interfering with their central ly mediated analgesic effect . Several large r and omized clinical trials have demonstrated that alvimopan accelerates the return of gastrointestinal function after surgery and subsequent hospital discharge by approximately 20 hours after elective open segmental colectomy . However , it has not been tested in patients undergoing laparoscopic surgery and is less effective in patients receiving nonsteroidal anti-inflammatory agents in a narcotic sparing postoperative pain control regimen . Safety concerns seen with chronic low dose administration of alvimopan for opioid bowel dysfunction have not been noted with its acute use for POI Introduction We sought to evaluate the cost effectiveness of perioperative use of alvimopan in cystectomy and urinary diversion . A recent r and omized controlled trial demonstrated the efficacy of alvimopan in reducing postoperative ileus and length of stay in cystectomy ; however , a major limitation was the exclusion of epidural analgesia . Material s and methods Eighty – six cystectomy and urinary diversion procedures performed by seven surgeons were analyzed between January 2008 and April 2012 . The first 50 patients did not receive alvimopan perioperatively , while the subsequent 36 received a single dose of 12 mg preoperatively and then 12 mg every 12 hours for 15 doses or until discharge . Results The groups were equal with respect to age , gender , indication , surgeon , and type of diversion . Patients who received alvimopan experienced a shorter length of stay ( LOS ) versus those in who did not receive alvimopan ( 10.5 vs. 8.6 days , p = 0.005 , 95 % CI 0.6–3.3 ) . Readmission for ileus was low in both alvimopan and control groups ( 0 % and 4.4 % , respectively ) . Costs were significantly lower in the alvimopan group than the control groups ( 2012 USD 32,443 vs. 40,604 p < 0.001 ) . This difference stood up to multivariate analysis with a $ 7,062 difference in hospital stay . Conclusions Use of alvimopan in the routine perioperative care of our cystectomy and urinary diversion patients has decreased LOS by 1.9 days . Additionally , institution of routine perioperative alvimopan has reduced costs by $ 7,062 per admission ( 20 % reduction ) . This demonstrates a real world application of alvimopan at a moderate volume center Background : Laparoscopic colonic surgery has been cl aim ed to hasten recovery and reduce hospital stay compared with open operation . Recently , enforced multimodal rehabilitation ( fast-track surgery ) has improved recovery and reduced hospital stay in both laparoscopic and open colonic surgery . Since no comparative data between laparoscopic and open colonic resection with multimodal rehabilitation are available , the value of laparoscopy per se is unknown . Methods : In a r and omized , observer- and -patient , blinded trial , 60 patients ( median age 75 years ) underwent elective laparoscopic or open colonic resection with fast-track rehabilitation and planned discharge after 48 hours . Functional recovery was assessed in detail during the first postoperative month . Results : Median postoperative hospital stay was 2 days in both groups , with early and similar recovery to normal activities as assessed by hours of mobilization per day , computerized monitoring of motor activity assessed , pulmonary function , cardiovascular response to treadmill exercise , pain , sleep quality , fatigue , and return to normal gastrointestinal function . There were no significant differences in postoperative morbidity , mortality , or readmissions , although 3 patients died in the open versus nil in the laparoscopic group . Conclusion : Functional recovery after colonic resection is rapid with a multimodal rehabilitation regimen and without differences between open and laparoscopic operation . Further large-scale studies are required on potential differences in serious morbidity and mortality INTRODUCTION Radical cystectomy is associated with significant morbidity and cost , with rates of gastrointestinal complications as high as 30 % . Alvimopan is a mu opioid receptor antagonist that has been shown in r and omized-control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis . We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan and cost benefit associated . MATERIAL S AND METHODS Between January 2008 and October 2012 , 80 patients underwent radical cystectomy with urinary diversion at two institutions . Forty-two patients in our study did not receive alvimopan preoperatively . Thirty-eight patients received perioperative alvimopan and were without postoperative nasogastric decompression . Return of bowel function , initiation of diet , and gastrointestinal complications and estimated cost of hospitalization were evaluated . RESULTS Times to first flatus ( 3.1 days versus 4.7 days , p < 0.01 , 95 % CI 0.96 - 2.24 ) and bowel movement ( 3.9 days versus 4.9 days , p < 0.01 , 95 % CI 0.45 - 1.55 ) were significantly shorter in those patients who received alvimopan . Additionally , the initiation of clear liquid diet ( 4.1 days versus 5.5 days , p < 0.01 , 95 % CI 0.70 - 2.10 ) , regular diet ( 5.2 days versus 6.3 days , p < 0.01 , 95 % CI 0.39 - 1.81 ) and hospital discharge ( 6.1 days versus 7.7 days , p = 0.04 , 95 % CI 0.01 - 3.21 ) were accelerated in the alvimopan cohort . There were no incidences of prolonged ileus in patients who received perioperative alvimopan ( 0 % versus 26.2 % , p < 0.01 ) . With an approximate average cost of alvimopan administration $ 825 per hospitalization , the average cost benefit of administration over control was $ 1515 per hospitalization . The cost benefit was mainly a result of a shorter inpatient hospitalization and lack of gastrointestinal morbidity which accumulated a majority of the difference . CONCLUSION In our experience , the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge , eliminates the need for nasogastric tube decompression , and reduces the incidence of post-operative ileus in patients following radical cystectomy and urinary diversion Postoperative ileus ( POI ) after open abdominal surgery and bowel resection can lead to significant patient discomfort , morbidity , and prolonged length of stay in the hospital . Several factors have been implicated in the pathophysiology of POI , including surgical manipulation of the bowel , inflammation , inhibitory neural reflexes , and endogenous and exogenous opioids . Alvimopan ( Entereg ) , approved by the FDA to accelerate upper and lower gastrointestinal ( GI ) recovery following partial large-bowel or small- bowel resection with primary anastomosis , represents a potential advance in the care of these patients . In five r and omized , double-blind , placebo-controlled , phase 3 clinical trials , alvimopan , compared with placebo , accelerated the time to GI recovery and hospital discharge status after bowel resection . In this article , we review the formulary details of alvimopan for in-hospital management of POI following this procedure Background Alvimopan is a peripherally acting mu-opioid receptor ( PAM-OR ) antagonist for accelerating gastrointestinal recovery after surgery . Methods Patients undergoing open laparotomy ( bowel resection , n = 418 ; hysterectomy , n = 197 ) were r and omized to receive alvimopan 6 or 12 mg or placebo orally ≥2 h before surgery and then b.i.d . until hospital discharge ( up to 7 days ) . The primary efficacy endpoint was time to gastrointestinal ( GI ) recovery ( measured by toleration of solid food and passage of flatus/stool ; GI-3 ) . Secondary endpoints included time to GI-2 recovery ( toleration of solid food and passage of stool ) and hospital discharge order written ( DCO ) . Results Alvimopan did not significantly accelerate GI-3 compared with placebo [ 6 mg : hazard ratio ( HR ) = 1.20 , p = 0.080 ; 12 mg : HR = 1.24 , p = 0.038 ) . However , after adjustment for significant covariates ( sex/surgical duration ) , benefits were significant for both doses ( 6 mg : HR = 1.24 , p = 0.037 ; 12 mg : HR = 1.26 , p = 0.028 ) . Alvimopan also significantly accelerated time to GI-2 ( 6 mg : HR = 1.37 , p = 0.008 ; 12 mg : HR = 1.33 , p = 0.018 ) and DCO ( 6 mg : HR = 1.31 , p = 0.008 ; 12 mg : HR = 1.28 , p = 0.015 ) . Adverse events were similar between groups . Conclusions Alvimopan ( 6 or 12 mg ) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy INTRODUCTION Radical cystectomy is associated with significant morbidity , with rates of gastrointestinal complications as high as 30 % . Alvimopan is a mu opioid receptor antagonist that has been shown in r and omized control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis . We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan . MATERIAL S AND METHODS Between January 2008 and August 2011 , 50 consecutive patients underwent radical cystectomy with urinary diversion at our institution . The first 27 patients in our study did not receive alvimopan preoperatively . The latter 23 patients received perioperative alvimopan and were without postoperative nasogastric decompression . Return of bowel function , initiation of diet , and gastrointestinal complications were evaluated . RESULTS Times to first flatus ( 3.1 versus 5.6 days , p < 0.001 , 95 % CI 1.66 - 3.26 ) and bowel movement ( 3.8 versus 6.0 days , p < 0.001 , 95 % CI 1.35 - 2.99 ) were significantly shorter in those patients who received alvimopan . Additionally , the initiation of clear liquid diet ( 4.1 versus 6.3 days , p < 0.001 , 95 % CI 1.20 - 3.12 ) , regular diet ( 5.7 versus 7.3 days , p = 0.023 , 95 % CI 0.57 - 2.63 ) and hospital discharge ( 7.4 versus 9.5 days , p = 0.04 , 95 % CI 0.03 - 4.21 ) were accelerated in the alvimopan cohort . There were no incidences of prolonged ileus in patients who received perioperative alvimopan ( 0 % versus 25.9 % , p = 0.012 ) . CONCLUSION In our experience , the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge , eliminates the need for nasogastric tube decompression , and reduces the incidence of postoperative ileus in patients following radical cystectomy and urinary diversion |
13,951 | 21,932,113 | The efficacy was more potent for the second and the third generation of BPs than the first generation .
Conclusions The overall moderate evidence from the RCTs confirmed the significantly short-term and middle-term efficacy of BPs on periprosthetic bone loss after joint arthroplasty . | Summary The present meta- analysis aim ed to evaluate the middle-term efficacy of bisphosphonates on maintaining periprosthetic bone mass after joint arthroplasty and the potential influential factors .
It was found that the protective effect of bisphosphonates , probably modified by its generation and the prosthesis location , could persist in a middle-term follow-up after surgery and after drug discontinuation .
Introduction A previous meta- analysis of 6 RCTs with follow-up of 12 months suggested that bisphosphonates ( BPs ) could prevent bone loss after arthroplasty up to 6 months .
Our meta- analysis based on 14 RCTs involving 671 patients with follow-up up to 72 months aim ed to evaluate the middle-term efficacy of BPs , underst and the sources of heterogeneity , and comprehensively identify the potential influential factors . | The efficacy of clodronate to reduce bone loss around uncemented stems after total hip arthroplasty ( THA ) was evaluated . Ninety-one patients operated with uncemented THA were r and omized to receive either intramuscular clodronate at a dose of 100 mg weekly for 12 months or no treatment . Periprosthetic and contralateral bone mineral density ( BMD ) scans were performed and biochemical markers of bone turnover measured at baseline and at 3 , 6 , and 12 months . At month 12 , with the exception of Gruen zones 4 and 5 , patients treated with clodronate showed less bone loss at all zones , reaching statistical significance ( P < 0.05 ) in Gruen zones 2 and 6 ( difference of 6.6 and 5.9 % , respectively ) . Analysis of data according to gender revealed sex-related differences in bone loss and efficacy of treatment . After 12 months , the difference in bone loss between treated and untreated women in five out of seven Gruen zones ranged from 6.2 to 13.3 % ( SS at zones 2 and 6 ) , whereas comparison between treated and untreated men showed no BMD differences in all zones ( P > 0.05 ) . Median percent changes in serum levels of markers of bone metabolism by gender were consistent with BMD changes . A 1-year treatment with intramuscular clodronate determined a significant reduction of bone loss after THA . This was mainly attributed to its greater efficacy in the female population , which is at higher risk for bone loss . This observation suggests the need for the characterization of high-risk subjects as potential c and i date s for prevention strategies Summary Forty-three patients who had undergone cementless THA were r and omly assigned to receive no osteoactive drug or oral risedronate for 6 months . Postoperative decrease of BMD in the risedronate group was significantly lower than that seen in the control group in zones 1 , 2 , 3 , 6 , and 7 . Introduction Proximal bone resorption around the femoral stem often has been observed after total hip arthroplasty ( THA ) , could lead to late stem loosening . We previously reported the efficacy of etidronate on periprosthetic bone resorption after cementless THA . Recently risedronate is suggested to be effective for the prevention and treatment of for osteoporosis . The purpose of the present study was to evaluate the effects of risedronate on periprosthetic bone loss after cementless THA . Methods Forty-three patients who had undergone cementless THA were r and omly assigned to receive no osteoactive drug ( 21 patients ) or oral risedronate 2.5 mg/day ( 22 patients ) for 6 months . Three patients were eliminated from the risedronate group because of dyspepsia . Periprosthetic bone mineral density ( BMD ) in seven regions of interest based on the zones of Gruen et al. was measured with dual energy X-ray absorptiometry at 3 weeks and 6 months postoperatively . Results At 6 months after surgery , postoperative decrease of BMD in the risedronate group was significantly lower than that seen in the control group in zones 1 , 2 , 3 , 6 , and 7 ( p < 0.05 , p < 0.01 , p < 0.01 , p < 0.05 , and p < 0.05 , respectively ) . Conclusion These outcomes suggested that risedronate might reduce the periprosthetic bone resorption after cementless THA Background and Aims : Periprosthetic bone loss , especially in the proximal part of the femur , is common after cemented and uncemented total hip arthroplasty ( THA ) . Short-term studies suggest that bisphosponates can minimize this bone loss related to stress-shielding phenomenon . The aim of the present r and omized study was to investigate whether the positive effect of a 6 months alendronate treatment postoperatively still exists at five-year follow up . Material s and Methods : Sixteen uncemented primary THA patients were r and omized to receive either 10 mg alendronate + 500 mg calcium ( n = 7 ) or 500 mg calcium only ( n = 9 ) daily for 6 months postoperatively . Periprosthetic bone mineral density ( BMD ) was measured with the dual X-ray absorptiometry ( DXA ) postoperatively and at 6 , 12 , 24 , 36 and 60 months follow-up . Results : At the 5-year follow up , the calcium group showed mean BMD decreases of 23.1 % ( SD 14.6 ) in the proximal part of the femur ( prROI ) and 9.6 % ( SD 14.9 ) in total femoral regions of interest ( totROI ) . In the alendronate group the corresponding BMD decreases were 13.6 % ( SD 19.0 ) and 3.9 % ( SD 7.6 ) respectively . The positive effect of alendronate was already demonstrated during the first six months postoperatively . Subsequently the bone loss was equal in both groups , and the 5-year BMD changes were not significantly different between the groups . Conclusions : Alendronate seems to decrease early periprosthetic bone loss after arthroplasty but this pilot study could not provide enough evidence that the positive effect noted in the early postoperative period is still maintained 5 years after the operation BACKGROUND Bone mineral density decreases after total knee arthroplasty and is believed to affect prosthetic fixation . Treatment with alendronate has been shown to improve short-term bone mineral density after total knee arthroplasty ; however , the long-term effects of this therapy are unknown . The purpose of this study was to evaluate the long-term effects of a six-month course of alendronate on bone mineral density after total knee arthroplasty . METHODS Sixty patients were r and omly assigned to receive either oral alendronate at a dosage of 10 mg/day for six months or no alendronate . The bone mineral density in the distal aspect of the femur and the proximal aspect of the tibia was measured preoperatively and at six , twelve , and thirty-six months after total knee arthroplasty . RESULTS Fifty-four patients ( twenty-nine in the alendronate group and twenty-five in the control group ) completed the study . The alendronate group showed significant increases in bone mineral density in the distal aspect of the femur compared with the controls at six months ( + 4.8 % and -14.2 % , respectively ; p < 0.01 ) and twelve months ( + 1.6 % and -11.5 % , respectively ; p < 0.01 ) . No significant difference in bone mineral density was detected between the groups at thirty-six months ( -3.9 % and -12.2 % , respectively ; p = 0.08 ) . Similar trends in bone mineral density changes were also observed in the proximal aspect of the tibia . CONCLUSIONS A six-month course of alendronate initially increased bone mineral density at six and twelve months after total knee arthroplasty , but no difference was noted after thirty-six months . The effect of alendronate on bone mineral density after total knee arthroplasty may be limited after discontinuation of therapy Acute periprosthetic bone loss occurs after total hip arthroplasty . Bone loss undermines the support of the implant and may contribute to prosthetic failure . At present , there is no established prophylaxis for this process . We studied the effect of a single-dose infusion of 90 mg of pamidronate on early periprosthetic bone mineral density ( BMD ) , biochemical markers of bone turnover , radiological , and clinical outcome in a 26-week , prospect i ve , r and omized , double-blinded study of 47 men and women undergoing total hip arthroplasty . Pamidronate therapy led to a significant reduction in bone loss compared with placebo for both the proximal femur and the pelvis ( repeated measures analysis of variance [ ANOVA ] ) ; p = 0.001 and p = 0.01 , respectively ) . Pamidronate therapy was associated with suppression of all biochemical markers of bone turnover compared with placebo ( repeated measures ANOVA ; p < 0.05 for all comparisons ) , with the exception of urinary free deoxypyridinoline . Pamidronate did not interfere with the clinical improvement in symptoms after total hip arthroplasty , or radiological outcome , and was not associated with an increase in adverse events . This study provides clinical data on the efficacy and safety of bisphosphonates for the prevention of bone loss after total hip arthroplasty and supports the establishment of larger-scale clinical trials to determine the long-term clinical efficacy of this intervention using implant failure as the primary endpoint Periprosthetic bone loss after arthroplasty may threaten prosthesis survival . The current study investigated the effect of etidronate therapy on periprosthetic , contralateral hip , and spine bone mineral density ( BMD ) in a one-year , prospect i ve , r and omized , double-blind study on 46 patients after cemented hip arthroplasty . BMD was measured with dual-energy X-ray absorptiometry ( DXA ) . There were no significant differences between mean BMD measurements of the etidronate and placebo groups , with the exception of the mean percent change in the spine at six months and 12 months and in Gruen zone 3 at six months ; in all three cases , the etidronate group had significantly greater mean values . These findings suggest that cyclic etidronate therapy has no significant effect in suppressing periprosthetic bone loss following cemented hip arthroplasty . RésuméLa perte osseuse périprothétique après arthroplastie peut mettre en danger la survie de la prothèse . Nous avons étudié l'effet de l'étidronate sur la densité minérale ( DM ) de l'os en zone périprothétique , au niveau de la hanche opposée et du rachis . L'étude à un an , prospect i ve , r and omisée et en double-aveugle a inclue 46 malades après arthroplastie de la hanche cimentée . La DM était mesurée par absorptiométrie biphotonique ( DXA ) . En général , il n'y avait pas de différence significative entre la DM moyenne du groupe étidronate et du groupe placebo . Les seules exceptions étaient les changements en pourcentage sur le rachis après 6 et 12 mois et en Zone 3 de Gruen après 6 mois ; dans tous ces cas , le groupe étidronate avait des valeurs moyennes significativement plus gr and es . Ces résultats indiquent que la thérapie cyclique par étidronate n'a pas d'effet significatif pour enrayer la perte osseuse périprothétique après arthroplastie cimentée de la hanche Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis . We hypothesized that alendronate plus vitamin D(3 ) ( ALN + D ) would increase fractional calcium absorption ( FCA ) . In this r and omized , double-blind , placebo-controlled multicenter clinical trial , 56 postmenopausal women with 25-hydroxyvitamin D [ 25(OH)D ] concentrations of 25 ng/mL or less and low bone mineral density ( BMD ) received 5 weekly doses of placebo or alendronate 70 mg plus vitamin D(3 ) 2800 IU ( ALN + D ) . Calcium intake was stabilized to approximately 1200 mg/d prior to r and omization . FCA was determined using a dual-tracer stable-calcium isotope method . FCA and 25(OH)D were similar between treatment groups at baseline ( 0.31 ± 0.12 ng/mL and 19.8 ± 4.7 ng/mL , respectively ) . After 1 month of treatment , subjects r and omized to ALN + D experienced a significant least squares ( LS ) mean [ 95 % confidence interval ( CI ) ] increase in FCA [ 0.070 ( 0.042 , 0.098 ) ] , whereas FCA did not change significantly in the placebo group [ -0.016 ( -0.044 , 0.012 ) ] . After ALN + D treatment , patients had higher 25(OH)D levels ( LS mean difference 7.3 ng/mL , p < .001 ) . The rise in serum 1,25-dihydroxyvitamin D(3 ) ( p < .02 ) and parathyroid hormone ( p < .001 ) were greater in the ALN + D group than in placebo-treated patients . ALN + D was associated with an increase in FCA of 0.07 . To our knowledge , there is no other trial showing such a marked rise in calcium absorption owing to treatment with a bisphosphonate or owing to a small rise in 25(OH)D. This unique response of ALN + D is important for the treatment of osteoporosis , but the exact mechanism requires further study Undesired bone loss around implants is considered to occur mainly because of a stress-shielding phenomenon . Bone surrounding the total knee arthroplasty ( TKA ) adjusts its mineral density and structure to meet new mechanical dem and s. Immobilization , in combination with local operative trauma to the bone and soft tissues , has an additional impact on bone loss . The clinical survival of TKA is associated with the quality and quantity of the surrounding bone environment . Poor bone quality and quantity may predispose to aseptic implant loosening and periprosthetic fractures . We investigated the efficacy of oral bisphosphonate ( alendronate , Fosamax ) with calcium ( Calcichew ) for the inhibition of early bone mineral density ( BMD ) loss after TKA in a prospect i ve , r and omized , one-year follow-up study . Periprosthetic BMD changes were measured with fan-beam dual-energy X-ray absorptiometry ( DXA ) in 19 patients with knee osteoarthrosis . Patients ( n = 8) treated with 10 mg alendronate and 500 mg calcium daily maintained distal femoral BMD values close to the baseline values ( P > 0.04 ) , while patients receiving only 500 mg of calcium daily ( n = 11 ) showed significant bone loss during the one-year follow-up ( P < 0.015 ) . The treatment groups differed significantly in metaphyseal anterior , posterior , diaphyseal , and metaphyseal total regions of interest ( ROIs ) ( repeated measures ANOVA analyses , P = 0.019 , P = 0.010 , P = 0.022 , and P = 0.024 , respectively ) . Our results indicate that oral alendronate reduces early postoperative periprosthetic bone loss significantly . This therapeutic strategy may improve the results and longevity of primary total knee arthroplasties In this trial we studied the effect of pamidronate on periprosthetic bone turnover and pelvic implant migration over 2 years after hybrid total hip arthroplasty ( THA ) . Twenty-two patients received 90 mg of pamidronate and 22 received placebo at r and omization 5 days after surgery . Rapid periprosthetic bone loss occurred in the placebo group over the first 6 months and was accompanied by transient increases in biochemical markers of bone turnover . Partial recovery in bone mass occurred in most regions after this period . No recovery of bone mass occurred at the femoral calcar or the medial wall of the acetabulum . Femoral calcar bone loss at 2 years was strongly predicted by acute biomarker changes at week 6 . Pamidronate therapy reduced femoral bone loss in the region of the femoral calcar ( P = 0.01 ) , but did not affect pelvic bone loss . Pamidronate therapy also inhibited the transient rise in biochemical markers of bone turnover during this period . Pamidronate therapy did not affect acetabular cup migration . Cup migration was inversely related to subject age , but unrelated to initial post-operative bone mineral density , or subsequent bone loss . In summary , early periprosthetic bone loss is associated with a transient expansion of the bone remodeling space . Bisphosphonate therapy reduces femoral calcar bone loss and bone turnover after THA , but did not influence cup migration in this study . Acute changes in biochemical markers predict femoral periprosthetic bone loss Summary INTRODUCTION : Periprosthetic bone loss occurs after insertion of a total hip prosthesis and is often a result of stress shielding or altered loading of the proximal femur . Preventing the bone loss , which may threaten the prosthesis survival , with an antiresorptive drug would be highly advantageous . MATERIAL S AND METHODS : Our study investigated the effect of cyclic etidronate therapy on periprosthetic , contralateral hip , and spine bone mineral density ( BMD ) in a one-year , prospect i ve , r and omized , double-blind study in 31 patients after cemented hip arthroplasty . Etidronate was taken orally in a regimen repeated every 14 weeks , and periprosthetic BMD was measured with dual energy X-ray absorptiometry ( DXA ) in the total periprosthetic area and in the seven Gruen zones at 1 week ( baseline ) , 6 weeks , 3 months , 6 months , and 12 months postoperatively . RESULTS : In the etidronate group there were significant temporal BMD decreases measured in Gruen zones 2 , 3 , 6 , and 7 and in the entire proximal femur ; the greatest decrease was 12.9 % and was measured in zone 7 at six months . Also in the etidronate group , there was a significant 2.8 % temporal BMD increase in the spine at 12 months . In the placebo group there were significant temporal BMD decreases measured in Gruen zones 1 , 2 , 3 , 5 , 6 , and 7 and in the entire proximal femur ; the greatest decrease was 25.5 % and was measured in zone 7 at 12 months . There were no significant differences between the mean BMD measurements of the etidronate and placebo groups . CONCLUSION : These findings suggest that cyclic etidronate therapy has no significant effect in suppressing periprosthetic bone loss after cemented hip arthroplasty Proximal bone resorption around the femoral stem is one of the major complications of cementless total hip arthroplasty ( THA ) . The potential complications result ing from proximal bone resorption include femoral fracture and late stem loosening . The purpose of this study was to evaluate the effects of cyclic therapy with etidronate on periprosthetic bone mineral density ( BMD ) after cementless THA . Fifty-two patients who had undergone cementless THA were r and omized for this study . Group A consisted of 30 hips in 29 patients without osteoactive drugs . Group B consisted of 23 hips in 23 patients with cyclic therapy with etidronate ( i.e. , 400 mg/day of oral etidronate for 2 weeks followed by 12 weeks of 500 mg/day of calcium lactate and repeated every 14 weeks ) , one of whom was excluded from the study because of side effects attributed to the drug . Periprosthetic BMD in seven regions of interest based on the zones of Gruen et al. ( Clin . Orthop . 141 ( 1979 ) , 17 - 27 ) was measured with dual energy X-ray absorptiometry ( DXA ) at 3 weeks , 6 months , and 12 months postoperatively . The postoperative decreases of BMD in group B were significantly lower than those in group A in zones 1 and 7 ( P < 0.05 and P < 0.05 , respectively ) at 6 months and in zones 1 , 2 , 6 , and 7 ( P < 0.05 , P < 0.05 , P < 0.05 , and P < 0.001 , respectively ) at 12 months . The BMD change appeared to be stabilized at 6 months in all zones in group B , while in group A there was a progressive decrease of average BMD ( 6.1 % ) in zone 7 between 6 months and 12 months . These findings suggested that cyclic therapy with etidronate may help to reduce the resorptive changes in the proximal part of the femur after cementless THA . Further follow-up study with larger population s will be required to define the potential efficacy of intermittent cyclic etidronate therapy on postoperative bone loss The aims of the present study were to investigate how changes in the cumulative dose and the frequency of dosing influence the short-term antiresorptive efficacy of oral ib and ronate treatment and whether serial measurements of bone markers could provide a useful diagnostic tool for the revelation of noncompliance to established treatments with antiresorptive drugs . Study participants were 200 healthy women 50 - 70 years old ( mean 63.1 years ) with a lumbar spine BMD t-score of -1 to -5 . Women were r and omly allocated to receive treatment with oral ib and ronate according to one of the following eight dosing regimes : ( 1 ) 2.5 mg daily for 84 days ; ( 2 ) 20 mg weekly for 84 days ; ( 3 ) 2.5 mg daily for 28 days + no treatment for 56 days ; ( 4 ) 2.5 mg daily for 28 days + 2.5 mg weekly for 56 days ; ( 5 ) 2.5 mg daily for 28 days + 2.5 mg three times weekly for 56 days ; ( 6 ) 2.5 mg daily for 14 days + 2.5 mg three times weekly for 56 days ; ( 7 ) 2.5 mg three times weekly for 84 days ; ( 8) no treatment for 168 days . Study parameters were the serum concentration of the C-terminal telopeptide of collagen type I ( s-CTX , resorption marker ) and N-MID osteocalcin ( formation marker ) measured by enzyme-linked immunosorbent assay . Oral treatment with ib and ronate 20 mg weekly ( cumulative dose 240 mg ) result ed in greater final inhibition in s-CTX and area under the curve ( AUC ) compared to the 2.5 mg daily treatment ( cumulative dose 210 mg ) , indicating that as long as optimal doses are administered the frequency of dosing has secondary importance for overall efficacy . When the cumulative dose was 130 mg or less , the final degree of inhibition was still the function of the cumulative dose , but the overall efficacy estimated by the AUC was also under the influence of the frequency of dosing . These observations suggest that serial measurements of s-CTX may provide a useful diagnostic tool for the early revelation of suboptimal dosing or noncompliance to already optimized therapies with antiresorptive agents Periprosthetic bone loss , especially in the proximal part of the femur , is common after cemented and uncemented total hip arthroplasty ( THA ) . Bone loss can be progressive and , in the extreme , may threaten survival of the prosthesis . To study whether alendronate therapy can reduce bone loss adjacent to prostheses , 13 uncemented primary THA patients were r and omized to the study . They received 10 mg alendronate + 500 mg calcium ( n = 8) or 500 mg calcium only ( n = 5 ) daily for 6 months follow-up after THA . Periprosthetic bone mineral density ( BMD ) was measured with dual energy X-ray absorptiometry ( DXA ) . Decreases in periprosthetic BMD in the alendronate-treated group were lower compared with the changes in the calcium-only group in the same regions of interest at the same follow-up time . In the proximal femur , the mean BMD decrease was 17.1 % in the calcium-only group , whereas in the alendronate-treated group the decrease was only 0.9 % ( p = 0.019 ) . The mean periprosthetic BMD change was also significantly different in the total periprosthetic area between the study groups at the end of the follow-up ( calcium-only group -9.9 % vs. alendronate-treated group -2.6 % ; p = 0.019 ) . Alendronate therapy led to a significant reduction in periprosthetic bone loss after primary uncemented THA compared with the changes found in patients without therapy . This kind of bone response may improve the support of the prosthesis and may result in better survival of the prosthesis . However , in this study the follow-up time was too short and the study population was too small to make any long-term conclusions as to the prognosis for THA patients treated with alendronate Following total hip arthroplasty ( THA ) , femoral periprosthetic bone undergoes a remodeling process that results in bone loss in its proximal regions that may compromise the long-term outcome of THA . Periprosthetic bone loss mainly occurs during the first postoperative months . The question is whether a postoperative treatment with alendronate is effective in reducing periprosthetic bone loss and which doses and duration of treatment are required . In a 12-month prospect i ve , r and omized double-blind study , 51 patients undergoing cementless THA were treated postoperatively either with a daily dose of 20 mg alendronate for 2 months and 10 mg for 2 months thereafter ( group I ) , with 20 mg of alendronate for 2 months and 10 mg for 4 months thereafter ( group II ) , or treated with placebo ( group III ) . Proximal femoral bone mineral density ( BMD ) was measured with dual-energy X-ray absorptiometry ( DEXA ) and serum biochemical markers of bone turnover bone specific alkaline phosphatase , osteocalcin , and C-terminal telopeptides ( CTX-I ) were assayed . Six months of alendronate treatment significantly reduced ( p<0.001 ) bone loss in proximal medial region ( -10 % ) compared with placebo ( -26 % ) . All biochemical markers of bone turnover were suppressed by alendronate . These data suggest that alendronate administered for the first 6 postoperative months following THA was effective in preventing early periprosthetic bone loss The purpose of this study was to evaluate the remaining effects of 12-month intervention of alendronate and exercise on selected risk factors of fragility fractures in 15-month follow-up after withdrawal of intervention among early postmenopausal women . The trial consisted four experimental groups : ( 1 ) 5 mg of alendronate daily + exercise ( Al+Ex+ ) , ( 2 ) 5 mg alendronate daily ( Al+Ex- ) , ( 3 ) placebo + exercise ( Al-Ex+ ) , and ( 4 ) placebo ( Al-Ex- ) . At the follow-up measurements , bone mass and physical fitness of 102 women ( mean age 53.5 + /- 2.5 years ) out of initial 150 subjects could be evaluated . Alendronate increased bone mass significantly [ mean ; 95 % confidence interval ( CI ) ] during the intervention at the lumbar spine ( 3.9 % ; 2.2 % to 5.7 % ) and femoral neck ( 2.1 % ; 0.9 % to 3.4 % ) . After withdrawal of alendronate , bone loss resumed to the rate comparable to that evident in the placebo group . Despite the declining bone mass , the between-group mean difference ( 3.2 % ; 1.0 % to 5.4 % ) remained at the lumbar spine . However , the benefits at the femoral neck had disappeared 15 months after the withdrawal of alendronate . The 12-month exercise training result ed in significant increases in muscle power , dynamic balance , and aerobic capacity with no benefits on bone mass . Fifteen months later , these performance variables had declined among both the exercisers and nonexercisers . Although the between-group differences were no longer statistically significant , muscle power , dynamic balance , and aerobic capacity of those who exercised still remained above the pretraining levels . In conclusion , 12-month treatment with alendronate prevented postmenopausal bone loss , and residual effect was seen 15 months after withdrawal of the drug at the lumbar spine . Similarly , exercise improved muscle power , agility , and aerobic capacity during the intervention , but the improvement was lost after the cessation of the exercise program . Based on these results , it was evident that to maintain the benefits of alendronate or exercise , therapy should be continued AIM Periprosthetic bone loss occurs in the first six months after total hip arthroplasty ( THA ) and is felt to be largely the result of initial operative irritation , immobilization , and stress shielding . This study ( a prospect i ve , r and omized , open , blinded endpoint evaluation ) aims at preventing bone loss around the stem with an oral bisphosphonate . METHOD 66 healthy subjects with uncemented THA and low lumbar bone mass density ( BMD ) ( negative T score ) were treated post-operatively with alendronate as follows : n = 21 with 10 mg/d for 10 weeks ( A ) , n = 21 20 mg/d for 5 weeks ( B ) , n = 24 no treatment for controls ( C ) . The periprosthetic BMD in the Gruen zones ( ROI ) was measured after the 2nd , 4th , 6th , and 12th month by DEXA as a percentage of the value measured one week after surgery . RESULTS In C , there was significant bone loss in all ROI during the first months and a deficit of 29 % in ROI 7 following one year . In B , bone loss was completely prevented up to the second month , in ROI 7 , a significant difference in comparison to C was registered for the entire year . In A , significant bone loss reduction during 12 months was seen . CONCLUSION Alendronate , therefore , is capable of preventing initial periprosthetic bone loss . A dosage of 20 mg/d is required initially with daily treatment lasting at least 10 weeks Bisphosphonates reduce peri-prosthetic bone loss in the short term after total hip replacement but the mid- and longer term effects are not known . The aims of this r and omised trial were to examine the effect of a single dose of 90 mg of pamidronate on the clinical and radiological outcome and peri-prosthetic bone mineral density in 50 patients ( 56 hips ) over a five-year period , following total hip replacement . At five years , 37 patients ( 42 hips ) returned for assessment . The Harris hip scores were similar in the pamidronate and placebo groups throughout the study . Also at five years , four patients , two from each group had osteolytic lesions on plain radiography . These were located around the acetabular component in three patients and in the femoral calcar in one . The femoral and acetabular peri-prosthetic bone mineral density in the pamidronate group and the control group was similar at five years . Pamidronate given as a single post-operative dose does not appear to influence the clinical outcome or prevent the development of osteolytic lesions at five years after total hip replacement We previously reported the effects of cyclic therapy with etidronate ( CTE ) on periprosthetic bone mineral density ( BMD ) after cementless total hip arthroplasty ( THA ) . This study aim ed to evaluate the effects of withdrawal and intervention of CTE after cementless THA . The control group consisted of 24 patients without osteoactive drugs . Sixteen patients continued on CTE ( i.e. , 400 mg/day oral etidronate for 2 weeks followed by 12 weeks of 500 mg/day calcium lactate , repeated every 14 weeks ) for the first 12 months followed by no treatment for 18 months ( early-etidronate group ) . Fifteen patients received no treatment for the first 18 months followed by CTE for 12 months ( late-etidronate group ) . Periprosthetic BMD in seven regions of interest based on the zones of Gruen et al. was measured with dual energy X-ray absorptiometry at 3 weeks , 6 , 12 , 18 , 24 , and 30 months postoperatively . At 12 months after operation ( off therapy point in the early-etidronate group ) , postoperative decreases of BMD in the early-etidronate group were significantly smaller than those in the control group in zones 1 , 2 , 5 , 6 , and 7 and those in the late-etidronate group in zones 1 , 5 , 6 , and 7 ( P < 0.05 for each ) . In the early-etidronate group , significant decreases in BMD were found during months 12 - 30 ( off therapy period ) after withdrawal of CTE in zones 1 and 7 ( P < 0.05 for each ) . In the late-etidronate group , BMD increased significantly in zones 4 and 6 ( P < 0.05 for each ) during months 18 - 30 ( on therapy period ) after intervention trial , while in the controls , BMD decreased significantly in zone 3 ( P < 0.05 ) over this period . At the final follow-up ( 30 months ) , BMD loss in zone 7 was significantly less in the early-etidronate group than in the other groups ( P < 0.05 ) . BMD changes in the early-etidronate group and late-etidronate group were associated with changes in biochemical bone markers PURPOSE OF THE STUDY Bone remodeling and osteolysis around total hip prostheses , with its inevitable corollary , prosthesis loosening , remains a difficult problem in orthopedic surgery . Alendronate ( bisphosphonate ) has proven its efficacy for the treatment of osteoporosis of the lumbar spine and femoral neck . A few in vitro studies have pointed out its inhibiting effect on particle-induced osteolysis . In vivo , one study has demonstrated its usefulness in preventing osteolysis around non-cemented total hip arthroplasties ( THA ) . The purpose of this work was to study the efficacy of this agent for the prevention of changes in peri-prosthetic bone mineral density ( BMD ) after primary THA . MATERIAL AND METHODS The study series included 38 patients with degenerative hip disease who underwent THA . The patients were r and omized in double-blind fashion to two treatment arms : 10 alendronate and 600 mg calcium per day for 2 years ( 20 patients ) or placebo and 600 mg calcium per day for 2 years ( 18 patients ) . Conventional x-rays and x-ray biphotonic absorptiometry ( DPX ) was performed on day four postop and at 3 , 6 , 12 , and 24 months postop . The periprosthetic zones described by Grüen were used for analysis . RESULTS DPX demonstrated a significant reduction in BMD in all patients included in the study . The bone loss was the same in both groups during the early postoperative period reaching maximum loss at 3 months . Differences were observed after this time . In the placebo group , bone loss reached a plateau at 6 months then BMD started to increase progressively , reaching 12.7 % bone loss at 2 years follow-up ( p<0.002 ) . In the alendronate group , there was no plateau , BMD increased continuously starting from three months and reached 6.857 % bone loss at 2 years ( p<0.003 ) . DISCUSSION Administration of alendronate led to a significant reduction in peri-prosthetic bone loss at 2 years follow-up . These results are the first to our knowledge demonstrating the beneficial effect in vivo of alendronate on bone behavior around cemented THAs . CONCLUSION This beneficial effect observed in vivo should be confirmed in further studies including a larger number of patients and longer follow-up . The action of alendronate could facilitate and even retard revision surgery by preserving bone stock BACKGROUND Bone mineral density around the knee is related to the mechanical properties of bone . Alendronate has been shown to be effective for the treatment of osteoporosis and for reducing the rate of osteoporotic fractures . The purpose of the present study was to investigate the effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty in women . METHODS Ninety-six women with an average age of seventy years who were undergoing total knee arthroplasty were r and omly divided into two groups . Patients in the study group received oral alendronate at a dose of 10 mg/day for six months , whereas patients in the control group did not . The bone mineral density in the distal part of the femur and proximal part of the tibia was determined preoperatively and at six and twelve months postoperatively . RESULTS In the control group , the bone mineral density showed significant decreases of 13.8 % ( p < 0.001 ) and 7.8 % ( p = 0.003 ) in the distal part of the femur and of 6.5 % ( p = 0.002 ) and 3.6 % ( p = 0.141 ) in the proximal part of the tibia at six and twelve months , respectively . In the study group , however , the bone mineral density showed significant increases of 10.0 % ( p = 0.010 ) and 1.9 % ( p = 0.049 ) in the distal part of the femur and of 9.4 % ( p < 0.001 ) and 5.4 % ( p = 0.032 ) in the proximal part of the tibia at six and twelve months , respectively . The overall differences in bone mineral density between the study and control groups were significant ( p = 0.011 for the proximal part of the tibia , and p = 0.033 for the distal part of the femur ) . CONCLUSIONS We found significant postoperative decreases in bone mineral density in the distal part of the femur and proximal part of the tibia in women who had undergone total knee arthroplasty . Oral administration of alendronate for six months postoperatively significantly improved the bone mineral density . While the clinical benefits of alendronate after total knee arthroplasty remain unproven and the duration of follow-up in the present study was quite short , the improvement in bone mineral density may have a clinical ly important effect on prosthetic fixation and the rate of periprosthetic fractures after total knee arthroplasty Forty-four women who had undergone cementless total hip arthroplasty ( THA ) were selected for determination of the optimum dosage of etidronate in the treatment of stress shielding after surgery . Patients were 55–86 years of age . The patients were r and omized into three groups . The control group ( n = 17 ) was not treated with osteoactive drugs . The low-dose group ( n = 12 ) and the high-dose group ( n = 15 ) received 200 mg or 400 mg etidronate daily for 2 weeks , followed by 12 weeks of calcium supplementation of 500 mg/day . These patients received four cycles of therapy over 1 year postoperatively . Periprosthetic bone mineral density ( BMD ) was measured with dual-energy X-ray absorptiometry at 3 weeks , 6 months , and 12 months . At 12 months , bone loss in the low-dose and high-dose groups was significantly lower compared with the control group in Gruen zones 1 and 7 . There were additional significant differences with regard to bone loss between the control group and the high-dose group in zones 2 , 4 , and 6 . Our data suggest that high dosages are more effective in reducing postoperative bone loss after cementless THA ABSTRACT Objective : Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis . Supplemental calcium is also generally recommended . This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementation on alendronate treatment . Methods : This 2-year , r and omized , double-blind , multicenter trial enrolled healthy , postmenopausal women with low bone mineral density ( BMD ) . Patients with a dietary calcium intake ≥ 800 mg/day received daily vitamin D 400 IU and alendronate 10 mg/calcium-placebo , alendronate 10 mg/elemental calcium 1000 mg , or alendronate-placebo/calcium 1000 mg ( 2:2:1 ) . Endpoints included BMD , bone turnover markers ( BTMs ) , and adverse events . Results : R and omized patients ( N = 701 ) were an average of 20.4 years postmenopausal . After 24 months , increases in lumbar spine BMD differed significantly between patients receiving calcium alone ( 0.8 % ) and either alendronate alone ( 5.6 % ) or alendronate + calcium ( 6.0 % ) ( p < 0.001 ) . Significant differences were also seen at the trochanter and femoral neck ( p < 0.001 ) . BTMs were significantly lower with alendronate-containing treatments than calcium alone ( p < 0.001 ) . Addition of calcium supplementation to alendronate did not significantly increase BMD compared to alendronate alone ( p = 0.29 to 0.97 ) , but did result in a statistically significant , though small , additional reduction in urinary NTx . Adverse events were similar among treatment groups . Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30 % , although discontinuation rates were similar among treatment groups . Conclusions : In postmenopausal women with a daily intake of ≥ 800 mg calcium and 400 IU vitamin D , 24-month treatment with alendronate 10 mg daily with or without calcium 1000 mg result ed in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone . Addition of supplemental calcium to alendronate treatment had no effect on BMD and result ed in a small , though statistically significant , additional reduction in NTx Earlier osteodensitometric results of femoral periprosthetic bone showed that postoperative antiresorptive treatment with alendronate following total hip arthroplasty ( THA ) reduces the periprosthetic bone loss that commonly occurs in the first months after surgery . However , whether alendronate can prevent periprosthetic bone loss over the long term , or if bone loss occurs after discontinuing alendronate is unknown . Femoral periprosthetic bone mineral density ( BMD ) was assessed in 49 patients 6 years after cementless total hip arthroplasty using dual energy X-ray absorptiometry . Twenty-nine patients were treated postoperatively with alendronate and 20 control patients received no treatment . All patients were followed up at 12 months after surgery in a prospect i ve r and omized study . The bone mineral density was evaluated in 7 regions of interest according to the Gruen protocol . Six years after total hip arthroplasty , no significant changes were detected in femoral periprosthetic BMD when compared with results at 1 year , and the bone loss in patients with postoperative alendronate treatment was still significantly less than those without treatment . These results suggest that the prevention of femoral periprosthetic bone loss following THA achieved by postoperative antiresorptive treatment with alendronate is of long-st and ing effect , and further bone loss does not occur after the first postoperative year |
13,952 | 28,947,636 | Conclusions All four currently recommended drugs show limitations in their efficacy profile .
While only albendazole showed good efficacy against hookworm infection , all drugs had low efficacy against T trichiura . | & NA ; Objective To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates . | Background The control of soil-transmitted helminth ( STH ) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole . However , these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates ( CR ) , whereas fecal egg reduction rates ( ERR ) are generally high for all common STH species . We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based r and omized controlled trial in the People 's Republic of China . Methodology /Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who su bmi tted two stool sample s before and 3–4 weeks after administration of single-dose oral albendazole ( 400 mg ) or mebendazole ( 500 mg ) or triple-dose albendazole ( 3 × 400 mg over 3 consecutive days ) or mebendazole ( 3 × 500 mg over 3 consecutive days ) . Efficacy against T. trichiura , Ascaris lumbricoides , and Taenia spp . was also assessed . Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens ( single dose : respective CRs 69 % ( 95 % confidence interval [ CI ] : 55–81 % ) and 29 % ( 95 % CI : 20–45 % ) ; triple dose : respective CRs 92 % ( 95 % CI : 81–98 % ) and 54 % ( 95 % CI : 46–71 % ) ) . ERRs followed the same pattern ( single dose : 97 % versus 84 % ; triple dose : 99.7 % versus 96 % ) . Triple-dose regimens outperformed single doses against T. trichiura ; three doses of mebendazole – the most efficacious treatment tested – cured 71 % ( 95 % CI : 57–82 % ) . Both single and triple doses of either drug were highly efficacious against A. lumbricoides ( CR : 93–97 % ; ERR : all > 99.9 % ) . Triple dose regimens cured all Taenia spp . infections , whereas single dose applications cured only half of them . Conclusions / Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole . To achieve high CRs against both hookworm and T. trichiura , triple-dose regimens are warranted . Trial Registration www.controlled-trials.com IS RCT A r and omized clinical trial was conducted to compare the effectiveness of albendazole alone and albendazole combined with praziquantel in the treatment of Trichuris trichiura infection . The drug regimens consisted of single dose of albendazole 400 mg ( A1 , n=34 ) , 3 days of albendazole 400 mg daily ( A3 , n=34 ) , 5 days of albendazole 400 mg daily ( A5 , n=35 ) , single dose of albendazole 400 mg plus praziquantel 40 mg/kg ( AIP1 , n=34 ) , and 3 days of albendazole 400 mg plus praziquantel 40 mg/kg daily ( A3P3 , n=36 ) . It was found that treatment with 3 or more consecutive days of albendazole with or without praziquantel result ed in a significant reduction in density of Trichuris eggs in stools while a single dose of such drug did not . Praziquantel was not shown to have synergistic or antagonistic effects with albendazole . A regimen of 400 mg of albendazole daily for 3 days was found to be the most suitable therapy for Trichuris infection The comparative efficacy of albendazole and mebendazole in the treatment of intestinal nematode infections were compared 3 weeks after treatment in a r and omized trial among schoolchildren on Pemba Isl and , Tanzania . Egg counts were compared 3 weeks , 4 months and 6 months after treatment of 731 children seen on each occasion . Differences in the efficacies were apparent with some nematodes 21 d after treatment , but these were no longer apparent 4 months after treatment , and by 6 months intensities of infection were similar to pre-treatment levels . These findings suggest that treatment of schoolchildren every 4 months may be necessary in this highly endemic area in order to have an impact on the intensity of intestinal nematode infections sufficient to be likely to reduce morbidity Background To control soil-transmitted helminth ( STH ) infections , the World Health Organization recommends school-based deworming programs with a health hygiene education component . The effect of such health hygiene interventions , however , has not been adequately studied . The objective of the present study was to determine the effectiveness of a health hygiene education intervention on the occurrence of STH re-infection four months post-de-worming . Methodology /Principal Findings An open-label pair-matched cluster-r and omized trial was conducted in Grade 5 schoolchildren of 18 primary schools ( 9 intervention and 9 control ) in the Peruvian Amazon . Baseline assessment included interview with a pre-tested question naire and collection of single stool specimens that were examined using the single Kato-Katz thick smear . All schoolchildren were then treated with single-dose albendazole ( 400 mg ) . Schoolchildren in intervention schools then received 1 ) an initial one hour in-class activity on health hygiene and sanitation and 30-minute refresher activities every two weeks over four months ; and 2 ) a half-day workshop for teachers and principals , while children in control schools did not . Four months later , STH infection was re-assessed in all schools by laboratory technologists blinded to intervention status . From April 21–October 20 , 2010 , a total of 1,089 schoolchildren ( 518 and 571 from intervention and control schools , respectively ) participated in this study . Intervention children scored significantly higher on all aspects of a test of STH-related knowledge compared with control children ( aOR = 18·4 ; 95 % CI : 12·7 to 26·6 ) . The intensity of Ascaris lumbricoides infection at follow-up was statistically significantly lower ( by 58 % ) in children in intervention schools compared with children in control schools ( aIRR = 0·42 ; 95 % CI = 0·21 to 0·85 ) . No significant changes in hookworm or Trichuris trichiura intensity were observed . Conclusions / Significance A school-based health hygiene education intervention was effective in increasing STH knowledge and in reducing Ascaris lumbricoides infection . The benefits of school-based periodic deworming programs are likely to be enhanced when a sustained health hygiene education intervention is integrated into school curricula BACKGROUND Commonly used drugs for preventive chemotherapy against soil-transmitted helminths ( ie , albendazole and mebendazole ) show low efficacy against Trichuris trichiura . Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura . We aim ed to assess the nature of the dose-response relation to determine the optimum dose . METHODS We did a parallel , r and omised , placebo-controlled , single-blind trial with oxantel pamoate in school-aged children ( aged 6 - 14 years ) infected with T trichiura on Pemba Isl and , Tanzania . Children were asked to provide two stool sample s and children positive for T trichiura were eligible to participate in the trial . Children were excluded if they suffered from any systematic illness . Children were r and omly assigned to six different oxantel pamoate doses ( 5 - 30 mg/kg ) or a placebo . R and omisation was stratified by baseline infection intensity using r and om block sizes of seven and 14 . The primary endpoints were cure rates and egg-reduction rates against T trichiura , both analysed by available case . Drug safety was assessed 2 h and 24 h after treatment . The trial is registered at www.is rct n.com , number IS RCT N86603231 . FINDINGS Between Oct 14 , and Nov 28 , 2014 , we enrolled 480 participants and r and omly assigned 350 children to the different oxantel pamoate doses or the placebo . 5 mg/kg oxantel pamoate was the minimum effective dose ( 10 of 46 children cured [ cure rate 22 % , 95 % CI 11 - 36 ] ; egg-reduction rate 85·0 % , 64·5 - 92·9 ) . An increased probability of being cured and reduced egg counts with escalating doses was recorded . At 25 mg/kg oxantel pamoate 27 of 45 children were cured ( cure rate 60 % , 95 % CI 44 - 65 ) with an egg-reduction rate of 97·5 % ( 94·4 - 98·9 ) , and at 30 mg/kg 27 of 46 children were cured ( 59 % , 43 - 73 ) with an egg-reduction rate of 98·8 % ( 96·8 - 99·6 ) . Oxantel pamoate was well tolerated across all treatment groups ; only mild adverse events were reported by the participants 2 h ( 27 [ 10 % ] ) and 24 h ( 12 [ 4 % ] ) after treatment . INTERPRETATION Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura . An optimum therapeutic dose range of 15 - 30 mg/kg oxantel pamoate was defined . With a weight independent dose of 500 mg oxantel pamoate 95 % of children aged 7 - 14 years in sub-Saharan Africa would receive doses of 11·7 - 32·0 mg/kg . Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes . FUNDING Swiss National Science Foundation Background The currently used anthelmintic drugs , in single oral application , have low efficacy against Trichuris trichiura infection , and hence novel anthelmintic drugs are needed . Nitazoxanide has been suggested as potential drug c and i date . Methodology The efficacy and safety of a single oral dose of nitazoxanide ( 1,000 mg ) , or albendazole ( 400 mg ) , and a nitazoxanide-albendazole combination ( 1,000 mg–400 mg ) , with each drug administered separately on two consecutive days , were assessed in a double-blind , r and omized , placebo-controlled trial in two schools on Pemba , Tanzania . Cure and egg reduction rates were calculated by per- protocol analysis and by available case analysis . Adverse events were assessed and grade d before treatment and four times after treatment . Principal Findings Complete data for the per- protocol analysis were available from 533 T. trichiura-positive children . Cure rates against T. trichiura were low regardless of the treatment ( nitazoxanide-albendazole , 16.0 % ; albendazole , 14.5 % ; and nitazoxanide , 6.6 % ) . Egg reduction rates were 54.9 % for the nitazoxanide-albendazole combination , 45.6 % for single albendazole , and 13.4 % for single nitazoxanide . Similar cure and egg reduction rates were calculated using the available case analysis . Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients . Most of the adverse events were mild and had resolved within 24 hours posttreatment . Conclusions / Significance Nitazoxanide shows no effect on T. trichiura infection . The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed . There is a pressing need to develop new anthelmintics against trichuriasis . Trial Registration Controlled-Trials.com IS RCT Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010 . The treatment used in Vietnam is single dose oral mebendazole ( Phardazone ) 500 mg . We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a r and omized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren . The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo , with a reduction in mean eggs per gram of feces relative to placebo of 31 % ( 95 % CI -9 to 56 % , P = 0.1 ) . In light of these findings we then carried out a similar r and omized trial comparing triple dose mebendazole , single dose albendazole , and triple dose albendazole against placebo in 209 adults in the same area . The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63 % ( 95 % CI 30 - 81 % ) for triple mebendazole , 75 % ( 47 - 88 % ) for single albendazole , and 88 % ( 58 - 97 % ) for triple albendazole . Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam , and that it should be replaced by albendazole . These findings are of major public health relevance given the opportunity costs of treating entire population s with ineffective therapies . We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs OBJECTIVE To evaluate the comparative efficacy of 400 mg albendazole ( Smith Kline Beecham ) as a single dose and three br and s of mebendazole ( Janssen , Unibios and East African Pharmaceuticals ) at doses of 100 mg twice a day for three consecutive days in the treatment of single or mixed infections with Ascaris lumbricoides and or Trichuris trichiura in four treatment groups of school children . DESIGN R and omized trial . SETTING Wondo-Genet , southern Ethiopia . SUBJECTS School children , aged six to nineteen years . RESULTS The percentage cure rate and egg reduction rate obtained with albendazole and mebendazole from the three br and s were not significantly different in the treatment of ascariasis . However , significant differences were found among the percentage cure rates and egg reduction rates of the four treatment groups in the treatment of trichuriasis . Comparatively , high cure rate ( 89.8 % ) and egg reduction rate ( 99.1 % ) were observed in vermox ( Janssen ) treated group followed by Unibios ( India ) treated group ( 53.3 % and 96.53 % cure and egg reduction rates , respectively ) , whereas low cure rate ( 17.1 % ) and egg reduction rate ( 69.8 % ) were seen in the albendazole treated group . CONCLUSION The results of this study suggest that in areas of single or mixed infections with Trichuris trichiura and /or Ascaris lumbricoides are common public health problems and where laboratory facilities are not available to make parasite identification , mebendazole ( particularly vermox , a product of Janssen laboratory ) would be the drug of choice to treat trichuriasis and ascariasis . However , either mebendazole from the different br and s or albendazole is effective in the treatment of ascariasis in areas where trichuriasis is not prevalent One hundred two children ( 43 males and 59 females ) aged 6 to 14 years with positive stool examination by Kato-Katz and /or Harada-Mori culture techniques for N. americanus , were r and omly divided into two groups . Group I with 48 children were treated with a single dose albendazole , 400 mg . Group II , 54 children , received a single dose mebendazole , 600 mg . After treatment , repeated stool examination was performed on Day 14 , Day 21 and Day 28 . The children were considered cured when stool examination was negative on all three occasions by both methods . The cure rate was 64 % in Group I and 11 % in Group II . The difference was statistically significant ( p less than 0.05 ) . The eggs reduction rate was 98 % in Group I and 95 % in Group II . Mild and transient side effects such as nausea , dizziness and headache were observed in both groups . Albendazole , 400 mg , as a single dose treatment was shown to be superior to mebendazole , 600 mg , single dose for the mass treatment of hookworm infection , especially that of Necator americanus , in an endemic area BACKGROUND Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis . The combination of albendazole with ivermectin improves efficacy , but a mebendazole-ivermectin combination has not been previously investigated . METHODS We performed a r and omized controlled trial in 2 schools in Zanzibar , Tanzania , to assess the efficacy and safety of albendazole ( 400 mg ) plus placebo , albendazole plus ivermectin ( 200 μg/kg ) , mebendazole ( 500 mg ) plus placebo , and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection . Cure rate ( CR ) and egg reduction rate were assessed by intent-to-treat analysis . Adverse events were monitored within 48 h after treatment . RESULTS Complete data records were available for 548 children . The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination ( 55 % ) . Low CRs were observed with albendazole-ivermectin ( 38 % ) , mebendazole ( 19 % ) , and albendazole ( 10 % ) . Compared with placebo , the use of ivermectin statistically significantly increased the CRs from 14 % to 47 % ( odds ratio , 0.19 ; 95 % confidence interval [ CI ] , 0.12 - 0.28 ) . The highest egg reduction rate ( 97 % ; 95 % CI , 95%-98 % ) was observed using the mebendazole-ivermectin combination , followed by albendazole-ivermectin ( 91 % ; 95 % CI , 87%-94 % ) , mebendazole ( 67 % ; 95 % CI , 52%-77 % ) , and albendazole ( 40 % ; 95 % CI , 22%-56 % ) . The adverse events , reported by 136 children , were generally mild , with no significant difference between the treatment arms . CONCLUSIONS Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N08336605 The efficacies and side effects of single dose treatments with 500 mg mebendazole ( Janssen Pharmaceutica ) and 400 mg albendazole ( SmithKline Beecham ) against intestinal nematodes were compared in a single-blind , r and omized controlled trial among 2294 children aged 6 to 12 years on Pemba Isl and , Zanzibar , among whom infections with Ascaris , hookworms and Trichuris were highly prevalent . Both drugs were highly effective against Ascaris , with cure rates of over 97 % . The cure rates for Trichuris were low , but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count . Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count . There was no difference in the frequency of side effects reported by heavily infected children treated with either drug . In a trial on 402 children , 500 mg mebendazole ( Janssen ) was compared with a generic version of the drug , 500 mg mebendazole ( Pharmamed ) . No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied OBJECTIVE To evaluate the efficacy of and resistance to mebendazole ( 500 mg ) and levamisole ( 40 or 80 mg ) , alone or in combination , for the treatment of Ascaris lumbricoides , Trichuris trichiura and hookworm infections on Pemba Isl and - an area exposed to periodic school-based mebendazole treatment since 1994 . METHODS A r and omized , placebo-controlled trial was carried out in 914 children enrolled from the first and fifth grade s of primary schools . Stool sample s collected at baseline and 21 days after treatment were examined by the Kato-Katz technique to assess the prevalence and intensity of helminth infection . FINDINGS Efficacies of mebendazole and levamisole as single treatments against intestinal nematode infections were comparable with those in previous trials , but mebendazole treatment of hookworm infections gave significantly lower cure ( 7.6 % ) and egg reduction ( 52.1 % ) rates than reported in a study undertaken before the beginning of periodic chemotherapy ( cure rate , 22.4 % ; egg reduction rate , 82.4 % ) . Combined treatment with mebendazole and levamisole had a significantly higher efficacy against hookworm infections ( cure rate , 26.1 % ; egg reduction rate , 88.7 % ) than either drug given alone . No difference in mebendazole efficacy was found in children who had been treated repeatedly compared with those who had not been treated previously . CONCLUSION The overall efficacy of mebendazole against hookworm infections after periodic chemotherapy is reduced . The efficacy of benzimidazoles in chemotherapy-based control programmes should be monitored closely . Combined treatment with mebendazole and levamisole may be useful as a tool to delay the development of benzimidazole resistance The quality and efficacy of two locally manufactured generic albendazole ( ABZ ) products ( Curex and Royal Drug ) used for deworming children in Nepal since 1999 were tested against the originator product ( GlaxoSmithKline ( GSK ) ) . The study included disintegration and dissolution testing according to the Indian Pharmacopoeia ( IP ) and the United States Pharmacopeia ( USP ) , respectively , as well as a r and omised controlled clinical trial comparing cure rates ( CR ) and egg reduction rates ( ERR ) for Ascaris lumbricoides , Trichuris trichiura and hookworm infections . Stool sample s from 1277 children were examined before and 21 days after treatment . For A. lumbricoides , GSK ( 97.0 % ) and Royal Drug ( 95.0 % ) ABZ achieved significantly higher CRs than Curex ABZ ( 82.6 % ) ; however , all products achieved ERRs > 90 % . For T. trichiura , Curex ABZ showed significantly lower ERRs ( 63.2 % ) . For hookworms , GSK ABZ performed significantly better ( CR 74.3 % , ERR 87.1 % ) than Royal Drug ABZ ( CR 53.3 % , ERR 80.8 % ) and Curex ABZ ( CR 50.7 % , ERR 73.1 % ) . Only the GSK product passed both disintegration and dissolution tests according to the IP and USP . Both generic products failed the dissolution tests . Curex ABZ showed poor disintegration . Despite its lower efficacy , the cheaper Curex product achieved good results in controlling morbidity due to soil-transmitted helminth infections . This study shows that the cost effectiveness of drugs used in mass deworming campaigns should not be inferred on the basis of a single quality testing parameter This r and omized , placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths ( albendazole ) and lymphatic filariasis ( ivermectin ) . Children were infected with Ascaris ( 29.2 % ) , Trichuris ( 42.2 % ) , and hookworm ( 6.9 % ) , with 54.7 % of children having one or more of these parasites . Wuchereria bancrofti microfilaria were found in 13.3 % of the children . Children were r and omly assigned to treatment with placebo , albendazole , ivermectin , or combined therapy . Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone . Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone . Only combination therapy result ed in significantly greater gains in height ( hookworm-infected children ) or weight ( Trichuris-infected children ) compared with the placebo group . Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and result ed in nutritional benefits not found with either drug alone BACKGROUND Soil-transmitted helminths are among the most prevalent sources of human infections globally . We determined the effect of an educational package at rural schools in Linxiang City District , Hunan province , China , where these worms are prevalent . The intervention aim ed to increase knowledge about soil-transmitted helminths , induce behavioral change , and reduce the rate of infection . METHODS We conducted a single-blind , unmatched , cluster-r and omized intervention trial involving 1718 children , 9 to 10 years of age , in 38 schools over the course of 1 school year . Schools were r and omly assigned to the health-education package , which included a cartoon video , or to a control package , which involved only the display of a health-education poster . Infection rates , knowledge about soil-transmitted helminths ( as assessed with the use of a question naire ) , and h and -washing behavior were assessed before and after the intervention . Albendazole was administered in all the participants at baseline and in all the children who were found to be positive for infection with soil-transmitted helminths at the follow-up assessment at the end of the school year . RESULTS At the follow-up assessment , the mean score for the knowledge of helminths , calculated as a percentage of a total of 43 points on a question naire , was 90 % higher in the intervention group than in the control group ( 63.3 vs. 33.4 , P<0.001 ) , the percentage of children who washed their h and s after using the toilet was nearly twice as high in the intervention group ( 98.9 % , vs. 54.2 % in the control group ; P<0.001 ) , and the incidence of infection with soil-transmitted helminths was 50 % lower in the intervention group than in the control group ( 4.1 % vs. 8.4 % , P<0.001 ) . No adverse events were observed immediately ( within 15 minutes ) after albendazole treatment . CONCLUSIONS The health-education package increased students ' knowledge about soil-transmitted helminths and led to a change in behavior and a reduced incidence of infection within 1 school year . ( Funded by UBS Optimus Foundation , Zurich , Switzerl and ; Australian New Zeal and Clinical Trials Registry number , ACTRN12610000048088 . ) OBJECTIVE To determine the efficacy of single doses of albendazole , ivermectin and diethylcarbamazine , and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp . METHODS In a r and omized , placebo-controlled trial , infected children were r and omly assigned to treatment with albendazole + placebo , ivermectin + placebo , diethylcarbamazine + placebo , albendazole + ivermectin , or albendazole + diethylcarbamazine . The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis . The chi2 test was used to determine the significance of cure rates , repeated measures analysis of variance for the comparison of mean log egg counts , the Newman-Keuls procedure for multiple comparison tests , and logistic regression for the comparison of infection rates at days 180 and 360 after treatment . FINDINGS Albendazole , ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine . For trichuriasis , albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments : the infection rates were lower 180 and 360 days after treatment . CONCLUSION Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis , this combination appears to be a suitable tool for the integrated or combined control of both public health problems Background Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth ( STH ) infections . We assessed the efficacy of single oral doses of albendazole ( 400 mg ) and mebendazole ( 500 mg ) for the treatment of hookworm infection in school-aged children in Lao PDR . Since Opisthorchis viverrini is co-endemic in our study setting , the effect of the two drugs could also be determined against this liver fluke . Methodology We conducted a r and omized , open-label , two-arm trial . In total , 200 children infected with hookworm ( determined by quadruplicate Kato-Katz thick smears derived from two stool sample s ) were r and omly assigned to albendazole ( n = 100 ) and mebendazole ( n = 100 ) . Cure rate ( CR ; percentage of children who became egg-negative after treatment ) , and egg reduction rate ( ERR ; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline ) at 21–23 days posttreatment were used as primary outcome measures . Adverse events were monitored 3 hours post treatment . Principal Findings Single-dose albendazole and mebendazole result ed in CRs of 36.0 % and 17.6 % ( odds ratio : 0.4 ; 95 % confidence interval : 0.2–0.8 ; P = 0.01 ) , and ERRs of 86.7 % and 76.3 % , respectively . In children co-infected with O. viverrini , albendazole and mebendazole showed low CRs ( 33.3 % and 24.2 % , respectively ) and moderate ERRs ( 82.1 % and 78.2 % , respectively ) . Conclusions / Significance Both albendazole and mebendazole showed disappointing CRs against hookworm , but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole . Single-dose administrations showed an effect against O. viverrini , and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic . Clinical Trial Registration Current Controlled Trials IS RCT OBJECTIVE To compare the efficacy of a single dose mebendazole 500 mg from the original manufacturer and a formulation locally produced by State Pharmaceuticals Manufacturing Corporation of Sri Lanka and albendazole 400 mg in mass treatment of soil-transmitted nematode infections . DESIGN R and omised trial . SETTING Government owned plantations in low-country regions of Sri Lanka with poor sanitary facilities . SUBJECTS 399 children 3 to 15 years of age infected with at least one type soil-transmitted nematode . INTERVENTION Mebendazole 500 mg or albendazole 400 mg given as single dose treatment . MEASUREMENTS Cure rates and egg reduction rates calculated from egg counts of pre- and post-treatment stool sample s using the quantitative Kato-Katz technique . RESULTS All three drugs were effective against Ascaris infection with cure rates above 95 % . The efficacy against Trichuris trichuria was uniformly poor . For hookworm infection albendazole appeared to be more effective in a single dose with cure rates of 77.9 % compared with 28.7 % and 35.8 % for the two mebendazole formulations ; corresponding egg reduction rates were 95.4 % compared with 72.0 % and 74.5 % . CONCLUSION Albendazole is the drug of choice for mass deworming where hookworm disease is prominent . There was no statistically significant difference between the original and locally produced mebendazole The efficacy of broad-spectrum anthelmintics in current use was studied in Hengshan County , Hunan Province . The vermicides under study include albendazole ( 400 mg , single dose ) , mebendazole composite ( mebendazole 100 mg and levamisole 25 mg bid x 3d ) , oxantel pyrantel pamoate composite ( pyrantel pamoate 150 mg and oxantel pamoate 150 mg bid x 2d ) , and pyrantel pamoate composite ( base 10 mg/kg , single dose ) . Therapeutic effect assessed 2 weeks after medication revealed Ascaris egg negative rates or cure rates ( CR ) of 97.5 - 100 % for the former 3 regimens , and 80.9 % for the latter one ; while CR for hookworm infection were 95.4 % , 78.6 - 100 % , 96.7 % and 83.3 % , respectively . A follow-up survey pursued 4 weeks post treatment showed no significant difference in CR for the above regimens . Judging from CR in Trichuris trichiura infection , pyrantel pamoate composite was recommended as the drug of choice ( 89.3 % ) , which was followed by mebendazole composite ( 64.6 - 83.8 % ) and albendazole ( 28.2 - 42.6 % ) , whereas pyrantel pamoate was inefficacious . Obvious egg reduction rates were evidence d post application of the above drugs in trichuriasis treatment except pyrantel pamoate at single dose This r and omized , placebo-controlled trial investigated the tolerance , efficacy , and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis . Children were infected with Ascaris ( 30.7 % ) , Trichuris ( 53.4 % ) , and hookworm ( 9.7 % ) with 69.9 % having more than one of these parasites . A total of 15.8 % of the children had Wuchereria bancrofti microfilariae . Children were r and omly assigned treatment with placebo , albendazole ( ALB ) , diethylcarbamazine ( DEC ) , or combined therapy . The combination of DEC/ALB reduced microfilarial density compared with placebo , ALB , or DEC ( P < or = 0.03 ) . Albendazole and DEC/ALB reduced the prevalence of Ascaris , Trichuris , and hookworm more than placebo or DEC ( P < or = 0.03 ) . Among Trichuris-infected children , those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo ( P < or = 0.05 ) . Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia , DEC/ALB was more effective than DEC , with no increase in severity of adverse reactions A r and omised clinical trial was conducted in Kabale District , southwestern Ug and a , to compare the efficacies of single and double doses of a combination of 400 mg albendazole ( ALB ) and 500 mg mebendazole ( MBZ ) with those of single and double doses of each drug given alone in the treatment of Trichuris trichiura . Infected pupils ( n=611 ) were r and omised to six treatment groups . Three groups received either a single dose of ALB , MBZ or the combination ( ALB+MBZ ) . The other three groups received either a double dose of ALB ( ALB/ALB ) , MBZ ( MBZ/MBZ ) or the combination ( ALB+MBZ/ALB+MBZ ) . All double doses were given 8h apart . Children were followed-up weekly for 1 month . Cure rates were significantly higher using double doses compared with single doses ( irrespective of drug ; z=-4.02 , P<0.0005 ) as well as using the drug combination compared with single drugs ( irrespective of doses ; z=-7.64 , P<0.0005 ) . Cure rates measured at Day 7 were significantly higher than on Days 14 and 21 after treatment ( Day 14 , z=9.90 , P<0.0005 ; Day 21 , z=7.36 , P<0.0005 ) . Geometric mean ( GM ) intensities of positives were significantly lower on Day 7 compared with all other subsequent days ( P<0.00005 ) , and on Day 28 GM intensities reached pre-treatment levels ( P=0.096 ) . Whilst there was no difference in egg excretion between single and double doses of the same drug or drug combination ( F((df)(1))=0.28 , P=0.60 ) , the combination treatment result ed in lower egg excretion than use of single drugs ( F((df)(2))=50.90 , P<0.00005 ) . All the tested regimens of ALB and MBZ had low cure rates against T. trichiura in Ug and a , but both combination treatments showed satisfactory egg reduction rates 3 weeks after treatment OBJECTIVES AND DESIGN To test the efficacy of albendazole against the whipworm Trichuris trichiura for school-based deworming in the south-western Cape , South Africa . Children infected with Trichuris were r and omised to 3 doses of albendazole ( 400 , 800 or 1200 mg ) , each repeated 4 times . The boy/girl ratio was 1 . A group not infected with worms was treated with placebo , creating a negative control . SUBJECTS AND SETTING Pupils at a primary school serving a wine-producing area approximately 90 km east of Cape Town . OUTCOME MEASURES Trichuris cure rates and reduction in the number of eggs/g in faeces , as well as the infection dynamics of Trichuris and Ascaris during treatment with placebo . RESULTS Albendazole treatment was associated with Trichuris cure rates of 23 % ( 400 mg ) , 56 % ( 800 mg ) and 67 % ( 1200 mg ) after the final treatment . The corresponding reductions in the number of eggs/g of faeces were 96.8 % , 99.3 % and 99.7 % . Environmental pollution by human faeces was confirmed because worm egg-negative children in the placebo group became egg-positive while the study was in progress . CONCLUSION The 400 mg stat dose had a low Trichuris cure rate . To repeat the dose on 2 or 3 days would increase cost , reduce compliance and complicate management . Albendazole can not be used in deworming programmes in South Africa because it is a Schedule 4 prescription medicine . De-scheduling is needed urgently , particularly because of high efficacy against hookworm in KwaZulu-Natal and neighbouring countries OBJECTIVE To compare the efficacy of mebendazole 500 mg and albendazole 400 mg single-dose treatments of Trichuris trichiura infection in children in the Durban area of KwaZuluNatal , South Africa . DESIGN A single-blind r and omised trial in children with a documented moderate infection of T. trichiura . Ova were counted in stool specimens before and 10 days after treatment by the formal-ether concentration method . SETTING Two shelters for ab and oned and orphaned children in Durban . PARTICIPANTS Ninety-six children aged between 2 and 12 years . OUTCOME MEASURES The number of children who showed reduced T. trichiura ova counts after the treatments , and reductions in ova counts , both expressed as percentages . Statistical analysis using the Wilcoxon 2- sample test and the chi-square test . RESULTS Eighty-two children completed the trial ; 42 received mebendazole and 40 albendazole . Of the mebendazole group 85 % showed a reduction in T. trichiura ova count , compared with 75 % of children who received albendazole . Mebendazole treatment was associated with a median percentage reduction in ova count of 72.2 % , which significantly exceeded the 44.1 % reduction after albendazole ( P = 0.024 ) . CONCLUSION The mebendazole 500 mg single-dose therapy was more efficacious than the albendazole 400 mg single-dose therapy in treating T. trichiura infection in these children ABSTRACT In many regions where soil-transmitted helminth infections are endemic , single-dose albendazole is used in mass drug administration programs to control infections . There are little data on the efficacy of the st and ard single-dose administration compared to that of alternative regimens . We conducted a r and omized , controlled , assessor-blinded clinical trial to determine the efficacies of st and ard and extended albendazole treatment against soil-transmitted helminth infection in Gabon . A total of 175 children were included . Adequate cure rates and egg reduction rates above 85 % were found with a single dose of albendazole for Ascaris infection , 85 % ( 95 % confidence interval [ CI ] , 73 , 96 ) and 93.8 % ( CI , 87.6 , 100 ) , respectively , while two doses were necessary for hookworm infestation ( 92 % [ CI , 78 , 100 ] and 92 % [ CI , 78 , 100 ] , respectively ) . However , while a 3-day regimen was not sufficient to cure Trichuris ( cure rate , 83 % [ CI , 73 , 93 ] ) , this regimen reduced the number of eggs up to 90.6 % ( CI , 83.1 , 100 ) . The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 ( CI , 1.1 , 2.5 ) and 2.1 ( CI , 1.5 , 2.9 ) for Trichuris and 1.7 ( CI , 1.0 , 2.9 ) and 1.7 ( CI , 1.0 , 2.9 ) for hookworm . Albendazole was safe and well tolerated in all regimens . A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections . The single-dose option may still be the preferred regimen because it balances efficacy , safety , and compliance during mass drug administration , keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects . ( This study has been registered at Clinical Trials.gov under registration number NCT01192802 . Introduction Different br and s Albendazole are commercially available and the efficacious br and /s is/are required for effective control of STHs infection . Thus , this study is aim ed at determining the therapeutic efficacy of different br and s of albendazole against soil transmitted helminths among school children of Jimma town . Methods A cross sectional survey for prevalence of geohelminths and a r and omized trial for efficacy study of different br and s of albendazole was conducted among students Mendera Elementary School from March 29 to April 29 , 2010 . Positive subjects were r and omized into three treatment arms using lottery method . The collected stool sample s were examined by the McMaster method . CRs were calculated using SPSS windows version 16 and ERRs were calculated using appropriate formula . Results Of the 715 school children who had their stools examined , 326 were positive for STHs with a prevalence rate of 45.6 % . The cure rates ( CR ) for A. lumbricoides , T. trichiura and Hookworm were 99.4 , 59.9 and 93.7 % , respectively . Similarly , the egg reduction rates ( ERR ) were 97 , 99.9 and 99.9 % respectively . A statistical significant mean STH egg count difference were observed between pre and post-intervention study ( p < 0.001 ) . But no statistical significant curing effect difference were observed among the three br and s used against the three STHs ( p > 0.05 ) . Conclusion All the three br and s of Albendazole tested regardless of the br and type were therapeutically efficacious for Ascariasis , Trichuriasis and Hookworm infections irrespective of the infection status whether it was single or multiple Appetite and growth were studied in primary schoolboys ( 6 - 10 years ) infected with Ascaris lumbricoides ( 86 % ) and Trichuris trichiura ( 100 % ) who received a single dose of pyrantel pamoate ( which has little or no effect on Trichuris trichiura ) or a placebo . Boys were examined , allocated at r and om by descending Ascaris egg count to pyrantel ( PR , n = 36 ) or placebo ( PL , n = 36 ) groups , treated , and re-examined 3 and 7 weeks later . The 2 groups did not differ significantly before treatment in helminth infections , appetite , or growth . Three and 7 weeks after treatment , the PR group exhibited significantly greater increases than did the PL group in weight ( 0.2 kg and 0.4 kg more , respectively ) and percentage weight-for-age ( 0.6 % and 1.7 % points more , respectively ) . Appetite increased significantly in the PR group at 3 and 7 weeks ( P < 0.0005 and P < 0.01 , respectively ) but not in the PL group . The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks ( both P < 0.0001 ) but not in the PL group . We conclude that treatment with pyrantel pamoate may improve appetite and growth in school children in areas where A. lumbricoides infections and poor growth are highly prevalent A comparative study of the efficacy of albendazole and mebendazole was carried out in Pattani Province in the southern part of Thail and . One hundred and ninety-six patients with single or multiple infections with Ascaris , hookworm , and Trichuris were r and omized into 4 groups for different treatments . Stool examination by Kato-Katz technique were done before and on day 14 after treatment . Results of the study showed that ( 1 ) a single dose of 300 mg mebendazole ( locally produced ) result ed in cure rates of 50 % , 0 % and 0 % and egg reduction rates of 87.3 % , -15.3 % , and 28.3 % , for ascariasis , hookworm infection and Trichuris respectively ; ( 2 ) a single dose of 300 mg mebendazole ( original ) result ed in cure rates of 100.0 % , 9.1 % , and 43.3 % , and egg reduction rates of 100.0 % , 72.0 % , and 77.9 % , for Ascaris , hookworm , and Trichuris respectively ; ( 3 ) a single dose 500 mg mebendazole ( original ) result ed in cure rates of 100.0 % , 30.2 % , and 70.3 % , and egg reduction rates of 100.0 % , 70.4 % and 89.9 % , for Ascaris , hookworm , and Trichuris respectively and ( 4 ) a single dose of 400 mg albendazole ( original ) result ed in cure rates of 100.0 % , 84.3 % , and 67.4 % , and egg reduction rates of 100.0 % , 96.0 % and 87.0 % , for Ascaris , hookworm , and Trichuris respectively . Both mebendazole and albendazole are safe and no side effects were observed . The results of this study suggested that albendazole is the preferred benzimidazole derivative for mass treatment of multiple infections with Ascaris , hookworm , and Trichuris AIM To study the anthelmintic effect of albendazole composite ( containing 67 mg of albendazole and 83.3 mg base of pyrantel pamoate per tablet ) . METHODS A r and omized controlled study was carried out to compare the efficacy of a single dose of 3 or 2 tablets of albendazole composite versus a single dose of 400 mg of albendazole or 10 mg base/kg of pyrantel pamoate for treatment of intestinal nematodiasis including 1,864 cases infected with hookworm , 1,568 cases infected with Ascaris , 1,785 cases infected with Tricuris trichiura and 373 children infected with Enterobius vermicularis . RESULTS In adults , the egg negative conversion rate of a single dose of 3 or 2 tablets of albendazole composite reached 65.0 % and 52.7 % for hookworm infection ( P < 0.01 ) , 100 % and 100 % for Ascaris infection , and 26.5 % and 19.2 % for Trichuris infection ( P < 0.01 ) , respectively . There were significantly better effect against hookworm with 3 tablets of albendazole composite than that with single albendazole or pyrantel pamoate ( 65.0 % vs. 47.6 % and 38.5 % , P < 0.01 ) . The effect of 2 tablets of albendazole composite against hookworm was also higher than that of single pyrantel pamoate ( P < 0.01 ) and equal to single albendazole but the anthelmintic effect against Trichuris infection was lower than that of single albendazole ( 19.2 % vs. 26.5 % ) . In 2 - 6-year-old children , the effect of 1.5 tablets of albendazole composite against Enterobius vermicularis infection showed an egg negative conversion rate of 100 % which was higher than that of single pyrantel pamoate ( 100 % vs. 83.0 % , P < 0.01 ) . The worm collection data showed that the worm-expelling action of albendazole composite was much more rapid than that of albendazole . There were no adverse effects of albendazole composite on blood picture , liver or renal function and ECG . The side effect of both 3 and 2 tablets of albendazole composite was mild and transcient . CONCLUSION Albendazole composite exhibits a synergistic effect of both albendazole and pyrantel pamoate A r and omized controlled trial comparing the efficacy of pyrantel-oxantel ( 10 mg/kg ) with mebendazole ( 500 mg ) was performed on 1329 schoolchildren aged 6 - 9 years on Pemba Isl and in September-October 2000 to evaluate alternative single-dose drugs for regular treatment of intestinal nematode infections . Both mebendazole and pyrantel-oxantel were very effective in eliminating Ascaris lumbricoides infection , inducing cure rates of more than 96 % and reducing the mean egg counts by more than 95 % . Both drugs had a moderate efficacy against Trichuris trichiura infection , but pyrantel-oxantel had a higher cure rate ( 31.5 % vs. 23.3 % , P < 0.01 ) , though the reductions in egg counts did not differ significantly and were more than 80 % . Pyrantel-oxantel and mebendazole had a similar , poor efficacy in curing hookworm infections and had a moderate effect in reducing the egg counts by 67 % and 68 % , respectively . Pyrantel-oxantel ( 10 mg/kg ) offers a valuable alternative to mebendazole as a single-dose treatment for the control of intestinal nematode infections in children in endemic areas of sub-Saharan Africa , due to its comparable efficacy , its low cost and its suitability for use in young children In a trial involving 185 school children , pyrantel pamoate ( Combantrin ) at a dose of 20 mg/kg body weight for 1 - 3 days was found to be very effective against the Ascaris and moderately effective against the hookworm , with mean cure rates ranging from 93.3 - 96.7 % and 53.3 - 73.3 % respectively . No apparent action against the Trichuris was detected , a mean cure rate of between 34.2 and 46.1 % being only slightly , but not significantly , better than the 33.8 % cure for a placebo-treated control group . Single and multiple doses of the suspension and tablet formulations of the drug were well tolerated . From the series of r and omized and controlled trials conducted , we recommend that , in this area , the appropriate dose of the drug to use for treating ascariasis is 10 mg/kg per day for 1 day , and for infections which include hookworm , 20 mg/kg per day for 3 days A clinical trial was carried out on 793 school-children aged six to 12 years to compare the efficacy of pyrantel pamoate , oxantel-pyrantel pamoate , levamisole and mebendazole , in the treatment of infections with Ascaris lumbricoides , Trichuris trichiura and Necator americanus . All four drugs were effective against ascariasis , giving cure rates and egg reduction rates in excess of 92 % . The cure rates ( and egg reduction rates ) for trichuriasis with single-dose treatment were 32·1 % ( 71·9 % ) with pyrantel pamoate , 47·6 % ( 86·2 % ) with oxantel-pyrantel pamoate , 21·8 % ( 66·5 % ) with levamisole and 64·;8 % ( 89·8 % ) with a three-day course of mebendazole . The corresponding rates for necatoriasis were 26·8 % ( 64·1 % ) with pyrantel pamoate , 35·;2 % ( 70·2 % ) with oxantel-pyrantel pamoate , 52·h;4 ( 89·7 % ) with levamisole and 48·7 % ( 87·7 % ) with mebendazole . In terms of cost effectiveness , the best anthelmintic for the treatment of A. lumbricoides appeared to be pyrantel pamoate , followed by levamisole and oxantel-pyrantel pamoate A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis . The study sites were in China and the Philippines , including 2 strains of Schistosoma japonicum , and 2 different regions of Kenya , 1 each with endemic Schistosoma mansoni or Schistosoma haematobium . Neither medication affected the cure rate of the other . There was no difference between the side effect rate from albendazole or the double placebo . Praziquantel-treated children had more nausea , abdominal pain , and headache but these side effects were statistically more common in children with schistosomiasis , suggesting a strong influence of dying parasites . The subjects were followed for 6 months for changes in infection status , growth parameters , hemoglobin , and schistosomiasis morbidity . In all 4 sites , a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel , strongly supporting population -based mass treatment This study was conducted to evaluate the efficacy of 100 mg mebendazole administered twice a day for three consecutive days and a single dose of 400 mg albendazole for the treatment of single or mixed Ascaris lumbricoides and Trichuris trichiura infections . Both drugs were found to be highly effective against Ascaris lumbricoides infection , with cure rate of over 96 % and egg reduction of over 99.8 % . However , the efficacy of the two drugs against Trichuris trichiura infection was low . Mebendazole appeared to be more effective against Trichuris trichiura in that it exhibited a cure rate of 34.7 % and egg reduction of 92.3 % as opposed to albendazole , which exhibited a cure rate and egg reduction rate of 13.9 % and 63.4 % , respectively . The two drugs appeared to have little effect on Schistosoma mansoni infection . More complaints were reported by individuals treated with albendazole than with mebendazole . In conclusion , mebendazole appears to be safer and more effective for the treatment of single or mixed infections with Trichuris trichiura and Ascaris lumbricoides as compared to albendazole A r and omized , placebo-controlled trial of the efficacy of pyrantel ( single dose 12.5 mg/kg bodyweight ) , mebendazole ( single 500 mg dose ) and albendazole ( single 400 mg dose ) in the treatment of hookworm infections ( Necator americanus ) was carried out in January 1998 in the Southern Region of Mali , West Africa , during the period of Ramadan ( Islamic fast ) . Statistical analysis of the pre-intervention faecal egg counts showed that there was a significant pre-treatment chance bias , despite r and omization of subjects into treatment groups , arising from the main effect of sex ( heavier infections among males ) and a sex x treatment interaction ( the sex bias was not evident in the pyrantel-treatment group ) . The participants were re-examined 10 days after treatment , and after controlling for the drift in faecal egg counts in the placebo-treated subset , age , sex , fasting and intensity of infection , albendazole was clearly the most effective drug showing consistently efficacies in the range 92.1 to 99.7 % , depending on the method of evaluation and the particular subset of the treatment group . Neither mebendazole nor pyrantel was as effective , with efficacies ranging from 60.9 to 89.8 % and 4.8 to 89.7 % , respectively . Fasting made no difference to drug efficacy . On the basis of our results the single 400 mg dose of albendazole is the treatment of choice for hookworm infections in this region of Mali . We emphasize the need for st and ardization of the methods used for trial design s , for calculation of summary data relating to drug efficacies and the accompanying statistical tests Efficacite en dose unique contre les parasitoses intestinales . Dans le cas des ankylostomiases , il est tres efficace et bien BACKGROUND Existing anthelmintic drugs ( eg , albendazole and mebendazole ) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted . We aim ed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened . METHODS In this r and omised controlled trial , we compared three drug combinations and one st and ard drug alone in children aged 6 - 14 years in two schools on Pemba Isl and , Tanzania infected with T trichiura and concomitant intestinal nematodes . We assigned children , via a r and omisation list with block sizes of either four or eight , to orally receive albendazole ( 400 mg ) plus ivermectin ( 200 μg/kg ) ; albendazole ( 400 mg ) plus mebendazole ( 500 mg ) ; albendazole ( 400 mg ) plus oxantel pamoate ( 20 mg/kg ) ; or mebendazole ( 500 mg ) alone . The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means , both analysed by available case . This study is registered with IS RCT N , number IS RCT N80245406 . FINDINGS We r and omly assigned 440 eligible children infected with T trichiura between Sept 2 , and Oct 18 , 2013 , to one of the four treatment groups ( 110 children per group ) . Data for 431 children were included in the analysis for the primary endpoints . Albendazole plus oxantel pamoate ( 74 of 108 children cured [ 68·5 % , 95 % CI 59·6 - 77·4 ] ; egg reduction 99·2 % , 98·7 - 99·6 ) and albendazole plus ivermectin ( 30 of 109 cured [ 27·5 % , 19·0 - 36·0 ] ; egg reduction 94·5 % , 91·7 - 96·3 ) were significantly more effective against T trichiura than mebendazole alone ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ] ; egg reduction 58·5 % , 45·2 - 70·9 ) . Albendazole plus mebendazole had similar low efficacy ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ; egg reduction 51·6 % , 35·0 - 65·3 ) to mebendazole alone . About a fifth of the children reported adverse events , which were mainly mild . Abdominal cramps and headache were the most common adverse events after treatment ; abdominal cramps were reported by 13 ( 12·0 % ) children for albendazole plus ivermectin , 10 ( 9·3 % ) for albendazole plus mebendazole , 20 ( 18·2 % ) for albendazole plus oxantel pamoate , and 16 ( 14·5 % ) for mebendazole ; headaches were reported by 5 ( 4·6 % ) children for albendazole plus ivermectin , 6 ( 5·6 % ) for albendazole plus mebendazole , 12 ( 10·9 % ) for albendazole plus oxantel pamoate , and 7 ( 6·4 % ) for mebendazole . INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes . FUNDING Medicor Foundation and Swiss National Science Foundation A multicentre , r and omized trial was carried out to compare the efficacy of two single-dose treatments for ascariasis : mebendazole 200 mg , and pyrantel 10 mg/kg . Each centre enrolled 200 patients with a suspected diagnosis of ascariasis , 100 for each treatment , and the treatments were r and omized for each centre . To confirm the diagnosis , stools were examined for eggs of Ascaris lumbricoides by Kato 's thick smear method . Efficacy was evaluated by stool examination repeated three weeks after treatment by a " blind " technician using two methods , viz . Kato 's thick smear method and the zinc sulfate flotation method . Cure was defined as absence of ascaris eggs in the stools by both methods . Of the 600 enrolled patients , 32 were excluded from analysis as their initial stool examination was negative , and 568 completed the trial : 284 on each treatment . The cure rate was 80 per cent in the mebendazole group and 90 per cent in the pyrantel group ( P less than 0.01 ) . Thus pyrantel was found to be significantly more efficacious than mebendazole for single-dose treatment of ascariasis A survey of 108 individuals from a coastal Aboriginal community in north Western Australia revealed that two species of gastrointestinal protozoan parasites ( Giardia duodenalis--39.8 % , Entamoeba coli--40.7 % ) and five gastrointestinal helminths ( Hymenolepis nana--54.6 % , Hookworm [ Ancylostoma duodenale]--30.6 % , Enterobius vermicularis--6.5 % , Trichuris trichiura--2.8 % , Strongyloides stercoralis 1.9 % ) were present . A total of 29 individuals infected with hookworm were offered treatment with either pyrantel pamoate at a single dose rate of 10 mg/kg body weight or albendazole ( single 400 mg dose ) . Seven days after treatment stool sample s were examined . Pyrantel had no significant effect against hookworm . In contrast , albendazole cleared hookworm infections completely and reduced the prevalence of Giardia . The former result suggests that locally A. duodenale is resistant to pyrantel and despite its relatively low cost and wide availability , should not be considered a drug of choice at this dose rate in the treatment of hookworm infections ( A. duodenale ) in endemic regions Three r and omized clinical studies were conducted in 2000 to evaluate the efficacy of nitazoxanide paediatric suspension compared to albendazole in the treatment of ascariasis and trichuriasis and praziquantel in the treatment of hymenolepiasis in children from Cajamarca , Peru . Nitazoxanide was administered at a dose of 100 mg ( age 1 - 3 years ) or 200 mg ( age 4 - 11 years ) twice daily for 3 days , albendazole as a 400-mg single dose and praziquantel as a 25-mg/kg single dose . Post-treatment parasitological examinations were carried out on 3 faecal sample s , each collected on a different day between 21 and 30 days following initiation of treatment . Nitazoxanide cured 89 % ( 25/28 ) , 89 % ( 16/18 ) and 82 % ( 32/39 ) of the cases of ascariasis , trichuriasis and hymenolepiasis respectively compared with 91 % ( 32/35 ) , 58 % ( 11/19 ) and 96 % ( 47/49 ) for the comparator drugs . Each of the drugs produced egg reduction rates in excess of 98 % . There were no significant adverse events or abnormalities in haematology or clinical chemistry values or urinalysis Abstract The effect of pyrantel pamoate was compared with that of piperazine phosphate in the treatment of ascariasis , the results being expressed in terms of quantitative egg counts . Pyrantel pamoate , in a single oral dose of 10.0 mg per kg of body weight , achieved a cure rate of 90 % on day 3 and 100 % on day 10 after treatment . Administration of 5.0 mg and 2.5 mg per kg similarly achieved early and pronounced reduction of egg output with a cure rate of 90 % by day 10 . In patients not cured , mean reduction of egg output was almost complete with the 10.0-mg treatment and 88 % with the 2.5-mg treatment calculated throughout days 8 , 9 , and 10 . St and ard oral treatment with piperazine phosphate achieved a cure rate of 71 % by day 10 , significantly less than that with 2.5 mg of pyrantel pamoate . In patients not cured , a mean reduction in egg output of 72 % was achieved , as calculated throughout days 1 , 2 , and 3 , with no further improvement . Other than transient abdominal colic in a few patients during the early posttreatment period , no obvious drug-related symptoms were observed . No trend of abnormality was noted in either serum glutamic pyruvic transaminase or alkaline phosphatase levels after pyrantel pamoate treatment Preliminary studies indicated that single-dose ( 500 mg ) mebendazole gave disappointing results in the treatment of hookworm infections ( Necator americanus ) in Mali . A placebo-controlled , r and omized trial conducted with the participation of 103 infected subjects ( background hookworm prevalence > 50 % ) confirmed that mebendazole ( Vermox ) did not reduce parasite burdens significantly , as assessed through fecal egg counts . In contrast , a group of subjects treated with pyrantel ( Combantrin ) experienced a significant reduction in fecal worm egg counts ( overall , both sexes combined showed a 75 % reduction ) . Male subjects carried significantly more intense infections compared with females , but there was no gender difference in response to treatment . A st and ard egg hatch assay showed that N. americanus from our subjects in Mali was more resistant to benzimidazoles compared with a laboratory-maintained strain that had not been exposed to anthelmintics in more than 100 generations ( 50 % effective dose = 0.12 and 0.07 microg/ml of thiabendazole , respectively ) , suggesting that , among other possibilities , the development of resistance to the benzimidazoles by N. americanus may have contributed to the drug failure . Whatever the underlying explanation , our results indicate that single-dose treatment with mebendazole is an ineffective treatment for hookworm infections and despite its relatively cheap cost and wide availability , mebendazole should not be considered a drug of choice in the mass treatment of hookworm infections in this region of Mali A r and omized open-label trial , including 834 pregnant women , examined efficacy and recorded adverse events of ivermectin ( ivc ) and albendazole ( alb ) alone and combined ( comb ) on soil-transmitted helminth infections ( STHs ) in the second trimester of pregnancy . One abortion occurred in the alb group and 10 stillbirths ( 1 , 5 , 3 , and 1 ) in the ivc , alb , comb , and the reference group ( ref ) with no STHs , respectively . Two babies were born with congenital abnormalities ( 1 [ ivc ] and 1 [ ref ] ) . The prevalence of anemia at first antenatal care ( ANC ) visit was 20.6 % ( 23.7 % [ ivc ] , 21.1 % [ alb ] , 22.2 % [ comb ] , and 16.1 % [ ref ] ) . Anemia was reduced to 8.5 % at 36 weeks of gestation with 10.9 % ( ivc ) , 11.5 % ( alb ) , 7.7 % ( comb ) , and 6.9 % ( ref ) . Hookworm cure rates were 29.4 % ( ivc ) , 95.5 % ( alb ) , and 92.6 % ( comb ) . No severe adverse events were reported by the women after the administration of ivc , alb , or comb during the second trimester of pregnancy , but long-term pharmacovigillance is needed to assess safety of ivc , alb , or comb in pregnancy The effect of pyrantel pamoate , levamisole , mebendazole , thiabendazole and bephenium hydroxynaphthoate on various intestinal helminths were evaluated among the inhabitants of four villages in the Dezful area southwest of Iran . A total number of 328 persons , all infected simultaneously with Ascaris and hookworm ( Ancylostoma duodenale ) and 49.2 % with Trichostrongylus spp . , were r and omly divided into six groups . One group was kept as the control and the other five were each treated with one compound . Follow-up examinations showed that all of the drugs used were highly effective on Ascaris , and the differences in the cure rate were not statistically significant except for bephenium hydroxynaphthoate which showed a lower cure rate . For hookworm , cure rates of 100 , 90 , and 85 % were observed with levamisole , pyrantel pamoate and bephenium hydroxynaphthoate , respectively . Cure rates observed with mebendazole and thiabendazole were 35 and 51 % , respectively . For Trichostrongylus , the highest cure rate was achieved with levamisole , followed by thiabendazole and mebendazole . While the percentage of people showing side-effects was rather low for all drugs , thiabendazole and bephenium hydroxynaphthoate produced a higher , and levamisole a lower , percentage of side effects |
13,953 | 31,325,241 | Few areas demonstrated statistically significant effects across studies ; school‐based approaches and health care initiatives reduced energy consumed , education reduced energy consumed and increased energy expended , and social‐group approaches increased energy expenditure .
Conclusions Despite the amount of research on obesity prevention interventions , very few studies have provided relevant information on energy intake and expenditure , two factors determining weight gain . | Objective Obesity is preventable and yet continues to be a major risk factor for chronic disease .
Multiple prevention approaches have been proposed across multiple setting s where people live , work , learn , worship , and play .
This review search ed the vast literature on obesity prevention interventions to assess their effects on daily energy consumed and energy expended . | OBJECTIVES Motivating adolescents to adopt proper nutrition and physical activity behaviors is important in this nation 's fight to prevent obesity and chronic diseases . This study was conducted to determine which health education delivery method would elicit a greater behavior change . METHOD The intervention was conducted in three schools ( control , computer-based , and traditional education ) . RESULTS Students who received the computer-based intervention showed increased knowledge ( p<0.001 ) , physical activity ( p=0.001 ) , self-efficacy ( p<0.001 ) , and social support ( p<0.001 ) , and decreased meals skipped ( p<0.001 ) . CONCLUSION The computer-based group showed more positive behavior changes . However , future programs may be enhanced by including group discussion and individual feedback Background Age‐related endothelial dysfunction and vascular stiffening are associated with increased cardiovascular ( CV ) risk . Many groups have encouraged goals of ≥10 000 steps/day or ≥30 min/day of moderate intensity physical activity ( MPA ) to reduce age‐related CV risk . The impact of MPA on the vasculature of older adults remains unclear . Methods and Results We r and omized 114 sedentary older adults ages ≥50 to 12 weeks of either no intervention ( group 1 ) , a pedometer‐only intervention ( group 2 ) , or a pedometer with an interactive website employing strategies to increase the adoption of habitual physical activity ( PA , group 3 ) . Endothelial function by brachial flow‐mediated dilation ( FMD% ) , vascular stiffness by tonometry , step‐count by pedometer , and PA intensity/distribution by accelerometer were measured . Step‐count increased in groups 2 ( 5136±1554 to 9596±3907 , P<0.001 ) and 3 ( 5474±1512 to 8167±3111 , P<0.001 ) but not in group 1 ( 4931±1667 to 5410±2410 ) . Both groups 2 and 3 increased MPA ≥30 min/day . Only group 3 increased MPA in continuous bouts of ≥10 minutes ( P<0.001 ) and improved FMD% ( P=0.001 ) . Neither achievement of ≥10 000 steps/day nor ≥30 min/day of MPA result ed in improved FMD% . However , achieving ≥20 min/day in MPA bouts result ed in improved FMD% . No changes in vascular stiffness were observed . Conclusions MPA reverses age‐related endothelial dysfunction , but may require MPA to be performed in bouts of ≥10 minutes duration for ≥20 min/day to be effective . Commonly encouraged PA goals do not guarantee improved endothelial function and may not be as effective in reducing CV risk . Clinical Trial Registration URL : Clinical trials.gov . Unique identifier : NCT‐01212978 BACKGROUND Web-based interventions for weight control could promote more-widespread dissemination of weight-loss opportunities ; however , they remain limited in effectiveness . Incorporating weight-control practice s used by individuals with long-term weight-loss success ( " positive deviants " ) may improve the efficacy of web-based weight control interventions . PURPOSE To evaluate the efficacy of AchieveTogether , a web-based weight-loss intervention for adults based on user-generated weight-loss strategies from successful weight losers . DESIGN In 2009 - 2010 , participants were r and omized to either a 12-week web-based intervention , AchieveTogether , or a wait-list control condition . SETTING / PARTICIPANTS 100 overweight or obese adults participated in the study . INTERVENTION AchieveTogether was design ed to help individuals implement weight control practice s used by others who successfully lost and maintained weight . MAIN OUTCOME MEASURES The primary outcome was change in weight . Secondary outcomes included blood pressure , daily caloric intake , quality of life , and use of weight control practice s. ANCOVA , with adjustment for baseline values on outcome measures , was used to assess differences between groups in primary and secondary outcomes . Statistical analyses were conducted in 2010 - 2011 . RESULTS Most participants were women ( 69.7 % ) and white ( 90.8 % ) , with a mean age of 50.3 years and baseline BMI of 33.2 ; 88 % completed post-program assessment s. Mean weight loss among intervention participants was -1.4 kg ( 95 % CI= -2.2 , -0.5 ) , compared with a mean weight gain of 0.6 kg ( 95 % CI= -0.3 , 1.4 ) in control participants ( p<0.01 ) . CONCLUSIONS User-generated weight-loss practice s from " positive deviants " could promote weight control in web-based interventions ; however , further research is needed to improve program efficacy . TRIAL REGISTRATION This study is registered at Clinical Trials.govNCT00709501 BACKGROUND Given the dramatic increase in adolescent overweight and obesity , models are needed for implementing weight management treatment through readily accessible venues . We evaluated the acceptability and efficacy of a school-based intervention consisting of school nurse-delivered counseling and an afterschool exercise program in improving diet , activity , and body mass index ( BMI ) among overweight and obese adolescents . METHODS A pair-matched cluster-r and omized controlled school-based trial was conducted in which 8 public high schools were r and omized to either a 12-session school nurse-delivered cognitive-behavioral counseling intervention plus school-based after school exercise program , or 12-session nurse contact with weight management information ( control ) . Overweight or obese adolescents ( N = 126 ) completed anthropometric and behavioral assessment s at baseline and 8-month follow-up . Main outcome measures included diet , activity , and BMI . Mixed effects regression models were conducted to examine differences at follow-up . RESULTS At follow-up , students in intervention compared with control schools were not different in BMI , percent body fat , and waist circumference . Students reported eating breakfast ( adjusted mean difference 0.81 days ; 95 % confidence interval [ CI ] 0.11 - 1.52 ) on more days/week ; there were no differences in other behaviors targeted by the intervention . CONCLUSIONS While a school-based intervention including counseling and access to an after-school exercise program is theoretically promising with public health potential , it was not effective in reducing BMI or key obesogenic behaviors . Our findings are important in highlighting that interventions targeted at the individual level are not likely to be sufficient in addressing the adolescent obesity epidemic without changes in social norms and the environment Background : Theory-based interventions accessible to large groups of people are needed to induce favorable shifts in health behaviors and body weight . Purpose : The aim was to assess nutrition ; physical activity ; and , secondarily , body weight in the tailored , social cognitive Guide to Health ( GTH ) Internet intervention delivered in churches . Methods : Participants ( N=1,071 ; 33 % male , 23 % African American , 57 % with body mass index ≥25 , 60 % sedentary , Mdn age=53 years ) within 14 Baptist or United Method ist churches were r and omized to the GTH intervention only ( GTH-Only ; 5 churches ) , with church-based supports ( GTH-Plus ; 5 churches ) , or to a waitlist ( control ; 4 churches ) . Verified pedometer step counts , measured body weight , fat , fiber , and fruit and vegetable ( F&V ) servings from food frequency and supermarket receipts were collected at pretest , posttest ( 7 months after pretest ) , and follow-up ( 16 months after pretest ) . Results : Participants in GTH-Only increased F&V at post ( ∼1.50 servings ) compared to control ( ∼0.50 servings ; p=.005 ) and at follow-up ( ∼1.20 vs. ∼0.50 servings ; p=.038 ) and increased fiber at post ( ∼3.00 g ) compared to control ( ∼1.5 g ; p=.006 ) and follow-up ( ∼3.00 g vs. ∼2.00 g ; p=.040 ) . GTH-Plus participants compared to control increased steps at post ( ∼1,500 steps/day vs. ∼400 steps/day ; p=.050 ) and follow-up ( ∼1,000 steps/day vs. ∼−50 steps/day ; p=.010 ) , increased F&V at post ( ∼1.5 servings ; p=.007 ) and follow-up ( ∼1.3 servings ; p=.014 ) , increased fiber at post ( ∼3.00 g ; p=.013 ) , and follow-up ( ∼3.00 ; p=.050 ) and decreased weight at post ( ∼−0.30 kg vs. ∼+0.60 kg ; p=.030 ) . Conclusions : Compared to control , both GTH treatments improved nutrition at posttest , but church supports improved physical activity and nutrition at posttest and follow-up , suggesting environmental supports may improve Internet-based interventions Context : Menopausal-related weight gain and increased waist circumference have major cardiovascular health implication s for older women . The efficacy of a dietary and physical activity lifestyle intervention to prevent weight gain and elevations in cardiovascular disease ( CVD ) risk factors from the peri- to postmenopause is unknown . Objective : To report the 54-month results of a lifestyle dietary and physical activity program on weight , body composition , physical activity , diet , and other CVD risk factors . Design : Data are from a 5-year r and omized clinical trial known as the Women ’s Healthy Lifestyle Project , conducted from 1992 to 1999 . Participants : 535 healthy , premenopausal women ages 44 to 50 at study entry enrolled into the trial . Intervention : Participants were r and omly assigned to either a lifestyle intervention group receiving a 5-year behavioral dietary and physical activity program or to an assessment -only control group . The lifestyle intervention group was given modest weight loss goals ( 5–15 lb , or approximately 2.3–6.8 kg ) to prevent subsequent gain above baseline weight by the end of the trial . To achieve weight loss and lower low-density lipoprotein cholesterol levels , intervention participants followed an eating pattern consisting of 1,300 kcal/day ( 25 % total fat , 7 % saturated fat , 100 mg of dietary cholesterol ) and increased their physical activity expenditure ( 1,000–1,500 kcal/week).Main Outcome Measures : Regarding weight gain prevention , 55 % ( 136/246 ) of intervention participants were at or below baseline weight compared with 26 % ( 68/261 ) of controls after 4.5 years , χ(2 , N = 507 ) = 45.0 , p < .001 . The mean weight change in the intervention group was 0.1 kg below baseline ( SD = 5.2 kg ) compared with an average gain of 2.4 kg ( SD = 4.9 kg ) observed in the control group . Waist circumference also significantly decreased more in the intervention group compared with controls ( M = −2.9 cm , SD = 5.3 vs. M = −0.5 cm , SD = 5.6 , p < .001 ) . Moreover , participants in the lifestyle intervention group were consistently more physically active and reported eating fewer calories and less fat than controls . Long-term adherence to physical activity and a low-fat eating pattern was associated with better weight maintenance . Conclusions : In healthy women , weight gain and increased waist circumference during the peri- to postmenopause can be prevented with a long-term lifestyle dietary and physical activity intervention 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 Importance Strategies to improve the nutritional status of those participating in the Supplemental Nutrition Assistance Program ( SNAP ) are of interest to policymakers . Objective To evaluate whether the proposed policy of incentivizing the purchase of fruits and vegetables and prohibiting the purchase of less nutritious foods in a food benefit program improves the nutritional quality of participants ' diets . Design , Setting , and Participants Lower income participants ( n = 279 ) not currently enrolled in SNAP were r and omized to 1 of 4 experimental financial food benefit conditions : ( 1 ) incentive ( 30 % financial incentive for fruits and vegetables purchased using food benefits ) ; ( 2 ) restriction ( not allowed to buy sugar sweetened beverages , sweet baked goods , or c and ies with food benefits ) ; ( 3 ) incentive plus restriction ( 30 % financial incentive on fruits and vegetables and restriction of purchase of sugar sweetened beverages , sweet baked goods , or c and y with food benefits ) ; or ( 4 ) control ( no incentive or restrictions on foods purchased with food benefits ) . Participants in all conditions were given a study -specific debit card where funds were added every 4 weeks for a 12-week period . Outcome measures were collected at baseline and in the final 4 weeks of the experimental period . Main Outcomes and Measures Primary outcomes ( from 24-hour dietary recalls ) included intake of energy , discretionary calories , and overall diet quality . Results A number of favorable changes were observed in the incentive plus restriction condition that were significantly different from changes in the control condition . These included ( 1 ) reduced intake of energy ( -96 kcal/d , st and ard error [ SE ] , 59.9 ) ; ( 2 ) reduced intake of discretionary calories ( -64 kcal/d , SE 26.3 ) ; ( 3 ) reduced intake of sugar sweetened beverages , sweet baked goods , and c and ies ( -0.6 servings/d , SE 0.2 ) ; ( 4 ) increased intake of solid fruit ( 0.2 servings/d , SE 0.1 ) ; and ( 5 ) improved Healthy Eating Index score ( 4.1 points , SE 1.4 ) . Fewer improvements were observed in the incentive only and restriction only arms . Conclusions and Relevance A food benefit program that pairs incentives for purchasing more fruits and vegetables with restrictions on the purchase of less nutritious foods may reduce energy intake and improve the nutritional quality of the diet of participants compared with a program that does not include incentives or restrictions . Clinical Trial Registration clinical trials.gov Identifier : NCT02643576 Background The benefits of physical activity are well documented , but scalable programs to promote activity are needed . Interventions that assign tailored and dynamically adjusting goals could effect significant increases in physical activity but have not yet been implemented at scale . Objective Our aim was to examine the effectiveness of an open access , Internet-based walking program that assigns daily step goals tailored to each participant . Methods A two-arm , pragmatic r and omized controlled trial compared the intervention to no treatment . Participants were recruited from a workplace setting and r and omized to a no-treatment control ( n=133 ) or to treatment ( n=132 ) . Treatment participants received a free wireless activity tracker and enrolled in the walking program , Walkadoo . Assessment s were fully automated : activity tracker recorded primary outcomes ( steps ) without intervention by the participant or investigators . The two arms were compared on change in steps per day from baseline to follow-up ( after 6 weeks of treatment ) using a two-tailed independent sample s t test . Results Participants ( N=265 ) were 66.0 % ( 175/265 ) female with an average age of 39.9 years . Over half of the participants ( 142/265 , 53.6 % ) were sedentary ( < 5000 steps/day ) and 44.9 % ( 119/265 ) were low to somewhat active ( 5000 - 9999 steps/day ) . The intervention group significantly increased their steps by 970 steps/day over control ( P<.001 ) , with treatment effects observed in sedentary ( P=.04 ) and low-to-somewhat active ( P=.004 ) participants alike . Conclusions The program is effective in increasing daily steps . Participants benefited from the program regardless of their initial activity level . A tailored , adaptive approach using wireless activity trackers is realistically implementable and scalable . Trial Registration Clinical trials.gov NCT02229409 , https:// clinical trials.gov/ct2/show/NCT02229409 ( Archived by WebCite at http://www.webcitation.org/6eiWCvBYe 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 PURPOSE Physical activity in childhood has many health benefits ; however , the majority of children in many countries , including Mexico , are insufficiently active . The objective of this investigation was to test the effect of a school-based environmental intervention on the physical activity and physical fitness of students attending public primary schools in Mexico City . METHODS Twenty-seven schools were r and omly assigned to basic or plus intervention or control . The basic and plus groups were exposed to school environment and policy changes to enhance physical activity . Physical activity was evaluated in 699 r and omly selected fourth- and fifth- grade students by measuring school-day and all-day ( 24 h ) steps using pedometers worn for 5 d before and after the 6-month intervention . Physical fitness was assessed by measuring the 9-min run , flexibility , and sit-ups . We calculated the average change in school-day and all-day steps and fitness measures from baseline to follow-up . Using linear regression , we tested the effect of intervention on change controlling for baseline measures and covariates and accounting for the design effect of school . Using logistic regression , we tested the effect of intervention on reaching step cutoffs at baseline and follow-up . RESULTS The plus group significantly ( P < 0.05 ) increased school-day steps relative to control ( change = 687 vs -639 ) . Significantly ( P < 0.05 ) more participants in the basic ( 25.8 % ) and plus ( 36.4 % ) groups reached step cutoffs during school relative to control ( 12.0 % ) . The basic group significantly ( P < 0.05 ) increased all-day steps relative to control ( change = 581 vs -419 ) . The plus group significantly ( P = 0.05 ) increased sit-ups relative to control ( change = 0.3 vs -1.7 ) . CONCLUSIONS A school-based environmental intervention improved student physical activity during school in public schools in Mexico City Working mothers exhibit high levels of inactivity , and theory-based interventions to bolster physical activity within this population are needed . This study examined the effectiveness of a brief social cognitive theory-based intervention design ed to increase physical activity among working mothers . Participants ( N = 141 ) were r and omly assigned to an intervention only , intervention plus follow-up support , or waitlist control condition . The intervention consisted of two group-based workshop sessions design ed to teach behavior modification strategies using social cognitive theory . Data were collected at baseline , immediately post-intervention , and 6-month follow-up . Results showed intervention participants exhibited short-term increases in physical activity , which were partially maintained 6 months later . Improvements in physical activity were mediated by increases in self-regulation and self-efficacy . This study provides some support for the effectiveness of a brief intervention to increase physical activity among working mothers . Future programs should explore alternative support mechanisms which may lead to more effective maintenance of initial behavior changes 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 BACKGROUND Physical activity is important for weight control and good health ; however , activity levels decline in the adolescent years , particularly in girls . DESIGN Group r and omized controlled trial . SETTING / PARTICIPANTS Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States . R and om , cross-sectional sample s were drawn within schools : 6th grade rs in 2003 ( n=1721 ) and 8th grade rs in 2005 ( n=3504 ) and 2006 ( n=3502 ) . INTERVENTION A 2-year study -directed intervention ( fall 2003 to spring 2005 ) targeted schools , community agencies , and girls to increase opportunities , support , and incentives for increased physical activity . Components included programs linking schools and community agencies , physical education , health education , and social marketing . A third-year intervention used school and community personnel to direct intervention activities . MAIN OUTCOME MEASURES The primary outcome , daily MET-weighted minutes of moderate-to-vigorous physical activity ( MET-weighted MVPA ) , was assessed using accelerometry . Percent body fat was assessed using anthropometry . RESULTS After the staff-directed intervention ( pre-stated primary outcome ) , there were no differences ( mean= -0.4 , 95 % CI= -8.2 to 7.4 ) in adjusted MET-weighted MVPA between 8th- grade girls in schools assigned to intervention or control . Following the Program Champion-directed intervention , girls in intervention schools were more physically active than girls in control schools ( mean difference 10.9 MET-weighted minutes of MVPA , 95 % CI=0.52 - 21.2 ) . This difference is about 1.6 minutes of daily MVPA or 80 kcal per week . There were no differences in fitness or percent body fat at either 8th- grade timepoint . CONCLUSION A school-based , community-linked intervention modestly improved physical activity in girls Introduction The 15-minute work break provides an opportunity to promote health , yet few studies have examined this part of the workday . We studied physical activity and sedentary behavior among office workers and compared the results of the Booster Break program with those of a second intervention and a control group to determine whether the Booster Break program improved physical and behavioral health outcomes . Methods We conducted a 3-arm , cluster-r and omized controlled trial at 4 worksites in Texas from 2010 through 2013 to compare a group-based , structured Booster Break program to an individual-based computer-prompt intervention and a usual-break control group ; we analyzed physiologic , behavioral , and employee measures such as work social support , quality of life , and perceived stress . We also identified consistent and inconsistent attendees of the Booster Break sessions . Results We obtained data from 175 participants ( mean age , 43 y ; 67 % racial/ethnic minority ) . Compared with the other groups , the consistent Booster Break attendees had greater weekly pedometer counts ( P < .001 ) , significant decreases in sedentary behavior and self-reported leisure-time physical activity ( P < .001 ) , and a significant increase in triglyceride concentrations ( P = .02 ) ( levels remained within the normal range ) . Usual-break participants significantly increased their body mass index , whereas Booster Break participants maintained body mass index status during the 6 months . Overall , Booster Break participants were 6.8 and 4.3 times more likely to have decreases in BMI and weekend sedentary time , respectively , than usual-break participants . Conclusion Findings varied among the 3 study groups ; however , results indicate the potential for consistent attendees of the Booster Break intervention to achieve significant , positive changes related to physical activity , sedentary behavior , and body mass index Background Physicians are expected to serve as role models for healthy lifestyles , but long work hours reduce time for healthy behaviors . A hospital-based physical activity intervention could improve physician health and increase counseling about exercise . Methods We conducted a two-phase intervention among 104 medical residents at a large hospital in Boston , Massachusetts . Phase 1 was a 6-week r and omized controlled trial comparing daily steps of residents assigned to an activity monitor displaying feedback about steps and energy consumed ( intervention ) or to a blinded monitor ( control ) . Phase 2 immediately followed and was a 6-week non-r and omized team steps competition in which all participants wore monitors with feedback . Phase 1 outcomes were : 1 ) median steps/day and 2 ) proportion of days activity monitor worn . The Phase 2 outcome was mean steps/day on days monitor worn ( ≥500 steps/day ) . Physiologic measurements were collected at baseline and study end . Median steps/day were compared using Wilcoxon rank-sum tests . Mean steps were compared using repeated measures regression analyses . Results In Phase 1 , intervention and control groups had similar activity ( 6369 vs. 6063 steps/day , p = 0.16 ) and compliance with wearing the monitor ( 77 % vs. 77 % of days , p = 0.73 ) . In Phase 2 ( team competition ) , residents recorded more steps/day than during Phase 1 ( Control : 7,971 vs. 7,567 , p = 0.002 ; Intervention : 7,832 vs. 7,739 , p = 0.13 ) . Mean compliance with wearing the activity monitor decreased for both groups during Phase 2 compared to Phase 1 ( 60 % vs. 77 % , p<0.001 ) . Mean systolic blood pressure decreased ( p = 0.004 ) and HDL cholesterol increased ( p<0.001 ) among all participants at end of study compared to baseline . Conclusions Although the activity monitor intervention did not have a major impact on activity or health , the high participation rates of busy residents and modest changes in steps , blood pressure , and HDL suggest that more intensive hospital-based wellness programs have potential for promoting healthier lifestyles among physicians . Trial Registration Clinical trials.gov NCT01287208 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 Abstract : This study examined whether subjects who participated in a 12-mo intervention would maintain their diets 1 yr after the study ended and whether the diets of household members were affected . Premenopausal women , who had at least one first-degree relative with breast cancer ( n = 122 ) , were r and omized to one of four diets : control , low fat ( 15 % of energy ) , high fruit and vegetable ( FV , nine servings per day ) , and combination low fat , high FV . Study subjects and one household member were asked to complete the Block ‘ 95 food-frequency question naire ( FFQ ) at baseline , 1 yr , and 2 yr . Study subjects also completed 24-h recalls and 4-day food records at baseline and Year 1 . Fat and FV intakes by all three assessment methods compared reasonably well except that fat intakes by FFQ were somewhat higher . FV intakes by FFQ in the high-FV and combination arms increased significantly from 4 servings per day to about 10 servings per day at Year 1 and 7 servings per day at Year 2 . FV intakes increased much more modestly in the low-fat and control arms . Fat intakes in the low-fat and combination arms were lower at Year 1 than Year 2 , but mean Year 2 fat intakes of 26–28 % were still significantly lower than those at baseline . In household members , the only significant change was a small decrease in energy from fat at Year 1 in the household members of subjects who were in the combination arm . These results indicate that study subjects were making large dietary changes independently of their household members and that fat and FV intakes in study subjects 1 yr after intervention stopped were still substantially different from intakes at baseline OBJECTIVE To evaluate the costs and effects of incremental components of a weight-loss program . DESIGN A 3-arm , 12-month r and omized controlled clinical trial to evaluate 3 incremental levels of intervention intensity . SUBJECTS/ SETTING The study included 588 individuals ( BMI > 25 kg/m2 ) in a freest and ing health maintenance organizalion and achieved an 81 % completion rate . INTERVENTION Using a cognitive behavioral approach for tailoring lifestyle modification goals , the incremental levels of intervention included a ) a workbook alone , b ) the addition of computerized tailoring using onsite computer kiosks with touch screen monitors , and c ) the addition of both computers and staff consultation . MAIN OUTCOME MEASURES Endpoints included weight parameters , lipid profile , plasma glucose , blood pressure , intervention costs , dietary intake , and physical activity . STATISTICAL ANALYSIS PERFORMED Study endpoints were analyzed using analysis of variance for normally distributed variables and analysis of covariance to control for any baseline differences . Regression and correlation analysis assessed the relationship between weight loss and other variables . RESULTS For the increasing levels of intervention intensity , the mean 12-month weight losses were 2.2 , 4.7 , and 7.4 pounds , with the respective cost per participant being $ 12.33 , $ 41.99 , and $ 133.74 . The decreases in mean BMI s for these respective intervelation levels were 0.4 , 0.9 and 1.2 . All groups reported a decrease in energy and fat intake and an increase in blocks walked ( P<.01 ) . Intervention variables that correlated with weight loss included more computer log-ons , achieving computer-selected goals , more self-monitoring , increased walking , and decreased energy and fat intake , as well as higher attendance in staff consultation group sessions for that treatment condition . Weight loss correlated with decreases in fasting glucose and blood pressure . APPLICATIONS/ CONCLUSIONS In a weight-loss program , computers can facilitate selecting behavioral change goals . More frequent usage result ed in greater weight loss . Staff counseling to augment the computer intervention achieved the most weight loss OBJECTIVES To evaluate the effect of a school-based obesity prevention programme on physical self-perception and key physical-activity related cognitions in adolescent boys from disadvantaged secondary schools . A secondary objective was to determine if any psychological changes were associated with improved weight status . METHODS Participants ( n = 100 , age = 14.3[0.6 ] ) were r and omized to the PALS ( Physical Activity Leaders ) intervention ( n = 50 ) or a control group ( n = 50 ) and assessed at baseline , 3- and 6-month follow up . Measures included BMI , BMI z-score and % body fat ( bioelectrical impedance analysis ) . Students also completed the Children 's Physical Self-Perception Profile and a physical activity-related cognitions question naire . The findings include secondary data analyses . RESULTS Relative to the controls , the PALS group significantly increased their physical self worth ( p = .01 ) , perceived physical condition ( p = .02 ) , resistance training self efficacy ( p < .001 ) and their use of physical activity behavioural strategies ( p = .02 ) . CONCLUSIONS A school-based obesity prevention programme that targeted leadership skills improved psychological health in the physical domain in adolescent boys from disadvantaged schools BACKGROUND There is minimal information on the impact of replacing sugar-sweetened beverage ( SSB ) consumption with water on diet quality from r and omized controlled trials . OBJECTIVE We evaluated the effect of a water intake intervention on diet quality in overweight Mexican women . METHODS Women with a body mass index ≥25 and < 39 , 18 - 45 y old , and a self-reported high intake of SSBs ( ≥250 kcal/d ) were r and omly allocated to either the water and education provision ( WEP ) group ( n = 120 ) or the education provision ( EP ) only group ( n = 120 ) . Each group received monthly nutrition counseling , and the WEP group received biweekly water deliveries for 9 mo . Three 24-h recalls , anthropometry , and demographic information were collected at baseline , and 3 , 6 , and 9 mo . Energy , macronutrient , sugar , SSB , fruit and vegetable , salty snack , cake and cookie , and fast food intakes were assessed in study completers ( n = 189 ) classified by intervention assignment and by actual water intake at every time point ( low < 1200 vs. high ≥1200 mL/d ) . RESULTS The WEP group reported greater decreases in SSB intake than the EP group ( from 20.9 % to 10.3 % of energy/d vs. from 20.1 % to 17.8 % ) . Thirty-eight percent of the EP group and 84.3 % of the WEP group reported attaining a water intake ≥1200 mL/d . Reductions in energy intake and food groups were similar across intervention groups . However , the high actual water intake group reported greater increases vs. the lower intake group in intake of fruits and vegetables ( 117 vs. 47 g/d ) , as well as larger reductions in salty snacks ( 4.6 vs. 0.7 g/d ) and cakes and cookies ( 31.7 vs. 14.7 g/d ) . CONCLUSIONS Other than SSBs , improvements in food group intake did not differ by intervention group in overweight Mexican women . However , post hoc analyses suggested that achieving a high actual water intake was associated with additional beneficial changes in food group intake . This trial was registered at clinical trials.gov as NCT01245010 Objective : To determine the effectiveness of the 12-week workplace intervention ( WIP ) on energy intake , weight , physical activity ( PA ) and cardiovascular disease ( CVD ) risk and the effect of delivery method on outcomes . Methods : A prospect i ve clinical trial of a 12-week WIP comparing In-person and Internet-based delivery . All subjects received identical intervention with dietitian visits at baseline and weeks 6 , 12 and 26 . Subjects included overweight/obese academic health science center employees . Changes in weight , PA and CVD-risk were primary outcomes . Results : There was no significant treatment effect repeated-measure-ANOVA . Within subjects , significant main effects indicating improvement were noted at week-12 in weight , WC , body-fat , HRQOL and energy intake and at week-26 in weight , WC , body-fat , HRQOL , energy intake and systolic and diastolic BP . Conclusions : Improvements in some outcomes following a 12-week WIP were independent of delivery method Lifestyle interventions for weight loss are the cornerstone of obesity therapy , yet their optimal design is debated . This is particularly true for postmenopausal women ; a population with a high prevalence of obesity yet toward whom fewer studies are targeted . We conducted a year-long , 4-arm r and omized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced , low-fat diet ( D ) , a moderate-intensity , facility-based aerobic exercise program ( E ) , or the combination of both interventions ( D+E ) , vs. a no-lifestyle-change control ( C ) on change in body weight and composition . The group-based dietary intervention had a weight-reduction goal of ≥10 % , and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week . Participants were predominantly non-Hispanic whites ( 85 % ) with a mean age of 58.0 ± 5.0 years , a mean BMI of 30.9 ± 4.0 kg/m(2 ) and an average of 47.8 ± 4.4 % body fat . Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants ' intervention assignment . Three hundred and ninety nine women completed the trial ( 91 % retention ) . Using an intention-to-treat analysis , average weight loss at 12 months was -8.5 % for the D group ( P < 0.0001 vs. C ) , -2.4 % for the E group ( P = 0.03 vs. C ) , and -10.8 % for the D+E group ( P < 0.0001 vs. C ) , whereas the C group experienced a nonsignificant -0.8 % decrease . BMI , waist circumference , and % body fat were also similarly reduced . Among postmenopausal women , lifestyle-change involving diet , exercise , or both combined over 1 year improves body weight and adiposity , with the greatest change arising from the combined intervention This study investigated the effect of a 12-week pedometer-based intervention on daily step counts of 147 older adults r and omly assigned to an intervention or wait-list control group ( M age = 72.9 years , SD = 8.8 ) . The intervention group significantly increased their daily step counts after 12 weeks ( M = 639 , SD = 2,239 ) and continued to significantly increase during a 12-week maintenance period ( M = 680 , SD = 1,721 ) . The control group exhibited no change during the control period ( M = -393 , SD = 2,050 ) but had a significant increase in daily step counts ( M = 1,580 , SD = 2,305 ) when enrolled in the intervention . The pedometer-based intervention was effective in increasing participants ' daily step counts OBJECTIVE Data on the economic value of nutrition education programs , such as the Exp and ed Food and Nutrition Education Program ( EFNEP ) , can help decision makers choose among alternative programs based on costs and benefits . A cost-benefit analysis of EFNEP was conducted to determine if participants ' savings in food expenditures exceeded program implementation costs . DESIGN /SUBJECTS Costs were collected over 6 months using expenditure reports and other records . Benefits were determined using prospect i ve data from 371 women enrolled in EFNEP who completed a 24-hour food recall and behavior survey , and recorded the amount of money spent monthly on food at program entry and exit . Two treatment groups received nutrition education and one group did not receive education . One treatment group estimated food expenditures from recall and the other collected register receipts or recorded expenditures . Control group subjects reported expenditures from recall . Net present value ( NPV ) was calculated using mean EFNEP cost per participant subtracted from the mean change in family food expenditures per participant over a 5-year period at three discount rates . STATISTICAL ANALYSES Analysis was design ed to compare food expenditures among the two experimental groups and control group and food and nutrient intakes and survey scores between the combined experimental group and control group . RESULTS The average EFNEP program cost perparticipant was $ 388 , and graduating participants reported that family food expenditures decreased on average by $ 10 to $ 20 per month or $ 124 to $ 234 over a year . When benefits were projected to last 5 years , the NPV was $ 147 to $ 696 depending on the method of food expenditure estimation and the discount rate . At the same time individuals reduced food expenditures , they increased intakes of iron , vitamin C , vitamin B-6 , and fiber . They added less salt when cooking and read nutrition labels more often . They also reported not running out of food at the end of the month as often . APPLICATIONS/ CONCLUSIONS Findings from this research showed that EFNEP is cost-beneficial . The magnitude of the savings in food expenditures is sensitive to the method of food expenditure reporting and assumptions about how long participants will retain the behaviors they learn Objective . The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies : a st and ard behavioral group intervention , the st and ard intervention supplemented with spiritual strategies , or self-help strategies . Methods . Women were screened at baseline and after one year of participation . The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering . Because spiritual strategies were added to the st and ard intervention by participants themselves , the results from both active groups were similar and , thus , combined for comparisons with the self-help group . Results . A total of 529 women from 16 churches enrolled . Intervention participants exhibited significant improvements in body weight ( −1.1 lbs ) , waist circumference ( −0.66 inches ) , systolic blood pressure ( −1.6 mmHg ) , dietary energy ( −117 kcal ) , dietary total fat ( −8 g ) , and sodium intake ( −145 mg ) . The self-help group did not . In the active intervention group , women in the top decile for weight loss at one year had even larger , clinical ly meaningful changes in risk outcomes ( −19.8 lbs ) . Conclusions . Intervention participants achieved clinical ly important improvements in cardiovascular disease risk profiles one year after program initiation , which did not occur in the self-help group . Church-based interventions can significantly benefit the cardiovascular health of African American women PURPOSE This study examined covariation among changes in dietary , physical activity , and sedentary behaviors over 12 months among adolescents participating in a health behavior intervention . Evidence of covariation among behaviors would suggest multi-behavior interventions could have synergistic effects . METHODS Prospect i ve analyses were conducted with baseline and 12-month assessment s from a r and omized controlled trial to promote improved diet , physical activity , and sedentary behaviors ( experimental condition ) or SUN protection behaviors ( comparison condition ) . Participants were adolescent girls and boys ( N = 878 ) aged 11 - 15 years on entry . The main outcomes were : diet , based on multiple 24-hour recalls ( total fat , grams of fiber , servings of fruit and vegetables , total calories ) ; average daily energy expenditure ( kcals/kg ) based on 7-day physical activity recall interviews ; daily minutes of moderate-vigorous physical activity minutes from accelerometery ; and self-reported daily hours of sedentary behavior . RESULTS Covariation was found between fat and calories ( r = .16 ) , fiber and calories ( r = .53 ) , fiber and fruit/vegetables ( r = .53 ) , calories and fruit/vegetables ( r = .34 ) , and fruit and vegetables and sedentary behavior ( r = -.12 ) for the total sample ( all p values < .01 ) . The pattern of findings was similar for most subgroups defined by gender and study condition . CONCLUSIONS The strongest covariation was observed for diet variables that are inherently related ( calories and fat , fiber , and fruit/vegetables ) . Little covariation was detected within or between other diet , physical activity and sedentary behavior domains suggesting that interventions to improve these behaviors in adolescents need to include specific program components for each target behavior of interest Objective : This study determined the behavioral and clinical impact of a worksite chronic disease prevention program . Methods : Working adults participated in r and omized clinical trial of an intensive lifestyle intervention . Nutrition and physical activity behavior and several chronic disease risk factors were assessed at baseline , 6 weeks , and 6 months . Results : Cognitive underst and ing of the requirements for a healthy lifestyle increased at the end of the program . Program participants significantly improved their cognitive underst and ing of good nutrition and physical activity and had significantly better nutrition and physical activity behavior at both 6 weeks and 6 months . Participants had significantly lower body fat , blood pressure , and cholesterol . Conclusions : This worksite chronic disease prevention program can significantly increase health knowledge , can improve nutrition and physical activity , and can improve many employee health risks in the short term 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 An automated health counselor agent was design ed to promote both physical activity and fruit and vegetable consumption through a series of simulated conversations with users on their home computers . METHODS The agent was evaluated in a 4-arm r and omized trial of a two-month daily contact intervention comparing : ( a ) physical activity ; ( b ) fruit and vegetable consumption ; ( c ) both interventions ; and ( d ) a non-intervention control . Physical activity was assessed using daily pedometer steps . Daily servings of fruit and vegetables were assessed using the NIH/NCI self-report Fruit and Vegetable Scan . RESULTS Participants in the physical activity intervention increased their walking on average compared to the control group , while those in the fruit and vegetable intervention and combined intervention decreased walking . Participants in the fruit and vegetable intervention group consumed significantly more servings per day compared to those in the control group , and those in the combined intervention reported consuming more compared to those in the control group . CONCLUSION Automated health intervention software design ed for efficient re-use is effective at changing health behavior . PRACTICE IMPLICATION S Automated health behavior change interventions can be design ed to facilitate translation and adaptation across multiple behaviors BACKGROUND This study assessed the clinical impact of lifestyle change education on chronic disease risk factors within a community . DESIGN R and omized clinical trial . SETTING / PARTICIPANTS Participants included 337 volunteers age 43 to 81 years from the Rockford , IL , metropolitan area . INTERVENTION The intervention group attended a 40-hour educational course delivered over a 4-week period . Participants learned the importance of making healthful lifestyle choices and how to make improvements in nutrition and physical activity . MAIN OUTCOME MEASURES Changes in health knowledge , nutrition , and physical activity behavior , and several chronic disease risk factors were assessed at baseline and 6 weeks . RESULTS Beneficial mean changes in scores tended to be significant for the intervention group but not for the control group . Variables with improved scores included health knowledge , percent body fat , total steps per week , and most nutrition variables . Clinical improvements were seen in resting heart rate , total cholesterol , low-density lipoprotein cholesterol , and systolic and diastolic blood pressure . The control group experienced comparatively small but significant improvements in health knowledge , systolic and diastolic blood pressure , glucose , and in some nutrition variables . For almost all variables , the intervention group showed significantly greater improvements . CONCLUSIONS This lifestyle modification program is an efficacious nutrition and physical activity intervention in the short term and has the potential to dramatically reduce the risks associated with common chronic diseases in the long term Objective : America On the Move ( AOM ) is a national weight gain prevention initiative that promotes small lifestyle changes by increasing walking by 2000 steps/day and reducing energy intake by about 100 kcal/day . The study 's intent was to determine the impact of these small changes recommendations on steps/day and energy intake . Methods : In this cross-sectional study , food and fluid intake and physical activity in 116 healthy overweight adults ( BMI : 25–36 kg/m2 ; age : 18–60y ) was compared between a non-intervention and an intervention week using diet diaries and pedometers . The major outcomes were steps/day , daily caloric intake , macronutrient intake and meal size . Within subject ANOVAs were conducted to compare results between intervention and non-intervention weeks . Results : Total energy intake was lower during intervention week than non-intervention week ( P < .01 ) , including macronutrient contents ( all P 's < .01 ) , meal size ( P < .01 ) , consumption of sugar ( P < .01 ) , sugared sodas ( P < .01 ) and sodium ( P < .01 ) . Steps/day were higher during intervention week than non-intervention week ( P < .01 ) . Conclusions : The results support previous research showing that the message to increase steps/day results in an increase in physical activity . The results demonstrate for the first time that the message to reduce intake by 100 kcal/day does actually result in a lower intake in the short term . People seem to be able to make positive changes in diet and physical activity in response to these messages . If these small changes can be sustained , this approach could be effective in preventing further weight gain in the population BACKGROUND Few studies compare the influence of different types of dietary interventions on the dietary practice s of Latinas in the short and long term . The present study examined the 1-year impact of two innovative behavior-change approaches to reduce dietary fat and increase fiber . DESIGN Three-group r and omized controlled trial : ( 1 ) personalized dietary counseling via lay heath advisors ( promotoras ) plus tailored print material s delivered via the mail , ( 2 ) tailored mailed print material s only , and ( 3 ) targeted mailed " off-the-shelf " material s. SETTING / PARTICIPANTS A total of 357 Latinas were r and omly assigned to the three aforementioned conditions . INTERVENTION Promotora and tailored print material s. MAIN OUTCOME MEASURES Fat intake ( total grams of fat and percent calories from dietary fat ) and number of grams of dietary fiber . RESULTS Earlier work reported that at immediate post-intervention the promotora group achieved significantly lower levels of total fat grams , and lower levels of energy intake , total saturated fat , total carbohydrates , glucose , and fructose than the targeted group . However , the present longitudinal analyses suggest that the effects achieved by the promotoras dissipated over the 12-month follow-up period while the effects of the tailored group concurrently improved . CONCLUSIONS The high interactivity ( i.e. , calls , visits ) of the promotora condition may have been the most salient reinforcer and may have led to further tailoring , making this type of intervention more effective than the comparison groups in the short term . Further research should explore whether booster sessions involving promotoras help to maintain the impact over time OBJECTIVE Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups . METHOD Female college students at risk for these outcomes because of body image concerns ( N = 398 ) were r and omized to the Healthy Weight 2 group-based 4-hr prevention program , which promotes lasting healthy improvements to dietary intake and physical activity and nutrition science health behavior change principles , or an educational brochure control condition . RESULTS Intervention participants showed significantly less body dissatisfaction and eating disorder symptoms and lower eating disorder onset through 2-year follow-up versus controls , but the former 2 effects were small . There were no main effects for body mass index ( BMI ) , depressive symptoms , dieting , caloric intake , physical activity , or obesity onset . Moderator analyses revealed stronger eating disorder symptom effects for youths with initially elevated symptoms and lower pressure to be thin , stronger BMI effects for youths with initially elevated symptoms and BMI scores , and weaker eating disorder symptom effects for youths with initially elevated pressure to be thin . CONCLUSIONS The 60 % reduction in eating disorder onset over the 2-year follow-up was clinical ly significant and a novel effect for a prevention program , but the main effects on continuous outcomes were small , suggesting that adding nutrition science principles weakened the intervention efficacy . Effects on both eating disorder symptoms and BMI were greater for those with elevated eating disorder symptoms and BMI at pretest , implying that it might be useful to target these individuals in future trials OBJECTIVES : The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program ( Challenge ! ) on changes in BMI status , body composition , physical activity , and diet . METHODS : A total of 235 black adolescents ( aged 11–16 years ; 38 % overweight/obese ) were recruited from low-income urban communities . Baseline measures included weight , height , body composition , physical activity ( PA ) , and diet . PA was measured by 7-day play-equivalent physical activity ( ≥1800 activity counts per minute ) . Participants were r and omly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control . Postintervention ( 11 months ) and delayed follow-up ( 24 months ) evaluations were conducted . Longitudinal analyses used multilevel models with r and om intercepts and generalized estimating equations , controlling for baseline age/gender . Stratified analyses examined baseline BMI category . RESULTS : Retention was 76 % over 2 years ; overweight/obese status declined 5 % among intervention adolescents and increased 11 % among control adolescents . Among overweight/obese youth , the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up . Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations . CONCLUSIONS : At postintervention , there were intervention effects on diet and PA but not BMI category or body composition . At delayed follow-up , dietary changes were sustained and the intervention prevented an increase in BMI category . Body composition was improved for overweight/obese youth . Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention INTRODUCTION Older adults with a high number of chronic conditions and who live in environments that do not promote physical activity have great difficulty initiating and adhering to exercise programs . Novel lifestyle activity interventions that can effectively increase physical activity may address disparities in health in these population s. This study evaluates the effects of the Baltimore Experience Corps program , a community-based volunteer program , on walking activity in older adults . METHODS The Baltimore Experience Corps Trial is a sex-stratified RCT that recruited participants from 2006 to 2009 . Older adult participants aged ≥60 years ( n=123 ) were from a nested objective physical activity trial within the larger Baltimore Experience Corps Trial . Participants r and omized to the intervention group were placed as volunteers within the Baltimore public school system for 2 years . The primary study outcome was objective ly measured total amount of walking activity measured in steps/day . Differences between intervention and control groups were measured at 12 and 24 months using linear mixed effects models . Data were analyzed in 2014 . RESULTS At 24 months , women , but not men , in the intervention group showed an increased amount of walking activity , averaging 1,500.3 ( 95 % CI=77.6 , 2,922.9 ) greater steps/day compared with the control group . Women in the control group showed a decline of 1,191.6 ( 95 % CI=-2243.7 , -139.5 ) steps/day at 24 months compared to baseline . CONCLUSIONS A community-based volunteer intervention increased walking activity among older women , who were at elevated risk for both inactivity and adverse health outcomes . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00380562 OBJECTIVES We tested the effectiveness of a community-based , literacy-sensitive , and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income , Spanish-speaking Latinos at increased diabetes risk . METHODS Three hundred twelve participants from Lawrence , Massachusetts , were r and omly assigned to lifestyle intervention care ( IC ) or usual care ( UC ) between 2004 and 2007 . The intervention was implemented by trained Spanish-speaking individuals from the community . Each participant was followed for 1 year . RESULTS The participants ' mean age was 52 years ; 59 % had less than a high school education . The 1-year retention rate was 94 % . Compared with the UC group , the IC group had a modest but significant weight reduction ( -2.5 vs 0.63 lb ; P = .04 ) and a clinical ly meaningful reduction in hemoglobin A1c ( -0.10 % vs -0.04 % ; P = .009 ) . Likewise , insulin resistance improved significantly in the IC compared with the UC group . The IC group also had greater reductions in percentage of calories from total and saturated fat . CONCLUSIONS We developed an inexpensive , culturally sensitive diabetes prevention program that result ed in weight loss , improved HbA1c , and improved insulin resistance in a high-risk Latino population Importance Postpartum weight retention increases lifetime risk of obesity and related morbidity . Few effective interventions exist for multicultural , low-income women . Objective To test whether an internet-based weight loss program in addition to the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC program ) for low-income postpartum women could produce greater weight loss than the WIC program alone over 12 months . Design , Setting , and Participants A 12-month , cluster r and omized , assessor-blind , clinical trial enrolling 371 adult postpartum women at 12 clinics in WIC programs from the California central coast between July 2011 and May 2015 with data collection completed in May 2016 . Interventions Clinics were r and omized to the WIC program ( st and ard care group ) or the WIC program plus a 12-month primarily internet-based weight loss program ( intervention group ) , including a website with weekly lessons , web diary , instructional videos , computerized feedback , text messages , and monthly face-to-face groups at the WIC clinics . Main Outcomes and Measures The primary outcome was weight change over 12 months , based on measurements at baseline , 6 months , and 12 months . Secondary outcomes included proportion returning to preconception weight and changes in physical activity and diet . Results Participants included 371 women ( mean age , 28.1 years ; Hispanic , 81.6 % ; mean weight above prepregnancy weight , 7.8 kg ; mean months post partum , 5.2 months ) r and omized to the intervention group ( n = 174 ) or st and ard care group ( n = 197 ) ; 89.2 % of participants completed the study . The intervention group produced greater mean 12-month weight loss compared with the st and ard care group ( 3.2 kg in the intervention group vs 0.9 kg in st and ard care group , P < .001 ; difference , 2.3 kg ( 95 % CI , 1.1 to 3.5 ) . More participants in the intervention group than the st and ard care group returned to preconception weight by 12 months ( 32.8 % in the intervention group vs 18.6 % in the st and ard care group , P < .001 ; difference , 14.2 percentage points [ 95 % CI , 4.7 to 23.5 ] ) . The intervention group and st and ard care group did not significantly differ in 12-month changes in physical activity ( mean [ 95 % CI ] : −7.8 min/d [ −16.1 to 0.4 ] in the intervention group vs −7.2 min/d [ −14.6 to 0.3 ] in the st and ard care group ; difference , −0.7 min/d [ 95 % CI , −42.0 to 10.6 ] , P = .76 ) , calorie intake ( mean [ 95 % CI ] : −298 kcal/d [ −423 to −174 ] in the intervention group vs −144 kcal/d [ −257 to −32 ] in the st and ard care group ; difference , −154 kcal/d [ −325 to 17 ] , P = .06 ) , or incidences of injury ( 16 in the intervention group vs 16 in the st and ard care group ) or low breastmilk supply from baseline to month 6 ( 21 of 61 participants in the intervention group vs 23 of 72 participants in the st and ard care group ) and from month 6 to 12 ( 13 of 32 participants in the intervention group vs 14 of 37 participants in the st and ard care group ) . Conclusions and Relevance Among low-income postpartum women , an internet-based weight loss program in addition to the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC program ) compared with the WIC program alone result ed in a statistically significant greater weight loss over 12 months . Further research is needed to determine program and cost-effectiveness as part of the WIC program . Trial Registration clinical trials.gov Identifier : OBJECTIVE The results of an 18-month worksite intervention to prevent obesity among metropolitan transit workers are reported . METHODS Four garages in a major metropolitan area were r and omized to intervention or control groups . Data were collected during the fall of 2005 prior to the start of the intervention and during the fall of 2007 , after the intervention ended . Intervention program components at the garage included enhancement of the physical activity facilities , increased availability of and lower prices on healthy vending machine choices , and group behavioral programs . Mixed model estimates from cross-sectional and cohort sample s were pooled with weights inverse to the variance of their respective estimates of the intervention effects . RESULTS Measurement participation rates were 78 % at baseline and 74 % at follow-up . The intervention effect on garage mean BMI change was not significant ( -0.14 kg/m(2 ) ) . Energy intake decreased significantly , and fruit and vegetable intake increased significantly in intervention garages compared to control garages . Physical activity change was not significant . CONCLUSION Worksite environmental interventions for nutrition and physical activity behavior change may have limited impact on BMI among transit workers who spend most of their workday outside the worksite OBJECTIVES We assessed the effectiveness of an intervention targeting home food and activity environments to reduce energy intake and increase physical activity among overweight and obese patients from 3 community health centers in rural Georgia . METHODS We conducted a r and omized controlled trial ( n = 349 ) from 2011 to 2013 , with follow-up at 6 and 12 months . Health coaches delivered the 16-week intervention by using tailored home environment profiles showing areas in need of improvement and positive aspects of the home environment , behavioral contracts for healthy actions , and mailed support material s. RESULTS Participants were mostly African American women ( 84.8 % ) , with a mean age of 50.2 years and a mean body mass index ( weight in kilograms divided by the square of height in meters ) of 38.3 . Daily energy intake decreased more for the intervention than control group at 6 ( -274 vs -69 kcal ) and 12 months ( -195 vs -76 kcal ) . We observed no change for either objective or self-reported physical activity . At 12 months , 82.6 % of intervention participants had not gained weight compared with 71.4 % of control participants . CONCLUSIONS The intervention was effective in changing home environments and reducing energy intake BACKGROUND This study reports the results of a 9-week intervention on the physical activity levels of adolescent males . METHODS Participants were 473 10- to 14-year-old Houston Boy Scouts ( 42 troops ) with troops r and omly assigned to intervention or control conditions . Data were collected in spring ( 16 troops ) and fall ( 26 troop ) waves during 2003 . Intervention participants received a 9-week troop and Internet program to increase physical activity skills , self-efficacy and goal - setting . Physical activity was assessed at baseline , end of the intervention ( Post#1 ) and post-6 months ( Post#2 ) by accelerometer . Minutes of sedentary , light and moderate to vigorous physical activity were calculated . Repeated measure analyses were performed to test differences in physical activity over time between groups with participants nested in troops . RESULTS A three-way interaction ( group * time * wave ) that approached significance ( P = 0.051 ) indicated a 12-min reduction in sedentary behavior among spring intervention participants . A significant three-way interaction ( P = 0.011 ) ( group * time * wave ) indicated a 12-min increase in light intensity activity among the spring intervention group . CONCLUSION Participation in the Fit for Life badge program result ed in a trend towards a small decrease in sedentary behavior and increased light intensity physical activity among spring participants only . There was no effect on moderate to vigorous physical activity Importance Prevention of obesity during childhood is critical for children in underserved population s , for whom obesity prevalence and risk of chronic disease are highest . Objective To test the effect of a multicomponent behavioral intervention on child body mass index ( BMI , calculated as weight in kilograms divided by height in meters squared ) growth trajectories over 36 months among preschool-age children at risk for obesity . Design , Setting , and Participants A r and omized clinical trial assigned 610 parent-child pairs from underserved communities in Nashville , Tennessee , to a 36-month intervention targeting health behaviors or a school-readiness control . Eligible children were between ages 3 and 5 years and at risk for obesity but not yet obese . Enrollment occurred from August 2012 to May 2014 ; 36-month follow-up occurred from October 2015 to June 2017 . Interventions The intervention ( n = 304 pairs ) was a 36-month family-based , community-centered program , consisting of 12 weekly skills-building sessions , followed by monthly coaching telephone calls for 9 months , and a 24-month sustainability phase providing cues to action . The control ( n = 306 pairs ) consisted of 6 school-readiness sessions delivered over the 36-month study , conducted by the Nashville Public Library . Main Outcomes and Measures The primary outcome was child BMI trajectory over 36 months . Seven prespecified secondary outcomes included parent-reported child dietary intake and community center use . The Benjamini-Hochberg procedure corrected for multiple comparisons . Results Participants were predominantly Latino ( 91.4 % ) . At baseline , the mean ( SD ) child age was 4.3 ( 0.9 ) years ; 51.9 % were female . Household income was below $ 25 000 for 56.7 % of families . Retention was 90.2 % . At 36 months , the mean ( SD ) child BMI was 17.8 ( 2.2 ) in the intervention group and 17.8 ( 2.1 ) in the control group . No significant difference existed in the primary outcome of BMI trajectory over 36 months ( P = .39 ) . The intervention group children had a lower mean caloric intake ( 1227 kcal/d ) compared with control group children ( 1323 kcal/d ) ( adjusted difference , −99.4 kcal [ 95 % CI , −160.7 to −38.0 ] ; corrected P = .003 ) . Intervention group parents used community centers with their children more than control group parents ( 56.8 % in intervention ; 44.4 % in control ) ( risk ratio , 1.29 [ 95 % CI , 1.08 to 1.53 ] ; corrected P = .006 ) . Conclusions and Relevance A 36-month multicomponent behavioral intervention did not change BMI trajectory among underserved preschool-age children in Nashville , Tennessee , compared with a control program . Whether there would be effectiveness for other types of behavioral interventions or implementation in other cities would require further research . Trial Registration Clinical Trials.gov Identifier : BACKGROUND Low-income Latinas ( Hispanics ) face risk for cardiovascular disease due to high rates of overweight/obesity , sedentary lifestyle , and other factors . Limited access to health care and language barriers may prevent delivery of health promotion messages . Targeted approaches , including the integration of community health workers , may be required to promote healthy lifestyle and prevent chronic disease in underserved ethnic minority groups . The term commonly used to refer to female community health workers in Latino communities is " promotora(s ) . " OBJECTIVES This study evaluates the outcomes and feasibility of a promotora-led lifestyle behavior intervention for overweight , immigrant Latinas . METHODS A community prevention model was employed in planning and implementing this study . A r and omized controlled trial design was used . A Community Advisory Board provided expertise in evaluating feasibility of study implementation in the community and other important guidance . The sample was comprised of 223 women aged 35 - 64 years , predominantly with low income and ≤8th grade education . The culturally tailored Lifestyle Behavior Intervention included group education ( 8 classes based upon Su Corazon , Su Vida ) , followed by 4 months of individual teaching and coaching ( home visits and telephone calls ) . The control group received a comparable length educational program and follow-up contacts . Evaluations were conducted at baseline and at 6 and 9 months using a dietary habits question naire , accelerometer readings of physical activity , and clinical measures ( body mass index , weight , waist circumference , blood pressure , lipids , blood glucose ) . Data were collected between January 2010 and August 2012 . RESULTS Women in the intervention group improved significantly in dietary habits , waist circumference , and physical activity in comparison to those in the control group . A treatment dosage effect was observed for weight and waist circumference . Knowledge about heart disease increased . High attendance at classes and participation in the individual teaching and counseling sessions and high retention rates support the feasibility and acceptability of the promotora-led lifestyle behavior intervention . CONCLUSIONS Our findings demonstrate that lifestyle behaviors and other risk factors of overweight Latina women may be improved through a promotora-led lifestyle behavior intervention . Feasibility of implementing this intervention in community setting s and engaging promotoras as facilitators is supported OBJECTIVE The purpose of this study was to compare weight regain in a group of perimenopausal women ( 48.0+/-4.4 years old ) , r and omized to a 12-month weight maintenance Internet intervention or to self-directed weight maintenance after a 4-month weight loss treatment . METHODS AND PROCEDURES After a 4-month behavioral weight loss program , 135 women were r and omized to either Internet or self-directed groups . The Internet group ( n=66 ) used a website to gain information and complete logs concerning their weight , diet , and exercise progress over a 12-month follow-up . The 69 self-directed women had no contact with study staff . All women were measured for weight and body composition , and diet intake , and were interviewed using the 7-day physical activity question naires at baseline , 4 months , and 16 months . RESULTS At the end of the 12-month follow-up , the Internet and self-directed groups had regained on average 0.4+/-5.0 kg and 0.6+/-4.0 kg , respectively ( P=0.5 ) . In within-group analyses , Internet diet-log entries were correlated with follow-up weight change ( r=-0.29 ; P<0.05 ) and moderately with change in exercise energy expenditure ( EEE ; r=0.44 ; P<0.01 ) . Follow-up weight change was not correlated with change in dietary intake . DISCUSSION While significant weight loss was maintained over follow-up by both groups of women , Internet use did not surpass self-direction in helping to sustain weight loss . Among Internet users , Internet use was related to weight change and EEE |
13,954 | 31,520,113 | There is no evidence to suggest that there is any superiority of one protocol above another in the published literature .
Appropriate use of opioids ± NSAIDs ± acetaminophen alone appears to be sufficient to control pain post-UFE . | Uterine fibroid embolisation ( UFE ) is an effective treatment for fibroids .
There are varying analgesia protocol s published to control procedure associated pain .
We aim ed to assess what protocol s are most effective in controlling post-procedural pain . | PURPOSE To investigate whether dexmedetomidine infusion could reduce opioid consumption and opioid-related side effects after uterine artery embolization ( UAE ) . MATERIAL S AND METHODS Fifty patients undergoing UAE for symptomatic leiomyomas or adenomyosis were r and omized into two groups . In 25 patients , dexmedetomidine infusion was started at 0.2 μg/kg/h at 30 minutes before the procedure , followed by 0.4 μg/kg/h for 6 hours after the procedure . In another 25 patients ( control group ) , volume-matched normal saline solution was administered . Both groups received fentanyl-based intravenous patient-controlled analgesia ( PCA ; fentanyl 10 μg/h with a bolus dose of 20 μg ) during the 24 hours after the procedure . Nonspherical polyvinyl alcohol particles were used . Pain scores , fentanyl consumption , need for additional analgesics , and side effects were assessed for 24 hours after UAE . RESULTS Compared with the control group , patients in the dexmedetomidine group required 28 % less PCA fentanyl during the 24 hours after UAE ( P = .006 ) . Numeric rating scale scores for pain ( 5.0±2.4 vs 7.0±2.2 ; P = .026 ) and the need for additional analgesics ( two of 25 vs 17 of 25 ; P<.001 ) were lower in the dexmedetomidine group than in the control group during the first 1 hour after UAE . The incidence and severity of nausea and vomiting during the 24 hours after UAE were lower in the dexmedetomidine group than in the control group ( P < .05 ) . CONCLUSIONS The addition of dexmedetomidine infusion to fentanyl PCA provides better analgesia , fentanyl-sparing effect , and less nausea and vomiting , without significant hemodynamic instability PURPOSE To assess the efficacy of the superior hypogastric nerve block ( SHNB ) in permitting uterine artery embolization ( UAE ) to be performed as a routine outpatient procedure . MATERIAL S AND METHODS One hundred thirty-nine patients who underwent UAE in a prospect i ve single-arm clinical trial in an academic institution underwent SHNB from an anterior abdominal approach to control acute postprocedural pain , in addition to conventional conscious sedation . They were discharged and prescribed one of two drug combinations started during the in-hospital recovery period . Regimen A included short-acting morphine tablets and indomethacin rectal suppositories and regimen B included long-acting morphine tablets for baseline pain supplemented with short-acting morphine tablets for breakthrough pain , and naproxen rectal suppositories . All patients were contacted by phone on the third and fifth postprocedural days and their peak pain experience was recorded on a scale of 0 to 10 . RESULTS All patients were able to be discharged the day of the procedure . Seven patients ( 5 % ) returned to the hospital because of pain . One was discharged after undergoing a second SHNB and four were discharged after receiving intravenous analgesics ; two required longer admission for intravenous analgesia . The mean ( + /-SD ) peak pain score in the first 5 days after the procedure for all patients was 4.8 + /- 2.6 . There was a significant difference between regimens A ( mean pain score , 5.7 + /- 2.2 ) and B ( mean pain score , 2.7 + /- 2.5 ; Mann-Whitney , 5.94 ; P < .01 ) . CONCLUSION The addition of SHNB to the more conventional post-UAE pain management methodology enhances pain control , enabling the procedure to be offered with minimum pain on a routine outpatient basis PURPOSE To evaluate whether it is safe to perform uterine artery embolization ( UAE ) as an outpatient procedure . MATERIAL S AND METHODS This retrospective study was approved by the institutional review board and included 234 patients ( age range , 24 - 58 years ; mean age , 40.5 years ) who underwent UAE as an outpatient procedure with polyvinyl alcohol particles between January 2007 and March 2008 . Patients were given acid-suppressing drugs , nonsteroidal anti-inflammatory drugs , anti-histaminic drugs , and laxatives twice on the day before UAE and once on the morning of UAE . Pain score , rated from 0 to 10 , was evaluated by using a numeric pain scale during UAE , after the procedure , at discharge , at the night of discharge , and on the following morning . The outcome of UAE was evaluated at 6 months by means of pelvic magnetic resonance imaging and clinical observation . RESULTS The mean pain score was 0.9 during embolization , 2.5 4 - 8 hours after embolization , 0.9 at discharge , 1.1 the first night after discharge , and 0.7 the next morning . All patients were discharged from the hospital 4 - 8 hours after the procedure , with no overnight hospital admissions . At 6 months , 146 of 158 patients ( 92.4 % ) reported an improvement in menorrhagia , 39 of 44 ( 88.6 % ) reported an improvement in bulk symptoms , and 20 of 25 ( 80 % ) reported an improvement in pain . The volumes of the uterus and the dominant fibroid decreased 33.7 % and 39.3 % , respectively . CONCLUSIONS With acid-suppressing , anti-inflammatory , and anti-histaminic drugs started on the day before UAE , the procedure can be performed safely as an outpatient procedure The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization ( UFE ) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia ( PCA ) versus fentanyl PCA . We carried out a prospect i ve , nonr and omized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE . Pain perception levels were obtained on a 0–10 scale for the 24-h period after UFE . Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scores and patient covariates . One hundred eighty-five patients ( 92.5 % ) reported greater-than-baseline pain after UFE , and 198 patients ( 99 % ) required IV opioid PCA . One hundred thirty-six patients ( 68.0 % ) developed nausea during the 24-h period . Seventy-two patients ( 36 % ) received morphine PCA and 128 ( 64 % ) received fentanyl PCA , without demographic differences . The mean dose of morphine used was 33.8 ± 26.7 mg , while the mean dose of fentanyl was 698.7 ± 537.4 μg . Using this regimen , patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA ( p < 0.0001 ) . We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE . Morphine PCA is more effective in reducing post – uterine artery embolization pain than fentanyl PCA . Nausea is a significant adverse effect from opioid PCA BACKGROUND Post-procedural pain control after uterine artery embolization ( UAE ) of urethral leiomyomata remains a major problem . METHODS This double-blind , r and omized study tested the possibility to obtain a quicker onset of analgesia by using effect-compartment controlled remifentanil patient-controlled analgesia ( remifentanil TCI-PCA ) than by using i.v . morphine PCA . Both systems were connected to an i.v . catheter . Active drug or matching placebo administration was activated by a single push-button . Pain was assessed using a numerical rating scale ( NRS ) from 0 to 10 . RESULTS NRS values were lower in the remifentanil group ( with a possible difference from two to seven points on the scale ) during the initial 4 h post-embolization . After the fourth hour , the NRS values were identical between the groups . No major respiratory or haemodynamic side-effect was observed . CONCLUSIONS Remifentanil PCA-TCI with a slow and progressive adapted algorithm without any associated premedication or co-medication is feasible in young healthy women undergoing UAE & NA ; Twenty‐six patients with extensive gynecologic , colorectal or genitourinary cancer who suffered uncontrolled , incapacitating pelvic pain were enrolled in this study during a 1‐year period . All the patients receiving oral opioids who developed poor pain response due to the progression of disease or untoward side effects necessitating other modes of therapy were eligible to participate . Bilateral percutaneous neurolytic superior hypogastric plexus blocks with 10 % phenol were performed in every patient , 1 day after receiving successful diagnostic blocks using 0 . 25 % bupivacaine ( BUP ) . All patients reported a visual analog pain score ( VAPS ) of 10 of 10 before the block . Eighteen patients ( 69 % ) had satisfactory pain relief ( VAPS < 4 of 10 ) : 15 ( 57 % ) after 1 block and 3 ( 12 % ) after a second block . The remaining 8 patients ( 31 % ) had moderate pain control ( VAPS 4–7 of 10 ) after 2 blocks and received epidural bupivacaine‐morphine ( BUP‐MS ) therapy with good results . Both groups experienced significant reductions in oral opioid therapy after the neurolytic blocks . No additional blocks were required by patients who had a good response during a follow‐up period of 6 months . No complications related to the block were experienced by any patient . In conclusion , neurolytic superior hypogastric plexus block was both effective in relieving pain in 69 % of the patients studied ( 95 % confidence interval of 48–85 % ) . Additional neurolytic blocks using higher volumes of the neurolytic agent may be needed in patients with extensive retroperitoneal disease , a group in whom moderate or poor results should be expected PURPOSE Uterine artery embolization ( UAE ) is gaining popularity as an alternative to hysterectomy for the treatment of fibroids . Although minimally invasive treatments such as UAE offer the potential of fewer complications , shorter hospital stay , and quicker recovery than surgery , there have been few published data on tolerance and recovery in patients undergoing UAE . MATERIAL S AND METHODS This was a multicenter prospect i ve single-arm clinical treatment trial involving the practice s of 11 interventional radiologists in eight Ontario university-affiliated and community hospitals . Between November 1998 and November 2000 , 555 women underwent UAE for symptomatic uterine fibroids . Follow-up included ultrasound examinations and telephone interviews . UAE was performed under conscious sedation . Polyvinyl alcohol particles ( 355 - 500 micro m ) were the primary embolic agent , and the procedural endpoint involved stasis in the uterine arteries . Pain protocol s included antiinflammatory medications and narcotics and a planned overnight hospital admission . Tolerance and recovery were measured by patient-reported pain intensity ( 10-point numeric rating and five-point descriptor scale ) , hospital length of stay ( LOS ) , and time until return to work . RESULTS Intraprocedural pain was reported by 30 % of patients and postprocedural pain was reported by 92 % of patients ( mean pain rating + /- SD , 7.0 + /- 2.47 ) . The mean hospital LOS was 1.3 nights . Postprocedural pain was the most common indication for an LOS greater than 1 night ( 18 % ) or 2 nights ( 5 % ) . Return visits to the hospital ( 10 % ) and readmissions ( 3 % ) were primarily for pain . The overall postprocedural complication rate was 8.0 % ( 95 % CI : 5.9%-10.6 % ) . Of the 44 complications , 32 ( 73 % ) were pain-related . The mean recovery time after UAE was 13.1 days ( median , 10.0 d ) . CONCLUSION The majority of patients had a 1-night LOS after UAE and recovered within 2 weeks . Postprocedural pain varied considerably and was the major indication for extended hospital stay and recovery Abstract When compared in a uterine artery embolization ( UAE ) animal model , Embospheres ( ES ) ( Biosphere Medical , Rockl and , MA ) were found to induce less uterine ischemia than polyvinyl alcohol ( PVA ) particles . Given this finding , we aim ed to test the hypothesis that ES is associated with less pain after UAE than PVA in human patients . We performed retrospective analysis on data from 72 consecutive UAE patients , collected from a prospect ively acquired data base . Patient-controlled analgesia ( PCA ) pump-delivered morphine sulfate ( MS ) dosages were compared between patients who received ES versus PVA . Subjective pain scores ( SPS ) were also compared between the two groups . Secondary outcome measures , including embolic volume and clinical outcome data , were also collected . Linear regression and t-test statistical analyses were performed . Null hypotheses were rejected at the p < 0.05 level . Mean follow-up period in the PVA population was 178 days ( range 28–426 ) , versus 96 days ( range 24–197 ) in the ES population . The mean MS doses used by ES and PVA patients were 37.2 ( s.d . 23.5 ) versus 47.1 ( s.d . 26.8 ) , respectively . This difference was not significant ( p > 0.15 ) . Utilizing a st and ard 0–10 pain scale , the mean peak SPS for the ES and PVA groups were 5.58 ( s.d . 2.77 ) and 5.07 ( s.d . 2.99 ) , respectively . The difference was not significant . The mean amount of embolic material used in each ES and PVA patient was 4.86 cc ( s.d . 3.01 ) and 3.52 cc ( s.d . 1.63 ) , respectively . The difference revealed a strong trend toward statistical significance ( p = 0.05 ) . There was one treatment failure in each group of patients . Within both patient sample s , no significant correlation was found when comparing the volume of embolic used and subsequent MS dose . Despite a strong trend toward a significantly higher volume of ES used per patient , there is no subjective or objective difference in pain after UAE with ES when compared to PVA Twelve women with symptomatic fibroids were treated with transcatheter uterine artery embolisation with the use of polyvinyl alcohol ( PVA ) particles . For the nine women who were due for follow-up , reduction in uterine volume and dominant fibroid size were observed on magnetic resonance imaging . All the nine women had normal luteinising hormone ( LH ) and follicle stimulating hormone ( FSH ) levels before the procedure and during the follow-up . Seven of the nine women reported noticeable symptomatic improvement during the follow-up . Pain experienced was of variable level , but well controlled . Adequate analgesia is essential for the procedure . Longer follow-up and prospect i ve fertility studies are required to evaluate the long-term effects before this procedure could be safely extended to younger age groups PURPOSE To evaluate whether electroacupuncture is a safe and effective alternative to pharmacologic sedation/analgesia in uterine artery embolization ( UAE ) for leiomyomas . MATERIAL S AND METHODS A nonr and omized prospect i ve study was undertaken in 70 consecutive patients ( mean age , 39.5 years ) undergoing UAE with polyvinyl alcohol ( PVA ) particles between August 2006 and January 2007 . Thirty-three patients chose to undergo UAE under electroacupuncture anesthesia ( EAA ; group A ) and 37 were treated under local pharmacologic anesthesia ( group B ) . Pain scores ( rated from 0 to 10 ) in both groups were compared during and after the procedure . The outcome of UAE was evaluated at 6 months . RESULTS Mean pain scores during embolization were 0.36 in group A and 0.84 in group B ; scores after embolization and before discharge were 3.00 in group A and 4.49 in group B ; and scores at discharge were 0.97 in group A and 2.11 in group B. These differences were statistically significant after embolization and at hospital discharge ( P= .02 and P= .0001 , respectively ) . All patients except one in each group were discharged from the hospital 4 - 8 hours after UAE ; the two who remained longer had severe pain . There were no significant differences in clinical outcomes , nor in uterine and leiomyoma volumes , at discharge and at 6 months ( P > 0.99 and P= .72 , respectively ) . CONCLUSIONS There was a statistically significant postembolization pain reduction in patients treated under EAA versus local pharmacologic anesthesia and no differences in UAE outcomes between groups at 6 months Purpose To evaluate the safety and efficacy of uterine artery embolization ( UAE ) and hysterectomy for symptomatic uterine fibroids by means of a r and omized controlled trial . The present paper analyses short-term outcomes , i.e. , pain and return to daily activities . Methods Patients were r and omized ( 1:1 ) to UAE or hysterectomy . Pain was assessed during admission and after discharge , both quantitatively and qualitatively , using a numerical rating scale and question naires . Time to return to daily activities was assessed by question naire . Results Seventy-five patients underwent hysterectomy and 81 patients underwent UAE . UAE patients experienced significantly less pain during the first 24 hr after treatment ( p = 0.012 ) . Non-white patients had significantly higher pain scores . UAE patients returned significantly sooner to daily activities than hysterectomy patients ( for paid work : 28.1 versus 63.4 days ; p < 0.001 ) . In conclusion , pain appears to be less after UAE during hospital stay . Return to several daily activities was in favor of UAE in comparison with hysterectomy PURPOSE To assess efficacy of two different techniques of lidocaine injection in the uterine arteries to reduce pain following uterine artery embolization ( UAE ) for leiomyomas . MATERIAL S AND METHODS This prospect i ve r and omized single-blinded study was performed with 60 patients enrolled between November 2014 and December 2015 equally r and omized to 3 arms . Group A received 10 mL lidocaine 1 % ( 100 mg ) mixed with polyvinyl alcohol particles ( 355 - 500 μm ) . Group B received the same dose of lidocaine injected after embolization . Group C was a control group . Pain was assessed on a 100-point visual analog scale at 4 , 7 , and 24 hours after the procedure . Narcotic agent dose to 24 hours was recorded . Outcomes were examined by analysis of variance and pairwise comparison . Leiomyoma infa rct ion was assessed with magnetic resonance imaging 3 months after the procedure . RESULTS Technical success rate of UAE was 100 % . Mean pain score at 4 hours was significantly lower in the lidocaine groups ( group A , 28.6 ; group B , 35.8 ) compared with the control group ( 59.4 ; P = .001 ) . Pain scores at 7 and 24 hours were not statistically different among the 3 arms . The mean in-hospital narcotic agent dose was significantly lower in both lidocaine groups than in the control group ( group A , 8.5 mg [ P = .002 ] ; group B , 11.1 mg [ P = .03 ] ; group C , 17.4 mg ) . There were no adverse events related to the use of lidocaine . The number of patients with complete infa rct ion of leiomyomas at 3 months was significantly lower in group A at 38.9 % ( group B , 77.8 % ; group C , 75 % ; P = .0451 ) . CONCLUSIONS Lidocaine injected in the uterine arteries reduced postprocedural pain and narcotic agent dose after UAE . There were more cases of incomplete necrosis when lidocaine was mixed with the particles AIM To evaluate if pre- and post-procedure administration of controlled-release oxycodone ( CRO ) in combination with st and ard analgesia improves pain control and decreases the amount of required post-procedure opioids in uterine fibroid embolisation ( UFE ) . MATERIAL S AND METHODS Between January 2009 and March 2010 , 60 consecutive women were prospect ively r and omised in two groups for UFE : the control group , in which 30 patients underwent the st and ard anaesthetic procedure and the CRO group , in which 30 patients underwent the st and ard anaesthetic procedure with the addition of CRO . Age , pain , nausea/vomiting , fibroid volume , length of hospital stay , and use and dose of morphine received via the patient-controlled analgesia ( PCA ) device in both groups were evaluated to compare the two methods of pain control . Fibroid volume as measured at magnetic resonance imaging ( MRI ) was evaluated for correlation with post-embolisation pelvic pain over a period of 24 hours . RESULTS A significant difference was seen in the pain scores at 24 hours ( p=0.029 ) , with less pain in the CRO group . More patients from the control group required morphine ( p=0.017 ) , and at higher levels ( p=0.130 ) . Pruritus was lower in patients of the CRO group , probably because they received less morphine ( p=0.029 ) . No correlation was seen between leiomyoma volume and pain levels over 24 hours ( Spearman 's ρ=0.02 ; p=0.881 ) . Length of hospital stay was not different between the two groups . CONCLUSION The addition of CRO to st and ard analgesia for UFE provides more effective analgesia , with a reduction in pain scores in 24 hours , less morphine use , and decreased side effects , mainly pruritus PURPOSE To evaluate the effectiveness of intraarterial lidocaine in controlling pain after uterine artery embolization ( UAE ) . MATERIAL S AND METHODS In this double-blind prospect i ve study , patients undergoing UAE received preservative-free 1 % lidocaine or saline solution ( control ) in the uterine arteries before embolization . Postprocedural pain was managed with patient-controlled intravenous morphine . Attempted doses , number of doses received , total morphine dose , and maximum pain numeric rating scale ( NRS ) score during the postprocedural hospitalization were recorded and compared . Three-month follow-up magnetic resonance ( MR ) imaging and symptomatic question naires were collected and compared . RESULTS Ten patients received lidocaine and eight patients received placebo . Moderate to severe vasospasm was noted in seven patients after lidocaine injection , whereas no vasospasm was noted in the placebo group ( P = .004 ) . Patients in the lidocaine group had lower NRS pain scores than those in the placebo group ( P = .012 ) , whereas there was no difference in morphine requirement between treated patients and control subjects . The study was terminated after 18 patients were treated as a result of unexpected vasospasm . CONCLUSIONS Intraarterial 1 % lidocaine is associated with moderate to severe vasospasm . Lidocaine significantly lowers subjective pain , but there is no difference in analgesic requirements . The routine use of intraarterial lidocaine is not recommended for pain control until the long-term effects of vasospasm on outcome is known STUDY OBJECTIVE To compare perioperative pain and institutional use for women undergoing transcatheter uterine artery embolization ( UAE ) and transcatheter uterine artery occlusion ( UAO ) for the treatment of heavy uterine bleeding associated with uterine leiomyomas . DESIGN A pilot double-blind , r and omized clinical trial ( Canadian Task Force classification I ) . SETTING Large , university-affiliated community hospital with multiple residency programs including obstetrics and gynecolgoy and radiology . PATIENTS Premenopausal women with heavy uterine bleeding related to uterine leiomyomas were enrolled . INTERVENTIONS Either a st and ard UAE with microspheres or UAO using vascular coils was used . The main outcome measures were analgesic use , institutional stay , and postprocedural numeric pain scales . MEASUREMENTS AND MAIN RESULTS Sixteen women were enrolled and 14 underwent study procedures ( UAE n = 8 , UAO n = 6 ) . Baseline Aberdeen Menorrhagia Severity Scale scores , also known as the Ruta scores , were similar in each group ( UAE = 54 , UAO = 53 ) . Median preprocedural uterine volume was similar for each group ( UAE = 557 mL , UAO = 612 mL ) . The median postprocedural pain scale was less for UAO than UAE ( UAO 1 , UAE 5 ; p < .05 ) . Six patients with UAE and no patients with UAO required parenteral narcotic analgesia in the recovery room ( p < .05 ) ( median UAO 0 and UAE 1 ) . Patients with UAE used 6 hospital nights and patients with UAO used 1 hospital night ( p = .09 ) ( median UAO 0 and UAE 1 ) . Three-month Aberdeen Menorrhagia Severity Scale scores were reduced to a similar degree in each group ( UAE = 58 % , UAO = 63 % ) . CONCLUSION Transcatheter UAO is a promising alternative transcatheter technique for the treatment of symptoms related to uterine leiomyomas , with less postprocedural pain , reduced requirements for analgesics , and shorter hospital stays than transcatheter UAE . Although the results of the study are promising , larger-scale trials with longer follow-up are needed to both confirm these results and evaluate the long-term efficacy of transcatheter UAO Purpose To evaluate the effectiveness of superior hypogastric nerve block ( SHNB ) in reducing narcotic use after uterine artery embolization ( UAE ) . Material s and Methods This study was a prospect i ve , r and omized , double-blind , parallel clinical trial in patients referred to a tertiary care university teaching hospital for UAE . Forty-four participants were enrolled ( mean age , 46 years ; range , 32 - 56 years ) . No consenting patient was excluded . All participants were r and omized 1:1 to undergo either a sham procedure or SHNB . There were 22 participants in each group . One participant was lost to follow-up regarding home survey results . Use of narcotics and antiemetics was recorded in-hospital . Pain scores were recorded at home for 10 days with use of a visual analog scale ( range , 1 - 10 ) . Statistical analysis was performed by using the t test and χ2 test , with P < .05 considered indicative of a statistically significant difference . The full study protocol can be found at www . clinical trials.gov ( NCT02270255 ) . Results Participant demographic characteristics , fibroid volume , symptoms , and perceived sensitivity to pain were similar in both groups . Immediately after embolization , the pain score was lower in the SHNB group than in the sham group ( mean , 1.0 ± 2.1 vs 2.6 ± 2.0 , respectively ; P = .01 ) . The total need for fentanyl in the postanesthesia care unit was lower in the SHNB group than in the sham group ( mean , 56 μg ± 67 vs 124 μg ± 91 , respectively ; P = .009 ) . The morphine-equivalent dose needed was lower in the SHNB group than in the sham group ( mean , 5.1 mg ± 5.8 vs 11.0 mg ± 9.0 , respectively ; P = .014 ) . Of the 22 participants in the SHNB group , five ( 23 % ) needed antiemetics versus 12 of 22 participants ( 55 % ) in the sham group ( P = .03 ) . No difference in hospital admissions was observed between the two groups , and no major complications occurred from the SHNB . Conclusion Use of superior hypogastric nerve block reduces the amount of pain-related narcotics and antiemetics after uterine artery embolization . © RSNA , 2018 |
13,955 | 31,542,733 | There is insufficient evidence to support or refute the effectiveness of eradication therapy in preventing gastric carcinoma in H. pylori-infected , high-risk population s. Rigorously conducted large RCTs of healthy infected adults only would provide evidence of the true efficacy of successful eradication . | OBJECTIVES Recent meta-analyses of eradication therapy in Helicobacter pylori-infected adults reported significant reductions in gastric carcinoma risk .
However , concerns about supporting unfocused screening and eradication programme in healthy , asymptomatic population s have arisen .
We performed a systematic review and Bayesian meta- analysis to provide an accurate interpretation of r and omised evidence on the preventive effectiveness of eradication therapy on gastric carcinoma risk . | In the Sh and ong Intervention Trial , 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions , whereas 7.3 years of oral supplementation with garlic extract and oil ( garlic treatment ) or vitamin C , vitamin E , and selenium ( vitamin treatment ) did not . Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 r and omly assigned subjects in this masked factorial placebo-controlled trial . Conditional logistic regression was used to estimate the odds of gastric cancer incidence , and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality . All statistical tests were two-sided . Gastric cancer was diagnosed in 3.0 % of subjects who received H pylori treatment and in 4.6 % of those who received placebo ( odds ratio = 0.61 , 95 % confidence interval = 0.38 to 0.96 , P = .032 ) . Gastric cancer deaths occurred among 1.5 % of subjects assigned H pylori treatment and among 2.1 % of those assigned placebo ( hazard ratio [ HR ] of death = 0.67 , 95 % CI = 0.36 to 1.28 ) . Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality . Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer , a secondary endpoint ( HR = 0.51 , 95 % CI = 0.30 to 0.87 ; P = .014 ) BACKGROUND To reduce cancer mortality , effective screening should be implemented properly . In Japan , the Research Group for Cancer Screening developed screening guidelines ; however , the development process was not well established . METHODS Based on the development processes of other guidelines , an original method , unique to Japan , was established to develop the Japanese cancer screening guidelines . RESULTS The guideline development process involved the following steps : topic selection , development of the analytic framework , systematic literature review , translation to recommendations , consultation and publication . Mortality reduction related to cancer screening was evaluated using both direct and indirect evidence . To select appropriate articles , an analytic framework for cancer screening program with key questions was developed . Direct evidence was defined as a single body of evidence that established the linkage between screening and health outcomes such as mortality and incidence . The use of indirect evidence to determine the level of evidence was limited to situations where test accuracy could be compared with that of a method whose evidence was supported by r and omized , controlled trials . Eight levels of evidence were defined based on the study design and quality . The benefits of each screening modality were determined based on the level of evidence according to the results of the systematic review . Balancing the benefits and harms , five grade s of recommendation were formulated for population -based and opportunistic screening . After organized consultations , three types of guidelines were published . CONCLUSION We developed a unique , st and ardized method for developing cancer screening guidelines in Japan . Based on this process , previously developed cancer screening guidelines have been revised BACKGROUND A causal relationship between Helicobacter pylori infection and gastric cancer has been established . A nonr and omized study has shown eradication of H. pylori after endoscopic resection ( ER ) of early gastric cancer inhibits development of new carcinomas . SUBJECTS AND METHODS Eligible subjects are patients with H. pylori infection who are newly diagnosed with early gastric cancer and plan to have ER or who are in the post-resection follow-up phase after ER time of enrollment . Patients are r and omly allocated to the eradication or the control arms ( no eradication and st and ard of care ) . Patients will be evaluated by endoscopy at 0.5 , 1 , 2 , and 3 years after r and omization . Diagnosis of a new carcinoma at another site of the stomach is defined as primary endpoint , and recurrence of tumors at the resection site as a secondary endpoint . In addition to intention-to-treat and per- protocol analyses using proportional hazards models , time to recurrence will be compared between treatment and control using multiple logistic regression analyses . In the latter two situations , the models will be adjusted for the factors exerting significant influences on the results . RESULTS Five hundred and forty-two subjects have been enrolled into the study and are being followed-up . CONCLUSIONS This study will have the statistical power to demonstrate whether H. pylori eradication therapy exerts any clinical ly relevant inhibitory effects on occurrence or recurrence of gastric cancer . In addition , it will be able to test the hypothesis that H. pylori infection is a promoter in gastric carcinogenesis Objective Helicobacter pylori infection and overexpression of cyclo-oxygenase-2 ( COX-2 ) are associated with gastric cancer and its precursors . To evaluate the effect of a selective COX-2 inhibitor alone and combined with H pylori eradication on the evolution of precancerous gastric lesions , a r and omised , placebo-controlled trial was conducted in Linqu County , Sh and ong Province , China . Methods A total of 1024 participants aged 35–64 years with H pylori infection and advanced gastric lesions were r and omly assigned in a factorial design to two interventions or placebo : anti-H pylori treatment for 7 days , and a COX-2 inhibitor ( celecoxib ) for 24 months . The effects of the interventions were evaluated by the regression or progression of advanced gastric lesions . Results Of the 1024 participants who received anti-H pylori treatment or placebo , 919 completed a subsequent 24-month treatment with celecoxib or placebo . The H pylori eradication rate by per- protocol analysis was 78.2 % . Compared with placebo , the proportions of regression of gastric lesions significantly increased in the celecoxib treatment ( 52.8 % vs 41.2 % ) and anti-H pylori treatment ( 59.3 % vs 41.2 % ) group , and OR by per- protocol analysis was 1.72 ( 95 % CI 1.07 to 2.76 ) for celecoxib and 2.19 ( 95 % CI 1.32 to 3.64 ) for H pylori eradication . No statistically significant effect was found for H pylori eradication followed by celecoxib on the regression of advanced gastric lesions ( OR 1.48 , 95 % CI 0.91 to 2.40 ) . Conclusion This population -based intervention trial revealed that celecoxib treatment or H pylori eradication alone had beneficial effects on the regression of advanced gastric lesions . No favourable effects were seen for H pylori eradication followed by celecoxib treatment . Trial registration HARECCTR0500053 in accordance with WHO ICTRP requirements OBJECTIVES : Helicobacter pylori causes gastric adenocarcinoma . We assessed the success of H. pylori eradication therapy in a medically underserved population in Chiapas , Mexico , that is at high risk for gastric cancer risk . METHODS : Healthy volunteers with both antibodies to CagA and gastrin levels ≥25 ng/ml were r and omly assigned to receive either a combination of omeprazole , amoxicillin , and clarithromycin or matched placebo for 1 wk . Endoscopy with seven biopsies was performed at baseline , at 6 wk , and 1 yr after treatment . Treatment success was defined as loss of H. pylori by histological analysis . Cure was assessed using change in serology based on the st and ardized absorbance of a H. pylori ELISA . RESULTS : H. pylori eradication rates were high ( intent-to-treat analysis : 76.3 % [ 95 % CI = 68.7–84.0 % ] after 6 wk and 76.1 % [ 95 % CI = 67.7–84.6 % ] after 1 yr ; per protocol analysis : 77.8 % [ 95 % CI = 70.1–85.4 % ] after 6 wk and 75.2 % [ 95 % CI = 66.5–84.0 % ] after 1 yr ) . Nine subjects on active treatment and one subject on placebo who were without H. pylori at 6 wk were infected at 1 yr ( recurrence rates 10.7 % and 33.3 % , respectively , p = 0.31 ) . Median changes in st and ardized absorbance at 1 yr were 47 % and 1 % for successfully and unsuccessfully treated patients , respectively . A 10 % decline in st and ardized absorbance after 1 yr had 84 % sensitivity and 100 % specificity for H. pylori eradication . CONCLUSIONS : Even with a short course of treatment against H. pylori , a high rate of eradication rate can be achieved in population s at high risk for stomach cancer . Serum antibodies are useful in assessing efficacy of therapy CONTEXT Although chronic Helicobacter pylori infection is associated with gastric cancer , the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown . OBJECTIVE To determine whether treatment of H pylori infection reduces the incidence of gastric cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , r and omized , placebo-controlled , population -based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province , China , recruited in July 1994 and followed up until January 2002 . A total of 988 participants did not have precancerous lesions ( gastric atrophy , intestinal metaplasia , or gastric dysplasia ) on study entry . INTERVENTION Patients were r and omly assigned to receive H pylori eradication treatment : a 2-week course of omeprazole , 20 mg , a combination product of amoxicillin and clavulanate potassium , 750 mg , and metronidazole , 400 mg , all twice daily ( n = 817 ) ; or placebo ( n = 813 ) . MAIN OUTCOME MEASURES The primary outcome measure was incidence of gastric cancer during follow-up , compared between H pylori eradication and placebo groups . The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions , compared between the 2 groups . RESULTS Among the 18 new cases of gastric cancers that developed , no overall reduction was observed in participants who received H pylori eradication treatment ( n = 7 ) compared with those who did not ( n = 11 ) ( P = .33 ) . In a subgroup of patients with no precancerous lesions on presentation , no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo ( 0 vs 6 ; P = .02 ) . Smoking ( hazard ratio [ HR ] , 6.2 ; 95 % confidence interval [ CI ] , 2.3 - 16.5 ; P<.001 ) and older age ( HR , 1.10 ; 95 % CI , 1.05 - 1.15 ; P<.001 ) were independent risk factors for the development of gastric cancer in this cohort . CONCLUSIONS We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China . In the subgroup of H pylori carriers without precancerous lesions , eradication of H pylori significantly decreased the development of gastric cancer . Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted BACKGROUND & AIMS : Helicobacter pylori eradication improves the prognosis of peptic ulcer disease ( PUD ) , dyspepsia , and possibly gastric cancer . H pylori screening tests are accurate and eradication therapy is effective . H pylori population screening seems attractive . The aim of this study was to evaluate the long‐term effect of H pylori population screening and eradication on dyspepsia prevalence and the incidence of PUD , and as secondary outcomes to assess the effect on health care consumption and quality of life . METHODS : At baseline in 1998 to 1999 , 20,011 individuals aged 40 to 65 years were r and omized to H pylori screening and eradication or a control group with no screening . Both groups received a question naire on dyspepsia and quality of life . Register data were obtained for all r and omized individuals . RESULTS : The baseline question naire response rate was 63 % . Of the 5749 individuals screened , 1007 ( 17.5 % ) were H pylori positive . Complete symptom data were obtained for 8658 ( 69 % ) individuals after 13 years . Dyspepsia prevalence decreased in both groups during the follow‐up period , but multivariate analysis showed no effect of H pylori screening and eradication ( adjusted odds ratio , 0.93 ; 95 % confidence interval , 0.82–1.04 ) ; compared with usual care . Intention‐to‐treat and per‐ protocol analyses of register data provided similar results . H pylori screening neither reduced PUD incidence significantly ( adjusted odds ratio , 0.88 ; 95 % confidence interval , 0.70−1.11 ) nor did it have a beneficial effect on health care consumption . H pylori screening had no long‐term effect on quality of life . CONCLUSIONS : This r and omized clinical trial with 13 years of follow‐up evaluation , design ed to provide evidence on the effect of H pylori population screening , showed no significant long‐term effect when compared with usual care in this low‐prevalence area . Clinical Trials.gov identifier : NCT02001727 Introduction Population -based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines . However , the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied . An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions , in particular gastric atrophy ; pepsinogen tests are the best currently available alternative . The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals . The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events , including effects on microbiome . Methods and analysis Individuals are recruited from general population ( 50 % men ) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history question naire before being r and omly allocated to intervention or control groups . The intervention group undergoes H pylori testing and is offered eradication therapy if positive ; in addition , pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy . All participants are offered faecal occult blood testing as an incentive for study participation . Effectiveness of eradication and the spectrum of adverse events are evaluated in study sub population s. A 35 % difference in gastric cancer mortality between the groups is expected to be detectable at 90 % power after 15 years if 30 000 individuals are recruited . Biological material s are biobanked for the main and ancillary studies . The study procedure and assumptions will be tested during the pilot phase . Ethics and dissemination The study was approved by the respective ethics committees . An independent Data Safety and Monitoring Board has been established . The findings will be published in peer- review ed journals and presented at scientific meetings . Trial registration number Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To investigate the relationship between Helicobacter pylori ( Hp ) infection and gastric cancer through the changes of gastric mucosa histopathology within 5 years after Hp eradication in Hp-positive subjects in the high incidence region of gastric cancer . METHODS One thous and and six adults were selected from general population in Yantai , Sh and ong Province , the high incidence region of gastric cancer . Gastroscopy and CLO test were performed in all subjects . Biopsy sample s from the gastric antrum and body were obtained for histology and assessment of Hp infection . All the Hp-positive subjects were then r and omly divided into two groups : treatment group receiving OAC triple therapy and placebo as controls . These subjects were endoscopically followed up in the second and fifth year . In this article , we compared the endoscopic appearance and histology of the biopsy specimens from the same site obtained at the first and final visit . Statistical analysis was done by chi(2 ) test . RESULTS All the 552 Hp-positive subjects were r and omly divided into treatment group or control group , 276 in each . During the five-year follow-up , the number of patients who continued to be negative or positive for Hp was 161 and 198 , respectively . Statistical analysis revealed that : ( 1 ) At the initial visit , there were no significant differences in the severity and activity of inflammation between the biopsy specimens from the antrum ( P = 0.105 ) and body ( P = 0.084 ) in both groups . But the proportion of atrophy and intestinal metaplasia in the antrum was much higher than that in the body ( P = 0.000 ) . ( 2 ) The severity and activity of inflammation in both the antrum and body were markedly reduced after Hp eradication ( P = 0.000 ) . ( 3 ) Within the five years after Hp eradication , intestinal metaplasia in the antrum regressed or had no progression , while the proportion of intestinal metaplasia in the Hp-positive group increased significantly ( P = 0.032 ) . ( 4 ) After Hp eradication , the atrophy in both the antrum and body had no significant regression . P value was 0.223 and 0.402 , respectively . CONCLUSIONS Hp eradication results in remarkable reduction in the severity and activity of chronic gastritis , marked resolution of intestinal metaplasia in the antrum . On the other h and , continued Hp infection leads to progressive aggrevation of atrophy and intestinal metaplasia Background : Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer . Underst and ing long term effects result ing from the cure of this infection is needed to design cancer prevention strategies . Methods : A cohort of 795 adults with preneoplastic gastric lesions was r and omised to receive anti-H pylori treatment and /or antioxidants . At the end of six years of intervention , those who did not receive anti-H pylori treatment were offered it . Gastric biopsies were obtained at baseline , and at 3 , 6 , and 12 years . A histopathology score was utilised to document changes in gastric lesions . Non-linear mixed models were used to estimate the cumulative effect of H pylori clearance on histopathology scores adjusted for follow up time , interventions , and confounders . Results : Ninety seven per cent of subjects were H pylori positive at baseline , and 53 % were positive at 12 years . Subjects accumulated 1703 person years free of infection . A multivariate model showed a significant regression in histopathology score as a function of the square of H pylori negative time . Subjects who were H pylori negative had 14.8 % more regression and 13.7 % less progression than patients who were positive at 12 years ( p = 0.001 ) . The rate of healing of gastric lesions occurred more rapidly as years free of infection accumulated , and was more pronounced in less advanced lesions . Conclusions : Preneoplastic gastric lesions regress at a rate equal to the square of time in patients rendered free of H pylori infection . Our findings suggest that patients with preneoplastic gastric lesions should be treated and cured of their H pylori infection OBJECTIVES To investigate the relationship between H. pylori infection , gastric cancer and other gastric diseases through the changes in gastric mucosa and the status of different gastric diseases within 5 years after H. pylori eradication in H. pylori-positive subjects in a high incidence region of gastric cancer . METHODS One thous and and six adults were selected from the general population in Yantai , Sh and ong province , a high incidence region for gastric cancer in China . Gastroscopy and Campylobacter-like organism ( CLO ) testing were performed on all subjects . Biopsy sample s from the gastric antrum and body were obtained for histology and assessment of H. pylori infection . All H. pylori-positive subjects were then r and omly divided into two groups : treatment group receiving Omeprazole Amoxicillin Clarythromycin ( OAC ) triple therapy and placebo as controls . These subjects were endoscopically followed up in the second and fifth year . We compared the endoscopic appearance and histology of the biopsy specimens from the same site obtained at the first and last visits . RESULTS All 552 H. pylori-positive subjects were r and omly and evenly divided into treatment group or control group . During the five-year follow-up , the numbers of patients who continued to be negative or positive for H. pylori were 161 and 198 , respectively . Statistical analysis revealed that : ( 1 ) At the initial visit , there were no significant differences in the severity and activity of inflammation , atrophy and intestinal metaplasia between the biopsy specimens from the antrum and body respectively in both groups . ( 2 ) The severity and activity of inflammation in both the antrum and body were markedly reduced after H. pylori eradication ( P = 0.000 ) . ( 3 ) Within five years after H. pylori eradication , intestinal metaplasia in the antrum either regressed or had no progression , while the proportion of intestinal metaplasia in the H. pylori-positive group increased significantly ( P = 0.032 ) . ( 4 ) After H. pylori eradication , the atrophy in both the antrum and body had no significant regression . The P value was 0.223 and 0.402 , respectively . CONCLUSIONS H. pylori eradication results in remarkable reduction in the severity and activity of chronic gastritis , marked resolution of intestinal metaplasia in the antrum . On the other h and , continuous H. pylori infection leads to progressive aggravation of atrophy and intestinal metaplasia Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND R and omized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions . We conducted a r and omized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions . METHODS Most of the adults aged 35 - 64 years in 13 r and omly selected villages in Linqu County , Sh and ong Province , China , were identified and given baseline endoscopies in 1994 . In 1995 , 3365 eligible subjects were r and omly assigned in a factorial design to three interventions or placebos : amoxicillin and omeprazole for 2 weeks in 1995 ( H. pylori treatment ) ; vitamin C , vitamin E , and selenium for 7.3 years ( vitamin supplement ) ; and aged garlic extract and steam-distilled garlic oil for 7.3 years ( garlic supplement ) . Subjects underwent endoscopies with biopsies in 1999 and 2003 , and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven st and ard biopsy sites . The 3365 eligible r and omized subjects represented 93.5 % of those with baseline endoscopy and included all baseline histologic categories except gastric cancer . Only 0.18 % had normal gastric mucosa . Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions , and t-tests were used to assess effects on histologic severity . All statistical tests were two-sided . RESULTS H. pylori treatment result ed in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis , intestinal metaplasia , dysplasia , or gastric cancer in 1999 ( odds ratio [ OR ] = 0.77 ; 95 % confidence interval [ CI ] = 0.62 to 0.95 ) and in 2003 ( OR = 0.60 ; 95 % CI = 0.47 to 0.75 ) , and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003 . H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer . However , fewer subjects receiving H. pylori treatment ( 19/1130 ; 1.7 % ) than receiving placebo ( 27/1128 ; 2.4 % ) developed gastric cancer ( adjusted P = .14 ) . No statistically significant favorable effects were seen for garlic or vitamin supplements . CONCLUSION H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence , but further data are needed to prove the latter point . Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence AIM To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease . METHODS It is a prospect i ve , r and omized , double blind , placebo controlled multinational multicenter trial . Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are r and omized to receive a 7 day course of omeprazole 2 X 20 mg , clarithromycin 2 X 500 mg , and amoxicillin 2 X 1 g for 7 days , or omeprazole 2 X 20 mg plus placebo . Follow-up endoscopy is scheduled 3 months after therapy , and thereafter in one-year intervals . Predefined study endpoints are gastric cancer , precancerous lesions ( dysplasia , adenoma ) , other cancers , and death . RESULTS Since March 1998 , 1524 target patients have been screened , 279 patients ( 18.3 % ) had a corpus dominant type of H. pylori gastritis , and 167 of those were r and omized ( 58.8 % ) . In the active treatment group ( r = 86 ) , H. pylori infection infection was cured in 88.9 % of patients . Currently , the cumulative follow-up time is 3046 months ( 253.38 patient years , median follow up 16 months ) . So far , none of the patients developed gastric cancer or any precancerous lesion . Three ( 1.8 % ) patients reached study endpoints other than gastric cancer . CONCLUSION Among men between 55 and 65 years of age , the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected . Further follow up and continuing recruitment are necessary to fulfil the main aim of the study Background Helicobacter pylori ( Hp ) is a common and potentially curable cause of gastric mucosa lesion . This study investigated the relationship of Hp infection with histological changes in gastric mucosa and gastric cancer in Hp‐positive patients compared with Hp‐eradication patients followed up for ten years . Methods From an initial group of 1 006 adults , 552 Hp‐positive subjects were r and omly assigned to a treatment group ( T ; n = 276 ) or a placebo group ( P ; n = 276 ) . In the r and omized , double‐blind , placebo‐controlled , parallel trial , T group subjects received oral doses of omeprazole , amoxicillin and clarithromycin for 1 week ; those in the P group received a placebo . One month after treatment ended , a 13C urea breath test was performed , and Hp was undetectable in 88.89 % of the T group . All subjects were followed at 1 , 5 , 8 , and 10 years after treatment , with endoscopy and biopsies for histological examination . Results Gastric mucosa inflammation was significantly milder in the T group than that in the P group one year after Hp eradication and this persisted for 10 years . Gl and ular atrophy and intestinal metaplasia ( IM ) had deteriorated in both groups during ten years . However , the increased score of gl and ular atrophy at both the gastric antrum and corpus , and IM only at the gastric antrum , in the P group was more obvious than that in the T group . During the 10 years , 9 patients were diagnosed with gastric cancer ( 2 in the T group ; 7 in the P group ; P=0.176 ) . When mucosal atrophy was absent at the gastric antrum and corpus when entering the study , the incidence of gastric cancer in the P group ( n=6 ) was much higher than that in the T group ( n = 0 , P=0.013 ) . Conclusions Hp eradication may significantly diminish and help halt progression of gastric mucosal inflammation and delay the development of IM and atrophy gastritis . Hp eradication is helpful for reducing the risk for gastric cancer , especially in the early stage of Hp infection BACKGROUND AND AIMS : Helicobacter pylori ( H. pylori ) screening and eradication may reduce the incidence of gastric cancer , peptic ulcer , and ulcer complications , and it may reduce symptoms in a small proportion of individuals with functional dyspepsia . This study aim ed to assess the effect of community H. pylori screening and treatment on the prevalence of dyspepsia , and as secondary outcomes , the effect on dyspepsia-related health-care consumption and quality of life over 5 yr . METHODS : In 1998–1999 , individuals aged 40–65 yr were r and omized to H. pylori screening and treatment or to the control group . Five years later , the participants were sent a question naire to assess the prevalence of dyspepsia and quality of life . In addition , we obtained information from registers on the use of endoscopies and prescription medication . An economic evaluation was done alongside the r and omized trial . RESULTS : Of 12,530 participants attending the study at baseline , 11,065 ( 88 % ) were traced and contacted at the 5-yr follow-up . The response rate was 94 % . At baseline , 17.5 % in the screened group were H. pylori-positive . The absolute reduction in dyspepsia during the first year was 4 % in the screened group , whereas no change was observed in the unscreened group ; this rate remained constant during the next 4 yr . Quality of life did not change . A small effect was found for dyspepsia-related consultations and sick leave days , but not on the prescription rate of ulcer drugs . A 33 % lower ulcer incidence ( 107 ulcers vs 148 ulcers ) was seen in the screened group compared to the unscreened group . CONCLUSION : A population H. pylori screening and treatment program in an H. pylori low-prevalence area had only a modest , but insignificant , effect on the rate of dyspepsia , and a modest , significant effect on the consultation rate and sick leave days for dyspepsia , but result ed in a decreased ulcer incidence . The intervention result ed in an increased cost due to H. pylori screening and treatment Helicobacter pylori screening and treatment has been proposed as a cost‐effective method of preventing gastric cancer Stomach cancer is the second cause of death in Mexico in patients with malignant tumors . This disease represents a public health problem . A strong association has been described between chronic infection with Helicobacter pylori and gastric cancer . This malignancy is preceded by a series of preneoplastic conditions , including chronic atrophic gastritis ( CAG ) , intestinal metaplasia ( IM ) , and dysplasia . The objective of this study was to establish the prevalence of preneoplastic conditions associated with infection of Helicobacter pylori in the state of Chiapas and its eradication with antibiotics . Persons infected with Helicobacter pylori and with CAG were identified by serology against CagA protein and serologic levels of gastrin . An endoscopy with biopsy was performed at the beginning of the study , and at 6 weeks and 1 year thereafter . A total of 281 people were enrolled and r and omly assigned to treatment or placebo group . CAG was found in 59 % , IM in 51 % , and dysplasia in 13 % . In intent-to-treat and per- protocol analysis , Helicobacter pylori was eliminated in 70 and 76 % , respectively . These results indicate high frequency of preneoplastic conditions associated with Helicobacter pylori and an excellent eradication rate . They also offer a possible alternative for preventing gastric cancer The bacteriumHelicobacter pylori ( HP ) has been implicated in the etiology of precancerous lesions of the stomach and there is evidence suggesting that it may influence the efficacy of chemoprevention of gastric cancer with vitamin C. Eradication seldom has been attempted in population s from developing countries , with a high prevalence of HP frequently resistant to metronidazole . A r and omized , double-blind , controlled trial to evaluate the efficacy of colloidal bismuth subcitrate ( 120 mg q.i.d . ) and amoxycillin ( 500 mg q.i.d . ) in eradicating HP was conducted in 220 subjects drawn from a population with a high prevalence of metronidazole-resistant HP in Tachira state , Venezuela . One month after completion of two weeks ' treatment , eradication rates of 6.5 percent in the treatment group and two percent in the placebo group were estimated on the basis of HP diagnosis in biopsies , and of 13.9 percent compared with 3.9 percent on the basis of a14C-urea breath test , although the negative predictive value of the breath test was very low compared with HP diagnosis in biopsies . In the treatment group , particularly among males , a significant decrease in bacterial load was detected . Reasons for failure of treatment in high HP-prevalence areas are discussed , and it is suggested that primary prevention of HP infection may be the optimal approach to reducing levels of stomach cancer in these high-risk groups BACKGROUND & AIMS Helicobacter pylori ( Hp ) is strongly correlated with peptic ulcer and is a risk factor for gastric cancer . The aim of this study was to assess whether screening and eradication of Hp in a general population would reduce the prevalence of dyspepsia and the incidence of peptic ulcer and thus save health care re sources and improve quality of life . METHODS Twenty thous and individuals aged 40 to 65 years were r and omized to screening and eradication for Hp or to the control group . Hp status was assessed by a whole blood Hp test , a positive result confirmed by a (13)C-urea breath test . Hp-positive individuals were offered Hp eradication therapy . The prevalence of dyspepsia and the quality of life were assessed through a mailed question naire . Information on the use of endoscopies and the use of prescription medication was obtained from registers . RESULTS The response rate was 62.6 % . The prevalence of Hp was 17.5 % . The Hp eradication rate was 95 % . In the intervention group , the prevalence of dyspepsia decreased from 24.3 % at inclusion to 20.5 % at 1-year follow-up . The reduction was similar in Hp-negative and Hp-positive persons . In the control group , dyspepsia increased from 20.3 % to 21.5 % . Gastroesophageal reflux symptoms improved slightly in Hp-eradicated participants . Except for a decreased consultation rate for dyspepsia , there were no visible savings in health care . CONCLUSIONS Dyspepsia was modestly reduced after the screening and treatment procedure , and the result was not sufficiently extensive to have an effect on the use of health care or to improve quality of life A double-blind , placebo-controlled trial is being conducted in a population at high risk for gastric cancer in Venezuela . The main aim of the trial is to assess the effect of antioxidant vitamins ( beta-carotene , vitamin C and vitamin E ) in blocking the progression of precancerous lesions of the stomach . Within the framework of a screening programme for stomach cancer , 2200 subjects of 35 - 69 years of age have been recruited . At study entry , a dietary question naire was completed , and gastroscopy with the collection of seven gastric biopsies was performed . After baseline examinations , the study participants were r and omized to receive antioxidant treatment or placebo for three years . The treatment phase will be completed in mid-1998 . At the end of the treatment phase , the investigations performed at study entry will be repeated . Before the initiation of the trial , various pilot studies were carried out that showed an extremely high prevalence of Helicobacter pylori infection ( over 90 % ) . Two eradication trials using anti-H. pylori treatments that give good results in Europe and North America gave very poor results in our study population . The low eradication rates achieved ( 5 - 20 % ) suggest a high prevalence of antibiotic-resistant H. pylori strains or high reinfection rates . These disappointing results led to deletion of an anti-H. pylori treatment phase of the main trial BACKGROUND Population Helicobacter pylori screening and treatment has been advocated as a means of reducing mortality from gastric cancer . The optimum Helicobacter pylori eradication therapy to use in this setting is uncertain . AIMS To compare efficacy of seven days of omeprazole , clarithromycin and either metronidazole , or amoxycillin in Helicobacter pylori positive subjects detected by population screening . PATIENTS Helicobacter pylori positive patients from the placebo group of a population screening and treatment trial were invited to take part in the investigation . METHODS Patients were r and omised to receive either omeprazole , clarithromycin and metronidazole or omeprazole , clarithromycin and amoxycillin , and Helicobacter pylori eradication was verified with a 13C-urea breath test at least four weeks after completion of therapy . RESULTS A total of 221 patients took part in the study and 210 completed the protocol . Treatment was successful in 93/111 [ 84 % ) patients allocated to omeprazole , clarithromycin and metronidazole and in 96/110 ( 87 % ) allocated to omeprazole , clarithromycin and amoxycillin in an intention-to-treat analysis ( p=0.46 ) . Per protocol eradication rates were 93/107 ( 87 % ) in the metronidazole , and 96/103 ( 93 % ) amoxycillin group ( p=0.129 ) . CONCLUSIONS There was no significant difference between the two regimens . The eradication rates achieved are comparable with previous studies in both dyspepsia and peptic ulcer patients In the fall of 1995 , 3411 subjects in 13 rural villages in Linqu County , Sh and ong Province , China , began participating in a blinded , r and omized 23 factorial trial to determine whether interventions can reduce the prevalence of dysplasia and other precancerous gastric lesions . One intervention is treatment for infection by Helicobacter pylori with amoxicillin and omeprazole . A second is dietary supplementation with capsules containing vitamin C , vitamin E , and selenium . A third is dietary supplementation with capsules containing steam-distilled garlic oil and Kyolic aged garlic extract . Investigators will evaluate histopathologic endpoints after gastroscopies with biopsies from seven st and ard sites in 1999 . Initial data from pill counts and sample d blood levels of vitamin E , vitamin C , and S-allylcysteine indicate excellent compliance . Subjects have tolerated all interventions well , although 3.1 % of those assigned to amoxicillin and omeprazole developed rashes , compared to 0.3 % to those in the control group . Preliminary breath tests demonstrate substantial reductions in gastric urease activity , an indication of infection by Helicobacter pylori , among those assigned to amoxicillin and omeprazole Aim To explore a low-cost and highly-effective therapy for eradication of Helicobacter pylori ( H. pylori ) , a placebo-controlled trial of quadruple therapy was conducted in a population at high risk of gastric cancer in Linqu County of Sh and ong Province , China . Methods Two hundred and seventy-seven adults aged 35–54 years with H. pylori infection in three villages were assigned to two groups : treatment ( n=189 in two villages ) and placebo ( n=88 in one village ) . Participants received either a 10-day oral quadruple therapy regimen with omeprazole ( 20 mg , twice daily ) ; tetracycline ( 750 mg , three times daily ) ; metronidazole ( 500 mg , three times daily ) and bismuth potassium citrate ( 300 mg , twice daily ) , or a similar lookalike placebo regimen . The status of H. pylori infection in each trial participant before and after six weeks of treatment was determined by a 13C-urea breath test . Results One hundred and seventy-four of 189 participants completed the quadruple therapy ( 92.1 % ) and 84 participants completed the placebo therapy ( 95.5 % ) . The H. pylori eradication rate by intention-to-treat analysis was 76.7 % ( 145 of 189 ) in the treatment group and 1.1 % ( 1 of 88 ) in the placebo group , respectively ; by per- protocol analysis it was 83.3 % ( 145 of 174 ) in the treatment group and 1.2 % ( 1 of 84 ) in the placebo group , respectively . Conclusion In a high-risk area of gastric cancer , we conducted a high compliance , tolerable , low side-effect and lowcost therapy of anti-H. pylori . The eradication rate of the 10-day quadruple treatment was more than 80 % and significantly higher than the triple therapy regimen used in this population in an earlier trial BACKGROUND Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural population s living in the province of Nariño , Colombia , in the And es Mountains . METHODS A r and omized , controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and /or intestinal metaplasia , two precancerous lesions . Individuals were assigned to receive anti-Helicobacter pylori triple therapy and /or dietary supplementation with ascorbic acid , beta-carotene , or their corresponding placebos . Gastric biopsy specimens taken at baseline were compared with those taken at 72 months . Relative risks of progression , no change , and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects . All statistical tests were two-sided . RESULTS All three basic interventions result ed in statistically significant increases in the rates of regression : Relative risks were 4.8 ( 95 % confidence interval [ CI ] = 1.6 - 14.2 ) for anti-H. pylori treatment , 5 . 1 ( 95 % CI = 1.7 - 15.0 ) for beta-carotene treatment , and 5.0 ( 95 % CI = 1.7 - 14.4 ) for ascorbic acid treatment in subjects with atrophy . Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 ( 95 % CI = 1.0 - 9.3 ) , 3.4 ( 95 % CI = 1.1 - 9.8 ) , and 3.3 ( 95 % CI = 1.1 - 9.5 ) . Combinations of treatments did not statistically significantly increase the regression rates . Curing the H. pylori infection ( which occurred in 74 % of the treated subjects ) produced a marked and statistically significant increase in the rate of regression of the precursor lesions ( relative risks = 8.7 [ 95 % CI = 2.7 - 28.2 ] for subjects with atrophy and 5.4 [ 95 % CI = 1.7 - 17.6 ] for subjects with intestinal metaplasia ) . CONCLUSIONS In the very high-risk population studied , effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process , mostly by increasing the rate of regression of cancer precursor lesions , and may be an effective strategy to prevent gastric carcinoma Objective To evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions . Design 795 adults with precancerous gastric lesions were r and omised to receive anti-H. pylori treatment at baseline . Gastric biopsies were obtained at baseline and at 3 , 6 , 12 and 16 years . A total of 456 individuals attended the 16-year visit . Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up . Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis ( versus no change/regression ) as well as gastric cancer risk by intestinal metaplasia ( IM ) subtype . For a more detailed analysis of progression , we also used a histopathology score assessing both severity and extension of the gastric lesions ( range 1–6 ) . The score difference between baseline and 16 years was modelled by generalised linear models . Results Individuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline ( p=0.001 ) . Incomplete-type IM was associated with higher risk of progression to cancer than complete-type ( OR , 11.3 ; 95 % CI 1.4 to 91.4 ) . The average histopathology score increased by 0.20 units/year ( 95 % CI 0.12 to 0.28 ) among individuals continuously infected with H. pylori . The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy ( without IM ) than for individuals with IM ( p<0.001 ) . Conclusions Long-term exposure to H. pylori infection was associated with progression of precancerous lesions . Individuals infected with H. pylori with these lesions may benefit from eradication , particularly those with atrophic gastritis without IM . Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer |
13,956 | 28,463,618 | CONCLUSIONS Robotics in spine surgery is an emerging technology that holds promise for future applications .
Surgical accuracy in instrumentation implanted using robotics appears to be high .
However , the impact of robotics on radiation exposure is not clear and seems to be dependent on technique and robot type | OBJECTIVE Surgical robotics has demonstrated utility across the spectrum of surgery .
Robotics in spine surgery , however , remains in its infancy .
Here , the authors systematic ally review the evidence behind robotic applications in spinal instrumentation . | Even though robotic technology holds great potential for performing spinal surgery and advancing neurosurgical techniques , it is of utmost importance to establish its practicality and to demonstrate better clinical outcomes compared with traditional techniques , especially in the current cost-effective era . Several systems have proved to be safe and reliable in the execution of tasks on a routine basis , are commercially available , and are used for specific indications in spine surgery . However , workflow , usability , interdisciplinary setups , efficacy , and cost-effectiveness have to be proven prospect ively . This article includes a short description of robotic structures and workflow , followed by preliminary results of a r and omized prospect i ve study comparing conventional free-h and techniques with routine spine navigation and robotic-assisted procedures . Additionally , we present cases performed with a spinal robotic device , assessing not only the accuracy of the robotic-assisted procedure but also other factors ( eg , minimal invasiveness , radiation dosage , and learning curves ) . Currently , the use of robotics in spinal surgery greatly enhances the application of minimally invasive procedures by increasing accuracy and reducing radiation exposure for patients and surgeons compared with st and ard procedures . Second-generation hardware and software up grade s of existing devices will enhance workflow and intraoperative setup . As more studies are published in this field , robot-assisted therapies will gain wider acceptance in the near future Study Design . A retrospective chart review was performed for 112 consecutive minimally invasive spinal surgery patients who underwent pedicular screw fixation in a community hospital setting . Objective . To assess the clinical accuracy and deviation in screw positions in robot-assisted pedicle screw placement . Summary of Background Data . Accuracy of pedicle screw placement in in vivo studies varies widely , especially when minimally invasive techniques are used . Robotic guidance was recently introduced to increase screw placement accuracy but still reported accuracies vary . Methods . Reproducibility of the surgeon 's plan using robotic guidance was assessed by fusing individual vertebras from the preoperative computed tomography ( CT ) containing the planning with a postoperative CT . Deviation in entry point and difference in angle of insertion was measured on axial and sagittal planes . Grading of pedicle screw placement was performed on postoperative CTs using the Gertzbein-Robbins classification . Results . CT-to-CT fusion succeeded for 178 screws , but these appeared to be r and om , with no apparent selection bias . Mean deviation in entry point was 2.0 ± 1.2 mm . Mean difference in angle of insertion was 2.2 ° ± 1.7 ° on the axial plane and 2.9 ° ± 2.4 ° on the sagittal plane . Assessment of pedicle screw accuracy showed that 477 of 487 screws ( 97.9 % ) were safely placed ( < 2 mm , category A+B ) , 8 screws in category C and 1 in category D. None of the screws necessitated resurgery for revised placement . Conclusion . Preoperative planning of robotic guidance is reproduced intraoperatively within acceptable deviations . We conclude that robotic guidance allows for highly accurate execution of the preoperative plan , leading to accurate screw placement . Level of Evidence : Study Design : This is a prospect i ve r and omized comparison study between the fluoroscopy-guided and navigation coupled with O-arm – guided pedicle screw placement in the thoracic and lumbosacral spines . Objective : The objective of the study was to evaluate the accuracy and clinical benefits of a navigation coupled with O-arm – guided method in the thoracic and lumbar spines by comparing with a C-arm fluoroscopy-guided method . Methods : Under fluoroscopy guidance , 138 pedicle screws were inserted from T9 to S1 in 20 patients , and 124 pedicle screws were inserted from T9 to S1 in 20 patients using the navigation . The position of the screws within the pedicle was assessed from grade 0 ( no violation cortex ) to grade 3 ( > 4 mm violation ) , and the location of the violated cortex was determined . Preparation time of each equipment setting , time for screwing , and the number of x-ray shots were evaluated . Results : The number of screws observed as grade 0 was 121 ( 87.7 % ) in the fluoroscopy-guided group and 114 ( 91.9 % ) in the navigation-guided group . The lateral cortex was most commonly involved in the fluoroscopy-guided group ( 6 cases , 35.3 % ) , and the medial cortex was most common in the navigation-guided group ( 4 cases , 40 % ) . The mean time required for preparation for screw placement was 3.7 minutes in the fluoroscopy-guided group and 14.2 minutes in the navigation-guided group . Average screwing time was 3.6 minutes in the fluoroscopy-guided group and 4.3 minutes in the navigation-guided group . The mean number of x-ray shots for each screw placement in the fluoroscopy-guided group was 6.5 . Postoperatively , 2 patients with misplacement of a screw under fluoroscopy guidance presented ipsilateral leg paresthesia , possibly related to the screw position . Conclusions : The present prospect i ve study reveals that the pedicle screw placement guided by the navigation coupled with O-arm system was more accurate and safer than that under fluoroscopy guidance Abstract This purpose of this retrospective study is validation of an intraoperative robotic grading classification system for assessing the accuracy of Kirschner-wire ( K-wire ) placements with the postoperative computed tomography (CT)-base classification system for assessing the accuracy of pedicle screw placements . We conducted a retrospective review of prospect ively collected data from 35 consecutive patients who underwent 176 robotic assisted pedicle screws instrumentation at Kaohsiung Medical University Hospital from September 2014 to November 2015 . During the operation , we used a robotic grading classification system for verifying the intraoperative accuracy of K-wire placements . Three months after surgery , we used the common CT-base classification system to assess the postoperative accuracy of pedicle screw placements . The distributions of accuracy between the intraoperative robot-assisted and various postoperative CT-based classification systems were compared using kappa statistics of agreement . The intraoperative accuracies of K-wire placements before and after repositioning were classified as excellent ( 131/176 , 74.4 % and 133/176 , 75.6 % , respectively ) , satisfactory ( 36/176 , 20.5 % and 41/176 , 23.3 % , respectively ) , and malpositioned ( 9/176 , 5.1 % and 2/176 , 1.1 % , respectively)In postoperative CT-base classification systems were evaluated . No screw placements were evaluated as unacceptable under any of these systems . Kappa statistics revealed no significant differences between the proposed system and the aforementioned classification systems ( P < 0.001).Our results revealed no significant differences between the intraoperative robotic grading system and various postoperative CT-based grading systems . The robotic grading classification system is a feasible method for evaluating the accuracy of K-wire placements . Using the intraoperative robot grading system to classify the accuracy of K-wire placements enables predicting the postoperative accuracy of pedicle screw placements OBJECT Minimally invasive transforaminal lumbar interbody fusion ( TLIF ) is an increasingly popular procedure . The technique involves use of fluoroscopy to assist with pedicle screw ( PS ) placement . The potential exists for both the surgeon and the patient to become exposed to significant amounts of radiation . The authors undertook this study to quantify the radiation dose to the surgeon and patient during minimally invasive TLIF . METHODS The authors undertook a prospect i ve study of 24 consecutive patients who underwent minimally invasive TLIF . All surgeries were performed by the senior author ( R.K.B. ) , who used techniques previously described . The surgeon wore a radiation monitor under an apron-style lead shield at waist level , at an unshielded collar location , and as a sterile ring badge containing a thermoluminescent dosimeter on the dominant ( right ) h and ring finger . Dosimeter readings were obtained for each case . A total of 33 spinal levels were treated in 24 patients . All treated levels were between L3 - 4 and L5-S1 . In all cases of 1-level disease , 4 PSs were placed , and in all cases of 2-level disease , 6 screws were placed . RESULTS Mean fluoroscopy time was 1.69 minutes per case ( range 3.73 - 0.82 minutes ) . Mean exposure per case to the surgeon on his dominant h and was 76 mRem , at the waist under a lead apron was 27 mRem , and at an unprotected thyroid level was 32 mRem . Mean exposure to the patient 's skin was 59.5 mGy ( range 8.3 - 252 mGy ) in the posteroanterior plane and 78.8 mGy ( range 6.3 - 269.5 mGy ) in the lateral plane . CONCLUSIONS To the authors ' knowledge , this is the first study of radiation exposure to the surgeon or patient in minimally invasive TLIF . Patient exposures were low and compare favorably with exposures involving other common interventional fluoroscopically guided procedures . Surgeon exposures are limited but require careful monitoring . Annual dose limits could be exceeded if a large number of these and other fluoroscopically guided procedures were performed Study Design . A prospect i ve r and omized clinical trial . Objective . To compare the impact of robotic guidance in a minimally invasive spine surgery ( MIS ) to a fluoroscopy-guided open approach in lumbar fusions . Summary of Background Data . MIS requires a protracted learning curve and excessively exposes the patient and surgical team to harmful radiation . Robotic-guidance has been shown to improve accuracy and radiation in most studies , but there is conflicting prospect i ve data . Methods . Patients indicated to undergo a 1 or 2 level spinal fusion were r and omized between robotic-guided MIS ( RO ) and fluoroscopic-guided open surgery ( FA ) . Patient demographics and outcomes were recorded . Results . Thirty patients were recruited to each arm . Average age was 66.7 years , 71.5 % were females , and average body mass index was 25.2 . Thirty-five levels were instrumented with 130 pedicle screws in RO versus 40 levels with 140 screws in FA , or 4.3 and 4.7 screws per surgery , respectively . Use of fluoroscopy was 3.5 versus 13.3 seconds in the RO and FA respectively ( P < 0.001 ) . C-arm output in mSv was 0.13 versus 0.27 in the RO and FA respectively ( P = 0.015 ) . By thermoluminescent dosimeters , the average per-screw radiation in the RO arm was 37.5 % of that in the FA arm , demonstrating a mean reduction of 62.5 % in use of radiation . There was no difference in the improvement in Visual Analog Scale scores for back and leg or the Oswestry Disability Index . All screws were accurate in RO whereas two screws breached ( > 2 mm and > 4 mm ) in FA ( P = 0.500 ) . One proximal facet violation occurred in the study , it was in FA ( P = 1.000 ) . The average distance from the proximal facets was 5.8 versus 4.6 mm in the RO and FA respectively ( P < 0.001 ) . The average length of stay was 6.8 versus 9.4 days in RO compared with FA ( P = 0.020 ) . Conclusion . MIS using robotic-guidance significantly reduced radiation exposure and length of stay . Patient outcomes were not affected by the surgical technique . Level of Evidence : Bone-mounted robotic guidance for pedicle screw placement has been recently introduced , aim ing at increasing accuracy . The aim of this prospect i ve study was to compare this novel approach with the conventional fluoroscopy assisted freeh and technique ( not the two- or three-dimensional fluoroscopy-based navigation ) . Two groups were compared : 11 patients , constituting the robotical group , were instrumented with 64 pedicle screws ; 23 other patients , constituting the fluoroscopic group , were also instrumented with 64 pedicle screws . Screw position was assessed by two independent observers on postoperative CT-scans using the Rampersaud A to D classification . No neurological complications were noted . Grade A ( totally within pedicle margins ) accounted for 79 % of the screws in the robotically assisted and for 83 % of the screws in the fluoroscopic group respectively ( p = 0.8 ) . Grade C and D screws , considered as misplacements , accounted for 4.7 % of all robotically inserted screws and 7.8 % of the fluoroscopically inserted screws ( p = 0.71 ) . The current study did not allow to state that robotically assisted screw placement supersedes the conventional fluoroscopy assisted technique , although the literature is more optimistic about the former Study Design . Single-center prospect i ve r and omized controlled study . Objective . To evaluate the accuracy of robot-assisted ( RO ) implantation of lumbar/sacral pedicle screws in comparison with the freeh and ( FH ) conventional technique . Summary of Background Data . SpineAssist is a miniature robot for the implantation of thoracic , lumbar , and sacral pedicle screws . The system , studied in cadaver and cohort studies , revealed a high accuracy , so far . A direct comparison of the robot assistance with the FH technique is missing . Methods . Patients requiring mono- or bisegmental lumbar or lumbosacral stabilization were r and omized in a 1:1 ratio to FH or RO pedicle screw implantation . Instrumentation was performed using fluoroscopic guidance ( FH ) or robot assistance . The primary end point screw position was assessed by a postoperative computed tomography , and screw position was classified ( A : no cortical violation ; B : cortical breach < 2 mm ; C : ≥2 mm to < 4 mm ; D : ≥4 mm to < 6 mm ; E : ≥6 mm ) . Secondary end points as radiation exposure , duration of surgery/planning , and hospital stay were assessed . Results . A total of 298 pedicle screws were implanted in 60 patients ( FH , 152 ; RO , 146 ) . Ninety-three percent had good positions ( A or B ) in FH , and 85 % in RO . Preparation time in the operating room ( OR ) , overall OR time , and intraoperative radiation time were not different for both groups . Surgical time for screw placement was significantly shorter for FH ( 84 minutes ) than for RO ( 95 minutes ) . Ten RO screws required an intraoperative conversion to the FH . One FH screw needed a secondary revision . Conclusion . In this study , the accuracy of the conventional FH technique was superior to the RO technique . Most malpositioned screws of the RO group showed a lateral deviation . Attachment of the robot to the spine seems a vulnerable aspect potentially leading to screw malposition as well as slipping of the implantation cannula at the screw entrance point Purpose While image guidance and neuronavigation have enabled a more accurate placement of pedicle implants , they can inconvenience the surgeon . Robot-assisted placement of pedicle screws appears to overcome these disadvantages . However , recent data concerning the superiority of currently available robots in assisting spinal surgeons are conflicting . The aim of our study was to evaluate the percentage of accurately placed pedicle screws , inserted using a new robotic-guidance system . Method 20 Patients were operated on successively by the same surgeon using robotic assistance ( ROSA ™ , Medtech ) ( Rosa group 10 patients , n = 40 screws ) or by the freeh and conventional technique ( Freeh and group 10 patients , n = 50 screws ) . Patient characteristics as well as the duration of the operation and of exposure to X rays were recorded . Results The mean age of patients in each group ( RG and FHG ) was 63 years . Mean BMI and operating time among the RG and FHG were , respectively , 26 and 27 kg/m2 , and 187 and 119 min . Accurate placement of the implant ( score A and B of the Gertzbein Robbins classification ) was achieved in 97.3 % of patients in the RG ( n = 36 ) and in 92 % of those in the FHG ( n = 50 ) . Four implants in the RG were placed manually following failed robotic assistance . Conclusion We report a higher rate of precision with robotic as compared to the FH technique . Providing assistance by permanently monitoring the patient ’s movements , this image-guided tool helps more accurately pinpoint the pedicle entry point and control the trajectory . Limitations of the study include its small sized and non-r and omized sample . Nevertheless , these preliminary results are encouraging for the development of new robotic techniques for spinal surgery Introduction Many laparoscopic surgeons report musculoskeletal symptoms that are thought to be related to the ergonomic stress of performing laparoscopy . Robotic surgical systems may address many of these limitations . To date , however , there have been no studies exploring the quantitative ergonomics of robotic surgery . In this study , we sought to compare the activation of bilateral biceps , triceps , deltoid , and trapezius muscle groups during traditional laparoscopic surgery ( TLS ) and robot-assisted laparoscopic surgery ( RALS ) procedures , as quantified by surface electromyography ( sEMG ) . Methods One surgeon with expertise in TLS and RALS performed 18 operative procedures ( 13 TLS , 5 RALS ) while sEMG measurements were obtained from bilateral biceps , triceps , deltoid , and trapezius muscles . sEMG measurements were normalized to the maximum voluntary contraction of each muscle ( % MVC ) . We compared mean % MVC values for each muscle group during TLS and RALS with unpaired t-tests and considered differences with a p value < 0.05 to be statistically significant . Results Muscle activation was higher during TLS compared to RALS in bilateral biceps ( L Biceps RALS:1.01 % MVC , L Biceps TLS:3.14 , p = 0.01 ; R Biceps RALS:1.81 % MVC , R Biceps TLS:4.53 , p = 0.0002 ) . Muscle activation was higher during TLS compared to RALS in bilateral triceps ( L Triceps RALS:1.73 % MVC , L Triceps TLS:3.58 , p = 0.04 ; R Triceps RALS:1.59 % MVC , R Triceps TLS:5.11 , p = 0.02 ) . Muscle activation was higher during TLS compared to RALS in bilateral deltoids ( L Deltoid RALS:1.50 % MVC , L Deltoid TLS:3.68 , p = 0.03 ; R Deltoid RALS:1.19 % MVC , R Deltoid TLS:2.57 , p = 0.01 ) . Significant differences were not detected in the bilateral trapezius muscles ( L Trapezius RALS:1.50 % MVC , L Trapezius TLS:3.68 , p = 0.03 ; R Trapezius RALS:1.19 % MVC , R Trapezius TLS:2.57 , p = 0.01 ) . Discussion We have quantitatively examined the ergonomics of TLS and RALS and shown that in a single surgeon , TLS procedures are associated with significantly elevated biceps , triceps , and deltoid activation bilaterally when compared to RALS procedures BACKGROUND Spinal fusion is a commonly performed procedure for a variety of conditions . Pedicle screw fixation has become the st and ard of care for stabilization of the thoracic and lumbar spine . Precise screw placement is essential to avoid injury to adjacent neural structures . Patients with severe deformity or prior surgery present a challenge to the accurate placement of pedicle screws . Additionally , minimally invasive and percutaneous surgical techniques also present a greater challenge to accurate screw placement and require heavier reliance on intraoperative fluoroscopic imaging , which presents an occupational hazard for the surgeon and the operating-room ( OR ) staff . The purpose of this paper is to introduce the SpineAssist , a miniature robotic guidance system , developed to assist spine surgeons in the accurate placement of pedicle screws . METHODS The operative technique is described , as is the experience and results with 14 patients during a 6 month period during which this system was used . RESULTS The SpineAssist performed successfully in 93 % of the cases in which it was used . 96 % of the screws placed were determined to be within 1 mm of their planned trajectory . CONCLUSIONS Difficulties encountered with use of the SpineAssist , while minimal , will be described and suggestions made for future improvements BACKGROUND CONTEXT There have been conflicting results on the surgical outcome of lumbar fusion surgery using two different techniques : robot-assisted pedicle screw fixation and conventional freeh and technique . In addition , there have been no studies about the biomechanical issues between both techniques . PURPOSE This study aim ed to investigate the biomechanical properties in terms of stress at adjacent segments using robot-assisted pedicle screw insertion technique ( robot-assisted , minimally invasive posterior lumbar interbody fusion , Rom-PLIF ) and freeh and technique ( conventional , freeh and , open approach , posterior lumbar interbody fusion , Cop-PLIF ) for instrumented lumbar fusion surgery . STUDY DESIGN This is an additional post-hoc analysis for patient-specific finite element ( FE ) model . PATIENT SAMPLE The sample is composed of patients with degenerative lumbar disease . OUTCOME MEASURES Intradiscal pressure and facet contact force are the outcome measures . METHODS Patients were r and omly assigned to undergo an instrumented PLIF procedure using a Rom-PLIF ( 37 patients ) or a Cop-PLIF ( 41 ) , respectively . Five patients in each group were selected using a simple r and om sampling method after operation , and 10 preoperative and postoperative lumbar spines were modeled from preoperative high-resolution computed tomography of 10 patients using the same method for a vali date d lumbar spine model . Under four pure moments of 7.5 Nm , the changes in intradiscal pressure and facet joint contact force at the proximal adjacent segment following fusion surgery were analyzed and compared with preoperative states . RESULTS The representativeness of r and om sample s was verified . Both groups showed significant increases in postoperative intradiscal pressure at the proximal adjacent segment under four moments , compared with the preoperative state . The Cop-PLIF models demonstrated significantly higher percent increments of intradiscal pressure at proximal adjacent segments under extension , lateral bending , and torsion moments than the Rom-PLIF models ( p=.032 , p=.008 , and p=.016 , respectively ) . Furthermore , the percent increment of facet contact force was significantly higher in the Cop-PLIF models under extension and torsion moments than in the Rom-PLIF models ( p=.016 under both extension and torsion moments ) . CONCLUSIONS The present study showed the clinical application of subject-specific FE analysis in the spine . Even though there was biomechanical superiority of the robot-assisted insertions in terms of alleviation of stress increments at adjacent segments after fusion , cautious interpretation is needed because of the small sample size BACKGROUND The purpose of this study was to compare the accuracy and safety of an instrumented posterior lumbar interbody fusion ( PLIF ) using a robot-assisted minimally invasive ( Robot-PLIF ) or a conventional open approach ( Freeh and -PLIF ) . METHODS Patients undergoing an instrumented PLIF were r and omly assigned to be treated using a Robot-PLIF ( 37 patients ) and a Freeh and -PLIF ( 41 patients ) . RESULTS For intrapedicular accuracy , there was no significant difference between the groups ( P = 0.534 ) . For proximal facet joint accuracy , none of the 74 screws in the Robot-PLIF group violated the proximal facet joint , while 13 of 82 in the Freeh and -PLIF group violated the proximal facet joint ( P < 0.001 ) . The average distance of the screws from the facets was 5.2 ± 2.1 mm and 2.7 ± 1.6 mm in the Robot-PLIF and Freeh and -PLIF groups , respectively ( P < 0.001 ) . CONCLUSION Robotic-assisted pedicle screw placement was associated with fewer proximal facet joint violations and better convergence orientations INTRODUCTION Transforaminal lumbar interbody fusion with a minimally invasive approach ( MIS TLIF ) has become a very popular technique in the treatment of degenerative diseases of the lumbar spine , as it allows a decrease in muscle iatrogenic . However , iterative radiological controls inherent to this technique are responsible for a significant increase in exposure to ionizing radiation for the surgeon . New techniques for radiological guidance ( O-arm navigation-assisted ) would overcome this drawback , but this remains unproven . OBJECTIVES To analyze the exposure of the surgeon to intraoperative X-ray during a MIS TLIF under fluoroscopy and under O-arm navigation-assisted . MATERIAL S AND METHODS This prospect i ve study was conducted at the University Hospital of Lille from February to May 2013 . Twelve patients underwent a MIS TLIF for the treatment of low- grade spondylolisthesis ; six under st and ard fluoroscopy ( group 1 ) and six under O-arm system ( group 2 ) . Passive dosimeters ( rings and glasses ) and active dosimeters for thorax were used to measure the radiation exposure of the surgeon . RESULTS For group 1 , the average time of fluoroscopy was 3.718 minutes ( 3.13 - 4.56 ) while no radioscopy was perform on group 2 . For the first group , the average exposure dose was 12 μSv ( 5 - 20 μSv ) on the thorax , 1168 μSv ( 510 - 2790 μSv ) on the main h and and 179 μSv ( 103 - 486 μSv ) on the lens . The exposure dose was measured zero on the second group . CONCLUSION The maximum recommended doses can be reached , mainly for the lens . In addition to the radioprotection measures , O-arm navigation systems are safe alternatives to significantly reduce surgeon exposure |
13,957 | 26,692,557 | CONCLUSIONS Collaborative depression care did not lead to a sustained reduction in the primary MACE end point .
Small effects were observed for depression , depression remission , anxiety and mental QOL . | OBJECTIVES To systematic ally review the efficacy of collaborative care ( CC ) for depression in adults with coronary heart disease ( CHD ) and depression . | This paper describes the rationale and design of the vanguard for the Comparison of Depression Interventions after Acute Coronary Syndrome ( CODIACS ) , a multicenter , r and omized , controlled trial of a patient preference-based , stepped care protocol for persistent depressive symptoms after acute coronary syndrome ( ACS ) . The overall aim of the vanguard phase was to determine whether the patient-preference , stepped care protocol , which is based on the intervention used in the recent Coronary Psychosocial Evaluation Studies ( COPES ) trial , was feasible in patients with recent ACS who were recruited from 5 geographically diverse sites . Innovative design features of this trial include r and omization to either initial patient-preference of treatment or to a referred care arm in which the primary care provider decided upon care . Additionally , delivery of psychotherapy was accomplished by telephone , or webcam , depending upon patient preference . The vanguard phase provides estimates of eligibility and screening/enrollment ratios , patient acceptance of screening , and retention . In this report , we describe the innovative features and the baseline results of the vanguard phase of CODIACS . The data from this vanguard study will be used to finalize planning for a large , phase III clinical trial design ed to evaluate the effect of treatment on depressive symptoms , coronary events , and death CONTEXT Depression and low perceived social support ( LPSS ) after myocardial infa rct ion ( MI ) are associated with higher morbidity and mortality , but little is known about whether this excess risk can be reduced through treatment . OBJECTIVE To determine whether mortality and recurrent infa rct ion are reduced by treatment of depression and LPSS with cognitive behavior therapy ( CBT ) , supplemented with a selective serotonin reuptake inhibitor ( SSRI ) antidepressant when indicated , in patients enrolled within 28 days after MI . DESIGN , SETTING , AND PATIENTS R and omized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients ( 1084 women , 1397 men ) enrolled from 8 clinical centers . Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression ( HRSD ) ; LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) Social Support Instrument ( ESSI ) . R and om allocation was to usual medical care or CBT-based psychosocial intervention . INTERVENTION Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months , plus group therapy when feasible , with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50 % reduction in Beck Depression Inventory scores after 5 weeks . MAIN OUTCOME MEASURES Composite primary end point of death or recurrent MI ; secondary outcomes included change in HRSD ( for depression ) or ESSI scores ( for LPSS ) at 6 months . RESULTS Improvement in psychosocial outcomes at 6 months favored treatment : mean ( SD ) change in HRSD score , -10.1 ( 7.8 ) in the depression and psychosocial intervention group vs -8.4 ( 7.7 ) in the depression and usual care group ( P<.001 ) ; mean ( SD ) change in ESSI score , 5.1 ( 5.9 ) in the LPSS and psychosocial intervention group vs 3.4 ( 6.0 ) in the LPSS and usual care group ( P<.001 ) . After an average follow-up of 29 months , there was no significant difference in event-free survival between usual care ( 75.9 % ) and psychosocial intervention ( 75.8 % ) . There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups ( depression , LPSS , and depression and LPSS patients ) . CONCLUSIONS The intervention did not increase event-free survival . The intervention improved depression and social isolation , although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients Background Community studies reveal people with coronary heart disease ( CHD ) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions . There is evidence for the efficacy of collaborative care and case management for depression treatment , and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological , pharmacological , or combined treatments , these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care setting s. Methods This pilot r and omised controlled trial will evaluate whether a simple intervention involving a personalised care plan , elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients . The comparator group will be usual general practitioner ( GP ) care.81 participants have been recruited from CHD registers of 15 South London general practice s. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale ( HADS-D ) together with symptomatic CHD identified using the Modified Rose Angina Question naire . Consenting participants are r and omly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant ’s physical and mental health needs which are documented in a care plan , followed by regular telephone review s by the case manager over a 6-month period . At each review , the intervention participant ’s mood , function and identified problems are review ed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient ’s self efficacy to solve their problems . Depressive symptoms measured by HADS score will be collected at baseline and 1 , 6- and 12 months post r and omisation . Other outcomes include CHD symptoms , quality of life , wellbeing and health service utilisation . Discussion This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care . Trial registration IS RCT N21615909 Background In the presence of type 2 diabetes ( T2DM ) or coronary heart disease ( CHD ) , depression is under diagnosed and under treated despite being associated with worse clinical outcomes . Our earlier pilot study demonstrated that it was feasible , acceptable and affordable for practice nurses to extend their role to include screening for and monitoring of depression alongside biological and lifestyle risk factors . The current study will compare the clinical outcomes of our model of practice nurse-led collaborative care with usual care for patients with depression and T2DM or CHD . Methods This is a cluster-r and omised intervention trial . Eighteen general practice s from regional and metropolitan areas agreed to join this study , and were allocated r and omly to an intervention or control group . We aim to recruit 50 patients with co-morbid depression and diabetes or heart disease from each of these practice s. In the intervention group , practice nurses ( PNs ) will be trained for their enhanced roles in this nurse-led collaborative care study . Patients will be invited to attend a practice nurse consultation every 3 months prior to seeing their usual general practitioner . The PN will assess psychological , physiological and lifestyle parameters then work with the patient to set management goals . The outcome of this assessment will form the basis of a GP Management Plan document . In the control group , the patients will continue to receive their usual care for the first six months of the study before the PNs undergo the training and switch to the intervention protocol . The primary clinical outcome will be a reduction in the depression score . The study will also measure the impact on physiological measures , quality of life and on patient attitude to health care delivered by practice nurses . Conclusion The strength of this programme is that it provides a sustainable model of chronic disease management with monitoring and self-management assistance for physiological , lifestyle and psychological risk factors for high-risk patients with co-morbid depression , diabetes or heart disease . The study will demonstrate whether nurse-led collaborative care achieves better outcomes than usual care BACKGROUND Patients with depression and poorly controlled diabetes , coronary heart disease , or both have an increased risk of adverse outcomes and high health care costs . We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients . METHODS We conducted a single-blind , r and omized , controlled trial in 14 primary care clinics in an integrated health care system in Washington State , involving 214 participants with poorly controlled diabetes , coronary heart disease , or both and coexisting depression . Patients were r and omly assigned to the usual-care group or to the intervention group , in which a medically supervised nurse , working with each patient 's primary care physician , provided guideline -based , collaborative care management , with the goal of controlling risk factors associated with multiple diseases . The primary outcome was based on simultaneous modeling of glycated hemoglobin , low-density lipoprotein ( LDL ) cholesterol , and systolic blood-pressure levels and Symptom Checklist-20 ( SCL-20 ) depression outcomes at 12 months ; this modeling allowed estimation of a single overall treatment effect . RESULTS As compared with controls , patients in the intervention group had greater overall 12-month improvement across glycated hemoglobin levels ( difference , 0.58 % ) , LDL cholesterol levels ( difference , 6.9 mg per deciliter [ 0.2 mmol per liter ] ) , systolic blood pressure ( difference , 5.1 mm Hg ) , and SCL-20 depression scores ( difference , 0.40 points ) ( P<0.001 ) . Patients in the intervention group also were more likely to have one or more adjustments of insulin ( P=0.006 ) , antihypertensive medications ( P<0.001 ) , and antidepressant medications ( P<0.001 ) , and they had better quality of life ( P<0.001 ) and greater satisfaction with care for diabetes , coronary heart disease , or both ( P<0.001 ) and with care for depression ( P<0.001 ) . CONCLUSIONS As compared with usual care , an intervention involving nurses who provided guideline -based , patient-centered management of depression and chronic disease significantly improved control of medical disease and depression . ( Funded by the National Institute of Mental Health ; Clinical Trials.gov number , NCT00468676 . ) Objectives To determine the effectiveness of collaborative care in reducing depression in primary care patients with diabetes or heart disease using practice nurses as case managers . Design A two-arm open r and omised cluster trial with wait-list control for 6 months . The intervention was followed over 12 months . Setting Eleven Australian general practice s , five r and omly allocated to the intervention and six to the control . Participants 400 primary care patients ( 206 intervention , 194 control ) with depression and type 2 diabetes , coronary heart disease or both . Intervention The practice nurse acted as a case manager identifying depression , review ing pathology results , lifestyle risk factors and patient goals and priorities . Usual care continued in the controls . Main outcome measure A five-point reduction in depression scores for patients with moderate-to-severe depression . Secondary outcome was improvements in physiological measures . Results Mean depression scores after 6 months of intervention for patients with moderate-to-severe depression decreased by 5.7±1.3 compared with 4.3±1.2 in control , a significant ( p=0.012 ) difference . ( The plus – minus is the 95 % confidence range . ) Intervention practice s demonstrated adherence to treatment guidelines and intensification of treatment for depression , where exercise increased by 19 % , referrals to exercise programmes by 16 % , referrals to mental health workers ( MHWs ) by 7 % and visits to MHWs by 17 % . Control- practice exercise did not change , whereas referrals to exercise programmes dropped by 5 % and visits to MHWs by 3 % . Only referrals to MHW increased by 12 % . Intervention improvements were sustained over 12 months , with a significant ( p=0.015 ) decrease in 10-year cardiovascular disease risk from 27.4±3.4 % to 24.8±3.8 % . A review of patients indicated that the study 's safety protocol s were followed . Conclusions TrueBlue participants showed significantly improved depression and treatment intensification , sustained over 12 months of intervention and reduced 10-year cardiovascular disease risk . Collaborative care using practice nurses appears to be an effective primary care intervention . Trial registration ACTRN12609000333213 ( Australia and New Zeal and Clinical Trials Registry ) Objective : To present the design of the Bypassing the Blues ( BtB ) study to examine the impact of a collaborative care strategy for treating depression among patients with cardiac disease . Coronary artery bypass graft ( CABG ) surgery is one of the most common and costly medical procedures performed in the US . Up to half of post-CABG patients report depressive symptoms , and they are more likely to experience poorer health-related quality of life ( HRQoL ) , worse functional status , continued chest pains , and higher risk of cardiovascular morbidity independent of cardiac status , medical comorbidity , and the extent of bypass surgery . Methods : BtB was design ed to enroll 450 post-CABG patients from eight Pittsburgh-area hospitals including : ( 1 ) 300 patients who expressed mood symptoms preceding discharge and at 2 weeks post hospitalization ( Patient Health Question naire ( PHQ-9 ) ≥10 ) ; and ( 2 ) 150 patients who served as nondepressed controls ( PHQ-9 < 5 ) . Depressed patients were r and omized to either an 8-month course of nurse-delivered telephone-based collaborative care supervised by a psychiatrist and primary care expert , or to their physicians ’ “ usual care . ” The primary hypothesis will test whether the intervention can produce an effect size of ≥0.5 improvement in HRQoL at 8 months post CABG , as measured by the SF-36 Mental Component Summary score . Secondary hypotheses will examine the impact of our intervention on mood symptoms , cardiovascular morbidity , employment , health services utilization , and treatment costs . Results : Not applicable . Conclusions : This effectiveness trial will provide crucial information on the impact of a widely generalizable evidence -based collaborative care strategy for treating depressed patients with cardiac disease PURPOSE We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications , depression outcomes , and blood pressure control among older primary care patients . METHODS Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were r and omly assigned to an integrated care intervention or usual care . Outcomes were assessed at baseline , 2 , 4 , and 6 weeks using the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression , an electronic monitor to measure blood pressure , and the Medication Event Monitoring System to assess adherence . RESULTS In all , 64 participants aged 50 to 80 years participated . Participants in the integrated care intervention had fewer depressive symptoms ( CES-D mean scores , intervention 9.9 vs usual care 19.3 ; P < .01 ) , lower systolic blood pressure ( intervention 127.3 mm Hg vs usual care 141.3 mm Hg ; P < .01 ) , and lower diastolic blood pressure ( intervention 75.8 mm Hg vs usual care 85.0 mm Hg ; P < .01 ) compared with participants in the usual care group at 6 weeks . Compared with the usual care group , the proportion of participants in the intervention group who had 80 % or greater adherence to an antidepressant medication ( intervention 71.9 % vs usual care 31.3 % ; P < .01 ) and to an antihypertensive medication ( intervention 78.1 % vs usual care 31.3 % ; P < .001 ) was greater at 6 weeks . CONCLUSION A pilot , r and omized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes . Integrated interventions may be more feasible and effective in real-world practice s , where there are competing dem and s for limited re sources Background To systematic ally review in- and outpatient costs in patients with coronary artery disease ( CAD ) and comorbid mental disorders . Methods A comprehensive data base search was conducted for studies investigating persons with CAD and comorbid mental disorders ( Medline , EMBASE , PsycINFO , Psyndex , EconLit , IBSS ) . All studies were included which allowed a comparison of in- and outpatient health care costs ( assessed either monetarily or in terms of health care utilization ) of CAD patients with comorbid mental disorders ( mood , anxiety , alcohol , eating , somatoform and personality disorders ) and those without . R and om effects meta-analyses were conducted and results reported using forest plots . Results The literature search result ed in 7,275 potentially relevant studies , of which 52 met inclusion criteria . Hospital readmission rates were increased in CAD patients with any mental disorder ( pooled st and ardized mean difference ( SMD ) = 0.34 [ 0.17;0.51 ] ) . Results for depression , anxiety and posttraumatic stress disorder pointed in the same direction with heterogeneous SMDs on a primary study level ranging from −0.44 to 1.26 . Length of hospital stay was not increased in anxiety and any mental disorder , while studies on depression reported heterogeneous SMDs ranging from −0.08 to 0.82 . Most studies reported increased overall and outpatient costs for patients with comorbid mental disorders . Results for invasive procedures were non-significant respectively inconclusive . Conclusions Comorbid mental disorders in CAD patients are associated with an increased healthcare utilization in terms of higher hospital readmission rates and increased overall and outpatient health care costs . From a health care point of view , it is requisite to improve the diagnosis and treatment of comorbid mental disorders in patients with CAD to minimize incremental costs Background Co-morbid major depression is a significant problem among patients with type 2 diabetes mellitus and /or coronary heart disease and this negatively impacts quality of life . Subthreshold depression is the most important risk factor for the development of major depression . Given the highly significant association between depression and adverse health outcomes and the limited capacity for depression treatment in primary care , there is an urgent need for interventions that successfully prevent the transition from subthreshold depression into a major depressive disorder . Nurse led stepped-care is a promising way to accomplish this . The aim of this study is to evaluate the cost-effectiveness of a nurse-led indicated stepped-care program to prevent major depression among patients with type 2 diabetes mellitus and /or coronary heart disease in primary care who also have subthreshold depressive symptoms . Methods / design An economic evaluation will be conducted alongside a cluster-r and omized controlled trial in approximately thirty general practice s in the Netherl and s. R and omization takes place at the level of participating practice nurses . We aim to include 236 participants who will either receive a nurse-led indicated stepped-care program for depressive symptoms or care as usual . The stepped-care program consists of four sequential but flexible treatment steps : 1 ) watchful waiting , 2 ) guided self-help treatment , 3 ) problem solving treatment and 4 ) referral to the general practitioner . The primary clinical outcome measure is the cumulative incidence of major depressive disorder as measured with the Mini International Neuropsychiatric Interview . Secondary outcomes include severity of depressive symptoms , quality of life , anxiety and physical outcomes . Costs will be measured from a societal perspective and include health care utilization , medication and lost productivity costs . Measurements will be performed at baseline and 3 , 6 , 9 and 12 months . Discussion The intervention being investigated is expected to prevent new cases of depression among people with type 2 diabetes mellitus and /or coronary heart disease and subthreshold depression , with subsequent beneficial effects on quality of life , clinical outcomes and health care costs . When proven cost-effective , the program provides a viable treatment option in the Dutch primary care system . Trial registration Dutch Trial Register Objective To test the effectiveness of an integrated collaborative care model for people with depression and long term physical conditions . Design Cluster r and omised controlled trial . Setting 36 general practice s in the north west of Engl and . Participants 387 patients with a record of diabetes or heart disease , or both , who had depressive symptoms ( ≥10 on patient health question aire-9 ( PHQ-9 ) ) for at least two weeks . Mean age was 58.5 ( SD 11.7 ) . Participants reported a mean of 6.2 ( SD 3.0 ) long term conditions other than diabetes or heart disease ; 240 ( 62 % ) were men ; 360 ( 90 % ) completed the trial . Interventions Collaborative care included patient preference for behavioural activation , cognitive restructuring , grade d exposure , and /or lifestyle advice , management of drug treatment , and prevention of relapse . Up to eight sessions of psychological treatment were delivered by specially trained psychological wellbeing practitioners employed by Improving Access to Psychological Therapy services in the English National Health Service ; integration of care was enhanced by two treatment sessions delivered jointly with the practice nurse . Usual care was st and ard clinical practice provided by general practitioners and practice nurses . Main outcome measures The primary outcome was reduction in symptoms of depression on the self reported symptom checklist-13 depression scale ( SCL-D13 ) at four months after baseline assessment . Secondary outcomes included anxiety symptoms ( generalised anxiety disorder 7 ) , self management ( health education impact question naire ) , disability ( Sheehan disability scale ) , and global quality of life ( WHOQOL-BREF ) . Results 19 general practice s were r and omised to collaborative care and 20 to usual care ; three practice s withdrew from the trial before patients were recruited . 191 patients were recruited from practice s allocated to collaborative care , and 196 from practice s allocated to usual care . After adjustment for baseline depression score , mean depressive scores were 0.23 SCL-D13 points lower ( 95 % confidence interval −0.41 to −0.05 ) in the collaborative care arm , equal to an adjusted st and ardised effect size of 0.30 . Patients in the intervention arm also reported being better self managers , rated their care as more patient centred , and were more satisfied with their care . There were no significant differences between groups in quality of life , disease specific quality of life , self efficacy , disability , and social support . Conclusions Collaborative care that incorporates brief low intensity psychological therapy delivered in partnership with practice nurses in primary care can reduce depression and improve self management of chronic disease in people with mental and physical multimorbidity . The size of the treatment effects were modest and were less than the prespecified effect but were achieved in a trial run in routine setting s with a deprived population with high levels of mental and physical multimorbidity . Trial registration IS RCT N80309252 IMPORTANCE Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events . There has been minimal study of collaborative care ( CC ) management models for mental health disorders in high-risk cardiac in patients , and no prior CC intervention has simultaneously managed depression and anxiety disorders . OBJECTIVE To determine the impact of a low-intensity CC intervention for depression , generalized anxiety disorder , and panic disorder among patients hospitalized for an acute cardiac illness . DESIGN , SETTING , AND PARTICIPANTS Single-blind r and omized clinical trial , with study assessors blind to group assignment , from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome , arrhythmia , or heart failure and found to have clinical depression , generalized anxiety disorder , or panic disorder on structured assessment . INTERVENTIONS Participants were r and omized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders ( n = 92 ) or to enhanced usual care ( serial notification of primary medical providers ; n = 91 ) . The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate . MAIN OUTCOMES AND MEASURES Improvement in mental health-related quality of life ( Short Form-12 Mental Component Score [ SF-12 MCS ] ) at 24 weeks , compared between groups using a r and om-effects model in an intent-to-treat analysis . RESULTS Patients r and omized to CC had significantly greater estimated mean improvements in SF-12 MCS at 24 weeks ( 11.21 points [ from 34.21 to 45.42 ] in the CC group vs 5.53 points [ from 36.30 to 41.83 ] in the control group ; estimated mean difference , 5.68 points [ 95 % CI , 2.14 - 9.22 ] ; P = .002 ; effect size , 0.61 ) . Patients receiving CC also had significant improvements in depressive symptoms and general functioning , and higher rates of treatment of a mental health disorder ; anxiety scores , rates of disorder response , and adherence did not differ between groups . CONCLUSIONS AND RELEVANCE A novel telephone-based , low-intensity model to concurrently manage cardiac patients with depression and /or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01201967 IMPORTANCE Controversy remains about whether depression can be successfully managed after acute coronary syndrome ( ACS ) and the costs and benefits of doing so . OBJECTIVE To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs . DESIGN Multicenter r and omized controlled trial . SETTING Patients were recruited from 2 private and 5 academic ambulatory centers across the United States . PARTICIPANTS A total of 150 patients with elevated depressive symptoms ( Beck Depression Inventory [ BDI ] score ≥10 ) 2 to 6 months after an ACS , recruited between March 18 , 2010 , and January 9 , 2012 . INTERVENTIONS Patients were r and omized to 6 months of central ized depression care ( patient preference for problem-solving treatment given via telephone or the Internet , pharmacotherapy , both , or neither ) , stepped every 6 to 8 weeks ( active treatment group ; n = 73 ) , or to locally determined depression care after physician notification about the patient 's depressive symptoms ( usual care group ; n = 77 ) . MAIN OUTCOME MEASURES Change in depressive symptoms during 6 months and total health care costs . RESULTS Depressive symptoms decreased significantly more in the active treatment group than in the usual care group ( differential change between groups , -3.5 BDI points ; 95 % CI , -6.1 to -0.7 ; P = .01 ) . Although mental health care estimated costs were higher for active treatment than for usual care , overall health care estimated costs were not significantly different ( difference adjusting for confounding , -$325 ; 95 % CI , -$2639 to $ 1989 ; P = .78 ) . CONCLUSIONS For patients with post-ACS depression , active treatment had a substantial beneficial effect on depressive symptoms . This kind of depression care is feasible , effective , and may be cost-neutral within 6 months ; therefore , it should be tested in a large phase 3 pragmatic trial . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01032018 BACKGROUND Given the prevalence of cardiovascular disease and the high rates of depression among cardiac patients , there is a need to develop practical ways to identify this population and provide pragmatic general-practitioner-based interventions for managing depression as a comorbid condition . METHOD The Identifying Depression As a Comorbid Condition ( IDACC ) study employed a hybrid design , incorporating a r and omized controlled trial nested within a prospect i ve cohort study . IDACC screened for depression in patients hospitalized in South Australia for a range of cardiac conditions , with outcome measures monitored for 12 months after discharge . The subgroup identified as depressed was entered into the nested IDACC trial , which tests the hypothesis that identifying depression and offering an evidence -based intervention to general practitioners , incorporating multidisciplinary telephone case conferencing , will reduce levels of depression , improve quality of life , and reduce associated economic costs . RESULTS At baseline , 46.3 % of 1455 participants screened were classified as depression cases on the basis of their score on the Center for Epidemiological Studies Depression Scale ( > or = 16 ) or the Hospital Anxiety and Depression Scale ( > or = 8) . Elevated scores were associated with being younger , female , divorced or separated , not employed , living alone , having a lower level of education , and having poorer health and quality of life . Nearly one fifth ( 19.4 % ) of participants had Center for Epidemiological Studies Depression Scale scores > 27 , which is indicative of major depression . CONCLUSIONS This project confirms , in an Australian setting , the high prevalence of depressive symptoms among hospitalized cardiac patients . Follow-up over 12 months will enhance underst and ing of the natural history of depression in cardiac patients , while the nested trial will inform on effectiveness of an intervention involving tailored advice and support to general practitioners OBJECTIVE The Patient Health Question naire-9 ( PHQ-9 ) is increasingly used as a depression assessment tool in cardiac patients . However , in contrast to older depression instruments , there is little data linking PHQ-9 scores to adverse cardiac outcomes . Our goal was to evaluate whether higher PHQ-9 scores were predictive of subsequent cardiac readmissions among depressed patients hospitalized for an acute cardiac event . METHODS Patients diagnosed with depression during hospitalization for acute coronary syndrome , heart failure , or arrhythmia were enrolled in a r and omized depression management trial . Participants were administered PHQ-9 at enrollment , and data was collected regarding cardiac readmissions and mortality over the next 6months . To evaluate the independent association of PHQ-9 score with subsequent cardiac readmission , Cox regression analysis that included relevant sociodemographic and medical covariates was used . Survival analysis examining time to first event , stratified by quartile of initial PHQ-9 score , was performed using Kaplan-Meier curves and log-rank test for trend . Analyses were then repeated using a composite ( cardiac readmission or mortality ) outcome . RESULTS Among 172 subjects , 62 ( 36.0 % ) had a cardiac-related rehospitalization . Higher initial PHQ-9 score predicted cardiac-related rehospitalization , independent of multiple relevant covariates ( hazard ratio 1.09 [ 95 % confidence interval=1.02 - 1.17 ] ; p=0.015 ) . On survival analysis , log-rank test for trend revealed a significant rise in event rates across increasing PHQ-9 quartiles ( χ(2)=6.36 ; p=0.012 ) . Findings were similar ( p<.05 ) for the composite outcome . CONCLUSION In depressed cardiac patients , each additional point on the PHQ-9 was independently associated with a 9 % greater risk of cardiac readmission over the subsequent 6months OBJECTIVE To determine the 12-month cost-effectiveness of a collaborative care ( CC ) program for treating depression following coronary artery bypass graft ( CABG ) surgery versus physicians ' usual care ( UC ) . METHODS We obtained 12 continuous months of Medicare and private medical insurance cl aims data on 189 patients who screened positive for depression following CABG surgery , met criteria for depression when reassessed by telephone 2 weeks following hospitalization ( nine-item Patient Health Question naire ≥10 ) and were r and omized to either an 8-month central ized , nurse-provided and telephone-delivered CC intervention for depression or to their physicians ' UC . RESULTS At 12 months following r and omization , CC patients had $ 2068 lower but statistically similar estimated median costs compared to UC ( P=.30 ) and a variety of sensitivity analyses produced no significant changes . The incremental cost-effectiveness ratio of CC was -$9889 ( -$11,940 to -$7838 ) per additional quality -adjusted life-year ( QALY ) , and there was 90 % probability it would be cost-effective at the willingness to pay threshold of $ 20,000 per additional QALY . A bootstrapped cost-effectiveness plane also demonstrated a 68 % probability of CC " dominating " UC ( more QALYs at lower cost ) . CONCLUSIONS Central ized , nurse-provided and telephone-delivered CC for post-CABG depression is a quality -improving and cost-effective treatment that meets generally accepted criteria for high-value care BACKGROUND Depression and anxiety in cardiac patients are independently associated with adverse cardiovascular outcomes , including mortality . Collaborative care ( CC ) programs , which use care managers to assess patients , coordinate care , and perform therapeutic interventions , have proven effective in managing depression in this population . However , no prior CC intervention has simultaneously managed depression and anxiety disorders , and there has been minimal study of CC in high-risk cardiac in patients . MATERIAL S AND METHODS The Management of Sadness and Anxiety in Cardiology ( MOSAIC ) study was a prospect i ve r and omized trial of a low-intensity CC intervention , compared to enhanced usual care , for patients hospitalized for acute coronary syndrome , heart failure , or arrhythmia , and diagnosed with depression , generalized anxiety disorder ( GAD ) , or panic disorder ( PD ) . The primary outcome measure for MOSAIC was mental health-related quality of life ( HRQoL ) , measured using the Medical Outcomes Study Short Form-12 . Additional outcomes included psychological , functional , and medical outcomes , including rehospitalizations . RESULTS A total of 183 eligible participants were enrolled ( 92 collaborative care , 91 enhanced usual care ) ; 94 % of depressed patients reported being depressed for > 1month , and 53 % of those with GAD reported clinical ly significant anxiety for > 1year . One hundred thirty-three patients had depression , 118 had GAD , and 19 had PD ; 74 participants ( 40 % ) had two or more of the disorders . CONCLUSION The MOSAIC trial will provide data regarding whether an intervention that concurrently manages these common psychiatric disorders results in meaningful improvements in HRQoL , psychiatric symptoms , and medical outcomes in cardiac patients at high risk for adverse outcomes BACKGROUND Depressive symptoms are an established predictor of mortality and major adverse cardiac events ( defined as nonfatal myocardial infa rct ion or hospitalization for unstable angina or urgent/emergency revascularizations ) in patients with acute coronary syndrome ( ACS ) . This study was conducted to determine the acceptability and efficacy of enhanced depression treatment in patients with ACS . METHODS A 3-month observation period to identify patients with ACS and persistent depressive symptoms was followed by a 6-month r and omized controlled trial . From January 1 , 2005 , through February 29 , 2008 , 237 patients with ACS from 5 hospitals were enrolled , including 157 persistently depressed patients r and omized to intervention ( initial patient preference for problem-solving therapy and /or pharmacotherapy , then a stepped-care approach ; 80 patients ) or usual care ( 77 patients ) and 80 nondepressed patients who underwent observational evaluation . The primary outcome was patient satisfaction with depression care . Secondary outcomes were depressive symptom changes ( assessed with the Beck Depression Inventory ) , major adverse cardiac events , and death . RESULTS At the end of the trial , the proportion of patients who were satisfied with their depression care was higher in the intervention group ( 54 % of 80 ) than in the usual care group ( 19 % of 77 ) ( odds ratio , 5.4 ; 95 % confidence interval [ CI ] , 2.2 - 12.9 [ P < .001 ] ) . The Beck Depression Inventory score decreased significantly more ( t(155 ) = 2.85 [ P = .005 ] ) for intervention patients ( change , -5.7 ; 95 % CI , -7.6 to -3.8 ; df = 155 ) than for usual care patients ( change , -1.9 ; 95 % CI , -3.8 to -0.1 ; df = 155 ) ; the depression effect size was 0.59 of the st and ard deviation . At the end of the trial , 3 intervention patients and 10 usual care patients had experienced major adverse cardiac events ( 4 % and 13 % , respectively ; log-rank test , chi(2)(1 ) = 3.93 [ P = .047 ] ) , as well as 5 nondepressed patients ( 6 % ) ( for the intervention vs nondepressed cohort , chi(2)(1 ) = 0.48 [ P = .49 ] ) . CONCLUSION Enhanced depression care for patients with ACS was associated with greater satisfaction , a greater reduction in depressive symptoms , and a promising improvement in prognosis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00158054 BACKGROUND Depression in cardiac patients is common , under-recognized , and independently associated with mortality . OBJECTIVES Our objectives in this initial report from a 6-month longitudinal trial were to determine whether a collaborative care program improves rates of depression treatment by discharge among patients hospitalized with acute cardiovascular disease , and to assess key clinical characteristics of depression in this cohort . METHOD This was a prospect i ve , r and omized trial comparing collaborative care and usual care interventions for depressed cardiac patients who were admitted to cardiac units in an urban academic medical center . For collaborative care subjects , the care manager performed a multi-component depression intervention in the hospital that included patient education and treatment coordination ; usual care subjects ' inpatient providers were informed of the depression diagnosis . RESULTS The mean Patient Health Question naire-9 for subjects ( N = 175 ) was 17.6 ( SD 3.5 ; range 11 - 26 ) , consistent with moderate-severe depression . The majority of subjects had depression for over one month ( n = 134 ; 76.6 % ) and a prior depressive episode ( n = 124 ; 70.8 % ) ; nearly one-half ( n = 75 ; 42.9 % ) had thoughts that life was not worth living in the preceding 2 weeks . Collaborative care subjects were far more likely to receive adequate depression treatment by discharge ( 71.9 % collaborative care vs. 9.5 % usual care ; p < 0.001 ) . CONCLUSION Depression identified by systematic screening in hospitalized cardiac patients appears was prolonged , and of substantial severity . A collaborative care depression management model appears to vastly increase rates of appropriate treatment by discharge Objective Although depression is a risk and prognostic factor for cardiovascular disease ( CVD ) , depression trials involving cardiac patients have not observed the anticipated cardiovascular benefits . To test our hypothesis that depression treatment delivered before clinical CVD onset reduces risk of CVD events , we conducted an 8-year follow-up study of the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) r and omized controlled trial . Methods Participants were 235 primary care patients 60 years or older with major depression or dysthymia who were r and omized to a 12-month collaborative care program involving antidepressants and psychotherapy ( 85 without and 35 with baseline CVD ) or usual care ( 83 without and 32 with baseline CVD ) . Hard CVD events ( fatal/nonfatal ) were identified using electronic medical record and Medicare/Medicaid data . Results A total of 119 patients ( 51 % ) had a hard CVD event . As hypothesized , the treatment × baseline CVD interaction was significant ( p = .021 ) . IMPACT patients without baseline CVD had a 48 % lower risk of an event than did usual care patients ( 28 % versus 47 % , hazard ratio = 0.52 , 95 % confidence interval = 0.31–0.86 ) . The number needed to treat to prevent one event for 5 years was 6.1 . The likelihood of an event did not differ between IMPACT and usual care patients with baseline CVD ( 86 % versus 81 % , hazard ratio = 1.19 , 95 % confidence interval , 0.70–2.03 ) . Conclusions Collaborative depression care delivered before CVD onset halved the excess risk of hard CVD events among older , depressed patients . Our findings raise the possibility that the IMPACT intervention could be used as a CVD primary prevention strategy . Trial Registration : clinical trials.gov Identifier : NCT01561105 Depression and sub-syndromal depressive symptoms are important predictors of morbidity and mortality after acute coronary syndrome ( ACS ) . Prior trials of depression treatment in post-ACS patients have demonstrated no improvement for event-free survival , and only modest improvement in depression symptoms . These trials have raised a number of important issues regarding timing of depression intervention , acceptability of depression treatment to ACS patients , and safety for subsets of the treated population . This article describes Project COPES ( Coronary Psychosocial Evaluation Studies ) , a multi-center Phase-I r and omized clinical trial . Project COPES uses a patient preference depression treatment that has previously been found acceptable to medical patients , and a 3-month pre-r and omization observation period to insure depression status . The study sample will include 200 post-ACS patients . The primary outcome is patient satisfaction with depression care . Secondary , exploratory aims include the acceptability of depression treatment , reduction in depressive symptoms , and the effects of treatment on two key pathways -- medication adherence and inflammation -- hypothesized to link depression to post-ACS prognosis . These analyses will provide important data to inform subsequent clinical trials with this population BACKGROUND The presence of depression after an acute coronary syndrome ( ACS ) is associated with worse prognosis and lower adherence to risk-reducing behaviors . We reported earlier that an enhanced depression care intervention reduces depression symptoms and major adverse cardiac events . This study evaluates the impact of the depression intervention on health behavior and blood pressure control . METHODS Between 2005 and 2008 , 157 patients who remained persistently depressed 3 months after ACS were r and omized to a 6-month depression intervention ( initial patient preference for problem-solving therapy and /or pharmacotherapy , followed by stepped care ; 80 patients ) or to usual care ( 77 patients ) . At r and omization , and then 2 , 4 , and 6 months later , patients were asked if they ( 1 ) missed taking their aspirin ; ( 2 ) followed a heart healthy diet ; ( 3 ) exercised regularly ; and ( 4 ) used tobacco products . Blood pressure was measured before r and omization and 6 months later . RESULTS At the end of the intervention , there was no significant improvement in the percentage of intervention compared to control group patients who adhered to aspirin ( + 3 % versus -1 % , P = .23 ) , followed a healthy diet ( + 10 % versus + 8 % , P = .39 ) , exercised regularly ( + 5 % versus + 4 % , P = .65 ) , abstained from tobacco ( -3 % versus -1 % , P = .77 ) , or had controlled blood pressure ( + 6 % versus + 16 % , P = .26 ) . CONCLUSION Despite improving depression , enhanced depression care after an ACS did not improve health behavior or blood pressure control compared to usual care . Research is needed to test whether adding an adherence intervention to enhanced depression care can improve adherence and cardiovascular prognosis in depressed patients post-ACS CONTEXT Depressive symptoms commonly follow coronary artery bypass graft ( CABG ) surgery and are associated with less positive clinical outcomes . OBJECTIVE To test the effectiveness of telephone-delivered collaborative care for post-CABG depression vs usual physician care . DESIGN , SETTING , AND PARTICIPANTS Single-blind effectiveness trial at 7 university-based and community hospitals in or near Pittsburgh , Pennsylvania . Participants were 302 post-CABG patients with depression ( 150 , intervention ; 152 , usual care ) and a comparison group of 151 r and omly sample d post-CABG patients without depression recruited between March 2004 and September 2007 and observed as out patients until June 2008 . INTERVENTION Eight months of telephone-delivered collaborative care provided by nurses working with patients ' primary care physicians and supervised by a psychiatrist and primary care physician from this study . MAIN OUTCOME MEASURES Mental health-related quality of life ( HRQL ) measured by the Short Form-36 Mental Component Summary ( SF-36 MCS ) at 8-month follow-up ; secondary outcome measures included assessment of mood symptoms ( Hamilton Rating Scale for Depression [ HRS-D ] ) , physical HRQL ( SF-36 PCS ) , and functional status ( Duke Activity Status Index [ DASI ] ) ; and hospital readmissions . RESULTS The intervention patients reported greater improvements in mental HRQL ( all P < or = .02 ) ( SF-36 MCS : Delta , 3.2 points ; 95 % confidence interval [ CI ] , 0.5 - 6.0 ) , physical functioning ( DASI : Delta , 4.6 points ; 95 % CI , 1.9 - 7.3 ) , and mood symptoms ( HRS-D : Delta , 3.1 points ; 95 % CI , 1.3 - 4.9 ) ; and were more likely to report a 50 % or greater decline in HRS-D score from baseline ( 50.0 % vs 29.6 % ; number needed to treat , 4.9 [ 95 % CI , 3.2 - 10.4 ] ) than usual care patients ( P < .001 ) . Men with depression were particularly likely to benefit from the intervention ( SF-36 MCS : Delta , 5.7 points ; 95 % CI , 2.2 - 9.2 ; P = .001 ) . However , the mean HRQL and physical functioning of intervention patients did not reach that of the nondepressed comparison group . CONCLUSION Compared with usual care , telephone-delivered collaborative care for treatment of post-CABG depression result ed in improved HRQL , physical functioning , and mood symptoms at 8-month follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00091962 OBJECTIVE This study examined whether a collaborative care model for depression would improve clinical and functional outcomes for depressed patients with chronic general medical conditions in primary care practice s in Puerto Rico . METHODS A total of 179 primary care patients with major depression and chronic general medical conditions were r and omly assigned to receive collaborative care or usual care . The collaborative care intervention involved enhanced collaboration among physicians , mental health specialists , and care managers paired with depression-specific treatment guidelines , patient education , and follow-up . In usual care , study personnel informed the patient and provider of the diagnosis and encouraged patients to discuss treatment options with their provider . Depression severity was assessed with the Hopkins Symptom Checklist ; social functioning was assessed with the 36-item Short Form . RESULTS Compared with usual care , collaborative care significantly reduced depressive symptoms and improved social functioning in the six months after r and omization . Integration of collaborative care in primary care practice s considerably increased depressed patients ' use of mental health services . CONCLUSIONS Collaborative care significantly improved clinical symptoms and functional status of depressed patients with coexisting chronic general medical conditions receiving treatment for depression in primary care practice s in Puerto Rico . These findings highlight the promise of the collaborative care model for strengthening the relationship between mental health and primary care services in Puerto Rico |
13,958 | 12,069,563 | The second hypothesis was that survival of truth should be higher for negative conclusions than for positive conclusions .
A negative conclusion has a better chance of survival because the only way it would not continue to be negative is if it were found to be false .
A positive conclusion risks being found to be false or becoming obsolete .
Conclusions from older research are at greater risk for being refuted or becoming obsolete than are conclusions from more recent studies . | Science progresses through a series of paradigms that are held to be true until they are replaced by a better approximation of reality ( 1 ) .
Since the development of the steam engine in the late 18th century , economists have recognized 50-year cycles during which critical technological innovation is introduced ( 2 ) .
In 1997 , Hall and Platell ( 3 ) estimated the half-life of dogma relating to the practice of surgery .
From their analysis of 260 abstract s published from 1935 to 1994 , they estimated that the half-life of truth for clinical conclusions in the surgical literature was 45 years .
We hypothesized that some factors should be related to this truth survival .
The first hypothesis was that conclusions derived from better methodology should have a longer half-life .
If correct , this observation could be a validation of good methodology , often called evidence -based medicine ( 4 ) .
An example of a false conclusion is the efficacy of corticosteroids for treating acute viral hepatitis . | From a review of thirty published papers it is clear that the variety of options for treatment of hepatitis B have led to a large number of small exploratory trials . However , small groups lead to imprecise estimates of seroconversion rates ; for example a result of 4/10 gives an estimate of 40 % with 80 % confidence limits of 20 % and 60 % . A number of possible prognostic factors have been proposed and , whilst their importance is generally unproven , their estimated effects are considerable . Comparison between studies can therefore be misleading ; for example comparing two treatments A and B of identical efficacy in two common population s could give a 1 in 4 chance of declaring B to give double the seroconversion rate of A. Larger , r and omised , controlled trials on homogeneous patient groups are needed to give conclusive evidence of the efficacy or otherwise of various treatment regimes R and omized clinical trials ( RCTs ) provide the most reliable therapeutic information available . Unfortunately , there are no systemic listing of RCTs . We compared a MEDLARS search of 3686 biomedical journals for RCTs with a manual search of the medical literature for the period 1966 - 1982 . For the former search we used subject headings ( 1 ) liver disease or ( 2 ) biliary tract disease and subheadings ( 1 ) drug therapy , ( 2 ) surgery , ( 3 ) radiotherapy , or ( 4 ) therapy , and check tags ( 1 ) comparative study or ( 2 ) clinical research . For the manual search , the contents of 34 arbitrarily selected , gastroenterologic , hepatologic , surgical , or general journals were perused . The MEDLARS search identified 160 RCTs and 29 others were found in the references of the 160 . One hundred fifty-four RCTs were identified by both methods . The manual search identified 208 RCTs and an additional 34 were found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found manually in the 36 journals , an efficiency rate of 51 % . We estimate that 330 hepatobiliary RCTs had been published during this 17-year period . Sixty percent of the RCTs found by MEDLARS used the key word " r and omized , " " double blind , " or " controlled " in the title , compared to 36 % in those found by the manual search . In order to retrieve RCTs , it is essential that editors require that RCTs be identified in their titles or key words by specific terms such as " controlled , " " r and omized , " and " double blind , " that papers be so catalogued and indexed , and that search ers be instructed in appropriate search strategies In a double-blind study human leucocyte interferon was given for six weeks to 8 of 16 patients with chronic HBsAg-positive hepatitis . In the first week 12 x 10(6 ) reference units were administered daily , and thereafter the dose was halved every week . During the first two weeks leucopenia was observed in 6 of the 8 interferon-treated patients . Apart from a drop in DNA-polymerase activity in the first week , no effect was found on indices of hepatitis-B-virus infection 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 A grid devised to evaluate the method ological quality of r and omized therapeutic trials is presented . Fourteen items are analysed : description of the principal criterion of assessment , criteria of inclusion , number of subjects seen and excluded , number of subjects r and omized to each group , number of subjects excluded who are alive or lost to follow-up and reasons for the fall-outs , blind character of the doctors , patients and persons responsible for the assessment criteria , calculation of the number of subjects required before starting the trial , method of r and omization and its blind character , analysis and discussion of covariables , statistical tests used , taking into account of the fall-outs and power of the trials with non-significant results . This grid , used for the analysis of 527 r and omized trials , showed that about one-half of them were of mediocre quality , the most frequent defects encountered being the multiplicity of assessment criteria , the lack of description of the subjects excluded , the absence of calculation of the number of subjects required before starting the trial and the small number of subjects in trials with non-significant results 46 male chronic hepatitis B virus ( HBV ) carriers with active viral replication were r and omised , with stratification for histology and sexual preference , to receive six months ' lymphoblastoid interferon or no therapy . After nine to eighteen months ' follow-up , HBeAg was no longer detectable and anti-HBe was present in 6 of the 23 treated patients . HBsAg was not detectable in 5 of these patients and 3 had anti-HBs . All of the controls remained positive for HBeAg and HBsAg . Seroconversion from HBeAg to anti-HBe was preceded in all cases by a pronounced increase in serum aspartate aminotransferase levels of more than ten times the upper limit of normal at eight to twelve weeks ; this response was exclusively associated with interferon therapy . These results suggest that loss of HBsAg and a hepatitis-like illness in the third month of therapy are direct effects of interferon treatment BACKGROUND & AIMS Long-term ursodeoxycholic acid ( UDCA ) therapy slows the progression of primary biliary cirrhosis . This study examined the effect of UDCA therapy on survival free of liver transplantation in a large group of patients . METHODS Data from three clinical trials were combined in which patients with primary biliary cirrhosis were r and omly assigned to receive UDCA ( n = 273 ) or placebo ( n = 275 ) . After 2 years , patients from French and Canadian studies received UDCA for up to 2 years . Patients from the American study remained on their assigned treatment for up to 4 years . RESULTS Survival free of liver transplantation was significantly improved in the patients treated with UDCA compared with the patients originally assigned to placebo ( P < 0.001 ; relative risk , 1.9 ; 95 % confidence interval , 1.3 - 2.8 ) . Subgroup analyses showed that survival free of liver transplantation was significantly improved in medium- and high-risk groups ( serum bilirubin level , 1.4 to 3.5 or > 3.5 mg/dL ; P < 0.0001 and P < 0.03 , respectively ) and histological stage IV subgroup ( P < 0.01 ) . CONCLUSIONS Long-term UDCA therapy improves survival free of liver transplantation in patients with moderate or severe disease . An effect in patients with mild disease is probably not found because they do not progress to end-stage disease in 4 years Forty-five patients with chronic hepatitis B were entered into a r and omized controlled trial of recombinant human alpha-interferon therapy . All patients had hepatitis B surface antigen in serum for at least 1 yr and had stable serum levels of both hepatitis B virus deoxyribonucleic acid and hepatitis B e antigen . During the 4-mo period of therapy , 10 of 31 ( 32 % ) treated patients and only 1 of 14 ( 7 % ) control patients became negative for serum hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase . All 10 patients who became negative for serum hepatitis B virus deoxyribonucleic acid subsequently had a marked improvement in serum aminotransferase activities and lost hepatitis B e antigen from serum , and 9 of them had improvement in liver histology . Comparison of responders to nonresponders indicated that female sex and a high initial level of serum aspartate aminotransferase correlated best with response to interferon therapy . These findings indicate that a 4-mo course of recombinant alpha-interferon can induce a remission in disease in approximately one-third of patients with chronic hepatitis |
13,959 | 9,667,624 | The results suggest that dynamic exercise therapy is effective in increasing aerobic capacity and muscle strength .
No detrimental effects on disease activity and pain were observed .
The effects of dynamic exercise therapy on functional ability and radiological progression are unclear .
It is concluded that dynamic exercise therapy has a positive effect on physical capacity . | The aim of this systematic review was to determine the effectiveness of dynamic exercise therapy in improving joint mobility , muscle strength , aerobic capacity and daily functioning in patients with rheumatoid arthritis ( RA ) .
In addition , possible unwanted effects such as an increase in pain , disease activity and radiological progression were studied . | The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity . Maximal O2 uptake increased significantly , whereas heart rate at stage 2 and rate of perceived exertion decreased significantly , in the training group compared with the controls . Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training . Training did not induce changes in blood mononuclear cell sub population s , proliferative response , or natural killer cell activity . Furthermore the plasma concentrations of interleukin-1 alpha , interleukin-1 beta , and interleukin-6 did not change in response to training . It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis OBJECTIVE To investigate physical fitness and work capacity in women with rheumatoid arthritis ( RA ) . METHODS The 42 subjects were a subset of a prospect i ve trial of conditioning exercise in rheumatic disease . Assignment to an exercise or nonexercise group was determined by proximity to the intervention , a 3-month supervised group exercise program . Physical fitness and work capacity were assessed at baseline , 3 months , and 12 months . RESULTS At baseline , subjects were deconditioned and limited in h and function , lifting ability , and lower extremity mobility . Only the exercise group improved their aerobic capacity and exercise tolerance . There were no significant changes in measured work capacity in either group . Moderate to strong correlations were found between aerobic capacity , mobility , h and function , and work capacity . Grip strength was a strong and consistent correlate of work capacity . CONCLUSION Our findings suggest that physical capacity , particularly h and function , may be important in the complex phenomenon of work disability in RA The objective was to study the long-term effect ( 2 years ) of different training programs in patients with rheumatoid arthritis . The method was a r and omized trial with 75 patients participating . The measured variables included morning stiffness , a pain score , number of swollen joints , a health assessment score , a functional score , ESR , Hb , the cost of medicine , and progression using X-rays of h and s and feet . The results showed no effect of training on the disease activity or on the progression of the disease . The conclusion is that although most patients are in favour of training , the present study does not support that training lessons per se affect the disease activity or the progression of the disease Twenty-six patients with rheumatoid arthritis ( RA ) participated either in a 21 day , community sponsored , in-patient multidisciplinary rehabilitation program ( N = 20 ) or ; received traditional , out-patient physiotherapy design ed by the patient 's rheumatologist ( N = 6 ) . Clinical assessment s were made ( prior to , immediately after , and 6 months after rehabilitation ) to evaluate the response to these two quite different rehabilitative measures that included : functional classification , joint score index , subjective VAS of pain , HAQ , pain disability index , Comprehensible psychopathological rating scale , hemoglobin , and CRP measurements . Economic assessment s included salary , direct and community sponsored costs , for rehabilitation and costs for sick days and production losses . No clear-cut differences between the two rehabilitation modes were detected . Both modes showed improvement in different assessment parameters ; patients with higher education and , therefore , with a less joint-disturbing work profile appeared to profit more from an extensive in-patient rehabilitation program . Patients with less education and a more manually-oriented working profile , did worse and had a higher tendency to seek medical pensioning , in spite of rehabilitative measures . As the total costs for out-patient rehabilitation only add up to 15.8 % of the total costs for in-patient rehabilitation , this study setting cautiously suggests that out-patient rehabilitation might be an acceptable alternative to individualized patient groups that might not compromise clinical and vocational outcome . Larger patient groups are needed , however , to confirm these findings The aim of the study was to evaluate the effects of a dynamic training program versus a muscle relaxation training program as home exercise in patients with inflammatory rheumatic diseases . Fifty-four patients ( mean age 54 years , mean symptom duration 14 years ) were r and omized to one of the two programs . After personal instructions every patient exercised at home for half an hour , 5 days a week during 3 months . Before and after the interventions , all patients were assessed for health-related quality of life , joint tenderness and physical capacities . The dynamic training group had improved in perceived exertion at the walking test ( p < or = 0.05 ) , while the relaxation training group had improved their total Nottingham Health Profile ( p < or = 0.01 ) , its subscale for lack of energy ( p < or = 0.05 ) , Ritchie 's articular index ( p < or = 0.05 ) , muscle function of the lower extremities ( p < or = 0.01 ) , and arm endurance ( p < or = 0.01 ) . Regarding changes in muscle function of the lower extremities during the intervention period , there was a significant difference ( p < or = 0.05 ) between the groups in favour of the relaxation training group . The results of the study thus indicated that progressive muscle relaxation training might improve health related quality of life , reduce joint tenderness and be superior to dynamic muscle training in improving the muscle function of the lower extremities in patients with inflammatory rheumatic diseases . The clinical effects were small and the results have to be interpreted with caution Thirty-nine consecutive patients with recent-onset rheumatoid or psoriatic arthritis were r and omly allotted for six months period either to the experimental progressive dynamic strength training group ( EG , 10 women and 11 men ; 41 + /- 10 yrs ) , or to the control group ( CG , 10 women and 8 men ; 45 + /- 11 yrs ) who just maintained their habitual physical activities . All patients received antirheumatic medication throughout the experimental period . During the study period significant improvements took place in the EG in maximal muscle strength of all examined muscle groups ( 31.5 % for the knee extensors , p < 0.001 ; 14.8 % and 10.7 % for the trunk flexors and extensors , p < 0.01 ; 27.8 % and 20.4 % for grip strength , p < 0.001 ) as well as in erytrocyte sedimentation rate ( p < 0.05 ) . Ritchie 's articular index ( RI ) ( p < 0.001 ) and HAQ ( p < 0.01 ) . In the CG only the decrease in RI was statistically significant ( p < 0.05 ) . Erosive changes in joints increased only slightly and less in the EG than in the CG . The present results suggest that dynamic strength training in early arthritis increases the neuromuscular performance without detrimental effects on disease activity or joint damage The effectiveness of an exercise prescription and unsupervised home exercise programme was tested on 37 subjects with rheumatoid arthritis and 34 with systemic lupus erythematosus . Subjects were r and omly assigned to control or stationary bicycling at home , using loaned bicycles . Exercise subjects ( with bicycles ) did better than controls , but not significantly , on all outcome d measures ( exercise tolerance test , fatigue , depression and helplessness ) at 3 months . Bicycles were recl aim ed at 3 months and all subjects in both groups given instructions for home exercise . Exercise in the second 3 months was predicted primarily by baseline exercise habits and fatigue . It is concluded that although safe , unsupervised home exercise programmes may benefit few patients . Future research should address methods of stimulating and maintaining unsupervised exercise programmes in patients with systemic rheumatic disease OBJECTIVE The aim of this study was to evaluate the therapeutic effects of hydrotherapy which combines elements of warm water immersion and exercise . It was predicted that hydrotherapy would result in a greater therapeutic benefit than either of these components separately . METHODS One hundred thirty-nine patients with chronic rheumatoid arthritis were r and omly assigned to hydrotherapy , seated immersion , l and exercise , or progressive relaxation . Patients attended 30-minute sessions twice weekly for 4 weeks . Physical and psychological measures were completed before and after intervention , and at a 3-month followup . RESULTS All patients improved physically and emotionally , as assessed by the Arthritis Impact Measurement Scales 2 question naire . Belief that pain was controlled by chance happenings decreased , signifying improvement . In addition , hydrotherapy patients showed significantly greater improvement in joint tenderness and in knee range of movement ( women only ) . At followup , hydrotherapy patients maintained the improvement in emotional and psychological state . CONCLUSIONS Although all patients experienced some benefit , hydrotherapy produced the greatest improvements . This study , therefore , provides some justification for the continued use of hydrotherapy OBJECTIVE To determine whether hydrotherapy in a thermomineral institution is superior to the same hydrotherapy in an ordinary hospital exercise-bath . DESIGN Controlled therapeutic trial . SETTING The thermomineral institution at Arcen and the exercise bath at the Maasl and Hospital in Sittard , the Netherl and s. PATIENTS AND METHODS 46 patients with rheumatoid arthritis were treated in a by a skilled physiotherapist , according to a st and ardized exercise-scheme : 27 were treated in the thermomineral institution and 19 ( control-group ) in the hospital exercise-bath . Each patient received 12 treatments in 12 weeks . ENDPOINTS PARAMETERS : Morning stiffness , erythrocyte sedimentation rate , Ritchie index , amount of pain , answers to 11 questions concerning the activities of daily life , and psychosocial aspects of the disease . The various subjective and objective parameters were scored by the same physician . RESULTS Statistically significant improvement was observed in both groups concerning morning stiffness . Other subjective parameters improved , but did not reach significance . Objective parameters did not change significantly . Between-group differences were not found . CONCLUSION Hydrotherapy has a positive effect on some subjective but not on objective parameters in patients with rheumatoid arthritis , whether it is applied in a thermomineral institution or an ordinary hospital exercise bath The importance of pain in the health status and health behavior of patients with chronic rheumatic disease was evaluated . The Arthritis Impact Measurement Scales were used to estimate physical disability , psychological status , and pain in a large set of rheumatic disease patients . Explanatory regression models were built to explore the contribution of pain in physician and patient assessment s of overall health , medication usage , and changes in health status over time . Results confirm that pain makes a highly significant contribution to explaining both physician and patient overall health assessment s ( P less than 0.001 ) . Pain is also the most important of the 3 health status components in explaining medication usage ( P less than 0.001 ) . Finally , using prospect i ve data , it is shown that current pain , rather than current physical or psychological disability , is the best predictor of subsequent pain ( P less than 0.001 ) . Current pain also is most associated with subsequent physical disability ( P less than 0.05 ) . These findings confirm the importance of pain in determining the health status and health behavior of individuals with chronic rheumatic disease , and suggest that doctors and other health professionals should continue to solicit and address the patient 's complaints of pain This study aim ed at evaluating the effects of a dynamic physical training programme on circulating levels of corticotropin-releasing hormone ( CRH ) , beta-lipotropin ( beta-LPH ) , and beta-endorphin ( beta-EP ) after high-intensity training for 6 weeks ( 60 min twice a week ) and after low-intensity training ( home-training ) for another 6 months in patients with rheumatoid arthritis ( RA ) and in healthy subjects . Additionally , differences in neuropeptide levels between the two groups were studied . A total of 30 patients with RA were r and omly allocated to the study , 15 in the training group ( TG ) and 15 in the control group ( CG ) . In addition , 20 healthy subjects ( 10 in TG ; 10 in CG ) participated . In addition to the biochemical analyses , the following variables were assessed for the RA group : pain and disability ( Stanford health assessment question naire ) , joint tenderness ( Ritchie articular index ) , disease activity , muscle function , aerobic capacity , sociodemographic data and attitudes . The results obtained at the start revealed significant differences ( p < 0.05 ) between RA patients and healthy subjects concerning CRH levels , RA patients showing the lower levels ( RA-group Md = 24 pmol/L , healthy group Md = 29 pmol/L ) . No significant differences concerning beta-LPH and beta-EP were found here . After the high-intensity training period , a significant increase of the CRH levels were found for the RA-TG ( pretest Md = 24 pmol/L , after 6 weeks Md = 27 pmol/L , p < 0.05 ) . No such results were found for the healthy-TG or the control groups . Concerning beta-EP , significant differences between the RA-TG and healthy-TG were found after the training . RA patients generally showing higher levels as compared with the healthy ( RA-group Md = 42 pmol/L , healthy group Md = 36 pmol/L , p < 0.05 ) . The same pattern was found for the beta-LPH levels . In conclusion , the effects of physical training on circulating neuropeptides remain still incompletely examined , and there is no definite answer to the question whether increased beta-EP levels are good or bad A group of 120 patients with rheumatoid arthritis or osteoarthritis volunteered to be subjects for this study of aerobic versus nonaerobic exercise . Patients were stratified by diagnosis and r and omized into an exercise program of aerobic walking , aerobic aquatics , or nonaerobic range of motion ( controls ) . The retention rate for the 12-week program was 83 % . Exercise tolerance , disease-related measures , and self-reported health status were assessed . The aquatics and walking exercise groups showed significant improvement over the control group in aerobic capacity , 50-foot walking time , depression , anxiety , and physical activity after the 12-week exercise program . There were no significant between-group group differences in the change scores for flexibility , number of clinical ly active joints , duration of morning stiffness , or grip strength . Our findings document the feasibility and efficacy of conditioning exercise for people who have rheumatoid arthritis or osteoarthritis Twenty-three patients with rheumatoid arthritis ( RA ) have been given physical training for 4 to 8 years . To compare , we have had a control group of equal size and with the same disease severity . The training program consisted of home-training and for most of the patients also group-training led by a physiotherapist . During the observation period we have found a significantly less pronounced progress of X-ray changes in the joints of the active patients compared with control patients . Physiological tests and clinical parameters , including sick-pension and sick-leave , show unanimously a better disease outcome in the active group of patients . There is probably a risk of overuse or disuse of the joints in RA but we believe that it is better to be overactive rather than the reverse . As in many other diseases , the general prescription of rest in RA is not adequate A self- appraisal and coping model was examined using a longitudinal data set involving 56 classical or definite rheumatic arthritis patients r and omly assigned to either dynamic ( n = 28 ) or static ( n = 28 ) physiotherapeutic training . The model considers both adaptational consequences and antecedents of training ( muscular endurance , pain , self- appraisal , and coping through avoidance or painful problem-solving ) . Measures were obtained prior to and after a 6-week training period ( partly supervised and partly self-training ) at a health-care centre , and after an additional 3 months of self-training only . Path analysis supported the mediating role of self- appraisal and of avoidance in influencing muscular endurance in dynamic training patients . Regression analyses likewise supported these conclusions , suggesting some patients in dynamic training to be caught in a vicious circle of avoidance and low self- appraisal . Theoretical issues are discussed , and suggestions made for developing more effective interventions in rheumatic patients Twenty-three patients with rheumatoid arthritis have been given physical training for 4 - 8 years . They are compared with a control group of patients with the same disease . In order to evaluate disease outcome , patients were given a self-administered question naire to report ADL capacity and some attitudes and feelings concerning their situation . Results are in agreement with earlier reports and show a significantly higher ADL capacity in the trained group compared with the control group . There is a positive correlation between ADL capacity and reported amount of physical training and a negative correlation between ADL capacity and X-ray findings and findings at clinical examination . The feeling of weakness is more pronounced in the control group and patients in this group get more discomfort from joints after physical strain than patients in the trained group . A majority of patients in the two groups wish to participate in organized group-training Sixty-seven patients with classical or definite rheumatoid arthritis ( RA ) were studied concerning the effects of st and ardized physical training on muscle function in the lower extremities . The patients were r and omly assigned to four different training groups and were given 6 weeks of training supervised by a physiotherapist at a health care centre . The groups differed according to type ( dynamic or static ) and extent ( 12 or 4 times ) of training . During this training period as well as for an additional 3 months , the patients carried out programs of exercise at home ( either dynamic or static ) . A significantly greater increase in function during the 6-week period as regards muscle strength , endurance , aerobic capacity , and functional ability was found for the dynamic as compared with the static groups . The findings at follow-up 3 months later were similar . The effectiveness of the programs did not vary with the extent of training . In conclusion , in RA patients , dynamic training gives a greater increase in physical capacity than does static training This study investigated factors related to an initial exercise experience to explain exercise maintenance in 120 adults with rheumatoid arthritis or osteoarthritis . Integral secondary analysis was used to incorporate data from a prospect i ve , controlled trial of exercise ( Minor et al. : Arthritis Rheum 32:1396 , 1989 ) with data collected at 18 months follow-up . The dependent variable was self-directed exercise ( min/wk ) reported at 3 , 9 , and 18 or more months after exercise class participation . Predictor variables included physical , psychosocial , disease , and programmatic factors . The all possible regressions search procedure result ed in three explanatory models ( p = .0001 ) . At 3 months the model ( R2 = .45 ) included initial aerobic capacity , depression , and anxiety ; and changes in depression and social activity . The 9-month model ( R 2 = .35 ) consisted of initial anxiety and physical activity , change in depression , support of friends for exercise , and exercise behavior at prior assessment . At 18 or more months ( R2 = .42 ) , model variables were initial aerobic capacity , change in pain , and exercise behavior at the two prior assessment s. Neither disease nor program factors appeared as significant . This limited study indicates that factors associated with exercise behavior in this sample are similar to those in the general population ; explanatory factors change over time , and changes ascribed to a trial behavior may influence subsequent decision making ABSTRACT Cardiorespiratory function and exercise tolerance appear very limited in persons with rheumatoid arthritis ( RA ) . Many studies have demonstrated that aerobic exercise training is beneficial to prevent physical deconditioning without inducing adverse effects on an individual 's joints and general health . The present study was conducted to demonstrate that a dance-based exercise program is a safe and efficient activity to improve physical fitness and psychological state in persons with RA . A group of 19 persons ( mean age , 49.3 ± 13 yr ) participated in a 12-wk exercise program ( twice weekly ) , whereas 10 persons ( mean age , 49.4 ± 12 yr ) served as controls . Health status , use of medication , joint pain and swelling , physical fitness , activity of daily living and psychological state were assessed at baseline , after the 12-wk training program and 6 mo after the end of the program . Exercise training induced a mean improvement of 13 % in aerobic power , with the highest values reaching 40 % . No significant changes were observed in joint status , even though the count of painful joints tended to decrease in the exercise group . Positive changes in depression , anxiety , fatigue and tension were observed after the 12-wk exercise program . These findings provide some evidence s in favor of aerobic exercise in individuals with RA . Furthermore , it is of primary interest to note that a weight-bearing activity with limited ground impacts do not provoke short-term adverse effects on joint status . Further studies , however , are required to determine the long-term effect of weight-bearing exercise on the health status of individuals with RA The effects of physical training on elderly , fragile patients with rheumatoid arthritis ( RA ) who are on low-dose steroids were investigated . The controlled study included 24 patients who had been treated with low-dose steroids for 2 years . Each patient was assigned either to a treatment group receiving training or to an untrained control group . The training took place over a 3-month period and was based on a protocol using progressive interval training consisting of bicycle exercises , heel lifts , and step-climbing . The exercises were performed twice weekly for 45 minutes . Comparison of the two groups showed that disease activity did not increase in the trained group and that fewer , but not significantly fewer , swollen joints were observed in this group ( p = 0.06 ) . No significant changes were noticed in erythrocyte sedimentation rate , tender joints , or morning stiffness . The work capacity of the trained patients were doubled and the numbers of repetitions increased 76 % . Individually adapted exercise programs can therefore be recommended for elderly rheumatoid arthritis patients on steroid treatment |
13,960 | 25,888,484 | Conclusions There is limited evidence to support the effectiveness of SDF applications or daily toothbrushing with fluoride toothpaste in arresting or slowing down the progression of active dentin caries in primary teeth in preschool children . | Background Untreated dentin caries in primary teeth is commonly found in preschool children worldwide .
Recently , the use of simple non-surgical approaches to manage the situation has been advocated .
The aim of the study was to systematic ally review and evaluate the literature on effectiveness of non-surgical methods in arresting or slowing down the progression of active dentin caries in primary teeth in preschool children . | OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome OBJECTIVE To explore whether dentists ' beliefs and attitudes to providing preventive and restorative dental care for young children can form a barrier to the provision of care . BASIC RESEARCH DESIGN The Barriers to Childhood Caries Treatment ( BaCCT ) Question naire , a st and ardised international measure was developed and applied . PARTICIPANTS Through a research consortium , each site was asked to recruit 100 dentists . The sample participating was not intended to be nationally representative . Dentists were mainly r and omly selected and contacted by mail with one or more mailings depending on site . RESULTS 2,333 dentists in 14 countries and 17 sites participated . Factor analysis identified four factors as potential barriers . Two factors were found to be barriers in many sites . First , in most countries , dentists agreed that young children 's coping skills limit their ability to accept dental care . Secondly , dentists with negative personal feelings , for example , that providing care can be stressful and troublesome and that they feel time constrained . Differences in dentists ' beliefs can be partly explained by their work profile , with those treating children often , and those working under systems where they feel they can provide quality care being least likely to identify barriers to providing care for children . CONCLUSIONS The BaCCT Question naire was determined to be a valid psychometric measure . Separately , it was found that health systems do impact on dentists ' ability to deliver preventive and restorative care for children but that these effects vary across countries and further work is needed to determine how best these should be examined Since there is no consensus on the anticaries effectiveness of low-fluoride ( F ) dentifrice , this r and omized clinical trial evaluated its effect in children at different caries activity status . One hundred and twenty 2- to 4-year-old children , half with and half without active caries lesions , were r and omly divided into 2 groups which used 500- or 1,100-µg F/g ( NaF ) dentifrices during 1 year . Caries progression or regression were evaluated as the number of lesions becoming active/cavities or inactive , respectively . The anticaries effect of the low-F dentifrice was similar to the conventional F dentifrice when used by caries-inactive children . However , in children with active caries lesions the low-F dentifrice was less effective than the 1,100-µg F/g dentifrice in controlling the progression of lesions . The data suggest that the child caries activity may be taken into account to recommend a low-F dentifrice Background Dental caries is a major public health problem in many countries . Since the last territority-wide dental survey of Hong Kong preschool children was conducted in 2001 , a survey to up date the information is necessary . This study aim ed to describe the dental caries experience of preschool children in Hong Kong and factors affecting their dental caries status . Methods A stratified r and om sample of children from seven kindergartens in Hong Kong was surveyed in 2009 . Ethical approval from IRB and parental consent was obtained . Clinical examinations of the children were performed by two calibrated examiners using disposable dental mirrors , an intra-oral LED light and ball-ended periodontal probes . A question naire to investigate possible explanatory factors for caries status was completed by the children ’s parents . Caries experience was recorded using the dmft index . Multifactor-ANOVA was used to study the relationship between dental caries experience , and the background and oral health-related behaviours of the children . Results Seven hundred children ( 53 % boys ) , mean age 5.3 ± 0.7 years were examined . The mean dmft score of the surveyed children was 2.2 and 51 % of them had no caries experience ( dmft = 0 ) . Most ( > 95 % ) of the decayed teeth were untreated . Statistically significant correlations were found between dental caries experience of the children and their oral health-related habits , family income , parental education level and parental dental knowledge . Conclusions Early childhood dental caries was prevalent among the preschool children in Hong Kong . Their caries experience was associated with their oral health-related behaviours , socio-economic background , and parental education and dental knowledge Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries among very young children and to evaluate the effect of xylitol in reducing acute otitis media in a subsequent study . DESIGN Double-blind r and omized controlled trial . SETTING Communities in the Republic of the Marshall Isl and s. PARTICIPANTS One hundred eight children aged 9 to 15 months were screened , and 100 were enrolled . Intervention Children were r and omized to receive xylitol topical oral syrup ( administered by their parents ) twice a day ( 2 xylitol [ 4.00-g ] doses and 1 sorbitol dose ) ( Xyl-2 x group ) or thrice per day ( 3 xylitol [ 2.67-g ] doses ) ( Xyl-3x group ) vs a control syrup ( 1 xylitol [ 2.67-g ] dose and 2 sorbitol doses ) ( control group ) . MAIN OUTCOME MEASURES The primary outcome end point of the study was the number of decayed primary teeth . A secondary outcome end point was the incidence of acute otitis media for reporting in a subsequent report . RESULTS Ninety-four children ( mean [ SD ] age , 15.0 [ 2.7 ] months at r and omization ) with at least 1 follow-up examination were included in the intent-to-treat analysis . The mean ( SD ) follow-up period was 10.5 ( 2.2 ) months . Fifteen of 29 of the children in the control group ( 51.7 % ) had tooth decay compared with 13 of 32 children in the Xyl-3x group ( 40.6 % ) and eight of 33 children in the Xyl-2x group ( 24.2 % ) . The mean ( SD ) numbers of decayed teeth were 1.9 ( 2.4 ) in the control group , 1.0 ( 1.4 ) in the Xyl-3x group , and 0.6 ( 1.1 ) in the Xyl-2x group . Compared with the control group , there were significantly fewer decayed teeth in the Xyl-2x group ( relative risk , 0.30 ; 95 % confidence interval , 0.13 - 0.66 ; P = .003 ) and in the Xyl-3x group ( 0.50 ; 0.26 - 0.96 ; P = .04 ) . No statistical difference was noted between the 2 xylitol treatment groups ( P = .22 ) . CONCLUSION Xylitol oral syrup administered topically 2 or 3 times daily at a total daily dose of 8 g was effective in preventing early childhood caries The recording of multiple interval-censored failure times is common in dental research . Modeling multilevel data has been a difficult task . This paper aims to use the Bayesian approach to analyze a set of multilevel clustered interval-censored data from a clinical study to investigate the effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting active dentin caries in Chinese pre-school children . The time to arrest dentin caries on a surface was measured . A three-level r and om-effects Weibull regression model was used . Analysis was performed with WinBUGS . Results revealed a strong positive correlation ( 0.596 ) among the caries lesions ’ arrest times on different surfaces from the same child . The software WinBUGS made the above complicated estimation simple . In conclusion , the annual application of silver diamine fluoride on caries lesions , and caries removal before the application , were found to shorten the arrest time To investigate the effectiveness of topical fluorides in preventing fissure caries , we conducted a r and omized controlled trial with parallel groups . In total , 501 children ( 1,539 molars , 3,078 sites ) , mean age 9.1 years , who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited . They were r and omly allocated among four groups : ( 1 ) resin sealant , single placement ; ( 2 ) 5 % NaF varnish , semi-annual application ; ( 3 ) 38 % silver diamine fluoride ( SDF ) solution , annual application ; and ( 4 ) placebo control . Follow-up examinations were conducted every 6 months by a masked examiner . After 24 months , 485 children ( 97 % ) were examined . Proportions of pit/fissure sites with dentin caries in the sealant , NaF , SDF , and control groups were 1.6 % , 2.4 % , 2.2 % , and 4.6 % , respectively . A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls ( p < 0.05 ) . We concluded that placement of resin sealant , semi-annual application of NaF varnish , and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars ( Clinical Trials.gov number CT01446107 ) Background There is growing interest in the use of diammine silver fluoride ( DSF ) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world . While DSF has been available in various formulations for many years , most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized . Methods This preliminary study determined the applied doses ( 3 teeth treated ) , maximum serum concentrations , and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode , and silver was determined using inductively coupled plasma-mass spectrometry . The mean amount of DSF solution applied to the 3 teeth was 7.57 mg ( 6.04 μL ) . Results Over the 4 hour observation period , the mean maximum serum concentrations were 1.86 μmol/L for fluoride and 206 nmol/L for silver . These maximums were reached 3.0 h and 2.5 h for fluoride and silver , respectively . Conclusions Fluoride exposure was below the U.S. Environmental Protection Agency ( EPA ) oral reference dose . Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime , but for occasional use was well below concentrations associated with toxicity . This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults . Clinical trials registration NCT01664871 This study compared the ability of two sodium fluoride dentifrices , one containing 5,000 ppm fluoride ( Prevident 5000 Plus ) and the other 1,100 ppm fluoride ( Winterfresh Gel ) , to reverse primary root caries lesions ( PRCLs ) . A total of 201 subjects with at least one PRCL each entered the study and were r and omly allocated to use one of the dentifrices . After 6 months , 186 subjects were included in statistical analyses . At baseline and after 3 and 6 months , the lesions were clinical ly assessed and their electrical resistance measured using an electrical caries monitor . After 3 months , 39 ( 38.2 % ) of the 102 subjects in the 5,000 ppm F– group and 9 ( 10.7 % ) of 84 subjects using the 1,100 ppm F– dentifrice , had one or more PRCLs which had hardened ( p = 0.005 ) . Between baseline and 3 months , the log10 mean ± SD resistance values of lesions for subjects in the 1,100 ppm F– group had decreased by 0.06±0.55 , whereas those in the 5,000 ppm F– group had increased by 0.40±0.64 ( p<0.001 ) . After 6 months , 58 ( 56.9 % ) of the subjects in the 5,000 ppm F– group and 24 ( 28.6 % ) in the 1,100 ppm F– group had one or more PRCLs that had become hard ( p = 0.002 ) . Between baseline and 6 months , the log10 mean ± SD resistance values of lesions for subjects in the 1,100 ppm F– group decreased by 0.004±0.70 , whereas in the 5,000 ppm F– group , they increased by 0.56±0.76 ( p<0.001 ) . After 3 and 6 months , the distance from the apical border of the root caries lesions to the gingival margin increased significantly in the 5,000 ppm F– group when compared with the 1,100 ppm F– group . The plaque index in the 5,000 ppm F– group was also significantly reduced when compared with the 1,100 ppm F– group . The colour of the lesions remained unchanged . It was concluded that the dentifrice containing 5,000 ppm F– was significantly better at remineralising PRCLs than the one containing 1,100 ppm BACKGROUND In this article , the authors present evidence -based clinical recommendations regarding the use of nonfluoride caries preventive agents . The recommendations were developed by an expert panel convened by the American Dental Association (ADA)Council on Scientific Affairs . The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries . TYPES OF STUDIES REVIEW ED A panel of experts convened by the ADA Council on Scientific Affairs , in collaboration with ADA Division of Science staff , conducted a MEDLINE search to identify all r and omized and nonr and omized clinical studies regarding the use of non fluoride caries-preventive agents . RESULTS The panel review ed evidence from 50 r and omized controlled trials and 15 nonr and omized studies to assess the efficacy of various nonfluoride caries-preventive agents . CLINICAL IMPLICATION S The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries . These recommendations are presented as a re source for dentists to consider in the clinical decision-making process . As part of the evidence based approach to care , these clinical recommendations should be integrated with the practitioner ’s professional judgment and the patient ’s needs and preferences BACKGROUND Silver diamine fluoride ( SDF ) is an effective agent for the arrest of caries in children , is easy to apply and can be used outside the clinical environment . Interim restorative treatment ( IRT ) using glass ionomer cement has also been cl aim ed to be a simple and effective method to arrest caries in deciduous teeth . OBJECTIVE To examine whether , for underprivileged schoolchildren with cavities , treatment with 30 % SDF gives better results than IRT for carries arrest . METHOD This r and omised controlled study compares the effect of IRT ( FUJI IX ) with 30 % SDF in 91 children aged 5 - 6 years . RESULTS After 1 year , treatment with SDF was more effective [ relative risk ( RR ) = 66.9 % ] than IRT ( RR = 38.6 % ) for the arrest of caries ; this was statistically significant ( P < 0.05 ) . CONCLUSION The SDF technique showed better results than IRT for the arrest of cavities in deciduous teeth , indicating that its use for underprivileged communities may justify a paradigm shift in paediatric dentistry Untreated dental caries in Chinese pre-school children is common . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . Three hundred seventy-five children , aged 3 - 5 years , with carious upper anterior teeth were divided into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . Sodium fluoride varnish ( 22,600 ppm F ) was applied every three months to the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . Three hundred eight children were followed for 30 months . The respective mean numbers of arrested carious tooth surfaces in the five groups were 2.5 , 2.8 , 1.5 , 1.5 , and 1.3 ( p < 0.001 ) . Silver diamine fluoride was found to be effective in arresting dentin caries in primary anterior teeth in pre-school children The purpose of this paper is to report clinical observations on the stabilisation of dentine caries in two chewing gum studies carried out in young subjects . One study focused on the permanent dentition of 1,277 initially 10-year old subjects , while the other study was carried out on 510 initially 6-year old subjects and focused on the primary dentition . In both trials , several chewing gum formulas containing dietary polyols ( xylitol and sorbitol , or their combinations ) were used for up to 40 months ( 10-year olds ) or up to 24 months ( 6-year olds ) . The daily consumption level of both polyols was up to 10.7 g per subject , used normally in 5-minute chewing episodes 3 to 5 times per day . Supervised chewing in schools lasted 5 min per episode , and for variable times during non-school days . Rehardening of dentine caries lesions was observed clinical ly by experienced , blinded examiners using sharp dental explorers and fibre optic light . After 40 months ( permanent dentition ) or after 18 months ( primary dentition ) , rehardening ( caries arrest ) generally occurred more frequently in subjects who used polyol gums than in subjects who did not receive gum as part of the programmes , or who received sucrose gum . Arrest or non-progression of dentine caries was most frequently observed in subjects who used 100 per cent xylitol gums or mixtures of xylitol and sorbitol , but the differences between gums were not consistently significant . However , the usage of 100 per cent xylitol pellet-shaped gum was more frequently associated with arrest of dentine caries than other treatments . These results and previous studies suggest that high-xylitol chewing gum usage can retard or arrest even rampant dentine caries in conditions where effective restoration and prevention programmes have not been instituted , and can also provide additional protection against further caries development during full implementation of restorative procedures by holding the lesion in a non-progressive condition We hypothesized that the six-monthly application of silver diamine fluoride ( SDF ) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars . A prospect i ve controlled clinical trial was conducted on the efficacy of a 38 % SDF solution for caries reduction . Four hundred and twenty-five six-year-old children were divided into two groups : One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos . The second group served as controls . The 36-month follow-up was completed by 373 children . The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls . The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls . The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren Background : The prevalence of proximal caries in primary molar teeth is high in many countries . Aims : ( 1 ) To study by means of a split-mouth design the 1- and 2.5-year efficacy of sealing proximal lesions vs. flossing instructions ( control ) on primary molar teeth . ( 2 ) To assess children ’s behaviour and pain perception during the procedure . Methods : Ninety-one 4- to 6-year-old children from Bogotá , Colombia participated . Participants had to have at least two proximal lesions scored according to the following radiographic classification system : radiolucency ( 1 ) in enamel outer half , ( 2 ) restricted to enamel-dentine junction , or ( 3 ) restricted to dentine outer third . Baseline , 1- and 2.5-year follow-up bitewing radiographs were taken . Test and control lesions were r and omly selected . After temporary separation test lesions were sealed ( adhesive ) . Parents/caregivers received a flossing leaflet for their children . Progression of the lesions was assessed by means of independent reading of conventional bitewing radiographs . Results : One-year ( n = 73 ) test vs. control lesion progression was 27.4 vs. 50.7 % , respectively ( p < 0.01 , McNemar ’s test ) , and 2.5-year ( n = 56 ) test vs. control lesion progression was 46.4 vs. 71.4 % , respectively ( p < 0.01 ) . The dropouts did not differ from those who remained in the study regarding relevant caries baseline data . More than 88 % of the participants presented positive to definitively positive behaviour and very low or low pain intensity at both first and second appointments . Conclusion : The sealing technique was superior to flossing instructions both after 1 and 2.5 years of follow-up and the majority of the participants had no anxiety or pain during the treatment Dental caries in Chinese pre-school children is common , and restorative treatment is not readily available . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . We divided 375 children ( aged 3 - 5 yrs ) with carious upper anterior teeth into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . NaF varnish ( 22,600 ppm F ) was applied every three months onto the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . We followed 341 children for 18 months . The mean numbers of new caries surfaces in the five groups were 0.4 , 0.4 , 0.8 , 0.6 , and 1.2 , respectively ( p = 0.001 ) . The respective mean numbers of arrested carious tooth surfaces were 2.8 , 3.0 , 1.7 , 1.5 , and 1.0 ( p < 0.001 ) The effect of 2-year chewing-gum use on the caries rates of primary teeth was studied in a combined school and home program in a sample of 510 initially 6-year-old subjects with high caries experience , low availability of fluoride , and difficult access to dental care . The gum , formed into either sticks or pellets , comprised either xylitol , sorbitol , or mixtures thereof . The gum was chewed for 5 min under supervision five times a day during the school year , and for variable times during nonschool days . Seven groups were studied . One group received no gum ; two xylitol gum groups received either pellet or stick gum as did , two sorbitol gum groups , and two groups received either of two types of xylitol/sorbitol pellet gum . The response variable was the development of a frank carious lesion detectable by physical loss of enamel and probable extension to the dentin for those surfaces of primary teeth that were not cavitated at baseline . Caries rates associated with the use of each of the gum types were compared to the caries rates in the no-gum group . The usage of all polyol gums result ed in a significant decrease of the caries onset rate ( p < 0.05 ) . The caries onset risk for a primary surface in the xylitol pellet and the sorbitol pellet groups was 35 and 44 % of that in the no-gum group ( relative risk , 0.35 ; 95 % confidence interval , 0.21 - 0.59 ; relative risk , 0.44 ; 95 % confidence interval , 0.30 - 0.63 , respectively ) . The caries onset risk in the xylitol stick gum group was 53 % of that in the no-gum group ( relative risk , 0.53 ; 95 % confidence interval , 0.39 - 0.72 ) , which was marginally ( p = 0.1520 ) lower than in the sorbitol stick gum group ( relative risk , 0.70 ; 95 % confidence interval , 0.52 - 0.94 ) . The usage of both xylitol/sorbitol mixtures in pellet form was associated with a caries onset rate comparable with the usage of the xylitol stick gum . The largest caries risk reduction was observed in the group receiving xylitol pellet gum The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
13,961 | 24,813,322 | In all articles review ed , the authors reported a good clinical outcome , with many achieving marked improvement in clinical scores or overall satisfaction with the treatment .
Ultrasound-guided barbotage is a safe technique , with a high success rate and low complication rate . | PURPOSE A systematic review was performed to assess the outcomes and complications of ultrasound-guided barbotage ( repeated injection and aspiration ) for calcific tendonitis of the shoulder . | We carried out a prospect i ve , r and omised controlled trial on two groups of 40 patients with painful calcific tendonitis and a mean age of 48.4 years ( 32.5 to 67.3 ) . All were to undergo arthroscopic removal of the calcific deposit within six months after r and omisation . The 40 patients in group I received ultrasound-guided needling followed by high-energy shock-wave therapy and the 40 in group II had shock-wave therapy alone . In both groups one treatment consisting of 2500 impulses of shock waves with an energy flux density of 0.36 mJ/mm(2 ) was applied . The clinical and radiological outcome was assessed using the 100-point Constant shoulder scoring system and st and ardised radiographs . The mean follow-up was 4.1 months and no patient was lost to follow-up . Both groups had significant improvement in their Constant shoulder score . Radiographs showed disappearance of the calcific deposit in 60.0 % of the shoulders in group I and in 32.5 % of group II ( p < 0.05 ) . Significantly better clinical and radiological results were obtained in group I than in group II . Arthroscopic removal of the deposit was avoided in 32 patients of group I and in 22 of group II . No severe side-effects were recorded . Ultrasound-guided needling in combination with high-energy shock-wave therapy is more effective than shock-wave therapy alone in patients with symptomatic calcific tendonitis , giving significantly higher rates of elimination of the calcium deposits , better clinical results and reduction in the need for surgery PURPOSE To evaluate clinical response to treatment of calcified tendinitis of the shoulder by using a modified percutaneous ultrasonography (US)-guided fine-needle technique . MATERIAL S AND METHODS Thirty shoulders of 30 consecutive patients ( 23 women , seven men ; mean age , 47.4 years ) with chronic shoulder pain ( average duration , 43.1 months ) refractory to medical treatment were treated percutaneously by using a fine needle and US guidance . Patients were prospect ively evaluated by using a shoulder pain and disability index consisting of 13 items and divided into two subcategories : pain and disability . The patient completed the question naire before the procedure and during the follow-up visit approximately 1 month later . A diagnostic US examination was also performed at that time . RESULTS There was a statistically significant improvement in the shoulder pain and disability index total score ( 27.0 % ) and the pain ( 30.5 % ) and disability ( 23.9 % ) scores . According to the index , these results indicate a significant clinical response . CONCLUSION This modified US-guided fine-needle technique for calcified tendinitis of the shoulder appears to be an effective therapy and was less aggressive than previously described percutaneous techniques PURPOSE To compare short- and long-term outcomes of patients with rotator cuff calcific tendonitis who did and did not undergo ultrasonographically (US)-guided percutaneous treatment . MATERIAL S AND METHODS Institutional review board approval and informed patient consent were obtained . Of patients referred for US-guided treatment of rotator cuff calcific tendonitis , 219 ( 86 men , 133 women ; mean age , 40.3 years + /- 10.9 [ st and ard deviation ] ) were treated ; 68 ( 31 men , 37 women ; mean age , 40.2 years + /- 11.3 ) patients refused treatment and served as control subjects . After local anesthesia was induced , two 16-gauge needles were inserted into the calcific deposit . Saline solution was injected through one needle , and the dissolved calcium was extracted through the other needle . Shoulder joint function was assessed by using Constant scores , and pain was assessed by using visual analogue scale ( VAS ) scores . Mann-Whitney U and chi(2 ) tests were performed . RESULTS At baseline , no significant difference in age or sex distribution , Constant score , or VAS score was detected between treated and nontreated ( control ) patients . Compared with control subjects , treated patients reported a significant decrease in symptoms at 1 month ( mean Constant score , 73.2 + /- 6.2 vs 57.5 + /- 3.9 ; mean VAS score , 4.8 + /- 0.6 vs 9.1 + /- 0.5 ) , 3 months ( mean Constant score , 90.2 + /- 2.6 vs 62.6 + /- 7.2 ; mean VAS score , 3.3 + /- 0.4 vs 7.3 + /- 1.8 ) , and 1 year ( mean Constant score , 91.7 + /- 3.1 vs 78.4 + /- 9.5 ; mean VAS score , 2.7 + /- 0.5 vs 4.5 + /- 0.9 ) ( P < .001 ) . Symptom scores were not significantly different between the groups at 5 years ( mean Constant score , 90.9 + /- 3.6 vs 90.5 + /- 4.8 ; mean VAS score , 2.6 + /- 0.5 vs 2.8 + /- 0.7 ) ( P > or= .795 ) and 10 years ( mean Constant score , 91.8 + /- 5.0 vs 91.3 + /- 9.6 ; mean VAS score , 2.5 + /- 0.6 vs 2.7 + /- 0.6 ) ( P > or= .413 ) . CONCLUSION US-guided percutaneous treatment facilitated prompt shoulder function recovery and pain relief . Treated patients had better outcomes than did nontreated patients at 1 year . However , 5 and 10 years after the procedure , the nontreated group reported outcomes similar to those of the treated group OBJECTIVE The purpose of our study was to evaluate the short- and long-term effectiveness of sonographically guided percutaneous needle aspiration and lavage in calcific tendinitis of the shoulder and to study the progress of calcifications and symptoms in the first year after treatment . MATERIAL S AND METHODS Symptoms and radiologic findings after percutaneous aspiration of calcific tendinitis were prospect ively evaluated in the short and the long term using a shoulder pain and disability index , evaluation of shoulder motion , and a survey of the self-perception by the patients regarding the progress of their disease . RESULTS Sixty-seven consecutive shoulders were treated . A significant improvement was seen in shoulder motion , pain , and disability in the short term and in the long term ( p < 0.0001 ) . One year after treatment , 91 % of shoulders had substantially or completely improved , 64 % had perfect motion , and calcifications on radiography had resolved completely or nearly completely in 89 % . A transitory recurrence was observed approximately 15 weeks after treatment in 44.3 % of shoulders that improved . CONCLUSION Percutaneous needle aspiration and lavage is effective in the short term and in the long term in calcific tendinitis of the shoulder , with results similar to or better than those published for other techniques , and it is only slightly invasive and painful . Progress after treatment may include a transitory period of recurrence of the pain Objective To determine the effectiveness of ultrasound-guided aspiration and lavage in the treatment of patients with calcific tendinosis of the shoulder . Material s and methods Retrospective chart review result ed in 44 patients who were identified as having received ultrasound-guided aspiration of calcific tendinosis of the shoulder between 2000 and 2003 . Of these , 36 patients were interviewed by telephone for pre- and posttreatment assessment of pain , shoulder function , prior shoulder surgery , injury , and prescribed treatment modalities with a follow-up time of 8 months to 3.1 years ( mean = 22.5 months ) . L’Insalata score , numeric rating scale ( NRS ) , and patient satisfaction score served as outcome measures . Results Our criteria for a successful outcome included ( 1 ) 12-point or greater improvement in the L’Insalata shoulder rating question naire , ( 2 ) 2-point or greater improvement in the NRS , ( 3 ) patient satisfaction rating of “ good ” , “ very good ” , or “ excellent ” , ( 4 ) patients ’ willingness to undergo the procedure again if they experienced recurrent symptoms , and ( 5 ) 1 month or less of analgesic medication use after the aspiration procedure . We determined that ultrasound-guided aspiration of calcific tendinosis of the shoulder result ed in a successful outcome for 75 % ( 27/36 ) of patients with a mean 20.2-point improvement in the L’Insalata shoulder rating question naire score and a mean 6.4-point improvement in the NRS ( p < 0.01 ) . Conclusion : This retrospective study suggests that ultrasound-guided aspiration and lavage of calcific shoulder deposits appears to be an efficacious therapeutic modality for treatment of calcific tendinosis . Further studies involving prospect i ve r and omized controlled trials would be helpful to further assess the long-term efficacy of this procedure as a minimally invasive treatment for calcific tendinosis of the shoulder A self-administered question naire was design ed to assess the severity of symptoms related to and the functional status of the shoulder . It includes domains of global assessment , pain , daily activities , recreational and athletic activities , work , satisfaction , and areas for improvement . Each domain is grade d separately and is weighted to arrive at the total score . The over-all scale and each domain were prospect ively tested for validity , reliability , and responsiveness to clinical change . One hundred patients who were seen for evaluation of the shoulder were enrolled in the study . The validity of the scale was demonstrated by moderate-to-high correlation of the domains and individual questions of the Shoulder Rating Question naire with those of the Arthritis Impact Measurement Scales 2 . Validity was supported further by significant correlation of the scores in each domain with the level of satisfaction in that domain and by significantly lower scores in domains that patients selected as areas important for improvement . The over-all scale and each domain were internally consistent ( Cronbach alpha , 0.71 to 0.90 ) . Reproducibility was evaluated by repeated administration of the question naire after a mean of three days to forty patients whose condition was clinical ly stable . Reproducibility of the over-all question naire and individual domains was excellent ( Spearman-Brown index , 0.94 to 0.98 ) . Individual questions were reproducible , with a weighted kappa value of more than 0.7 for each . Responsiveness was evaluated by comparison of the preoperative and postoperative scores of thirty patients who had a satisfactory result one year after an operation on the shoulder . The over-all Shoulder Rating Question naire and each domain were responsive to clinical change as demonstrated by favorable st and ardized response means ( range , 1.1 to 1.9 ) and indices of responsiveness ( range , 1.1 to 2.0 ) . Similar analysis performed for individual diagnostic groups supported the validity , reliability , and responsiveness of the question naire in each group . The self-administered shoulder question naire was found to be valid , reliable , and responsive to clinical change . These qualities should make it a useful instrument for the prospect i ve assessment of the outcome of treatment of disorders related to the shoulder CONTEXT Extracorporeal shock wave therapy ( ESWT ) has been used to treat calcific tendonitis of the shoulder , but trials of ESWT for this purpose have had method ological deficiencies and thus there is limited evidence for its effectiveness . OBJECTIVE To determine whether fluoroscopy-guided ESWT improves function , reduces pain , and diminishes the size of calcific deposits in patients with chronic calcific tendonitis of the shoulder . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial conducted between February 1997 and March 2001 among 144 patients ( of 164 screened ) recruited from referring primary care physicians , orthopedic surgeons , and sports physicians in 7 orthopedic departments in Germany and Austria . INTERVENTIONS Either high-energy ESWT , low-energy ESWT , or placebo ( sham treatment ) . The 2 ESWT groups received the same cumulative energy dose . Patients in all 3 groups received 2 treatment sessions approximately 2 weeks apart , followed by physical therapy . MAIN OUTCOME MEASURES The primary end point was the change in the mean Constant and Murley Scale ( CMS ) score from baseline to 6 months after the intervention . Secondary end points were changes in the mean CMS scores at 3 and 12 months , as well as changes in self-rated pain and radiographic change in size of calcific deposits at 3 , 6 , and 12 months . RESULTS Of 144 patients enrolled , all completed treatment as r and omized and 134 completed the 6-month follow-up . Both high-energy and low-energy ESWT result ed in significant improvement in the 6-month mean ( 95 % confidence interval [ CI ] ) CMS score compared with sham treatment ( high-energy ESWT : 31.0 [ 26.7 - 35.3 ] points ; low-energy ESWT : 15.0 [ 10.2 - 19.8 ] points ; sham treatment : 6.6 [ 1.4 - 11.8 ] points ; P<.001 for both comparisons ) . Patients who received high-energy ESWT also had significant 6-month CMS improvements compared with those who received low-energy ESWT ( P<.001 ) . We found similar results for both the 3-month and 12-month CMS comparisons , as well as for self-rated pain and radiographic changes at 3 , 6 , and 12 months . CONCLUSIONS Both high-energy and low-energy ESWT appeared to provide a beneficial effect on shoulder function , as well as on self-rated pain and diminished size of calcifications , compared with placebo . Furthermore , high-energy ESWT appeared to be superior to low-energy ESWT A prospect i ve quasir and omized study was performed to compare the effects of surgical extirpation ( Group I , 29 patients ) with the outcome after high-energy extracorporeal shock wave therapy ( Group II , 50 patients ; 3000 impulses of an energy flux density of 0.6 mJ/mm2 ) in patients with a chronic calcifying tendinitis in the supraspinatus tendon . Symptoms and demographic data of the two groups were comparable . According to the University of California Los Angeles Rating System , the mean score in Group I was 30 points with 75 % good or excellent results after 12 months , and 32 points with 90 % good or excellent results after 24 months . Radiologically , there was no calcific deposit in 85 % of the patients after 1 year . In Group II , the mean score was 28 points with 60 % good or excellent results after 12 months , and 29 points with 64 % good or excellent results after 2 years . Radiologically , complete elimination of the deposit was observed in 47 % of the patients after 1 year . Clinical ly , according to the University of California Los Angeles score , there was no significant difference between both groups at 1 year . At 2 years , there was a significantly better result in Group II . Both groups then were subdivided into patients who had a homogenous deposit as seen on radiographs and patients who had an inhomogenous deposit before treatment . Surgery was superior compared with high-energy shock wave therapy for patients with homogenous deposits . For patients with inhomogenous deposits , high-energy extracorporeal shock wave therapy was equivalent to surgery and should be given priority because of its noninvasiveness |
13,962 | 27,863,993 | RESULTS Although not all studies found consistent results , the weight of the evidence suggests that high intakes and /or circulatory levels of magnesium , as well as vitamin D and the vitamin B group , may be associated with lower carotid IMT or reduced progression of carotid IMT .
The majority of studies did not find any significant association between vitamin E and C and carotid IMT .
Less evidence was available for associations of retinol , zinc , and iron with carotid IMT .
CONCLUSIONS In general , the current evidence concerning micronutrient intake and carotid IMT is largely inconclusive .
Pragmatic clinical trials are required to determine whether dietary or supplemental intake of specific micronutrients alters carotid IMT , which is a surrogate measure of cardiovascular risk | BACKGROUND Carotid intima media thickness ( IMT ) is a noninvasive marker of the extent and severity of sub clinical atherosclerosis .
Micronutrient intake may affect atherosclerosis and play a major role in the development of cardiovascular diseases ( CVDs ) .
OBJECTIVE The primary aim of this review was to synthesize the evidence regarding the association between carotid IMT and selected micronutrients . | Background —Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease . The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis . Methods and Results —Epidemiology : Progression of intima-media thickness ( IMT ) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a r and omly sample d cohort of utility employees age 40 to 60 years ( n=480 ) . Coculture : The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima . Mouse models : The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein ( 0.2 % by weight ) and LDL receptor-null mice to Western diet or Western diet plus lutein . IMT progression declined with increasing quintile of plasma lutein ( P for trend=0.007 , age-adjusted;P = 0.0007 , multivariate ) . Covariate-adjusted IMT progression ( mean±SEM ) was 0.021±0.005 mm in the lowest quintile of plasma lutein , whereas progression was blocked in the highest quintile ( 0.004±0.005 mm;P = 0.01 ) . In the coculture , pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner ( P < 0.05 ) . Finally , in the mouse models , lutein supplementation reduced lesion size 44 % in apoE-null mice ( P = 0.009 ) and 43 % in LDL receptor-null mice ( P = 0.02 ) . Conclusions —These epidemiological , in vitro , and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis BACKGROUND AND AIMS Cardiovascular diseases are the major cause of mortality among diabetic patients . The concentration of malondialdehyde ( MDA ) and homocysteine is believed to play a role in cardiovascular diseases . Omega-3 fatty acid supplementation could be effective in some diabetes complications and in the control of the glycemic index . However , it may increase lipid peroxidation . The objective of this study was to determine the effect of omega-3 fatty acids on the concentration of homocysteine and MDA in diabetic patients . METHODS AND RESULTS A r and omized double-blind , placebo-controlled clinical trial was conducted on 81 patients with type 2 diabetes . The patients were r and omly assigned to either the treatment or control groups . Each subject received three capsules of omega-3 fatty acids or a placebo every day for a period of 2months . The two groups were similar in terms of body mass index and food intake . At the beginning of the study and after 2months of supplementation their levels of HbA(1)c , homocysteine , MDA , C-reactive protein ( CRP ) , total cholesterol , LDL-cholesterol and fasting blood sugar ( FBS ) were determined . Due to omega-3 fatty acid supplementation , homocysteine was changed significantly in both treatment and control groups up to -3.10mumol/L and 0.10mumol/L respectively , and HbA(1)c decreased by 0.75 % in the treatment group and increased by 0.26 % in the control group . However , the changes in fasting blood sugar ( FBS ) , malondialdehyde ( MDA ) , C-reactive protein ( CRP ) , total cholesterol and LDL-cholesterol levels were not significant . CONCLUSION The consumption of omega-3 fatty acid supplements ( 3g/day ) for 2months decreases the levels of homocysteine in diabetic patients with no change in FBS , MDA and CRP levels Background —Some epidemiological studies have shown that increased iron stores are associated with increased cardiovascular events . Redox-active iron may contribute to lipid peroxidation , endothelial cell activation , and generation of reactive oxygen species ( especially hydroxyl radical , via Fenton chemistry ) . Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis . Methods and Results —To test the hypothesis that reducing vascular iron stores would reverse endothelial dysfunction , we examined the effects of the iron chelator deferoxamine ( 500 mg intra-arterially over 1 hour ) on vasomotor function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography . Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to methacholine compared with healthy control subjects ( P < 0.001 ) . Deferoxamine infusion decreased serum iron levels ( P < 0.001 ) . Deferoxamine improved the blood flow response to methacholine in patients with coronary artery disease ( P < 0.01 by 2-way repeated- measures ANOVA ) but had no effect on the response to sodium nitroprusside . In normal volunteers , deferoxamine had no effect on the response to methacholine . The nitric oxide synthase inhibitor NG-monomethyl-l-arginine abolished augmentation of the methacholine response associated with deferoxamine . The hydroxyl radical scavenger mannitol had no effect on the methacholine response . Conclusions —Deferoxamine improved nitric oxide – mediated , endothelium-dependent vasodilation in patients with coronary artery disease . These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis BACKGROUND Oxidative stress and inflammation are crucial in atherogenesis . alpha-Tocopherol is both an antioxidant and an antiinflammatory agent . OBJECTIVE We evaluated the effect of RRR-alpha-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease ( CAD ) on drug therapy . DESIGN R and omized , controlled , double-blind trial compared RRR-alpha-tocopherol ( 1200 IU/d for 2 y ) with placebo in 90 patients with CAD . Intimal medial thickness ( IMT ) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0 , 1 , 1.5 , and 2 y. At 6-mo intervals , plasma alpha-tocopherol concentrations , C-reactive protein ( CRP ) , LDL oxidation , monocyte function ( superoxide anion release , cytokine release , and adhesion to endothelium ) , and urinary F(2)-isoprostanes were measured . RESULTS alpha-Tocopherol concentrations were significantly higher in the alpha-tocopherol group but not in the placebo group . High-sensitivity CRP concentrations were significantly lowered with alpha-tocopherol supplementation than with placebo ( 32 % ; P < 0.001 ) . alpha-Tocopherol supplementation significantly reduced urinary F(2)-isoprostanes ( P < 0.001 ) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo ( P < 0.001 ) . No significant difference was observed in the mean change in total carotid IMT in the placebo and alpha-tocopherol groups . In addition , no significant difference in cardiovascular events was observed ( P = 0.21 ) . CONCLUSIONS High-dose RRR-alpha-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 INTRODUCTION Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease . The Homocysteine Lowering Trialists ' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25 % . Aim of this study was to investigate the effect of daily supplementation of folic acid ( 5 mg ) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor . METHODS We enrolled 103 patients with at least one cardiovascular risk factor who were r and omized to receive either a daily dose of 5 mg folic acid ( group I , n=53 ) or placebo ( group II , n=50 ) for 18 months . RESULTS After 18 months of folic acid supplementation , homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group . Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter . Significant regression of carotid IMT was observed ( 0.961+/-0.092 to 0.933+/-0.077 mm , p<0.001 ) compared to significant IMT progression in the placebo group ( 0.964+/-0.099 to 0.984+/-0.094 mm ) . CONCLUSION Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk OBJECTIVE Hyperhomocysteinemia is an independent risk factor for atherosclerotic vascular disease in chronic hemodialysis patients . This stratified r and omized controlled trial was design ed to measure the effect of high dose oral vitamin B6 , vitamin B12 , and folic acid on homocysteine levels , and to evaluate the effect on atherosclerosis as measured by Intima-Media Thickness ( IMT ) of carotid arteries . MATERIAL AND METHOD Fifty-four chronic hemodialysis patients with hyperhomocysteinemia were r and omized to receive oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 daily ( treatment group ) or oral 5 mg folic acid alone ( control group ) for 6 months . Homocysteine level and IMT were measured in both groups . RESULTS At 6 months , homocysteine levels in the treatment group were significantly reduced from 27.94 + /- 8.54 to 22.71 + /- 3.68 mmol/l ( p = 0.009 ) and were not significantly increased from 26.81 + /- 7.10 to 30.82 + /- 8.76 mmol/l in control group ( p = 0.08 ) . Mean difference between both groups was statistically significant ( p = 0.002 ) . There was no significant difference of IMT of carotid arteries , however , a tendency that the treatment group would have less thickness was observed ( 0.69 + /- 0.29 mm and 0.62 + /- 0.16 mm , p = 0.99 ) . CONCLUSION Treatment of hyperhomocysteinemia in chronic hemodialysis patients with daily oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 for 6 months decreases homocysteine levels and tends to reduce IMT of carotid arteries . A long term study for the prevention of atherosclerosis is warranted Abstract —Although a number of epidemiological studies have evaluated the association between & bgr;-carotene and the risk of cardiovascular diseases , there has been little research on the role of lycopene , an acyclic form of & bgr;-carotene , with regard to the risk of cardiovascular disease . We investigated the relationship between plasma concentrations of lycopene and intima-media thickness of the common carotid artery wall ( CCA-IMT ) in 520 middle-aged men and women ( aged 45 to 69 years ) in eastern Finl and . They were examined from 1994 to 1995 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention ( ASAP ) study , a r and omized trial concerning the effect of vitamin E and C supplementation on atherosclerotic progression . The subjects were classified into 2 categories according to the median concentration of plasma lycopene ( 0.12 & mgr;mol/L in men and 0.15 & mgr;mol/L in women ) . Mean CCA-IMT of the right and left common carotid arteries was 1.18 mm in men and 0.95 mm in women with plasma lycopene levels lower than the median and 0.97 mm in men ( P < 0.001 for difference ) and 0.89 mm in women ( P = 0.027 for difference ) with higher levels of plasma lycopene . In ANCOVA adjusting for cardiovascular risk factors and intake of nutrients , in men , low levels of plasma lycopene were associated with a 17.8 % increment in CCA-IMT ( P = 0.003 for difference ) . In women , the difference did not remain significant after the adjustments . We conclude that low plasma lycopene concentrations are associated with early atherosclerosis , manifested as increased CCA-IMT , in middle-aged men living in eastern Finl and Background —Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis . The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E ( SECURE ) , a sub study of the Heart Outcomes Prevention Evaluation ( HOPE ) trial , was a prospect i ve , double-blind , 3 × 2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients . Methods and Results —A total of 732 patients ≥55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were r and omly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E ( RRR-&agr;-tocopheryl acetate ) 400 IU/d or their matching placebos . Average follow-up was 4.5 years . Atherosclerosis progression was evaluated by B-mode carotid ultrasound . The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group , 0.0180 mm/year in the ramipril 2.5 mg/d group , and 0.0137 mm/year in the ramipril 10 mg/d group ( P = 0.033 ) . There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo . Conclusions —Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression . Vitamin E had a neutral effect on atherosclerosis progression Background —Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease ( CVD ) risk . In contrast , r and omized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events . Methods and Results —The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L ( 130 mg/dL ) and no clinical signs or symptoms of CVD . Eligible participants were r and omized to DL-&agr;-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years . The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness ( IMT ) assessed by computer image-processed B-mode ultrasonograms . A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates . Compared with placebo , & agr;-tocopherol supplementation significantly raised plasma vitamin E levels ( P < 0.0001 ) , reduced circulating oxidized LDL ( P = 0.03 ) , and reduced LDL oxidative susceptibility ( P < 0.01 ) . However , vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects r and omized to placebo . Conclusions —The results are consistent with previous r and omized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD Objective —Limited data exist from r and omized trials evaluating , noninvasively , the impact of antioxidant supplementation on vascular structure and function . Methods and Results —This is a sub study of the SU.VI.MAX Study , which is a r and omized , double-blind , placebo-controlled , cardiovascular and cancer primary prevention trial . Eligible participants ( free of symptomatic chronic diseases and apparently healthy ) were r and omly allocated to daily receive either a combination of antioxidants ( 120 mg vitamin C , 30 mg vitamin E , 6 mg beta carotene , 100 μg selenium , and 20 mg zinc ) or placebo and followed-up over an average of 7.2±0.3 years . At the end-trial examination , the carotid ultrasound examination and carotid – femoral pulse-wave velocity ( PWV ) measurement were performed blindly in 1162 subjects aged older than 50 years and living in the Paris area . The percentage of subjects with carotid plaques was higher in the intervention group compared with the placebo group ( 35.2 % versus 29.5 % , P = 0.04 ) . Common carotid intima-media thickness ( mean±SD ) was not different between the 2 groups ( 0.70±0.08 versus 0.70±0.08 mm , P = 0.38 ) . Mean PWV tended to be lower ( indicating less stiff aortic arteries ) in the intervention group but the difference did not reach statistical significance ( P = 0.13 ) . Conclusion —These results suggest no beneficial effects of long-term daily low-dose supplementation of antioxidant vitamins and minerals on carotid atherosclerosis and arterial stiffness Background Few studies have examined the association between global diet , assessed through dietary patterns , and arterial structure and function . The aim of this study was to investigate the relationship between carotid-femoral pulsewave velocity ( PWV ) , common carotid-arteries intima-media thickness ( CCA-IMT ) and plaques with dietary patterns measured 7.5 years earlier . Design A prospect i ve cohort study between diet and markers of structure and function of large arteries . Methods Dietary patterns ( linear combination of food consumption ) were identified using principal component analysis among 1026 middle-aged participants in the SUpplémentation en VItamines et Minéraux AntioXydants ( SU.VI.MAX ) vascular sub study . Dietary data were based on repeated 24-h dietary records ( at least three records during 2 years ) obtained at inclusion . Carotid-femoral PWV was used to assess aortic stiffness . Carotid ultrasound examination included measurements of CCA-IMT and carotid plaques . Results Four dietary patterns were identified . In multivariate models , a significant positive association was observed between PWV and a dietary pattern positively correlated with meat and alcohol consumption and negatively correlated with fibers , vitamins B9 and C , β-carotene and calcium consumption . Adjusted PWV mean across tertiles of this pattern score was 11.15,11.26 and 11.58 m/s in the first , second and third tertiles , respectively ( P for trend = 0.03 ) . Others dietary patterns were not associated with PWV and we detected no association between dietary patterns and IMT or plaques . Conclusion This study suggests that a nutritionally poor dietary pattern , characterized by a high meat and alcohol consumption and low micronutrients intake , is related to an increased stiffening of large arteries BACKGROUND Patients with HIV infection are at increased risk of cardiovascular disease ( CVD ) . Vitamin D insufficiency has been associated with increased CVD risk in non-HIV population s. This study sought to determine the relationship between vitamin D status and markers of CVD and HIV-related factors in HIV-positive patients . METHODS Patients with HIV infection on antiretroviral therapy and healthy controls were prospect ively enrolled . Fasting lipids , glucose , insulin , inflammatory markers ( soluble tumour necrosis factor-α receptor I , interleukin-6 and high-sensitivity C-reactive protein ) and endothelial markers ( soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 ) were measured . Fasting 25-hydroxyvitamin D ( 25(OH)D ) was measured from stored serum sample s. The internal carotid artery and common carotid artery ( CCA ) intima-media thickness ( IMT ) were measured in a subset of HIV-positive patients . Baseline cross-sectional data were analysed . RESULTS A total of 149 HIV-positive patients ( 56 with carotid IMT ) and 34 controls were included . Controls had higher adjusted mean 25(OH)D levels than HIV-positive patients ( P=0.02 ) . In multivariable linear regression among the HIV-positive patients , 25(OH)D was positively associated with CD4(+ ) T-cell restoration after antiretroviral therapy ( ΔCD4 = current - nadir CD4(+ ) T-cell ; P<0.01 ) , but was not associated with inflammatory or endothelial markers . In multivariable logistic regression , odds of having CCA IMT above the median were more than 10 × higher in those with lower 25(OH)D levels ( OR=10.62 , 95 % CI 1.37 - 82.34 ; P<0.01 ) . CONCLUSIONS Vitamin D status in HIV-positive patients was positively associated with improved immune restoration after antiretroviral therapy and negatively associated with CCA IMT . These findings suggest that vitamin D may play a role in HIV-related CVD and in immune reconstitution after antiretroviral therapy Despite aggressive treatment of cardiovascular disease ( CVD ) risk factors individuals with type 2 diabetes ( T2D ) still have increased risk of cardiovascular morbidity and mortality . The primary aim of this study was to examine the cross-sectional association between total ( 25-hydroxy vitamin D ( 25(OH)D ) ) and risk of CVD in patients with T2D . Secondary objective was to examine the association between 25(OH)D and bone health . A Danish cohort of patients with T2D participating in a r and omised clinical trial were analysed . In total 415 patients ( 68 % men , age 60±9 years ( mean±s.d . ) , duration of diabetes 12±6 years ) , including 294 patients ( 71 % ) treated with insulin . Carotid intima – media thickness ( IMT ) and arterial stiffness ( carotid artery distensibility coefficient ( DC ) and Young 's elastic modulus ( YEM ) ) were measured by ultrasound scan as indicators of CVD . Bone health was assessed by bone mineral density and trabecular bone score measured by dual energy X-ray absorptiometry . In this cohort , 214 patients ( 52 % ) were vitamin D deficient ( 25(OH)D < 50 nmol/l ) . Carotid IMT was 0.793±0.137 mm , DC was 0.0030±0.001 mmHg , YEM was 2354±1038 mmHg and 13 ( 3 % ) of the patients were diagnosed with osteoporosis . A 25(OH)D level was not associated with carotid IMT or arterial stiffness ( P>0.3 ) or bone health ( P>0.6 ) after adjustment for CVD risk factors . In conclusion , 25(OH)D status was not associated with carotid IMT , arterial stiffness or bone health in this cohort of patients with T2D . To explore these associations and the association with other biomarkers further , multicentre studies with large numbers of patients are required OBJECTIVES To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis , hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins . DESIGN AND SUBJECTS Double-masked two-by-two factorial trial , r and omization in four strata ( by gender and smoking status ) to receive twice daily either 91 mg ( 136 IU ) of d-alpha-tocopherol , 250 mg of slow-release vitamin C , a combination of these or placebo for three years . A r and omized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45 - 69 years with serum cholesterol > /= 5.0 mmol L-1 were studied . SETTING The population of the city of Kuopio in Eastern Finl and . INTERVENTION Twice daily either a special formulation of 91 mg of d-alpha-tocopherol , 250 mg of slow-release vitamin C , a combination of these ( CellaVie(R ) ) or placebo for three years . MEASUREMENTS Atherosclerotic progression , defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness ( IMT ) , was calculated over semi-annual assessment s. RESULTS The average increase of the mean IMT was 0.020 mm year-1 amongst men r and omized to placebo and 0.018 mm year-1 in vitamin E , 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group ( P = 0.008 for E + C vs. placebo ) . The respective means in women were 0.016 , 0.015 , 0.017 and 0.016 mm year-1 . The proportion of men with progression was reduced by 74 % ( 95 % CI 36 - 89 % , P = 0.003 ) by supplementation with the formulation containing both vitamins , as compared with placebo . CONCLUSIONS Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men . This may imply benefits with regard to other atherosclerosis-based events Objective Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness . We aim ed to study the impact of vitamin B-12 supplementation on these markers , in the vegetarians . Design Double-blind , placebo controlled , r and omised crossover study . Setting Community dwelling vegetarians . Participants Fifty healthy vegetarians ( vegetarian diet for at least 6 years ) were recruited . Intervention : Vitamin B-12 ( 500µg/day ) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover ( n=43 ) , and then open label vitamin B-12 for additional 24 weeks (n=41).MeasurementHow-mediated dilation of brachial artery ( FMD ) and intima-media thickness ( IMT ) of carotid artery were measured by ultrasound . Results The mean age of the subjects was 45 + 9 years and 22 ( 44 % ) were male . Thirty-five subjects ( 70 % ) had serum B-12 levels < 150pmol/l . Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels ( p<0.0001 ) and lowered plasma homocysteine ( p<0.05 ) . After vitamin B-12 supplementation but not placebo , significant improvement of brachial FMD ( 6.3±1.8 % to 6.9±1.9 % ; p<0.0001 ) and in carotid IMT ( 0.69±0.09 mm to 0.67±0.09 mm , p<0.05 ) were found , with further improvement in FMD ( to 7.4±1.7 % ; p<0.0001 ) and IMT ( to 0.65±0.09 mm ; p<0.001 ) after 24 weeks open label vitamin B-12 . There were no significant changes in blood pressures or lipid profiles . On multivariate analysis , changes in B-12 ( β=0.25 ; p=0.02 ) but not homocysteine were related to changes in FMD , ( R=0.32 ; F value=3.19 ; p=0.028 ) . Conclusions Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels , proposing a novel strategy for atherosclerosis prevention BACKGROUND AND AIM Plant foods may lower the risk of cardiovascular disease . METHODS AND RESULTS We assessed changes in the intima media thickness ( IMT ) of the carotid artery and diet in elderly men . Men ( n=563 ) aged 70+/-5 years were r and omly assigned to 1 of 4 groups ( dietary intervention , omega-3 supplementation , both or neither ) using a 2 x 2 factorial design . B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years . We previously showed that omega-3 supplementation did not influence the IMT , thus the dietary intervention ( n=233 ) and no dietary intervention ( n=231 ) groups were pooled . The dietary intervention group had less progression in the carotid IMT compared with the controls ( 0.044+/-0.091 mm versus 0.062+/-0.105 mm ; P=0.047 ) . This group increased their daily vitamin C intake ( P=0.005 ) and intake of fruit , berries and vegetables ( P < or=0.001 ) . Increased intake of vitamin C and of fruit and berries was inversely associated with IMT progression ( r=-0.181 ; P=0.006 and r=-0.125 ; P=0.056 , respectively ) . Multivariate linear regression analysis showed that increased intakes of vitamin C and of fruit and berries were associated with less IMT progression in the intervention group and in the total study population , after adjustment for consumption of dietary cholesterol , cheese , saturated fat and group assignment . CONCLUSION Vitamin C containing foods may protect against the progression of carotid atherosclerosis in elderly men Background The atherosclerotic process progresses more dynamically in hemodialysis ( HD ) patients than in the general population . In HD patients , lower magnesium levels were reported to be associated with increased atherosclerosis of the common carotid artery . We tested the hypotheses that magnesium supplementation helps to improve carotid intima media thickness ( IMT ) in HD patients . Material s and methods A total of 47 patients on HD were included in the study . Patients were r and omly divided into two groups : group A ( Mg group ) , in which patients were given magnesium citrate orally at a dosage of 610 mg every other day for 2 months and group B ( control group ) , in which patients received only calcium acetate therapy as a phosphate binder . At baseline and 2 months later , all patients underwent a carotid artery ultrasound scan to measure carotid IMT . Results At the end of 2 months , mean serum calcium , phosphorus , and calcium × phosphorus product were not changed in both groups . As expected , mean serum Mg level significantly increased in the Mg group at the end of 2 months . In addition , serum parathyroid hormone ( PTH ) level significantly decreased in the Mg group at the end of 2 months ( P = 0.003 ) . Baseline carotid IMT was similar between the groups . Bilateral carotid IMT was significantly improved in patients treated with magnesium citrate compared to initial values ( P = 0.001 for left , P = 0.002 for right ) . Conclusion Based on the present data , magnesium may play an important protective role in the progression of atherosclerosis in patients on dialysis . Further studies are needed to assess more accurately the role of magnesium in atherosclerotic regression in dialysis patients BACKGROUND There is accumulating experimental , epidemiological , and clinical evidence of an association between anti-oxidant vitamin intake and reduced risk of coronary heart disease . Using data from the Cholesterol Lowering Atherosclerosis Study ( CLAS ) , we explored the association of self-selected supplementary antioxidant vitamin intake on the rate of progression of early preintrusive atherosclerosis . METHODS AND RESULTS CLAS was an arterial imaging trial in which nonsmoking 40- to 59-year-old men with previous coronary artery bypass graft surgery were r and omized to colestipol/niacin plus diet or placebo plus diet . The rate of progression of early preintrusive atherosclerosis was determined in 146 subjects using high-resolution B-mode ultrasound quantification of the distal common carotid artery far wall intima-media thickness ( IMT ) . From the nutritional supplement data base , 22 subjects had an on-trial average supplementary vitamin E intake of > or = 100 IU per day ( high users ) and 29 subjects had an average on-trial supplementary vitamin C intake of > or = 250 mg per day ( high users ) . Within the placebo group , less carotid IMT progression was found for high supplementary vitamin E users when compared with low vitamin E users ( 0.008 versus 0.023 mm/y , P = .03 ) . No effect of vitamin E within the drug group was found . No effect of vitamin C within the drug or placebo group was found . CONCLUSIONS Supplementary vitamin E intake appears to be effective in reducing the progression of atherosclerosis in subjects not treated with lipid-lowering drugs while the process is still confined to the arterial wall ( early preintrusive atherosclerosis ) The relationship between dietary Zn intake and the risk of atherosclerosis remains unclear , and no epidemiological studies have been reported on the effects of dietary Zn intake on morphological changes in the vascular wall . We examined the relationship between dietary Zn intake and common carotid intima-media thickness ( IMT ) as a marker of sub clinical atherosclerosis among the middle-aged and elderly population s. A cross-sectional analysis of a prospect i ve cohort baseline study was performed with 4564 adults aged 40 - 89 years and free of clinical CVD . Dietary data were collected by trained interviewers using an FFQ . Common carotid IMT was measured using a B-mode ultrasound imaging technique . Sub clinical atherosclerosis was determined using carotid IMT , and defined as > 80th percentile of carotid IMT or ≥ 1 mm of carotid IMT . After adjustment for potential confounders , the mean carotid IMT in the low Zn intake group was higher than that in the high Zn intake group . When sub clinical atherosclerosis was defined as > 80th percentile value of IMT or ≥ 1 mm of carotid IMT , after adjustment for potential confounders , Zn intake was inversely related to sub clinical atherosclerosis ( 5th v. 1st quintile , OR 0.64 , 95 % CI 0.45 , 0.90 , P for trend = 0.069 ; 5th v. 1st quintile , OR 0.34 , 95 % CI 0.16 , 0.70 , P for trend = 0.005 , respectively ) . In persons free of clinical CVD , dietary Zn intake was inversely correlated with sub clinical atherosclerosis . The present findings suggest a putative protective role of dietary Zn intake against the development of atherosclerosis BACKGROUND Fe2 + released from tissue iron stores may accelerate lipid peroxidation by virtue of its pro-oxidant properties and thus promote early atherogenesis . METHODS AND RESULTS The present prospect i ve survey addresses the potential association between serum ferritin concentrations and the 5-year progression of carotid atherosclerosis as assessed by ultrasonographic follow-up evaluations . The study population comprises a r and om sample of 826 men and women 40 to 79 years old . Serum ferritin was one of the strongest risk predictors of overall progression of atherosclerosis . The main part of this association appeared to act through modification of the atherogenic potential of LDL cholesterol ( OR [ 95 % CI ] for a 1-SD unit increase in ferritin at LDL levels of 2.5 , 3.6 , and 4.9 mmol/L : 1.55 [ 1.30 to 1.85 ] , 1.77 [ 1.40 to 2.24 ] , and 2.05 [ 1.50 to 2.80 ] ; P=.0012 for effect modification ) . Changes in iron stores during the follow-up period modified atherosclerosis risk , in that a lowering was beneficial and further iron accumulation exerted unfavorable effects . All these findings applied equally to incident atherosclerosis and the extension of preexisting atherosclerotic lesions . The significance of prominent iron stores in the development of carotid stenosis was clearly less pronounced . Finally , ferritin and LDL cholesterol showed a synergistic association with incident cardiovascular disease and death ( n=59 ) . CONCLUSIONS The present study provided strong epidemiological evidence for a role of iron stores in early atherogenesis and suggests promotion of lipid peroxidation as the main underlying pathomechanism . This hypothesis could in part explain the sex difference in atherosclerotic vascular disease OBJECTIVE Hyperhomocysteinemia is associated with atherosclerotic risk . Although vitamins can lower homocysteine ( Hcy ) , information about effects on atherosclerosis is scarce . METHODS We used carotid intima-media thickness ( IMT ) as an accepted marker of atherosclerotic changes . Fifty patients ( 60 + /- 8 years ) with IMT > or = 1 mm were included . In a double blind , r and omized trial they received daily 2.5 mg folic acid , 25 mg Vitamin B6 , and 0.5 mg Vitamin B12 or placebo for 1 year . RESULTS In the treatment group , Hcy decreased from 10.50 + /- 3.93 to 6.56 + /- 1.53 micromol/l ( P < 0.0001 ) , whereas it remained unchanged in the placebo group ( 10.76 + /- 2.36 versus 10.45+/-3.30 micromol/l ) . IMT decreased from 1.50 + /- 0.44 to 1.42 + /- 0.48 mm ( P = 0.034 ) in the treatment group , whereas it increased from 1.47 + /- 0.57 to 1.54 + /- 0.71 mm in the placebo group . The mean individual changes of IMT between both groups differed significantly ( -0.08 + /- 0.17 versus 0.07 + /- 0.25 mm , P = 0.019 ) . Multiple regression analysis revealed that the observed effect on IMT depended only on medication . CONCLUSIONS Vitamin supplementation significantly reduces IMT in patients at risk . This effect is independent of Hcy concentration |
13,963 | 26,363,559 | Patients with PTUCD arthroplasty had also less radiological degenerative changes at the upper adjacent level .
Overall adverse events were twice more frequent in patients with ACDF .
The rate of revision surgery including both adjacent and index level was slightly higher in patients with ACDF , showing no statistically significant difference .
Conclusions According to this review , PTUCD arthroplasty showed a global superiority to ACDF in clinical outcomes .
The impact of both surgical techniques on the cervical spine ( radiological spine deterioration and /or complications ) was more severe in patients undergoing ACDF .
However , the rate of revision surgeries at any cervical level was equivalent for ACDF and PTUCD arthroplasty | Purpose To contrast the clinical and radiologic outcomes and adverse events of anterior cervical discectomy and fusion ( ACDF ) with a single cervical disc arthroplasty design , the polyurethane on titanium unconstrained cervical disc ( PTUCD ) . | Study Design Prospect i ve , r and omized , controlled . Level 1 evidence . Objective To report functional outcomes at 48 months follow-up on prospect ively r and omized patients to either the Bryan cervical disc prosthesis or anterior cervical discectomy and fusion ( ACDF ) at a single site . Summary of Background Data Surgical treatment of cervical disc pathology can involve discectomy and fusion ( ACDF ) , the gold st and ard technique . The safety and effectiveness of this procedure has been established and demonstrated in the literature , however , limitations have evolved and alternatives such as disc replacement are being investigated . Intervertebral disc replacement is design ed to preserve motion , both at affected and adjacent levels avoiding limitations of fusion such as adjacent level degeneration . New onset degenerative changes and possible recurring neurologic symptoms may be deferred or eliminated with cervical disc replacement . A recent multicenter trial with 24 months follow-up has shown the Bryan disc to compare favorably with ACDF . Continued follow-up is needed to further evaluate and compare functional outcomes in both these cohorts . Methods A total of 47 patients were enrolled at our site as part of an ongoing multicenter prospect ively r and omized study investigating ACDF versus Bryan cervical disc prosthesis . Functional outcomes are now reported at 48 months follow-up for our cohort of participants . Neck disability index score ( NDI ) , VAS neck and arm and SF-36 both physical and mental as well as complications and reoperations will be reported . Results Functional outcome data collected at routine follow-up for 48-months has favorably demonstrated improved functional outcomes for NDI , neck/arm pain VAS scores , and the SF-36 physical/mental health component scores for the Bryan arthroplasty and ACDF cohorts . The NDI scores for the Bryan arthroplasty preoperatively was 51 and at 48 months 10 . For ACDF preoperative NDI score was also 51 and at 48 months 16.7 . At 48 months NDI success , measured by ≥15 points NDI improvement demonstrated a 93.3 % success for Bryan arthroplasty and an 82.4 % success for ACDF . VAS neck pain scores for the Bryan arthroplasty preoperatively was 76.2 and at 48 months was 13.6 . VAS neck pain scores for ACDF preoperatively was 80.6 and at 48 months was 28.1 . Arm Pain scores were also measured and for the Bryan arthroplasty preoperatively measured 78.8 and at 48 months 10.8 . For ACDF arm pain scores preoperatively measured 77.1 and at 48 months 21.7 . These outcomes have not been associated with any degradation of outcome measures from 2 to 4 years . During the 48 months of follow-up at our institution we also report 6 secondary surgeries in our control group ( ACDF ) and only 1 in our investigational group ( Bryan ) . Of the 6 surgeries in the control group performed , 3 or 12 % to date were for adjacent level degenerative disease and 1 or 4 % for remote level degenerative disc disease . The remaining 2 surgeries were performed on the same patient for a pseudarthrosis . In the investigational group there was only 1 secondary surgery performed to date for adjacent level disease 5 % . Conclusions At 48 months , cervical arthroplasty with the Bryan cervical disc prosthesis continues to compare favorably to ACDF at our institution . There has been no degradation of functional outcomes from 24 to 48 months for NDI , VAS of neck and arm , and SF-36 . There has been a lower incidence of secondary surgeries for the Bryan arthroplasty cohort to date OBJECT Spinal arthroplasty is becoming more widely performed in the treatment of degenerative cervical disc disease . Although this new technology may offer benefits over arthrodesis , it also requires that the surgeon acquire new operative techniques , and new potential complications are introduced . To determine the incidence and distribution of perioperative complications , the authors analyzed their early data obtained in a series of patients treated with the Bryan Cervical Disc prosthesis . METHODS The authors prospect ively recorded operative data , complications , and clinical and radiographic outcome data in all patients treated with Bryan prosthesis-based arthroplasty at two tertiary care centers since 2001 . Patients underwent st and ard anterior cervical discectomy followed by one- to three-level arthroplasty . Ninety-six discs were implanted in 74 patients . The perioperative complication rate was 6.2 % per treated level . In one patient a retropharyngeal hematoma developed , requiring evacuation . Neurological worsening occurred in three patients . Intraoperative migration of the prosthesis was observed in one two-level case , whereas delayed migration occurred in one patient with postoperative segmental kyphosis . In another patient with severe postoperative segmental kyphosis , revision was required with a customized lordotic prosthesis . Heterotopic ossification and spontaneous fusion occurred in two cases ; motion was preserved in the remaining 94 prostheses . Partial dislocation of the prosthesis in extension occurred in one patient with preoperative segmental hypermobility , the first reported failure of a Bryan prosthesis . Twenty-five percent of patients reported neck and shoulder pain during the late follow-up period . There was a trend toward increased kyphosis of the C2 - 7 curvature postoperatively . CONCLUSIONS The Bryan prosthesis was effective in maintaining spinal motion . Major perioperative and device-related complications were infrequent Study Design . R and omized controlled study . Objective . To compare the rates of adverse events associated with disc arthroplasty versus those of anterior cervical discectomy and arthrodesis with allograft and plate . Summary of Background Data . Cervical disc arthroplasty as a substitute for fusion has been developed to maintain motion and , theoretically , prevent adjacent segment degeneration . Currently , cervical arthroplasty devices are undergoing clinical testing for safety and efficacy . The evaluation of safety is performed by critical analysis of all adverse occurrences following surgery to determine if the new device has a beneficial risk profile for the patient . Methods . Adverse events associated with Bryan Disc arthroplasty and arthrodesis were compared in a prospect i ve r and omized study . Four hundred sixty-three ( 463 ) patients having cervical radiculopathy and or myelopathy at a single level were treated at 31 sites . A total of 242 patients received the disc and 221 patients had anterior cervical discectomy and fusion . All patients were evaluated before surgery and at 1.5 , 3 , 6 , 12 , and 24 months after surgery . Adverse events were recorded concurrently and categorized by severity and as medically or surgically related . Results . No differences in overall medical events occurred between groups . Surgically related events occurred more frequently in the investigational group secondary to more complaints of postoperative dysphagia and late medical events occurred more frequently in the investigational patients . However , the more severe World Health Organization Grade 3 and 4 events occurred more frequently in the arthrodesis patients related to treatment of pseudarthrosis and persistent symptoms . Significantly , more cervical spine reoperations occurred in the fusion group . Only one spinal cord injury occurred and it was in the arthrodesis group and no patients had deep infection or death related to either procedure . Conclusion . Bryan cervical disc replacement and anterior cervical fusion are both safe procedures with a low incidence of significant adverse events related to the procedure . Statistically , more serious adverse events and reoperations occurred in the fusion group while a greater number of less serious surgically related events were seen in the investigational group BACKGROUND CONTEXT The Neck Disability Index ( NDI ) , the short form-36 ( SF-36 ) physical component summary ( PCS ) , and pain scales for arm and neck pain are increasingly used to evaluate treatment effectiveness after cervical spine surgery . The minimum clinical ly important difference ( MCID ) is a threshold of improvement that is clinical ly relevant to the patient . However , the true goal is to provide the patient with a substantial clinical benefit ( SCB ) . PURPOSE This study determines the MCID and SCB using common anchor-based methods for NDI , PCS , and pain scales for arm and neck pain in patients undergoing cervical spine fusion for degenerative disorders . STUDY DESIGN / SETTING The study setting is a longitudinal cohort in a multisurgeon spine specialty clinic . PATIENT SAMPLE The sample comprises 505 patients who underwent a cervical fusion for degenerative spine conditions and who have prospect ively collected outcome scores with a minimum 1-year follow-up . OUTCOME MEASURES The outcome measures of the study were NDI , SF-36 , and numeric rating scales for arm and neck pain . METHODS The MCID and SCB values for NDI , PCS , and pain scales for arm and neck pain were determined using receiver operating characteristic ( ROC ) curve analysis with the Health Transition Item of the SF-36 as an anchor . The Health Transition Item asks a patient " Compared to one year ago , how would you rate your health in general now ? " with answers ranging from " Much Better , " " Somewhat Better , " " About the Same , " " Somewhat Worse , " to " Much Worse . " An ROC curve was constructed for each measure . The ROC curve-derived MCID was the change score with equal sensitivity and specificity to distinguish the " Somewhat Better " from the " About the Same " patients . The ROC curve-derived SCB was the change score with equal sensitivity and specificity to distinguish the " Much Better " from the " Somewhat Better " patients . Distribution-based methods including the st and ard error of the mean and the minimum detectable change were also used to calculate MCID . RESULTS The calculated MCID is 7.5 for the NDI , 4.1 for SF-36 PCS , and 2.5 for arm and neck pain . The calculated SCB is 9.5 for the NDI , 6.5 for SF-36 PCS , and 3.5 for arm and neck pain . CONCLUSIONS Patients with an eight-point decrease in NDI , a 4.1-point increase in PCS , and a three-point decrease in arm or neck pain can detect a minimally clinical ly important change . Patients with a 10-point decrease in NDI , a 6.5-point increase in PCS , and a four-point decrease in arm or neck pain can detect an SCB after cervical spine fusion Study Design . Prospect i ve , r and omized , controlled study of patients with lumbar disc herniations , operated either in a full-endoscopic or microsurgical technique . Objective . Comparison of results of lumbar discectomies in full-endoscopic interlaminar and transforaminal technique with the conventional microsurgical technique . Summary of Background Data . Even with good results , conventional disc operations may result in subsequent damage due to trauma . Endoscopic techniques have become the st and ard in many areas because of the advantages they offer intraoperatively and after surgery . With the transforaminal and interlaminar techniques , 2 full-endoscopic procedures are available for lumbar disc operations . Methods . One hundred seventy-eight patients with full-endoscopic or microsurgical discectomy underwent follow-up for 2 years . In addition to general and specific parameters , the following measuring instruments were used : VAS , German version North American Spine Society Instrument , Oswestry Low-Back Pain Disability Question naire . Results . After surgery 82 % of the patients no longer had leg pain , and 14 % had occasional pain . The clinical results were the same in both groups . The recurrence rate was 6.2 % with no difference between the groups . The full-endoscopic techniques brought significant advantages in the following areas : back pain , rehabilitation , complications , and traumatization . Conclusion . The clinical results of the full-endoscopic technique are equal to those of the microsurgical technique . At the same time , there are advantages in the operation technique and reduced traumatization . With the surgical devices and the possibility of selecting an interlaminar or posterolateral to lateral transforaminal procedure , lumbar disc herniations outside and insidethe spinal canal can be sufficiently removed using the full-endoscopic technique , when taking the appropriate criteria into account . Full-endoscopic surgery is a sufficient and safe supplementation and alternative to microsurgical procedures BACKGROUND Although there have been case reports describing the use of cervical disc arthroplasty for the treatment of myelopathy , there is a concern that motion preservation may maintain microtrauma to the spinal cord , negatively affecting the clinical results . As we are not aware of any studies on the use of arthroplasty in this scenario , we performed a cross-sectional analysis of two large , prospect i ve , r and omized multicenter trials to evaluate the efficacy of cervical disc arthroplasty for the treatment of myelopathy . METHODS The patients in the current study were a cohort of patients who were enrolled in the United States Food and Drug Administration Investigational Device Exemption studies of the Prestige ST and Bryan disc replacements ( Medtronic , Memphis , Tennessee ) . The inclusion criteria were myelopathy and spondylosis or disc herniation at a single level from C3 to C7 . Clinical outcome measures were collected preoperatively and at six weeks , three months , six months , twelve months , and twenty-four months postoperatively . RESULTS A total of 199 patients were included in the present study ; 106 patients ( 53 % ) underwent arthroplasty , whereas ninety-three ( 47 % ) underwent arthrodesis . The Neck Disability Index , Short Form-36 scores , and specific arm and neck pain scores improved significantly from baseline at all time points . Patients in all four groups had improvement in the postoperative neurological status and gait function ; at twenty-four months after surgery , 90 % ( 95 % confidence interval , 77.8 % to 96.6 % ) of the patients in the arthroplasty group and 81 % ( 95 % confidence interval , 64.9 % to 92.0 % ) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Prestige ST trial and 90 % ( 95 % confidence interval , 75.8 % to 97.1 % ) of the patients in the arthroplasty group and 77 % ( 95 % confidence interval , 57.7 % to 90.1 % ) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Bryan trial . CONCLUSIONS We found that patients in both the arthroplasty and arthrodesis groups had improvement following surgery ; furthermore , improvement was similar between the groups , with no worsening of myelopathy in the arthroplasty group . While the findings at two years postoperatively suggest that arthroplasty is equivalent to arthrodesis for the treatment of cervical myelopathy for a single-level abnormality localized to the disc space , the present study did not evaluate the treatment of retrovertebral compression as occurs in association with ossification of the posterior longitudinal ligament , and we can not comment on the treatment of this condition In this prospect i ve study , our aim was to compare the functional results and radiographic outcomes of fusion and Bryan Cervical Disc replacement in the treatment of two-level cervical disc disease . A total of 65 patients with two-level cervical disc disease were r and omly assigned to two groups , those operated on with Bryan Cervical Disc replacement ( 31 ) and those operated on with anterior cervical fusion with an iliac crest autograft and plate ( 34 ) . Clinical evaluation was carried out using the visual analogue scale ( VAS ) , the Short Form 36 ( SF-36 ) and the neck disability index ( NDI ) during a two year follow-up . Radiological evaluation sought evidence of range of motion , stability and subsidence of the prosthesis . Substantial reduction in NDI scores occurred in both groups , with greater percent improvement in the Bryan group ( P = 0.023 ) . The arm pain VAS score improvement was substantial in both groups . Bryan artificial cervical disc replacement seems reliable and safe in the treatment of patients with two-level cervical disc disease . RésuméCette étude prospect i ve a pour but de comparer les résultats fonctionnels et radiographiques des patients ayant bénéficié soit d’une fusion , soit d’une athrodèse , soit d’une prothèse discale dans le traitement des lésions dégénératives des disques cervicaux portant sur deux niveaux . 65 patients présentant de telles lésions ont été r and omisés en deux groupes , ceux traités par la prothèse discale de Bryan ( 31 ) et ceux traités par ostéosynthèse antérieure avec autogreffe illiaque et plaque ( 34 ) . L’évaluation clinique a été réalisée en utilisant le score douleur VAS , ( échelle analogique ) , le score SF-36 , la raideur de la nuque index NDI , après deux ans de recul . L’évaluation radiologique permet de mettre en évidence les secteurs de mobilité de stabilité et la migration de la prothèse . Une diminution significative du score NDI est observée dans les deux groupes avec un pourcentage plus important d’amélioration dans le groupe des prothèses de type Bryan ( p = 0.023 ) . Le score douleur est nettement amélioré dans les deux groupes néanmoins il semble que la prothèse de type Bryan permet d’avoir des résultats beaucoup plus fiables et beaucoup plus sûrs dans le traitement de ces patients présentant des lésions discales dégénératives cervicales sur deux niveaux BACKGROUND CONTEXT The rationale for motion preservation by disc replacement after anterior cervical discectomy is to diminish long-term morbidity secondary to adjacent segment degeneration . However , these disc prostheses will be subject to wear and its possible adverse consequences . PURPOSE Assess the in vitro and in vivo wear properties of the Bryan Cervical Disc and the early clinical results . STUDY DESIGN In vitro mechanical testing , caprine animal model and prospect i ve European human trial . OUTCOME MEASURE In vitro mechanical testing used American Society for Testing and Material s st and ards to measure wear rates and debris . Caprine results were analyzed by histopathologic analysis by a blinded veterinary pathologist . Clinical outcomes were measured by Odoms 's criteria , independent radiologic analysis and Short Form-36 . METHODS In vitro wear testing in cervical spine simulator for up to 40 M cycles . Wear rates were determined and particles analyzed microscopically . The in vivo inflammatory response was studied in goats that had discectomy at C4-C5 . They were sacrificed between 3 and 12 months and histopathologically were compared with controls who had fusions with titanium plates . A prospect i ve clinical trial of 136 patients with minimum 1-year follow-up was analyzed using vali date d question naires and radiographs . RESULTS In vitro wear averaged approximately 1.76 % by weight at 10 M cycles and 18 % at 40 M cycles . Wear debris were present in the periprosthetic tissues in 4 of 11 animals without inflammatory response . The early clinical results were satisfactory in over 90 % of patients . CONCLUSION The in vivo and in vitro wear properties are satisfactory for the expected duration of life of the prosthesis . The early clinical results are satisfactory and equal to fusion Study Design . A prospect i ve , r and omized , multicenter study of surgical treatment of cervical disc disease . Objective . To assess the safety and efficacy of cervical disc arthroplasty using a new arthroplasty device at 24-months follow-up . Summary of Background Data . Cervical disc arthroplasty preserves motion in the cervical spine . It is an alternative to fusion after neurologic decompression , whereas anterior decompression and fusion provides a rigorous comparative benchmark of success . Methods . We conducted a r and omized controlled multicenter clinical trial enrolling patients with cervical disc disease . Ultimately 242 received the investigational device ( Bryan Cervical Disc ) , and 221 patients underwent a single-level anterior cervical discectomy and decompression and fusion as a control group . Patients completed clinical and radiographic follow-up examinations at regular intervals for 2 years after surgery . Results . Analysis of 12- and 24-month postoperative data showed improvement in all clinical outcome measures for both groups ; however , 24 months after surgery , the investigational group patients treated with the artificial disc had a statistically greater improvement in the primary outcome variables : Neck disability index score ( P = 0.025 ) and overall success ( P = 0.010 ) . With regard to implant- or implant/surgical-procedure-associated serious adverse events , the investigational group had a rate of 1.7 % and the control group , 3.2 % . There was no statistical difference between the 2 groups with regard to the rate of secondary surgical procedures performed subsequentto the index procedure . Patients who received the artificial cervical disc returned to work nearly 2 weeks earlier than the fusion patients ( P = 0.015 ) . Conclusion . Two-year follow-up results indicate that cervical disc arthroplasty is a viable alternative to anterior cervical discectomy and fusion in patients with persistently symptomatic , single-level cervical disc disease BACKGROUND The published two-year results of the pivotal U.S. Food and Drug Administration investigational device exemption trial with the use of the Bryan cervical disc arthroplasty compared with anterior cervical discectomy with fusion for treating single-level degenerative cervical disc disease revealed a significantly superior overall success rate in the arthroplasty group . The purpose of this study was to evaluate the midterm safety and effectiveness of the Bryan disc as an alternative to arthrodesis following anterior cervical discectomy . METHODS A prospect i ve , multicenter r and omized clinical trial was undertaken for the treatment of persistent radiculopathy or myelopathy due to single-level cervical disc herniations or spondylosis . Patients were r and omized to treatment with either the Bryan disc ( the arthroplasty group ; 242 patients ) or anterior cervical discectomy and fusion ( the fusion group ; 221 patients ) . Patients completed preoperative and postoperative self- assessment forms at specified intervals and had radiographs made preoperatively , at six weeks , and at three , six , twelve , twenty-four , and forty-eight months after surgery . The primary outcome measure was overall success , a composite variable of safety and efficacy measures . Numerous secondary measures were assessed . The follow-up data for up to twenty-four months have been previously published . We report in the present study the forty-eight-month data collected on 181 patients who received the Bryan disc and 138 patients who underwent anterior cervical discectomy and fusion . RESULTS The study groups were demographically similar . Substantial reduction in Neck Disability Index scores occurred in both groups compared with preoperative values . The greater improvement in the Neck Disability Index score in the Bryan disc cohort persisted through the four-year follow-up period ( p < 0.001 ) . The four-year overall success rates were 85.1 % and 72.5 % for the arthroplasty and fusion groups , respectively ( p = 0.004 ) . The improvement in the arm pain score was substantial for both groups and significantly greater in the Bryan disc cohort ( p = 0.028 ) , and the neck pain scores showed persistently greater improvement in the Bryan disc group at forty-eight months of follow-up ( p = 0.001 ) . Short Form-36 physical component score improvement remained greater among the Bryan disc cohort ( p = 0.007 ) . The mean range of motion for the Bryan disc was 8.08 ° and 8.48 ° at twenty-four and forty-eight months , respectively . Total and serious adverse event rates were similar between the groups . CONCLUSIONS The forty-eight-month follow-up data in the present report showed consistent , sustained significantly superior outcomes for cervical spine arthroplasty compared with cervical spine fusion . The arthroplasty cohort continued to show significantly greater improvements in Neck Disability Index , neck pain score , arm pain score , and Short Form-36 physical component score , as well as the primary outcome measure , overall success , at forty-eight months following surgery Study Design . Retrospective study of patients enrolled in a prospect i ve r and omized Food and Drug Administration trial with single level cervical disc replacement ( CDR ) with the ProDisc-C ( Synthes , Paoli , PA ) . Objective . Evaluate the segmental range of motion ( ROM ) in the cervical spine pre- and postoperative after CDR . Summary of Background Information . Each cervical level is believed to have its own biomechanical characteristics , ultimately leading to different sagittal and lateral ROM . Our underst and ing of the factors that influence motion after CDR continues to change and exp and . Methods . One hundred sixty-four patients with single level ProDisc-C arthroplasty were evaluated radiographically using Medical Metrics ( QMATM , Medical Metrics , Inc. , Houston , TX ) . Pre- and postoperative disc height and ROM were measured from st and ing lateral and flexion-extension radiographs . Of these 164 patients , 44 had a CDR at C6/C7 , 96 at C5/C6 , 18 at C4/C5 , and 6 at C3/C4 . The mean follow-up was of 24 months . Statistical analysis evaluated the difference in mean ROM between the groups . Results . Before surgery , C4/C5 had more sagittal ROM compared with C3/C4 , C5/C6 , and C6/C7 ( P < 0.001 . ) Before surgery , C4/C5 also had more lateral ROM compared with C3/C4 , C5/C6 , and C6/C7 ( P = 0.015 ) . After surgery , there were no significant differences in sagittal and lateral ROM between C3/C4 , C4/C5 , C5/C6 , and C6/C7 . The delta ( difference between pre- and postoperative ) proved that the C4/C5 CDR actually lost sagittal ROM ( −2.5 ° ) compared with the other levels , which gained sagittal ROM , C3/C4 ( 0.9 ° ) , C5/C6 ( 1.8 ° ) , and C6/C7 ( 1.6 ° ) ; P = 0.037 . There was no significant difference in the delta lateral ROM between the segments : C3/C4 , C4/C5 , C5/C6 , and C6/C7 . Conclusion . CDR approximates the different segmental sagittal and lateral ROM . Although C4/C5 had negative delta ROM in the sagittal and lateral planes , it provided a satisfactory final ROM . Long-term clinical outcome studies are needed to properly evaluate if these differences could ultimately affect the patients everyday life BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions BACKGROUND Although there have been case reports describing the use of cervical disc arthroplasty for the treatment of myelopathy , there is a concern that motion preservation may maintain microtrauma to the spinal cord , negatively affecting the clinical results . As we are not aware of any studies on the use of arthroplasty in this scenario , we performed a cross-sectional analysis of two large , prospect i ve , r and omized multicenter trials to evaluate the efficacy of cervical disc arthroplasty for the treatment of myelopathy . METHODS The patients in the current study were a cohort of patients who were enrolled in the United States Food and Drug Administration Investigational Device Exemption studies of the Prestige ST and Bryan disc replacements ( Medtronic , Memphis , Tennessee ) . The inclusion criteria were myelopathy and spondylosis or disc herniation at a single level from C3 to C7 . Clinical outcome measures were collected preoperatively and at six weeks , three months , six months , twelve months , and twenty-four months postoperatively . RESULTS A total of 199 patients were included in the present study ; 106 patients ( 53 % ) underwent arthroplasty , whereas ninety-three ( 47 % ) underwent arthrodesis . The Neck Disability Index , Short Form-36 scores , and specific arm and neck pain scores improved significantly from baseline at all time points . Patients in all four groups had improvement in the postoperative neurological status and gait function ; at twenty-four months after surgery , 90 % ( 95 % confidence interval , 77.8 % to 96.6 % ) of the patients in the arthroplasty group and 81 % ( 95 % confidence interval , 64.9 % to 92.0 % ) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Prestige ST trial and 90 % ( 95 % confidence interval , 75.8 % to 97.1 % ) of the patients in the arthroplasty group and 77 % ( 95 % confidence interval , 57.7 % to 90.1 % ) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Bryan trial . CONCLUSIONS We found that patients in both the arthroplasty and arthrodesis groups had improvement following surgery ; furthermore , improvement was similar between the groups , with no worsening of myelopathy in the arthroplasty group . While the findings at two years postoperatively suggest that arthroplasty is equivalent to arthrodesis for the treatment of cervical myelopathy for a single-level abnormality localized to the disc space , the present study did not evaluate the treatment of retrovertebral compression as occurs in association with ossification of the posterior longitudinal ligament , and we can not comment upon the treatment of this condition Study Design . Prospect i ve , r and omized , controlled study of patients with lateral cervical disc herniations , operated either in a full-endoscopic posterior or conventional microsurgical anterior technique . Objective . Comparison of results of cervical discectomies in full-endoscopic posterior foraminotomy technique with the conventional microsurgical anterior decompression and fusion . Summary of Background Data . Anterior cervical decompression and fusion is the st and ard procedure for operation of cervical disc herniations with radicular arm pain . Mobility-preserving posterior foraminotomy is the most common alternative in the case of lateral localization of the pathology . Despite good clinical results , problems may arise due to traumatization of the access . Endoscopic techniques are considered st and ard in many areas , since they may offer advantages in surgical technique and rehabilitation . These days , all disc herniations of the lumbar spine can be operated in full-endoscopic technique . With the full-endoscopic posterior cervical foraminotomy a procedures is available for cervical disc operations . Methods . One hundred and seventy-five patients with full-endoscopic posterior or microsurgical anterior cervical discectomy underwent follow-up for 2 years . In addition to general and specific parameters , the following measuring instruments were used : VAS , German version North American Spine Society Instrument , Hilibr and Criteria . Results . After surgery 87.4 % of the patients no longer had arm pain , and 9.2 % had occasional pain . The clinical results were the same in both groups . There were no significant difference between the groups in the revision or complication rate . The full-endoscopic technique brought advantages in operation technique , preserving mobility , rehabilitation , and traumatization . Conclusion . The recorded results show that the full-endoscopic posterior foraminotomy is a sufficient and safe supplement and alternative to conventional procedures when the indication criteria are fulfilled . At the same time , it offers the advantages of a minimally invasive intervention Anterior cervical decompression and fusion ( ACDF ) is the st and ard for cervical discectomies . With the full-endoscopic anterior cervical discectomy ( FACD ) a minimally invasive procedure is available . The objective of this prospect i ve , r and omised , controlled study was to compare the results of FACD with those of ACDF in mediolateral soft disc herniations . A total of 103 patients with ACDF or FACD were followed up for two years . In addition to general parameters specific measuring instruments were used . Postoperatively 85.9 % of the patients no longer had arm pain , and 10.1 % had occasional pain . There were no significant clinical differences between the decompression with or without fusion . The full-endoscopic technique afforded advantages in operation technique , rehabilitation and soft tissue injury . The recorded results show that FACD is a sufficient and safe alternative to conventional procedures when the indication criteria are fulfilled . At the same time , it offers the advantages of a minimally invasive intervention . RésuméLa décompression cervicale antérieure avec greffe ( ACDF ) est un st and ard de la chirurgie cervicale avec discectomies . La discectomie endoscopique FACD par voie mini-invasive est également possible . L’objectif de cette étude prospect i ve r and omisée est de comparer les résultats de cette technique endoscopique mini-invasive FACD avec la technique classique ACDF . 103 patients ayant bénéficié soit d’une ACDF soit d’une FACD ont été suivis pendant une moyenne de deux ans . après l’intervention , 85,9 % des patients ne présentent aucune douleur au niveau brachial et 10,1 % des douleurs occasionnelles . Il n’y a pas de différence significative que l’on ait réalisé ou non une greffe . La technique par endoscopie présente des avantages pratiques notamment en ce qui concerne la rééducation et les lésions des tissus en post-opératoires . le résultat montre que la technique FACD est une technique suffisamment sûre et es-t une alternative valable à la technique conventionnelle lorsque les critères d’indication ont été respectés . Cette technique a par ailleurs les avantages de la voie mini-invasive The purpose of this paper is to compare the new functional intervertebral cervical disc prosthesis replacement and the classical interbody fusion operation , including the clinical effect and maintenance of the stability and segmental motion of cervical vertebrae . Twenty-four patients with single C5 - 6 intervertebral disk hernias were specifically selected and divided r and omly into two groups : One group underwent artificial cervical disc replacement and the other group received interbody fusion . All patients were followed up and evaluated . The operation time for the single disc replacement was ( 130 ± 50 ) minutes and interbody fusion was ( 105 ± 53 ) minutes . Neurological or vascular complications were not observed during or after operation . There was no prosthesis subsidence or extrusion . The JOA score of the group with prosthesis replacement increased from an average of 8.6 to 15.8 . The JOA score of the group with interbody fusion increased from an average of 9 to 16.2 . The clinical effect and the ROM of the adjacent space of the two groups showed no statistical difference . The short follow-up time does not support the advantage of the cervical disc prosthesis . The clinical effect and the maintenance of the function of the motion of the intervertebral space are no better than the interbody fusion . At least 5 years of follow-up is needed to assess the long-term functionality of the prosthesis and the influence on adjacent levels . RésuméL’objectif de ce travail est de comparer les prothèses discales , cervicales à la classique arthrodèse intercorporéale , en analysant les aspects cliniques , la stabilité et la mobilité des vertèbres cervicales . 24 patients ayant présenté une hernie discale c5 c6 ont été sélectionnés et séparés en deux groupes r and omisés . Un groupe a bénéficié d’une prothèse discale et l’autre groupe d’une arthrodèse intercorporéale . Tous les patients ont été suivis et évalués . Résultats : le temps opératoire pour la prothèse discale a été de 50 à 130 minutes et le temps opératoire de l’arthrodèse de 53 à 105 minutes . Aucune complication neurologique ou vasculaire n’a été observée après les interventions . Le score JOA dans le groupe des prothèses a évolué de 8.6 à 15.8 et dans le groupe des arthrodèses de 9 à 16.2 . la symptopathologie clinique et la mobilité des espaces inter vertébraux adjacents à l’intervention chirurgicale ne montrent pas de différence statistique . En conclusion : ce suivi à court terme ne permet pas de mettre en évidence un avantage à la prothèse discale cervicale . Les résultats fonctionnels et la mobilité ne sont pas supérieurs à ceux d’une arthrodèse intercorporéale . Il faudra au moins cinq ans de suivi avant de mettre en évidence une éventuelle fonctionnalité à long terme des prothèses et leur influence bénéfique au niveau des espaces adjacents à l’intervention si tant est qu’il y en ait OBJECTIVE Patients with cervical radiculopathy and /or myelopathy are often treated with anterior cervical discectomy and fusion . Cervical arthroplasty has recently been advocated as an alternative treatment . Theoretically , arthroplasty should permit early return to activity and protect against adjacent segment disease . Early mobilization and return to activity may , theoretically , reduce cost to the workers ' compensation program . METHODS A subgroup analysis of workers ' compensation patients from the r and omized controlled trials comparing Prestige ST and Bryan ( Medtronic Sofamor Danek , Memphis , TN ) cervical arthroplasty to fusion was performed . Primary outcome measures were work status , time to return to work , and neck disability . Secondary outcome measures were neck and arm pain and Medical Outcomes Study Short-Form 36-Item Health Survey score . RESULTS One thous and four patients were enrolled in the studies , 93 of whom were workers ' compensation patients . At 6 weeks and 3 months , significantly more patients in the arthroplasty group were working compared with the fusion group . At 6 months and later , there was no significant difference in return-to-work rates . Overall , patients returned to work at a median of 101 days after arthroplasty , compared with 222 days after anterior cervical discectomy and fusion . This difference was not significant when controlling for sex , study , and preoperative work status . At all time points , the Neck Disability Index was consistently lower in the arthroplasty group compared with the fusion group ; however , the difference was not significant at 24 months . There was no statistically significant difference in secondary outcomes , neurological events , or pain-related events . CONCLUSION In this workers ' compensation cohort , it was observed that a greater number of patients in the arthroplasty group returned to work at 6 weeks and 3 months after surgery . A trend toward an earlier return to work was also seen , although this was not statistically significant when controlling for differences in the studies BACKGROUND CONTEXT Cervical arthroplasty theoretically reduces the risk of adjacent level disc degeneration and segmental instability that may be seen after a cervical fusion . An essential argument in confirming the utility of cervical arthroplasty is long-term confirmation that cervical disc replacements can maintain physiological kinematics at the index and adjacent levels . PURPOSE The purpose of this in vivo prospect i ve study was to characterize the long-term segmental kinematic outcomes after cervical arthroplasty . STUDY DESIGN / SETTING Prospect i ve cohort study . PATIENT SAMPLE Twenty patients with a 5-year clinical follow-up who underwent anterior cervical discectomy with insertion of the Bryan cervical disc . OUTCOME MEASURES Physiological measures ( kinematic analysis of lateral neutral , flexion , and extension radiographic imaging ) . METHODS Twenty consecutive patients with degenerative disc disease were followed with regular radiographic imaging after implantation of the Bryan cervical disc prosthesis . Lateral neutral , flexion , and extension radiographs ( n=240 ) were analyzed using Quantitative Motion Analysis software ( Medical Metrics , Inc. , Houston , TX , USA ) to measure the biomechanical profile at the index level and adjacent levels up to 5 years after surgery . Parameters collected included range of motion ( ROM ) , functional spinal unit ( FSU ) angle , anterior and posterior disc heights , sagittal translation , and center of rotation ( COR ) . RESULTS Biomechanics of the implanted artificial cervical disc was maintained up to 5 years with no significant changes in ROM , FSU angle , disc height , sagittal translation , and COR values when compared with early postoperative performance . Artificial discs were able to adequately restore and maintain preoperative kinematics . Early differences seen in disc height and FSU angle did not change during the duration of follow-up . No significant kyphotic changes or decrease in ROM were seen at the adjacent spinal levels . CONCLUSIONS The Bryan cervical disc prosthesis provides for a durable solution for functional spinal motion at the operated level and maintained the preoperative kinematics at adjacent levels at the 5-year follow-up The object of this study is to compare radiographic outcomes of anterior cervical decompression and fusion ( ACDF ) versus cervical disc replacement using the Bryan Cervical Disc Prosthesis ( Medtronic Sofamor Danek , Memphis , TN ) in terms of range of motion ( ROM ) , Functional spinal unit ( FSU ) , overall sagittal alignment ( C2–C7 ) , anterior intervertebral height ( AIH ) , posterior intervertebral height ( PIH ) and radiographic changes at the implanted and adjacent levels . The study consisted of 105 patients . A total of 63 Bryan disc were placed in 51 patients . A single level procedure was performed in 39 patients and a two-level procedure in the other 12 . Fifty-four patients underwent ACDF , 26 single level cases and 28 double level cases . The Bryan group had a mean follow-up 19 months ( 12–38 ) . Mean follow-up for the ACDF group was 20 months ( 12–40 months ) . All patients were evaluated using static and dynamic cervical spine radiographs as well as MR imaging . All patients underwent anterior cervical discectomy followed by autogenous bone graft with plate ( or implantation of a cage ) or the Bryan artificial disc prosthesis . Clinical evaluation included the visual analogue scale ( VAS ) , and neck disability index ( NDI ) . Radiographic evaluation included static and dynamic flexion-extension radiographs using the computer software ( Infinitt PiviewSTAR 5051 ) program . ROM , disc space angle , intervertebral height were measured at the operative site and adjacent levels . FSU and overall sagittal alignment ( C2–C7 ) were also measured pre-operatively , postoperatively and at final follow-up . Radiological change was analyzed using χ2 test ( 95 % confidence interval ) . Other data were analyzed using the mixed model ( SAS enterprises guide 4.1 versions ) . There was clinical improvement within each group in terms of VAS and NDI scores from pre-op to final follow-up but not significantly between the two groups for both single ( VAS p = 0.8371 , NDI p = 0.2872 ) and double ( VAS p = 0.2938 , NDI p = 0.6753 ) level surgeries . Overall , ROM and intervertebral height was relatively well maintained during the follow-up in the Bryan group compared to ACDF . Regardless of the number of levels operated on , significant differences were noted for overall ROM of the cervical spine ( p < 0.0001 ) and all other levels except at the upper adjacent level for single level surgeries ( p = 0.2872 ) . Statistically significant ( p < 0.0001 and p = 0.0172 ) differences in the trend of intervertebral height measurements between the two groups were noted at all levels except for the AIH of single level surgeries at the upper ( p = 0.1264 ) and lower ( p = 0.7598 ) adjacent levels as well as PIH for double level surgeries at the upper ( p = 0.8363 ) adjacent level . Radiological change was 3.5 times more observed for the ACDF group . Clinical status of both groups , regardless of the number of levels , showed improvement . Although clinical outcomes between the two groups were not significantly different at final follow-up , radiographic parameters , namely ROM and intervertebral heights at the operated site , some adjacent levels as well as FSU and overall sagittal alignment of the cervical spine were relatively well maintained in Bryan group compared to ACDF group . We surmise that to a certain degree , the maintenance of these parameters could contribute to reduce development of adjacent level change . Noteworthy is that radiographic change was 3.5 times more observed for ACDF surgeries . A longer period of evaluation is needed , to see if all these radiographic changes will translate to symptomatic adjacent level disease OBJECT Cervical total disc replacement ( TDR ) was developed to address some of the shortcomings associated with anterior cervical discectomy and fusion ( ACDF ) by preserving motion at the treated level . To establish an evidence -based rationale for cervical TDR to serve as a viable alternative to ACDF , cervical arthroplasty must establish equivalent or superior clinical outcomes while maintaining motion . The authors report on 98 patients from a single investigational site involved in 3 separate prospect i ve , r and omized , controlled investigational device exemption multicenter trials comparing cervical arthroplasty to ACDF with a 2 - 6-year follow-up . METHODS Patients with 1- and 2-level cervical disc disease producing radiculopathy and /or myelopathy were r and omized prospect ively under 3 separate investigational device exemption pivotal trials to undergo ACDF with plate or artificial disc placement . The 3 arthroplasty systems evaluated were the Bryan cervical disc , Kineflex/C disc , and Discover cervical disc . The patients were evaluated with pre- and postoperative serial neurological examinations , radiographs , and clinical outcome indices at 1 , 3 , 6 , 12 , 24 , 36 , 48 , and 60 months . RESULTS Ninety-eight patients were treated at the authors ' single investigational site . Fifty-seven of these patients underwent cervical arthroplasty and 41 underwent ACDF . A minimum 24-month follow-up was available for 90 patients ( 92 % ; 53 in the combined arthroplasty group and 37 in the combined ACDF group ) with a follow-up duration ranging from 24 to 67 months ( mean 38 months ) . Clinical success , defined as a composite measure consisting of 5 separate components , was significantly higher in the combined arthroplasty group ( 85 % ) compared with the combined ACDF group ( 70 % ; p = 0.035 ) . The Neck Disability Index and visual analog scale patient self-report measures were evaluated at 3 - 24-months follow-up , and all groups showed excellent clinical outcomes . All groups ( Bryan , Kineflex/C , Discover , and ACDF ) showed statistically significant improvement from the preoperative period to a minimum 2-year follow-up ( p < 0.0001 ) . Overall , angular motion was improved by 0.91 ° in the combined arthroplasty group and reduced by 7.8 ° in the combined ACDF group ( p < 0.0001 ) . In the ACDF group there was a fusion rate of 97 % ( 36 of 37 cases ) . In the arthroplasty group there was a 5.6 % incidence of bridging heterotopic ossification ( 3 cases ) . There were a total of 4 reoperations ( 7.5 % ) in the combined arthroplasty group with 1 ( 1.9 % ) at the adjacent level . There were 3 reoperations ( 8.1 % ) in the ACDF group , all at the adjacent level . CONCLUSIONS The prospect i ve , intermediate-term ( average follow-up > 3 years ) results of cervical TDR at the authors ' site are encouraging . Patients treated with the artificial discs showed significantly better clinical results , maintained motion at the treated level , and trended toward less adjacent-level disease Study Design . Prospect i ve , r and omized , controlled , multicenter clinical trial . Objective . To compare outcomes of cervical disc arthroplasty with those of anterior cervical decompression and fusion ( ACDF ) in a Chinese population . Summary of Background Data . Cervical disc arthroplasty has been found to be superior to ACDF for maintaining range of motion ( ROM ) at the index spinal segment and possibly will avoid abnormal stress to adjacent segments . Methods . A total of 120 patients from 3 large hospitals in China were r and omly assigned to treatment with cervical disc arthroplasty ( n = 60 ) using the BRYAN prosthesis or ACDF ( n = 60 ) and were observed postoperatively for 24 months . Results . The 2 groups had similar preoperative demographics and baseline characteristics including ROM , neck disability index , and visual analogue scale for neck and arm pain . The total disc replacement ( TDR ) group had a significantly longer operation time than the ACDF group ( P < 0.001 ) . Outcome data obtained after 24 months revealed a significant difference between the groups in mean change from baseline in ROM at the index level ( P < 0.001 ) ; ROM was maintained in the TDR group but reduced in the ACDF group . There were no significant between-group differences in the baseline changes in neck disability index or visual analogue scale scores for pain . One patient in the TDR group and 4 patients in the ACDF group required reoperations . Conclusion . At 24 months after surgery , the cervical disc prosthesis yielded good clinical results while maintaining ROM at the index level . Cervical disc arthroplasty appears to be a viable alternative to ACDF |
13,964 | 26,515,604 | In comparison with NCT alone , NCT plus bevacizumab significantly improve ORR and R0 hepatic resection rate but not for hepatic resection rate . | PURPOSE To assess the efficacy of neoadjuvant chemotherapy ( NCT ) plus targeted agents versus NCT alone for the treatment of colorectal liver metastases ( CRLM ) patients . | PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different The present exploratory analysis examined the efficacy , safety , and quality -of-life effects of everolimus ( EVE ) + exemestane ( EXE ) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting . In BOLERO-2 , patients with hormone-receptor-positive ( HR+ ) , human epidermal growth factor receptor-2-negative ( HER2− ) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor ( NSAI ) were r and omly assigned ( 2:1 ) to receive EVE ( 10 mg/day ) + EXE ( 25 mg/day ) or placebo ( PBO ) + EXE . The primary endpoint was progression-free survival ( PFS ) by local assessment . Overall , 137 patients received first-line EVE + EXE ( n = 100 ) or PBO + EXE ( n = 37 ) . Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE ( hazard ratio = 0.39 ; 95 % CI 0.25–0.62 ) , while maintaining quality of life . This was confirmed by central assessment ( 15.2 vs 4.2 months ; hazard ratio = 0.32 ; 95 % CI 0.18–0.57 ) . The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting . Furthermore , the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR+ , HER2− advanced breast cancer in postmenopausal patients BACKGROUND The BOLERO-2 study previously demonstrated that adding everolimus ( EVE ) to exemestane ( EXE ) significantly improved progression-free survival ( PFS ) by more than twofold in patients with hormone-receptor-positive ( HR(+ ) ) , HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors ( NSAIs ) . The overall survival ( OS ) analysis is presented here . PATIENTS AND METHODS BOLERO-2 is a phase III , double-blind , r and omized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo ( PBO ) + EXE 25 mg/day in postmenopausal women with HR(+ ) advanced breast cancer with prior exposure to NSAIs . The primary end point was PFS by local investigator assessment ; OS was a key secondary end point . RESULTS At the time of data cutoff ( 3 October 2013 ) , 410 deaths had occurred and 13 patients remained on treatment . Median OS in patients receiving EVE + EXE was 31.0 months [ 95 % confidence interval ( CI ) 28.0 - 34.6 months ] compared with 26.6 months ( 95 % CI 22.6 - 33.1 months ) in patients receiving PBO + EXE ( hazard ratio = 0.89 ; 95 % CI 0.73 - 1.10 ; log-rank P = 0.14 ) . Post study treatments were received by 84 % of patients in the EVE + EXE arm versus 90 % of patients in the PBO + EXE arm . Types of post study therapies were balanced across arms , except for chemotherapy ( 53 % EVE + EXE versus 63 % PBO + EXE ) . No new safety concerns were identified . CONCLUSIONS In BOLERO-2 , adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinical ly meaningful and statistically significant improvement in the primary end point , PFS ( 4.6-months prolongation in median PFS ; P < 0.0001 ) . Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting . TRIAL REGISTRATION NUMBER NCT00863655 Background Few targeted therapies ( TTs ) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after st and ard treatment escape . The French Sarcoma Group - Bone Tumor Study Group ( GSF-GETO ) created a national registry to evaluate the outcome of patients treated with off-label TTs . Methods Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included . The objective was to describe this patient efficacy and safety data in routine practice . Results From October 2008 to October 2011 , 249 patients in 24 centers received 278 treatment lines with TTs . Twenty-five histological subtypes were included : most frequent were leiomyosarcoma ( n = 48 , receiving sorafenib in 63 % , and sunitinib in 27 % ) , GIST ( n = 39 , receiving sorafenib in 79 % ) , and angiosarcoma ( n = 18 , receiving sorafenib in 78 % ) . The overall response rate to TTs was 15 % ( 95 % CI [ 10,6 - 20,2 ] ) , the disease control rate at 2 months was 59 % . The median progression-free survival was 4,1 months ( IC 95 % [ 3,2 - 4,8 ] ) . Three complete responses were observed . No toxic death occurred , grade 3 and 4 toxicities were reported in 74 ( 27 % ) and 14 patients ( 5 % ) respectively . Conclusion Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-r and omized clinical trials BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care ( 287 patients ) or best supportive care alone ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) BACKGROUND Postmenopausal women with hormone receptor-positive ( HR(+ ) ) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor ( NSAI ) are usually treated with exemestane ( EXE ) , but no single st and ard of care exists in this setting . The BOLERO-2 trial demonstrated that adding everolimus ( EVE ) to EXE improved progression-free survival ( PFS ) while maintaining quality of life when compared with EXE alone . Because many women with HR(+ ) advanced breast cancer are elderly , the tolerability profile of EVE plus EXE in this population is of interest . PATIENTS AND METHODS BOLERO-2 , a phase III r and omized trial , compared EVE ( 10 mg/d ) and placebo ( PBO ) , both plus EXE ( 25 mg/d ) , in 724 postmenopausal women with HR(+ ) advanced breast cancer recurring/progressing after treatment with NSAIs . Safety and efficacy data in elderly patients are reported at 18-month median follow-up . RESULTS Baseline disease characteristics and treatment histories among the elderly subsets ( ≥ 65 years , n = 275 ; ≥ 70 years , n = 164 ) were generally comparable with younger patients . The addition of EVE to EXE improved PFS regardless of age ( hazard ratio , 0.59 [ ≥ 65 years ] and 0.45 [ ≥ 70 years ] ) . Adverse events ( AEs ) of special interest ( all grade s ) that occurred more frequently with EVE than with PBO included stomatitis , infections , rash , pneumonitis , and hyperglycemia . Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths . CONCLUSION Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+ ) advanced breast cancer . Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population 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 The authors present the long‐term follow‐up ( > 25 years ) data from 1 of the original prospect i ve , r and omized trials that compared adjuvant chemotherapy with expectant management in patients with high‐ grade , localized osteosarcoma . In addition , the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease‐free and overall survival Background Osteosarcoma is the most frequent primary malignant bone tumor . In Europe and the United States , its prognosis has been greatly improved by the use of multimodal treatment , including preoperative and postoperative chemotherapy as well as surgery . In Japan , however , only a few clinical studies on osteosarcoma have been carried out . Methods To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic , operable osteosarcoma arising in the extremities , a prospect i ve multiinstitutional phase II trial , the Neoadjuvant Chemotherapy for Osteosarcoma ( NECO ) study , was conducted . Preoperative chemotherapy included high-dose methotrexate ( HD-MTX ) , cisplatin ( CDDP ) , and adriamycin ( ADR ) . If the induction therapy was assessed as not effective , high-dose ifosfamide ( IFO ) was added to the chemotherapy regimen . A total of 124 patients were enrolled in this trial , and ultimately 113 patients were eligible . Results The 5-year overall survival ( OAS ) and event-free survival ( EFS ) rates in the NECO study were 77.9 % and 65.5 % , respectively . A good histological response to the induction chemotherapy result ed in favorable OAS ( 78.7 % ) . The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes ( OAS 89.5 % , EFS 68.2 % ) . There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy . Conclusions We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan . The results suggest efficacy of the high-dose IFO addition to the st and ard three-drug chemotherapy regimen . However , a r and omized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma |
13,965 | 19,250,346 | Although feedback from the patient 's perspective is generally recommended , most SPs provided feedback on clinical skills and communication skills .
DISCUSSION There appear to be no clear st and ards with regard to effective feedback training for SPs . | OBJECTIVES Although the importance of feedback by simulated patients ( SPs ) is generally recognised , knowledge is scarce about the most effective ways in which SPs can provide feedback .
In addition , little is known about how SPs are trained to provide feedback .
This study aim ed to provide a systematic overview of the ways in which SPs provide feedback to undergraduate medical students , the domains in which SPs provide feedback and the ways in which SPs are trained to provide feedback . | OBJECTIVE : To determine whether residents perceived oral , face-to-face feedback about their continuity clinic performance as better than a similar , written version . DESIGN : Single-blind , r and omized controlled trial . SETTING : Two university-based , internal medicine residency clinics . PARTICIPANTS : All 68 internal medicine and combined program ( medicine-pediatrics , medicine-psychiatry , medicine-neurology , and preliminary year ) residents and their clinic preceptors . MEASUREMENTS AND MAIN RESULTS : Residents at each program were separately r and omized to oral or written feedback sessions with their clinic preceptors . The oral and written sessions followed similar , structured formats . Both groups were later sent question naires about aspects of the clinic . Sixty-five ( 96 % ) of the residents completed the question naire . Eight of the 19 questions dealt with aspects of feedback . A feedback scale was developed from the survey responses to those eight questions ( α=.86 ) . There were no significant differences in the responses to individual questions or in scale means ( p>.20 ) between the two feedback groups . When each university was analyzed separately , one had a higher scale mean ( 3.10 vs 3.57 , p=.047 ) , but within each university , there were no differences between the oral and written feedback groups ( p>.20 ) . CONCLUSIONS : No differences were observed between the oral and written feedback groups . In attempting to provide better feedback to their residents , medical educators may better apply their efforts to other aspects , such as the frequency of their feedback , rather than the form of its delivery Second-year medical students performed a head-to-toe screening physical examination on trained patient instructors ( PIs ) as a high-stakes examination before beginning clinical clerkships . PIs completed a 138-item checklist and instructed the students in the proper performance of any incorrectly executed or omitted items . To assess the accuracy of the PI ratings , ' monitor ' PIs watching the encounter by video completed checklists for 11 retests of failed students in 2001 and for 28 r and omly selected encounters in 2002 . Checklist-level discrepancies measured by mean absolute checklist difference were 8 % in 2001 and 9 % in 2002 . Case-level mean difference between raters in 2002 was -2.9 % . The inter-rater reliability for a single rater , estimated by the intra-class correlation coefficient for total encounter scores , was 0.95 . The assessment and feedback were well received by the students . The Head-to-Toe examination provides a reliable assessment of a student 's ability to carry out a complete screening physical examination . Patient instructors can be trained to acceptable accuracy and reliability despite the length and complexity of the exercise , and can provide effective feedback and teaching targeted to individual student deficiencies Learning proper techniques in physical examinations is m and atory for a physician . Although students may examine each other in early training , examination of the female pelvis does not readily conform to this reciprocity . A r and omized study was conducted , comparing teaching methods utilizing professional patients or plastic models . Training on a professional patient significantly increased a student 's chance of palpating one or both ovaries , reduced the student 's anxiety about performing a pelvic examination , and may have improved the student 's gentleness . Costs of the professional patient method were minimal . It is recommended that teaching pelvic examinations with the professional patient replace teaching on the plastic model PURPOSE : To evaluate two smoking-cessation practice exercises , one using st and ardized patients ( SPs ) , the other using role playing by medical students . METHOD : In the spring of 1994 all 120 first-year University of California , San Francisco , School of Medicine Students were given lectures on the health effects of smoking and how physicians can help patients quit . Afterward some of the students were r and omly assigned to two groups in which to practice counseling patients : Group 1 ( n = 35 ) used SPs , Group 2 ( n = 37 ) used role playing . Each of the Group 1 students practice d smoking-cessation techniques with an SP ; the SP evaluated the student on cognitive and communication skills , assigned an overall rating , and provide feedback using a st and ardized form . The Group 2 students ( as well as the 48 students not assigned to a group ) role-played in pairs and used the same form to provide feedback . All the students evaluated their respective practice practice s. Two weeks later 24 Group 1 and 31 Group 2 students participated in a clinic-skills- assessment exercise using SPs . As in the Group 1 practice exercise , each student was evaluated by an SP on cognitive and communication skills and assigned an overall rating . Data were analyzed through a number of statistical methods . The cost of the SP program was determined . RESULTS : The Group 1 students rated their practice exercise much more favorably than did the Group 2 students . However , there was no significant difference between the groups in their ratings by the SPs on the clinical -skills- assessment exercise . The use of SPs cost a great deal more than did the use of role playing . CONCLUSION : Although the students rated the SPs higher than they did the role playing , the two tools produced similar levels of skills attainment . The data suggest that having students practice smoking-cessation techniques through role playing may be as effective as using the more extensive SPs Purpose To compare two methods of teaching physical assessment , a traditional faculty-taught course and a course with components taught by specially trained st and ardized patients ( SPs ) , with respect to students ' performances and costs . Method Medical students in their second year and without preliminary course work in physical assessment were taught by faculty-led small groups . Students in their first year were taught by faculty-led lecture — demonstrations and exercises led by physical examination teaching associates ( PETAs ) . Both groups of students were tested with a performance-based examination that involved six identical stations . The costs of both courses were calculated using faculty and SP salaries . Results There was no difference in students ' performances on two of the stations , those involving the eye and abdominal examinations . The class that had been taught by PETAs , however , demonstrated a statistically significant performance advantage on the remaining four stations . The cost saving from using the PETAs was conservatively estimated at $ 24,155 . Conclusion Specially trained SPs can effectively teach the normal physical examination to medical students and are a less expensive alternative to traditional faculty small-group teaching methods The area of communication skills in adolescent medicine is emerging as a distinct and important part of the undergraduate curriculum . An appropriate level of confidence in dealing with the adolescent population is deemed a necessary educational requirement . Skills in psychosocial communication with adolescents differ from those required for younger patients and adults ; they include discussing confidentiality and adolescent risk-taking activities . Simulated patients can be used effectively in teaching and evaluating of communication skills . However , there is no report of using adolescent simulated patients to teach communication skills . The evidence available is inconclusive regarding the teaching time required to promote retention of communication skills , although a recent review suggests that one day ’s training or less is not effective . Long-term retention of these skills has been supported by only one paper , suggesting a need to follow students over time to ascertain the effect of communication skills training . Our study addressed two questions : ( 1 ) does feedback from a simulated adolescent patient and simulated mother lead to improvements in fourth-year medical students ’ psychosocial interviewing of adolescent patients ? and ( 2 ) does this skill persist following the intervention A class of 100 second-year medical students was r and omly divided into two groups for instruction in the techniques of the gynecologic examination . Each group received a lecture and a demonstration film . The control group then had practical instruction on office or clinic patients . The study group was instructed by specially trained clinical teaching associates who acted both as professional patients and as teachers . After practice in clinics and offices , both groups received a common evaluation by gynecologists and teaching associates . Students who were instructed by clinical teaching associates performed better on subsequent pelvic examinations and demonstrated superior communications skills compared with the control group Two nonphysician mothers were each trained to give a consistent and authentic history of a child 's common medical problem . At the beginning of a Pediatric Clerkship , one half the students were r and omly assigned to interview one of the trained mothers . The interviews were videotaped and then replayed in an evaluative feedback session with each student . At the end of the clerkship these students were rated significantly higher on the process of interviewing than those students who did not have the initial evaluative feedback session OBJECTIVES Facing dramatic reductions of inpatient beds and fewer faculty tutors , the Queen 's University medical school has had to consider alternatives to the traditional inpatient encounter for the early acquisition of clinical skills . The purpose of this study was to investigate the feasibility and impact on students of a model for a first-year clinical skills course , using exclusively st and ardized patients in place of in patients , and using a smaller ratio of faculty to students . DESIGN Twenty volunteers were selected from the first-year class of 75 students to participate as the experimental group . The remaining 55 students formed the control group . SETTING Queen 's University medical school , Ontario , Canada . SUBJECTS First-year medical students . RESULTS In measures of student satisfaction with the amount of performance feedback received during the course , there was a non-significant trend towards greater satisfaction among the experimental group compared to the control group . This occurred despite a tutor to student ratio of 1.5:10 in the experimental group compared to 3:10 in the control group . In the student evaluation of their tutors , mean scores for the two groups were 4.28 for the experimental group and 4 . 06 for the control group ( P = 0.10 ) . The mean OSCE scores for the two groups were 76.4 for the experimental group and 76.5 for the control group ( P = 0.93 ) . There is no practical or statistical difference in either of these two scores . CONCLUSIONS We conclude that this new model is feasible , was well received by the students and that the reduced tutor to student ratio and lack of inpatient encounters did not appear to adversely affect their learning The increasing difficulty in obtaining appropriate hospitalized patients to give enlarging classes of medical students their first exposure to abnormal physical findings has led to the development of an instructor-patient program . Sixteen community residents with relatively stable respiratory , cardiovascular , musculoskeletal , or neurological findings were recruited and trained as instructor- patients to teach the technical elements of the examination of the affected organ system . Evaluation of the technical skills of 46 second-year students trained by instructor- patients and those of 41 r and omly selected students trained in these skills by physician instructors demonstrated that the two have comparable technical skills five to eight weeks after the training sessions . Faculty recruitment , instructor-patient recruitment and training , and evaluation are discussed PURPOSE : This r and omized controlled study compared the interviewing skills of first-year medical students receiving feedback primarily from st and ardized patients ( SPs ) with those of students receiving feedback primarily from faculty . METHOD : All 154 first-year students at the University of Oklahoma College of Medicine in 1993 - 94 were video-taped to assess baseline and post-instruction interviewing skills . All the students , r and omized to one of three study groups , attended two four-hour workshops on interviewing skills . Instruction in the groups was as similar as possible except in the matter of who provided feedback . Two rating systems were used to rate the videotaped interviews for performances of targeted skills . RESULTS : Complete , usable data were available for 120 ( 78 % ) of the students . Skill ratings using the Arizona Clinical Interview Rating Scale were significantly higher for the “ types of questions used ” and “ use of empathy ” items in the SP-led feedback group . No significant difference in ratings was detected among the groups as measured by the Rotor Interactional Analysis System . CONCLUSION : The SPs were at least as effective as the faculty in effecting behavioral changes in the first-year medical students ' interviewing skills |
13,966 | 30,157,005 | For employment , strong evidence was found for the Individual Placement and Support ( IPS ) model and cognitive interventions .
For education , moderate evidence was found for supported education interventions .
This systematic review supports the role of occupational therapy practitioners in promoting the implementation of IPS , cognitive‐based , and social skills programs to improve vocational and educational outcomes for adults with SMI .
& NA ; Evidence supports the role of occupational therapy practitioners in promoting the implementation of IPS , cognitive‐based , and social skills programs to improve vocational and educational outcomes for adults with SMI | OBJECTIVE .
Many of the estimated 9.8 million American adults with serious mental illness ( SMI ) want to engage in employment and education , yet the majority report a need for more skills training .
This review presents evidence for the effectiveness of interventions that occupational therapy practitioners can provide to help people with SMI improve and maintain performance and participation in employment and education . | Background There is evidence from North American trials that supported employment using the individual placement and support ( IPS ) model is effective in helping individuals with severe mental illness gain competitive employment . There have been few trials in other parts of the world . Aims To investigate the effectiveness and cost-effectiveness of IPS in the UK . Method Individuals with severe mental illness in South London were r and omised to IPS or local traditional vocational services ( treatment as usual ) ( IS RCT N96677673 ) . Results Two hundred and nineteen participants were r and omised , and 90 % assessed 1 year later . There were no significant differences between the treatment as usual and intervention groups in obtaining competitive employment ( 13 % in the intervention group and 7 % in controls ; risk ratio 1.35 , 95 % CI 0.95–1.93 , P = 0.15 ) , nor in secondary outcomes . Conclusions There was no evidence that IPS was of significant benefit in achieving competitive employment for individuals in South London at 1-year follow-up , which may reflect suboptimal implementation . Implementation of IPS can be challenging in the UK context where IPS is not structurally integrated with mental health services , and economic disincentives may lead to lower levels of motivation in individuals with severe mental illness and psychiatric professionals BACKGROUND An international six-centre r and omised controlled trial comparing individual placement and support ( IPS ) with usual vocational rehabilitation for people with serious mental illness found IPS to be more effective for all vocational outcomes . AIMS To determine which patients with severe mental illness do well in vocational services and which process and service factors are associated with better outcomes . METHOD Patient characteristics and early process variables were tested as predictors of employment outcomes . Service characteristics were explored as predictors of the effectiveness of IPS . RESULTS Patients with previous work history , fewer met social needs and better relationships with their vocational workers were more likely to obtain employment and work for longer . Remission and swifter service uptake were associated with working more . Having an IPS service closer to the original IPS model was the only service characteristic associated with greater effectiveness . CONCLUSIONS The IPS service was found to be more effective for all vocational outcomes . In addition , maintaining high IPS fidelity and targeting relational skills would be a valuable focus for all vocational interventions , leading to improved employment outcomes . Motivation to find work may be decreased by satisfaction with current life circumstances This report describes the results of a r and omized controlled feasibility study of the Mindfulness Intervention for Rehabilitation and Recovery in Schizophrenia ( MIRRORS ) . MIRRORS is an adaptation of Mindfulness-Based Stress Reduction design ed to help persons with schizophrenia to persist and perform better at work . Thirty-four participants with schizophrenia or schizoaffective disorder who were engaged in outpatient services were enrolled in a vocational rehabilitation program that included a job placement and then were r and omized to receive MIRRORS ( n = 18 ) or Intensive Support ( n = 16 ) over a period of 16 weeks . The number of hours worked was recorded weekly and job performance was assessed monthly using the Work Behavior Inventory . Results of t-tests revealed that participants in the MIRRORS group worked a significantly greater number of hours and performed significantly better at the end of the 4-month intervention than those in the Intensive Support condition . Repeated- measures analysis of variance revealed that the MIRRORS group worked more hours each week on average and that this difference increased over time as well as having generally better work performance compared with the Intensive Support group . Results suggest a link between MIRRORS and higher levels of work performance and persistence in people with schizophrenia . Further research is indicated to evaluate MIRRORS in a fully powered r and omized controlled trial OBJECTIVE This purpose of this study was to determine whether participation in the Work-Ordered Day program of the Clubhouse model has a positive effect on vocational outcomes . METHOD The longitudinal study followed a group of individuals with severe mental illness who were r and omly assigned either to a Clubhouse program or a Program of Assertive Community Treatment team . Study participants were tracked for 135 weeks . These analyses evaluated the relationship between Work-Ordered Day participation and employment duration for the 43 study participants enrolled in the Clubhouse program who were active throughout the study and competitively employed during the study . RESULTS Participation in the Work-Ordered Day program had a significant positive impact on average duration of employment . On average , a 1-hr increase in participation prior to employment led to an increase of 2.3 weeks in competitive employment . CONCLUSIONS AND IMPLICATION S FOR PRACTICE Participants with more Work-Ordered Day program participation prior to employment had significantly longer average competitive employment duration even when controlling for prior work history . Participation in the Work-Ordered Day program is likely to improve work readiness . Further research is warranted to study which elements of the program may foment employment success . This could lead to increased implementation of the Work-Ordered Day program and its elements as precursors to employment for adults with severe mental illness OBJECTIVES The present study aims to investigate the synergistic effects of cognitive remediation training ( CRT ) on Integrated Supported Employment ( ISE ) . ISE blends individual placement support service with work-related social skills training for Chinese people suffering from schizophrenia or schizoaffective disorder . METHOD Ninety participants with schizophrenia or schizoaffective disorders were recruited from two psychiatric outpatient services in Hong Kong . They were r and omly assigned into the ISE+CRT ( n=45 ) and ISE ( n=45 ) conditions . Blinded assessment s on vocational , clinical , psychological , and neurocognitive outcomes were conducted by independent assessors . The two groups were followed up at 7 and 11months . RESULTS Both groups yielded similar improvements across several outcome domains assessed immediately after the interventions and at 7 and 11month follow-ups , but no significant group differences were found . Significant positive trends over time in vocational , clinical and cognitive outcomes consistently favored the ISE+CRT condition . CONCLUSION While both the ISE+CRT and ISE groups demonstrated improvement in vocational , clinical , psychological , and neurocognitive outcomes , there was no evidence to show that cognitive remediation facilitated further improvement in these domains beyond gains associated with ISE alone . Further investigation is needed to fully exploit the synergistic potential of ISE combined with CRT , and to better underst and which individuals experience a maximal benefit from the specific rehabilitation program components OBJECTIVE Schizophrenia is a mental disorder and characterized by abnormal social behavior and failure to recognize what is real . The current study was to explore the long-term effects of cognitive rehabilitation training on schizophrenia . METHODS Eighty six cases of hospitalized patients with schizophrenia were r and omly divided into study group and control group . The relapse and employment ( attending school ) rates were used as indicators to assess the treatment effect . All patients were followed up by 2 years . Kaplan-Meier survival analysis was conducted with relapse and employment ( attending school ) rates . RESULTS The rates of relapse in the study group and the control group were 18 % and 41 % , and relapse free survival time was 22.22 months and 18.55 months ; the rates of employment ( attending school ) were 64 % and 43 % , and not employment ( attending school ) time were 10.68 months and 15.74 months , respectively . There was significant difference between the two groups ( P<0.05 ) . CONCLUSIONS We found that the cognitive rehabilitation training could significantly reduce schizophrenic relapse rate , prolong the time of patients without relapse , improve the employment ( attending school ) rate , and shorten the discharged time , which is a powerful treatment method to improve social competence in schizophrenia patients Hoffmann H , Jäckel D , Glauser S , Kupper Z. A r and omised controlled trial of the efficacy of supported employment Abstract Background Although the effectiveness of individual placement and support ( IPS ) has been well established , little is known about clients ’ perceptions of the model compared to usual vocational rehabilitation , nor about their experiences of search ing for and returning to work with this kind of support . This qualitative study aim ed to explore clients ’ views of the difficulties of obtaining and maintaining employment , their experiences of the support received from their IPS or Vocational Service workers and the perceived impact of work on clients ’ lives . MethodS emi-structured interviews were conducted with 48 people with psychotic disorders participating in a six-centre international r and omised controlled trial of IPS compared to usual vocational rehabilitation . To assess their experiences of the services and the perceived effects of working , two IPS and two Vocational Service clients at each centre who had found work during the study period were interviewed , along with two IPS and two Vocational Service clients at each centre who had not . Results IPS clients reported having received more help seeking and maintaining employment , whereas Vocational Service clients reported having received more help in finding sheltered employment or placements . Clients who had worked associated this with financial stability , improved social lives , increased self-esteem , integration into society and amelioration of their symptoms , as well as reduced feelings of boredom and isolation , but also reported increased levels of stress . IPS clients as well as Vocational Service ones reported not receiving enough follow-up support , despite this being proposed as a key feature of the model . Conclusion Findings from the in-depth interviews reflect differences in service models that have also been tested quantitatively but further work in disaggregating the IPS model and assessing the impact of each component would be valuable Several studies in schizophrenia found a positive association between cognitive performance and work status , and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions . However little has been done to investigate whether vocational interventions itself benefit cognitive performance . To test this hypothesis we performed a r and omized , placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance . We recruited 112 remitted and clinical ly stable schizophrenic patients who aim ed to enter a vocational rehabilitation program . From these , 57 immediately entered a 6-months vocational rehabilitation program , whereas the remaining 55 were allocated to a waiting-list ; the latter formed our control group , which received during the 6 months out-clinic follow-up treatment . Before and after the 6-months period we assessed changes in cognitive performance through a neuropsychological test battery , as well as changes in the psychopathological status and in quality of life . We found that vocational rehabilitation significantly improved patients ' performance in cognitive measures that assess executive functions ( concept formation , shifting ability , flexibility , inhibitory control , and judgment and critics abilities ) . Moreover , after 6 months the vocational group improved significantly in the negative symptoms and in quality of life , as compared to controls . Together with results from the literature , our findings reinforce the notion that the inclusion of vocational interventions may enhance the effectiveness of therapeutic strategies for schizophrenia patients BACKGROUND Concerns are frequently expressed that working might worsen the mental health of people with severe mental illness ( SMI ) . Several studies of Individual Placement and Support ( IPS ) , however , have found associations between working and better nonvocational outcomes . IPS has been found to double the return to work of people with SMI in 6 European countries . AIMS To explore separately associations between IPS , returning to work , and clinical and social outcomes . METHODS Patients ( n = 312 ) in a r and omized controlled trial of IPS in 6 European centers were followed up for 18 months . RESULTS There were no differences in clinical and social functioning between IPS and control patients at 18 months . Those who worked had better global functioning , fewer symptoms , and less social disability at final follow-up ; greater job tenure was associated with better functioning . Working was associated with concurrently better clinical and social functioning , but this contrast was stronger in the control group , suggesting that IPS was better than the control service at helping more unwell patients into work . Working was associated with having been in remission and out of hospital for the previous 6 months . It was also associated with a slight decrease in depression and with being in remission over the subsequent 6 months . CONCLUSIONS Concerns among clinicians about possible detrimental effects of working and supported employment have been misplaced . Although some of the associations found may have been selection effects , there is sufficient evidence of work having beneficial effects on clinical and social functioning to merit further exploration OBJECTIVE Despite the large number of Latinos living in the United States , little research has evaluated the effectiveness of different vocational rehabilitation programs for individuals with severe mental illness in this rapidly growing minority population . This article presents a secondary analysis of a r and omized , controlled trial comparing supported employment with 2 other vocational rehabilitation programs in 3 ethnic/racial groups of participants with severe mental illness : Latinos , non-Latino African Americans , and non-Latino Whites . METHOD The data were drawn from a previously published r and omized , controlled trial comparing supported employment with st and ard vocational rehabilitation services and a psychosocial clubhouse program in persons with severe mental illness ( Mueser et al. , 2004 ) , including 64 Latinos , 91 non-Latino African Americans , and 43 non-Latino Whites . Comparisons were made between the 3 groups at baseline on demographic characteristics , clinical and psychosocial functioning , and quality of life . Within each ethnic/racial group , competitive employment and all paid employment outcomes were compared between the 3 vocational rehabilitation programs over the 2-year study period . RESULTS At baseline , the Latino participants had lower levels of education and disability income , were less likely to have worked competitively over the previous 5 years , had more severe symptoms , and worse psychosocial functioning than the non-Latino African American or non-Latino White participants . Latinos r and omized to supported employment had better competitive and all-paid work outcomes than those assigned to either st and ard services or the psychosocial clubhouse program , similar to the non-Latino consumers . Rates of competitive work for consumers in supported employment were comparable across all 3 racial/ethnic groups . DISCUSSION Supported employment is effective at improving competitive work in Latinos with severe mental illness . Efforts should be made to increase access to supported employment in the growing population of Latinos with severe mental illness Cognitive remediation ( CR ) has demonstrated good outcomes when paired with supported employment , however little is known about its effectiveness when integrated into a supported education program . This r and omized controlled trial examined the effectiveness of integrating CR within a supported education program compared with supported education without CR . Thirty-seven students with psychosis were recruited into the study in the 2012 academic year . Academic functioning , cognition , self-esteem , and symptomatology were assessed at baseline , at 4months following the first academic term in which CR was provided , and at 8months assessing maintenance of gains . The treatment group demonstrated better retention in the academic program and a trend of improvement across a range of academic functional domains . While both treatment and control groups showed improvement in cognitive measures , the outcomes were not augmented by CR training . CR was also associated with significant and sustained improvements in self esteem . Further research , investigating specific intervention components is required to clarify the mixed findings regarding the effectiveness of CR in an education setting Design ed to help persons with schizophrenia to persist and perform better at job placements , the Indianapolis Vocational Intervention Program ( IVIP ) is a program of cognitive-behavioral group and individual interventions . While its feasibility has been previously demonstrated , it is unknown whether IVIP assists persons to achieve greater levels of participation in vocational rehabilitation and higher levels of job performance . In this study , 100 participants with schizophrenia or schizoaffective disorder were offered a six month job placement and r and omized to receive IVIP ( n=50 ) or support services ( n=50 ) matched for treatment intensity . Number of hours worked was recorded weekly and job performance was assessed biweekly using the Work Behavior Inventory with raters blind to condition . t-tests revealed that participants in the IVIP group worked a significantly greater number of weeks than those in the support condition . Also , repeated measures ANOVA revealed the IVIP group worked more hours across that 26 week period as well . And with regards to work performance , repeated measures of the 56 participants who worked for at least two-thirds of the intervention revealed that participants in the IVIP group had generally better work performance than those in the support condition . Results suggest a connection between cognitive-behavioral interventions and higher levels of work performance in people with schizophrenia Objective : To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a r and omized controlled trial for individuals with early course schizophrenia . Method : Early course schizophrenia out patients ( N = 58 ) were r and omly assigned to cognitive enhancement therapy ( CET ) or an enriched supportive therapy ( EST ) control and treated for 2 years . Comprehensive data on cognition and employment were collected annually . Results : Individuals treated with CET were significantly more likely to be competitively employed , had greater earnings from employment , and were more satisfied with their employment status by the end of treatment compared to EST recipients . Mediator analyses revealed that improvements in both social and nonsocial cognition mediated CET effects on employment . Conclusion : CET can help facilitate employment in early schizophrenia by addressing the cognitive impairments that limit functioning in the disorder . Inclusion of cognitive rehabilitation in social work practice can support more optimal functional recovery from schizophrenia 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 OBJECTIVE Cognitive impairment presents a serious and common obstacle to competitive employment for people with severe mental illness , including those who receive supported employment . This study evaluated a cognitive enhancement program to improve cognition and competitive employment in people with mental illness who had not responded to supported employment . METHOD In a r and omized controlled trial , 107 people with severe mental illness ( 46 % with schizophrenia or schizoaffective disorder ) who had not obtained or kept competitive work despite receiving high-fidelity supported employment were assigned to receive either enhanced supported employment ( with specialized cognitive training of employment specialists ) or enhanced supported employment plus the Thinking Skills for Work program , a st and ardized cognitive enhancement program that includes practice of computer cognitive exercises , strategy coaching , and teaching of coping and compensatory strategies . Research assistants tracked competitive employment weekly for 2 years , and assessors blind to treatment assignment evaluated cognitive functioning at baseline , at the end of cognitive enhancement training , and 12 and 24 months after baseline . RESULTS Participants in the Thinking Skills for Work group improved more than those in the enhanced supported employment only group on measures of cognitive functioning and had consistently better competitive employment outcomes during the follow-up period , including in jobs obtained ( 60 % compared with 36 % ) , weeks worked ( 23.9 compared with 9.2 ) , and wages earned ( $ 3,421 compared with $ 1,728 ) . CONCLUSIONS The findings suggest that cognitive enhancement interventions can reduce cognitive impairments that are obstacles to work , thereby increasing the number of people who can benefit from supported employment and competitive work OBJECTIVE The individual placement and support model of supported employment has been shown to be more effective than other vocational approaches in improving competitive work over 1 - 2 years in persons with severe mental illness . The authors evaluated the longer-term effects of the model compared with traditional vocational rehabilitation over 5 years . METHOD A r and omized controlled trial compared supported employment to traditional vocational rehabilitation in 100 unemployed persons with severe mental illness . Competitive work and hospital admissions were tracked for 5 years , and interviews were conducted at 2 and 5 years to assess recovery attitudes and quality of life . A cost-benefit analysis compared program and total treatment costs to earnings from competitive employment . RESULTS The beneficial effects of supported employment on work at 2 years were sustained over the 5-year follow-up period . Participants in supported employment were more likely to obtain competitive work than those in traditional vocational rehabilitation ( 65 % compared with 33 % ) , worked more hours and weeks , earned more wages , and had longer job tenures . Reliance on supported employment services for retaining competitive work decreased from 2 years to 5 years for participants in supported employment . Participants were also significantly less likely to be hospitalized , had fewer psychiatric hospital admissions , and spent fewer days in the hospital . The social return on investment was higher for supported employment participants , whether calculated as the ratio of work earnings to vocational program costs or of work earnings to total vocational program and mental health treatment costs . CONCLUSIONS The results demonstrate that the greater effectiveness of supported employment in improving competitive work outcomes is sustained beyond 2 years and suggest that supported employment programs contribute to reduced hospitalizations and produce a higher social return on investment OBJECTIVE This study examines the long-term effects of evidence -based supported employment services on three vocational outcomes : labor force participation , earnings , and attainment of Social Security Administration ( SSA ) nonbeneficiary status through suspension or termination of disability cash payments due to work ( NSTW ) . METHOD Data from 449 individuals with psychiatric disabilities who participated in a multisite controlled trial of supported employment were matched to SSA data over a 13-year period ( 2000 - 2012 ) following supported employment services . Long-term outcomes were analyzed using r and om effects regression models comparing participants in the experimental and control conditions on measures of employment , earnings , and attainment of NSTW . The authors adjusted for time , age , race/ethnicity , gender , education , schizophrenia diagnosis , substance abuse history , and geographic region . RESULTS Overall outcomes were modest across the 13-year follow-up , with 32.9 % of participants having any earned income and 13.1 % ever attaining NSTW . Supported employment recipients were almost three times as likely as control subjects to be employed over 13 years ( odds ratio=2.89 ) . Although earnings were low , supported employment participants had significantly higher earnings per month than control subjects over time ( parameter estimate=$23.82 ) and were more likely than control subjects to attain NSTW ( odds ratio=12.99 ) . The supported employment effect diminished and was completely attenuated over time . CONCLUSIONS The study 's findings indicate a small but significant vocational advantage accruing to recipients of evidence -based supported employment in the decade following service delivery , adding to the evidence on the durability of supported employment effects . Results can inform policies design ed to help workers enhance economic security and reduce dependence on Social Security disability benefits Studies from North America have concluded that supported employment using the Individual Placement and Support ( IPS ) model is effective in helping individuals with severe and persistent mental illness gain competitive employment . The aim of this study was to investigate the effectiveness and cost-effectiveness of IPS in Engl and in patients followed up for 2 years . Patients with severe mental illness were r and omised to IPS or local vocational services ( treatment as usual ) . Service use and costs were measured . Two hundred-nineteen participants were r and omised , and 86 % re-assessed 2 years later . In the multivariate analysis , relatively low rates of competitive employment were found in both the intervention group and the treatment as usual group , although significantly more patients obtained competitive employment in the treatment arm ( 22 % vs. 11 % , p=0.041 ) . There were no significant differences in costs . The employment rate among participants receiving IPS was lower than in previously published reports , and the number needed to treat to obtain the benefit of IPS was relatively high . This may reflect difficulties in the implementation of IPS where it is not structurally integrated within mental health teams , as well as economic disincentives which lead to lower levels of motivation for patients and mental health professionals Objectives To evaluate whether adjuvant occupational therapy ( OT ) can improve the effectiveness of treatment-as-usual ( TAU ) in sick-listed employees with major depression . Methods In total , 117 employees sick-listed for a median duration of 4.8 months ( IQR=2.6 to 10.1 months ) because of major depression were r and omised to TAU ( n=39 ) or adjuvant OT ( TAU+OT ; n=78 ) . OT ( 18 sessions ) focussed on a fast return to work ( RTW ) and improving work-related coping and self-efficacy . The primary outcome was work participation ( hours of absenteeism+ duration until partial/full RTW ) . Secondary outcomes were depression , at-work functioning , and health-related functioning . Intermediate outcomes were work-related , coping and self-efficacy . Blinded assessment s occurred at baseline and 6 , 12 and 18 months follow-up . Results The groups did not significantly differ in their overall work participation ( adjusted group difference=−1.9 , 95 % CI −19.9 to + 16.2 ) . However , those in TAU+OT did show greater improvement in depression symptoms ( −2.8 , −5.5 to −0.2 ) , an increased probability of long-term symptom remission ( + 18 % , + 7 % to + 30 % ) , and increased probability of long-term RTW in good health ( GH ) ( + 24 % , 12 % to 36 % ) . There were no significant group differences in the remaining secondary /intermediate outcomes . Conclusions In a highly impaired population , we could not demonstrate significant benefit of adjuvant OT for improving overall work participation . However , adjuvant OT did increase long-term depression recovery and long-term RTW in GH ( ie , full RTW while being remitted , and with better work and role functioning ) . Trial Registration Dutch Trial Register NTR2057 BACKGROUND Individuals with schizophrenia have low employment rates and the job interview presents a critical barrier for them to obtain employment . Virtual reality training has demonstrated efficacy at improving interview skills and employment outcomes among multiple clinical population s. However , the effects of this training on individuals with schizophrenia are unknown . This study evaluated the efficacy of virtual reality job interview training ( VR-JIT ) at improving job interview skills and employment outcomes among individuals with schizophrenia in a small r and omized controlled trial ( n=21 VR-JIT trainees , n=11 waitlist controls ) . METHODS Trainees completed up to 10h of virtual interviews using VR-JIT , while controls received services as usual . Primary outcome measures included two pre-test and two post-test video-recorded role-play interviews scored by blinded raters with expertise in human re sources and self-reported interviewing self-confidence . Six-month follow-up data on employment outcomes were collected . RESULTS Trainees reported that the intervention was easy-to-use , helpful , and prepared them for future interviews . Trainees demonstrated increased role-play scores between pre-test and post-test while controls did not ( p=0.001 ) . After accounting for neurocognition and months since prior employment , trainees had greater odds of receiving a job offer by 6month follow-up compared to controls ( OR : 8.73 , p=0.04 ) and more training was associated with fewer weeks until receiving a job offer ( r=-0.63 , p<0.001 ) . CONCLUSIONS Results suggest that VR-JIT is acceptable to trainees and may be efficacious for improving job interview skills in individuals with schizophrenia . Moreover , trainees had greater odds of receiving a job offer by 6-month follow-up . Future studies could evaluate the effectiveness of VR-JIT within community-based services Many middle-aged and older people with severe mental illness are interested in working or volunteering . However , very few vocational rehabilitation programs target older clients with psychiatric illness . We examined employment outcomes among 50 middle-aged and older participants with schizophrenia or schizoaffective disorder in a 12-month r and omized controlled trial comparing two work rehabilitation programs : Individual Placement and Support ( IPS ; a supported employment model ) and conventional vocational rehabilitation ( CVR ) . Compared with CVR , IPS result ed in statistically better work outcomes , including attainment of competitive employment , number of weeks worked , and wages earned . Cohen 's d effect sizes for these variables were medium to large ( .66–.81 ) . Treatment group predicted future attainment of competitive work , but demographic and clinical variables ( e.g. , age , gender , ethnicity , education , illness duration , and medication dose ) did not predict employment outcomes . Participants who obtained competitive employment reported improved quality of life over time compared with those who did not . These findings suggest that for middle-aged and older clients with schizophrenia , supported employment results in better work outcomes than does conventional vocational rehabilitation . Furthermore , age was not significantly associated with attainment of competitive work . Finally , the therapeutic value of work is reflected in improved quality of life Objective : Cognitive remediation is an intervention to overcome cognitive deficits through drills and use of strategies . Previous studies have reported positive effects for cognitive remediation on neurocognition , but research ers ’ allegiance effects are not always adequately controlled . Furthermore , its efficacy amongst the Asian population has not been established . Hence , this study aim ed to determine if cognitive remediation would have positive effects on neurocognition and functioning within an English-speaking Asian population , when compared against the effects of a credible and balanced control provided by therapists blinded to the study hypothesis . Method : A total of 70 participants with schizophrenia who attended vocational training or day rehabilitation programmes were r and omised to receive a 60-hour programme of either cognitive remediation or physical exercise . Neurocognition and functional outcomes were measured at baseline , upon completion of treatment , 6 months after treatment and 1 year after treatment . Results : Participants who received cognitive remediation had significantly greater improvement in all neurocognitive domains . Furthermore , the cognitive remediation group achieved greater attainment of vocational or independent living skills and better functional outcomes at post-intervention and at the end of the 1-year follow-up . Conclusions : When compared against a credible intervention such as physical exercise , cognitive remediation was able to show significant positive effects on both neurocognition and functional outcomes among the Asian population of schizophrenia patients UNLABELLED Neurocognitive enhancement therapy ( NET ) is a remediation program for the persistent and function-limiting cognitive impairments of schizophrenia . In a previous study in veterans , NET improved work therapy outcomes as well as executive function and working memory . The present study aim ed to determine whether NET could enhance functional outcomes among schizophrenia and schizoaffective patients in a community mental health center receiving community-based vocational services . METHOD Patients ( N=72 ) participated in a hybrid transitional and supported employment program ( VOC ) and were r and omized to either NET+VOC or VOC only . NET+VOC included computer-based cognitive training , work feedback and a social information information-processing group . VOC only also included two weekly support groups . Active intervention was 12 months with 12 month follow-up . Follow-up rate was 100 % . RESULTS NET+VOC patients worked significantly more hours during the 12 month follow-up period , reached a significantly higher cumulative rate of competitive employment by the sixth quarter , and maintained significantly higher rates of employment . CONCLUSION NET training improved vocational outcomes , suggesting the value of combining cognitive remediation with other rehabilitation methods to enhance functional outcomes OBJECTIVES Supported employment is an evidence -based practice that has proved to be consistently more effective than conventional vocational rehabilitation in helping people with severe mental illness find and sustain competitive employment . Most research on the effectiveness of supported employment comes from the United States . This study examined the effectiveness and applicability of a supported employment program based on the individual placement and support model in a Hong Kong setting . METHODS Ninety-two unemployed individuals with long-term mental illness who desired competitive employment were r and omly assigned to either a supported employment program or a conventional vocational rehabilitation program and followed up for 18 months . Both vocational and nonvocational outcomes were measured . RESULTS Over the 18-month study period , compared with participants in the conventional vocational rehabilitation program , those in the supported employment group were more likely to work competitively ( 70 % versus 29 % ; odds ratio=5.63 , 95 % confidence interval=2.28 - 13.84 ) , held a greater number of competitive jobs , earned more income , worked more days , and sustained longer job tenures . Repeated- measures analysis of variance found no substantive differences between participants in the two groups and no significant change from baseline over time for psychiatric symptoms and self-perceived quality of life . CONCLUSIONS Consistent with previous research findings in the United States , the supported employment program was more effective than the conventional vocational rehabilitation program in helping individuals with long-term mental illness find and sustain competitive employment in a Hong Kong setting . The supported employment program based on the individual placement and support model can thus be recommended for wider use in local mental health practice OBJECTIVE Whereas in the U.S. and Canada the Individual Placement and Support ( IPS ) model has proven to be highly effective in enhancing employment perspectives for persons with severe mental illnesses , the evidence base is less abundant in countries with a different socioeconomic climate . The aim of this study was to examine the effectiveness of IPS in the Dutch socioeconomic context . METHOD A multisite r and omized controlled trial was performed following 151 persons with severe mental illnesses expressing an explicit wish for regular employment , comparing IPS with traditional vocational rehabilitation ( TVR ) . Primary outcome was the proportion of persons who were competitively employed over a period of 30 months . Secondary outcomes were self-reported quality of life , self-esteem and mental health . Additionally , the impact of being engaged in competitive employment on these secondary outcomes was examined . RESULTS In 30 months , 44 % of IPS participants found competitive work , compared with 25 % of participants supported by TVR . No direct effect of IPS on mental health , self-esteem or quality of life was found . Being competitively employed before follow-up measurements was significantly associated with an increase in mental health , self-esteem and quality of life . CONCLUSIONS AND IMPLICATION S FOR PRACTICE This study strongly confirms that IPS is an effective method in helping people with severe mental illnesses find competitive work also in countries characterized by a relatively protective socioeconomic climate putting up unintended barriers to employment . The implementation of IPS on a larger scale seems warranted , and new studies are needed on the mechanisms through which IPS works BACKGROUND Work attention in persons with chronic schizophrenia is an important issue in vocational rehabilitation . Some of the research literature indicates that background music may influence visual attention performance . OBJECTIVES Based on the theory of occupational therapy , environmental sounds , colors and decorations may affect individual performance , this study thus examined the influence of music on work attention in persons with schizophrenia . PARTICIPANTS Participants were recruited from a halfway house in Taipei . Forty-nine ( 49 ) patients with chronic schizophrenia volunteered . They had been accepted into vocational rehabilitation and a work-seeking program . The sample included 20 females and 29 males . The participant ages ranged between 29 and 63 years old , and their average age was 47 years old . METHODS Using a r and omized controlled trial ( RCT ) study , the participants were assigned to one of three conditions : quiet environment as the control group ( n= 16 ) , classical light music as background music ( n= 16 ) , and popular music as background music ( n= 17 ) . RESULTS For Group 1 ( control group/quiet environment ) , there was no significant variance ( sig = 0.172 ) . For Group 2 ( Classical light music ) , the intervention revealed significant variance ( sig = 0.071 * ) . For Group 3 ( popular music ) , the intervention had significant variance ( sig = 0.048 * * ) . CONCLUSIONS The introduction of background music tended to increase attention test scores of persons with schizophrenia . Moreover , the increase in test attention scores was statistically significant when popular music was played in the background . This result suggested that background music may improve attention performance of persons with chronic schizophrenia . Future research is required with a larger sample size to support the study results OBJECTIVE This study assessed the effectiveness of a supported education program for adults with psychiatric disabilities . METHOD Thirty-eight adults with psychiatric disabilities were r and omly assigned to an experimental group ( n = 21 ) that received supported education services or to a control group ( n = 17 ) that received treatment as usual . RESULTS We found a statistically significant difference between experimental and control group participant scores on the five instruments used to measure the program 's effectiveness . Sixteen of the 21 experimental group participants ( 76 % ) completed the program . At 6-month follow-up , 10(63 % ) had enrolled in an educational program , had obtained employment , or were applying to a specific program . Only 1 of the control group participants was enrolled in an educational program . CONCLUSION The results support the effectiveness of the supported education program . A significant number of participants were able to improve their basic academic skills , enhance professional behaviors and social skills , and return to the school or work environment Individual placement and support ( IPS ) has not been tested experimentally among people recently housed with a scattered-site Housing First program . Ninety recently housed people were r and omized to IPS or usual services . Regression models estimated via GEE were used to compare employment outcomes . Over 8 months of follow-up with good fidelity , fifteen ( 34 % ) people in the IPS group versus nine ( 22 % ) in the control group found competitive employment ( p = 0.16 ) . Adjusted odds of obtaining competitive employment were greater in the IPS group ( OR 2.42 , 95 % CI 1.13–5.16 ) . Other employment outcomes were not significantly different between groups . Satisfaction with services was greater in the group receiving IPS . In this study , IPS was a modestly useful adjunct to scattered-site Housing First for people with mental illness who have been homeless Research on vocational rehabilitation for clients with severe mental illness over the past 2 decades has yielded inconsistent findings regarding client factors statistically related to employment . The present study aim ed to eluci date the relationship between baseline client characteristics and competitive employment outcomes —job acquisition and total weeks worked during an 18-month follow-up — in Individual Placement and Support ( IPS ) . Data from 4 recent r and omized controlled trials of IPS were aggregated for within-group regression analyses . In the IPS sample ( N = 307 ) , work history was the only significant predictor for job acquisition , but receiving Supplemental Security Income — with or without Social Security Disability Insurance — was associated with fewer total weeks worked ( 2.0%–2.8 % of the variance ) . In the comparison sample ( N = 374 ) , clients with a diagnosis of mood disorder or with less severe thought disorder symptoms were more likely to obtain competitive employment . The findings confirm that clients with severe mental illness interested in competitive work best benefit from high-fidelity supported employment regardless of their work history and sociodemographic and clinical background , and highlight the needs for changes in federal policies for disability income support and insurance regulations We examined the effectiveness of an integrated supported employment ( ISE ) program , which augments Individual Placement & Support ( IPS ) with social skills training ( SST ) in helping individuals with SMI achieve and maintain employment . A total of 163 participants were r and omly assigned to three vocational rehabilitation programs : ISE , IPS , and traditional vocational rehabilitation ( TVR ) . After fifteen months of services , ISE participants had significantly higher employment rates ( 78.8 % ) and longer job tenures ( 23.84 weeks ) when compared with IPS and TVR participants . IPS participants demonstrated better vocational outcomes than TVR participants . The findings suggested that ISE enhances the outcomes of supported employment , endorsing the value of SST in vocational rehabilitation Cognitive Adaptation Training ( CAT ) improves functional outcomes in schizophrenia out patients living in the United States . The effectiveness of CAT for patients living outside the US as well as for long-term hospitalized patients remains to be determined . In addition , it has not yet been studied whether CAT can be successful if patients receive the treatment from psychiatric nurses . This pilot study investigated the effectiveness and feasibility of CAT as a nursing intervention in the Netherl and s. Thirty schizophrenia patients ( long-term hospitalized patients : 63 % ) participated in this study . Sixteen patients received treatment as usual (TAU)+CAT , and fourteen patients received TAU . Patients in CAT participated in the treatment for eight months , consisting of weekly home-visits by a psychiatric nurse , supervised by a psychologist . After eight months , CAT interventions were integrated in the usual treatment . Outcome measures were the Multnomah Community Ability Scale ( MCAS ) , the Social and Occupational Functioning Scale ( SOFAS ) , and the Negative Symptom Assessment -Motivation subscale ( NSA-M ) . For in patients , work-related activities were also tracked for 16 months after baseline . Patients receiving TAU+CAT had better scores on the MCAS ( trend ) , compared to TAU patients . Moreover , in patients ' work-related activities increased in TAU+CAT , relative to TAU in patients , reaching significance after ten months . Improvements on the SOFAS and NSA-M were not significant . These results indicate that CAT as a nursing intervention may improve outcomes in patients with schizophrenia living in the Netherl and s , including long-term hospitalized patients . However , since the current study was design ed for exploratory purpose s , larger r and omized controlled studies are needed to confirm our results and to investigate the long-term effects of CAT as a nursing intervention systematic ally OBJECTIVE Employment is a key to participation in community life for people with severe mental illness , especially those who have been involved in the criminal justice system . Although the Individual Placement and Support ( IPS ) model of supported employment has been established as an evidence -based practice for helping people with severe mental illness attain competitive employment , little is known about whether IPS is effective for people with severe mental illness who have a history of arrest or incarceration . This study examined this question . METHODS A r and omized controlled trial examined competitive employment outcomes for 85 participants with severe mental illness and justice involvement who were assigned to IPS or to a comparison group that offered a job club approach with peer support . RESULTS At one-year follow-up , a greater proportion of participants in the IPS group than in the comparison group had obtained competitive employment ( 31 % versus 7 % ; p<.01 ) . The IPS and comparison groups did not differ significantly during follow-up in rates of hospitalization ( 51 % versus 40 % ) or justice involvement-either arrests ( 24 % versus 19 % ) or incarceration ( 2 % for both groups ) . CONCLUSIONS Although IPS was shown to be an effective model for helping justice-involved clients with severe mental illness achieve employment , the outcomes were modest compared with those in prior IPS studies . The IPS model provided a useful framework for employment services for this population , but augmentations may be needed Individuals with severe mental disorders continue to experience low employment rates . Occupational therapists play an important role in helping these individuals develop the skills and obtain the supports necessary for productive living . This retrospective cohort study aim ed to explore employment outcomes and identify factors predictive of the outcomes of an in-house prevocational training program design ed for newly discharged psychiatric in patients . Data retrieved from the files of 58 participants including demographics , diagnostic history , physical fitness , functional assessment results , the use of vocational counselling service and employment status were analyzed . The overall employment rates among the participants were high ( 67.2 - 79.3 % ) within the 6 months following the prevocational training program . No significant differences were found in the employment rates across the 1 , 3 and 6-month time periods post-training . Vocational counselling service post-training and h and function were two factors predictive of participants ' employment outcomes . Occupational therapists should attend to the clients ' need for continuous vocational support and carefully identify the personal , functional and environmental factors contributing to successful employment . Caution in interpreting the results is warranted because of the lack of control and r and omization in this retrospective study . Additional longitudinal cohort or experimental studies would add further certainty to the current findings Abstract Objective : To investigate the effectiveness of Individual Placement and Support ( IPS ) with regard to non-vocational outcomes among individuals with severe mental illness . Methods : A r and omized controlled trial was carried out , comparing IPS with traditional vocational rehabilitation . The Empowerment Scale , the Worker Role Interview , the Profile of Occupational Engagement , and the Manchester Short Assessment of Quality of Life were administered to 120 clients , at baseline , six , and 18 months . Results : IPS participants showed higher scores in quality of life ( p = 0.002 ) , empowerment ( p = 0.047 ) , and work motivation ( p = 0.033 ) at 18 months . Within the IPS group , a significant change in QOL was shown at six ( p = 0.002 ) and 18 months ( p = 0.000 ) , and in occupational engagement ( p = 0.003 ; p = 0.012 ) . Conclusions : IPS can be part of a recovery process as individuals may increase their life satisfaction and time spent in daily occupations and community life OBJECTIVE Supported employment is the evidence -based treatment of choice for assisting individuals with severe mental illness to achieve competitive employment , but few supported employment programs specifically target older clients with psychiatric illness . The purpose of this study was to evaluate the efficacy of supported employment for middle-aged or older people with schizophrenia . METHOD Participants included 58 out patients with schizophrenia or schizoaffective disorder aged 45 or older who were recruited from a community mental health clinic . Participants were r and omly assigned to receive Individual Placement and Support ( IPS ; the manualized version of supported employment ) or conventional vocational rehabilitation ( CVR ) for one year , and completed assessment s at baseline , six months , and twelve months . RESULTS IPS was superior to CVR on nearly all work outcome measures , including attainment of competitive employment , weeks worked , and wages earned . Fifty-seven percent of IPS participants worked competitively , compared with 29 % of CVR participants ; 70 % of IPS participants obtained any paid work , compared with 36 % of CVR participants . Within the IPS group , better baseline functional capacity ( as measured by the UCSD Performance Based Skills Assessment ) and more recent employment were modestly associated with better work outcomes . CONCLUSIONS Middle-aged and older adults with schizophrenia are good c and i date s for supported employment services Employment provides schizophrenic patients with a positive identity and hope . Cognitive impairments have been suggested to slow down the progress in work rehabilitation . The purpose of this study was to investigate the efficacy and effectiveness of VR as a cognitive intervention for enhancing vocational outcomes . 95 in patients with schizophrenia were r and omly assigned to a virtual reality-based vocational training group ( VRG ) , a therapist-administered group ( TAG ) and a conventional group ( CG ) . Twenty-five of them in each group had completed the study . Their performances were evaluated , before and after interventions , by Brief Neuropsychological Cognitive Examination , Digit Vigilance Test , Rivermead Behavioural Memory Test , Wisconsin Card Sorting Test ( WCST ) and Vocational Cognitive Rating Scale . Patients in the VRG were found to perform better than patients in the TAG and CG in cognitive functioning , as shown by the WCST-percentage of error ( F ( 2 , 72)=7.146 , p<0.001 ) and the WCST-percentage of conceptual level response ( F ( 2 , 72)=8.722 , p<0.001 ) . The post-hoc test revealed that the VRG showed a better performance than both the TAG ( p=0.03 ) and the CG ( p<0.001 ) in the WCST-percentage of error . The VRG also showed a better performance than patients in both the TAG ( p=0.01 ) and the CG ( p<0.001 ) in the WCST-percentage of conceptual level response . The VRG also showed a better self-efficacy score than CG . Both VRG and TAG showed a better work performance as reflected by the on-site tests . Further studies on the use of VR in schizophrenia rehabilitation and for vocational success are discussed BACKGROUND / AIM The Individual Placement and Support ( IPS ) approach is an evidence -based form of supported employment for people with severe and persistent mental illness . This approach is not yet widely available in Australia even though there is mounting evidence of its generalisability outside the USA . One previous Australian r and omised controlled trial found that IPS is effective for young people with first episode psychosis . The aim of the current trial was to assess the effectiveness of evidence -based supported employment when implemented for Australian adult consumers of public mental health services by utilising existing service systems . METHODS A four-site r and omised control trial design ( n = 208 ) was conducted in Brisbane ( two sites ) , Townsville and Cairns . The intervention consisted of an IPS supported employment service hosted by a community mental health team . The control condition was delivered at each site by mental health teams referring consumers to other disability employment services in the local area . RESULTS At 12 months , those in the IPS condition had 2.4 times greater odds of commencing employment than those in the control condition ( 42.5 % vs. 23.5 % ) . The conditions did not differ on secondary employment outcomes including job duration , hours worked , or job diversity . Attrition was higher than expected in both conditions with 28.4 % completing the baseline interview but taking no further part in the study . CONCLUSION The results support previous international findings that IPS-supported employment is more effective than non-integrated supported employment . IPS can be successfully implemented this way in Australia , but with a loss of effect strength compared to previous USA trials |
13,967 | 20,460,624 | It is unclear if the prevalence of food allergies is increasing .
In high-risk infants , hydrolyzed formulas may prevent cow 's milk allergy but st and ardized definitions of high risk and hydrolyzed formula do not exist .
The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis | CONTEXT There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies .
OBJECTIVE To perform a systematic review of the available evidence on the prevalence , diagnosis , management , and prevention of food allergies . | Background . There is controversy regarding whether hypersensitivity to food proteins contributes to colic among breastfed infants . Methods . A r and omized , controlled trial of a low-allergen maternal diet was conducted among exclusively breastfed infants presenting with colic . In the active arm , mothers excluded cow 's milk , eggs , peanuts , tree nuts , wheat , soy , and fish from their diet ; mothers in the control group continued to consume these foods . Outcomes were assessed after 7 days , as the change in cry/fuss duration over 48 hours , with vali date d charts . The primary end point was a reduction in cry/fuss duration of ≥25 % from baseline . Mothers also assessed the responses to diet with categorical and visual analog scales . Results . Of 107 infants , 90 completed the trial ( mean age : 5.7 weeks ; range : 2.9–8.6 weeks ; 54 male infants ) . Infants in both groups presented with significant distress ( geometric mean : low-allergen group : 690 minutes per 48 hours ; control group : 631 minutes per 48 hours ) . In follow-up assessment s on days 8 and 9 , there were significantly more responders in the low-allergen group ( 74 % vs 37 % ) , ie , an absolute risk reduction of 37 % ( 95 % confidence interval : 18–56 % ) . Cry/fuss duration per 48 hours was reduced by a substantially greater amount in the low-allergen group ; the adjusted geometric mean ratio was 0.79 ( 95 % confidence interval : 0.63–0.97 ) , ie , an average reduction of 21 % ( 95 % confidence interval : 3–37 % ) . Mothers ' subjective assessment s of the responses to diet indicated little difference between the groups . Conclusion . Exclusion of allergenic foods from the maternal diet was associated with a reduction in distressed behavior among breastfed infants with colic presenting in the first 6 weeks of life OBJECTIVE To determine the effect of brief early exposure to cows ’ milk on atopy in the first 2 years of life . DESIGN Double blind , placebo controlled , r and omised feeding intervention trial ( Bokaal study ) . SETTING Dutch midwifery practice s. PARTICIPANTS 1533 breast fed neonates . INTERVENTION Exposure to cows ’ milk protein ( n = 758 ) or a protein free placebo ( n = 775 ) during the first 3 days of life . MAIN OUTCOME MEASURES Clinical atopic disease and any positive radioallergosorbent ( RAST ) tests at 1 year of age . RESULTS Atopic disease in the first year was found in 10.0 % ( cows ’ milk)v 9.3 % ( placebo ) of the children , with a relative risk of 1.07 ; in the second year , atopic disease was found in 9.6 % v 10.2 % , respectively , with a relative risk of 0.94 . Per protocol analysis showed similar results . Any RAST positive test was found in 9.4 % ( cows ’ milk)v 7.9 % ( placebo ) of children , with a relative risk of 1.19 . Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention . CONCLUSION Early and brief exposure to cows ’ milk in breast fed children does not increase the risk of atopic disease in the first 2 years Background : Little is known about the diagnostic accuracy of atopy patch tests ( APT ) in the clinical practice of pediatric gastroenterology . Moreover , APTs containing purified food extracts have recently become available , but their diagnostic accuracy is largely undefined Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers ' diets affected their skin condition . Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows ' milk , and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond . Babies were examined at the beginning and end of each dietary period , and the extent and severity of the rash were given a numerical score . The eczema improved in six infants when their mothers avoided egg and cows ' milk and worsened again when these were reintroduced . Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows ' milk , one developing colitis . Maternal dietary exclusion seems to benefit some breast fed babies with eczema A mixture of neutral short-chain galactooligosaccharides ( scGOS ) and long-chain fructooligosaccharides ( lcFOS ) has been shown to reduce the incidence of atopic dermatitis ( AD ) and infectious episodes during the first 6 mo of life . This dual protection occurred through the intervention period . The present study evaluated if these protective effects were lasting beyond the intervention period . In a prospect i ve , r and omized , double-blind , placebo-controlled design , healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . Following this intervention period , blind follow-up continued until 2 y of life . Primary endpoints were cumulative incidence of allergic manifestations . Secondary endpoints were number of infectious episodes and growth . Of 152 participants , 134 infants ( 68 in placebo , 66 in intervention group ) completed the follow-up . During this period , infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations . Cumulative incidences for AD , recurrent wheezing , and allergic urticaria were higher in the placebo group , ( 27.9 , 20.6 , and 10.3 % , respectively ) than in the intervention group ( 13.6 , 7.6 , and 1.5 % ) ( P < 0.05 ) . Infants in the scGOS/lcFOS group had fewer episodes of physician-diagnosed overall and upper respiratory tract infections ( P < 0.01 ) , fever episodes ( P < 0.00001 ) , and fewer antibiotic prescriptions ( P < 0.05 ) . Growth was normal and similar in both groups . Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections . The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action BACKGROUND Early feeding with cow 's milk ( CM ) may increase the risk of cow 's milk allergy ( CMA ) . OBJECTIVE We sought to examine prospect ively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula . METHODS We studied 6209 unselected healthy , full-term infants , of whom 5385 ( 87 % ) required supplementary milk while in the hospital . The infants were r and omly assigned to receive CM formula ( 1789 infants ) , pasteurized human milk ( 1859 infants ) , or whey hydrolysate formula ( 1737 infants ) . The comparison group ( 824 infants ) was composed of infants who were exclusively breast-fed . The infants were followed for 18 to 34 months for symptoms suggestive of CMA . The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet . RESULTS The cumulative incidence of CMA in the infants fed CM was 2.4 % compared with 1.7 % in the pasteurized human milk group ( odds ratio [ OR ] , 0.70 ; 95 % confidence interval [ CI ] , 0 . 44 - 1.12 ) and 1.5 % in the whey hydrolysate group ( OR , 0.61 ; 95 % CI , 0 . 38 - 1.00 ) . In the comparison group , CMA developed in 2.1 % of the infants . Among the infants who required supplementary feeding at hospital , both exposure to CM while in the hospital ( OR , 1.54 ; 95 % CI , 1.04 - 2.30 ; P = .03 ) and obvious parental atopy ( OR , 2.32 ; 95 % CI , 1.53 - 3.52 ; P < .001 ) increased the risk of CMA . CONCLUSIONS Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements , but exclusive breast-feeding does not eliminate the risk The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis ( AD ) in infancy . This study is part of a dietary clinical trial in a prospect i ve cohort of healthy term newborns at risk of atopy . It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period . Eight hundred and sixty-five infants exclusively breast-fed , and 256 infants partially or exclusively formula-fed , were followed-up until the end of the first year following birth . AD and sensitization to milk and egg were considered as study end-points . The 1-year incidence of AD was compared between the two study groups . Adjusted odds ratios ( OR ) with 95 % confidence intervals ( CI ) were calculated by multiple logistic regression . The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given . In the breast-fed group , the adjusted OR for AD was 0.47 ( 95 % CI 0.30 - 0.74 ) . The strongest risk factor was the occurrence of AD in the subject 's core family . The risk of infants with AD to be sensitized to milk was four times higher , and to egg eight times higher , than in infants without AD . Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence . We conclude that in infants at atopic risk , exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life BACKGROUND Recommendations for primary prevention of allergic diseases in high-risk children include feeding with hydrolyzed formulas if breast-feeding is insufficient . OBJECTIVE The primary objective of the German Infant Nutritional Intervention study was to investigate the allergy preventive effect of 3 hydrolyzed formulas compared with cow 's milk formula in the first 3 years of life in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were allocated to a group receiving cow 's milk formula , partially or extensively hydrolyzed whey formula , or extensively hydrolyzed casein formula as a milk substitute for the first 4 months if breast-feeding was insufficient . Main outcome parameters were allergic manifestations , atopic dermatitis ( AD ) , and asthma . RESULTS After 3 years , 396 of 2252 children ( 17.6 % ) had dropped out . Breast-fed infants without formula feeding during the intervention ( n = 889 ) were considered separately . A significant reduction of the incidence of AD was achieved with the extensively hydrolyzed casein formula in the intention-to-treat ( ITT ; n = 1363 ) and per protocol ( PP ; n = 904 ) analyses ( ITT : population odds ratio [ 95 % CI ] , 0.67 [ 0.45 - 0.99 ] ; PP : adjusted odds ratio [ OR(adj ) ] , 0.53 [ 0.32 - 0.88 ] ) , and with the partially hydrolyzed whey formula in the PP analysis ( ITT : population odds ratio , 0.76 [ 0.52 - 1.11 ] ; PP : OR(adj ) , 0.60 [ 0.37 - 0.97 ] ) . None of the formulas reduced the incidence of asthma . CONCLUSION The risk for AD , but not for asthma , can be reduced with certain cow 's milk hydrolyzates in high-risk infants when breast-feeding is insufficient . CLINICAL IMPLICATION S Early nutritional intervention in high-risk children has significant influence on the incidence of AD , but not of asthma A recent increase in the prevalence of atopic disorders and the enormous costs of management of atopic patients have prompted attempts at prevention . We have examined the effect of exclusive breast feeding and of feeding different infant formulas on incidence of atopic disease in a prospect i ve r and omized controlled study . Seventy-two infants were recruited into each of the following groups : cow milk whey hydrolysate formula ( NAN/HA ) conventional cow milk formula ( Similac ) , soy-based formula ( Isomil ) , and exclusive breast feeding for greater than 4 months . The cumulative incidence of atopic eczema , recurrent wheezing , rhinitis , gastrointestinal symptoms , and colic were noted . Skin prick tests and radioallergosorbent tests for IgE antibodies to milk and soy were performed . At 12 and 18 months of age , the incidence of atopic eczema as also that of all atopic symptoms was significantly lower and similar in the breast-fed and whey hydrolysate groups , compared with the cow milk and soy formula groups . IgE antibodies were detected more often in the cow milk and soy formula groups , especially the former . Among symptomatic infants , fewer skin positive prick tests were seen in the soy group compared with the cow milk group . Our observations show that among infants at high risk of developing atopic disease because of positive family history , exclusive breast feeding or whey hydrolysate formula is associated with a lower incidence and thus a delay in the occurrence of allergic disorders compared with groups fed conventional cow milk or soy formulas In a prospect i ve study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk , a casein hydrolysate ( Nutramigen ) or a new ultrafiltrated whey hydrolysate ( Profylac ) on the development of cow milk protein allergy/intolerance ( CMPA/CMPI ) was assessed and compared . All the infants had biparental or severe single atopic predisposition , the latter combined with cord blood IgE > or = 0.5 kU/L. At birth all infants were r and omized to Nutramigen or Profylac , which was used when breastfeeding was insufficient or not possible during the first 6 months of life . During the same period this regimen was combined with avoidance of solid foods and cow milk protein . All mothers had unrestricted diets and were encouraged to do breastfeeding only . Moreover , avoidance of daily exposure to tobacco smoking , furred pets and dust-collecting material s in the bedroom was advised . The infants were followed prospect ively from birth to 18 months of age . All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI . A total of 154 ( 97 % ) were followed up and 141 followed the diet strictly . Eighty-eight ( 62 % ) of the infants were breastfed for at least 6 months , 20 ( 14 % ) were breastfed exclusively , 59 and 62 had varying amounts of Nutramigen or Profylac respectively . CMPA/CMPI was diagnosed in 1/20 , 1/59 and 3/62 in the breastfed , the Nutramigen and Profylac groups respectively , but 1 of the latter also had Nutramigen . None of the infants showed reactions against Nutramigen or Profylac . In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract . One hundred and twenty‐one women with history of a previous child with atopic disease were r and omly allocated during the next pregnancy to antigen avoidance or control groups . Dietary advice consisted of almost complete exclusion of milk and dairy products , egg , fish , beef and peanut throughout pregnancy and lactation . A total of 109 completed the study . Maternal antigen avoidance was associated with reduced occurrence of atopic eczema and the skin involvement was less extensive and milder . The beneficial effect was observed mainly in the breast‐fed group . Among the fifty‐five who completed the trial of antigen avoidance , seventeen infants developed atopic eczema , five out of thirty‐five who were breast‐fed and twelve out of twenty who were formula‐fed . Among the offspring of fifty‐four control mothers given no dietary restriction , eczema was observed in twenty‐four infants , eleven out of thirty‐six breast‐fed and thirteen of eighteen formula‐fed . Avoidance of common dietary allergens during pregnancy and lactation enhanced the preventive beneficial effect of exclusive breast feeding on the incidence of atopic eczema among infants at high risk BACKGROUND Early recognition of dietary allergies in infants with atopic dermatitis is essential for avoidance of unnecessary elimination diets , amelioration of the skin disease , and secondary prevention of the development of multiple food allergies . Simple and accurate methods of identifying provocative foods are urgently needed . METHODS The usefulness of skin prick and patch tests as indicators of cow milk allergy was evaluated in 183 patients ranging in age from 2 to 36 months with double-blind , placebo-controlled ( n = 118 ) or open ( n = 65 ) cow milk challenges . RESULTS The oral cow milk challenges were interpreted as positive in 54 % of both challenge types . Positive challenge rapidly elicited pruritus , urticaria , and /or exanthema in 49 % of cases and delayed-onset eczematous lesions in 51 % . The skin prick and patch tests gave markedly discrepant results ; prick tests were positive in 67 % of the cases with acute-onset reactions to milk challenge , whereas patch tests tended to be negative . Patch tests were positive in 89 % of those with delayed-onset reactions , although prick tests were frequently negative . CONCLUSIONS The observations indicate that IgE and T cell-mediated responses to cow milk can be distinguished in atopic dermatitis . Parallel skin testing with combined prick and patch tests can significantly enhance the accuracy in diagnosis of specific dietary allergies in patients with atopic dermatitis The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease . A r and omised controlled trial examined the effects of withholding cows ' milk protein during the first three months of life and replacing cows ' milk with soya milk . The children were followed up to the age of 7 years . Withholding cows ' milk did not reduce the incidence of allergy or wheezing . Children who had ever been breast fed had a lower incidence of wheeze than those who had not ( 59 % and 74 % respectively ) . The effect persisted to age 7 years in the non-atopics only , the risk of wheeze being halved in the breast fed children after allowing for employment status , sex passive smoking , and overcrowding . Allergic disease was not associated with exposure to tobacco smoke , house dust mite antigen , or cats . Breast feeding may confer long term protection against respiratory infection Early feeding with cows ' milk ( CM ) may cause cows ' milk allergy ( CMA ) . Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant . We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA , the effects of formula and breast feeding on the subsequent immunologic types of CMA , and the importance of immune factors present in colostrum in the immune responses of infants with CMA . In a cohort of 6209 infants , 824 were exclusively breast-fed and 87 % required supplementary milk while in the maternity hospital : 1789 received CM formula , 1859 pasteurized human milk , and 1737 whey hydrolysate formula . The cumulative incidence of CMA , verified by a CM elimination-challenge test , was 2.4 % in the CM , 1.7 % in the pasteurized human milk and 1.5 % in the whey hydrolysate group . Among these infants , exposure to CM at hospital and a positive atopic heredity increased the risk of CMA . Of the exclusively breast-fed infants , 2.1 % had CMA . Risk factors for the development of IgE-mediated CMA were : exposure to CM at hospital , breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding . The content of transforming growth factor-beta1 ( TGF-beta1 ) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA . In infants with CMA , TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM , but positively with infants ' IgA and IgG antibodies to CM proteins . Feeding of CM formula at maternity hospital increases the risk of CMA , but exclusive breast-feeding does not eliminate the risk . Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA . Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( < 4 months ) ; ( iii ) feeding beef ( < 6 months ) ; ( iv ) early introduction of cow 's milk ( < 6 months ) ; and ( v ) parental smoking in the presence of the babies and early day care admission ( < 2 years of life ) . All the preventive measures used in this study ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions Aims : To determine the effect of brief early exposure to cows ' milk on the expression of atopy during the first five years of life . Methods : Follow up analysis of a double blind , placebo controlled , r and omised feeding intervention trial ( BOKAAL study ) . Subjects were 1108 children from 1533 initially r and omised breast fed neonates in the Netherl and s. Atopic disease and prevalence of allergic symptoms at age 1 , 2 , and 5 , and specific IgE at age 1 and 5 were determined . Results : Atopic disease in the first year was found in 10.0 % ( cows ' milk ) versus 9.3 % ( placebo ) of the children , with a relative risk ( RR ) of 1.07 . No differences were found in the second year either . At age 5 , atopic disease was found in 26.3 % ( cows ' milk ) versus 25.0 % ( placebo ) , RR 1.05 . There was no difference in the prevalence of allergic symptoms . Specific IgE to cows ' milk ( RAST positive 2 + or more ) was 5.8 % ( cows ' milk ) versus 4.1 % ( placebo ) at age 1 ( RR 1.43 ) , and 5.3 % versus 3.0 % at age 5 ( RR 1.77 ) . There was no difference in sensitisation to other common allergens between the two groups . Conclusion : Early , brief exposure to cows ' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5 Cow milk allergy is a common disease of infancy , often associated with atopic dermatitis ( AD ) . Avoidance of cow milk ( CM ) implies the use of alternative dietary supports such as mammalian milks . In this study , we assessed the tolerability and clinical effect of ass 's milk ( AM ) , when compared with the largely used goat 's milk ( GM ) in a single-blind , controlled , r and omized crossover . Twenty-eight children with AD and ascertained allergy to CM were enrolled . The children were r and omized to AM or GM for 6 months , then switched to the other milk for further 3 months . The SCORAD index ( SI ) and a visual analog scale ( VAS ) were evaluated blindly . After termination of the study , food challenges with GM and AM were performed . An SDS-PAGE analysis of different milks was performed . Two children from the GM group dropped out after r and omization and 26 completed the study . Ass milk invariantly led to a significant improvement of SI and VAS of symptoms ( p < 0.03 vs. baseline and inter-group ) , whereas GM had no measurable clinical effect . At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM . Ass 's milk had a protein profile closer to human milk than GM . Ass milk is better tolerated and more effective than GM in reducing symptoms of AD . It may represent a better substitute of CM than the currently used GM BACKGROUND About 20 % of infants fed with breast-milk substitutes suffer from Gastro Esophageal Reflux ( GER ) and 1/3 of them also show Cow 's Milk Allergy ( CMA ) symptoms . METHODS We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow 's Milk Formula ( eHF ) in infants suffering from GER . Ten infants showing GER symptoms and 10 normal babies , all fed with breast-milk substitutes , were enrolled . Clinical symptom scores related to GER were assessed for one week . The Gastric Emptying Time ( GET ) was determined by means of dynamic echography after feeding with cow 's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms . RESULTS All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects ( 205 vs 124 min , p = 0.000 ) . Switching to the eHF led to a significant clinical improvement ( p = 0.0039 ) especially in babies skin-test and RAST positive to cow 's milk , and to a significant decrease toward the normal value of the GET ( 167 min , p < 0.001 ) . CONCLUSIONS The eHF tested improves GER symptoms in infants suffering from this disease . Our experience confirms and supports the use of dynamic echography as a reliable , simple , and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER BACKGROUND An altered microbial exposure may underlie the increase of allergic diseases in affluent societies . Probiotics may alleviate and even prevent eczema in infants . OBJECTIVE To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri . METHODS Double-blind , r and omized , placebo-controlled trial , which comprised 232 families with allergic disease , of whom 188 completed the study . The mothers received L reuteri ATCC 55730 ( 1 x 10(8 ) colony forming units ) daily from gestational week 36 until delivery . Their babies then continued with the same product from birth until 12 months of age and were followed up for another year . Primary outcome was allergic disease , with or without positive skin prick test or circulating IgE to food allergens . RESULTS The cumulative incidence of eczema was similar , 36 % in the treated versus 34 % in the placebo group . The L reuteri group had less IgE-associated eczema during the second year , 8 % versus 20 % ( P = .02 ) , however . Skin prick test reactivity was also less common in the treated than in the placebo group , significantly so for infants with mothers with allergies , 14 % versus 31 % ( P = .02 ) . Wheeze and other potentially allergic diseases were not affected . CONCLUSION Although a preventive effect of probiotics on infant eczema was not confirmed , the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease . CLINICAL IMPLICATION Probiotics may reduce the incidence of IgE-associated eczema in infancy BACKGROUND Previous studies have suggested that the atopy patch test ( APT ) may make oral challenge superfluous in diagnosing children with food hypersensitivity . OBJECTIVE To investigate the clinical relevance of APT in predicting hypersensitivity to cow 's milk and hen 's egg in 486 unselected children 3 years of age . METHOD The children were examined by APT , skin prick ( SPT ) , histamine release ( HR ) , and specific IgE followed by oral challenge when hypersensitivity to cow 's milk or hen 's egg was suspected . RESULTS Food hypersensitivity confirmed by oral challenge was 1.6 % to hen 's egg and 0.6 % to cow 's milk . No hypersensitivity to cow 's milk or hen 's egg was predicted by APT alone . CONCLUSION APT could not predict food hypersensitivity not predicted by SPT , HR , or specific IgE. Thus , APT can not be recommended in daily practice for the diagnosis of hypersensitivity to cow 's milk and hen 's egg in children 3 years of age The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas , in infants with a high risk for development of allergic disease . High-risk infants from four Danish centres were included in the period from June 1994 to July 1995 . Five-hundred and ninety-five high-risk infants were identified . High-risk infants were defined as having biparental atopy , or a single atopic first-degree relative combined with cord blood immunoglobulin E ( IgE ) > or = 0.3 kU/l . At birth all infants were r and omized to one of three different blinded formulas . All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively . If breast-feeding was insufficient , one of the three formulas , according to r and omization , was given during the first 4 months . It was recommended not to introduce cow 's milk , cow 's milk products . and solid foods until the age of 4 months . After the age of 4 months a normal unrestricted diet and conventional cow 's milk-based formula were given when needed . All infants were followed-up prospect ively with interview and physical examination at the age of 6 , 12 , and 18 months , and if any possible atopic symptoms were reported . If food allergy was suspected , controlled elimination/challenge procedures were performed in a hospital setting . Of 550 infants included in the study , 514 were seen at all visits and 36 were excluded owing to noncompliance . Of 478 infants who completed the study , 232 were exclusively breast-fed , 79 received an extensively hydrolyzed casein formula ( Nutramigen ) , 82 an extensively hydrolyzed whey formula ( Profylac ) , and 85 a partially hydrolyzed whey formula ( Nan HA ) , during the first 4 months of life . These four groups were identical in regard to atopic predisposition , cord blood IgE , birthplace , and gender . Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes , whereas the three formula groups were identical concerning environmental factors . The frequency of breast-feeding was high ; only eight ( 2 % ) children were not breast-fed at all . The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods . No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms . The cumulative incidence of parental-reported cow 's milk allergy was significantly higher in children fed partially hydrolyzed formula ( Nan HA ) compared with extensively hydrolyzed formula ( Nutramigen or Profylac ) at 12 and 18 months ( NanHA , 7.1 % ; Nutramigen , 2.5 % ; Profylac , 0 % ; p=0.033 ) . The cumulative incidence of confirmed cow 's milk allergy was 1.3 % ( three of 232 ) in exclusively breast-fed infants , 0.6 % ( one of 161 ) in infants fed extensively hydrolyzed formula ( Nutramigen or Profylac ) , and 4.7%(four of 85 ) in infants fed partially hydrolyzed formula ( Nan HA ) . Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow 's milk allergy , 0.6 % vs. 4.7 % ( p=0.05 ) , but because of the small number of cases the results should be interpreted with caution . Compared with other similar studies the frequency ofatopic symptoms was low , even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate . We decided to evaluate the safety and efficacy of st and ardized protocol s for oral desensitization with the most common food allergens . Forty-two children ( ages up to 16 years ) diagnosed as affected by food allergy ( on the basis of clinical history , skin prick tests , measurement of specific IgE , and double-blind , placebo-controlled food challenge ) underwent a sublingual-oral desensitizing treatment according to new st and ardized protocol s. The control group consisted of 10 patients who followed an elimination diet . The treatment was successfully completed by 85.7 % of the patients . Specific IgE showed a significant decrease , while specific IgG4 showed a significant increase , in all treated patients . The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy BACKGROUND Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults . Currently , preventive treatment consists of avoidance , which is difficult because of the widespread and often disguised use of peanuts in the food industry . METHODS Twelve patients with immediate hypersensitivity to ingestion of peanuts were recruited . Half were treated with injections of peanut extract : a maintenance level of tolerance was first achieved by a rush protocol , then maintained with weekly injections for at least 1 year . The other six were untreated control subjects . All patients underwent double-blind , placebo-controlled , oral peanut challenges initially , after approximately 6 weeks , and after 1 year . RESULTS All treated patients achieved the maintenance dose of 0.5 ml of 1:100 wt/vol peanut extract by the rush injection protocol . All experienced increased tolerance to double-blind , placebo-controlled peanut challenge and decreased sensitivity on titrated skin prick testing with peanut extract , whereas the threshold to oral peanut challenge and cutaneous reactivity to peanut extract were unchanged in the untreated control subjects . Systemic reactions were common in the treated group both during rush immunotherapy and with maintenance injections . Only three patients remained tolerant of the full maintenance dose . The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses , but there was partial ( n = 2 ) or complete ( n = 1 ) loss of protection in the patients who required dose reduction because of systemic reactions . CONCLUSIONS Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts . Injections result in repeated systemic reactions in most patients , even during maintenance injections . For clinical application of this method of treatment , a modified peanut extract is needed We conducted a prospect i ve study at King Chulalongkorn Memorial Hospital , from June 2001 to November 2003 , to identify the contribution of food allergy to urticaria in children . During the study period , 100 children with urticaria were enrolled , 36 of whom had a history suspicious of food allergy . Fifteen of 100 patients had fever ( 9 from upper respiratory tract infections , 4 from diarrhea and 2 from skin infections ) . A skin prick test ( SPT ) was positive in 15 of the 36 children who were suspected of having food allergy ; 5 patients out of the positive SPT group had anaphylaxis due to food ( 2 from cow milk , 2 from wheat and 1 from egg ) . Six patients in the positive SPT group had a negative food challenge test ( 4 from open challenges and 2 from double-blind placebo-controlled food challenges [ DBPCFC ] ) . The other 4 patients of the positive SPT group refused the food challenge test . The parents of a patient who had urticaria from egg refused the skin prick test ; an oral challenge test confirmed the diagnosis of egg allergy . One of the 21 patients that had a negative SPT had shrimp allergy proven by DBPCFC . Of the 64 patients who had no history related to food , SPT was done in 27 patients and revealed a positive result in 7 patients , all of whom had a negative food challenge test ( 4 with open challenge and 3 with DBPCFC ) . Urticaria from food was found in 7 % and was suspected in another 4 % of the patients . Severe reactions to food like anaphylaxis may occur . SPT alone is not adequate in making the diagnosis of food allergy ; it must be confirmed by a food challenge test . Thirty percent of patients that did not have a history related to food had false positive SPT . Without a history suspicious of food allergy , SPT yields only minimal benefit Infants born to atopic parents have been found to be at high risk of allergy development . The present study investigated the effect of a maternal milk-free diet during late pregnancy and lactation on the immune response and allergy incidence in at-risk and control infants . Atopic mothers were r and omly allocated into an intervention group ( n 12 ) or an unrestricted-diet group ( n14 ) and compared with non-atopic mothers following an unrestricted diet ( n 12 ) . The intervention involved a maternal milk-free diet during late pregnancy and lactation . Infants were followed up for 18 months postnatally . A significant fall in maternal serum beta-lactoglobulin (beta-Lg)-immunoglobulin G ( IgG ) antibody levels ( P < 0.05 ) was observed after a 7-week milk-exclusion diet . In maternal and cord serum sample s the levels of beta-Lg-IgG and alpha-casein-IgG antibodies were significantly correlated ( r 0.89 , P < 0.0001 and r 0.71 , P < 0.001 respectively ) . Higher levels of beta-Lg-IgG ( P < 0.05 ) were observed in the cord serum sample s compared with paired maternal serum sample s. Single-blind allergy assessment by a paediatrician at 12 and 18 months showed that the infants born in the non-atopic group had a significantly lower allergy incidence compared with the infants born in the atopic group following an unrestricted diet ( P < 0.008 and P < 0.02 respectively ) . The allergy incidence in the infants born in the atopic diet group was significantly lower compared with that of the atopic group following an unrestricted diet ( P < 0.04 ) . It was observed that the atopic nature of the parents significantly affected the allergy incidence in their children . A trend towards a beneficial effect of a maternal milk-free diet during late pregnancy and lactation was also observed in infants born to atopic parents Ninety-one high atopy-risk infants were prospect ively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization . They were r and omized into one of two feeding groups , i.e. , a hydrolyzed , ultrafiltered cow 's milk whey formula , Profylac ( n = 32 ) , or an ordinary cow 's milk formula ( n = 39 ) , for 12 months , started after exclusive breast-feeding for 0 - 9 ( median 6.0 ) months . Lactating mothers avoided milk , egg , and fish , as did the infants up to 12 months of age . Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group . All infants were followed-up by question naires , physical examinations , skin prick tests , and determination of serum total IgE and cow ' milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups . However , all three infants who developed cow 's milk allergy with skin symptoms belonged to the cow 's milk formula group . The skin prick test with whey hydrolysate was negative in all , while with cow 's milk it was positive in eight infants . Growth was similar in the three groups . The study comprises too few infants to allow us to make statistically based statements . However , the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden The 209 mothers to be , enrolled in a r and omized , prospect i ve , allergy-prevention study from allergy-prone families , totally abstained from cow 's milk and egg from gestational week 28 to delivery . This article presents the development of allergic disease at 5 years of age in their children , compared with the development of allergic disease in the children of the control mothers who took normal food throughout pregnancy . The prevalence of allergic disease could be evaluated in 198 children ( 95 % ) . Allergic disease was monitored with question naires , skin prick testing , serum-IgE determinations , and physical examination . Eczema , allergic rhinoconjunctivitis , and asthma was equally common in the groups . Persistent food intolerance to egg was significantly more common in children of the mothers receiving the diet . This long-term follow-up confirms our previous findings that maternal elimination diet during late pregnancy does not prevent the development of allergic disease in the genetically predisposed child Aim : A r and omized , double‐blind study was conducted to evaluate whether use of protein hydrolysate‐based preterm formulas in infants with an atopic predisposition helps prevent the development of allergic diseases . Methods : Preterm infants ( n= 122 ) with at least one first‐degree relative ( parent or sibling ) with allergic disease were r and omly assigned to receive an extensively or partially hydrolysed preterm formula ( intervention groups ) or a st and ard preterm formula until 4 to 5 mo of age . Infants whose parents preferred that they be breastfed received their mothers ' fortified breast milk . Results : Intention‐to‐treat analysis showed that the overall incidence of allergic diseases did not significantly differ between groups at both 4–5 and 12 mo of age . However , by 12 mo , use of the extensively hydrolysed versus the st and ard preterm formula had significantly reduced the risk of atopic dermatitis . At 4–5 and 12 mo , there was a significantly increased risk of non‐acceptance of the extensively hydrolysed formula compared with the other formulas Previous studies have suggested various diagnostic cut-offs of allergy tests for the diagnosis of clinical peanut allergy in children . There are few data relating to the use of combinations of these tests in children . We aim ed to determine the validity of previously reported diagnostic cut-off levels of peanut allergen skin tests and peanut specific-immunoglobulin ( Ig ) E , as well as the usefulness of combinations of these , for predicting clinical peanut allergy in our Allergy Clinic . Children attending the Allergy Clinic with a positive peanut skin prick test ( SPT ; n = 84 ) were included in the study . Immediate skin application food tests ( I-SAFT ) using 1 g of peanut butter ( positive if any wheals were detected at 15 min ) , peanut specific-IgE levels and open-label peanut food challenges were performed . Fifty-two of 85 peanut challenges were positive . Skin prick test specificity was 67 % at > or=8 mm and 100 % at > or=15 mm . The I-SAFT was 82 % specific . A peanut specific-IgE level of 0.37 kU/l was 98 % sensitive but 33 % specific . A level of 10 kU/l was 100 % specific . Combinations of a SPT of > or=8 mm with a positive I-SAFT and a peanut specific-IgE > or=0.37 kU/l were 88 % specific with a sensitivity of 38 % . Using challenge outcomes as the st and ard , available in vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and specificity and combining them does not significantly improve their clinical usefulness . Previously described diagnostic cut-off levels do not have general applicability . Allergy practitioners may need to interpret results of allergy tests in the context of their own practice One hundred and sixty‐two women with respiratory allergy to animal d and ers and /or pollens were r and omly allocated to a diet consisting of either a very low ingestion of hens ' egg and cows ' milk or a daily ingestion of one hens ' egg and about 11 of cows ' milk during the last 3 months of pregnancy . One hundred and sixty‐three infants were followed prospect ively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly . No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy . The numbers of skin‐prick tests positive to ovalbumin , ovomucoid , β‐lactoglobulin and cows ' milk were likewise not influenced by differences in the maternal diet during late pregnancy . Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy Background : Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome ( AEDS ) in food‐allergic infants . We aim ed to investigate whether probiotic bacteria have any beneficial effect on AEDS The effect of feeding different infant formulas on incidence of atopic disease was assessed in a prospect i ve double-blind r and omized controlled trial among " high risk " infants with family history of atopy among first-degree relatives . The incidence of atopic eczema , wheezing , rhinitis , gastrointestinal symptoms , and colic was noted and serum IgE antibodies to milk were estimated . Seventy-two infants were recruited into each of the following groups : cow milk whey hydrolysate formula ( NAN/HA ) , conventional cow milk formula ( Similac ) , soy-based formula ( Isomil ) , and exclusive breast feeding for greater than or equal to 4 months . The number of infants who exited for reasons other than atopy and were excluded from analysis were 4 , 5 , 4 , and 12 in the four groups , respectively . The incidence of one or more symptoms of possible allergic etiology was five of 68 infants fed NAN/HA , 24 of 67 infants fed Similac , 25 of 68 infants fed Isomil , and 12 of 60 breast-fed infants . Among symptomatic infants , skin prick test to milk proteins was positive in four out of five infants fed NAN/HA , 16 of 24 fed Similac , 2 of 25 fed Isomil , and 7 of 12 breast-fed . IgE antibodies to milk were found in 2 of 68 , 9 of 67 , 0 of 68 , and 6 of 60 infants in the four groups , respectively . It is concluded that exclusive breast feeding for more than 4 months is partially protective against the development of atopic disease among high risk infants . ( ABSTRACT TRUNCATED AT 250 WORDS At the age of 5 years , the prevalence of atopic manifestations was analysed in 58 formula-fed “ at risk ” infants because of a history of atopic disease in at least two first degree relatives . Infants were r and omly assigned to receive either a partial whey-hydrolysate formula ( n : 28 ) or a regular cow 's milk formula ( n : 30 ) during the first 6 months of life ; thereafter , feeding was unrestricted . Only non-breastfed infants were included . The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease . At 6 months , the prevalence of cow 's milk protein ( CMP ) sensitivity was significantly decreased in the hydrolysate group ( 7 % versus 43%;P : 0.002 ) . At the age of 12 ( 21 % versus 53%;P : 0.029 ) , 36 ( 25 % versus 57%;P : 0.018 ) and 60 months ( 29 % versus 60%;P : 0.016 ) there was still a significant difference in the number of atopic manifestations , if calculated cumulatively . There was no difference between the groups if only the new cases after the age of 6 months were considered . Eczema was less frequent in the whey-hydrolysate group , but only during the 1st year of life , suggesting a decreased prevalence of CMP sensitivity . During the first 6 months , diarrhoea of non-infectious origin occurred in 8/30 infants ( 27 % ) of the adapted formula group , and in no infant in the hydrolysate group . “ Colic as single manifestation ” was considered of “ allergic ” origin in 1/28 infants in the hydrolysate group , and in 4/30 infants in the adapted formula group . If gastro-intestinal symptoms such as “ diarrhoea and colic as single manifestation ” are not considered , the number of infants with CMP sensitivity remains only significant for the first 6 months ( P : 0.004 ) . At 12 , 36 and 60 months , differences are not significant ( 0.106 , 0.116 and 0.07 , respectively ) . The results of this study support the hypothesis that allergy prevention is antigen specific . Conclusion If mother 's milk is not available and other studies confirm these results , there might be an indication for partial hydrolysates in infants with a family history of atopy , since these formulae reduce the incidence of CMP sensitivity In a previously published prospect i ve study , we followed the development of allergic symptoms in term infants with a slightly reduced birthweight ( − 1 SD to − 2 SD ) . These children received , according to local routing early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia . Of 216 infants 207 were observed for allergic symptoms up to 18 months of age . One group ( F ) received cow milk formula during the first days of life before the mother 's breastmilk production started and was then breastfed ; the other ( B ) was not given any formula before normal breastfeeding started . Unexpectedly , we found fewer allergic symptoms , in particular allergic skin problems , in the group fed cow milk , the difference being concentrated to children with a family fistory of allergic symptoms . At 5 Years of age 183 of the 207 children have been reinvestigated . Mild symptoms of allergy ( suspected and obvious ) were found in 22 % ( F ) and 27 % ( B ) respectively(NS ) . Moderate and severe symptoms of allergy ( obvious ) were found in 4.2 % ( F ) and 4.5 % ( B ) . In the subgroup with a double family history of allergic symptoms , 28 % ( 7/25 , F ) and 59 % ( 10/17 , B ) had symptoms of allergy ( p<0.05 ) . This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included , 1.4 % ( F ) and 53%(B ) respectively ( p < 0.05 ) . Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms . This difference was mainly caused by a reduced incidence of mild symptoms , some of which might not be true allergic symptoms . The incidence of moderate to severe disease was not affected , which can possibly be due to the relatively small number of children , expecially in the high risk group . Thus feeding with a high allergenic load during the first days of life seems , in the long run , to be ineffective in inhibiting the development of Significant ( moderate and severe ) atopic disease BACKGROUND There are no published prospect i ve , r and omized , double-blind , placebo-controlled studies of urticaria prevention in children . OBJECTIVE Our objective was to study the effect of long-term treatment with the H(1)-receptor antagonist cetirizine in the prevention of urticaria in young children with atopic dermatitis . METHODS In the prospect i ve , double-blind , parallel-group Early Treatment of the Atopic Child study , 817 children with atopic dermatitis who were 12 to 24 months of age at study entry were r and omized to receive either cetirizine , 0.25 mg/kg , or matching placebo twice daily for 18 months and to be followed up for an additional 6 months , during which time the study medication code remained unbroken . During both these double-blind phases of the study , for a total of 24 months , caregivers prospect ively recorded all symptoms and events , including hives , in a diary on a weekly basis when the child was well and on a daily basis when a symptom or event was observed . The diaries were review ed and vali date d with the investigators at each regularly scheduled study visit . RESULTS Acute urticaria occurred in 16.2 % of the placebo-treated children and in 5.8 % of the children treated with cetirizine ( P < .001 ) . The protective effect of cetirizine disappeared when treatment was stopped . In the study population as a whole , urticaria episodes were most commonly associated with intercurrent infection or with food ingestion or direct skin contact . CONCLUSION Acute urticaria is common in toddlers with atopic dermatitis and can be prevented with cetirizine in this high-risk population Several studies have demonstrated that early intervention may modulate the natural course of atopic disease . Our objective was to prevent sensitization to house-dust mite and food allergens , as well as the development of atopic symptoms during infancy , by the combination of an educational package and the use of mite allergen-impermeable mattress encasings . A multicentre European , population -based , r and omized , controlled study of children at increased atopic risk [ Study on the Prevention of Allergy in Children in Europe ( SPACE ) ] was performed in five countries ( Austria , Germany , Greece , the UK , and Lithuania ) , and included three cohorts - schoolchildren , toddlers , and newborns . We report on the newborn cohort . A total of 696 newborns were included from Austria , the UK , and Germany . Inclusion criteria were : a positive history of parental allergy ; and a positive skin-prick test or specific immunoglobulin E ( IgE ) ( IgE > or = 1.43 kU/L ) against at least one out of a panel of common aeroallergens in one or both parents . At 1 year of age , the overall sensitization rate against the tested allergens [ dust-mite allergens : Dermatophagoides pteronyssinus and Dermatophagoides farinae ( Der p and Der f ) ] and food allergens ( egg , milk ) in the prophylactic group was 6.21 % vs. 10.67 % in the control group . The prevalence of sensitization against Der p was 1.86 % in the prophylactic group vs. 5 % in the control group . In conclusion , we were able to demonstrate , in a group of newborns at risk for atopic diseases , that the sensitization rate to a panel of aero- and food allergens could be effectively decreased through the use of impermeable mattress encasings and the implementation of easy-to-perform preventive measures OBJECTIVE To determine whether chicken-based formula can replace soy-based formula in infants with cow milk allergy . SUBJECTS AND METHODS Thirty-eight infants with cow 's milk allergy , aged between 2 - 24 months of age were r and omized to receive either chicken-based formula or soy-based formula for 14 days . RESULTS In the group of soy-based formula , 12 out of 18 infants had evidence of intolerance and could not continue with the formula . However , only 4 out of 20 infants in the chicken-based formula group had evidence of clinical intolerance . All other 16 infants were fed the chicken-based formula with success . The number of infants who were intolerant to chicken formula was significantly lower than the number of those fed soy-based formula ( p = 0.009 ) . CONCLUSION Chicken-based formula can be used more effectively than soy-based formula in infants with cow milk allergy Of 5,500 newborn infants whose family histories were screened , 900 were found to have anamnestic risk . Cord-blood IgE was evaluable in 4,677 of these newborns , of which 394 had levels > or = 1 IU/mL ; 84 infants had both anamnestic risk and elevated cord-blood IgE levels . Parents of infants with anamnestic risk were informed of their child 's risk of atopy . Additionally , for 391 infants at two of the three participating hospitals , a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life , with maternal diet restricted to no more than 200 dL of cow milk per day , no more than one egg per week , and no tomato , fish , shellfish , nuts , or foods allergenic to the mother . Only soy formula was recommended , and introduction of solid foods was also carefully prescribed . Furthermore , doctors recommended against exposure to tobacco smoke , animal allergens , and early entrance into daycare . Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life ( 13.3 % , n = 158 ) than infants whose parents had ignored the prescribed diet ( 54.7 % , n = 86 ) or infants whose parents were offered no dietary recommendations ( 28.9 % , n = 218 ) . Differences between the compliant group and the two groups with unrestricted diets were significant , indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life Ten children with challenge-proven egg hypersensitivity and atopic dermatitis were enrolled in a double-blind crossover trial of oral cromolyn sodium . After receiving up to 40 mg/kg/day of cromolyn or placebo for 1 week , patients underwent double-blind placebo-controlled oral food challenges . In the eight subjects who reacted to the food challenge , there was no significant difference in the amount of food allergen eliciting the positive response , the timing of onset until first subjective or objective symptoms developed , symptoms provoked , or the duration of the symptoms in either phase of the study . This study demonstrates no benefit in the treatment of children with atopic dermatitis and food hypersensitivity with oral cromolyn sodium BACKGROUND Peanut allergy is receiving increasing attention . Only one study has estimated the prevalence in North America , but it did not corroborate history with diagnostic testing . OBJECTIVE We estimated the prevalence of peanut allergy in Montreal by administering question naires regarding peanut ingestion to children in kindergarten through grade 3 in r and omly selected schools . METHODS Respondents were stratified as follows : ( 1 ) . peanut tolerant , ( 2 ) . never-rarely ingest peanut , ( 3 ) . convincing history of peanut allergy , and ( 4 ) . uncertain history of peanut allergy . Groups 2 , 3 , and 4 underwent peanut skin prick tests ( SPTs ) , and if the responses were positive in groups 2 or 4 , measurement of peanut-specific IgE were undertaken . Children in group 3 with a positive SPT response were considered allergic to peanut without further testing . Children in groups 2 and 4 with peanut-specific IgE levels of less than 15 kU/L underwent oral peanut challenges . RESULTS Of the 7768 children surveyed , 4339 responded , 94.6 % in group 1 . The prevalence of peanut allergy was 1.50 % ( 95 % CI , 1.16%-1.92 % ) . When multiple imputation was used to incorporate data on those responding to the question naire but withdrawing before testing , the estimated prevalence increased to 1.76 % ( 95 % CI , 1.38%-2.21 % ) . When data regarding the peanut allergy status of nonresponders ( as declared to the school before the study ) were also incorporated , the estimated prevalence was 1.34 % ( 95 % CI , 1.08%-1.64 % ) . CONCLUSION Our prevalence study is the first in North America to corroborate history with confirmatory testing and the largest worldwide to incorporate these techniques . We have shown that , even with conservative assumptions , prevalence exceeds 1.0 % The prevalence of atopic diseases is increasing throughout the Western world , and means of primary prevention are needed to reverse this trend . The role of breast-feeding , the best source of infant nutrition , in protection against atopic disease remains elusive . In this double-blinded , placebo-controlled study of 62 mother-infant pairs , it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk , as assessed by the amount of anti-inflammatory transforming growth factor beta2 ( TGF-beta2 ) in the milk ( 2885 pg/mL [ 95 % CI , 1624 - 4146 ] in mothers receiving probiotics vs 1340 pg/mL [ 95 % CI , 978 - 1702 ] in mothers receiving placebo ; P = .018 ) . The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo ( 15 % and 47 % , respectively ; relative risk , 0.32 [ 95 % CI , 0.12 - 0.85 ] ; P = .0098 ) . Maternal atopy was a clear risk factor for atopic eczema in the infant . The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration . Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life BACKGROUND Studies suggest that peanut allergy prevalence might be increasing , but these results have not yet been substantiated . OBJECTIVE We conducted a follow-up study to determine whether peanut allergy prevalence in Montreal is increasing . METHODS Question naires regarding peanut ingestion were administered to parents of children in r and omly selected kindergarten through grade 3 classrooms between December 2000 and September 2002 and between October 2005 and December 2007 . Respondents were stratified as ( 1 ) peanut tolerant , ( 2 ) never/rarely ingest peanut , ( 3 ) convincing history of peanut allergy , or ( 4 ) uncertain history of peanut allergy . Children in group 3 with positive skin prick test responses were considered to have peanut allergy . Children in groups 2 and 4 with positive skin prick test responses had peanut-specific IgE levels measured , and if the value was less than 15 kU/L , an oral peanut challenge was performed . Multiple imputation was used to generate prevalence estimates that incorporated respondents providing incomplete data and nonrespondents . RESULTS Of 8,039 children surveyed in 2005 - 2007 , 64.2 % of parents responded . Among those providing complete data , the prevalence was 1.63 % ( 95 % CI , 1.30 % to 2.02 % ) in 2005 - 2007 versus 1.50 % ( 95 % CI , 1.16 % to 1.92 % ) in 2000 - 2002 . After adjustment for missing data , the prevalence was 1.62 % ( 95 % credible interval , 1.31 % to 1.98 % ) versus 1.34 % ( 95 % credible interval , 1.08 % to 1.64 % ) , respectively . The differences between the prevalences in 2005 - 2007 and 2000 - 2002 were 0.13 % ( 95 % credible interval , -0.38 % to 0.63 % ) among those providing complete data and 0.28 % ( 95 % credible interval , -0.15 % to 0.70 % ) after adjustment for missing data . CONCLUSIONS This is the first North American study to document temporal trends in peanut allergy prevalence by corroborating history with confirmatory tests . The results suggest a stable prevalence , but wide CIs preclude definitive conclusions BACKGROUND Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms . However , the natural history is left unchanged . OBJECTIVE To search for a beneficial effect of an oral desensitization protocol to allergenic foods in IgE-dependent milk or egg allergies in children . METHODS 60 children with documented cow 's milk allergy ( 13 months-6.5 years ) , and 90 children with egg allergy ( 12 months-8 years ) , were consecutively included after 6 - 12 months of avoidance diet , if a SBPCFC to 60 ml milk ( 60 ml ) or to 965 mg of raw egg white was negative . They were r and omized for uninterrupted avoidance or oral desensitization ( group A or OD ) . Six months later , a new SBPCFC was performed with , up to 200 ml of milk or 7 g of raw egg white . Prick tests and specific IgE levels were carried out simultaneously . RESULTS Data were obtained for 57 children with CMA ( 30 A and 27 OD ) , and 84 children with EA ( 35 A and 49 OD ) . The two groups ( AD or OD group ) were similar with regard to means of ages , the size of PT wheals and the level of IgEs at baseline . MILK ALLERGY : A SBPCFC to milk was positive in 11.1 % of those following OD vs. 40 % after A ( p < .025 ) . The size of PT decreased after OD and increased after A ( -3.4 mm vs. + 0.84 mm ; p < .002 ) . EGG ALLERGY : The SBPCFC to egg was positive in 30.6 % after OD vs. 48.6 % after A ( p < .1 ) . After 6 months , in the OD group , the mean size of the PT and the level of specific IgE were significantly reduced compared to the A group . In the A group , the threshold of reactivity was often lower , or more serious symptoms were observed . CONCLUSION Oral desensitization helps the egg and milk allergic children to overcome their allergies . Since the avoidance of these foods is likely to increase sensitization as well as to lower the threshold of reactivity , an active treatment is required . Further attempts to st and ardize the procedures of oral desensitization are expected BACKGROUND A milk-free diet with substitute formula should be established when immediate symptomatic hypersensitivity to cows ' milk protein ( CMP ) is diagnosed , and therefore an accurate diagnosis is very important . OBJECTIVE This study aims to find the optimal cutoff values for specific IgE antibody levels that discriminate between allergic and tolerant infants by using cows ' milk and its principal proteins as allergens . METHODS A prospect i ve study was carried out on 170 patients under 1 year old ( mean , 4.8 months ) . These patients were seen consecutively over a 4-year period in our outpatient clinic and for the first time because of a reaction suggesting immediate hypersensitivity after ingestion of cows ' milk formula . A clinical history , prick test with cows ' milk and its proteins ( alpha-lact-albumin , beta-lactoglobulin , and casein ) , determination of specific IgE antibodies with the CAP system FEIA for the same allergens as for the prick test , and a challenge test according to the diagnostic protocol were performed in all of the children . A study of validity of the prick test ( cutoff point , 3 mm ) and CAP system by using different cutoff points in the specific IgE values for cows ' milk and its proteins were also analyzed . RESULTS Prevalence of immediate symptomatic hypersensitivity to CMP in this study was 44 % . When both the whole milk and its principal milk proteins were used in the prick test , the negative predictive value was very high , and a negative value excluded allergy in 97 % of the patients . When the different cutoff points of the specific IgE for milk were analyzed , 2.5 KU(A)/L had a positive predictive value of 90 % and 5 KU(A)/L had a positive predictive value of 95 % . CONCLUSIONS When diagnosing immediate hypersensitivity to CMP in infants , negative skin test responses exclude allergy in most of the patients . If the prick test response is positive , specific IgE levels for cows ' milk may be helpful . If these values are 2.5 KU(A)/L or greater , the challenge test should not be performed because of its high positive predictive value ( 90 % ) BACKGROUND The diagnosis of peanut allergy must be based on reliable , safe criteria . Double-blind , placebo-controlled food challenges ( DBPCFCs ) are the gold st and ard but are costly and dangerous because they can trigger severe reactions . OBJECTIVE The aim of this study was to develop a new strategy for diagnosing peanut allergy while reducing the need for DBPCFCs . METHODS We studied 363 children referred for an evaluation of suspected food hypersensitivity . They all benefited from the same diagnostic strategy , which included , in order , clinical history , a skin prick test ( SPT ) , and a specific IgE assay . DBPCFCs were performed on all the children by personnel who were unaware of the results of the other tests . To assess the performance characteristics of the SPT ( comparing commercial and raw peanut extracts ) and the specific IgE assay , we compared the results with those provided by the DBPCFCs . For SPTs and specific IgE assays , we sought to determine the cutoff values required to exclude false-positive and false-negative results . RESULTS According to DBPCFC results , 177 children were allergic to peanut , and 186 were not . The performance characteristics of the SPTs were superior with the raw extract because the negative predictive value was 100 % ( 95 % confidence interval [ CI ] , 97.5 - 100 ) . If the skin reaction with the raw extract was less than 3 mm , we could be quite certain that the child was not allergic . On the other h and , if the SPT result ed in a wheal diameter of larger than 3 mm , we could only be 74 % certain that the children were allergic . Furthermore , if the SPT result ed in a wheal diameter of 16 mm or larger , we could be quite certain that the child was allergic because the positive predictive value was 100 % ( 95 % CI , 86.8 - 100 ) . Specific IgE concentrations of 57 kU(A)/L or greater were associated with a positive predictive value of 100 % ( 95 % CI , 87.2 - 100 ) . The combined use of the tests result ing in a positive diagnosis if the SPT result was 16 mm or larger or specific IgE concentration was 57 kU(A)/L or greater and in a negative diagnosis if the SPT result was less than 3 mm and the specific IgE concentration was less than 57 kU(A)/L allowed us to classify subjects with almost complete certainty as being allergic or not because the predictive values were 100 % . CONCLUSION Commercial extracts could not be used to reliably predict tolerance of peanut . Peanut DBPCFCs can be avoided when SPTs with raw extracts result ed in wheals with a largest diameter of less than 3 mm and a specific IgE concentration of less than 57 kU(A)/L and also when wheal diameters were 16 mm or larger or specific IgE values were 57 kU(A)/L or greater . Otherwise , DBPCFCs were indispensable for the unequivocal diagnosis of peanut allergy During 90 days of elimination diet nineteen children with food allergy manifesting atopic dermatitis were treated with either 120 mg/day of thymomodulin ( 10 subjects ) or placebo ( 9 subjects ) in a double blind design . After this period an improvement in skin lesions was observed in both groups . Subsequently a food challenge was performed for two weeks : in the group treated with thymomodulin skin lesions did not modify while they worsened in the placebo group and the comparison was statistically significant ( p less than 0.01 ) . Before the beginning of the trial laboratory assessment s evidence d an increase in total and specific IgE serum levels , which decreased by the end of the study only in the group receiving the thymic derivative ( p less than 0.05 ) Background : The efficacy of specific immunotherapy ( SIT ) in pollen allergy is well established . However , its effect on pollen associated food allergy particularly the oral allergy syndrome ( OAS ) is not definitely ascertained Background : Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast‐feeding is not possible . We studied the specific cellular and humoral immune response to cow 's milk proteins and occurrence of atopic dermatitis under different feeding regimens : two hydrolyzed infant milk formulas ( partially [ pHF ] and extensively hydrolyzed [ eHF ] ) and under exclusive breast‐feeding ( BF ) BACKGROUND Orally administered , food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals . OBJECTIVE We sought to determine whether milk oral immunotherapy ( OIT ) is safe and efficacious in desensitizing children with cow 's milk allergy . METHODS Twenty children were r and omized to milk or placebo OIT ( 2:1 ratio ) . Dosing included 3 phases : the build-up day ( initial dose , 0.4 mg of milk protein ; final dose , 50 mg ) , daily doses with 8 weekly in-office dose increases to a maximum of 500 mg , and continued daily maintenance doses for 3 to 4 months . Double-blind , placebo-controlled food challenges ; end-point titration skin prick tests ; and milk protein serologic studies were performed before and after OIT . RESULTS Nineteen patients , 6 to 17 years of age , completed treatment : 12 in the active group and 7 in the placebo group . One dropped out because of persistent eczema during dose escalation . Baseline median milk IgE levels in the active ( n = 13 ) versus placebo ( n = 7 ) groups were 34.8 kUa/L ( range , 4.86 - 314 kUa/L ) versus 14.6 kUa/L ( range , 0.93 - 133.4 kUa/L ) . The median milk threshold dose in both groups was 40 mg at the baseline challenge . After OIT , the median cumulative dose inducing a reaction in the active treatment group was 5140 mg ( range 2540 - 8140 mg ) , whereas all patients in the placebo group reacted at 40 mg ( P = .0003 ) . Among 2437 active OIT doses versus 1193 placebo doses , there were 1107 ( 45.4 % ) versus 134 ( 11.2 % ) total reactions , with local symptoms being most common . Milk-specific IgE levels did not change significantly in either group . Milk IgG levels increased significantly in the active treatment group , with a predominant milk IgG4 level increase . CONCLUSIONS Milk OIT appears to be efficacious in the treatment of cow 's milk allergy . The side-effect profile appears acceptable but requires further study ABSTRACT . The success of familial compliance with a dietary manipulation programme was studied prospect ively in 91 newborn babies from atopic families for up to 12 months . The control group consisted of 72 infants from non‐atopic families . The percentages of infants breast‐fed at the age of six months were 58 % and 38 % in the study group and control group , respectively . The introduction of cow 's milk based formulas was postponed until the age of three months in 63 % of the infants in the study group and 47 % of the infants in the control group . Solid food was avoided during the first three months in 76 % and 45 % of the infants in the study group and control group , respectively . Maternal age , smoking and low social class were associated with poor compliance . The existence of atopic dermatitis in any member of the family was associated with good compliance . The main advantages of our programme were the increased number of children breast‐fed until the age of six months , and the reduced number of infants introduced to cow 's milk based formulas or solid food before three months of age BACKGROUND The double-blind , placebo-controlled food challenge is considered the gold st and ard for diagnosing food allergy . However , in a retrospective analysis of children and adolescents with atopic dermatitis and food allergy , discrete food-specific IgE concentrations were established that could predict clinical reactivity to egg , milk , peanut , and fish with greater than 95 % certainty . OBJECTIVE The purpose of this investigation was to determine the utility of these 95 % predictive decision points in a prospect i ve evaluation of food allergy . METHODS Sera from 100 consecutive children and adolescents referred for evaluation of food allergy were analyzed for specific IgE antibodies to egg , milk , peanut , soy , wheat , and fish by using the Pharmacia CAP System FEIA . Food-specific IgE values were compared with history and the results of skin prick tests and food challenges to determine the efficacy of previously established 95 % predictive decision points in identifying patients with increased probability of reacting during a specific food challenge . RESULTS One hundred children ( 62 % male ; median age , 3.8 years ; range , 0.4 - 14.3 years ) were evaluated for food allergy . The diagnosis of food allergy was established by means of history or oral food challenge . On the basis of the previously established 95 % predictive decision points for egg , milk , peanut , and fish allergy , greater than 95 % of food allergies diagnosed in this prospect i ve study were correctly identified by quantifying serum food-specific IgE concentrations . CONCLUSION In a prospect i ve study of children and adolescents referred for evaluation of food allergy , previously established 95 % predictive decision points of food-specific IgE antibody concentrations for 4 major food allergens were effective in predicting clinical reactivity . Quantification of food-specific IgE is a useful test for diagnosing symptomatic allergy to egg , milk , peanut , and fish in the pediatric population and could eliminate the need to perform double-blind , placebo-controlled food challenges in a significant number of children A group of 129 infants were r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) or a casein hydrolysate formula ( CHF ) during the first 3 days of life . Blood sample s were taken on at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . Macromolecular absorption was analysed by measuring the serum concentration of human α‐lactalbumin ( S‐α‐LA ) with a competitive radioimmunoassay ( RIA ) . Total serum IgE was measured by RIA . A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age ( p= 0.03 and p= 0.04 respectively ) . In none of the three groups did correlation exist between the duration of breastfeeding and serum α‐LA , serum IgE , family history of allergy , frequency of allergic symptoms and proportion of infants with infections BACKGROUND Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States . TNX-901 is a humanized IgG1 monoclonal antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the high-affinity Fc(epsilon ) receptor on mast cells and basophils . METHODS We conducted a double-blind , r and omized , dose-ranging trial in 84 patients with a history of immediate hypersensitivity to peanut . Hypersensitivity was confirmed and the threshold dose of encapsulated peanut flour established by a double-blind , placebo-controlled oral food challenge at screening . Patients were r and omly assigned in a 3:1 ratio to receive either TNX-901 ( 150 , 300 , or 450 mg ) or placebo subcutaneously every four weeks for four doses . The patients underwent a final oral food challenge within two to four weeks after the fourth dose . RESULTS From a mean base-line threshold of sensitivity of 178 to 436 mg of peanut flour in the various groups , the mean increases in the oral-food-challenge threshold were 710 mg in the placebo group , 913 mg in the group given 150 mg of TNX-901 , 1650 mg in the group given 300 mg of TNX-901 , and 2627 mg in the group given 450 mg of TNX-901 ( P<0.001 for the comparison of the 450-mg dose with placebo , and P for trend with increasing dose < 0.001 ) . TNX-901 was well tolerated . CONCLUSIONS A 450-mg dose of TNX-901 significantly and substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut ( 178 mg ) to one equal to almost nine peanuts ( 2805 mg ) , an effect that should translate into protection against most unintended ingestions of peanuts Cow 's milk protein allergy ( CMPA ) is best treated by complete elimination of cow 's milk from the diet . For infants with CMPA who can not be breast-fed , formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow 's milk-based formulas . In this study , we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose ( eHF ) with those who were fed an amino acid formula ( AAF ) . This was a prospect i ve , multi-center , r and omized , reference-controlled study . Seventy-seven infants < 12 months old with suspected CMPA were enrolled . In 66 of these , CMPA was confirmed by oral challenge in a double-blind , placebo-controlled food challenge ( DBPCFC ) or by a medical history of severe allergic reaction to cow 's milk and a positive skin prick test . These infants were then tested for their reaction to eHF and AAF in a DBPCFC . All infants tolerated both formulas and were r and omized to receive either eHF ( n = 34 ) or AAF ( n = 32 ) for 180 days . Growth ( weight , length , and head circumference ) and tolerance [ skin , gastro-intestinal , and respiratory tract symptoms of allergy ] were evaluated after 30 , 60 , 90 , and 180 days . There were no significant differences between the two groups in any of the growth measurements . Length and head circumference were similar to Euro-growth st and ards , but weight was slightly lower . Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups . However , whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF , there was a slight decrease in those fed AAF . Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools . The new eHF is safe and well tolerated in infants diagnosed with CMPA Peripheral blood mononuclear cells ( P BMC s ) from patients with atopic dermatitis ( AD ) selected as being sensitive to hen 's egg or cow 's milk responded to food antigens , ovalbumin , or bovine serum albumin , with significantly enhanced DNA synthesis compared with the DNA synthesis in P BMC s from nonatopic control subjects and food-sensitive patients with immediate symptoms . Patients were treated with elimination diets . Symptoms of AD had been in remission during elimination diets . The levels of specific IgE antibodies to hen 's egg or cow 's milk decreased during elimination diets in patients with positive radioallergosorbent test ( RAST ) . In patients with negative RAST , specific IgE antibodies remained negative during elimination diets . The proliferative responses of P BMC s to food antigens also decreased during elimination diets in patients with proliferative responses before elimination diets . Taken together , specific IgE antibodies to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and positive RAST , and proliferative responses of P BMC s to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and proliferative responses of P BMC The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally r and omized , controlled trial of infants of atopic parents . The diet of the prophylactic-treated group ( N = 103 ) included ( 1 ) maternal avoidance of cow 's milk , egg , and peanut during the third trimester of pregnancy and lactation and ( 2 ) infant use of casein hydrolysate ( Nutramigen ) for supplementation or weaning , and avoidance of solid foods for 6 months ; cow 's milk , corn , soy , citrus , and wheat , for 12 months ; and egg , peanut , and fish , for 24 months . In the control group ( N = 185 ) , mothers had unrestricted diets , and infants followed American Academy of Pediatrics feeding guidelines . The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated ( 16.2 % ) compared to the control ( 27.1 % ) group ( p = 0.039 ) , result ing from reduced food-associated atopic dermatitis , urticaria and /or gastrointestinal disease by 12 months ( 5.1 % versus 16.4 % ; p = 0.007 ) , and any positive food skin test by 24 months ( 16.5 % versus 29.4 % ; p = 0.019 ) , caused primarily by fewer positive milk skin tests ( 1 % versus 12.4 % ; p = 0.001 ) . The prevalences of allergic rhinitis , asthma , and inhalant skin tests were unaffected . Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months . Thus , reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life OBJECTIVES We conducted a prospect i ve , r and omized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow 's milk allergy . STUDY DESIGN Infants ( n = 170 ) with documented cow 's milk allergy were r and omly assigned to receive either a soy formula or an extensively hydrolyzed formula . If it was suspected that the formula caused symptoms , a double-blind , placebo-controlled challenge ( DBPCFC ) with the formula was performed . The children were followed to the age of 2 years , and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years . RESULTS An adverse reaction to the formula was confirmed by challenge in 8 patients ( 10 % ; 95 % confidence interval , 4.4%-18.8 % ) r and omly assigned to soy formula and in 2 patients ( 2.2 % ; 95 % confidence interval , 0.3 % to 7.8 % ) r and omly assigned to extensively hydrolyzed formula . Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow 's milk allergy ( 11 % and 9 % , respectively ) . IgE to soy was detected in only 2 infants with an adverse reaction to soy . Adverse reactions to soy formula were more common in younger ( < 6 months ) than in older ( 6 to 12 months ) infants ( 5 of 20 vs 3 of 60 , respectively , P = .01 ) . CONCLUSIONS Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow 's milk allergy . Development of IgE-associated allergy to soy was rare . Soy formula can be recommended as a first-choice alternative for infants > or=6 months of age with cow 's milk allergy The effect of treatment with astemizole ( Hismanal ® ) on symptoms elicited by ingestion of hazelnuts in birch pollen‐allergic patients ( the oral allergy syndrome ) was investigated . Thirty patients with a well‐documented allergy to silver birch , experiencing symptoms when ingesting hazelnuts , were included in the study . All had a positive skin prick test ( SPT ) to birch , whereas 29 and 27 , respectively , showed a positive RAST and basophil histamine release test ( HR ) to birch . In contrast , only 15 patients had a positive SPT to hazelnut , 13 had a positive RAST , whereas 24 had a positive HR . Alter two oral provocations with hazelnuts the patients were r and omized to receive either 10 mg of astemizole or placebo daily for 2 weeks in a double blind protocol followed by two oral provocations . Treatment with astemizole significantly reduced the symptoms compared with placebo ( P= 0.004 ) ; however , without completely abolishing the symptoms Objectives : For breast-fed infants with rectal bleeding , maternal restriction of dietary protein such as cow 's milk proteins is often recommended ; however , poor response to dietary protein restriction is of concern . This pilot study was design ed to assess the effectiveness of Lactobacillus GG ( LGG ) in breast-fed infants with rectal bleeding . Patients and Methods : Breast-fed infants < 6 months of age with rectal bleeding ( defined as the presence of visible specks or streaks of blood mixed with mucus in the stool in otherwise healthy infants ) were enrolled in a double-blind r and omized controlled trial in which they received LGG 3 × 109 colony-forming units ( n = 14 ) or placebo ( n = 15 ) twice daily for 4 weeks as an adjunct to cow 's milk restriction in the mother 's diet . Analyses were based on allocated treatment and included data from 26 infants . Results : Mean duration of rectal bleeding was similar in the LGG and control groups ( 17.3 ± 10.6 vs 15.4 ± 11 days ; mean difference −1.9 ( 95 % confidence interval [ CI ] −4 to 7 ) . No difference was found in the number of infants with clinical resolution of rectal bleeding within 72 hours and no relapse afterward ( 2/11 vs 3/15 , relative risk [ RR ] 0.9 , 95 % CI 0.2–3.9 ) and the number of infants with clinical resolution of rectal bleeding within 72 hours followed by relapse of symptoms ( 5/11 vs 5/15 , RR 1.4 , 95 % CI 0.5–3.5 ) . Breast-feeding cessation was not needed in any infant . Conclusions : These results do not support the use of LGG as an adjunct to maternal cow 's milk restriction in breast-fed infants with rectal bleeding BACKGROUND The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system . Probiotics , live health-promoting microbes , might offer such stimulation . OBJECTIVE We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases . METHODS We r and omized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery . Their infants received the same probiotics plus galacto-oligosaccharides ( n = 461 ) or a placebo ( n = 464 ) for 6 months . At 2 years , we evaluated the cumulative incidence of allergic diseases ( food allergy , eczema , asthma , and allergic rhinitis ) and IgE sensitization ( positive skin prick test response or serum antigen-specific IgE level > 0.7 kU/L ) . Fecal bacteria were analyzed during treatment and at age 2 years . RESULTS Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated ( atopic ) diseases ( odds ratio [ OR ] , 0.71 ; 95 % CI , 0.50 - 1.00 ; P = .052 ) . Probiotic treatment reduced eczema ( OR , 0.74 ; 95 % CI , 0.55 - 0.98 ; P = .035 ) and atopic eczema ( OR , 0.66 ; 95 % CI , 0.46 - 0.95 ; P = .025 ) . Lactobacilli and bifidobacteria more frequently ( P < .001 ) colonized the guts of supplemented infants . CONCLUSION Probiotic treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema . The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics . CLINICAL IMPLICATION S The prevention of atopic eczema in high-risk infants is possible by modulating the infant 's gut microbiota with probiotics and prebiotics BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit . Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children Retraction On 28 October 2015 , The BMJ retracted this article , published in 1989 : Ch and ra RK , Puri S , Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants . BMJ 1989;299:228–30 . The BMJ has retracted the article after receiving a copy of an inquiry into the research of R K Ch and ra , which was conducted by the Memorial University of Newfoundl and and completed in August 1995 . The university did not publish the inquiry report at the time . Nor did it notify the editors of journals that had published articles by Ch and ra that were considered in the report . The BMJ obtained a copy of the report when it came into the public domain as a result of Ch and ra taking and losing a legal action against the Canadian Broadcasting Corporation ( CBC ) , which aired television programmes about Ch and ra in 2006 . The inquiring committee experienced great difficulty with its work , but its final conclusion was that “ scientific misconduct has been committed by Dr Ch and ra . ” It looked at three studies and found that : “ absolutely no raw data ( or files ) of any kind were exhibited ” “ the Committee can not identify anyone who did the recruiting , can not identify anyone who did or remembers a significant amount of work ” “ the coauathors had little or very likely nothing to do with the work ” “ it is unbelievable that there are essentially no hospital records to support the study in question ” “ the committee can not accept that the Carnation study was done anywhere near to completeness or with the accuracy reported in the Annals of Allergy and Journal of Clinical Nutrition , For that matter , the same can probably be said for the Mead Johnson work published in the British Medical Journal . ” When asked by The BMJ in 2015 why it had not published the report in 1995 , Memorial University of Newfoundl and said that the report “ was the product of a flawed investigation process and could not be relied upon . ” In the CBC programmes , however , a university spokesman said that the university had not acted on the report because of legal threats from Ch and ra . The university further told The BMJ : “ In the spirit of being helpful , we acknowledge that over the years serious questions have been raised about the 1989 publication , leading to much controversy . If [ The ] BMJ decides to retract the paper on the basis of evidence apart from the findings of the 1995 report , then we would underst and your decision in this regard . ” The BMJ is retracting the paper because of the 1995 report , and because of the convincing evidence given in the CBC television programmes and the court case that the work of R K Ch and ra is not to be trusted . For more information , see The BMJ 's feature article(1 ) and editorial,(2 ) published on 28 October 2015 |
13,968 | 18,646,169 | There is no evidence that interventions aim ed at reducing body temperature to between 35 degrees C and 37.5 degrees C in the first week after TBI improves patient outcomes . | BACKGROUND A recent retrospective study suggested that after traumatic brain injury , patients with a raised body temperature have an unfavourable outcome compared to patients that have a normal body temperature .
OBJECTIVES To assess the effects of modest cooling therapies ( defined as any drug or physical therapy aim ed at maintaining body temperature between 35 degrees C and 37.5 degrees C ) when applied to patients in the first week after traumatic brain injury . | Context Elevated temperature worsens injury in experimental focal and global ischemia and brain trauma . Fever is common in patients with acute neurologic illness and independently predicts poor outcome . Conventional means of treating fever are not very effective in this population . Objective To study the effectiveness of a catheter-based heat exchange system in reducing elevated temperatures in critically ill neurologic and neurosurgical patients . Design , Intervention , Setting , and Population This was a prospect i ve r and omized , nonblinded trial that compared conventional treatment of fever ( acetaminophen and cooling blankets ) with conventional treatment plus an intravascular catheter-based heat exchange system ( Alsius , Irvine , CA ) . Patients admitted to one of 13 neurologic intensive care units in academic medical centers were eligible if they a ) suffered subarachnoid hemorrhage , intracerebral hemorrhage , ischemic infa rct ion , or traumatic brain injury ; b ) had a temperature > 38 ° C on two occasions or for > 4 continuous hrs ; and c ) required central venous access . Main Outcome MeasureThe fever burden ( area under the curve > 38 ° C ) for 72 hrs was compared in an intention to treat analysis . Safety of the catheter system was monitored . Results A total of 296 patients were enrolled over 20 months . Forty-one percent had subarachnoid hemorrhage , 24 % had traumatic brain injury , 23 % had intracerebral hemorrhage , and 13 % had ischemic stroke . The groups were matched in terms of age , body mass index , sex , and Glasgow Coma Scale score distribution . Fever burden was 7.92 vs. 2.87 ° C-hrs in the conventional group and catheter groups , respectively ( 64 % reduction , p < .01 ) . There was no higher rate of infection or the use of sedatives , narcotics , or antibiotics in the catheter group . The catheter did not significantly increase risk to the patient beyond that of a central catheter . Conclusions The addition of this catheter-based cooling system to conventional management significantly improves fever reduction in neurologic intensive care unit patients BACKGROUND Pyrexia is common after brain injury ; it is generally believed to affect outcome adversely and the usual clinical methods of reducing temperature are not effective . The normal physiological mechanisms of brain cooling are heat loss from the upper airways and through the skull , and these can produce selective brain cooling . METHODS Air at room temperature and humidity was continuously administered to 15 brain-injured , intubated and mechanically ventilated patients via a sponge-tipped oxygen catheter in each nostril at a combined rate of 115 ml kg(-1 ) min(-1 ) . Brain temperature was measured using a pressure-temperature Camino catheter which is design ed to site the thermistor 1 cm into the parenchyma in the frontal lobe . Oesophageal temperature was measured using an oesophageal stethoscope with a thermistor . After establishing baseline for 30 min , patients were r and omized to receive airflow or no airflow for 6 h and then crossed over for a further 6 h. RESULTS Airflow replicating normal resting minute volume did not produce clinical ly relevant or statistically significant reductions in brain temperature [ 0.13 ( SD 0.55 ) degrees C ; 95 % CI , 0.43 - 0.17 degrees C ] . However , we serendipitously found some evidence of selective brain cooling via the skull , but this needs further substantiation . CONCLUSIONS A flow of humidified air at room temperature through the upper respiratory tracts of intubated brain-injured patients did not produce clinical ly relevant or statistically significant reductions in brain temperature measured in the frontal lobe Background Temperature management is used with increased frequency as a tool to mitigate neurological injury . Although frequently used , little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit ( ICU ) . In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury . Methods Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospect ively enrolled . Ten patients in each group were assigned in consecutive order to conventional cooling ( that is , rapid infusion of 30 ml/kg cold fluids , ice and /or coldpacks ) , cooling with water circulating blankets , air circulating blankets , water circulating gel-coated pads and an intravascular heat exchange system . In all patients the speed of cooling ( expressed as ° C/h ) was measured . After the target temperature was reached , we measured the percentage of time the patient 's temperature was 0.2 ° C below or above the target range . Rates of temperature decline over time were analyzed with one-way analysis of variance . Differences between groups were analyzed with one-way analysis of variance , with Bonferroni correction for multiple comparisons . A p < 0.05 was considered statistically significant . Results Temperature decline was significantly higher with the water-circulating blankets ( 1.33 ± 0.63 ° C/h ) , gel-pads ( 1.04 ± 0.14 ° C/h ) and intravascular cooling ( 1.46 ± 0.42 ° C/h ) compared to conventional cooling ( 0.31 ± 0.23 ° C/h ) and the air-circulating blankets ( 0.18 ± 0.2 ° C/h ) ( p < 0.01 ) . After the target temperature was reached , the intravascular cooling device was 11.2 ± 18.7 % of the time out of range , which was significantly less compared to all other methods . Conclusion Cooling with water-circulating blankets , gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets . The intravascular cooling system is most reliable to maintain a stable temperature OBJECT Hypothermia is by far the most potent neuroprotectant . Nevertheless , timely and safe delivery of hypothermia remains a clinical challenge . To maximize neuroprotection yet minimize systemic complications , ultra-early delivery of selective cerebral hypothermia by Emergency Medical Service ( EMS ) personnel in the field would be advantageous . The authors ( W.E. and H.W. ) have developed a cooling helmet by using National Aeronautics and Space Administration spinoff technology . In this study its effectiveness in lowering brain temperature in patients with severe stroke or head injury is examined . METHODS Patients were r and omly assigned to groups receiving either the cooling helmet or no cooling , and brain temperatures ( 0.8 cm below the cortical surface ) were continuously monitored for a mean of 48 to 72 hours with a Neurotrend sensor and then compared with the patients ' core temperatures . There were eight patients in the study group and six in the control group . The mean change in temperature ( brain-body temperature ) calculated from 277 data hours in the study group was -1.6 degrees C compared with a mean change in temperature of + 0.22 degrees C calculated from 309 data hours in the control group . This was statistically significant ( p < 0.0001 ) . On average , 1.84 degrees C of brain temperature reduction ( range 0.9 - 2.4 degrees C ) was observed within 1 hour of helmet application . It took a mean of 3.4 hours ( range 2 - 6 hours ) to achieve a brain temperature lower than 34 degrees C and 6.67 hours ( range 1 - 12 hours ) before systemic hypothermia ( < 36 degrees C ) occurred . Use of the helmet result ed in no significant complications . There was , however , one episode of asymptomatic bradycardia ( heart rate < 40 ) that responded to a 0.5 degrees C body temperature increase . CONCLUSIONS This helmet delivers initial rapid and selective brain cooling and maintains a significant temperature gradient between the core and brain temperatures throughout the hypothermic period to provide sufficient regional hypothermia yet minimize systemic complications . It results in delayed systemic hypothermia , creating a safe window for possible ultra-early delivery of regional hypothermia by EMS personnel in the field BACKGROUND Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia . We did a multicentre r and omised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy . METHODS 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography ( aEEG ) were r and omly assigned to either head cooling for 72 h , within 6 h of birth , with rectal temperature maintained at 34 - 35 degrees C ( n=116 ) , or conventional care ( n=118 ) . Primary outcome was death or severe disability at 18 months . Analysis was by intention to treat . We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before r and omisation -- ie , severe loss of background amplitude , and seizures-- and those with less severe changes . FINDINGS In 16 babies , follow-up data were not available . Thus in 218 infants ( 93 % ) , 73/110 ( 66 % ) allocated conventional care and 59/108 ( 55 % ) assigned head cooling died or had severe disability at 18 months ( odds ratio 0.61 ; 95 % CI 0.34 - 1.09 , p=0.1 ) . After adjustment for the severity of aEEG changes with a logistic regression model , the odds ratio for hypothermia treatment was 0.57 ( 0.32 - 1.01 , p=0.05 ) . No difference was noted in the frequency of clinical ly important complications . Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes ( n=46 , 1.8 ; 0.49 - 6.4 , p=0.51 ) , but was beneficial in infants with less severe aEEG changes ( n=172 , 0.42 ; 0.22 - 0.80 , p=0.009 ) . INTERPRETATION These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy , it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes Introduction Aim of this r and omized prospect i ve clinical trial is to compare two methods of antipyretics and evaluate their efficacy in controlling fever during the acute phase of brain damage . Methods Twenty-two febrile comatose patients : 12 severe traumatic brain injury and 10 subarachnoid hemorrhage divided in 2 groups : Diclofenac low-dose infusion ( 10 patients ) and extemporaneous boluses of NSAIDs ( CTRL , 12 patients ) . The primary outcome measure was length of time with temperature > 38 ° C . Secondary outcome measures were : 1 ) to assess the effects of each antipyretic strategy on intracranial pressure ( ICP ) , cerebral perfusion pressure ( CPP ) , mean arterial pressure ( MAP ) and heart rate ; 2 ) to monitor adverse effects of each antipyretic strategy . The baseline characteristics in the two treatment groups were similar . Results Primary findings : percentage of time per patient with temperature > 38 ° C was significantly lower ( P < 0.0001 ) in the DCF group , 4 % ( 0–22 % ) , vs. 34 % ( 8–56 % ) in CTRL group . In addition , mean T ° , max T ° were lower in DCF than in CTRL ( P < 0.05 ) . Secondary findings : CPP and MAP were significantly higher in DCF group ( P < 0.05 ) while ICP was not different ( NS ) . However , if ICP pre r and omization was < 25 mmHg , CTRL suffered a worst ICP ( 24 ± 11 vs. 16 ± 7 P = 0.01 ) , MAP ( 89 ± 10 vs. 104 ± 10 P = 0.01 ) and CPP ( 75 ± 10 vs. 94 ± 17 P = 0.01 ) compared to DCF . No differences between the two treatment were recorded when ICP ≥ 25 mmHg before r and omization . There was no gastrointestinal or intracranial bleeding . Conclusions Low dose DCF infusion is a potential useful strategy for a successful control temperature better than intermittent NSAIDs dosing , minimizing potentially brain-damaging effects of fever BACKGROUND Heat loss from the upper airways and through the skull are physiological mechanisms of brain cooling which have not been fully explored clinical ly . METHODS This r and omized , crossover , factorial trial in 12 brain-injured , orally intubated patients investigated the effect of enhanced nasal airflow ( high flow unhumidified air with 20 p.p.m . nitric oxide gas ) and bilateral head fanning on frontal lobe brain temperature and selective brain cooling . After a 30 min baseline , each patient received the four possible combinations of the interventions --airflow , fanning , both together , no intervention -- in r and omized order . Each combination was delivered for 30 min and followed by a 30 min washout , the last 5 min of which provided the baseline for the next intervention . RESULTS The difference in mean brain temperature over the last 5 min of the preceding washout minus the mean over the last 5 min of intervention , was 0.15 degrees C with nasal airflow ( P=0.001 , 95 % CI 0.06 - 0.23 degrees C ) and 0.26 degrees C with head fanning ( P<0.001 , 95 % CI 0.17 - 0.34 degrees C ) . The estimate of the combined effect of airflow and fanning on brain temperature was 0.41 degrees C. Selective brain cooling did not occur . CONCLUSION Physiologically , this study demonstrates that heat loss through the upper airways and through the skull can reduce parenchymal brain temperature in brain-injured humans and the onset of temperature reduction is rapid . Clinical ly , in ischaemic stroke , a temperature decrease of 0.27 degrees C may reduce the relative risk of poor outcome by 10 - 20 % . Head fanning may have the potential to achieve a temperature decrease of this order Objective : To evaluate the efficacy of an air-circulating cooling blanket for reducing body temperature in febrile neuro-ICU patients treated with acetaminophen . Methods : Two-hundred twenty consecutively admitted neuro-ICU patients whose tympanic membrane temperature reached or exceeded 101 ° F ( 38.3 ° C ) were r and omly assigned to receive acetaminophen ( 650 mg every 4 hours ) alone ( n = 107 ) or acetaminophen plus air blanket therapy ( n = 113 ) . After 24 hours of treatment , the authors compared the proportion of subjects who attained treatment success ( T ≤ 99 ° F ) or treatment failure ( T ≥ 101 ° F for 2 consecutive hours ) using the χ2 test and the time to reach these endpoints using Kaplan-Meier survival analysis . Main Results : Air blanket therapy result ed in a small increase in the proportion of subjects with treatment success ( 44 % versus 36 % , χ2 p = 0.19 , log rank p = 0.10 ) and a similar small reduction in the proportion of patients with treatment failure ( 42 % versus 53 % , χ2 p = 0.11 , log-rank p = 0.21 ) , compared with treatment with acetaminophen alone . Approximately one third of patients in both groups remained febrile after r and omization and “ failed ” after the first 2 hours of treatment . Twelve percent of patients assigned to air blanket therapy refused or were unable to tolerate treatment , compared with 2 % of patients treated with acetaminophen alone ( p = 0.005 ) . Conclusions : Treatment with an air-circulating cooling blanket did not effectively reduce body temperature in febrile neuro-ICU patients treated with acetaminophen . More effective interventions are needed to maintain normothermia in patients at risk for fever-related brain damage Objective : To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients . Design : Prospect i ve , unblinded , r and omized controlled trial . Setting : Neurologic intensive care unit in an urban teaching hospital . Patients : Forty-seven patients , the majority of whom were mechanically ventilated and se date d , with fever ≥38.3 ° C for > 2 consecutive hours after receiving 650 mg of acetaminophen . Interventions : Subjects were r and omly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient ( Cincinnati SubZero , Cincinnati OH ) or the A rct ic Sun Temperature Management System ( Medivance , Louisville CO ) , which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs . Measurements and Main Results : Diagnoses included subarachnoid hemorrhage ( 60 % ) , cerebral infa rct ion ( 23 % ) , intracerebral hemorrhage ( 11 % ) , and traumatic brain injury ( 4 % ) . The groups were matched in terms of baseline variables , although mean temperature was slightly higher at baseline in the A rct ic Sun group ( 38.8 vs. 38.3 ° C , p = .046 ) . Compared with patients treated with the SubZero blanket ( n = 24 ) , A rct ic Sun-treated patients ( n = 23 ) experienced a 75 % reduction in fever burden ( median 4.1 vs. 16.1 C ° -hrs , p = .001 ) . A rct ic Sun-treated patients also spent less percent time febrile ( T ≥38.3 ° C , 8 % vs. 42 % , p < .001 ) , spent more percent time normothermic ( T ≤37.2 ° C , 59 % vs. 3 % , p < .001 ) , and attained normothermia faster than the SubZero group median ( 2.4 vs. 8.9 hrs , p = .008 ) . Shivering occurred more frequently in the A rct ic Sun group ( 39 % vs. 8 % , p = .013 ) . Conclusion : The A rct ic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients Fever is common among neurologic patients and is usually treated by antipyretic drugs and external cooling . An alternative method for temperature management may be an intravascular approach . The aim of the study was to compare the effectiveness and the therapeutic costs of this new method with conventional treatment in neurologic patients . Twenty-six patients who suffered from subarachnoid hemorrhage or traumatic brain injury with febrile episodes were included the study and were r and omized into 2 different groups . In the “ Conventional ” group , fever was treated with antipyretic drugs and /or surface cooling techniques to achieve a body core temperature of 36.5 ° C . In the “ CoolGard ” group , patients were treated with an intravascular cooling catheter ( Coolgard , Alsius , CA ) . We compared the effectiveness of these 2 approaches by calculating the mean deviation from 36.5 ° C during a 48-hour period ( fever burden ) . We found a significant difference in the fever burden [ CoolGard : −0.49 to 1.22 ( median −0.06 ) ° C vs. Conventional : 1.05 - 2.34 ( median 1.41 ) ° C , P<0.05 ] . Costs varied significantly between the CoolGard and the Conventional groups , with markedly higher daily costs in the CoolGard group [ CoolGard : 15 to 140 US dollars ( USD ) ( median 39 USD ) vs. Conventional : 1 to 9 USD ( median 5 USD ) , P<0.05 ] . The effectiveness of the intravascular cooling catheter is excellent compared with conventional cooling therapies Critically ill patients who have sustained a severe cerebral insult will be actively cooled should they develop an elevated body core temperature . Patients who require therapeutic hypothermia for neuroprotection may require the same cooling strategies . A literature review suggested limited evidence to support cooling strategies currently used within one intensive care unit . An experimental approach was used to examine the effects of paracetamol and four external cooling strategies on patients with severe cerebral insult It is suggested that paracetamol is effective in reducing body core temperature and that fans may not . However , data obtained from the study of the four external cooling strategies were inconclusive Hypothermia has been proposed as a neuroprotective strategy . However , short-term cooling after hypoxia-ischemia is effective only if started immediately during resuscitation . The aim of this study was to determine whether prolonged head cooling , delayed into the late postinsult period , improves outcome from severe ischemia . Unanesthetized near term fetal sheep were subject to 30 min of cerebral ischemia . 90 min later they were r and omized to either cooling ( n = 9 ) or sham cooling ( n = 7 ) for 72 h. Intrauterine cooling was induced by a coil around the fetal head , leading initially to a fall in extradural temperature of 5 - 10 degrees C , and a fall in esophageal temperature of 1.5 - 3 degrees C. Cooling was associated with mild transient systemic metabolic effects , but not with hypotension or altered fetal heart rate . Cerebral cooling reduced secondary cortical cytotoxic edema ( P < 0.001 ) . After 5 d of recovery there was greater residual electroencephalogram activity ( -5.2+/-1.6 vs. -15.5+/-1.5 dB , P < 0.001 ) and a dramatic reduction in the extent of cortical infa rct ion and neuronal loss in all regions assessed ( e.g. , 40 vs. 99 % in the parasagittal cortex , P < 0.001 ) . Selective head cooling , maintained throughout the secondary phase of injury , is noninvasive and safe and shows potential for improving neonatal outcome after perinatal asphyxia |
13,969 | 17,554,100 | The use of a letter grade scale allowed an objective analysis of the quality of evidence .
A checklist-driven model that assesses and applies evidence to dental practice may substantially improve dentists ' decision making skill | Making decisions in dentistry should be based on the best evidence available .
The objective of this study was to demonstrate a practical procedure and model that clinicians can use to apply the results of well-conducted studies to patient care by critically appraising the evidence with checklists and letter grade scales .
To demonstrate application of this model for critically appraising the quality of research evidence , a hypothetical case involving an adult male with chronic periodontitis is used as an example . | Several types of air turbine scalers have recently been introduced as an alternative to ultrasonic equipment in periodontal therapy . The aim of this investigation was to compare clinical , periodontal healing after scaling with the Titan S air turbine scaler and h and instruments . Twelve patients referred to the School of Dental Hygiene , Jönköping , Sweden , for treatment of moderately advanced periodontitis participated in the study . After examination , diagnosis , treatment planning , and information , the teeth of the left and right quadrants were r and omly assigned to Titan S or h and instruments scaling ( " split mouth design ") . The treatment was given by 6 dental hygiene students . Final re-examination was performed 3 months after instrumentation . After treatment , a marked improvement of periodontal conditions , expressed as number of tooth surfaces with plaque , number of sites with probing pocket depth greater than or equal to 4 mm and percentage of sites showing bleeding on probing to the bottom of the pocket , was obtained . No difference in results was observed when comparing Titan S and h and instrumentation . The time required for instrumentation was , however , shorter for Titan S than for h and instruments . Based on the results of this study , it may be concluded that , in patients with moderately advanced periodontitis , periodontal healing after scaling with the Titan S and h and instruments is comparable Several studies have found incomplete calculus removal during periodontal treatment with traditional h and curets , sonic , and ultrasonic instruments . This study evaluated the speed and effectiveness of subgingival calculus removal with new diamond-coated ultrasonic tips on single-rooted teeth . Single session subgingival scaling and root planing was performed on 80 teeth with 5 to 12 mm probing depths in 15 patients . Each patient provided groups of 4 teeth that were r and omly treated with either h and curets ( H AND ) ; st and ard smooth ultrasonic tip ( US ) ; or fine grit ( FINDIAM ) or medium grit ( MEDDIAM ) diamond-coated ultrasonic tips . The time taken to reach the therapeutic endpoint of a clean , smooth root surface in a defined region on each tooth with each instrument by the 3 therapists with differing experience levels was recorded . The teeth were then atraumatically extracted , stored in a surfactant , photographed at 10X , and the percent of calculus present in the area of the pocket or on a comparable control surface calculated by histometric point counting . ANOVA and paired t tests showed that mean percent remaining calculus on treated versus control surfaces was H AND 4.6 + /- 5.3 versus 57.5 + /- 28.2 , US 4.7 + /- 6.4 versus 54.4 + /- 25.9 , FINDIAM 4.3 + /- 5.2 versus 37.5 + /- 22.1 , and MEDDIAM 3.4 + /- 4.2 versus 50.7 + /- 20.1 , respectively ( all P < 0.01 ) . The mean time in seconds to reach the clinical endpoint ranged from H AND 289 + /- 193 , US 194 + /- 67 , FINDIAM 167 + /- 71 , to MEDDIAM 147 + /- 92 . All powered instruments were significantly faster than H AND ( P < 0.05 ) , but did not differ from each other . On a 0 = " smooth " to 3 = " rough " scale , most often H AND result ed in " smooth " surfaces ( 10/20 ) , the powered tips of all types " slight " surface roughness ( 10/20 each ) , and US the most " moderate " roughness ( 7/20 ) . There were no differences in percent calculus remaining , surface roughness , or time spent among the 3 treating clinicians despite their varying experience levels . The results of this study showed that percent calculus remaining was < 5 % with all the instruments given time ad libitum on a given root surface . Root roughness was generally slightly greater with all 3 powered tips . All of the powered instruments took significantly less time than the H AND . Both DIAM tips took less time than US . Diamond-coated ultrasonic tips appeared to be much more efficient than H AND or US in removing calculus in moderate-deep probing depths on single-rooted teeth in vivo As practitioners strive to improve the delivery of patient care , it is increasingly important that they find it easier to identify studies with the highest level of evidence . Once found , there must be some assurance that the studies were carried out satisfactorily and the methodology was sound . To assist in meeting this challenge , the Consoli date d St and ards of Reporting Trials ( CONSORT ) guidelines were developed by a team of dedicated journal editors , epidemiologists , and statisticians . They determined the st and ards for authors reporting the findings of controlled clinical trials . CONSORT comprises a checklist and a flow diagram ( Figs 1 and 2 ) to help improve the quality of reports of r and omized controlled trials ( RCTs ) . It offers a st and ard way for research ers to report their findings . The checklist includes items , based on evidence , that should be addressed in the report ; the flow diagram gives readers a clear picture of the progress of all participants in the trial , from the time they are r and omized until the end of their involvement . The intent is to make the experimental process transparent , flawed or not , so that users of the data can more appropriately evaluate the validity for their purpose s. The key elements start when the research er su bmi ts an article for review and completes the st and ardized forms . The completed checklist should accompany the manuscript through the review process and identify the page on which each item is addressed . The completed flow diagram should appear as a figure in the manuscript . Nearly a year ago , the AJO-DO m and ated a structured abstract with each su bmi ssion ; this is one of the first items on the CONSORT checklist . There are good reasons for this change and for all other requests listed . According to Sharma and Harrison , “ the quality of information provided in journals with structured abstract s is greater than in those with nonstructured abstract s. ” These authors concluded that the quality of information in an abstract improves when a journal changes to a structured format . AIM The aim of this study was to evaluate in vivo the effectiveness of scaling and root planing of a power-driven mechanism compared with h and instruments and ultrasonic insert alone with a split-mouth design after 3 and 6 months . METHODS Healing events after initial periodontal therapy were investigated in 20 patients with moderate-to-severe adult periodontitis . Plaque index ( PlI ) , bleeding on probing ( PBI ) , probing pocket depth ( PPD ) , probing attachment level ( PAL ) and number of moderate and deep pockets ( NMP , NDP ) were recorded at baseline and 3 and 6 months after treatment . Oral hygiene instruction was provided for each patient . R and omly assigned quadrants per patient were scaled and root planed with h and instrumentation ( curettes , hoes and files ) , with reciprocating power-driven instruments , with ultrasonic scaler alone and with the combined use of ultrasonic scaler and power-driven inserts . The Friedman test was applied to test the significance of difference between the various methods of root instrumentation . Repeated measures of analysis of variance ( manova ) were used to analyse the time effect on the different treatments . RESULTS At the 6-month evaluation , all groups in the scaling and root planing treatment presented with an improvement in the measured clinical parameters , as compared with baseline . No statistical differences ( p>0.05 ) were observed in the assessed periodontal indices among the study sites between the four groups for either treatment . CONCLUSIONS Under our experimental conditions , this clinical study demonstrates that mechanized root planing with power-driven instruments , as effective as the usual procedures ( h and and sonic instruments ) , represents a satisfactory and alternative means of nonsurgical root therapy |
13,970 | 28,436,276 | Values and preferences studies generally found support for lay providers conducting HTS , particularly in non-hypothetical scenarios .
Uptake of this recommendation could exp and HIV testing to more people globally | ABSTRACT New strategies for HIV testing services ( HTS ) are needed to achieve UN 90 - 90 - 90 targets , including diagnosis of 90 % of people living with HIV .
Task-sharing HTS to trained lay providers may alleviate health worker shortages and better reach target groups . | Objective : Due to high rates of undiagnosed and untreated HIV infection in Africa , we compared HIV counseling and testing ( VCT ) uptake among household members of patients receiving antiretroviral therapy . Methods : HIV-infected persons attending an AIDS clinic were r and omized to a home-based or clinic-based antiretroviral therapy program including VCT for household members . Clinic arm participants were given free VCT vouchers and encouraged to invite their household members to the clinic for VCT . Home arm participants were visited , and their household members offered VCT using a 3-test rapid finger-stick testing algorithm . VCT uptake and HIV prevalence were compared . Findings : Of 7184 household members , 3974 ( 55.3 % ) were female and 4798 ( 66.8 % ) were in the home arm . Home arm household members were more likely to receive VCT than those from the clinic arm ( 55.8 % vs. 10.9 % , odds ratio : 10.41 , 95 % confidence interval : 7.89 to 13.73 ; P < 0.001 ) , although the proportion of HIV-infected household members was higher in the clinic arm ( 17.3 % vs. 7.1 % , odds ratio : 2.76 , 95 % confidence interval : 1.97 to 3.86 , P < 0.001 ) . HIV prevalence among all household members tested in the home arm was 56 % compared with 27 % in the clinic arm . Of 148 spouses of HIV-infected patients , 69 ( 46.6 % ) were uninfected . Persons aged 15 - 24 were less likely to test than other age groups , and in the home arm , women were more likely to test than men . Conclusions : Home-based VCT for household members of HIV-infected persons was feasible , associated with lower prevalence , higher uptake , and increased identification of HIV-infected persons than clinic-based provision OBJECTIVE Patient satisfaction with HIV screening is crucial for sustainable implementation of the Centers for Disease Control and Prevention ( CDC ) HIV testing recommendations . This investigation assesses patient satisfaction with rapid HIV testing in the emergency department ( ED ) of an urban tertiary academic medical center . METHODS After receiving HIV test results , participants in the Universal Screening for HIV Infection in the Emergency Room ( USHER ) r and omized controlled trial were offered a patient satisfaction survey . Questions concerned overall satisfaction with ED visit , time spent on primary medical problem , time spent on HIV testing , and test provider 's ability to answer HIV-related questions . Responses were reported on a 4-point Likert scale , ranging from very dissatisfied to very satisfied ( defined as optimal satisfaction ) . RESULTS Of 4,860 USHER participants , 2,025 completed testing and were offered the survey : 1,616 ( 79.8 % ) completed the survey . Overall , 1,478 ( 91.5 % ) were very satisfied . Satisfaction was less than optimal for 34.5 % ( 10 of 29 ) of participants with reactive results and for 7.5 % ( 115 of 1,542 ) with nonreactive results . The independent factors associated with less than optimal satisfaction were reactive test result , aged 60 years or older , black race , Hispanic/Latino ethnicity , and testing by ED provider instead of HIV counselor . CONCLUSION Most participants were very satisfied with the ED-based rapid HIV testing program . Identification of independent factors that correlate with patient satisfaction will help guide best practice s as EDs implement CDC recommendations . It is critical to better underst and whether patients with reactive results were negatively affected by their results or truly had concerns about the testing process Background Routine HIV screening in emergency department ( ED ) setting s may require dedicated personnel . We evaluated the outcomes , costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor . Methods We employed a mathematical model to extend data obtained from a r and omized clinical trial of provider- vs. counselor-based HIV screening in the ED . We compared the downstream survival , costs , and cost-effectiveness of three HIV screening modalities : 1 ) no screening program ; 2 ) an ED provider-based program ; and 3 ) an HIV counselor-based program . Trial arm-specific data were used for test offer and acceptance rates ( provider offer 36 % , acceptance 75 % ; counselor offer 80 % , acceptance 71 % ) . Undiagnosed HIV prevalence ( 0.4 % ) and linkage to care rates ( 80 % ) were assumed to be equal between the screening modalities . Personnel costs were derived from trial-based re source utilization data . We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates , undetected HIV prevalence , and costs . Results Estimated HIV screening costs in the provider and counselor arms averaged $ 8.10 and $ 31.00 per result received . The Provider strategy ( compared to no screening ) had an incremental cost-effectiveness ratio of $ 58,700/ quality -adjusted life year ( QALY ) and the Counselor strategy ( compared to the Provider strategy ) had an incremental cost-effectiveness ratio of $ 64,500/QALY . Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen , but were robust to changes in undiagnosed HIV prevalence and programmatic costs . Conclusions The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs . Despite its additional cost , counselor-based screening delivers just as much return on investment as provider based-screening . Investment in dedicated HIV screening personnel is justified in situations where ED staff re sources may be insufficient to provide comprehensive , sustainable screening services Introduction Lack of universal , annual testing for human immunodeficiency virus ( HIV ) in health facilities suggests that expansion of HIV testing and counselling ( HTC ) to non- clinical setting s is critical to the achievement of national goals for prevention , care and treatment . Consideration should be given to the ability of lay counsellors to perform home-based HTC in community setting s. Methods We implemented a community cluster r and omized controlled trial of home-based HTC in Sisonke District , South Africa . Trained lay counsellors conducted door-to-door HIV testing using the same rapid tests used by the local health department at the time of the study ( SD Bioline and Sensa ) . To monitor testing quality and counsellor skill , additional dry blood spots were taken and sent for laboratory-based enzyme-linked immunosorbent assay ( ELISA ) testing . Sensitivity and specificity were calculated using the laboratory result as the gold st and ard . Results and discussion From 3986 sample s , the counsellor and laboratory results matched in all but 23 cases . In 18 cases , the counsellor judged the result as indeterminate , whereas the laboratory judged 10 positive , eight negative and three indeterminate , indicating that the counsellor may have erred on the side of caution . Sensitivity was 98.0 % ( 95 % CI : 96.3–98.9 % ) , and specificity 99.6 % ( 95 % CI : 99.4–99.7 % ) , for the lay counsellor field-based rapid tests . Both measures are high , and the lower confidence bound for specificity meets the international st and ard for assessing HIV rapid tests . Conclusions These findings indicate that adequately trained lay counsellors are capable of safely conducting high- quality rapid HIV tests and interpreting the results as per the kit guidelines . These findings are important given the likely expansion of community and home-based testing models and the shortage of clinical ly trained professional staff Home-based voluntary HIV counselling and testing ( HB-VCT ) has been reported to have a high uptake , but it has not been rigorously evaluated . We design ed a model for HB-VCT appropriate for wider scale-up , and investigated the acceptance of home-based counselling and testing , equity in uptake and negative life events with a cluster-r and omized trial . Thirty six rural clusters in southern Zambia were pair-matched based on baseline data and r and omly assigned to the intervention or the control arm . Both arms had access to st and ard HIV testing services . Adults in the intervention clusters were offered HB-VCT by local lay counsellors . Effects were first analysed among those participating in the baseline and post-intervention surveys and then as intention-to-treat analysis . The study was registered with www.controlled-trials.com , number IS RCT N53353725 . A total of 836 and 858 adults were assigned to the intervention and control clusters , respectively . In the intervention arm , counselling was accepted by 85 % and 66 % were tested ( n = 686 ) . Among counselled respondents who were cohabiting with the partner , 62 % were counselled together with the partner . At follow-up eight months later , the proportion of adults reporting to have been tested the year prior to follow-up was 82 % in the intervention arm and 52 % in the control arm ( Relative Risk ( RR ) 1.6 , 95 % CI 1.4 - 1.8 ) , whereas the RR was 1.7 ( 1.4 - 2.0 ) according to the intention-to-treat analysis . At baseline the likelihood of being tested was higher for women vs. men and for more educated people . At follow-up these differences were found only in the control communities . Measured negative life events following HIV testing were similar in both groups . In conclusion , this HB-VCT model was found to be feasible , with a very high acceptance and to have important equity effects . The high couple counselling acceptance suggests that the home-based approach has a particularly high HIV prevention potential HIV-related stigma continues to be a prominent barrier to testing , treatment and care . However , few studies have investigated changes in stigma over time and the factors contributing to these changes , and there is no evidence of the impact of HIV testing and counselling on stigma . This study was nested within a pair-matched cluster-r and omized trial on the acceptance of home-based voluntary HIV counselling and testing conducted in a rural district in Zambia between 2009 and 2011 , and investigated changes in stigma over time and the impact of HIV testing and counselling on stigma . Data from a baseline survey ( n = 1500 ) and a follow-up survey ( n = 1107 ) were used to evaluate changes in stigma . There was an overall reduction of seven per cent in stigma from baseline to follow-up . This was mainly due to a reduction in individual stigmatizing attitudes but not in perceived stigma . The reduction did not differ between the trial arms ( β = -0.22 , p = 0.423 ) . Being tested for HIV was associated with a reduction in stigma ( β = -0.57 , p = 0.030 ) , and there was a trend towards home-based Voluntary Counselling and Testing having a larger impact on stigma than other testing approaches ( β = -0.78 , p = 0.080 vs. β = -0.37 , p = 0.551 ) , possibly explained by a strong focus on counselling and the safe environment of the home . The reduction observed in both arms may give reason to be optimistic as it may have consequences for disclosure , treatment access and adherence . Yet , the change in stigma may have been affected by social desirability bias , as extensive community mobilization was carried out in both arms . The study underscores the challenges in measuring and monitoring HIV-related stigma . Adjustment for social desirability bias and inclusion of qualitative methods are recommended for further studies on the impact of HIV testing on stigma HIV testing and counselling is a critical gateway to prevention and treatment . Yet , coverage remains insufficient , few couples are tested together and gender differences in access exist . We used an embedded mixed methods approach to investigate possible explanations for the high acceptance of home-based voluntary HIV counselling and testing ( HB-VCT ) in a pair-matched cluster-r and omized trial in Zambia . A baseline survey included 1694 individuals in 36 clusters . Adults in 18 intervention clusters were offered HB-VCT by lay counsellors . St and ard testing services were available in both trial arms . After the completion of the intervention , a follow-up survey was conducted in all trial clusters . In addition , 21 in-depth interviews and one focus group discussion were conducted with home-based VCT clients in the intervention arm . Informants favoured the convenience , confidentiality and credibility of HB-VCT . Counsellors were perceived as trustworthy owing to their closeness and conduct , and the consent process was experienced as convincing . Couple testing was selected by 70 % of cohabiting couples and was experienced as beneficial by both genders . Levels of first-time testing ( 68 % vs. 29 % , p < 0.0001 ) and re-testing ( 94 % vs. 74 % , p < 0.0001 ) were higher in the intervention than in the control arm . Acceptance of HIV testing and counselling is dependent on stigma , trust and gender . The confidentiality of home-based VCT was essential for overcoming stigma-related barriers , and the selection of local counsellors was important to ensure trust in the services . The high level of couple counselling within HB-VCT may contribute to closing the gender gap in HIV testing , and has benefits for both genders and potentially for prevention of HIV transmission . The study demonstrates the feasibility of achieving high test coverage with an opt-in consent approach . The embedded qualitative component confirmed the high satisfaction with HB-VCT reported in the quantitative survey and was crucial to fully underst and the intervention and its consequences |
13,971 | 20,363,195 | The results of some systematic review s show no significant overall effect on repeat pregnancy , whereas others show an overall significant reduction .
Youth development programmes are shown in some cases to lower pregnancy rates but in other cases to have no effect or even to increase them . | This article begins with an overview of teenage pregnancy within a social context . | Objective To evaluate the effectiveness of youth development in reducing teenage pregnancy , substance use , and other outcomes . Design Prospect i ve matched comparison study . Setting 54 youth service sites in Engl and . Participants Young people ( n=2724 ) aged 13 - 15 years at baseline deemed by professionals as at risk of teenage pregnancy , substance misuse , or school exclusion or to be vulnerable . Intervention Intensive , multicomponent youth development programme including sex and drugs education ( Young People ’s Development Programme ) versus st and ard youth provision . Main outcome measures Various , including pregnancy , weekly cannabis use , and monthly drunkenness at 18 months . Results Young women in the intervention group more commonly reported pregnancy than did those in the comparison group ( 16 % v 6 % ; adjusted odds ratio 3.55 , 95 % confidence interval 1.32 to 9.50 ) . Young women in the intervention group also more commonly reported early heterosexual experience ( 58 % v 33 % ; adjusted odds ratio 2.53 , 1.09 to 5.92 ) and expectation of teenage parenthood ( 34 % v 24 % ; 1.61 , 1.07 to 2.43 ) . Conclusions No evidence was found that the intervention was effective in delaying heterosexual experience or reducing pregnancies , drunkenness , or cannabis use . Some results suggested an adverse effect . Although method ological limitations may at least partly explain these findings , any further implementation of such interventions in the UK should be only within r and omised trials To test the effectiveness of a special health care program for adolescent mothers ( 17 years old or younger ) and their infants , 243 mother-infant pairs were r and omly assigned to one of two groups . All of the mothers were unwed , on Medicaid , and black . The control group received routine well-baby care . The experimental group received routine care and services that included rigorous follow-up , discussion s with the mother about her plans for return to school and use of family planning methods , and extra health teaching . The dropout rate in the experimental group ( 60 % ) was significantly less after 18 months than the control group ( 82 % ) . In spite of the high dropout rate , 91 % of the mothers were located for the 18 month follow-up interview . The repeat pregnancy rate in the experimental group was 12 % after 18 months , and 28 % in the control group . There was no significant difference in the percentage returning to school . After 12 months , the infants in the experimental group were more likely to be fully immunized ( 33 % ) than the infants in the control group ( 18 % ) . Mothers in the special care program who continued to attend clinic used the emergency room less than the mothers who continued to attend in the control group . These results suggest that a comprehensive health care program is one way to bring about better outcomes for both adolescent mothers and their infants OBJECTIVE To examine the long-term effects of the Seattle Social Development Project intervention in promoting positive adult functioning and preventing mental health problems , crime , and substance use ( including tobacco , alcohol , and other drugs ) at 21 years of age . DESIGN This nonr and omized controlled trial followed up participants to 21 years of age , 9 years after the intervention ended . We compared the following 3 intervention conditions : a full 6-year intervention ( grade s 1 through 6 ) ; a late 2-year intervention ( grade s 5 and 6 only ) ; and a no-treatment control condition . SETTING Eighteen public elementary schools serving diverse neighborhoods , including high-crime neighborhoods , of Seattle , Wash. PARTICIPANTS A sex-balanced , multiethnic sample of 605 participants across the 3 conditions who completed interviews at 21 years of age ( 94 % of the original sample in these conditions ) . INTERVENTIONS Teacher training in classroom instruction and management , child social and emotional skill development , and parent training . MAIN OUTCOME MEASURES Self-reports of functioning in school and work , emotional and mental health , and crime and substance use at 21 years of age and official court records . RESULTS Broad significant effects on functioning in school and work and on emotional and mental health were found . Fewer significant effects on crime and substance use were found at 21 years of age . Most outcomes had a consistent dose effect , with the strongest effects in subjects in the full-intervention group and effects in the late-intervention group between those in the full-intervention and control groups . CONCLUSIONS A theory-guided preventive intervention that strengthened teaching and parenting practice s and taught children interpersonal skills during the elementary grade s had wide-ranging beneficial effects on functioning in early adulthood CONTEXT . Rates of rapid second births among low-income black adolescent mothers range from 20 % to 50 % . Most efforts to prevent rapid second births have been unsuccessful . OBJECTIVES . There were 4 objectives : ( 1 ) to examine whether a home-based mentoring intervention was effective in preventing second births within 2 years of the adolescent mother 's first delivery ; ( 2 ) to examine whether greater intervention participation increased the likelihood of preventing a second birth ; ( 3 ) to examine whether second births were better predicted from a risk practice perspective or a family formation perspective , based on information collected at delivery ; and ( 4 ) to examine how risk practice s or family formation over the first 2 years of parenthood were related to a second birth . DESIGN . We conducted a r and omized , controlled trial of a home-based intervention curriculum , based on social cognitive theory , and focused on interpersonal negotiation skills , adolescent development , and parenting . The curriculum was delivered biweekly until the infant 's first birthday by college-educated , black , single mothers who served as mentors , presenting themselves as “ big sisters . ” The control group received usual care . Follow-up evaluations were conducted in the homes 6 , 13 , and 24 months after recruitment . METHODS . Participants were recruited from urban hospitals at delivery and were 181 first time , black adolescent mothers ( < 18 years of age ) ; 82 % ( 149 of 181 ) completed the 24-month evaluation . RESULTS . Intent-to-treat analyses revealed that control mothers were more likely than intervention mothers to have a second infant . The complier average causal effect was used to account for variability in intervention participation . Having ≥2 intervention visits increased the odds of not having a second infant more than threefold . Only 1 mother who completed ≥6 visits had a second infant . At delivery of their first infant , mothers who had a second infant were slightly older ( 16.7 vs 16.2 years ) and were more likely to have been arrested ( 30 % vs 14 % ) . There were no differences in baseline contraceptive use or other measures of risk or family formation . At 24 months , mothers who had a second infant reported high self-esteem , positive life events , and romantic involvement and residence with the first infant 's father . At 24 months , there were no differences in marital rates ( 2 % ) , risk practice s , or contraceptive use between mothers who did and did not have a second infant . Mothers who did not have a second infant were marginally more likely to report no plans for contraception in their next sexual contact compared with mothers who had a second infant ( 22 % vs 8 % , respectively ) . CONCLUSIONS . A home-based intervention founded on a mentorship model and targeted toward adolescent development , including negotiation skills , was effective in preventing rapid repeat births among low-income , black adolescent mothers . The effectiveness of the intervention could be seen after only 2 visits and increased over time . There were no second births among mothers who attended ≥8 sessions . There was no evidence that risk behavior or contraceptive use was related to rapid second births . There was some evidence that rapid second births among adolescent mothers were regarded as desirable and as part of a move toward increasing autonomy and family formation , thereby undermining intervention programs that focus on risk avoidance . Findings suggest the merits of a mentoring program for low-income , black adolescent mothers , based on a relatively brief ( 6–8 sessions ) curriculum targeted toward adolescent development and interpersonal negotiation skills OBJECTIVES To test the hypotheses that ( 1 ) a monetary incentive promotes peer-support group participation ; and ( 2 ) peer-support group participation decreases repeat adolescent pregnancies . DESIGN Two-year , prospect i ve , r and omized controlled trial . SETTING Denver , Colo. PARTICIPANTS A total of 286 primiparous girls younger than 18 years , whose infants were younger than 5 months . INTERVENTION Participants were r and omized to 4 interventions : monetary incentive and peer-support group , peer-support group only , monetary incentive only , or no intervention . MAIN OUTCOME MEASURES Consistency of participation in planned intervention and repeat pregnancy . RESULTS Participation in interventions was generally low . Hypothesis 1 was supported : 58 % of those offered a monetary incentive participated in the peer-support groups , compared with 9 % of those who were not offered the incentive . Hypothesis 2 was rejected : the peer-support group experience failed to prevent repeat pregnancies . The incidence of second pregnancies at 6 months ( 9 % , 22/248 ) , at 12 months ( 20 % , 49/248 ) , at 18 months ( 29 % , 72/248 ) , and at 24 months ( 39 % , 97/248 ) following delivery did not vary significantly in relation to intervention strategy . Background sociodemographic characteristics significantly affected the timing of subsequent conceptions but not intervention participation . CONCLUSION A monetary incentive draws adolescent mothers to sites where they can discuss the costs and benefits of contraception and conception with knowledgeable adults and supportive peers . These discussion s do not prevent repeat pregnancies . Further studies are needed to determine if an intervention that produces substantive changes in the daily living environment will eliminate the sexual practice s that are responsible for the high rate of repeat pregnancy in this population Parent training was provided for 80 low-income , black teenage mothers during their infants ' first six months . Half of the mothers were visited biweekly in their homes to be instructed in caregiving and in sensorimotor and interaction exercises , and half were trained as CETA ( Comprehensive Employment Training ACT)-paid , teacher 's aides in a medical school infant nursery that provided care for their infants and infants of medical faculty . Growth and development during the first two years were superior for the infants whose mothers received training , particularly those who received paid parent training as teacher 's aides in the infant nursery . Repeat pregnancy rates were lower and return to work/school rates were higher for the infant nursery mothers , most of whom subsequently pursued nurse 's aide training |
13,972 | 23,850,065 | The results of the current meta- analysis indicate that problem-based learning might help nursing students to improve their critical thinking . | OBJECTIVES The objective of this systematic review and meta- analysis was to estimate the effectiveness of problem-based learning in developing nursing students ' critical thinking . | Critical thinking is essential for professional nursing practice . Promoting critical thinking with teaching strategies has been a focus of nursing education and nursing research . Reading and writing assignments are teaching strategies for fostering critical thinking ability . We developed a course with the emphasis on critical reading and writing . The purpose s of this study were to explore the effect of the course and teaching strategies on promoting critical thinking and to underst and the learning experience and perception of nursing students as part of the course assessment plan . Quasi-experimental design and purposive sampling were used . 170 students of a two-year nursing program were grouped into an experimental and a control group depending on whether or not they took the course . The change in critical thinking ability was evaluated and determined based on performance in an article critique test before and after the course . Data was collected with an assessment tool developed for the purpose s of the research and was analyzed with descriptive statistics , paired t-test , and two-factor analysis of variance with repeated measures and content analysis . The findings were : ( 1 ) The scores on the critique test at the end of the course in both groups were significantly higher than before the course ( p<.001 ) . The improvement in score of the experimental group , however , was significantly higher than that of the control group ( p<.001 ) . ( 2 ) Changes in thinking pattern and learning attitude , as well as a feeling of growth and achievement , were found in content analysis of students ' self-evaluation of their learning experience and perception . Critical thinking skills were applied while learning the course . The results not only provide evidence to support the positive effect of reading and writing assignments on critical thinking ability but also confirm the teaching and learning activity design for the course Faculty in an associate degree nursing program at a community college in New York City noted that nursing students lacked critical analysis , problem-solving , and decision-making skills and the reflective ability essential to applying nursing knowledge in clinical situations . This study reports on the use of problem-based learning as a teaching strategy and its impact on the development of critical thinking and communication skills in nursing students BACKGROUND Educational approaches are thought to have facilitative or hindering effects on students ' critical thinking development . The aim of this study was to compare the effects of problem-based learning ( PBL ) and lecturing approaches on the development of students ' critical thinking . METHODS All 79 Year 1 undergraduate nursing students at a university in Hong Kong were r and omly assigned to 1 of 2 parallel courses delivered by either PBL ( n = 40 ) or lecturing ( n = 39 ) over 1 academic year . The primary outcome measure was students ' critical thinking disposition as measured by the California Critical Thinking Disposition Inventory ( CCTDI ) . Individual interviews were also conducted to elicit the students ' perceptions of their learning experience . Data were collected at 4 timepoints spanning 3 years . RESULTS The overall CCTDI and subscale scores for the PBL group were not significantly different from those of the lecture group at the first timepoint ( pretest ) . Compared with lecture students , PBL students showed significantly greater improvement in overall CCTDI ( P = 0.0048 ) , Truthseeking ( P = 0.0008 ) , Analyticity ( P = 0.0368 ) and Critical Thinking Self-confidence ( P = 0.0342 ) subscale scores from the first to the second timepoints ; in overall CCTDI ( P = 0.0083 ) , Truthseeking ( P = 0.0090 ) and Analyticity ( P = 0.0354 ) subscale scores from the first to the third timepoints ; and in Truthseeking ( P = 0.0173 ) and Systematic ity ( P = 0.0440 ) subscale scores from the first to the fourth timepoints . CONCLUSIONS There were significant differences in the development of students ' critical thinking dispositions between those who undertook the PBL and lecture courses , respectively The aim of this study was to compare the learning effectiveness of peer tutored problem-based learning and conventional teaching of nursing ethics in Taiwan . The study adopted an experimental design . The peer tutored problem-based learning method was applied to an experimental group and the conventional teaching method to a control group . The study sample consisted of 142 senior nursing students who were r and omly assigned to the two groups . All the students were tested for their nursing ethical discrimination ability both before and after the educational intervention . A learning satisfaction survey was also administered to both groups at the end of each course . After the intervention , both groups showed a significant increase in ethical discrimination ability . There was a statistically significant difference between the ethical discrimination scores of the two groups ( P < 0.05 ) , with the experimental group on average scoring higher than the control group . There were significant differences in satisfaction with self-motivated learning and critical thinking between the groups . Peer tutored problem-based learning and lecture-type conventional teaching were both effective for nursing ethics education , but problem-based learning was shown to be more effective . Peer tutored problem-based learning has the potential to enhance the efficacy of teaching nursing ethics in situations in which there are personnel and re source constraints |
13,973 | 25,225,849 | Moderate- quality evidence based upon four trials ( 974 participants ) indicated that NSAIDs and COXIBs produced similar benefits in terms of pain , swelling and global improvement , but COXIBs were associated with fewer adverse events .
The trials did not measure participant-reported global assessment and health-related quality of life .
Limited evidence supported the use of NSAIDs in the treatment of acute gout .
While these data were insufficient to draw firm conclusions , they did not conflict with clinical guideline recommendations based upon evidence from observational studies , other inflammatory arthritis and expert consensus , which support the use of NSAIDs in acute gout .
Moderate- quality evidence suggested that selective COX-2 inhibitors and non-selective NSAIDs are probably equally beneficial although COX-2 inhibitors are likely to be associated with significantly fewer total and gastrointestinal adverse events .
Moderate- quality evidence indicated that systemic glucocorticoids and NSAIDs were also equally beneficial in terms of pain relief .
There were no withdrawals due to adverse events and total adverse events were similar between groups .
There was low- quality evidence that there was no difference in function . | BACKGROUND Gout is an inflammatory arthritis that is characterised by the deposition of monosodium urate crystals in synovial fluid and other tissues .
The natural history of articular gout is generally characterised by three periods : asymptomatic hyperuricaemia , episodes of acute gout and chronic gouty arthritis .
Non-steroidal anti-inflammatory drugs ( NSAIDs ) including selective cyclo-oxygenase-2 ( COX-2 ) inhibitors ( COXIBs ) are commonly used to treat acute gout .
Published guidelines recommend their use to treat acute attacks , using maximum recommended doses for a short time .
OBJECTIVES To assess the benefit and safety of NSAIDs ( including COXIBs ) for acute gout . | Twenty-seven patients presenting within 5 days of the onset of crystalline proven acute gout were prospect ively treated with either indomethacin 50 mg tid or triamcinolone acetonide 60 mg intramuscularly . Patients with contraindications to therapy with indomethacin received triamcinolone acetonide . They were followed for 30 days . Resolution of all symptoms occurred at an average of 8 days for the indomethacin patients and 7 days in the triamcinolone patients . No side effects or episodes of rebound gout attacks occurred with the triamcinolone acetonide therapy . It is as safe and effective as indomethacin in the treatment of acute gout , and is particularly useful in patients with contraindications to therapy with nonsteroidal antiinflammatory drugs A double-blind , parallel group study was carried out in 61 patients suffering from acute gouty arthritis to compare the effectiveness of etodolac and naproxen in the relief of symptoms . Patients were allocated at r and om to receive either 300 mg etodolac twice daily ( 31 patients ) or 500 mg naproxen twice daily ( 30 patients ) for 7 days . Both groups were comparable for sex , age and weight of patients , but there was a tendency for patients in the etodolac group to have more severe gout as shown by baseline clinical assessment scores . The variables assessed on entry and on Days 2 , 4 and 7 of treatment were pain intensity , swelling , tenderness , erythema , joint heat , range of motion , and physician 's and patients ' overall evaluation of the condition . The results showed that there was a significant improvement from baseline in all of the variables at each time point in both treatment groups . However , more etodolac-treated patients ( 81 % ) than naproxen-treated patients ( 53 % ) showed overall improvement at Day 2 , and etodolac was significantly better than naproxen on the Day 2 evaluation of joint swelling and at the Day 4 evaluations of joint tenderness , range of motion and the physician 's global assessment . At the final evaluation on Day 7 , 97 % of the etodolac group reported that their condition had improved as compared to 93 % of the naproxen group . Both drugs were well tolerated and only a few mild side-effects were reported A double-blind study was carried out to compare the effects of ketoprofen and phenylbutazone in acute gouty arthritis . Two groups of patients , each consisting of 23 males , received intramuscular injections of either phenylbutazone ( 2 X 300 mg daily ) or ketoprofen ( 2 X 50 mg daily ) for a period of 7 days . The drug effects were assessed both subjectively and objective ly . There was an excellent therapeutic effect in both groups . In general , no statistically-significant differences were detected between the two preparations . However , ketoprofen appears to be slightly better tolerated with respect to the incidence of systemic and local side effects . Thus , the administration of ketoprofen can be recommended in cases of acute gouty arthritis Introduction In phase-3 clinical trials , the interleukin ( IL-1 ) blocker , rilonacept ( IL-1 Trap ) , demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy . This trial evaluated rilonacept added to a st and ard-of-care , indomethacin , for treatment of acute gout flares . Methods Adults , aged 18 - 70 years , with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were r and omized to subcutaneous ( SC ) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days ( n = 74 ) ; SC placebo at baseline plus oral indomethacin as above ( n = 76 ) ; or SC rilonacept 320 mg at baseline plus oral placebo ( n = 75 ) . The primary efficacy endpoint was change in pain in the index joint ( patient-reported using a Likert scale ( 0 = none ; 4 = extreme ) ) from baseline to the average of values at 24 , 48 and 72 hours ( composite time point ) for rilonacept plus indomethacin versus indomethacin alone . Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint . Safety evaluation included clinical laboratory and adverse event ( AE ) assessment s. Results Patient characteristics were comparable among the groups ; the population was predominantly male ( 94.1 % ) , white ( 75.7 % ) , with mean ± SD age of 50.3 ± 10.6 years . All treatment groups reported within-group pain reductions from baseline ( P < 0.0001 ) . Although primary endpoint pain reduction was greater with rilonacept plus indomethacin ( -1.55 ± 0.92 ) relative to indomethacin alone ( -1.40 ± 0.96 ) , the difference was not statistically significant ( P = 0.33 ) , so formal comparison between monotherapy groups was not performed . Pain reduction over the 72-hour period with rilonacept alone ( -0.69 ± 0.97 ) was less than that in the other groups , but pain reduction was similar among groups at 72 hours . Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept . Across all groups , the most frequent AEs were headache and dizziness . Conclusions Although generally well-tolerated , rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare . Trial registration Clinical Trials.gov registration number NCT00855920 A double-blind trial was carried out in 24 patients with acute gout to compare the efficacy and tolerance of feprazone , a non-steroidal anti-inflammatory drug , with that of phenylbutazone . Patients received 800 mg of either drug daily for 2 days and then 600 mg daily for up to 8 days . The results of patient assessment showed there was no significant difference between the two groups in time taken either to significant improvement or to final resolution of the gout attack . No side-effects were reported with either drug ABSTRACT Background and objective : Disease history and clinical features can influence treatment response in patients with acute gout . The purpose of this pooled subgroup analysis was to assess the association of baseline disease and patient characteristics with response to treatment in acute gout using data from two identical studies . Methods : Patients ≥ 18 years of age with onset of acute gout within 48 h associated with moderate , severe , or extreme pain involving less than four joints were eligible for inclusion in the primary studies , and were r and omized to etoricoxib 120 mg once daily ( N = 178 ) or indomethacin 50 mg three times daily ( N = 161 ) . The primary and secondary efficacy endpoints were analyzed using an analysis of covariance model to detect potential differential treatment responses across several subgroups : joint involvement ( mono-articular vs. oligo-articular ) , baseline pain severity ( moderate vs. severe ) , concomitant allopurinol and /or colchicine use ( users vs. nonusers ) , age ( < 45 , 45–55 , and > 55 years ) , gender , and race ( white or other ) . Results : Overall , etoricoxib and indomethacin demonstrated comparable efficacy across all subgroups . Compared with patients with oligo-articular disease , those with mono-articular disease had significantly greater improvements in patient assessment of pain , patient global assessment of response to therapy ( PGART ) , investigator global assessment of response to therapy ( IGART ) , and study joint tenderness ( p < 0.001 for all ) . Greater improvements were seen in patient assessment of pain ( p < 0.001 ) and study joint tenderness ( p < 0.05 ) for severe/extreme baseline pain compared with moderate baseline pain . Concomitant use of colchicine and /or allopurinol was associated with significantly worse IGART ( p < 0.05 ) . Conclusions : This pooled subgroup analysis demonstrated significantly greater response of acute gout to either etoricoxib or indomethacin among those with monoarticular disease , severe/extreme baseline pain , and non-use of colchicine and /or allopurinol . These results should be interpreted in the context of a pooled subgroup analysis with a limited sample size , and with the underst and ing that associations identified in such analyses do not define causation . Despite limitations , the results provide insights into the types of patients more likely to respond better to anti-inflammatory medication , and reiterate the importance of earlier effective control of the disease Objective . To evaluate the analgesic efficacy of high-dose celecoxib in the treatment of moderate to extreme pain and inflammation associated with acute gouty arthritis . Methods . A multinational , r and omized , double-blind , double-dummy , active-controlled trial was done with patients ( aged ≥ 18 years ) with acute gouty monoarthritis or oligoarthritis ( onset of pain ≤ 48 h before enrollment ) . Patients were treated for 8 days with 1 week followup and were r and omized 1:1:1:1 to receive celecoxib 50 mg bid , celecoxib 400 mg ( followed by 200 mg later on Day 1 and then 200 mg bid for 7 days ) , celecoxib 800 mg ( followed by 400 mg later on Day 1 and then 400 mg bid for 7 days ) , or indomethacin 50 mg tid . Results . Of 443 patients screened , 402 were r and omized and 400 received treatment . Baseline demographics were comparable among treatments . Patients receiving high-dose celecoxib ( 800/400 mg ) experienced a significantly greater reduction in pain intensity on Day 2 compared with low-dose celecoxib 50 mg bid [ least squares ( LS ) mean difference −0.46 ; p = 0.0014 ] . For high-dose celecoxib 800/400 mg , the change in pain scores from baseline to Day 2 was comparable with indomethacin 50 mg tid ( LS mean difference 0.11 ; p = 0.4331 ) . There were significant differences in adverse events when the combined celecoxib groups ( 29.5 % ) were compared with patients taking indomethacin ( 43.1 % ; p = 0.0116 ) . There was no change in median serum creatinine levels for any treatment . There were more discontinuations due to adverse events ( 8.8 % vs 3 % ; p = 0.0147 ) with indomethacin than with the combined celecoxib groups . Conclusion . High-dose celecoxib ( 800/400 mg ) was significantly more effective than low-dose celecoxib ( 50 mg bid ) and comparable to indomethacin in the treatment of moderate to extreme pain in patients with acute gouty arthritis . Further , celecoxib was well tolerated Eighteen patients ( 11 men and 7 women ) suffering from primary or secondary gout , were treated with either proquazone or indomethacin for acute attacks in a double-blind study . There were 9 patients in each treatment group . A marked improvement of clinical symptoms appeared in 2 - 3 days . In the proquazone group , complete remission was achieved in 6 patients , a good result in one , and a slight improvement in one patient , whereas one patient did not respond to treatment . The corresponding figures for the indomethacin group were 4 cases with complete remission , 4 with a good result , and one not responding to treatment . A significant decrease in s-uric acid values was noted in the proquazone group . In this group too , mild gastrointestinal symptoms appeared in 2 patients Study objective We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department ( ED ) . Methods This is a double-blind , r and omized , controlled study in a university hospital emergency department ( ED ) in the New Territories of Hong Kong . Patients older than 17 years and presenting between February 1 , 2003 , and June 30 , 2004 , with a clinical diagnosis of goutlike arthritis were r and omized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy . Primary outcome measures were pain scores , time to resolution of symptoms and signs , and adverse effects . Secondary outcome measures were the need for additional acetaminophen and relapse rate . Results There were 90 patients r and omized : 46 patients to the indomethacin group and 44 patients to the prednisolone group . Baseline characteristics , including pain scores , were similar in the 2 groups . Both treatment groups had a similar decrease in pain score in the ED . The mean rate of decrease in pain score with activity for indomethacin was −1.7±1.6 ( SD ) mm per day and for prednisolone was −2.9±2.0 ( SD ) mm per day ( mean difference 1.2 mm/day ; 95 % confidence interval 0.4 to 2.0 mm/day ; P=.0026 ) . Although these differences were statistically significant , at no time was the difference in mean pain score greater than 13 mm . Therefore , it is unclear whether these differences are clinical ly significant . The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group ( mean 10.3 g , range 1 to 21 g versus mean 6.4 g , range 1 to 21 g ) . Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects ( P<.05 ) . The commonest adverse effects in the indomethacin group were nausea , indigestion , epigastric pain , dizziness , and gastrointestinal bleeding ( N=5 ; 11 % ) . None of the patients in the prednisolone group developed gastrointestinal bleeding . The relapse rate for both groups was similar . Conclusion In the treatment of acute goutlike arthritis , oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects OBJECTIVES To demonstrate non-inferiority of lumiracoxib 400 mg once daily ( o.d . ) compared with indomethacin 50 mg three times daily ( t.i.d . ) in the treatment of acute gout , and to compare the safety and tolerability of these treatments . METHODS In this 1-week , multicentre , r and omized , double-blind , double-dummy , active-controlled , parallel-group study , patients with a clinical diagnosis of gout , an acute attack of gout in four or more joints within the 48 h prior to evaluation , and at least moderate pain intensity in the target joint were r and omized to treatment with lumiracoxib 400 mg o.d . ( n = 118 ) or indomethacin 50 mg t.i.d . ( n = 117 ) . The primary efficacy endpoint was the mean change in pain intensity from baseline over days 2 - 5 , assessed on a 5-point Likert scale , where non-inferiority could be cl aim ed if the lower limit of the confidence interval ( CI ) was greater than -0.5 . The patient 's and physician 's global assessment of response to treatment , and physician 's assessment of tenderness , swelling and erythema of the study joint were also assessed . RESULTS The estimated difference between treatments for the change from baseline in pain intensity over days 2 - 5 was -0.004 ( 95 % CI -0.207 to 0.199 , P > 0.05 ) , indicating that lumiracoxib 400 mg o.d . had comparable efficacy to indomethacin 50 mg t.i.d . for the primary efficacy variable . There was no significant difference between treatments in any of the secondary efficacy variables . Adverse events were reported by 10.2 % of patients treated with lumiracoxib and 22.2 % of those receiving indomethacin . CONCLUSIONS Lumiracoxib is as effective as indomethacin for treatment of acute gout and may have a better safety and tolerability profile BACKGROUND Non-steroidal anti-inflammatory drugs and colchicine used to treat gout arthritis have gastrointestinal , renal , and cardiovascular adverse effects . Systemic corticosteroids might be a beneficial alternative . We investigated equivalence of naproxen and prednisolone in primary care . METHODS We did a r and omised clinical trial to test equivalence of prednisolone and naproxen for the treatment of monoarticular gout . Primary -care patients with gout confirmed by presence of monosodium urate crystals were eligible . 120 patients were r and omly assigned with computer-generated r and omisation to receive either prednisolone ( 35 mg once a day ; n=60 ) or naproxen ( 500 mg twice a day ; n=60 ) , for 5 days . Treatment was masked for both patients and physicians . The primary outcome was pain measured on a 100 mm visual analogue scale and the a priori margin for equivalence set at 10 % . Analyses were done per protocol and by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N14648181 . FINDINGS Data were incomplete for one patient in each treatment group , so per- protocol analyses included 59 patients in each group . After 90 h the reduction in the pain score was 44.7 mm and 46.0 mm for prednisolone and naproxen , respectively ( difference 1.3 mm ; 95 % CI -9.8 to 7.1 ) , suggesting equivalence . The difference in the size of change in pain was 1.57 mm ( 95 % CI -8.65 to 11.78 ) . Adverse effects were similar between groups , minor , and resolved by 3 week follow-up . INTERPRETATION Oral prednisolone and naproxen are equally effective in the initial treatment of gout arthritis over 4 days 20 patients with an attack of acute gout participated in this double-blind study , ten patients received N-(2,6-dichloro-m-tolyl)anthranilic acid , sodium salt ( meclofenamate sodium , Meclomen ) and ten indometacin . The median time interval between onset of attack and onset of treatment was 11 h in the meclofenamate sodium group and 14 h in the indometacin group ; medication was started with a dose of 200 mg meclofenamate sodium or 25 mg indometacin followed by 100 mg meclofenamate sodium or 25 mg indometacin every 4 h for the first 24 h. Thereafter patients received 100 mg meclofenamate sodium or 50 mg indometacin at 8-h intervals for 6 days . Similar improvement of intensity of spontaneous pain , swelling , tenderness of touch and degree of limitation of function was noted in patients of both treatment groups . This improvement could already be noted after 24 h of treatment and was sustained throughout the medication period and follow-up period . Adverse reactions were reported by 2 patients in the meclofenamate sodium group and by 5 patients in the indometacin group . The results of this double-blind study indicate that meclofenamate sodium in the dose administered was equally effective in relieving pain and inflammation and restoring restricted function in patients with acute gout as indometacin when used in the generally recommended dose for this indication . Meclofenamate sodium , even at these high dosage levels , was better tolerated than indometacin STUDY OBJECTIVE To compare the analgesic effect of IM ketorolac tromethamine with that of oral indomethacin in the treatment of acute gouty arthritis . DESIGN Prospect i ve , r and omized , double-blind , controlled , parallel group clinical trial . SETTING Two urban emergency departments . PARTICIPANTS Twenty consecutive patients who presented to the ED with acute gout . INTERVENTIONS Each patient was r and omly assigned to receive in the ED ( 1 ) 60 mg of IM ketorolac and oral placebo or ( 2 ) 50 mg of oral indomethacin and IM placebo . The patients rated the intensity of their pain on a Wong-Baker pain scale ( which runs from 0 to 5 ) before treatment and 30 , 60 , 90 , and 120 minutes after treatment . All the patients were discharged with instructions to take oral indomethacin and to complete pain score cards at home at 6 , 12 , and 24 hours . RESULTS The 10 patients in each group were similar with regard to age , sex , race , and initial mean pain score . After 2 hours , the mean pain scores ( + /- SD ) for the ketorolac group had decreased from 4.5 + /- .71 to 1.4 + /- 1.43 ( P < .05 ) , and the mean score for the indomethacin group had decreased from 4.4 + /- .70 to 1.5 + /- 1.18 ( P < .05 ) . The difference between the two groups was not significant . At 6 hours , there was some pain rebound in the ketorolac group . CONCLUSION IM ketorolac and oral indomethacin are similar in the relief of the pain of acute gouty arthritis in the ED OBJECTIVE To evaluate the efficacy and safety of etoricoxib and indomethacin in the treatment of patients with acute gout . METHODS A r and omized , double-blind , active-comparator study was conducted at 42 sites . A total of 189 men and women ( > or = 18 years of age ) who were experiencing an acute attack ( < or = 48 hours ) of clinical ly diagnosed gout were treated for 8 days with etoricoxib , 120 mg/day ( n = 103 ) , or indomethacin , 50 mg 3 times a day ( n = 86 ) . The primary efficacy end point was the patient 's assessment of pain in the study joint ( 0 - 4-point Likert scale ) over days 2 - 5 . Safety was assessed by adverse experiences ( AEs ) occurring during the trial . RESULTS Etoricoxib demonstrated clinical efficacy comparable to that of indomethacin in terms of the patient 's assessment of pain in the study joint . The difference in the mean change from baseline over days 2 - 5 was -0.08 ( 95 % confidence interval -0.29 , 0.13 ) ( P = 0.46 ) , which fell within the prespecified comparability bounds of -0.5 to 0.5 . Secondary end points over the 8-day study , including the onset of efficacy , reduction in signs of inflammation , and patient 's and investigator 's global assessment s of response to therapy , confirmed the comparable efficacy of the two treatments . The etoricoxib-treated patients had a numerically lower incidence of AEs ( 43.7 % ) than did the indomethacin-treated patients ( 57.0 % ) and a significantly lower incidence of drug-related AEs ( 16.5 % versus 37.2 % ; P < 0.05 ) . CONCLUSION Etoricoxib at a dosage of 120 mg once daily was confirmed to be an effective treatment for acute gout . Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 3 times daily , and it was generally safe and well tolerated Flurbiprofen has been compared with phenylbutazone in a double-blind study involving 33 patients with acute gout . Patients received either flurbiprofen 400 mg daily for 48 h followed by 200 mg daily , or phenylbutazone 800 mg daily for 48 h followed by 400 mg daily . The drugs were of comparable efficacy , while side-effects were uncommon and relatively mild . Flurbiprofen appears to be a satisfactory alternative to phenylbutazone in the management of acute gouty arthritis BACKGROUND Acute attacks of gouty arthritis are characterized by the rapid onset of severe pain , swelling , and erythema of the affected joint . Nonsteroidal anti-inflammatory drugs are considered the drugs of first choice for treating acute gout . Rofecoxib is a specific cyclooxygenase-2 inhibitor , which has demonstrated analgesic efficacy in the setting of acute pain . Whether it is effective in the treatment of acute gouty arthritis remains to be evaluated . OBJECTIVE The aim of this study was to assess the efficacy and tolerability of rofecoxib compared with diclofenac sodium sustained release ( SR ) and meloxicam in the treatment of acute gouty arthritis . METHODS In this single-blind , r and omized , controlled , parallel-group study , patients aged > or = 18 years with acute gout within 48 hours of onset were r and omized to receive oral treatment with 2 tablets of rofecoxib ( 25 mg ) , diclofenac ( 75 mg ) , or meloxicam ( 7.5 mg ) once daily for 7 days . The primary outcome measures were patients global assessment of response to therapy and investigator assessment of response to therapy on days 3 and 8 . Other efficacy measurements included investigator assessment of total inflammatory scores on days 3 and 8 and patient assessment of pain intensity during the first 12 hours of treatment . RESULTS Sixty-two patients ( 53 men , 9 women ; mean [ SD ] age , 51.1 [ 12.1 ] years ) were assigned to receive rofexocib ( n = 20 ) , diclofenac ( n = 21 ) , or meloxicam ( n = 21 ) . For patient global response to therapy on days 3 and 8 , rofecoxib was associated with analgesic efficacy in significantly more patients compared with meloxicam ( 84.2 % vs 40.0 % of patients [ P=0.005 ] and 94.7 % vs 60.0 % of patients [ P=0.02 ] , respectively ) ; no significant differences versus diclofenac were found . Similarly , for investigator global assessment of response to therapy , a greater percentage of responders was found in the rofecoxib group compared with the meloxicam group on day 3 ( 88.9 % vs 40.0 % of patients [ P=0.02 ] ) , but the difference was not significant on day 8 . A greater percentage of responders was found in the rofecoxib group compared with the diclofenac group on day 3 ( 88.9 % vs 47.3 % [ P=0.007 ] ) , but the difference was not significant on day 8 . Compared with baseline , all regimens showed significant improvement in total inflammatory scores on days 3 and 8 ( all P<0.01 ) . During the first 12 hours after dosing , pain intensity score was significantly reduced with rofecoxib starting at 0.5 hours ( P<0.05 ) , but not with diclofenac or meloxicam . Clinical adverse events ( AEs ) were reported in 4 ( 20.0 % ) , 7 ( 33.3 % ) , and 6 ( 28.6 % ) patients in the rofecoxib , diclofenac , and meloxicam groups , respectively ; the most common AEs reported were edema in 1 patient each in the rofecoxib ( 5.0 % ) and meloxicam ( 4.8 % ) groups and 2 patients ( 9.5 % ) in the diclofenac group and abdominal ( 1 [ 5.0 % ] , 1 [ 4.8 % ] , and 2 [ 9.5 % ] , respectively ) . No significant differences in tolerability were found among the 3 treatment groups . CONCLUSIONS In this study of patients with acute gouty arthritis , rofecoxib 50 mg once daily provided more effective treatment than diclofenac sodium SR 150 mg and meloxicam 15 mg administered orally once daily for 7 days in > or = 1 efficacy assessment of overall analgesic effect on day 3 or day 8 . Rofecoxib achieved a rapid onset of pain relief , demonstrating significant improvement 30 minutes after dosing . All of the regimens appeared well tolerated in the population studied 1 The natural history of acute gouty arthritis was studied in 11 volunteers with podagra . 2 Two patients withdrew from the study on day 4 because of severe persistent pain . Of the remaining patients all showed some improvement in pain by day 5 and in swelling by day 7 . Tenderness improved in seven patients by day 7 but two continued to experience the same amount of discomfort as at trial entry . In spite of these improvements only three patients noted resolution of their pain during the study period . 3 These data indicate that while the majority of patients show spontaneous improvement , resolution is unlikely over a period of 7 days without the use of effective non-steroidal anti-inflammatory medication . 4 Documentation of the natural history of the acute gouty attack may assist clinical investigators in interpreting the results of uncontrolled evaluations of non-steroidal anti-inflammatory drugs Fifty-nine patients with acute gouty arthritis entered into a 7-day multicenter , double blind trial of ketoprofen versus indomethacin . Patients were r and omly assigned to receive 100 mg of ketoprofen ( n = 29 patients ) or 50 mg of indomethacin ( n = 30 patients ) 3 times a day . More than 90 % of the patients in each group reported pain relief within the 1st day of treatment . By Day 5 , 7 patients in the ketoprofen group and 6 in the indomethacin group discontinued treatment because of complete or substantial pain relief . At the end of the study , most patients in both groups were rated as having marked improvement both by the investigators and by self- assessment . Three patients in each group withdrew prematurely because of drug related gastrointestinal disorders . Ketoprofen compared favorably for efficacy and safety with indomethacin in the treatment of gouty arthritis |
13,974 | 26,058,039 | Interestingly , within these models , interpretational processes may also occur following attentional selection of emotionally relevant stimuli .
This contrasts with the Threat Interpretation Model in which interpretation precedes attention . | Attentional bias ( AB ) , the tendency for patients to pay attention selectively to information that is related to their current concerns , is a well-vali date d phenomenon in many forms of psychopathology .
Information processing models assume that AB plays a role not only in the maintenance of psychopathology but also in the causal development of anxiety and depression .
Sometimes referred to as hypervigilance , the investigation of AB has gained momentum in pain research .
Meta-analyses have shown that patients with chronic pain indeed display an AB towards pain-related information , but the field is marked by large variability in findings , and sometimes by patterns of results that do not accord well with hypotheses .
Some studies have added to the confusion by revealing that , instead of directing attention towards pain , there is sometimes a tendency to attend away from pain-related information .
As yet , most of the literature on AB investigates attending towards visual representations of pain ( pain words or pictures depicting facial expressions of pain ) , which may fundamentally differ from attentional processes towards pain itself or other bodily sensations .
In addition , to make use of eye-tracking methods , visual stimuli could be context ualized within the context of somatosensory pain , eg , by associating these stimuli with pain through conditioning processes or by presenting pain words or facial expressions that provide information about an upcoming painful experience that the participant will undergo .
The idea that interpretational processes are the key drivers of AB is already included in many models of pain and AB and has been variously discussed in terms of the threat value of pain and the appraisal of pain as threatening or catastrophic .
Despite some consensus , however , there is almost no research on the precise nature of these interpretational processes and their role on AB in pain .
Initial positive results with AB modification for psychopathology have been reported but seem not to be substantiated in recent review s. Attentional bias modification research in general is still in its infancy and is only beginning to be used within pain research . | Five experiments are reported showing that the interpretation of personally relevant emotional information can be modified by systematic exposure to congruent exemplars . Participants were induced to interpret ambiguous information in a relatively threatening or a benign way . Comparison with a baseline condition suggested that negative and positive induction had similar but opposing effects . Induction of an interpretative bias did not require active generation of personally relevant meanings , but such active processing was necessary before state anxiety changed in parallel with the induced interpretative bias . These findings provide evidence consistent with a causal link between the deployment of interpretative bias and anxiety and reveal something of the processes underlying this association |
13,975 | 23,977,533 | However , a small study assessing the feasibility of conducting a r and omized controlled trial for TMT versus conservative treatment reported poor short- and long-term outcomes for patients who underwent pneumonectomy .
Overall , results of the present systematic review suggest TMT may offer acceptable perioperative outcomes and long-term survival in selected patients treated in specialized centers | BACKGROUND Malignant pleural mesothelioma ( MPM ) is an aggressive form of cancer arising from the pleural mesothelium .
Trimodality therapy ( TMT ) involving extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy is a recognized treatment option with a curative intent .
Despite encouraging results from institutional studies , TMT in the treatment of MPM remains controversial .
The present systematic review aims to assess the safety and efficacy of TMT in the current literature . | BACKGROUND Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma ( MPM ) . A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy . Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM . The aim of our study was to evaluate the feasibility of this protocol and to estimate survival . METHODS From 2000 to 2003 , 21 patients with MPM ( 14 males and 7 females , median age 59 years ) were enrolled in the prospect i ve study . Induction chemotherapy consisted of Carboplatin ( AUC 5mg/mL/min on Day 1 ) and Gemcitabine ( 1000mg/m(2 ) on Days 1 , 8 , 15 ) for three to four cycles . EPP was performed 3 - 5 weeks after induction therapy , while post-operative RT was given 4 - 6 weeks after operation . RESULTS Ten patients received three cycles of chemotherapy , 10 patients received four cycles and 1 patient had two cycles . Grade s 3 - 4 haematological toxicity occurred in eight ( 38.1 % ) patients . Chemotherapy response rate was : complete 0 % , partial 33.3 % and stable disease 66.7 % . Seventeen ( 80.9 % ) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4 % . Median survival was 25.5 months , with an overall 1 , 3 and 5-year survival rate of 71 , 33 and 19 % , respectively . CONCLUSIONS In MPM , the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible , with good results in terms of survival and morbidity . Our results are similar to those of other studies using a heavier modality treatment Summary Background The effects of extra-pleural pneumonectomy ( EPP ) on survival and quality of life in patients with malignant pleural mesothelioma have , to our knowledge , not been assessed in a r and omised trial . We aim ed to assess the clinical outcomes of patients who were r and omly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery ( MARS ) feasibility study . Methods MARS was a multicentre r and omised controlled trial in 12 UK hospitals . Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included . In a prer and omisation registration phase , all patients underwent induction platinum-based chemotherapy followed by clinical review . After further consent , patients were r and omly assigned ( 1:1 ) to EPP followed by postoperative hemithorax irradiation or to no EPP . R and omisation was done central ly with computer-generated permuted blocks stratified by surgical centre . The main endpoints were feasibility of r and omly assigning 50 patients in 1 year ( results detailed in another report ) , proportion r and omised who received treatment , proportion eligible ( registered ) who proceeded to r and omisation , perioperative mortality , and quality of life . Patients and investigators were not masked to treatment allocation . This is the principal report of the MARS study ; all patients have been recruited . Analyses were by intention to treat . This trial is registered , number IS RCT N95583524 . Findings Between Oct 1 , 2005 , and Nov 3 , 2008 , 112 patients were registered and 50 were subsequently r and omly assigned : 24 to EPP and 26 to no EPP . The main reasons for not proceeding to r and omisation were disease progression ( 33 patients ) , inoperability ( five patients ) , and patient choice ( 19 patients ) . EPP was completed satisfactorily in 16 of 24 patients assigned to EPP ; in five patients EPP was not started and in three patients it was ab and oned . Two patients in the EPP group died within 30 days and a further patient died without leaving hospital . One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre . The hazard ratio [ HR ] for overall survival between the EPP and no EPP groups was 1·90 ( 95 % CI 0·92–3·93 ; exact p=0·082 ) , and after adjustment for sex , histological subtype , stage , and age at r and omisation the HR was 2·75 ( 1·21–6·26 ; p=0·016 ) . Median survival was 14·4 months ( 5·3–18·7 ) for the EPP group and 19·5 months ( 13·4 to time not yet reached ) for the no EPP group . Of the 49 r and omly assigned patients who consented to quality of life assessment ( EPP n=23 ; no EPP n=26 ) , 12 patients in the EPP group and 19 in the no EPP group completed the quality of life question naires . Although median quality of life scores were lower in the EPP group than the no EPP group , no significant differences between groups were reported in the quality of life analyses . There were ten serious adverse events reported in the EPP group and two in the no EPP group . Interpretation In view of the high morbidity associated with EPP in this trial and in other non-r and omised studies a larger study is not feasible . These data , although limited , suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients . Funding Cancer Research UK ( CRUK/04/003 ) , the June Hancock Mesothelioma Research Fund , and Guy 's and St Thomas ' NHS Foundation Trust Malignant pleural mesothelioma ( MPM ) is a rare tumour but with increasing incidence and a poor prognosis . In 2008 , the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to- date d guidelines on the management of MPM . To obtain an earlier and reliable diagnosis of MPM , the experts recommend performing thoracoscopy , except in cases of pre-operative contraindication or pleural symphysis . The st and ard staining procedures are insufficient in ∼10 % of cases . Therefore , we propose using specific immunohistochemistry markers on pleural biopsies . In the absence of a uniform , robust and vali date d staging system , we advice use of the most recent TNM based classification , and propose a three step pre-treatment assessment . Patient 's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM . Other potential parameters should be recorded at baseline and reported in clinical trials . MPM exhibits a high resistance to chemotherapy and only a few patients are c and i date s for radical surgery . New therapies and strategies have been review ed . Because of limited data on the best combination treatment , we emphasise that patients who are considered c and i date s for a multimodal approach should be included in a prospect i ve trial at a specialised centre The European Organisation for Research and Treatment of Cancer ( EORTC ; protocol 08031 ) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma ( with a severity of cT3N1M0 or less ) . Induction chemotherapy consisted of three courses of cisplatin 75 mg·m−2 and pemetrexed 500 mg·m−2 . Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy ( 54 Gy , 30 fractions ) . Our primary end-point was “ success of treatment ” and our secondary end-points were toxicity , and overall and progression-free survival . 59 patients were registered , one of whom was ineligible . Subjects ’ median age was 57 yrs . The subjects ’ TNM scores were as follows : cT1 , T2 and T3 , 36 , 16 and six patients , respectively ; cN0 and N1 , 57 and one patient , respectively . 55 ( 93 % ) patients received three cycles of chemotherapy with only mild toxicity . 46 ( 79 % ) patients received surgery and 42 ( 74 % ) had extrapleural pneumonectomy with a 90-day mortality of 6.5 % . Post-operative radiotherapy was completed in 37 ( 65 % ) patients . Grade 3–4 toxicity persisted after 90 days in three ( 5.3 % ) patients . Median overall survival time was 18.4 months ( 95 % CI 15.6–32.9 ) and median progression-free survival was 13.9 months ( 95 % CI 10.9–17.2 ) . Only 24 ( 42 % ) patients met the definition of success ( one-sided 90 % CI 0.36–1.00 ) . Although feasible , trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary Purpose : MORAb-009 is a chimeric monoclonal antibody that targets mesothelin , a tumor differentiation antigen overexpressed in pancreatic cancer , ovarian cancer , mesothelioma , and other malignancies . We conducted a phase I clinical trial of MORAb-009 in patients with advanced mesothelin-expressing cancers to determine its safety , dose-limiting toxicity ( DLT ) , and maximum tolerated dose ( MTD ) . Methods : Cohorts consisting of 3 to 6 subjects each received MORAb-009 intravenously on days 1 , 8 , 15 , and 22 at progressively increasing doses ranging from 12.5 to 400 mg/m2 . Disease evaluation with computed tomography occurred on day 35 . Subjects with responding or stable disease could receive additional cycles of MORAb-009 . Results : A total of 24 subjects were treated including 13 mesothelioma , 7 pancreatic cancer , and 4 ovarian cancer patients . The median number of MORAb-009 infusions was 4 ( range 1–24 infusions ) . At the 400 mg/m2 dose level , 2 subjects experienced DLT ( grade 4 transaminitis and a grade 3 serum sickness ) . Thus , although there were other contributing causes of these adverse events , 200 mg/m2 was considered the MTD . Other adverse events at least possibly related to MORAb-009 included 7 drug hypersensitivity events ( all grade 1 or 2 ) and a thromboembolic event ( grade 4 ) . Eleven subjects had stable disease . There was a dose-dependent increase in serum MORAb-009 concentration . Conclusion : MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m2 . In this group of previously treated patients , 11 subjects had stable disease . Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy . Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time BACKGROUND The aim of this multicenter trial was to prospect ively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy ( EPP ) and radiotherapy , including quality of life as outcome . PATIENTS AND METHODS Eligible patients had malignant pleural mesothelioma of all histological types , World Health Organization performance status of zero to two and clinical stage T1-T3 , N0 - 2 , M0 disease considered completely resectable . Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP . Postoperative radiotherapy was considered for all patients . RESULTS In all , 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy . Forty-five patients ( 74 % ) underwent EPP and in 37 patients ( 61 % ) the resection was complete . Postoperative radiotherapy was initiated in 36 patients . The median survival of all patients was 19.8 months [ 95 % confidence interval ( CI ) 14.6 - 24.5 ] . For the 45 patients undergoing EPP , the median survival was 23 months ( 95 % CI 16.6 - 32.9 ) . Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82 % ( N = 36 ) at baseline and 76 % ( N = 26 ) at 3 months after surgery ( P = 0.5 ) . CONCLUSIONS The observed rate of operability is promising . A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery . This approach was not associated with an increase in psychological distress PURPOSE To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients had MPM with clinical stage T1 - 3 , N0 - 2 , M0 disease considered to be completely resectable and a WHO performance status of 0 to 2 . Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 , given every 28 days . Surgery had to consist of a complete extrapleural pneumonectomy , including resection of pericardium and diaphragm . Postoperative radiotherapy was to be considered for all patients . RESULTS Nineteen patients with MPM were included in this pilot study . According to the European Organization for Research and Treatment of Cancer prognostic score , two patients were in the good prognosis group , and 17 patients were in the poor prognosis group . The response rate to neoadjuvant chemotherapy was 32 % . The major toxicity was thrombocytopenia . Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality . Major surgical complications occurred in six patients , and all were treated successfully . Thirteen patients received postoperative radiotherapy . The median survival time was 23 months . Two patients remain alive and free of disease 41 and 38 months after initiation of therapy . CONCLUSION For patients with potentially operable MPM , the availability of active and well-tolerated chemotherapy regimens , the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center , and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy AIM Even though followed by a prolonged survival in highly selected patients , the promising results of Sugarbaker 's trimodality treatment for malignant pleural mesothelioma ( MPM ) are debated and not yet uniformly replicated . The purpose of this study is to evaluate prospect ively the reproducibility of the trimodality treatment results in a patient population with mesothelioma staged by the IMIG classification . METHODS Fifty-four patients with MPM have been judged c and idable to extended pleuropneumonectomy ( EPP ) , to be followed by chemotherapy ( paclitaxel+carboplatin ) and radiotherapy ( 50 Gy ) . RESULTS At thoracotomy , 44 of the 54 surgical c and i date s ( 81 % ) underwent EPP ; 73 % of the operated patients completed the entire adjuvant chemo-radiotherapy with no major toxicity . The 30-day or in-hospital operative mortality rate was 4.5 % ( 2 deaths ) , the major morbidity 36 % , and the overall complication rate 50 % . At 5 years the projected survival of the 42 surgical survivors su bmi tted to EPP is 19 % ; median survival is 20 months . The restricted group of patients with epithelial , N0 - 1 , completely resected MPM ( microscopic negative margins ) exhibits a projected 50 % 5-year survival . Clinical understaging has shown up to be noticeable both at the thoracotomy exploration and pathology examination . Most of the disease recurrences are loco-regional and the current insufficiency of intraoperative or postsurgical radicality needs improvement , along with earlier diagnosis , more accurate staging , and preoperative induction for the multimodality treatment of pleural mesothelioma to become an established curative option . CONCLUSIONS This series confirms the reproducibility of the trimodality treatment for MPM , which is associated with prolonged survival for early-stage tumors at the cost of a not prohibitive treatment-related mortality rate Introduction : To compare the outcomes of two different multimodality regimens involving neoadjuvant chemotherapy , extrapleural pneumonectomy ( EPP ) and adjuvant radiotherapy versus pleurectomy/decortication ( P/D ) , hyperthermic pleural lavage with povidone-iodine , and adjuvant chemotherapy in patients with malignant pleural mesothelioma . Methods : Nonr and omized prospect i ve study of patients treated by multimodality therapy and operated on between January 2004 and June 2011 . Second-line treatments were administered when appropriate . Survival and prognostic factors were analyzed by the Kaplan Meier method , log rank test , and Cox regression analysis . Results : Twenty-five consecutive patients received neoadjuvant chemotherapy , 22 underwent EPP , and 17 received adjuvant radiotherapy . Over the same period , 54 consecutive patients underwent P/D and hyperthermic pleural lavage and received prophylactic radiotherapy and adjuvant chemotherapy . The 30-day mortality rate was 4.5%in the EPP group and nil in the P/D group . Fifteen patients ( 68 % ) in the EPP group and 15 ( 27.7 % ) in the P/D group experienced complications . There were no differences between the EPP and P/D groups for age , sex , histology , pathologic stage , and nodal status . Trimodality therapy was completed by 68%of the patients in the EPP group and 100%in the P/D group . Survival was significantly better in the P/D group : median survival was 23 months versus 12.8 months , 2-year survival was 49%versus 18.2 % , and 5-year survival was 30.1%versus 9 % , respectively ( p = 0.004 ) . At multivariate analysis , epithelioid histology , P/D , and completeness of resection were independent prognostic factors . Conclusions : In our experience , P/D , hyperthermic pleural lavage with povidone-iodine , and adjuvant chemotherapy were superior to neoadjuvant chemotherapy , EPP , and adjuvant radiotherapy PURPOSE Malignant pleural mesothelioma ( MPM ) remains associated with poor outcome . We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy ( EPP ) and adjuvant high-dose ( 50 to 60 Gy ) hemithoracic radiation therapy for MPM . PATIENTS AND METHODS We conducted a retrospective review of all patients prospect ively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution . RESULTS A total of 60 patients were suitable c and i date s. Histology was epithelioid ( n = 44 ) or biphasic ( n = 16 ) . Chemotherapy regimens included cisplatin/vinorelbine ( n = 26 ) , cisplatin/pemetrexed ( n = 24 ) , cisplatin/raltitrexed ( n = 6 ) , or cisplatin/gemcitabine ( n = 4 ) . EPP was performed in 45 patients , and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients . Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival ( median survival of 59 months v < or= 14 months in the remaining patients , P = .0003 ) . The type of induction chemotherapy had no significant impact on survival . Pathologic nodal status remained a significant predictor of poor survival despite completion of the trimodality therapy . After completion of the protocol , the 5-year disease-free survival was 53 % for patients with N0 disease , reaching 75 % in patients with ypT1 - 2N0 and 45 % in patients with ypT3 - 4N0 . CONCLUSION This large , single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol . The results are encouraging for patients with N0 disease . However , N2 disease remains a major factor impacting on survival , despite completion of the entire trimodality regimen PURPOSE Neoadjuvant pemetrexed plus cisplatin was administered , followed by extrapleural pneumonectomy ( EPP ) and hemithoracic radiation ( RT ) , to assess the feasibility and efficacy of trimodality therapy in stage I to III malignant pleural mesothelioma . PATIENTS AND METHODS Requirements included stage T1 - 3 N0 - 2 disease , no prior surgical resection , adequate organ function ( including predicted postoperative forced expiratory volume in 1 second > or = 35 % ) , and performance status 0 to 1 . Patients received pemetrexed 500 mg/m(2 ) plus cisplatin 75 mg/m(2 ) for four cycles . Patients without disease progression underwent EPP followed by RT ( 54 Gy ) . The primary end point was pathologic complete response ( pCR ) rate . RESULTS Seventy-seven patients received chemotherapy . All four cycles were administered to 83 % of patients . The radiologic response rate was 32.5 % ( 95 % CI , 22.2 to 44.1 ) . Fifty-seven patients proceeded to EPP , which was completed in 54 patients . Three pCRs were observed ( 5 % of EPP ) . Forty of 44 patients completed irradiation . Median survival in the overall population was 16.8 months ( 95 % CI , 13.6 to 23.2 months ; censorship , 33.8 % ) . Patients completing all therapy had a median survival of 29.1 months and a 2-year survival rate of 61.2 % . Radiologic response of complete or partial response was associated with a median survival of 26.0 months compared with 13.9 months for patients with stable disease or progressive disease ( P = .05 ) . CONCLUSION This multicenter trial showed that trimodality therapy with neoadjuvant pemetrexed plus cisplatin is feasible with a reasonable long-term survival rate , particularly for patients who completed all therapy . Radiologic response to chemotherapy , but not sex , histology , disease stage , or nodal status , was associated with improved survival |
13,976 | 24,261,909 | Within the limitation of this systematic review , the application of grafting material s and barrier membranes result ed in greater PD reduction and RBF , but there is a lack of high- quality comparative studies to support this statement . | BACKGROUND This systematic review was requested by the Task Force of the American Academy of Periodontology as a follow-up study of the 2013 report , with an aim to investigate the efficacy of different surgical approaches to treat peri-implantitis . | PURPOSE Porous titanium granules ( PTG ) may have potential as an osteoconductive bone graft substitute to treat peri-implant osseous defects . The aim of this study was to analyze clinical and radiographic outcomes of peri-implant osseous defects after treatment with PTG . MATERIAL S AND METHODS This prospect i ve , r and omized , case-control , clinical 12-month study compared open-flap debridement and surface decontamination with titanium curettes and 24 % ethylenediaminetetraacetic acid gel ( n = 16 ) to the same protocol but with the addition of PTG ( n = 16 ) . One- , two- , and three-wall infrabony defects were included . Patients were given amoxicillin and metronidazole 3 days before surgery and for 7 days afterwards . Implants were submerged and allowed to heal for 6 months . Probing pocket depths , bleeding on probing , implant stability using resonance frequency analysis , and radiographic evaluation were performed at baseline and at 12 months . The threshold for significance was set at .05 . RESULTS Change in radiographic defect height and percent fill of the peri-implant osseous defect significantly favored patients treated with PTG . Both treatment modalities demonstrated significant improvements in probing pocket depth , but significant differences between groups were not observed . The PTG-treated implants showed an increase in implant stability quotient ( ISQ ) of 1.6 units , compared with a decrease of 0.7 ISQ for the control group . No adverse effects were associated with PTG treatment . CONCLUSIONS Reconstruction with PTG result ed in significantly better radiographic peri-implant defect fill compared with controls ; however , the results do not necessarily imply reosseointegration or osseointegration of PTG particles . Improvements in clinical parameters were seen in both groups , but no differences between groups were demonstrated Objectives The aim of the present study is to report on preliminary clinical and radiographic results of using porous titanium granules for treatment of peri-implantitis lesions . Methods A retrospective cohort of 18 implants presenting with peri-implantitis in 16 consecutive patients from two private practice s had been evaluated . Treatment included open flap debridement of the lesion , implant surface decontamination using tetracycline , filling of the defect with porous titanium granules and apically positioning of the flaps . Patients ' demographics , site and implant characteristics , as well as clinical and radiographic evaluation as baseline and time of follow-up were recorded . Results Patients ' age ranged from 44 to 79 years with a mean of 61.3 ± 9.5 years . Follow-up time after treating peri-impantitis lesions ranged from 6 to 15 months ( mean 7.5 ± 3.9 ) . Two out of the 18 implants still presented with bleeding and suppuration at follow-up and thus the treatment was considered as a failure . This result ed in an overall success rate of 88 % for the treatment . Mean bone loss prior to treatment was 4.4 ± 2.1 mm and was reduced following treatment to 2.3 ± 2.1 mm . Conclusion The use of porous titanium granules might be a viable treatment option in cases of peri-implantitis lesions . Further large-scale long-term studies are warranted in order to assess the additional benefit from this treatment option compared to other available alternatives . BACKGROUND Limited evidence exists on the efficacy of regenerative treatment of peri-implantitis . MATERIAL AND METHODS Subjects receiving antibiotics and surgical debridement were r and omly assigned to placement of autogenous bone ( AB ) or bovine-derived xenograft ( BDX ) and with placement of a collagen membrane . The primary outcome was evidence of radiographic bone fill and the secondary outcomes included reductions of probing depth ( PD ) bleeding on probing ( BOP ) and suppuration . RESULTS Twenty-two subjects were included in the AB and 23 subjects in the BDX group . Statistical analysis failed to demonstrate differences for 38/39 variables assessed at baseline . At 12 months , significant better results were obtained in the BDX group for bone levels ( p < 0.001 ) , BOP ( p = 0.004 ) , PI ( p = 0.003 ) and suppuration ( p < 0.01 ) . When adjusting for number of implants treated per subject , a successful treatment outcome PD ≤ 5.0 mm , no pus , no bone loss and BOP at 1/4 or less sites the likelihood of defect fill was higher in the BDX group ( LR : 3.2 , 95 % CI : 1.0 - 10.6 , p < 0.05 ) . CONCLUSIONS Bovine xenograft provided more radiographic bone fill than AB . The success for both surgical regenerative procedures was limited . Decreases in PD , BOP , and suppuration were observed OBJECTIVES To evaluate the extent of bone fill over 3 years following the surgical treatment of peri-implantitis with bone grafting with or without a membrane . MATERIAL AND METHODS In a non-submerged wound-healing mode , 15 subjects with 27 implants were treated with a bone substitute ( Algipore ( ® ) ) alone and 17 subjects with 29 implants were treated with the bone substitute and a resorbable membrane ( Osseoquest ( ® ) ) . Implants with radiographic bone loss ≥1.8 mm following the first year in function and with bleeding and /or pus on probing were included . Following surgery , subjects were given systemic antibiotics ( 10 days ) and rinsed with chlorhexidine . After initial healing , the subjects were enrolled in a strict maintenance programme . RESULTS Statistical analysis failed to demonstrate changes in bone fill between 1 and 3 years both between and within procedure groups . The mean defect fill at 3 years was 1.3 ± ( SD ) 1.3 mm if treated with the bone substitute alone and 1.6 ± ( SD ) 1.2 mm if treated with an adjunct resorbable membrane , ( p=0.40 ) . The plaque index decreased from approximately 40 - 10 % , remaining stable during the following 2 years . CONCLUSION Defect fill using a bone substitute with or without a membrane technique in the treatment of peri-implantitis can be maintained over 3 years OBJECTIVES The aim of the present case series was to evaluate the 2-year results obtained following treatment of peri-implantitis lesions using either a nanocrystalline hydroxyapatite ( NHA ) or a natural bone mineral in combination with a collagen membrane ( NBM+CM ) . MATERIAL AND METHODS Twenty-two patients suffering from moderate peri-implantitis ( n=22 intra-bony defects ) were r and omly treated with ( i ) access flap surgery ( AFS ) and the application of NHA , or with AFS and the application of NBM+CM . Clinical parameters were recorded at baseline and after 12 , 18 , and 24 months of non-submerged healing . RESULTS Two patients from the NHA group were excluded from the study due to severe pus formation at 12 months . At 24 months , both groups revealed clinical ly important probing depth ( PD ) reductions ( NHA : 1.5+/-0.6 mm ; NBM+CM : 2.4+/-0.8 mm ) and clinical attachment level ( CAL ) gains ( NHA : 1.0+/-0.4 mm ; NBM+CM : 2.0+/-0.8 mm ) . However , these clinical improvements seemed to be better in the NBM+CM group ( difference between groups : PD reduction : 0.9+/-0.2 mm ; CAL gain : 1.0+/-0.3 mm ) . CONCLUSION Both treatment procedures have shown efficacy over a period of 24 months , however , the application of NBM+CM may result in an improved outcome of healing The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . & NA ; Between 1994 and 1999 , 50 patients were treated with either profound parodontopathy ( 30 ) or periimplantitis ( 20 ) . Half of each of the two groups of patients was treated conventionally , and the other half was treated with laser support . Before the operation , microbiological examinations were carried out , in addition to registering the clinical findings and taking x‐rays . These procedures were repeated after the operation , and again after 6 , 12 , 24 , 36 , 48 , and 60 months . The surgical part of therapy for each half of the patient groups included surface decontamination with diode laser light ( 1‐watt output , maximum of 20 seconds ) in addition to conventional procedures . The values of the laser‐supported therapy were lower than those specified in the relevant literature . The relapse rate of the two diseases ( 13 % for the periimplantitis and 23 % for the parodontopathy group ) after 5 years was lower than the comparative values of research ed literature where decontamination was not included in the therapy . We think that integrating diode laser light decontamination in the approved treatment schemes for periimplantitis and parodontitis contributes considerably to the success of this therapy . ( Implant Dent 2000;9:247‐251 AIM The objective of this r and omized , double-blind , placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride ( CPC ) on microbiological and clinical parameters . MATERIAL & METHODS Thirty patients ( 79 implants ) with peri-implantitis were treated with resective surgical treatment consisting of apically re-positioned flap , bone re-contouring and surface debridement and decontamination . Patients were r and omly allocated to decontamination with 0.12 % CHX + 0.05 % CPC ( test-group ) or a placebo-solution ( without CHX/CPC , placebo-group ) . Microbiological parameters were recorded during surgery ; clinical and radiographical parameters were recorded before ( pre- ) treatment ( baseline ) , and at 3 , 6 and 12 months after treatment . RESULTS Nine implants in two patients in the placebo-group were lost due to severe persisting peri-implantitis . Both decontamination procedures result ed in significant reductions of bacterial load on the implant surface , but the test-group showed a significantly greater reduction than the placebo-group ( log 4.21 ± 1.89 versus log 2.77 ± 2.12 , p = 0.006 ) . Multilevel analysis showed no differences between both groups in the effect of the intervention on bleeding , suppuration , probing pocket depth and radiographical bone loss over time . CONCLUSION Implant surface decontamination with 0.12 % CHX + 0.05 % CPC in resective surgical treatment of peri-implantitis leads to a greater immediate suppression of anaerobic bacteria on the implant surface than a placebo-solution , but does not lead to superior clinical results . The long-term microbiological effect remains unknown OBJECTIVES The study aim ed at investigating the impact of two surface debridement/decontamination ( DD ) methods on the clinical outcomes of combined surgical treatment of peri-implantitis . MATERIAL AND METHODS Thirty-two patients suffering from advanced peri-implantitis ( n=38 combined supra- and intra-bony defects ) were treated with flap surgery , granulation tissue removal , and implantoplasty at buccally and supracrestally exposed implant parts . The intra-bony aspects were r and omly allocated to surface DD using either ( i ) an Er : YAG laser ( ERL ) device , or ( ii ) plastic curets+cotton pellets+sterile saline ( CPS ) . In both groups , the intra-bony component was augmented with a natural bone mineral and covered with a collagen membrane . Clinical and radiographic parameters were recorded at baseline and after 6 months of non-submerged healing . RESULTS Two patients were lost during follow-up . At 6 months , ERL-treated sites failed to reveal higher reductions in mean bleeding on probing ( ERL : 47.8 ± 35.5 versus CPS : 55.0 ± 31.1 % ) and CAL values ( ERL : 1.5 ± 1.4 versus CPS : 2.2 ± 1.4 mm ) when compared with the CPS group . Both groups exhibited a comparable radiographic bone fill at the intra-bony defect component . CONCLUSION The study failed to demonstrate a significant impact of the method of surface DD on the clinical outcome following combined surgical therapy of advanced peri-implantitis lesions OBJECTIVES To investigate the impact of residual defect height ( RDH ) following guided bone regeneration ( GBR ) in dehiscence-type defects on the long-term stability of peri-implant health after a period of 4 years . MATERIAL AND METHODS The RDH values in dehiscence-type defects at titanium implants were clinical ly assessed after 4 months of submerged healing following augmentation using a natural bone mineral ( NBM ) and a r and omized application of either a cross-linked- ( VN ) or a native collagen membrane ( BG ) ( n=12 patients each ) . The RDH values were classified as absent ( 0 mm , control ; n=8 ) , minimal ( 1 mm , test 1 ; n=8 ) , or advanced ( > 1 mm , test 2 ; n=8 ) . Clinical parameters ( i.e. bleeding on probing [ BOP ] , probing pocket depth [ PD ] , mucosal recession [ MR ] ) were recorded ( mesio- , mid- , and disto-buccal aspects ) at 4 years after prosthesis installation . RESULTS The mean PD ( 2.9±0.7 , 2.8±0.7 , 2.7±0.8 mm ) values at 4 years were comparable in all the groups investigated . The mean MR values tended to be increased in both the test groups ( 0.5±0.7 , 0.4±0.6 mm , respectively ) , when compared with the control group ( 0.2±0.3 mm ) ( P>0.05 , respectively ) . The mean BOP values were also increased in both the test groups ( 45.8±30.5 % , 54.1±24.8 % , respectively ) , even reaching statistical significance when comparing test 2 and control ( 29.1±21.3 % ) groups ( P=0.02 ) . CONCLUSION The present study indicated that ( i ) implants exhibiting RDH values > 1 mm are at a higher risk of developing peri-implant disease and ( ii ) positive RDH values may be associated with an increase in MR and may therefore compromise the overall esthetic outcome of implant therapy AIM The aim of this prospect i ve cohort study was to evaluate an anti-infective surgical protocol for the treatment of peri-implantitis . MATERIAL S AND METHODS Thirty-six implants in 24 partially dentate patients with moderate to advanced peri-implantitis were treated using an anti-infective surgical protocol incorporating open flap debridement and implant surface decontamination , with adjunctive systemic amoxicillin and metronidazole . Treatment outcomes were assessed at 3 , 6 and 12 months . Patient-based statistical analyses using multiple regression analyses were performed . RESULTS There was 100 % survival of treated implants at 12 months . At 3 months , there were statistically significant ( P < 0.01 ) reductions in mean probing depths ( PD ) , Bleeding on Probing ( BoP ) and suppuration . The greater the mean PD at baseline , the greater the PD reduction at 3 months . At 3 months , there was also a significant mean facial mucosal recession of 1 mm ( P < 0.001 ) . All these changes were maintained at 6 and 12 months . At 12 months , all treated implants had a mean PD < 5 mm , while 47 % of the implants had complete resolution of inflammation ( BoP negative ) . At 12 months , 92 % of implants had stable crestal bone levels or bone gain . There were no significant effects of smoking on any of the treatment outcomes . CONCLUSIONS For the treatment of peri-implantitis , an anti-infective protocol incorporating surgical access , implant surface decontamination and systemic antimicrobials followed by a strict postoperative protocol was effective at 3 months with the results maintained for up to 12 months after treatment As part of an ongoing prospect i ve study , the treatment of peri-implantitis defects using autogenous bone grafts was evaluated . This present report is based on data from 25 ITI screw implants in 17 patients with progressive peri-implant tissue destruction during the maintenance phase . Treatment of these lesions included raising flaps , removal of the surrounding granulation tissue , and air-polishing of the implant surface . Subsequently , corticocancellous bone grafts or particulate bone were placed into the peri-implant osseous defects , and the flaps were sutured around the cervical segment of the implants , allowing for transmucosal healing . Two of the 25 cases result ed in a negative outcome of the procedure . One of the transplants had to be removed 40 days after augmentation because of flap dehiscence and graft mobility . In another patient , the healing period was uneventful until the re-entry surgery , but when the site was reopened , the total graft volume was resorbed . The primary therapeutic success at re-entry surgery evaluated by intraoperative measurements result ed in a median defect depth reduction of 6.9 to 0.7 mm ( P = .001 ) , corresponding to a bone repair of 90 % . The change in defect width was 1.9 mm ( P = .002 , repair 100 % ) . A positive result of the reconstructive therapy has been observed during a re-evaluation time of up to 3 years . Median marginal bone loss was reduced from 6.2 to 2.3 mm after 2 and 3 years , respectively . The median vertical bone resorption of 4.5 mm was completely repaired . The crevicular fluid volume , a parameter of the level of marginal inflammation , along with probing depths and attachment levels , were reduced to a physiologic rate . The implant observation period until the first appearance of the lesion seems to be crucial to the effectiveness of the therapy . Early failures appearing within the first 2 years after implant placement showed a more stable therapeutic result over time This clinical study reports on the results of a new method in the treatment of peri-implantitis . The surfaces of 24 plasma flame-sprayed cylindric implants in 17 patients who were diagnosed with peri-implantitis were decontaminated with a combination of toluidine blue ( 100 micrograms/mL ) and laser irradiation at a wavelength of 906 nm . Bone defects were filled with autogenous bone using e-PTFE membranes for retention of the grafting material . Premature membrane exposure occurred in all patients after an average of 3 weeks ( + /- 10 days ) , which required immediate removal of the exposed membrane in 1 patient . Since the soft tissue showed minimal signs of inflammation , the membranes were left in situ for another 6 weeks in all other patients . The mean radiographic peri-implant bone gain was 2 mm + /- 1.90 mm after 9.5 months ( maxilla 2.5 mm + /- 2.38 mm ; m and ible 1.9 mm + /- 1.87 mm ) . Two implants around which the initial bone defect had already reached the basket had to be removed after 10 months and 35 months , respectively , despite radiographic evidence of improvement of the peri-implant defect . The longer the membrane stayed in situ , the more bone was gained , as long as the membrane was covered by soft tissue ( P = .01 ) . However , the longer an exposed membrane was left in place , the smaller the result ant bone gain ( P = .0001 ) . Therefore , despite the absence of clinical signs of inflammation , exposed membranes should be removed immediately . The short-term results of this study corroborate the efficacy of the applied treatment method in prolonging the service time of dental implants involved with peri-implantitis OBJECTIVES The aim of this prospect i ve cohort study was to compare two regenerative surgical treatment modalities for peri-implantitis . MATERIAL AND METHODS Thirty-six patients having a minimum of one osseointegrated implant , with a progressive loss of bone amounting to > or =3 threads ( 1.8 mm ) following the first year of healing , combined with bleeding and /or pus on probing , were involved in this study . The patients were assigned to two different treatment strategies . After surgical exposure of the defect , granulomatous tissue was removed and the infected implant surface was treated using 3 % hydrogen peroxide . The bone defects were filled with a bone substitute ( Algipore ) . In 17 patients ( Group 1 ) , a resorbable membrane ( Osseoquest ) was placed over the grafted defect before suturing . In 19 patients ( Group 2 ) , the graft was used alone . RESULTS One-year follow-up demonstrated clinical and radiographic improvements . Probing depths were reduced by 2.9 mm in Group 1 and by 3.4 mm in Group 2 . Defect fill amounted to 1.5 and 1.4 mm , respectively . There was no significant difference between the groups . CONCLUSION It is possible to treat peri-implant defects with a bone substitute , with or without a resorbable membrane PURPOSE Implantoplasty , a procedure that is done to smooth contaminated implant surfaces , has been used in the treatment of peri-implantitis . It reduces the implant diameter , which might compromise the implant 's strength . This in vitro study was design ed to evaluate the effect of implantoplasty on implant strength . MATERIAL S AND METHODS Thirty-two tapered implants were used ; half were 3.75 mm in diameter ( narrow ) and the other half were 4.7 mm in diameter ( wide ) . All implants were connected to 20-degree angled abutments . The apical half of each implant was embedded in acrylic resin . Eight 3.75-mm- and eight 4.7-mm-diameter implants were r and omly assigned to receive implantoplasty . The remaining implants did not receive implantoplasty ( control group ) . Implantoplasty was performed with a series of diamond and polishing burs . The specimens were then loaded 30 degrees off-axis in a universal testing machine until fracture failure occurred . Bending and fracture strength values were recorded and analyzed statistically ( α = .05 ) . The fractured surfaces were evaluated under a scanning electron microscope . RESULTS All narrow implants failed by fracture at the implant platform . The mean bending strength of narrow implants was statistically significantly reduced by implantoplasty ( 511.4 ± 55.9 N versus 613.9 ± 42.8 N ) . Implantoplasty did not affect the strength of wide implants ; fracture failures occurred at the abutment screw . The fracture mode was ductile and the crack growth was oblique in direction , indicating complex stress distribution and concentration under loading . CONCLUSION Within the limits of this study , implantoplasty appeared to weaken the strength of narrower implants . Therefore , this procedure should be performed with caution on narrower , freest and ing implants that are subject to greater occlusal force ( eg , posterior regions ) . Validation of these results is needed for different implant systems OBJECTIVES The present case series aim ed at investigating the 4-year clinical outcomes following surgical regenerative therapy of peri-implantitis lesions using either a nanocrystalline hydroxyapatite ( NHA ) or a natural bone mineral in combination with a collagen membrane ( NBM+CM ) . MATERIAL S AND METHODS Twenty patients suffering from moderate peri-implantitis ( n=20 intrabony defects ) were r and omly treated with ( 1 ) access flap surgery ( AFS ) and the application of NHA ( n=9 ) , or with AFS and the application of NBM+CM ( n=11 ) . Clinical and radiographic ( R ) parameters were recorded at baseline ( R ) and after 36 and 48 ( R ) months of non-submerged healing . RESULTS One patient from the NBM+CM group was discontinued from the study due to severe pus formation at 36 months . Compared with NHA , the application of NBM+CM result ed in higher mean PD reductions ( NBM+CM : 2.5 + /- 0.9 mm versus NHA : 1.1 + /- 0.3 mm ) and clinical attachment-level gains ( NBM+CM : 2.0 + /- 1.0 mm versus NHA : 0.6 + /- 0.5 mm ) at 48 months . A radiographic bone fill was observed for five sites in the NHA group , and eight sites in the NBM+CM group . CONCLUSION While the application of NBM+CM result ed in clinical improvements over a period of 4 years , the long-term outcome obtained with NHA without barrier membrane must be considered as poor OBJECTIVES The aim of the present r and omized-controlled double-blinded clinical multicenter study was to assess the use of either a new cross-linked ( VN ) or a native collagen membrane ( BG ) for the treatment of dehiscence-type defects at titanium implants . MATERIAL AND METHODS A total of n=54 patients were recruited in four German university clinics . According to a parallel-groups design , dehiscence-type defects at titanium implants were filled with a natural bone mineral and r and omly assigned to either VN or BG . Submerged sites were allowed to heal for 4 months . Primary ( e.g. , changes in defect length - DeltaDL , quality of newly formed tissue [ 0 - 4 ] - TQ ) and secondary parameters ( e.g. , membrane exposure , tissue conditions at dehisced sites ) were consecutively recorded . RESULTS Four patients were excluded due to an early wound infection ( VN:3 ; BG:1 ) , and one patient was lost during follow-up ( VN ) . The mean DeltaDL was 3.0 + /- 2.5 mm in the VN , and 1.94 + /- 2.13 mm in the BG group . The assessment of TQ revealed comparable mean values in both groups ( VN : 3.05 + /- 1.66 , BG : 3.46 + /- 1.48 ) . A significant correlation between membrane exposure and inflammation of the adjacent soft tissue was observed in the VN group . In both groups , the mean DL and TQ values were not significantly different at either non-exposed or exposed implant sites . CONCLUSION The results of the present study have indicated that VN supported bone regeneration on a level non-inferior to BG . However , in case of a premature membrane exposure , cross-linking might impair soft-tissue healing or may even cause wound infections OBJECTIVES The aim of the present case series was to evaluate the healing of intrabony peri-implantitis defects following application of a nanocrystalline hydroxyapatite ( NHA ) or a bovine-derived xenograft in combination with a collagen membrane ( BDX+BG ) . MATERIAL AND METHODS Twenty-two patients having moderate peri-implantitis ( n=22 intrabony defects ) were r and omly treated with ( i ) access flap surgery ( AFS ) and the application of NHA , or with AFS and the application of BDX+BG . Clinical parameters were recorded at baseline and after 6 months of non-submerged healing . RESULTS Post-operative wound healing revealed that NHA compromized initial adhesion of the mucoperiosteal flaps in all patients . At 6 months after therapy , NHA showed a reduction in the mean PD from 7.0+/-0.6 to 4.9+/-0.6 mm and a change in the mean clinical attachment loss ( CAL ) from 7.5+/-0.8 to 5.7+/-1.0 mm . In the BDX+BC group , the mean PD was reduced from 7.1+/-0.8 to 4.5+/-0.7 mm and the mean CAL changed from 7.5+/-1.0 to 5.2+/-0.8 mm . CONCLUSION Within the limits of the present case series , it can be concluded that at 6 months after surgery both therapies result ed in clinical ly important PD reductions and CAL gains BACKGROUND Advanced peri-implant intrabony defects require comprehensive surgical treatment regimens different from periodontal therapy strategies . The purpose of this longitudinal trial was to evaluate the peri-implant outcomes following guided bone regeneration with 3 treatment protocol s. METHODS In 25 patients , 41 peri-implant defects with supporting bone loss > 50 % of the implant length were treated with flap surgery plus autogenous bone grafts alone ( FG ) ( controls , n = 12 ) plus non-resorbable ( FGM ) ( test 1 , n = 20 ) or bioabsorbable barriers ( FGRM ) ( test 2 , n = 9 ) and supportive antimicrobial therapy . Following submerged healing , the membranes were removed ( FGM ) , and the peri-implant probing depths ( PD ) , probing bone levels ( BL ) , mobility scores ( PT ) , and intrabony defect height ( DH ) were radiographically evaluated at baseline , 6 months , and 1 and 3 years post-therapy . RESULTS Non-surgical/anti-infective therapy result ed in a limited improvement of PD scores after 6 months . At the 3-year visit , surgical treatment revealed significant changes from baseline for the controls and both of the test groups for PD : 5.1 + /- 2.7 mm ( FG ) , 5.4 + /- 3.0 mm ( FGM ) , and 2.6 + /- 1.6 mm ( FGRM ) , and for BL : 3.2 + /- 2.4 mm ( FG ) , 3.4 + /- 2.4 mm ( FGM ) , and 2.3 + /- 1.6 mm ( FGRM ) , Mann-Whitney test , P < or = 0.05 . The changes for DH and PT were significant only for FG- and FGM-treated subjects . The overall improvement for FGRM-treated patients during the 3-year observation was less marked . However , the differences between the 3 surgical treatment protocol s did not affect the treatment outcomes after 3 years . CONCLUSIONS Autogenous bone grafting is an appropriate treatment regimen to augment open crater-formed peri-implant defects . Although certain clinical situations require an additional fixation of barrier membranes , their routine application should be approached with caution The purpose of this r and omized clinical trial was to compare the clinical outcome of two different surgical approaches for the treatment of peri-implantitis . Seventeen patients with ITI(R ) implants were included consecutively over a period of 5 years . The patients were r and omized with a lottery assignment . Ten patients were treated with resective surgery and modification of surface topography ( test group ) . The remaining seven patients were treated with resective surgery only ( control group ) . Clinical parameters ( suppuration , modified plaque index - mPI , modified bleeding index - mBI , probing pocket depth - PPD , pseudopocket - DIM , mucosal recession - REC , probing attachment level - PAL ) were recorded at baseline , as well as 6 , 12 , 24 and 36 months after treatment . The cumulative survival rate for the implants of the test group was 100 % after 3 years . After 24 months , two hollow-screw implants of control group were removed because of mobility . Consequently , the cumulative survival rate was 87.5 % . The recession index in the control group was significantly lower than in the test group at 24 months ( Student 's t-value of -2.14 ) . On the contrary , control group showed higher PPD , PAL and mBI indexes than test group ( Student 's t-values of + 5.5 , + 2.4 and + 9.61 , respectively ) . The PPD and mBI indexes for the implants of the control group were significantly higher at baseline than 24 months later ( Student 's t-values of + 3.18 and + 3.33 , respectively ) . Recession and PAL indexes result ed in values significantly lower than baseline ( Student 's t-values of -4.62 and -2.77 , respectively ) . For the implants of the test group PPD and mBI indexes were significantly higher at baseline than 36 months after ( Student 's t-values of + 11.63 and + 16.02 , respectively ) . Recession index result ed in values significantly lower at baseline ( Student 's t-value of -5.05 ) . No statistically significant differences were found between PAL index measurement at baseline and 36 months later ( Student 's t-value of + 0.89 ) . In conclusion , resective therapy associated with implantoplasty seems to influence positively the survival of oral implants affected by inflammatory processes OBJECTIVES The aim of this prospect i ve study was to evaluate a regenerative surgical treatment modality for peri-implantitis lesions on two different implant surfaces . MATERIAL S AND METHODS Twenty-six patients with one crater-like defect , around either TPS ( Control ) or SLA ( Test ) dental implants , with a probing depth ( PD ) ≥6 mm and no implant mobility , were included . The implant surface was mechanically debrided and treated using a 24 % EDTA gel and a 1 % chlorhexidine gel . The bone defect was filled with a bovine-derived xenograft ( BDX ) and the flap was sutured around the non-submerged implant . RESULTS One-year follow-up demonstrated clinical and radiographic improvements . PDs were significantly reduced by 2.1±1.2 mm in the Control implants and by 3.4±1.7 mm in the Test implants . Complete defect fill was never found around Controls , while it occurred in three out of 12 Test implants . Bleeding on probing decreased from 91.1±12.4 % ( Control ) and 75.0±30.2 % ( Test ) to 57.1±38.5 % ( p=0.004 ) and 14.6±16.7 % ( p=0.003 ) , respectively . Several deep pockets ( ≥6 mm ) were still present after surgical therapy around Controls . CONCLUSIONS Surface characteristics may have an impact on the clinical outcome following surgical debridement , disinfection of the contaminated surfaces and grafting with BDX . Complete fill of the bony defect seems not to be a predictable result OBJECTIVES The study aim ed at evaluating the 2-year results obtained following combined surgical resective and regenerative treatment of advanced peri-implantitis defects comparing two methods of surface debridement/decontamination ( DD ) . MATERIAL & METHODS Twenty-four patients ( n = 26 combined supra- and intrabony defects ) completed the 24 months follow-up observation following access flap surgery , granulation tissue removal and implantoplasty at bucally and supracrestally exposed implant parts . The remaining aspects were r and omly allocated to surface DD using either ( i ) an Er : YAG laser ( ERL ) device , or ( ii ) plastic curets + cotton pellets + sterile saline ( CPS ) were augmented with a natural bone mineral and covered with a collagen membrane . RESULTS At 24 months , ERL treated sites failed to reveal significantly higher reductions in mean BOP ( ERL : 75.0 ± 32.6 % versus CPS : 54.9 ± 30.3 % ) and CAL values ( ERL : 1.0 ± 2.2 mm versus CPS : 1.2 ± 2.2 mm ) when compared with the CPS group . In both groups , mean CAL values were not significantly different when compared with baseline . CONCLUSION The long-term stability of clinical outcomes obtained following combined surgical therapy of advanced peri-implantitis may be influenced by factors other than the method of surface debridement/decontamination AIM As the treatment of peri-implantitis-induced bone loss is still a problem , we studied the regenerative treatment of these defects with a mix of autologous bone and a new type of bone graft substitute ( demineralized xenogenic bone graft ) including growth factors . MATERIAL AND METHODS In a prospect i ve manner , 36 cases of peri-implantitis-induced bone loss ( depth > 4 mm ) in 22 patients were followed for 1 year . After resolving the acute infection by local rinsing , granulation tissue was removed . The implants were decontaminated with etching gel and the defects were filled with autologous bone mixed 1:1 with a xenogenic bone graft . The prosthetic reconstructions did not have to be removed . Values of probing depths as well as bone defects were analyzed . RESULTS The radiologic evaluation of the bone defects after regenerative treatment revealed a mean reduction of 3.5 mm comparing the values from 5.1 mm prior to surgery to 1.6 mm 1 year after treatment . Average reduction of the probing depth was 4 mm . The remaining bone defects were larger than 3 mm in 4 out of 36 implants 1 year after treatment . Probing depths of more than 4 mm were present in seven implants . CONCLUSION Within the limits of the study , we conclude that for bone defects larger than 4 mm in case of peri-implantitis , this single surgical intervention provided a reliable method to reduce bone defects |
13,977 | 17,943,796 | These results suggest that children with acute pyelonephritis can be treated effectively with oral antibiotics ( cefixime , ceftibuten and amoxycillin/clavulanic acid ) or with short courses ( 2 to 4 days ) of IV therapy followed by oral therapy .
If IV therapy is chosen , single daily dosing with aminoglycosides is safe and effective . | BACKGROUND Urinary tract infection ( UTI ) is one of the most common bacterial infection in infants .
The most severe form of UTI is acute pyelonephritis , which results in significant acute morbidity and may cause permanent renal damage .
Published guidelines recommend treatment of acute pyelonephritis initially with intravenous ( IV ) therapy followed by oral therapy for seven to 14 days though there is no consensus on the duration of either IV or oral therapy .
OBJECTIVES To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children . | Abstract Urinary tract infections ( UTI ) can cause acute morbidity and may result in severe problems , including hypertension and reduced renal function . Diagnosis of UTI is extremely important since prompt treatment may prevent damage . In the present study we compared the efficacy of oral cefixime to initial intramuscular ceftizoxime followed by cefixime for the treatment of UTI in children . Fifty-four children were studied . They were r and omized to receive either oral cefixime 8 mg/kg/day for 10 days or initial intramuscular ceftizoxime ( Cefızox ) 50 mg/kg twice a day for 2 days followed by oral cefixime for 8 days . Treatment groups were comparable regarding age , sex , clinical , and laboratory findings . Escherichia coli was isolated from 80 % of patients . Repeat urine cultures were sterile within 24 hours in all children . Cure rates were comparable in both groups ( 92 % vs 86 % at the end of treatment ) . No serious adverse effects were observed . We concluded that oral cefixime is a safe and effective alternative treatment Background . The st and ard recommendation for treatment of young , febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials . The availability of potent , oral , third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy . Methods . In a multicenter , r and omized clinical trial , we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection , in terms of short-term clinical outcomes ( sterilization of the urine and defervescence ) and long-term morbidity ( incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans ) . Children received either oral cefixime for 14 days ( double dose on day 1 ) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days . Results . Treatment groups were comparable regarding demographic , clinical , and laboratory characteristics . Bacteremia was present in 3.4 % of children treated orally and 5.3 % of children treated intravenously . Of the short-term outcomes , 1 ) repeat urine cultures were sterile within 24 hours in all children , and 2 ) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously , respectively . Of the long-term outcomes , 1 ) symptomatic reinfections occurred in 4.6 % of children treated orally and 7.2 % of children treated intravenously , 2 ) renal scarring at 6 months was noted in 9.8 % children treated orally versus 7.2 % of children treated intravenously , and 3 ) mean extent of scarring was ∼8 % in both treatment groups . Mean costs were at least twofold higher for children treated intravenously ( $ 3577 vs $ 1473 ) compared with those treated orally . Conclusions . Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection . Use of cefixime will result in substantial reductions of health care expenditures Abstract . The aim of this study was to compare , in children with acute pyelonephritis , the efficacy of 7 days ’ ( group A ) and 3 days ’ ( group B ) intravenous antibiotics , both followed by an oral treatment . Children were r and omized after 3 days of intravenous treatment . Technetium-99 m dimercaptosuccinic acid ( DMSA ) scintigraphy was performed within the first days after admission and repeated 6 months later . Total or partial persistence of renal abnormalities on the 6-month DMSA scintigraphy was used as the endpoint of the study . Among the 92 children included in the study , 87 were followed for at least 6 months ( 43 in group A and 44 in group B ) and were eligible for analysis . Late DMSA was abnormal in 9 kidneys of group A and 12 kidneys of group B , representing respectively 24 % and 44 % of kidneys with abnormalities on the initial DMSA ( difference statistically not significant ) . When the patients were stratified according to the delay of treatment , the percentage of patients with sequelae in group A was comparable , whether the delay was less or more than 1 week . In group B , the percentage of patients with sequelae was significantly higher ( P<0.01 ) when the delay was more than 1 week Objective . To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily ( OD ) gentamicin dosing in children with severe urinary tract infections ( UTI ) . Methods . An open , r and omized , controlled trial comparing OD with three times daily ( TD ) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI . Daily doses ( milligrams per kg per day ) of gentamicin in both groups were 7.5 ( < 5 years old ) , 6.0 ( 5 to 10 years old ) and 4.5 ( > 10 years old ) . Results . There were 179 children enrolled ( 90 OD , 89 TD ) . Baseline clinical characteristics and pathogens were similar , except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group . Median gentamicin treatment duration s were 3.0 ( OD ) and 2.7 ( TD ) days . Mean peak gentamicin concentrations were 17.3 ( OD ) vs. 6.4 ( TD ) mg/l ; 99 % of peak concentrations were > 7 mg/l in the OD group whereas 16 % of peak concentrations were < 5 mg/l in the TD group . Mean trough concentrations were 0.35 ( OD ) vs. 0.55 ( TD ) mg/l . In the OD group 4 % of trough concentrations were ≥2 mg/l , whereas in the TD group only 0.7 % were ≥2 mg/l . Age or prior elevated peak concentrations did not predict high trough concentrations . Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination . There were no clinical or bacteriologic failures . The two disease-related complications were confined to the OD group . No nephro- or ototoxicity was identified . Conclusions . With age-appropriate dosing and measurement of serum trough concentrations before the second dose , OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years The efficacy and safety of netilmicin , 5 mg/kg of body weight once daily or 2 mg/kg thrice daily for 10 days , for the treatment of gram-negative pyelonephritis in children were compared in a prospect i ve , r and omized trial . Explicit criteria were used to define the site of infection , treatment outcome , and adverse effects . Netilmicin was given to 74 children once daily and to 70 children three times daily . At 1 week posttreatment , 73 ( 99 % ) of 74 children treated with netilmicin once daily and 70 ( 100 % ) of 70 children treated with netilmicin three times daily were cured . At 4 weeks posttreatment , no relapse was detected and the rate of reinfection was essentially identical in the two treatment groups . Peak serum netilmicin concentrations were higher in patients given the once-daily regimen , whereas a higher trough level was detected in patients given the three-times-daily regimen . Nephrotoxicity , which was defined as an increase in the serum creatinine level of greater than or equal to 0.3 mg/dl over the baseline , was rare ( 3 % ) and reversible and occurred regardless of the treatment regimen . Ototoxicity , which was assessed by pure-tone audiometry ( 250 to 8,000 Hz ) and brain stem-evoked response ( 6,000 Hz ) , occurred in 2 of 32 children who were evaluated . In these two children , who were given the once-daily regimen , wave V was not evokable monolaterally below 25 and 40 dB normal hearing level , respectively . Thus , it may be possible to treat childhood pyelonephritis with netilmicin once daily . However , this new approach needs to be confirmed in other studies Aim : To examine the safety and efficacy of once‐daily ( OD ) gentamicin treatment compared with conventional 8‐hourly dosing ( TDS ) for urinary tract infection ( UTI ) . Methods : This was a prospect i ve , r and omized , controlled trial of children 1 mo to 13 y of age with presumed UTI . Children were r and omly assigned to OD gentamicin 5 mg kg−1 d−1 or TDS gentamicin 6 mg kg−1 d−1 divided 8 hourly . Microbiological efficacy , nephrotoxicity , ototoxicity and renal scarring were assessed at the end of treatment . Results : 210 patients with presumed UTI were recruited , of whom 172 were analysable ( OD 84 , TDS 88 ) . The median age was 7 mo , 50 % were male and 74 % ( n= 127 ) of patients had pyelonephritis . The majority of infections were due to Escherichia coli ( n= 153 , 89 % ) , of which 9 ( 5.2 % ) were bacteraemic . Comparing the two groups , there was no significant difference in age , gender , duration of fever before admission , pyuria , nitrite positivity or initial total white blood cell count . All patients had negative urine cultures after 2–3 d of treatment , demonstrating 100 % microbiological efficacy . There was no difference between the two groups in terms of ototoxicity , nephrotoxicity , duration of gentamicin treatment or time to fever defervescence BACKGROUND Acute pyelonephritis often leaves children with permanent renal scarring . AIMS To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days . METHODS In a prospect i ve two centre trial , 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy , were r and omly assigned to receive intravenous ceftriaxone ( 50 mg/kg once daily ) for 10 or three days , followed by oral cefixime ( 4 mg/kg twice daily ) to complete a 15 day course . After three months , scintigraphy was repeated in order to diagnose renal scars . RESULTS Renal scarring developed in 33 % of the 110 children in the 10 day intravenous group and 36 % of the 110 children in the three day group . Children older than 1 year had more renal scarring than infants ( 42 % ( 54/129 ) and 24 % ( 22/91 ) , respectively ) . After adjustment for age , sex , duration of fever before treatment , degree of inflammation , presence of vesicoureteric reflux , and the patients ' recruitment centres , there was no significant difference between the two treatments on renal scarring . During follow up , 15 children had recurrence of urinary infection with no significant difference between the two treatment groups . CONCLUSION In children with acute pyelonephritis , initial intravenous treatment for 10 days , compared with three days , does not significantly reduce the development of renal scarring Abstract To investigate the attitude of Belgian pediatricians toward the management and treatment of children with suspected acute pyelonephritis , a short letter was sent to all Belgian pediatricians ( 1200 ) . It contained a brief description of a clinical case strongly suggestive of acute pyelonephritis followed by a series of questions centered on complementary examinations to be performed , need of hospitalization and treatment . A total of 583 responses were received ( 49 % ) . In the acute phase , 99 % of pediatricians perform urine cultures , 87 % blood examinations , and 76 % renal ultrasound . Dimercaptosuccinate ( DMSA ) scintigraphy is performed during the acute phase by 37 % and during follow-up by 32 % of all pediatricians . A voiding cystogram is requested by 71 % . Ambulatory treatment is considered by 30 % of responders . Amoxicillin/clavulanic acid ( 44 % ) and trimethoprim/sulfonamide ( 22 % ) are the most frequently used oral antibiotics . Private pediatricians perform fewer examinations and more frequently consider ambulatory treatment of acute pyelonephritis , compared to pediatricians working in hospitals . Among Belgian pediatricians , attitudes toward the diagnosis and treatment of acute pyelonephritis are heterogeneous . This survey underlines the need for properly documented prospect i ve studies for the evaluation of different treatment modalities in childhood acute pyelonephritis Cefetamet pivoxil was investigated in an open , r and omized comparative study involving a total of 37 children with acute pyelonephritis , whose ages ranged from 2 to 14 years . The patients received either 10 mg/kg ( n = 18 ) or 20 mg/kg ( n = 8) cefetamet pivoxil twice daily , or 30–50 mg/kg amoxycillin/clavulanic acid three times daily ( n = 11 ) for a period of 7–10 days . Escherichia coli was the main causative agent isolated in 28 ( 75.7 % ) of the patients ; other pathogens included Proteus mirabilis ( three patients ) , Proteus species ( one patient ) , Klebsiella pneumoniae ( two patients ) , Pseudomonas diminuta ( one patient ) and mixed infections ( three patients ) . No differences in the overall treatment outcome could be observed between the treatment regimens used and , at the end of treatment , all pathogens were eradicated with neither relapse , nor persistence of the isolated pathogen , nor reinfection occurring . The clinical signs and symptoms had subsided in all patients at treatment end and the tolerability of the trial drugs was found to be satisfactory with no premature treatment withdrawal required . It is concluded that cefetamet pivoxil in the st and ard twice-daily dose of 10 mg/kg was equally effective and as well tolerated as 20 mg/kg cefetamet pivoxil given twice daily or 30–50 mg/kg amoxycillin/clavulanic acid given three times daily Seventy-nine children with symptoms of urinary tract infections were r and omly allocated to treatment with a single dose or a 7-day course of trimethoprim-sulphamethoxazole . Of the 42 patients ( 39 girls , 3 boys ) who fulfilled the criteria for the trial , 23 were given a single-dose regimen and 19 of them a 7-day regimen . Both groups of patients had sterile urine cultures 2 days after starting treatment . Eight patients had underlying structural renal abnormalities ( n = 3 , single-dose regimen ; n = 5 , 7-day regimen ) . One patient in the single dose group had a recurrence of infection on day 7 . These results show that single dose trimethoprim-sulphamethoxazole is as effective as the conventional 7-day course in children with symptomatic urinary tract infection . Further investigation of the renal tract is necessary regardless of the fact that the infection has been eradicated by single-dose treatment We conducted a r and omized prospect i ve multicenter study to compare the safety and efficacy of once daily oral cefixime ( 8 mg/kg ) to twice daily oral trimethoprim/sulfamethoxazole ( TMP/SMX ) ( 8/10 mg/kg/day ) for the treatment of acute urinary traet infection in children ages 6 months to 13 years . Seventy-six patients ( 38 in each group ) were studied . Thirty-seven percent were younger than 3 years of age . Escherichia coli was the most common isolate in both groups ( 85 % ) . Eighty-five percent of all Gramnegative organisms were susceptible to TMP/SMX and all were susceptible to cefixime . Seventy-two percent of all patients were febrile at the time of diagnosis . Both groups were treated for 7 to 10 days . Peripheral white blood Thirty-seven patients with a median age of 5 years with symptomatic lower or upper urinary tract infection , documented by a clean-catch midstream urine culture and sediment examination , completed a r and omized study comparing the effectiveness of a single dose of cefotaxime with 10-day treatment with an antibiotic chosen by in-vitro sensitivities . Eighteen patients were r and omly assigned to the cefotaxime group ( 50 mg/kg/im route ) and 19 patients were placed in the 10-day therapy group . In the cefotaxime group 4/18 patients had an upper urinary tract infection and 11/18 had a history of recurrences . The causal organisms were Escherichia coli ( 16 cases ) and Klebsiella pneumoniae ( two cases ) . All patients had sterile urine 48 hours after therapy , and 2/18 cases had recurred 28 days later . In the 10-day treatment group , 7/19 patients had an upper urinary tract infection , 6/19 had a history of recurrences , 17 cases were caused by E. coli , one case by Citrobacter freundii and one case by K. pneumoniae . Eighteen of 19 patients had sterile urine 48 hours after therapy and 1 case remained symptomatic with positive culture . The other 18 patients had no recurrences . Rates of cures and recurrence in the compared groups were not statistically different ( P greater than 0.05 ) Although urinary tract infections are of particular concern in young children , as they may lead to permanent health problems , there is no consensus for their acute management . We carried out a mailed survey of 455 general practitioners , 143 paediatricians ( r and omly selected from a list of physicians in the Rhône-Alpes region of France ) and 45 paediatric nephrologists ( all the members of the “ Société de Néphrologie Pédiatrique ” ) to examine their attitudes to the management of a fictious case of a young girl with symptoms indicative of acute pyelonephritis . The responses given by the general practitioners and paediatricians were similar , whereas those given by the paediatric nephrologists were often different , for example 20 % of the general practitioners and 17 % of the paediatricians said they would hospitalise the child , compared with 69 % of the paediatric nephrologists . The majority of the general practitioners and paediatricians favoured single oral antibiotic therapy , whereas the paediatric nephrologists were split between single and combined antibiotic therapy , but preferred intravenous administration . The most frequently prescribed drug was a penicillin . The heterogeneity of the results from this survey stresses the need for the assessment of various strategies in terms of their efficacy for preventing kidney scarring and their risk-to-benefit ratios in well- design ed r and omised controlled trials OBJECTIVE To determine whether the addition of a single dose of ceftriaxone sodium to a 10-day course of trimethoprim and sulfamethoxazole hastens urine sterilization or resolution of clinical symptoms in febrile children with urinary tract infections . DESIGN Prospect i ve , single-blind , r and omized study . SETTING Tertiary care children 's hospital emergency department . PATIENTS Febrile children aged 6 months to 12 years with a presumptive urinary tract infection based on history , physical examination , and urinalysis findings . INTERVENTIONS A history was taken , a physical examination and urinalysis and culture were performed , and a white blood cell count and erythrocyte sedimentation rate were obtained . Children were r and omized to receive an intramuscular dose of ceftriaxone then 10 days of trimethoprim-sulfamethoxazole ( IM + PO group ) or oral trimethoprim-sulfamethoxazole alone ( PO group ) . After receiving study medication , patients were discharged from the hospital to return in 48 hours for a follow-up evaluation and urine culture . Treatment failure was defined as the persistence of a positive culture at 48 hours or the need for hospital admission for intravenous rehydration or antibiotic therapy . RESULTS Sixty-nine children were enrolled , 34 in the IM + PO group and 35 in the PO group . The 2 groups were similar at the initial visit with respect to age , sex , clinical degrees of illness , white blood cell count , and erythrocyte sedimentation rate ( P>.05 ) . At the 48-hour follow-up visit , there were no differences between the 2 treatment groups in resolution of vomiting , fever , general appearance , abdominal tenderness , and hydration state ( P>.05 ) . There were 9 treatment failures , 4 in the IM + PO group and 5 in the PO group ( P = .93 ) . CONCLUSION The addition of a single dose of intramuscular ceftriaxone to a 10-day course of oral trimethoprim-sulfamethoxazole for urinary tract infection with fever result ed in no difference at 48 hours in the urine sterilization rate , degree of clinical improvement , or subsequent hospital admission rate In this study we compared the efficacy and safety of isepamicin versus amikacin at a dose of 7.5 mg/kg i.v . q12h for 10 - 14 days in children with pyelonephritis . Sixteen children were enrolled in the study ; ten received isepamicin and six amikacin . Urine cultures grew Escherichia coli in all patients . All patients were treated successfully with either isepamicin or amikacin . Clinical and bacteriological response rates were 100 % for both groups . No adverse events occurred . Peak serum levels ranged from 9.05 to 30.70 mg/l ( median : 16.165 ) and from 12.20 to 25.90 mg/l ( median : 19.05 ) for isepamicin and amikacin , respectively . Trough serum levels ranged from 0.11 to 3.20 mg/l ( median : 0.75 ) and from 0.1 to 2.1 mg/l ( median : 0.655 ) , respectively . Isepamicin was shown to be as effective and safe as amikacin in the treatment of children with pyelonephritis and might prove an advantageous alternative in areas with high incidence of resistance to other aminoglycosides A total of 118 children between 6 months and 10 years of age with acute urinary tract infection were treated in a r and om ; double-blind manner with 12 mg/kg/day of trimethoprim-sulfamethoxazole ( 61 patients ) or 50 mg/kg/day of sulfamethoxazole ( 57 patients ) for ten days . Mean trimethoprim and sulfamethoxazole susceptibilities of Escherichia coli isolated from these patients were 1.2 and 0.6 microgram/ml , respectively . Mean serum concentrations of trimethoprim and sulfamethoxazole were 1.8 and 62 microgram/ml , respectively , one hour after the dose . Of the children who completed the ten days of prescribed medication , clinical and bacteriological cure was confirmed immediately after treatment for all but one patient in each group . Most patients in each treatment group with recurrent infections had underlying urological abnormalities . Severe hematological , renal , or hepatic toxicity requiring interruption of treatment was not encountered . No advantage of trimethoprim-sulfamethoxazole over sulfamethoxazole alone for acute urinary tract infection was demonstrated Sixty-nine children with urinary tract infections were r and omly allocated to single dose gentamicin therapy ( n = 39 ) or a seven day course of an appropriate antibiotic ( n = 30 ) . During the following six weeks the response to treatments did not differ and this was not altered by the child 's clinical diagnosis , past history of infection or presence of radiological abnormalities . The poorest response was in those children with a history of recurrent infections ( p less than 0.01 ) and /or radiological abnormality ( p less than 0.02 ) . Single dose therapy had significantly less suppression upon rectal ( p less than 0.001 ) and periurethral ( p less than 0.02 ) flora . There was a tendency for those not cured by single dose treatment to relapse whereas those treated by conventional therapy tended to be reinfected A double blind , comparative study of the efficacy of cephalexin versus sulfis oxazole was conducted on 100 children with initial episodes of urinary tract infections . The overall bacteriologic and clinical cure rates were comparable for both antimicrobials . Children treated with cephalexin had a clinical cure rate of 86 per cent and a bacterial cure rate of 84 per cent , while those given sulfisoxazole were found to have rates of 82 and 92 per cent respectively . However , cephalexin was noted to have a rather high rate of failure in the therapy of Proteus mirabilis infections ( 4/8 ) , casting some doubt on its use in urinary infections caused by this organism . Untoward effects associated with either medication were minimal The activity of pidotimod ( (R)-3-[(S)-(5-oxo-2-pyrrolidinyl ) carbonyl]-thiazolidine-4-carboxylic acid , PGT/1A , CAS 121808 - 62 - 6 ) was studied vs. placebo in a double-blind , r and omized , multicentre trial , involving 60 pediatric patients with recurrent urinary tract infections . Recovery from acute events was quicker with pidotimod than with placebo ( 9.6 vs. 12.3 days ) . In treated patients antibiotic therapy was shorter ( 6.9 vs. 8.3 days ) and main symptomatic parameters ( body temperature , vesical tenesmus , stranguria , pollakiuria , total number of symptoms , total symptomatic intensity , rate of asymptomatic patients , haematuria , leukocyturia , positive urinary culture ) receded quickly . In patients receiving the drug as well as in patients treated with placebo changes in laboratory parameters were observed , indicating recovery from the acute infectious disease . A significant trend to normalization of the immune response , expressed by chemotaxis and index of leukocyte phagocytosis , was found only in patients treated with pidotimod . After the acute episode a significant decrease of risk of relapses ( 69 % ) was observed in these patients . If a relapse occurs , the response of treated patients is quicker ( duration of fever , total time of relapses ) than for control patients . These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy if the disease occurs and becomes clinical ly relevant . No side effects were observed . Mild reactions ( 4 nausea/vomiting , 1 erythema ) occurred only in 5 patients ( 2 pidotimod , 3 placebo ) but were attributed to concomitant antibiotic therapy . No alterations of main laboratory parameters were found . These findings confirm the tolerability of the drug also in long-term treatment . ( ABSTRACT TRUNCATED AT 250 WORDS It is very important to treat patients with upper urinary tract infections ( UTIs ) promptly and effectively because of the potential sequelae . In the present study we compare the efficacy of the two cephalosporins , ceftriaxone and cefotaxime , in childhood pyelonephritis . The study protocal included 10 days of drug therapy . Both in patients receiving ceftriaxone and cefotaxime , successful eradication was achieved at the second day of therapy . The overall cure rate was significantly better in the ceftriaxone group than the cefotaxime group in terms of recurrence and reinfections ( p < 0.05 ) . Furthermore , in the complicated group , ceftriaxone was slightly superior to cefotaxime , approaching significance in terms of preventing recurrent infections . No serious adverse effects were observed in either of the groups . The present study has shown that ceftriaxone exhibits favorable clinical and bacteriologic efficacy in patients with complicated and uncomplicated upper UTI . Once-daily injection of ceftriaxone in children is also an attractive advantage of the drug when compared to twice-daily cefotaxime Abstract Children older than one year of age with urinary-tract infection were r and omly allocated to treatment for three weeks with co-trimoxazole or ampicillin . Those with a raised serum-creatinine or with bacteria resistant to the allocated drug were excluded . During or within four days of the end of treatment , 11 out of 40 children treated with ampicillin developed recurrent bacteriuria , compared with only 3 out of 55 with co-trimoxazole ; the difference seemed to be more prominent in patients with abnormalities of the urinary tract . In vitro , of 11 strains cultured during recurrent bacteriuria in children treated with ampicillin , all were resistant to ampicillin but all except 1 were sensitive to co-trimoxazole . Of 3 strains appearing in the group treated with co-trimoxazole , 2 were resistant and 1 sensitive to both drugs . For the next three months , prophylactic nitrofurantoin was prescribed ; the rate of recurrent bacteriuria four days after the end of this prophylaxis was not different in the groups treated earlier with either ampicillin or co-trimoxazole . The broader spectrum of antibacterial action is believed to cause the better efficacy of co-trimoxazole . Thrombocytes decreased progressively to below 150,000 per c.mm . in 10 out of 55 children treated with co-trimoxazole , compared with only 1 out of 44 receiving ampicillin . As early as four days after the end of treatment with co-trimoxazole , counts returned to more than 150,000 in all children save 1 . No bleeding occurred in any child . Trimethoprim-induced interference with folate metabolism by inhibition of dihydrofolate reductase is supposed to cause the depression of thrombocytes Abstract . Pylkkänen , J. , Vilska , J. and Koskimies , O. ( The Children 's Hospital , University of Helsinki , Helsinki , Finl and ) . The length of antimicrobial therapy in upper vs. wer urinary tract infection of childhood . Acta Paediatr Sc and , 70 : 885 , 1981.‐235 infants and children were r and omized to a 10‐day and 42‐day treatment group and followed‐up for 12 months after their first urinary tract infection . The anatomical level of each symptomatic infection was determined using simple laboratory criteria . The two regimens prescribed were equally effective in eradicating the infection , but after the discontinuation of the 10‐day treatment with sulfafurazole , 17 ( 23 % ) of 73 patients with their first upper urinary tract infection experienced a recurrence within one month , as compared to only one ( 1 ) of 76 subjects in the 42‐day therapy group . After the phase of early recurrence , there was no difference in recurrence rate between these groups . The early recurrences were associated with the patient 's early age and a short duration of symptoms before therapy . The recurrence rate of first lower UTI after 10‐day therapy was significantly lower than that after 42‐day treatment . The duration of antimicrobial therapy for childhood urinary tract infection should be adjusted according to the patient 's age and the anatomical level of the infection . 10‐day treatment may not be sufficient to prevent early recurrence of pyelonephritic infections in infants under 6 months of age |
13,978 | 28,830,074 | Antimicrobial prophylaxis and metaphylaxis demonstrated moderate , yet highly variable relative risk reductions in BRD morbidity .
These were dependent on the antimicrobial classes used , dependent on metaphylaxis definition , BRD attack rates and duration of the RCTs .
Best relative risk reductions were from broad‐spectrum critically important antimicrobials , or combinations .
BRD prophylaxis/metaphylaxis represents major antimicrobial consumption for highly variable short‐term gains in absolute risk reduction of morbidity/mortality . | & NA ; A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications ( prophylaxis , metaphylaxis ) to healthy individuals .
The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease ( i.e. morbidity ) and /or die ( i.e. mortality ) .
Bovine respiratory disease ( BRD ) represents the major indication for cattle antimicrobials worldwide .
The objectives were to perform a systematic review and meta‐ analysis of r and omised controlled clinical trials ( RCTs ) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality . | The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals . Comparisons were made among calves receiving an " on-arrival " injection of tilmicosin , calves receiving a single injection of long-acting oxytetracycline , and calves receiving no prophylaxis . Morbidity and mortality attributable to pneumonia , morbidity and mortality attributable to all causes , and case fatality were significantly lower in the group of calves that received tilmicosin , compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic . Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis , compared with those that received no antibiotic on arrival at the feedlot . Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline . Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group . The majority of mortalities were attributable to fibrinous pneumonia ( 31/34 ) . Important bacterial isolates ( Pasteurella spp , Haemophilus somnus , Actinomyces pyogenes ) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia . However , bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates The objectives of this study were to determine ( i ) whether an association exists between individual pharmacokinetic parameters and treatment outcome when feeder cattle were diagnosed with bovine respiratory disease ( BRD ) and treated with gamithromycin ( Zactran ( ® ) ) at the label dose and ( ii ) whether there was a stronger association between treatment outcome and gamithromycin concentration in plasma or in the pulmonary epithelial lining fluid ( PELF ) effect compartment . The study design was a prospect i ve , blinded , r and omized clinical trial utilizing three groups of 60 ( 362 - 592 lb ) steers/bulls r and omly allocated within origin to sham injection or gamithromycin mass medication . Cattle were evaluated daily for signs of BRD by a veterinarian blinded to treatment . Animals meeting the BRD case definition were enrolled and allocated to a sample collection scheme consisting of sample s for bacterial isolation ( bronchoalveolar lavage fluid and nasopharyngeal swabs ) and gamithromycin concentration determination ( PELF and plasma ) . Gamithromycin susceptibility of M. haemolytica ( n = 287 ) and P. multocida ( n = 257 ) were determined using broth microdilution with frozen panels containing gamithromycin at concentrations from 0.03 to 16 μg/mL. A two-compartment plasma pharmacokinetic model with an additional compartment for gamithromycin in PELF was developed using rich data sets from published and unpublished studies . The sparse data from our study were then fit to this model using nonlinear mixed effects modeling to estimate individual parameter values . The result ing parameter estimates were used to simulate full time-concentration profiles for each animal in this study . These profiles were analyzed using noncompartmental methods so that PK/PD indices ( AUC24 /MIC , AUC∞ /MIC , CMAX /MIC ) could be calculated for plasma and PELF ( also T > MIC ) for each individual . The calculated PK/PD indices were indicative that for both M. haemolytica and P. multocida a higher drug exposure in terms of concentration , and duration of exposure relative to the MIC of the target pathogen , was favorable to a successful case outcome . A significant association was found between treatment success and PELF AUC0 - 24 /MIC for P. multocida . The calves in this study demonstrated an increased clearance and volume of distribution in plasma as compared to the healthy calves in two previously published reports . Ultimately , the findings from this study indicate that higher PK/PD indices were predictive of positive treatment outcomes The conduct of r and omized controlled trials in livestock with production , health , and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports . The objective of this project was to modify the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to reflect the unique aspects of reporting these livestock trials . A two-day consensus meeting was held on November 18 - 19 , 2008 in Chicago , IL , United States of America , to achieve the objective . Prior to the meeting , a Web-based survey was conducted to identify issues for discussion . The 24 attendees were biostatisticians , epidemiologists , food-safety research ers , livestock-production specialists , journal editors , assistant editors , and associate editors . Prior to the meeting , the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials . The consensus meeting result ed in the production of the REFLECT ( Reporting Guidelines For R and omized Control Trials ) statement for livestock and food safety ( LFS ) and 22-item checklist . Fourteen items were modified from the CONSORT checklist , and an additional sub-item was proposed to address challenge trials . The REFLECT statement proposes new terminology , more consistent with common usage in livestock production , to describe study subjects . Evidence was not always available to support modification to or inclusion of an item . The use of the REFLECT statement , which addresses issues unique to livestock trials , should improve the quality of reporting and design for trials reporting production , health , and food-safety outcomes Feedlot calves ( n = 3784 ) were systematic ally r and omized and allocated in a 2 × 2 factorial study to receive metaphylactic oxytetracycline ( OTC ) on arrival or no antimicrobial , as well as florfenicol once subcutaneously or twice intramuscularly ( 48 h apart ) if diagnosed with bovine respiratory disease ( BRD ) . Calves of different treatment groups were comingled and followed from placement to re-implantation ( ~100 days ) . Animals receiving OTC had a reduced risk of BRD , an increased risk of arthritis , and no significant differences in average daily gain , BRD relapse , overall mortality , or BRD mortality . There were no significant differences between treatment protocol s. Deep nasal swabs ( n = 233 ) taken at arrival ( n = 122 ) , treatment ( n = 77 ) , and swabs from lungs and joints at postmortem ( n = 34 ) were cultured for Mycoplasma bovis from 61 animals ill or dying of chronic pneumonia and arthritis and from 61 healthy calves . There was significant variation in diversity among isolates ( n = 51 ) between study years and different cattle . Metaphylaxis or antimicrobial treatment did not affect the diversity of isolates . Except for tilmicosin , isolates were largely susceptible to tested antimicrobials The efficacy of tulathromycin in the treatment ( phase 1 ) and prevention ( phase 2 ) of bovine respiratory disease ( BRD ) was evaluated on commercial farms in France , Germany , Italy , and Spain . In phase 1 , commingled cattle with clinical BRD were treated with tulathromycin ( n = 128 ) or florfenicol ( n = 125 ) on day 0 . Similar percentages of animals showed sustained clinical improvement at day 14 ( tulathromycin 83.3 % versus florfenicol 81.0 % ) and had not relapsed by day 60 ( tulathromycin 63.3 % versus florfenicol 58.4 % ) . In phase 2 , healthy in-contact cattle were treated with tulathromycin ( n = 492 ) , tilmicosin ( n = 494 ) , or saline ( n = 265 ) on day 0 . Significantly more ( P = .0001 ) tulathromycin-treated cattle remained healthy to day 14 ( 92.4 % ) than tilmicosin-treated ( 83.7 % ) or saline-treated ( 63.7 % ) cattle , and this was maintained through day 60 ( tulathromycin 85.4 % versus tilmicosin 75.1 % and saline 56.2 % ) . Tulathromycin was highly effective in the treatment and prevention of BRD OBJECTIVE To determine effects of vaccination prior to transit and prophylactic administration of florfenicol at time of arrival at a feedyard on health of cattle and colonization of the nasopharynx by Mannheimia haemolytica ( MH ) . ANIMALS 121 steers from Tennessee and 84 steers from New Mexico . PROCEDURE Half of the steers were vaccinated before transport to a feedyard . Steers from Tennessee were vaccinated with MH bacterin-toxoid , and steers from New Mexico were vaccinated intranasally with modified-live leukotoxin-deficient MH . Half of the vaccinates and nonvaccinates were r and omly selected to receive florfenicol on arrival at the feedyard . Steers were observed daily for respiratory tract disease ( RTD ) . RESULTS Administration of florfenicol at time of arrival reduced the incidence of RTD , delayed the interval before onset of RTD , and reduced the incidence of MH colonization of the nasopharynx for at least 4 days , but vaccination did not have any effect . Vaccination elicited an increase in serum antibody titers to MH . Administration of florfenicol at time of arrival reduced the development of serum antibody titers in intranasally vaccinated steers and both groups of nonvaccinated steers , but intranasal vaccination did not affect colonization by wild-type MH . CONCLUSIONS AND CLINICAL RELEVANCE Administration of florfenicol at time of arrival decreased the incidence of MH organisms in the nasopharynx and delayed the onset of RTD . Prophylactic use of suitable antibiotics is likely to reduce the incidence of acute RTD in calves for several days after arrival at feedyards , which is the period when they are most susceptible to infectious organisms The effectiveness of a feed-additive antimicrobial combination for improving feedlot performance and health was tested using 4325 high-risk feeder calves r and omly allocated to a control group or an experimental group . The experimental group received the conventional ration plus a feed additive containing 700 mg per head/day of chlortetracycline and sulfamethazine from arrival at the feedlot to day 56 of the feeding period . The inclusion of the feed additive to the ration significantly improved average daily gain for days 0 - 28 ( P = 0.0163 ) and 0 - 56 ( P = 0.0001 ) , and the feed conversion for days 0 - 28 ( P = 0.0061 ) and 0 - 56 ( P = 0.0004 ) . Additionally , the use of the feed additive significantly reduced the rate of bovine respiratory disease morbidity for days 0 - 28 ( P = 0.0014 ) and 0 - 56 ( P = 0.0001 ) , the rate of relapses and mortality for days 0 - 56 ( P = 0.0151 and P = 0.0209 , respectively ) , and the rate of animals diagnosed with chronic respiratory disease for days 0 - 28 and 0 - 56 ( P = 0.0009 and P = 0.0002 , respectively ) . Performance and health improvements produced by the use of the feed additive were cost-effective Three trials were conducted to evaluate the use of tilmicosin phosphate ( Micotil ) as a prophylactic medication for newly received , stressed beef cattle . In Trial 1 , 57 beef calves ( average initial BW = 170 kg ) were shipped to the research feedlot from Tennessee and either given no antibiotic at processing or treated with Micotil at 10 mg of tilmicosin phosphate/kg of BW . During a 28-d receiving period , treatment at processing with Micotil did not affect daily gain ( P < .17 ) or DMI ( P < .22 ) compared to control calves . Prophylactic treatment with Micotil decreased ( P < .01 ) the percentage of calves treated for symptoms of bovine respiratory disease from 46.4 to 0 % . In Trial 2 , 117 calves ( average initial BW = 191 kg ) were shipped from Tennessee and allotted r and omly to the same two treatments as in Trial 1 . All calves grazed a 24-ha pasture of irrigated winter wheat during the 28-d receiving period . Treatment of calves with Micotil at the time of arrival processing did not affect ( P > .50 ) daily gain during the trial ; however , as in Trial 1 , mass treatment with Micotil decreased ( P < .01 ) the percentage of calves treated for respiratory disease from 32.8 % to 12.1 % . In Trial 3 , two truckloads of beef calves ( 183 total ; average initial BW = 232 kg ) shipped from Tennessee were allotted r and omly to the same two treatments used in Trials 1 and 2 or to a third treatment that consisted of administration of Micotil at arrival processing if the rectal temperature of the calf was > or = 39.7 degrees C. ( ABSTRACT TRUNCATED AT 250 WORDS The objectives of this study were to 1 ) quantify effects of metaphylactic treatment for bovine respiratory disease ( BRD ) on growth performance , carcass characteristics , and lung lesion prevalence and severity ; 2 ) evaluate the association of lung lesion prevalence and severity with carcass characteristics ; and 3 ) evaluate effects of therapeutic treatment on carcass characteristics and lung lesion prevalence and severity . The study was conducted at a commercial feedlot in the Texas Panh and le in which steers ( n = 2,336 ) initially weighing 312.1 ± 9.6 kg were source d from auction markets and allocated in a r and omized complete block design to 1 of 3 treatments ( no metaphylactic [ no antimicrobial drug { ND } ] treatment , tilmicosin at 10 mg/kg BW [ TIL ] , and tulathromycin at 2.5 mg/kg BW [ TUL ] ) . Lungs of all steers were evaluated during harvest to assess presence and severity of pneumonic lesions in the anteroventral lobes and the presence and severity of pleural adherences . Compared to the ND treatment , steers treated via metaphylactic therapy had greater ( P < 0.05 ) metaphylactic cost , ADG , shrunk final BW , dressed carcass yield , HCW , 12th rib fat , calculated empty body fat ( EBF ) , and gross revenue , concurrent with reduced ( P < 0.05 ) BRD treatment costs and financial losses from BRD death and railed cattle , cumulatively result ing in greater financial returns . Lung lesions were present in 64.3 % of lungs and were distributed similarly between metaphylactic treatments ( 63.9 % ) and ND ( 65.1 % ) cattle . Steers with advanced lung lesions present at harvest were associated with reduced ( P < 0.05 ) HCW , KPH , 12th rib fat , calculated yield grade s , marbling scores , and calculated EBF as compared to steers without lung lesions . Steers pulled for BRD had increased ( P < 0.01 ) incidence of advanced lung lesions , mortality , and railers with decreased ( P < 0.05 ) HCW , 12th rib fat , KPH , marbling score , calculated EBF , and percentage choice carcasses when compared to non-BRD event steers . From the results of this study , controlling BRD through the use of metaphylactic treatments on arrival in heavier cattle improved financial returns primarily driven by reductions in cost of death loss and railers A r and omized , controlled , blinded clinical trial was performed at a research feedlot in western Canada . Auction-market-derived steers ( n = 288 ) were r and omly assigned to 1 of 3 treatments : 1 ) no antimicrobials on arrival ; 2 ) oxytetracycline in the starter ration for 14 d ; and 3 ) long-acting oxytetracycline subcutaneously on day 0 . Minimal inhibitory concentrations of 7 antimicrobials were determined for 3 generic fecal E. coli isolates per animal on arrival and throughout the feeding period . There was a low prevalence of antimicrobial resistance in generic E. coli isolates from calves on arrival . There were increased proportions of cattle with resistant E. coli isolates early in the feeding period among calves in groups 2 and 3 . Individual animal treatments were not associated with increased proportions of cattle with resistant E. coli isolates preslaughter . There was no difference in the proportion of animals with E. coli isolates resistant to tetracycline between the treatment groups preslaughter . However , there were significantly more animals with tetracycline resistant isolates of E. coli preslaughter than at arrival OBJECTIVE To examine the effectiveness of mass medication with long acting antibiotics at feedlot entry on lot-fed Australian domestic cattle during a period of high risk for bovine respiratory disease ( BRD ) . DESIGN Systematic allocation at feedlot entry of tilmicosin , long acting oxytetracycline or no antibiotic treatment , to cattle lot fed for the Australian domestic market . Comparisons of growth rate , disease occurrence and mortality were made between the groups at the conclusion of the feeding period . RESULTS Cattle medicated with tilmicosin at 10 mg/kg body weight on entry to the feedlot grew 0.08 kg/d faster than cattle medicated with oxytetracycline at 20 mg/kg body weight and non-medicated cattle . There was no significant difference in growth rate between oxytetracycline medicated cattle and cattle not medicated with antibiotic at feedlot entry . Cattle medicated with tilmicosin at feedlot entry had 8 fewer cases of disease per 100 animals compared with cattle not medicated with antibiotic at feedlot entry . There was no significant difference in disease occurrence between oxytetracycline medicated cattle and those not medicated with antibiotic at feedlot entry . CONCLUSION Mass medication with tilmicosin at feedlot entry of cattle destined for the Australian domestic market may be used to reduce disease occurrence and increase growth rate during periods of high risk for BRD The efficacy of tulathromycin in decreasing the incidence of morbidity and mortality due to bovine respiratory disease ( BRD ) in 1,239 high-risk cattle was investigated at four US feedlots . Calves not exhibiting clinical signs of BRD received one of three treatments administered subcutaneously in the neck : physiologic saline at 0.02 ml/kg , tulathromycin at 2.5 mg/kg , or tilmicosin at 10 mg/kg . Each treatment group consisted of 413 calves . Calves with clinical signs of BRD and rectal temperatures of 104 degrees F or higher on days 1 through 14 were considered treatment failures ( BRD morbidity ) . Nasopharyngeal swabs from saline-treated morbidities were su bmi tted for isolation and identification of BRD organisms . Respiratory disease morbidity was highest in calves treated with saline and significantly ( P < or = .0001 ) lower in calves administered tulathromycin or tilmicosin . Morbidity from BRD was significantly ( P < or = .0001 ) higher in calves treated with tilmicosin than in calves treated with tulathromycin . Under conditions of this study , tulathromycin , given to calves at high risk of developing BRD , was significantly more effective in reducing BRD morbidity when compared to both saline- and tilmicosin-treated calves |
13,979 | 29,270,615 | Conclusion and Relevance Checkpoint inhibitors , compared with docetaxel , are associated with significantly prolong overall survival in second-line therapy in NSCLC . | Importance Checkpoint inhibitors have replaced docetaxel as the new st and ard second-line therapy in advanced non – small cell lung carcinoma ( NSCLC ) , but little is known about the potential predictive value of clinical and molecular characteristics .
Objective To estimate the relative efficacy of checkpoint inhibitor vs docetaxel overall and in subgroups defined by clinicopathological characteristics . | BACKGROUND We assessed the efficacy and safety of programmed cell death 1 ( PD-1 ) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study . We also sought to define and vali date an expression level of the PD-1 lig and 1 ( PD-L1 ) that is associated with the likelihood of clinical benefit . METHODS We assigned 495 patients receiving pembrolizumab ( at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks ) to either a training group ( 182 patients ) or a validation group ( 313 patients ) . We assessed PD-L1 expression in tumor sample s using immunohistochemical analysis , with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 ( proportion score ) . Response was assessed every 9 weeks by central review . RESULTS Common side effects that were attributed to pembrolizumab were fatigue , pruritus , and decreased appetite , with no clear difference according to dose or schedule . Among all the patients , the objective response rate was 19.4 % , and the median duration of response was 12.5 months . The median duration of progression-free survival was 3.7 months , and the median duration of overall survival was 12.0 months . PD-L1 expression in at least 50 % of tumor cells was selected as the cutoff from the training group . Among patients with a proportion score of at least 50 % in the validation group , the response rate was 45.2 % . Among all the patients with a proportion score of at least 50 % , median progression-free survival was 6.3 months ; median overall survival was not reached . CONCLUSIONS Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer . PD-L1 expression in at least 50 % of tumor cells correlated with improved efficacy of pembrolizumab . ( Funded by Merck ; KEYNOTE-001 Clinical Trials.gov number , NCT01295827 . ) Purpose : Although clinical studies have shown promise for targeting programmed cell death protein-1 ( PD-1 ) and lig and ( PD-L1 ) signaling in non – small cell lung cancer ( NSCLC ) , the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood . Experimental Design : We performed an integrated analysis on the multiple-dimensional data types including genomic , transcriptomic , proteomic , and clinical data from cohorts of lung adenocarcinoma public ( discovery set ) and internal ( validation set ) data base and immunotherapeutic patients . Gene set enrichment analysis ( GSEA ) was used to determine potentially relevant gene expression signatures between specific subgroups . Results : We observed that TP53 mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature . More importantly , the TP53/KRAS comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of PD-L1+/CD8A+ . Meanwhile , TP53- or KRAS-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high ( TH ) cohort . Further analysis focused on the potential molecular mechanism revealed that TP53 or KRAS mutation altered a group of genes involved in cell-cycle regulating , DNA replication and damage repair . Finally , immunotherapeutic analysis from public clinical trial and prospect i ve observation in our center were further confirmed that TP53 or KRAS mutation patients , especially those with co-occurring TP53/KRAS mutations , showed remarkable clinical benefit to PD-1 inhibitors . Conclusions : This work provides evidence that TP53 and KRAS mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti – PD-1/PD-L1 immunotherapy . Clin Cancer Res ; 23(12 ) ; 3012–24 . © 2016 AACR 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 , The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression . These changes distinguish cancer cells from their normal counterparts , allowing tumours to be recognized as foreign by the immune system . However , tumours are rarely rejected spontaneously , reflecting their ability to maintain an immunosuppressive microenvironment . Programmed death-lig and 1 ( PD-L1 ; also called B7-H1 or CD274 ) , which is expressed on many cancer and immune cells , plays an important part in blocking the ‘ cancer immunity cycle ’ by binding programmed death-1 ( PD-1 ) and B7.1 ( CD80 ) , both of which are negative regulators of T-lymphocyte activation . Binding of PD-L1 to its receptors suppresses T-cell migration , proliferation and secretion of cytotoxic mediators , and restricts tumour cell killing . The PD-L1–PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections . Blocking PD-L1 should therefore enhance anticancer immunity , but little is known about predictive factors of efficacy . This study was design ed to evaluate the safety , activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A . Here we show that across multiple cancer types , responses ( as evaluated by Response Evaluation Criteria in Solid Tumours , version 1.1 ) were observed in patients with tumours expressing high levels of PD-L1 , especially when PD-L1 was expressed by tumour-infiltrating immune cells . Furthermore , responses were associated with T-helper type 1 ( TH1 ) gene expression , CTLA4 expression and the absence of fractalkine ( CX3CL1 ) in baseline tumour specimens . Together , these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1 , and is re-invigorated on antibody treatment 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 Introduction : The Blueprint Programmed Death Lig and 1 ( PD‐L1 ) Immunohistochemistry ( IHC ) Assay Comparison Project is an industrial‐academic collaborative partnership to provide information on the analytical and clinical comparability of four PD‐L1 IHC assays used in clinical trials . Methods : A total of 39 NSCLC tumors were stained with four PD‐L1 IHC assays ( 22C3 , 28‐8 , SP142 , and SP263 ) , as used in the clinical trials . Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity . Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs . Results : Analytical comparison demonstrated that the percentage of PD‐L1–stained tumor cells was comparable when the 22C3 , 28‐8 , and SP263 assays were used , whereas the SP142 assay exhibited fewer stained tumor cells overall . The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining . Of the 38 cases , 19 ( 50.0 % ) were classified above and five ( 13 % ) were classified below the selected cutoffs of all assays . For 14 of the 38 cases ( 37 % ) , a different PD‐L1 classification would be made depending on which assay/scoring system was used . Conclusions : The Blueprint PD‐L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained . All of the assays demonstrated immune cell staining , but with greater variability than with tumor cell staining . By comparing assays and cutoffs , the study indicated that despite similar analytical performance of PD‐L1 expression for three assays , interchanging assays and cutoffs would lead to “ misclassification ” of PD‐L1 status for some patients . More data are required to inform on the use of alternative staining assays upon which to read different specific therapy‐related PD‐L1 cutoffs 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 Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC . METHODS The open-label , phase 1 , multicohort study ( CheckMate 012 ) cohorts reported here were enrolled at eight US academic centres . Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV , chemotherapy-naive NSCLC . Patients were r and omly assigned ( 1:1:1 ) by an interactive voice response system to receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks , nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks , or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression , unacceptable toxicities , or withdrawal of consent . Data from the latter two cohorts , which were considered potentially suitable for further clinical development , are presented in this report ; data from the other cohort ( as well as several earlier cohorts ) are described in the appendix . The primary outcome was safety and tolerability , assessed in all treated patients . This ongoing study is registered with Clinical Trials.gov , number NCT01454102 . FINDINGS Between May 15 , 2014 , and March 25 , 2015 , 78 patients were r and omly assigned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks ( n=38 ) or nivolumab every 2 weeks plus ipilimumab every 6 weeks ( n=40 ) . One patient in the ipilimumab every-6-weeks cohort was excluded before treatment ; therefore 77 patients actually received treatment ( 38 in the ipilimumab every-12-weeks cohort ; 39 in the ipilimumab every-6-weeks cohort ) . At data cut-off on Jan 7 , 2016 , 29 ( 76 % ) patients in the ipilimumab every-12-weeks cohort and 32 ( 82 % ) in the ipilimumab every-6-weeks cohort had discontinued treatment . Grade 3 - 4 treatment-related adverse events occurred in 14 ( 37 % ) patients in the ipilimumab every-12-weeks cohort and 13 ( 33 % ) patients in the every-6-weeks cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( three [ 8 % ] and no patients ) , pneumonitis ( two [ 5 % ] and one [ 3 % ] patients ) , adrenal insufficiency ( one [ 3 % ] and two [ 5 % ] patients ) , and colitis ( one [ 3 % ] and two [ 5 % ] patients ) . Treatment-related serious adverse events were reported in 12 ( 32 % ) patients in the ipilimumab every-12-weeks cohort and 11 ( 28 % ) patients in the every-6-weeks cohort . Treatment-related adverse events ( any grade ) prompted treatment discontinuation in four ( 11 % ) patients in the every-12-weeks cohort and five ( 13 % ) patients in the every-6-weeks cohort . No treatment-related deaths occurred . Confirmed objective responses were achieved in 18 ( 47 % [ 95 % CI 31 - 64 ] ) patients in the ipilimumab every-12-weeks cohort and 15 ( 38 % [ 95 % CI 23 - 55 ] ) patients in the ipilimumab every-6-weeks cohort ; median duration of response was not reached in either cohort , with median follow-up times of 12·8 months ( IQR 9·3 - 15·5 ) in the ipilimumab every-12-weeks cohort and 11·8 months ( 6·7 - 15·9 ) in the ipilimumab every-6-weeks cohort . In patients with PD-L1 of 1 % or greater , confirmed objective responses were achieved in 12 ( 57 % ) of 21 patients in the ipilimumab every-12-weeks cohort and 13 ( 57 % ) of 23 patients in the ipilimumab every-6-weeks cohort . INTERPRETATION In NSCLC , first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response . To our knowledge , the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC , supporting further assessment of this combination in a phase 3 study . FUNDING Bristol-Myers Squibb 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 PURPOSE Programmed death 1 is an immune checkpoint that suppresses antitumor immunity . Nivolumab , a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody , was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts . We report overall survival ( OS ) , response durability , and long-term safety in patients with non-small-cell lung cancer ( NSCLC ) receiving nivolumab in this trial . PATIENTS AND METHODS Patients ( N = 129 ) with heavily pretreated advanced NSCLC received nivolumab 1 , 3 , or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks . Tumor burden was assessed by RECIST ( version 1.0 ) after each cycle . RESULTS Median OS across doses was 9.9 months ; 1- , 2- , and 3-year OS rates were 42 % , 24 % , and 18 % , respectively , across doses and 56 % , 42 % , and 27 % , respectively , at the 3-mg/kg dose ( n = 37 ) chosen for further clinical development . Among 22 patients ( 17 % ) with objective responses , estimated median response duration was 17.0 months . An additional six patients ( 5 % ) had unconventional immune-pattern responses . Response rates were similar in squamous and nonsquamous NSCLC . Eighteen responding patients discontinued nivolumab for reasons other than progressive disease ; nine ( 50 % ) of those had responses lasting > 9 months after their last dose . Grade 3 to 4 treatment-related adverse events occurred in 14 % of patients . Three treatment-related deaths ( 2 % of patients ) occurred , each associated with pneumonitis . CONCLUSION Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC . R and omized clinical trials with nivolumab in advanced NSCLC are ongoing |
13,980 | 31,275,523 | Friction force increased after intraoral aging in most of the studies .
However , there is lack of good quality evidence in this research area .
Conclusions Brackets present increased surface roughness after clinical use , and consequently increased coefficient of friction ( COF ) and Friction Force . | Background To evaluate the bracket-wire friction force after clinical use . | INTRODUCTION Self-ligating orthodontic brackets rely on clips , rather than ligatures , to hold the archwire in place . It is unknown whether replacing ligatures with clips affects the adherence of Streptococcus mutans . The aim of this research was to evaluate whether self-ligating brackets have an advantage over conventional brackets as determined by the adherence of S mutans . METHODS The sample consisted of 50 esthetic brackets , divided into 3 experimental groups and 2 control groups of 10 brackets each . Two experimental groups were active self-ligating brackets ( QuicKlear ; Forestadent , Pforzheim , Germany ; and In-Ovation C ; Dentsply GAC , Bohemia , NY ) ; the other was a passive self-ligating bracket ( Damon 3 ; Ormco , Glendora , Calif ) . The 2 control groups were conventional brackets ( Mystique ; Dentsply GAC ; and Clarity ; 3 M Unitek , Monrovia , Calif ) . The brackets were r and omly bonded to the canines , first and second premolars , and first and second molars in the m and ibular left hemiarch of 10 male participants . Biofilm was collected from the tooth surfaces before bonding and from the brackets on day 21 and placed in Petri dishes containing Mitis salivarius agar . The brackets were removed on day 28 and examined by using scanning electron microscopy . Statistical analysis , analysis of variance , and the Tukey correction with a P value of 0.05 were used . RESULTS The greatest numbers of colonies were found in an active self-ligating bracket group ( In-Ovation C ) , and the fewest colonies were in a conventional bracket group ( Clarity ) . The largest colonies formed on active self-ligating brackets . In the slot , the greatest formation was in a control group ( Mystique ) . CONCLUSIONS Self-ligating esthetic brackets do not promote greater or lesser S mutans colonization when compared with conventional brackets . Differences were found to be related to the material composition of the bracket INTRODUCTION Enamel decalcification is a common problem in orthodontics . The objectives of this r and omized clinical study were to enumerate and compare plaque bacteria surrounding 2 bracket types , self-ligating ( SL ) vs elastomeric ligating ( E ) , and to determine whether adenosine triphosphate (ATP)-driven bioluminescence could be used for rapid assessment of bacterial load in plaque . METHODS Patients ( ages , 11 - 17 years ) were bonded with SL and E brackets in 14 maxillary and 12 m and ibular arches by using a split-mouth design . Recall visits were at 1 and 5 weeks after bonding . Plaque specimens were assayed for oral bacteria and subjected to ATP-driven bioluminescence determinations with a luciferin-based assay . RESULTS In most patients , teeth bonded with SL attachments had fewer bacteria in plaque than did teeth bonded with E brackets . At 1 and 5 weeks after bonding , the means for SL vs E brackets were statistically lower for total bacteria and oral streptococci ( P < 0.05 ) . ATP bioluminescence values were statistically correlated to the total oral bacteria and oral streptococci , with correlation coefficients of 0.895 and 0.843 , respectively . CONCLUSIONS SL appliances promote reduced retention of oral bacteria , and ATP bioluminescence might be a useful tool in the rapid quantification of bacterial load and the assessment of oral hygiene during orthodontic treatment 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 Abstract . Aim : The purpose of the present study was to investigate the composition and to assess the microhardness and structure of asreceived , retrieved , and recycled stainless steel brackets . Material s and Methods : New , used , and recycled br and - , slot size- , and prescription-matched appliances were subjected to scanning electron microscopy ( SEM ) , energy dispersive ( EDS ) electron probe micro analysis , metallographic analysis , and Vickers microhardness testing . Elemental analysis was performed on r and omly selected bulk material base and wing areas . Basic metal content and microhardness results were statistically analyzed using a two-way ANOVA and the Tukey test , with treatment ( asreceived , retrieved , and recycled ) and bracket region ( base , wing ) serving as discriminating variables ( α = 0.05 ) . Results : The results showed that there was no alteration in the bulk composition of the brackets among the three conditions . In contrast , differences were noted between bracket base and wing with respect to elemental composition among all groups , implying that the base and wings were manufactured from different alloys . The metallographic etching identified no difference in grain structure between the bracket base and wing components for all groups , regardless of treatment . Vickers microhardness demonstrated significant differences in hardness between base and wing for all groups and between recycled and retrieved states for the wing component . Zusammenfassung . Ziel : Das Ziel dieser Studie war die Untersuchung der Zusammensetzung und die Bestimmung der Mikrohärte und Struktur von fabrikneuen , gebrauchten und recycelten Stahlbrackets . Material und Method en : Neue , gebrauchte und recycelte Brackets , die von einem Hersteller stammten und in Slotgröße und Vorprogrammierung übereinstimmten , wurden der Rasterelektronenmikroskopie ( SEM ) , der energiedispersiven Röntgenmikroanalyse ( EDS ) , der metallographischen Analyse und dem Vickers-Mikrohärtetest unterzogen . Eine elementare Analyse wurde an zufällig ausgewählten Bracketbasen und -flügeln durchgeführt . Die Ergebnisse der elementaren metallischen Best and teile und der Mikrohärte wurden statistisch mithilfe einer zweifaktoriellen Varianzanalyse ( ANOVA ) und eines Tukey-Tests untersucht , wobei die Vorbeh and lung ( fabrikneu , gebraucht und recycelt ) und die Bracketregion ( Basis , Flügel ) als diskriminierende Variablen dienten ( α = 0,05 ) . Ergebnisse : Die Ergebnisse zeigten , dass i m Bereich der Bracketbasen keine Veränderungen zwischen den drei Gruppen festzustellen waren . Es wurden hingegen Unterschiede zwischen Bracketbasis und -flügel hinsichtlich der elementaren Zusammensetzung in allen Gruppen beobachtet . Dies impliziert , dass Basen und Flügel aus verschiedenen Legierungen hergestellt wurden . Die metallographische Ätzung ergab bei allen Gruppen keinen Unterschied in der Kornstruktur der Bracketbasen und -flügel , ungeachtet ihrer Vorbeh and lung . Die Mikrohärte nach Vickers zeigte bei allen Gruppen signifikante Unterschiede bezüglich der Härte zwischen Basis und Flügel sowie zwischen recycelten und gebrauchten Flügelkomponenten |
13,981 | 20,393,966 | More participants experienced adverse events with codeine 60 mg than placebo ; the difference was not significant and none were serious .
Single dose codeine 60 mg provides good analgesia to few individuals , and does not compare favourably with commonly used alternatives such as paracetamol , NSAIDs and their combinations with codeine , especially after dental surgery ; the large difference between dental and other surgery was unexpected . | BACKGROUND Codeine is an opioid metabolised to active analgesic compounds , including morphine .
It is widely available by prescription , and combination drugs including low doses of codeine are commonly available without prescription .
OBJECTIVES To assess the efficacy , the time to onset of analgesia , the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain . | Ketoprofen , 25 , 50 , and 100 mg , was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth . Treatment was self-administered as a single oral dose under double-blind conditions in five parallel groups established by a r and om code in healthy young adults . Based on 129 patient evaluations of pain experience and pain relief , ketoprofen was shown to have a more rapid onset and longer duration of action than codeine . In the derived variables of SPID ( Sum of Pain Intensity Differences ) and TOPAR ( Total Pain Relief ) , all three doses of ketoprofen , with no dose-related differences among them , were found to provide statistically superior analgesia to codeine and placebo . All five treatments were associated with some adverse reactions Summary The efficacy and safety of ciramadol ( Cir ) as an analgesic in relieving moderate to severe pain after oral surgery has been studied in 79 patients r and omly assigned to receive single oral doses of Cir 15 , 30 or 60 mg , codeine 60 mg or placebo . During the 6-hour observation period , the three ciramadol-treated groups indicated greater pain relief than the codeine 60 mg or placebo groups . In general , Cir 60 mg was significantly more effective than codeine 60 mg , and all doses of Cir were superior to placebo . The proportion of patients in each Cir group reporting adverse experiences was significantly higher than in either the placebo or codeine groups . The experimental system proved very effective in demonstrating analgesic potency of Cir . The very high incidence of side-effects in the three ciramadol-treated groups makes it unfit for further clinical use in ambulant patients Meclofenamate sodium , a nonsteroidal anti-inflammatory drug with proven analgesic effects , was compared at two dose levels ( 200 mg and 100 mg ) with codeine ( 60 mg ) and placebo in a double-blind , r and omized study of 327 women experiencing episiotomy pain after normal delivery . Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief , and it had a longer duration of action . Adverse effects were minimal , and their frequency did not differ significantly among treatment groups . Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy 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 Tramadol hydrochloride is a novel , central ly acting analgesic with two complementary mechanisms of action : opioid and aminergic . Relative to codeine , tramadol has similar analgesic properties but may have fewer constipating , euphoric , and respiratory depressant effects . A two-center r and omized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg , tramadol 50 mg , codeine 60 mg , aspirin ( ASA ) 650 mg with codeine 60 mg , and placebo . Using a third molar extraction pain model , 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug . Of the 200 patients enrolled , seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up . Using st and ard measures of analgesia , including total pain relief score ( TOTPAR ) , maximum pain relief score ( MaxPAR ) , sum of pain intensity difference scores ( SPID ) , peak pain intensity difference ( Peak PID ) , remedication , and global evaluations , all active treatments were found to be numerically superior to placebo . ASA/codeine was found to be statistically superior to placebo for all measures of efficacy . Tramadol 100 mg was statistically superior to placebo for TOTPAR , SPID , and time of remedication , whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time . Codeine was not found to be statistically superior to placebo for any efficacy measure . A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study . The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different . Gastrointestinal side effects ( nausea , dysphagia , vomiting ) were reported more frequently with tramadol 100 mg , ASA/ codeine , and codeine 60 mg than with placebo In a double‐blind , r and omized , single‐dose trial the analgesic contribution of acetaminophen , 1000 mg , and codeine , 60 mg , was determined . The study was a 2 × 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of : 1000 mg acetaminophen , 60 mg codeine , 1000 mg acetaminophen plus 60 mg codeine , or placebo . The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant ( P < 0.05 ) contribution to the analgesic effectiveness of the combination on all measures of efficacy ( sum of pain intensity differences , largest pain intensity difference , total pain relief , largest pain relief , and time to remedication ) . The incidence of adverse effects did not appear to differ among the treatments , including placebo & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely To evaluate the analgesic efficacy of orally administered 50 mg propiram fumarate , 650 mg aspirin , 60 mg codeine phosphate , and placebo in acute post-impaction dental pain , 159 patients with moderate or severe pain were r and omly allocated to the four treatments in this single-dose double-blind , stratified , parallel-group study . A research nurse question ed the patients at 1/2 hour and hourly for 6 hours after medicating . A st and ard format was used to question subjects about their pain intensity and relief from the starting pain . Propiram , 50 mg , produced a level of analgesia approaching that of 650 mg aspirin in peak effect , total effect , and duration of action and was statistically superior to 60 mg codeine and placebo for every measure of analgesic efficacy . Several mild adverse effects were observed ; however , they appeared to be evenly distributed among the active treatments In a double-blind study , 198 out patients with pain after oral surgery were r and omly assigned to treatment with a single oral dose of naproxen sodium 550 mg , codeine sulfate 60 mg , a combination of naproxen sodium 550 mg with codeine sulfate 60 mg , aspirin 650 mg or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medication . Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia ; the codeine effect was significant for total and peak pain relief and patients ' overall evaluation . The naproxen-codeine interaction was not statistically significant for any measure , which suggests that the analgesic effect of the combination represents the additive effect of its constituents . Based on pairwise comparisons , aspirin was significantly superior to placebo for most measures of effect , naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients ' overall evaluation . No more patients experienced adverse effects with aspirin or naproxen than with placebo , but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo , codeine , and ibuprofen after oral surgery . Eighty-one patients undergoing complicated dental extraction s were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg , 30 minutes before surgery . After surgery , patients self administered one of three possible postsurgical medications , which included placebo , codeine 60 mg , and ibuprofen 400 mg , when their pain reached a moderate or severe intensity . The study was double-blind with the three postsurgical treatments being r and omly allocated within each presurgical treatment block . Pain intensity , pain relief , pain half gone , and overall evaluations were assessed for up to 6 hours . Ibuprofen was significantly more efficacious ( p < .05 ) than codeine or placebo for most analgesic measures . The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine . Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen , but surprisingly prolonged ( p < .05 ) the duration of its action . The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response , but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data A r and omized double-blind trial was carried out in 54 women to evaluate the effectiveness of ciramadol in a single ( 60 or 30 mg ) oral dose regimen , compared with 60 mg codeine and placebo , in the treatment of post-episiotomy pain . Ciramadol gave a significantly better analgesic effect , at both 2 and 6 hours , and produced negligible side-effects . Codeine did less well than placebo in this study To evaluate relative efficacy , safety , and time course of analgesia , propiram fumarate ( 50 and 100 mg ) , a new narcotic agonist-antagonist , was compared with codeine sulfate ( 60 mg ) and placebo in a clinical trial with a single peroral dose , parallel , stratified , r and omized , and double-blind design involving 80 hospitalized postpartum women with medium or severe episiotomy pain . Using verbal subjective reports as index of response , patients rated pain intensity and side effects at periodic interviews for 6 h. Relative efficacy findings based on peak effects and summed pain-intensity differences suggested dose-dependent analgesia with propiram and also that 60 mg codeine lay between 50 mg propiram and placebo . Moreover , after 50 or 100 mg propiram , 8 of 20 patients reported greater than 50 % reduction of initial pain compared with 7 of 20 after 60 mg codeine and 2 of 20 after placebo . After each of the propiram doses , distinct analgesia began within 1/2 h and reached peak effect between 1 h ( p less than 0.02 ) and 2 h ( p less than 0.05 ) . After f60 mg codeine , onset was slower and peak later ( 4 h , p less than 0.05 ) . All three active drugs continued to act until the 5th or 6th h. Drowsiness was the only statistically significant side effect reported after propiram . These results suggest that single 50 or 100 mg doses of propiram were effective in episiotomy pain , induced stronger analgesia than 60 mg codeine , and took effect more rapidly A double-blind , r and omized trial was carried out in 90 patients to compare the analgesic and anti-inflammatory efficacy of 500 mg diflunisal twice daily with that of 25 mg codeine phosphate 4-times daily and placebo in relieving pain and swelling after surgical removal of impacted third molars . Diflunisal was found to be superior to codeine and placebo on the first post-operative day , but the difference in efficacy of the drugs had diminished by the third post-operative day . In the diflunisal group of 30 patients , 10 ( 33 % ) developed ' dry socket ' or alveolitis sicca dolorosa . Only 2 patients in the codeine group and 1 patient in the placebo group developed this very painful condition . The possible explanation of ' dry socket ' is discussed Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone , codeine sulfate 60 mg alone , and placebo . One hundred ninety‐five patients with severe pain result ing from episiotomy , cesarean section , or gynecologic surgery completed a r and omized , double‐blind , stratified , parallel‐group study . Patients were observed during a 4‐hour period after medication . Based on the sum of the pain intensity differences ( SPID ) , total pain relief ( TOTPAR ) , and most of the hourly direct measures of pain and relief , both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo . Codeine 60 mg was statistically superior to placebo based on TOTPAR , the global ratings , and a few hourly measures . The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone ½ , 1 , and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID , TOTPAR , and other measures as well . The low‐dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg . Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg , particularly in the first few hours after medication , is more efficacious than its constituents Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of propiram fumarate 50 mg , codeine sulfate 60 mg and placebo in the relief of moderate to severe postoperative pain . One hundred and twenty patients completed a r and omized , double-blind , single-dose , stratified , parallel-groups trial and were observed for either 4 or 6 hours . Based upon each of the summary efficacy measures --SPID , % SPID and TOTAL -- propiram and codeine were approximately equally effective and both were statistically superior to placebo . Propiram was significantly more effective than codeine at hour 5 for Pain Intensity Difference . Two adverse effects were attributed to propiram . Propiram fumarate 50 mg is an effective oral analgesic similar to codeine sulfate 60 mg , with the possibility of a longer duration of action Meclofenamate sodium , a nonsteroidal anti-inflammatory agent , was compared at two dose levels ( 100 mg and 200 mg ) with codeine ( 60 mg ) and placebo in a double-blind , r and omized study of 218 women after normal vaginal delivery . The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain . Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity . The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain . Adverse experiences with the study medications were minimal ( 6.4 % ) . Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium . Meclofenamate sodium is a safe , effective analgesic for acute episiotomy pain & 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 Codeine , a relatively weak oral narcotic agent , is the most frequently prescribed oral opiate drug . It is also frequently utilized as a control drug in comparative analgesic efficacy studies . These studies are often single dose analysis of pain relief following surgery or childbirth . We conducted a single dose , post-operative analysis of 116 patients who were r and omly assigned to receive codeine 60 mg , acetaminophen 600 mg , the combination of codeine and acetaminophen at these doses , or a placebo . Only the combination agent was uniformly superior to placebo . Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis . A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic , in acceptable oral doses , in the single dose setting . Previous reports , however , suggest that the multiple doses of codeine may afford adequate analgesia . Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult A double‐blind , r and omized , parallel‐group study compared the analgesic efficacy of a single oral dose of 500 mg diflunisal , 60 mg codeine , 500 mg diflunisal plus 60 mg codeine given as separate agents , and placebo in 161 patients with moderate to severe postoperative pain . St and ard subjective measures were used to evaluate analgesia . Eight‐hour sum of pain intensity differences and total pain relief scores for all active treatments were significantly better than were those for placebo ( p < 0.05 ) . Diflunisal plus codeine performed the best followed by diflunisal , codeine , and placebo . Diflunisal plus codeine was better than placebo from 1½ to 8 hours ( p < 0.01 ) , better than codeine from 1½ to 6 hours ( p < 0.05 ) , and better than diflunisal alone from ½ to 1½ hours ( p < 0.05 ) for most measures of analgesia . Factorial analysis demonstrated a significant early codeine effect and a significant diflunisal effect throughout . No significant treatment group differences were observed regarding adverse effects . Our data demonstrate that diflunisal plus codeine is generally well tolerated and provides analgesia superior to that of diflunisal or codeine alone in the treatment of moderate to severe postoperative pain A double‐blind , parallel study was conducted to evaluate the analgesic effect and safety of a single 25 mg oral dose of picenadol , a central ly acting analgesic , and to compare it with a 60 mg dose of codeine and a placebo in patients with postoperative pain . Two sites using similar protocol s enrolled a total of 178 in patients with postoperative pain . Pain intensity , relief , and adverse experiences were then measured for up to 6 hours after administration of the test medications . Both picenadol and codeine were significantly more effective than placebo in reducing pain intensity ( mean sum of pain intensity difference scores : picenadol 5.21 , codeine 5.19 , and placebo 2.82 ) and increasing total relief ( mean total pain relief : picenadol 10.21 , codeine 11.07 , and placebo 6.96 ) . Adverse experience profiles were similar among the three treatment groups Two r and omized , double-blind , single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain . Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo . A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours , with a global assessment made at the completion of 24 hours . Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables , including the sum of the pain intensity differences ( SPID ) , total pain relief ( TOTAL ) , percent SPID , duration of effect , and time to remedication . Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures . Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication . Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo . Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication . Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference ( PID ) and relief scores , as well as for SPID and TOTAL . Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL . Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID , TOTAL , and hourly measures beginning with Hour 6 through Hour 12 . Piroxicam 20 mg was significantly better than aspirin for a few hourly measures : Hours 7 to 9 for relief and Hour 7 for PID . In addition , effects of piroxicam 20 mg had a significantly longer duration than aspirin . Similarly , piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo . The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given , under double-blind , r and omized conditions , a single dose of either codeine 60 mg , aspirin 650 mg , ibuprofen 400 mg , aspirin 650 mg + codeine 60 mg , ibuprofen 400 mg + codeine 60 mg , or placebo . A total of 249 subjects were included in the statistical analysis . On a report form , subjects recorded pain intensity , pain relief , and side effects hourly for four hours . They also gave an overall impression at the end of the observation period . Analysis of variance and pairwise contrasts were used to analyze the data . For the sum of pain intensity differences , the total of the hourly pain relief scores , and overall impression , there was a significant analgesic effect for codeine , aspirin , and ibuprofen and no significant interaction when they were used in combination . Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination . The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter , but it was not statistically superior to ibuprofen alone . The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model . There was no notable difference in the frequency or intensity of side effects among the treatment groups , and no subject had to withdraw due to an adverse effect . This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination . Codeine added a small amount of additional analgesia when used in combination with ibuprofen A single-dose , r and omized , double-blind , parallel-treatment study was performed in 200 out patients with acute pain caused by the surgical removal of impacted third molars . Meclofenamate 100 mg plus codeine 60 mg , meclofenamate 50 mg plus codeine 30 mg , meclofenamate 100 mg , codeine 60 mg , and placebo treatment groups were compared for sum of pain intensity differences , peak pain intensity difference , sum of pain relief scores , peak pain relief , number of observations at which pain was half relieved , overall evaluation of effectiveness , and time to remedication with a backup analgesic . Meclofenamate 100 mg plus codeine 60 mg was significantly more effective ( P less than .005 ) than codeine 60 mg for all variables except number of observations at which pain was half relieved . Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective ( P less than .005 ) than placebo for all variables . Eleven adverse experiences were reported in 7 patients ( 3.5 % ) ; the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg , in 2 treated with meclofenamate 50 mg plus codeine 30 mg , and in 1 treated with codeine 60 mg Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Meclofenamate sodium was compared , double-blind , with codeine and placebo for the treatment of acute episiotomy pain . One hundred sixty-eight women with moderate or severe episiotomy pain after normal delivery were assigned r and omly to one of four treatment groups : one received meclofenamate sodium 200 mg at dose 1 and 100 mg at doses 2 and 3 ; one received meclofenamate sodium 100 mg at dose 1 and 50 mg at doses 2 and 3 ; one received codeine 60 mg at all three doses ; and one received placebo at all three doses . Efficacy measurements were evaluated periodically for 6 hours after medication . After the first administration , both doses of meclofenamate sodium were significantly superior to placebo and to codeine from 2 - 6 hours in pain intensity difference and pain relief . For second and third doses , data were available for too few patients to allow valid analysis and interpretation . Adverse effects occurred in 4 patients in each meclofenamate sodium group , and in 8 in the codeine group and in 6 in the placebo group . The study indicates that single 100- and 200-mg doses of meclofenamate sodium are as safe as , and significantly more effective than , codeine 60 mg or placebo for episiotomy pain |
13,982 | 28,722,116 | No conclusions can be drawn about efficacy or harm in the use of opioids to treat cancer-related pain in children and adolescents .
As a result , there is no RCT evidence to support or refute the use of opioids to treat cancer-related pain in children and adolescents | BACKGROUND Pain is a common feature of childhood and adolescence around the world , and for many young people , that pain is chronic .
The World Health Organization ( WHO ) guidelines for pharmacological treatments for children 's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world .
Views on children 's pain have changed over time and relief of pain is now seen as important .
In the past , pain was largely dismissed and was frequently left untreated , and it was assumed that children quickly forgot about painful experiences .
We design ed a suite of seven review s in chronic non-cancer pain and cancer pain ( looking at antidepressants , antiepileptic drugs , non-steroidal anti-inflammatory drugs , opioids , and paracetamol ) to review the evidence for children 's pain using pharmacological interventions .As one of the leading causes of mortality and morbidity for children and adolescents in the world today , childhood cancer ( and its associated pain ) is a major health concern .
Cancer pain in infants , children , and adolescents is primarily nociceptive pain with negative long term effects .
Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs .
Cancer-related pain generally occurs as a result of perioperative procedures , nerve damage caused by radiation or chemotherapy treatments , or mucositis .
Opioids are used worldwide for the treatment of pain .
To achieve adequate pain relief in children using opioids , with an acceptable grade of adverse effects , the recommended method is to start with a low dose gradually titrated to effect or unacceptable adverse effect in the child .
OBJECTIVES To assess the analgesic efficacy , and adverse events , of opioids used to treat cancer-related pain in children and adolescents aged between birth and 17 years , in any setting . | & NA ; The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy ( DPN ) . The post hoc analysis is based on a 12 week , multinational , placebo‐controlled trial of pregabalin in which 401 patients were r and omized to treatment . Study measures included the Brief Pain Inventory short‐form ( BPI‐sf ) , EQ‐5D and other patient‐reported outcomes . Cutpoints were derived on the BPI‐sf 0–10 average pain numeric rating scale [ NRS ] to classify pain grade s of “ mild ” ( 1–3 ) , moderate ( 4–6 ) and severe ( 7–10 ) , adjusting for geographical regions where data were collected . Two different metrics were used to classify the importance of change in pain severity from baseline to 12 weeks : changes in pain severity grade s ( defined by cutpoint categories ) and percent reduction in the NRS ( categories ranging from 0–9 % to ≥50 % ) . An improvement in one pain grade or a ≥30 % reduction in the NRS served as determinants of a clinical ly important difference . Patients with a one‐ grade reduction in pain severity , either from “ severe‐to‐moderate ” or “ moderate‐to‐mild , ” had a 3‐point improvement the BPI‐sf Pain Interference Index ( PII ; a composite measure of function ) ; a reduction from “ severe‐to‐mild ” pain corresponded to a 6‐point improvement in the PII . Similarly , a reduction in the NRS of ≥30 % and ≥50 % corresponded to a 3‐point and a 5‐point improvement in the PII , respectively . Changes in pain were also associated with changes in health status . Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinical ly important changes in function and health status OBJECTIVES ( 1 ) To assess the feasibility and tolerability of the therapeutic transdermal fentanyl system ( TTS-fentanyl ) by using a clinical protocol developed for children with cancer pain . ( 2 ) To estimate the pediatric pharmacokinetic parameters of TTS-fentanyl . METHODS The drug was administered in open-label fashion ; and measures of analgesia , side effects , and skin changes were obtained for a minimum of 2 doses ( 6 treatment days ) . Blood specimens were analyzed for plasma fentanyl concentrations . The pharmacokinetics of TTS-fentanyl were estimated by using a mixed effect modeling approach . RESULTS Treatment was well tolerated . Ten of the 11 patients who completed the 2 doses continued treatment with TTS-fentanyl . The duration of treatment ranged from 6 to 275 days . The time to reach peak plasma concentration ranged from 18 hours to > 66 hours in patients receiving the 25 microg/h patch . Compared with published pharmacokinetic data from adults , the mean clearance and volume of distribution of transdermal fentanyl were the same , but the variability was less . CONCLUSIONS Treatment of children with TTS-fentanyl is feasible and well tolerated and yields fentanyl pharmacokinetic parameter estimates similar to those for adults . A larger study is required to confirm these findings and further test the clinical protocol & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy The World Health Organization ( WHO ) guidelines for the treatment of cancer pain recommend nonopioid analgesics as first-line therapy , so-called " weak " analgesics combined with nonopioid analgesics as second-line therapy , and so-called " strong " opioids ( with nonopioid analgesics ) only as third-line therapy . However , these guidelines can be question ed with regard to the extent of efficacy as well as the rationale for not using strong opioids as first-line treatment , especially in terminal cancer patients . The purpose of this r and omized study was to prospect ively compare the efficacy and tolerability of strong opioids as first-line agents with the recommendations of the WHO in terminal cancer patients . One hundred patients with mild-moderate pain were r and omized to treatment according to WHO guidelines or to treatment with strong opioids . Evaluated outcomes included pain intensity , need for change in therapy , quality of life , Karnofsky Performance Status , general condition of the patient , and adverse events . No between-treatment differences were observed for changes in quality of life or performance status , but patients started on strong opioids had significantly better pain relief than patients treated according to WHO guidelines ( P=0.041 ) . Additionally , patients started on strong opioids required significantly fewer changes in therapy , had greater reduction in pain when a change was initiated , and reported greater satisfaction with treatment than the comparator group ( P=0.041 ) . Strong opioids were safe and well-tolerated , with no development of tolerance or serious adverse events . These data suggest the utility of strong opioids for first-line treatment of pain in patients with terminal cancer |
13,983 | 21,530,321 | Arthroscopic stabilization was the preferred strategy after a primary anterior glenohumeral dislocation .
In clinical setting s where the likelihood of recurrent instability is low after nonoperative care or when an informed patient has an aversion to surgery , nonoperative treatment may be the preferred treatment strategy | BACKGROUND The optimal management strategy for primary traumatic anterior glenohumeral dislocation remains controversial .
Patients have traditionally been managed nonoperatively , but high recurrence rates in certain population s have led to increased interest in early operative stabilization .
The purpose of this study was to use expected-value decision analysis to determine the optimal management strategy --nonoperative treatment or arthroscopic stabilization -- for a first-time traumatic anterior shoulder dislocation . | BACKGROUND The prevalence and risk factors for recurrent instability and functional impairment following a primary glenohumeral dislocation remain poorly defined in younger patients . We performed a prospect i ve cohort study to evaluate these outcomes . We also aim ed to produce guidelines for the design of future clinical trials , assessing the efficacy of interventions design ed to improve the outcome after a primary dislocation . METHODS We performed a prospect i ve cohort study of 252 patients ranging from fifteen to thirty-five years old who sustained an anterior glenohumeral dislocation and were treated with sling immobilization , followed by a physical therapy program . Patients received regular clinical follow-up to assess whether recurrent instability had developed . Functional assessment s were made and were compared for two subgroups : those who had not had instability develop and those who had received operative stabilization to treat recurrent instability . RESULTS On survival analysis , instability developed in 55.7 % of the shoulders within the first two years after the primary dislocation and increased to 66.8 % by the fifth year . The younger male patients were most at risk of instability , and 86.7 % of all of the patients known to have recurrent instability had this complication develop within the first two years . A small but measurable degree of functional impairment was present at two years after the initial dislocation in most patients . Sample -size calculations revealed that a relatively small number of patients with a primary dislocation would be required in future clinical trials examining the effects of interventions design ed to reduce the prevalence of recurrent instability and improve the functional outcome . CONCLUSIONS Recurrent instability and deficits of shoulder function are common after primary nonoperative treatment of an anterior shoulder dislocation . There is substantial variation in the risk of instability , with younger males having the highest risk and females having a much lower risk . Future clinical trials to evaluate primary interventions should evaluate the prevalence of recurrent instability and functional deficits , with use of an assessment tool specifically for shoulder instability , during the first two years after the initial dislocation There are many measurement tools for assessing patients ’ shoulder symptoms ( pain ) and function ( what patients can do ) , but they do not measure activity ( how often a patient engages in activity ) . This is relevant because activity level can have an important impact on a patient ’s outcome . Our goal was to develop a short , easy to administer measure of shoulder activity which could be used to predict outcome of shoulder disorders . The activity scale was developed using established principles : item generation , item reduction , pretesting , and reliability and validity testing . The activity rating is a numerical sum of scores for five activities rated on a five-point frequency scale from never performed ( 0 points ) to daily ( 4 points ) . Patients were scored on the following criteria : carrying an object 8 lb or heavier by h and , h and ling objects overhead , weight training with arms , swinging motion ( ie , hitting tennis or golf ball ) , and lifting objects 25 lb or heavier . Two additional multiple choice questions provide a score assessing participation in contact and overhead sports . The activity scale showed excellent reliability and construct validity . It can be completed quickly and used in conjunction with patient-based measures of shoulder outcome to define patient population s for cohort studies , and to assess activity level as a prognostic factor in patients with shoulder disorders . Level of Evidence : Prognostic study , Level I. See the Guidelines for Authors for a complete description of levels of evidence BACKGROUND Anterior dislocation of the glenohumeral joint in younger patients is associated with a high risk of recurrence and persistent functional deficits . The aim of this study was to assess the efficacy of a primary arthroscopic Bankart repair , while controlling for the therapeutic effects produced by the arthroscopic intervention and joint lavage . METHODS In a single-center , double-blind clinical trial , eighty-eight adult patients under thirty-five years of age who had sustained a primary anterior glenohumeral dislocation were r and omized to receive either an arthroscopic examination and joint lavage alone or together with an anatomic repair of the Bankart lesion . Assessment of the rate of recurrent instability , functional outcome ( with use of three scores ) , range of movement , patient satisfaction , direct health-service costs , and treatment complications was completed for eighty-four of these patients ( forty-two in each group ) during the subsequent two years . RESULTS In the two years after the primary dislocation , the risk of a further dislocation was reduced by 76 % and the risk of all recurrent instability was reduced by 82 % in the Bankart repair group compared with the group that had arthroscopy and lavage alone . The functional scores were also better ( p < 0.05 ) , the treatment costs were lower ( p = 0.012 ) , and patient satisfaction was higher ( p < 0.001 ) after arthroscopic repair . The improved functional outcome appeared to be mediated through the prevention of instability since the functional outcome in patients with stable shoulders was similar , irrespective of the initial treatment allocation . The patients who had a Bankart repair and played contact sports were also more likely to have returned to their sport at two years ( relative risk = 3.4 , p = 0.007 ) . CONCLUSIONS Following a first-time anterior dislocation of the shoulder , there is a marked treatment benefit from primary arthroscopic repair of a Bankart lesion , which is distinct from the so-called background therapeutic effect of the arthroscopic examination and lavage of the joint . However , primary repair does not appear to confer a functional benefit to patients with a stable shoulder at two years after the dislocation Background Nonoperative treatment of traumatic shoulder dislocations leads to a high rate of recurrent dislocations . Hypothesis Early arthroscopic treatment for shoulder dislocation will result in a lower recurrence rate than nonoperative treatment . Study Design Prospect i ve , r and omized clinical trial . Methods Two groups of patients were studied to compare nonoperative treatment with arthroscopic Bankart repair for acute , traumatic shoulder dislocations in young athletes . Fourteen nonoperatively treated patients underwent 4 weeks of immobilization followed by a supervised rehabilitation program . Ten operatively treated patients underwent arthroscopic Bankart repair with a bioabsorbable tack followed by the same rehabilitation protocol as the nonoperatively treated patients . The average follow-up was 36 months . Results Three patients were lost to follow-up . Twelve nonoperatively treated patients remained for follow-up . Nine of these ( 75 % ) developed recurrent instability . Six of the nine have required subsequent open Bankart repair for recurrent instability . Of the nine operatively treated patients available for follow-up , only one ( 11.1 % ) developed recurrent instability . Conclusions Arthroscopic stabilization of traumatic , first-time anterior shoulder dislocations is an effective and safe treatment that significantly reduces the recurrence rate of shoulder dislocations in young athletes when compared with conventional , nonoperative treatment BACKGROUND An initial anterior dislocation of the shoulder becomes recurrent in 66 % to 94 % of young patients after immobilization of the shoulder in internal rotation . Magnetic resonance imaging and studies of cadavera have shown that coaptation of the Bankart lesion is better with the arm in external rotation than it is with the arm in internal rotation . Our aim was to determine the benefit of immobilization in external rotation in a r and omized controlled trial . METHODS One hundred and ninety-eight patients with an initial anterior dislocation of the shoulder were r and omly assigned to be treated with immobilization in either internal rotation ( ninety-four shoulders ) or external rotation ( 104 shoulders ) for three weeks . The primary outcome measure was a recurrent dislocation or subluxation . The minimum follow-up period was two years . RESULTS The follow-up rate was seventy-four ( 79 % ) of ninety-four in the internal rotation group and eighty-five ( 82 % ) of 104 in the external rotation group . The compliance rate was thirty-nine ( 53 % ) of seventy-four in the internal rotation group and sixty-one ( 72 % ) of eighty-five in the external rotation group ( p = 0.013 ) . The intention-to-treat analysis revealed that the recurrence rate in the external rotation group ( twenty-two of eighty-five ; 26 % ) was significantly lower than that in the internal rotation group ( thirty-one of seventy-four ; 42 % ) ( p = 0.033 ) with a relative risk reduction of 38.2 % . In the subgroup of patients who were thirty years of age or younger , the relative risk reduction was 46.1 % . CONCLUSIONS Immobilization in external rotation after an initial shoulder dislocation reduces the risk of recurrence compared with that associated with the conventional method of immobilization in internal rotation . This treatment method appears to be particularly beneficial for patients who are thirty years of age or younger BACKGROUND During 1978 and 1979 , we initiated a prospect i ve multicenter study to evaluate the results of nonoperative treatment of primary anterior shoulder dislocation . In the current report , we present the outcome after twenty-five years . METHODS Two hundred and fifty-five patients ( 257 shoulders ) with an age of twelve to forty years who had a primary anterior shoulder dislocation were managed with immobilization ( achieved by tying the arm to the torso with use of a b and age ) or without immobilization . All 227 living patients ( 229 shoulders ) completed the follow-up question naire , and 214 patients completed the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire . RESULTS Ninety-nine ( 43 % ) of 229 shoulders had not redislocated , and seventeen ( 7 % ) redislocated once . Thirty-three recurrent dislocations had become stable over time ( 14.4 % ) , and eighteen were considered to be still recurrent ( 7.9 % ) . Sixty-two shoulders ( 27 % ) had undergone surgery for the treatment of recurrent instability . Immobilization after the primary dislocation did not change the prognosis . Only two of twenty-four shoulders with a fracture of the greater tuberosity at the time of the primary dislocation redislocated ( p < 0.001 ) . When shoulders with a fracture of the greater tuberosity were excluded , forty-four ( 38 % ) of 115 shoulders in patients who had been twelve to twenty-five years of age at the time of the original dislocation and sixteen ( 18 % ) of ninety shoulders in patients who had been twenty-six to forty years of age had undergone surgical stabilization . At twenty-five years , fourteen ( 23 % ) of sixty-two shoulders that had undergone surgical stabilization were in patients who subsequently had a contralateral dislocation , compared with seven ( 7 % ) of ninety-nine shoulders in patients in whom the index dislocation had been classified as solitary ( p = 0.01 ) . Gender and athletic activity did not appear to affect the redislocation rate ; however , women had worse DASH scores than men did ( p = 0.006 ) . CONCLUSIONS After twenty-five years , half of the primary anterior shoulder dislocations that had been treated nonoperatively in patients with an age of twelve to twenty-five years had not recurred or had become stable over time PURPOSE To compare the results of arthroscopic repair in acute anterior shoulder traumatic dislocation with those of nonoperative treatment . TYPE OF STUDY A prospect i ve nonr and omized study was performed . METHODS Between August 1989 and April 1997 , 46 patients were seen after a first episode of traumatic anterior shoulder dislocation . The average age was 21 years ( range , 17 to 27 years ) . Most dislocations were in rugby players ( 36 patients ) . There were 18 patients treated by nonoperative methods and 28 patients treated by acute arthroscopic repair ; 22 patients using transglenoid suture and 6 patients with bone anchor suture fixation . RESULTS Of the patients treated nonoperatively , 94.5 % suffered a redislocation between 4 and 18 months ( average , 6 months ) . In the operative group , 96 % of the patients ( 27 ) obtained excellent results according to the Rowe scale . Only 1 patient suffered a redislocation 1 year after surgery . Three different types of lesions were found during surgery : group I , capsular tear with no labrum lesion ( 4 % ) ; group II , capsular tear with partial labrum detachment ( 32 % ) ; and group III , capsular tear and full anterior labrum detachment ( 64 % ) . The average follow-up was 67.4 months ( range , 28 to 120 ) . There were no surgical complications . CONCLUSIONS The operative group obtained 96 % excellent results , but the nonoperative group only obtained 5.5 % excellent results , according to the Rowe scale . The nonoperative group showed a high incidence of redislocation ( 94.5 % ) compared with the operative group ( 4 % ) . Based on the findings of this study , we recommend using an arthroscopic evaluation and repair after an initial anterior traumatic shoulder dislocation in young athletes A prospect i ve study evaluating nonoperative treatment versus arthroscopic Bankart suture repair for acute , ini tial dislocation of the shoulder was undertaken in young athletes . All patients met the following criteria : 1 ) sus tained an acute first-time traumatic anterior dislocation , 2 ) no history of impingement or occult subluxation , 3 ) the dislocation required a manual reduction , and 4 ) no concomitant neurologic injury . Thirty-six athletes ( average age , 20 years ) met the criteria for inclusion . Group I patients were immobilized for 1 month followed by rehabilitation ; they were allowed full activity at 4 months . Group II patients underwent arthroscopic Bankart repair followed by the same protocol as Group I. Group I consisted of 15 athletes . Twelve patients ( 80 % ) developed recurrent instability ; 7 of the 12 have required open Bankart repair for recurrent instability . Group I consisted of 21 patients ; 18 patients ( 86 % ) had no recurrent instability at last followup ( average , 32 months ; range , 15 to 45 ) ( P = 0.001 ) . One patient in Group II has required a subsequent open Bankart repair to treat symptomatic recurrence ( P = 0.005 ) . In this study , arthroscopic Bankart repair significantly reduced the recurrence rate in young athletes who sustained an acute , initial anterior dislocation of the shoulder Background Acute or recurrent anterior shoulder instability is a frequent injury for in-season athletes . Treatment options for this injury include shoulder immobilization , rehabilitation , and shoulder stabilization surgery . Purpose To determine if in-season athletes can be returned to their sports quickly and effectively after nonoperative treatment for an anterior instability episode . Methods Over a 2-year period , 30 athletes matched the inclusion criteria for this study . Nineteen athletes had experienced anterior dislocations , and 11 had experienced subluxations . All were treated with physical therapy and fitted , if appropriate , with a brace . These athletes were followed for the number of recurrent instability episodes , additional injuries , subjective ability to compete , and ability to complete their season or seasons of choice . Results Twenty-six of 30 athletes were able to return to their sports for the complete season at an average time missed of 10.2 days ( range , 0 - 30 years ) . Ten athletes suffered sport-related recurrent instability episodes ( range , 0 - 8 years ) . An average of 1.4 recurrent instability episodes per season per athlete occurred . There were no further injuries attributable to the shoulder instability . Sixteen athletes underwent surgical stabilization for their shoulders during the subsequent off-season . Conclusions Most of the athletes were able to return to their sport and complete their seasons after an episode of anterior shoulder instability , although 37 % experienced at least 1 additional episode of instability during the season PURPOSE To report the long-term results of a prospect i ve r and omized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation after a first traumatic anterior dislocation of the shoulder . TYPE OF STUDY R and omized clinical trial . METHODS Forty subjects younger than 30 years with a first traumatic anterior shoulder dislocation were r and omized to receive immediate anterior stabilization plus rehabilitation or immobilization followed by rehabilitation . Patients completed the American Shoulder and Elbow Surgeons ( ASES ) , Disabilities of the Arm , Shoulder and H and ( DASH ) , and the Western Ontario Shoulder Instability Index ( WOSI ) question naires . RESULTS At an average follow-up of 75 months , there was a significant difference in the rate of redislocation between the groups but no statistical significant difference in shoulder function with the ASES or the DASH . The mean difference between the 2 groups with the WOSI estimates a small , but clinical ly significant difference . CONCLUSIONS It is recommended that immediate arthroscopic stabilization is the treatment of choice in a subset of patients who are younger than 30 years and are higher level athletes , and the timing for surgery is good or their sport is risky , i.e. , rugby , football , kayaking , rock climbing . LEVEL OF EVIDENCE Level II Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder . Forty skeletally mature patients younger than 30 years of age were r and omly allocated to immobilization for 3 weeks followed by rehabilitation ( group T ) or arthroscopic stabilization ( within 4 weeks of injury ) followed by an identical immobilization and rehabilitation protocol ( group S ) . A blinded research assistant performed all follow-up evaluations . The dominant arm was involved in 35 % of subjects . The injury occurred in a sporting event in 70 % of subjects . At 24 months , there was a statistically significant difference in the rate of redislocation ( T = 47 % , S = 15.9 % , P = .03 ) . An intention-to-treat analysis comparing disease-specific quality of life using the vali date d Western Ontario Shoulder Instability ( WOSI ) index showed statistically significantly better results in the surgically treated group at the 33 months ( T = 633.93 v S = 287.1 , P = .03 ) and no significant difference in range of motion . At an average 32 months follow-up , a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first , traumatic , anterior dislocation of the shoulder BACKGROUND Shoulder dislocation may cause arthropathy , but the natural history of this evolution is not well described . We therefore conducted a radiographic follow-up 25 years after the primary shoulder dislocation . METHODS A prospect i ve Swedish multicenter study ( 1978 - 1979 ) included 257 shoulders in 255 patients ( age , 12 - 40 years ) with a first-time anterior shoulder dislocation . After 25 years , 227 patients ( 229 shoulders ) were alive and had follow-up . Radiographic imaging was performed in 223 shoulders ( 97 % ) . RESULTS Shoulders were normal in 44 % . Arthropathy was mild in 29 % , moderate in 9 % , and severe in 17 % . Of the shoulders without a recurrence , 18 % had moderate/severe arthropathy . The corresponding figures were 39 % for shoulders that recurred once or more ( without surgery ) and 26 % ( 16 of 62 ) for surgically stabilized shoulders . Seven of 221 patients ( 7 of 223 shoulders ) were considered alcoholic at 25 years and all had severe arthropathy ( P < .001 ) . Other factors that correlated with moderate/severe arthropathy were age older than 25 years at primary dislocation ( P = .01 ) and primary dislocation caused by high-energy sports activity ( P = .009 ) . Shoulders that had not recurred had less arthropathy than shoulders classified as recurrent ( P = .047 ) or stabilized over time ( P = .007 ) . Sixty-two surgically stabilized shoulders had less arthropathy than those that became stable over time ( P = .047 ) . Mild arthropathy at 10 years was associated with moderate/severe arthropathy at 25 years in 19 of 30 shoulders ( 63 % ) compared with 13 of 146 ( 9 % ) classified as normal at 10 years ( P < .001 ) . Joint incongruence at 10 years was associated with moderate/severe arthropathy at 25 years ( P = .001 ) . CONCLUSION Age at primary dislocation , recurrence , high-energy sports , and alcohol abuse were factors associated with the development of arthropathy . Also shoulders without a recurrence were associated with arthropathy |
13,984 | 26,011,665 | Diagnostic performance of TVS for detecting deep myometrial infiltration in women with endometrial cancer is moderate | OBJECTIVE To review the diagnostic accuracy of transvaginal ultrasound ( TVS ) in the preoperative detection of deep myometrial infiltration in patients with endometrial cancer , comparing subjective and objective methods . | OBJECTIVES To compare the accuracy of transvaginal sonography ( TVS ) and magnetic resonance imaging ( MRI ) in the preoperative staging of endometrial carcinoma . METHODS This was a prospect i ve study in which 74 women consecutively diagnosed with endometrial carcinoma were examined using TVS by physicians trained in gynecological sonography and MRI by radiologists with a special interest in gynecology . All patients underwent surgical-pathological staging after removal of the uterus , adnexa and pelvic lymph nodes . Sensitivity , specificity , and positive and negative predictive values were calculated for each imaging modality with regard to detection of neoplastic invasion of the outer half of the myometrium and cervical involvement . RESULTS TVS and MRI performed equally well in the preoperative staging of endometrial cancer , with no statistically significant differences between the two techniques . The sensitivity , specificity , positive and negative predictive values , and overall diagnostic accuracy for TVS in the evaluation of myometrial infiltration were 84 % , 83 % , 79 % , 88 % and 84 % , respectively . Respective values for MRI were 84 % , 81 % , 77 % , 87 % and 82 % . The corresponding statistics for detection of cervical involvement were 93 % , 92 % , 72 % , 98 % and 92 % for TVS ; and 79 % , 87 % , 58 % , 95 % and 85 % for MRI . CONCLUSIONS When carried out by expert practitioners , TVS shows good accuracy in the local staging of endometrial carcinoma . Because of its high costs , MRI should be offered only to those in whom TVS produces images of poor quality The depth of myometrial infiltration by endometrial cancer is an important prognostic factor . The examination of the depth of infiltration classifies the patients in the low- and high-risk groups , which influences the therapeutic approach . Transvaginal ultrasonography represents a first-choice diagnostic test for the assessment of the depth of myometrial infiltration as the time consumption and financial dem and s of magnetic resonance imaging need to be taken into account . In comparison with the MRI , the diagnostic accuracy of the transvaginal ultrasound depends more on the individual experience and professional potential of the examining physician . This fact can contribute to the heterogeneity of published results of transvaginal ultrasound on the determination of infiltration depth . Having in mind the aim to verify these indicators in our local conditions and environment , we decided to prospect ively study 150 endometrial cancer patients who were examined with the transvaginal ultrasound in the period 1/2009 - 10/ 2011 . Correlated firstly with the preoperative and then secondly with the definitive histopathological examination was the depth-of-infiltration-related data that had been taken from the ultrasound findings . The output being monitored was the exclusion or confirmation of the invasion exceeding half the thickness of myometrium . In our study , the diagnostic accuracy of the method reached 82.67 % , while the other indicators were as follows : sensitivity 92.31 % , specificity 79.28 % , positive predictive value ( PPV ) 61.02 % , negative predictive value ( NPV ) 96.7 % , the likelihood ratio of a positive test 4.455 and the likelihood ratio of a negative test 0.097 . The results of the depth of myometrial infiltration examination and their comparison with the data from similarly oriented clinical studies entitle us to include this examination in the set of st and ard preoperative methods used for the examination of patients with endometrial cancer ( Tab . 3 , Fig. 5 , Ref . 20 ) OBJECTIVE The purpose s of this study were to compare transvaginal sonography ( TVS ) , intraoperative sonography ( IOS ) , and gross visual inspection of the uterus with the histopathologic findings in patients with endometrioid adenocarcinoma , and to compare the accuracies of TVS , IOS , and gross visual inspection in staging of the tumor . SUBJECTS AND METHODS Sixteen patients with endometriod carcinoma were prospect ively evaluated with TVS and IOS . Intraoperative gross visual inspection was also performed . Gray-scale , duplex , and color Doppler findings were used to stage patients . The location and depth of myometrial invasion and the presence of cervical involvement were recorded . At gross visual inspection , only the absence or presence and the depth of myometrial invasion ( < or = 50 % or > 50 % ) were recorded . The data were analyzed three ways . First , in uterine specimens with myometrial invasion , a site-by-site comparison was made among the TVS and IOS findings and the final histologic results regarding location and depth of tumor invasion . Next , to determine tumor stage , myometrial invasion was defined in two ways : ( 1 ) absent , 50 % or less , or greater than 50 % ; and ( 2 ) 50 % or less or greater than 50 % . Then imaging findings , gross visual inspection , and the final histologic results were compared . RESULTS Of the 16 uterine specimens , eight had myometrial invasion , with 13 separate sites of tumor invasion . IOS correctly identified the location and depth ( + /- 10 % of the histologic depth ) of tumor invasion at four ( 31 % ) sites , and TVS at one ( 8 % ) site . TVS and IOS overestimated myometrial invasion due to adenomyosis , bulky intraluminal tumor , and lymphovascular invasion . When myometrial invasion was defined as absent , 50 % or less , or greater than 50 % , TVS was correct in 60 % of cases , IOS in 56 % , and gross visual inspection in 53 % . When myometrial invasion was defined as 50 % or less or greater than 50 % , TVS was correct in 93 % of cases , IOS in 81 % , and gross visual inspection in 80 % . CONCLUSION TVS and IOS are inaccurate in predicting the precise location and depth of myometrial tumor invasion . However , when a less rigorous definition of invasion is used , the accuracies of TVS and IOS are comparable to gross visual inspection in staging of the tumor OBJECTIVES To develop and vali date strategies , using new ultrasound-based mathematical models , for the prediction of high-risk endometrial cancer and compare them with strategies using previously developed models or the use of preoperative grading only . METHODS Women with endometrial cancer were prospect ively examined using two-dimensional ( 2D ) and three-dimensional ( 3D ) gray-scale and color Doppler ultrasound imaging . More than 25 ultrasound , demographic and histological variables were analyzed . Two logistic regression models were developed : one ' objective ' model using mainly objective variables ; and one ' subjective ' model including subjective variables ( i.e. subjective impression of myometrial and cervical invasion , preoperative grade and demographic variables ) . The following strategies were vali date d : a one-step strategy using only preoperative grading and two-step strategies using preoperative grading as the first step and one of the new models , subjective assessment or previously developed models as a second step . RESULTS One-hundred and twenty-five patients were included in the development set and 211 were included in the validation set . The ' objective ' model retained preoperative grade and minimal tumor-free myometrium as variables . The ' subjective ' model retained preoperative grade and subjective assessment of myometrial invasion . On external validation , the performance of the new models was similar to that on the development set . Sensitivity for the two-step strategy with the ' objective ' model was 78 % ( 95 % CI , 69 - 84 % ) at a cut-off of 0.50 , 82 % ( 95 % CI , 74 - 88 % ) for the strategy with the ' subjective ' model and 83 % ( 95 % CI , 75 - 88 % ) for that with subjective assessment . Specificity was 68 % ( 95 % CI , 58 - 77 % ) , 72 % ( 95 % CI , 62 - 80 % ) and 71 % ( 95 % CI , 61 - 79 % ) respectively . The two-step strategies detected up to twice as many high-risk cases as preoperative grading only . The new models had a significantly higher sensitivity than did previously developed models , at the same specificity . CONCLUSION Two-step strategies with ' new ' ultrasound-based models predict high-risk endometrial cancers with good accuracy and do this better than do previously developed models OBJECTIVE A prospect i ve study was design ed to compare transvaginal sonography with contrast-enhanced MR imaging to determine preoperatively the depth of myometrial invasion in patients with early-stage endometrial carcinoma . SUBJECTS AND METHODS In 40 patients , findings on transvaginal sonograms , unenhanced T2-weighted MR images , and contrast-enhanced T1-weighted Mr images were compared with histologic findings . The depth of myometrial invasion was classified as stage E ( tumor limited to endometrium , n = 12 ) , stage S ( superficial invasion : tumor invades up to 50 % of the myometrium , n = 15 ) , or stage D ( deep invasion : tumor invades more than 50 % of the myometrium , n = 13 ) . RESULTS Findings on transvaginal sonograms were accurate in 27 of 40 patients ( accuracy , 68 % ) ; the depth of invasion was overestimated in five patients and underestimated in eight patients . The results of unenhanced T2-weighted MR images were accurate in 27 patients ( accuracy , 68 % ) , with four overestimations and nine underestimations . The results of contrast-enhanced T1-weighted MR images were accurate in 34 patients ( accuracy , 85 % ) , with five underestimations and one overestimation . In the assessment of each stage of myometrial invasion , the sensitivity and specificity of contrast-enhanced T1-weighted imaging were higher than those of T2-weighted MR imaging and transvaginal sonography . The false-positive diagnoses based on transvaginal sonograms and T2-weighted images , respectively , involved polypoid tumors ( n = 4 and 2 ) , distension of the endometrial cavity by pyometra ( n = 2 and 1 ) , the presence of myoma ( n = 2 and 1 ) , atrophy of the myometrium ( n = 1 and 0 ) , and poor tumor/myometrium contrast ( n = 0 and 2 ) . On contrast-enhanced MR images , accuracy was influenced only in a case of polypoid tumor , because tumor , endometrial cavity , and myometrium were clearly distinguished and residual myometrium was clearly visualized . With all imaging techniques , false-negative diagnoses were caused mainly by tumors with superficially spreading growth or microscopic invasion . With transvaginal sonography , infiltrative tumor also tended to be understaged ( n = 3 ) . CONCLUSION Contrast-enhanced MR imaging is significantly superior to transvaginal sonography and unenhanced T2-weighted MR imaging for detecting myometrial invasion In recent years , the incidence of carcinoma of the endometrium has shown an upward trend , such that it is currently the most frequently encountered malignant tumor of the female genital tract . An accurate preoperative diagnosis of the extent and spread of such carcinomas is of crucial importance for the selection of a therapeutic approach appropriate to the stage and infiltration of each particular tumor . In a prospect i ve study of 80 patients with a carcinoma of the endometrium , performed at the Department of Obstetrics and Gynecology of the University of Mainz , we compared the preoperative findings of transvaginal sonography with the postoperative histological results with respect to the following parameters : endometrial thickness , demarcation of the boundary of the endometrium , myometrial infiltration depth and staging . In all of these patients , sonography revealed a distinct increase in the thickness of the endometrium . In all cases , the structure of the endometrium was found to be heterogenous , with an irregular and poorly delineated boundary . Assessment s of the depth of tumor infiltration and the tumor staging obtained by transvaginal sonography were found to correlate with the histological findings in 85 % and 87.5 % of the cases , respectively . Thus , in cases of endometrial carcinoma , transvaginal sonography has an essential role to play in devising an individualized operative treatment program that takes into account the extent , spread and stage of the tumor OBJECTIVE To compare the ability of transvaginal sonography and serum CA 125 levels to predict myometrial invasion in patients with endometrial carcinoma . DESIGN AND METHODS Prospect i ve study in 50 consecutive patients ( mean age 60 years , SD 10.5 , range 29 - 77 years ) diagnosed as having endometrial cancer and scheduled for surgical staging . All patients were evaluated by transvaginal ultrasonography . Endometrial thickness was measured in all cases and myometrial invasion was estimated as < 50 % or > or = 50 % . Serum CA 125 level was determined in each patient . A cut-off level of > or = 35 IU/ml was considered to predict myometrial invasion of > or = 50 % . All patients underwent surgical staging , and definitive histopathological findings regarding myometrial invasion were used as the ' gold st and ard ' . Sensitivity , specificity and positive predictive value ( PPV ) and negative predictive value ( NPV ) were calculated for transvaginal ultrasonography and CA 125 and compared . RESULTS On histopathological analysis , myometrial invasion was found to be < 50 % in 35 ( 70 % ) cases and > or = 50 % in 15 cases ( 30 % ) . Mean endometrial thickness in patients with superficial invasion was significantly lower than in those with deep invasion ( 13.4 mm ( 95 % CI 11.2 - 15.7 ) vs. 18.7 mm ( 95 % CI 15.0 - 22.3 ) , respectively ; p = 0.014 ) . Median CA 125 was significantly higher in patients with deep invasion than in those with superficial invasion ( 30 IU/ml , interquartile range ( IQR ) 46.0 vs. 16.9 IU/ml , IQR 13.9 , respectively ; p = 0.002 ) . The sensitivity , specificity , PPV and NPV for transvaginal ultrasonography were 86.7 % ( 95 % CI 59.5 - 98.3 ) , 94.3 % ( 95 % CI 80.8 - 99.3 ) , 86.7 % ( 95 % CI 59.5 - 98.3 ) and 94.3 % ( 95 % CI 80.8 - 99.3 ) , respectively . The sensitivity , specificity , PPV and NPV for CA 125 were 40 % ( 95 % CI 16.3 - 67.7 ) , 91.4 % ( 95 % CI 76.9 - 98.2 ) , 66.7 % ( 95 % CI 29.9 - 92.5 ) and 78 % ( 95 % CI 63.4 - 89.5 ) , respectively . The sensitivity of transvaginal ultrasonography was significantly higher than that of CA 125 ( p = 0.008 ) . No differences were found in terms of specificity , PPV or NPV . CONCLUSION Our results indicate that transvaginal ultrasonography is more sensitive than CA 125 in predicting myometrial invasion in endometrial cancer OBJECTIVES To identify major factors in the under- and overestimation of cervical and myometrial invasion by endometrial cancer at preoperative staging by ultrasound . METHODS This prospect i ve study involved all patients with histologically confirmed endometrial cancer referred consecutively for surgical staging between January 2009 and December 2011 . All patients underwent transvaginal ultrasound examination , obtaining metric and perfusion data , and the results were compared with final histology : myometrial invasion was defined at histology in the final pathology report as being either < or ≥ 50 % , while cervical stromal invasion was reported as being either present or absent , and sonographic over-/underestimation was determined relative to these . RESULTS Enrolled prospect ively into the study were 210 patients . The proportion of cases with sonographic underestimation , relative to final histology , of myometrial invasion ( i.e. false-negative estimation of no or superficial invasion < 50 % ) and of cervical invasion ( i.e. false-negative finding of absence of stromal invasion ) was comparable : 8.6 % ( n = 18 ) and 10.5 % ( n = 22 ) , respectively . Myometrial invasion was overestimated by ultrasound ( i.e. false-positive estimation of deep invasion ≥ 50 % ) in 15.7 % ( n = 33 ) of cases , and cervical invasion was overestimated ( i.e. false-positive finding of presence of stromal invasion ) in 4.8 % ( n = 10 ) of cases . These outcomes correspond to positive and negative predictive values of 67.6 % ( 95 % CI , 57.7 - 76.6 ) and 83.3 % ( 95 % CI , 74.9 - 89.8 ) , respectively , for the subjective assessment of myometrial invasion , and 60.0 % ( 95 % CI , 38.2 - 79.2 ) and 88.1 % ( 95 % CI , 82.5 - 92.4 ) , respectively , for that of cervical stromal invasion . The staging error in subjective assessment was not related to body mass index ( BMI ) , to the position of the uterus in the pelvis or to image quality . Cervical and myometrial invasion were more often underestimated in well-differentiated endometrial cancers that were smaller in size , with thick minimum tumor-free myometrium and lower perfusion , and more often overestimated in moderately and poorly differentiated cancers that were larger in size , with thin minimum tumor-free myometrium and richer perfusion . CONCLUSION The accuracy of subjective assessment of myometrial and cervical invasion by ultrasound was significantly influenced by tumor size , density of tumor vascularization , tumor vessel architecture and histological grading , while it was not significantly affected by BMI , uterine position and image quality OBJECTIVE To compare the diagnostic accuracy of subjective ultrasound assessment with that of objective measurement techniques in the evaluation of myometrial and cervical invasion in women with endometrial cancer . METHODS This was a prospect i ve multicenter study including 144 women with endometrial cancer undergoing transvaginal ultrasound . Myometrial and cervical invasion was evaluated subjectively , as well as objective ly measured in different ways : endometrial thickness , tumor/uterine anteroposterior ( AP ) diameter ratio , minimal tumor-free margin , minimal tumor-free margin/uterine AP diameter ratio , tumor volume ( three-dimensional ( 3D ) ) , tumor/uterine volume ( 3D ) ratio , and distance from outer cervical os to lower margin of tumor ( Dist-OCO ) . Histological assessment following hysterectomy was the gold st and ard . RESULTS The sensitivity ( 72 % ) and specificity ( 76 % ) of tumor/uterine AP diameter ( at cut-off , 0.53 ) were not significantly different from those of subjective evaluation ( sensitivity , 77 % ( P = 0.44 ) ; specificity , 81 % ( P = 0.32 ) ) for the prediction of deep myometrial invasion ; all other objective measurement techniques had either a significantly lower sensitivity or a lower specificity . For all objective measurement techniques , except minimal tumor-free margin/uterine AP diameter ratio , fixing the sensitivity at the same level as that of subjective evaluation ( i.e. 77 % ) gave a significantly lower specificity . Dist-OCO was the only parameter that might have potential to predict cervical invasion ; it had a non-significantly higher sensitivity than did subjective evaluation ( 73 % vs 54 % , P = 0.06 ) , but a significantly lower specificity ( 63 % vs 93 % , P < 0.001 ) . CONCLUSION Subjective assessment of cervical and myometrial invasion is as good as or better than any objective measurement technique . The tumor/uterine AP diameter ratio and minimal tumor-free margin/uterine AP diameter ratio seem to be the best objective measurement techniques to predict deep myometrial invasion . It remains to be shown if objective measurements are useful to predict cervical invasion OBJECTIVES Preoperative knowledge of the depth of myometrial infiltration is important in patients with endometrial carcinoma . This study aim ed at assessing the value of histopathological parameters obtained from an endometrial biopsy ( Pipelle de Cornier ; results available preoperatively ) and ultrasound measurements obtained after transvaginal sonography with color Doppler imaging in the preoperative prediction of the depth of myometrial invasion , as determined by the final histopathological examination of the hysterectomy specimen ( the gold st and ard ) . METHODS We first collected ultrasound and histopathological data from 97 consecutive women with endometrial carcinoma and divided them into two groups according to surgical stage ( Stages Ia and Ib vs. Stages Ic and higher ) . The areas ( AUC ) under the receiver-operating characteristics curves of the subjective assessment of depth of invasion by an experienced gynecologist and of the individual ultrasound parameters were calculated . Subsequently , we used these variables to train a logistic regression model and least squares support vector machines ( LS-SVM ) with linear and RBF ( radial basis function ) kernels . Finally , these models were vali date d prospect ively on data from 76 new patients in order to make a preoperative prediction of the depth of invasion . RESULTS Of all ultrasound parameters , the ratio of the endometrial and uterine volumes had the largest AUC ( 78 % ) , while that of the subjective assessment was 79 % . The AUCs of the blood flow indices were low ( range , 51 - 64 % ) . Stepwise logistic regression selected the degree of differentiation , the number of fibroids , the endometrial thickness and the volume of the tumor . Compared with the AUC of the subjective assessment ( 72 % ) , prospect i ve evaluation of the mathematical models result ed in a higher AUC for the LS-SVM model with an RBF kernel ( 77 % ) , but this difference was not significant . CONCLUSIONS Single morphological parameters do not improve the predictive power when compared with the subjective assessment of depth of myometrial invasion of endometrial cancer , and blood flow indices do not contribute to the prediction of stage . In this study an LS-SVM model with an RBF kernel gave the best prediction ; while this might be more reliable than subjective assessment , confirmation by larger prospect i ve studies is required Preoperative transvaginal ultrasonographic evaluation of myometrial invasion was performed in 33 patients with endometrial cancer and compared with histologic findings . TVU was remarkably precise in predicting deep myometrial invasion ( accuracy 91.7 % ) but superficial myometrial invasion ( sensitivity 20 % ) . TVU was highly accurate in patients with tumours limited to the endometrium ( sensitivity 100 % ) and the sensitivity of TVU in distinguishing nil or superficial versus deep invasion was 87.8 % . TVU appears to be an efficient , economic , and practical tool for this purpose , however its limitation leads to more complex imaging techniques , especially in patients in whom preoperative irradiation or conservative management is planned OBJECTIVE A prospect i ve study was design ed for patients previously diagnosed of endometrial carcinoma to evaluate the accuracy of transvaginal sonography ( TVS ) in determining both the presence and the depth of myometrial invasion . Patients with advanced stage disease ( III and IV ) were specifically excluded from the analysis . SUBJECTS AND METHODS Sixty patients with endometrial carcinoma underwent transvaginal ultrasonography . Ten of these patients were ruled out due to various reasons . In the remaining 50 cases , TVS findings were compared with those obtained after total abdominal hysterectomy and bilateral salpingo-oophorectomy ( AHT ) . RESULTS The sensitivity of TVS in detecting deep invasion , i.e. more than 50 % of the myometrial thickness was 94.1 % , while the specificity was 84.8 % and the overall accuracy was 88 % . Following the classification of the International Federation of Obstetrics and Gynecology , stage I , which divides myometrial invasion into three categories ( none , superficial involvement and deep invasion ) sensitivity was 66.2 % , specificity was 83.1 % and overall accuracy was 77.2 % . CONCLUSION These findings are consistent with those reported in literature with regard to overall accuracy of TVS . Results are similar to those obtained with magnetic resonance imaging ( MRI ) without contrast and slightly lower than MRI plus contrast OBJECTIVE To compare the accuracy of preoperative transvaginal sonography ( TVS ) and intraoperative frozen section ( FS ) in the assessment of myometrial invasion of endometrial carcinoma , having the definitive histological examination as gold st and ard . METHODS 155 consecutive women ( mean age 63 years , range 32 - 88 ) diagnosed as having endometrial carcinoma were prospect ively evaluated at TVS in order to preoperatively stage the disease . All the patients subsequently underwent complete surgical staging including total abdominal hysterectomy , bilateral oophorectomy , pelvic and lumboaortic lymphadenectomy . After removal of the uterus , intraoperative FS was performed by pathologists with special interest in gynaecologic oncology in a predefined , st and ardized manner . Sensitivity , specificity , positive and negative predictive values were calculated for both modalities as regards neoplastic invasion of the myometrium . RESULTS Overall , 131 women ( 84.5 % ) had an endometrioid adenocarcinoma , 8 ( 5.2 % ) an adenosquamos carcinoma , 7 ( 4.5 % ) a serous papillary carcinoma , 4 ( 2.6 % ) a clear cell carcinoma , 3 ( 1.9 % ) a mixed type carcinoma , 1 ( 0.6 % ) a carcinosarcoma , and 1 ( 0.6 % ) a mesodermal mixed malignant tumor . Sensitivity , specificity , positive and negative predictive values and accuracy for TVS in the evaluation of myometrial infiltration were : 75 % , 89 % , 86 % , 79 % and 81 % . Corresponding features for FS were : 92 % , 92 % , 89 % , 94 % and 92 % . The diagnostic performance of FS was higher than that of TVS ( Cohen 's K value : 0.841 ; p<0.0005 ) . CONCLUSION Intraoperative FS performed better than preoperative TVS in the assessment of myometrial invasion by endometrial cancer . Despite being time consuming , FS can be regarded as a useful modality in order to decide whether to perform lymphadenectomy in cases with poor visualization of the endometrium at TVS and when TVS gives inconclusive results OBJECTIVE To evaluate the diagnostic accuracy of preoperative transvaginal sonography ( TVS ) in the detection of deep myometrial invasion in endometrial cancer cases classified by the grade of disease , and in comparison to frozen section analysis in grade 1 cases . METHODS In a prospect i ve study , 91 patients with confirmed endometrial carcinoma underwent preoperative TVS for evaluation of myoinvasion . Sonographic results were categorized as superficial ( less than or equal to 1/2 myometrial depth ) and deep invasion ( greater than 1/2 myometrial depth ) . TAH-BSO followed by retroperitoneal lymph node sampling were performed in all patients with grade 2 - 3 tumors . In patients with grade 1 disease , the surgical specimen was intraoperatively evaluated by frozen section , and lymph node sampling was carried out if deep invasion was determined . The preoperative sonographic findings and the frozen section results were compared to the final histopathology report of myoinvasion . RESULTS In 77 of the 91 ( 84.6 % ) patients , the sonographic assessment of the depth of myoinvasion was in accord with the final histopathologic findings . TVS demonstrated a sensitivity of 87.8 % and a specificity of 82.7 % in detecting deep invasion in the entire study group ( grade 1 - 3 ) , with positive and negative predictive values ( PPV , NPV ) of 74.3 % and 92.3 % , respectively . TVS in grade 1 cases ( n=47 ) showed a sensitivity of 77.7 % , a specificity of 79 % , PPV of 46.6 % and NPV of 93.7 % . TVS in cases with grade 2 - 3 tumors ( n=44 ) showed a sensitivity of 90 % , specificity of 91.6 % , PPV of 90 % and NPV of 91.6 % . Thus , the accuracy of TVS in grade 2 - 3 cases was superior to that achieved in grade 1 cases ( 91 % vs 78.7 % ; p=.002 ) . The myometrial invasion was assessed by frozen section in 41 out of 47 patients with grade 1 disease and demonstrated a sensitivity of 85.7 % , a specificity of 100 % , PPV of 100 % and NPV of 97.1 % . The specificity ( 100 % ) and accuracy ( 97.5 % ) of the frozen section were found to be superior compared to that of the TVS ( 79 % and 78.7 % ) in detecting deep invasion in grade 1 cases ( p=.008 , p=.005 , respectively ) . No statistically significant difference was found between the sensitivity of either technique . CONCLUSIONS TVS appeared to be a more accurate method for preoperative assessment of myoinvasion in grade 2 - 3 endometrial cancer patients compared to grade 1 patients . In grade 1 cases , this method achieved lower accuracy in detecting deep invasion compared to the frozen section analysis . Based on these data , the value of preoperative TVS results as the sole criterion in the decision to perform extensive surgical procedures in grade 1 endometrial cancer is question able and warrants further evaluation OBJECTIVES The aim of this prospect i ve multicenter study was to evaluate and compare the diagnostic performance of PET/CT , MRI and transvaginal two-dimensional ultrasound ( 2DUS ) in the preoperative assessment of endometrial cancer ( EC ) . METHODS 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment . Preoperatively they were PET/CT- , MRI- , and 2DUS scanned . The imaging results were compared to the final pathological findings . This study was approved by the National Committee on Health Research Ethics . RESULTS For predicting myometrial invasion , we found sensitivity , specificity , PPV , NPV , and accuracy for PET/CT to be 93 % , 49 % , 41 % , 95 % and 61 % , for MRI to be 87 % , 57 % , 44 % , 92 % , and 66 % and for 2DUS to be 71 % , 72 % , 51 % , 86 % and 72 % . For predicting cervical invasion , the values were 43 % , 94 % , 69 % , 85 % and 83 % , respectively , for PET/CT , 33 % , 95 % , 60 % , 85 % , and 82 % , respectively , for MRI , and 29 % , 92 % , 48 % , 82 % and 78 % for 2DUS . Finally , for lymph node metastases , the values were 74 % , 93 % , 59 % , 96 % , and 91 % for PET/CT and 59 % , 93 % , 40 % , 97 % and 90 % for MRI . When comparing the diagnostic performance we found PET/CT , MRI and 2DUS to be comparable in predicting myometrial invasion . For cervical invasion and lymph node metastases , however , PET/CT was the best . CONCLUSIONS None of the modalities can yet replace surgical staging . However , they all contributed to important knowledge and were , furthermore , able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone Myometrial invasion greater than 33 % negatively affects the prognosis of endometrial carcinoma . Since the endometrium is readily differentiated from myometrium via high-resolution transvaginal sonography ( TVS ) , this prospect i ve study was undertaken to evaluate the efficacy of TVS in determining the depth of myometrial invasion in women with endometrial adenocarcinoma . Eighteen subjects underwent TVS utilizing 5.0- and 7.5-MHz probes by a single examiner blinded to stage and grade of adenocarcinoma . Predicted TVS ratios were categorized as less than 33 % or greater than or equal to 33 % and compared to actual histologic invasion . Ultrasound predicted that TVS ratios greater than or equal to 33 % are significantly associated with deep ( greater than 33 % ) histologic invasion ( P less than 0.01 , Fisher 's test ) . When histologic invasion was greater than or equal to 33 % , TVS was 100 % accurate with no false negatives . The two cases in which TVS ratios erroneously indicated invasion greater than or equal to 33 % contained adenomyosis and leiomyomas . TVS is a highly accurate and convenient method for preoperatively evaluating myometrial invasion . Potentially this evaluation could influence the selection of therapy for poor-surgical-risk c and i date s or direct appropriate referral of patients with deeper invasion to a gynecologic oncologist Objective : We aim ed to compare the diagnostic performance of transvaginal sonography ( TVS ) , magnetic resonance imaging ( MRI ) , and intraoperative frozen section in the assessment of myometrial invasion and to evaluate intratumoral blood flow in any myometrial invasion with transvaginal Color Doppler ultrasonography ( TV-CDU ) . Methods : This prospect i ve study included 64 women consecutively diagnosed with endometrial carcinoma . The subjects were evaluated by TVS , MRI , and TV-CDU by 2 radiologists with a special training in gynecology . Intraoperatively , a frozen section was obtained and processed for interpretation by a blinded pathologist . Sensitivity , specificity , negative , and positive predictive values were calculated for each imaging modality and frozen section with regard to assessment of myometrial invasion . The intratumoral blood flow was evaluated by TV-CDU . Results : Transvaginal sonography , MRI , and frozen section showed no statistical significant differences in overall diagnostic performance for the preoperative and intraoperative assessment of any myometrial invasion , although frozen section seemed to be slightly superior to the imaging techniques . The positive rate of intratumoral blood flow was higher in deep myometrial invasion , but statistical significance was not obtained . The mean value of resistance index was significantly lower in the cases with deep myometrial invasion . Conclusions : Transvaginal sonography with concomitant TV-UCD is low-cost , easily performed , and repeated technique for particularly deep myometrial invasion . Because of its high costs and time-consuming , MRI may be recommended in the cases with poor quality of TVS . Because depending solely on imaging methods could lead to insufficient treatment schedules , intraoperative frozen section should also be performed for myometrial assessment |
13,985 | 31,872,105 | Risk of bias was high for the studies on dental calculus , halitosis , and stain , and varied for the dental plaque and gingivitis studies .
Significant reductions in dental calculus and in halitosis were reported for the SnF2 dentifrice ; no differences in stain reduction were noted .
Conclusions The present review found that stabilized SnF2 toothpaste had a positive effect on the reduction of dental calculus build-up , dental plaque , gingivitis , stain and halitosis .
A tendency towards a more pronounced effect than using toothpastes not containing SnF2 was found .
Clinical relevance Adding a SnF2 toothpaste to the daily oral care routine is an easy strategy that may have multiple oral health benefits | Objectives The aim of the present systematic review was to examine the scientific evidence for the efficacy of stabilized stannous fluoride ( SnF2 ) dentifrice in relation to dental calculus , dental plaque , gingivitis , halitosis and staining . | The effects of a stabilized 0.454 % stannous fluoride dentifrice , currently marketed as Crest Gum Care , on supragingival plaque , gingivitis , gingival bleeding and oral soft tissue condition were studied in 328 adult male and female subjects who completed a six-month , double blind clinical study . Following initial examinations , subjects presenting with a minimum of five gingival bleeding sites received a thorough dental prophylaxis and were instructed to brush at least twice a day for three months with a commercially available fluoride dentifrice , packaged in such a way as to blind its identity to the study subjects . This constituted the three-month pre-test period . At the end of this period , subjects were again examined , given a second oral prophylaxis , and r and omly assigned to brush with one of the following dentifrices : 1 ) stabilized 0.454 % stannous fluoride , 2 ) 0.243 % sodium fluoride control , or 3 ) one of three experimental dentifrices . Subjects were instructed to brush their teeth as they normally would , at least twice a day for one minute per brushing . Follow-up examinations after three and six months of dentifrice use evaluated supragingival plaque , gingivitis , gingival bleeding , extrinsic tooth stain and oral soft tissue status . After six months , the stabilized stannous fluoride dentifrice significantly reduced gingivitis and gingival bleeding by 20.5 % and 33.4 % compared to the sodium fluoride control group . However , the stabilized stannous fluoride dentifrice group was not significantly different from the control dentifrice group with respect to supragingival plaque scores . As expected , accumulation of extrinsic tooth stain was greater in the stabilized stannous fluoride group than the control group . No unexpected nor clinical ly significant oral soft tissue health effects were associated with the use of the test dentifrices . The results from this clinical study demonstrate that over a six-month period , twice-daily use of a dentifrice containing 0.454 % stabilized stannous fluoride significantly reduced gingivitis and gingival bleeding , relative to a 0.243 % sodium fluoride control dentifrice This double-blind parallel- design clinical study compared the efficacy of a stabilized stannous fluoride dentifrice ( Crest Plus Gum Care ) , baking soda and peroxide ( NaF ) dentifrice ( Mentadent ) , and essential oil mouthrinse ( Listerine ) to a conventional NaF dentifrice ( Crest ) for the control of plaque , gingivitis and gingival bleeding over six months . Following an initial baseline examination and stratification , subjects received a complete oral prophylaxis and were distributed assigned test products . Following three and six months , subjects re-visited the clinic for examinations . Evaluations at baseline and at 3 and 6 months included soft tissue status . Löe-Silness gingivitis/gingival bleeding , Silness-Löe plaque and dental stain . Results subsequent to six months of product use were as follows : At six months , the stabilized stannous fluoride dentifrice was observed to produce statistically significant 17.5 % reductions in gingivitis and 27.5 % reductions in gingival bleeding relative to the NaF dentifrice . The combination of sodium fluoride dentifrice and essential oil mouthrinse produced statistically significant reductions of 7.4 % in gingivitis and 10.8 % in plaque as compared with the NaF dentifrice . The stabilized stannous fluoride dentifrice produced statistically significant reductions in both gingivitis ( 10.8 % ) and gingival bleeding ( 23.0 % ) relative to the combination of sodium fluoride dentifrice and essential oil mouthrinse . The baking soda and peroxide ( NaF ) dentifrice did not provide reductions in gingivitis , plaque or gingival bleeding as compared with the conventional NaF dentifrice . The stabilized stannous fluoride dentifrice provided statistically significant reductions in gingivitis as compared with the baking soda and peroxide dentifrice following six months of use , and both the essential oil mouthrinse and stabilized stannous fluoride dentifrice provided statistically significant reductions in gingivitis as compared with the baking soda and peroxide dentifrice following three months of use . These results support : 1 ) the efficacy of stabilized stannous fluoride dentifrice and the combination of sodium fluoride dentifrice and essential oil mouthrinse for the prevention of gingivitis ; 2 ) the superior activity of stabilized stannous fluoride dentifrice as compared with a combination of sodium fluoride dentifrice and essential oil mouthrinse for the control of gingivitis and gingival bleeding ; and 3 ) the lack of efficacy for baking soda and peroxide dentifrice for the control of plaque , gingivitis and gingival bleeding as compared with conventional fluori date d dentifrice A primary patient motivation for oral hygiene is effective cleaning . Dentifrice serves this function by including ingredients such as abrasives , surfactants , and specialized cleaning ingredients such as anticalculus agents . This introductory article aims to introduce professionals , educators , and research ers on the rationale behind the development of an improved cleaning dentifrice formulation , Crest Multicare Advanced Cleaning . This new dentifrice is based upon the application of an improved tartar control/cleaning ingredient that is a polymeric adjunct of a pyrophosphate anion commonly applied in tartar control and stain control whitening dentifrices . The polypyrophosphate anion , also referred to as sodium hexametaphosphate , produces superior activity and substantivity on oral surfaces as compared to both pyrophosphate and some other commonly used dental cleaning ingredients and cleaning/conditioning adjuncts . The increased activity and substantivity translate into significant improvements in the prevention of dental stains and supragingival calculus and in the non-abrasive removal of dental stains . This article describes the structure of polypyrophosphate as compared to the parent pyrophosphate molecule , the rationale for its improved chemistry , and , in particular , its tartar control chemistry . In addition , the fundamental mechanisms of calculus formation and inhibition are review ed . Lastly , a preliminary clinical study evaluating the improved efficacy of a polypyrophosphate dentifrice is described where the tartar control activity of the polypyrophosphate dentifrice is shown to be superior to that of a clinical ly established and marketed industry st and ard pyrophosphate dentifrice BACKGROUND AND AIMS R and omised , blind , controlled experimental gingivitis and home-use study protocol s are used to evaluate the efficacy of oral hygiene products . The present method ological study combined the two clinical trial design s to compare the preventive and therapeutic potentials of two toothpastes . MATERIAL AND METHODS The study was a parallel group , r and omised , double-blind design , initially involving 73 healthy dentate subjects . A 21-day experimental gingivitis protocol was combined with a 6-week ( 42 days ) home-use protocol . At baseline , modified gingival index ( MGI ) , gingival index ( GI ) and gingival bleeding ( GB ) were recorded . A dental prophylaxis was then performed . Subjects were allocated to either control fluoride or stannous fluoride toothpaste based on gender and GI . During the first 21-day period , subjects applied the allocated toothpaste , for 1 min twice a day , to a group of teeth in a plastic shield and brushed the remaining teeth with the same paste . From day 21 the shield was not placed , and subjects brushed all teeth with the toothpaste for 1 min twice per day up to day 42 . MGI , GB and a plaque index ( PI ) were recorded on days 21 and 42 . RESULTS Sixty-nine and 67 subjects completed to days 21 and 42 , respectively . For shielded teeth , PI , MGI and GB increased to day 21 and then after ceasing the use of the shield decreased to day 42 . At day 21 , PI favoured the stannous fluoride toothpaste , but differences did not achieve statistical significance for any parameter at days 21 or 42 . For unshielded teeth , there were no significant differences between the toothpastes for any parameter at either time point . CONCLUSION : The feasibility of combining two gingivitis clinical trial method ologies appears proven , and data on both the preventive and therapeutic chemical and mechanical efficacy of toothpastes can be obtained through such protocol s. Specifically from the present study and consistent with some other reports , the plaque inhibitory properties of the stannous fluoride product are limited and do not always translate into an antiplaque/antigingivitis effect The effects of stabilized 0.454 % stannous fluoride dentifrices on supragingival plaque , gingival inflammation and gingival bleeding were studied in 549 adult male and female subjects who completed a six-month , double blind clinical study . Following an oral prophylaxis , subjects were r and omly assigned to brush with one of the following dentifrices : 1 ) 0.454 % SnF2 stabilized with 2.08 % sodium gluconate , 2 ) 0.454 % SnF2 stabilized with 4.16 % sodium gluconate , 3 ) an experimental dentifrice , or 4 ) 0.243 % NaF control dentifrice . Follow-up examinations were conducted at 3 and 6 months . Compared to the control dentifrice at 6 months , stannous fluoride dentifrices stabilized with 2.08 % or 4.16 % sodium gluconate significantly reduced gingivitis by 18.8 % and 18.0 % , respectively . There were no statistically significant differences between the two stabilized SnF2 groups with respect to their beneficial effects on gingival health . Gingival bleeding was also reduced , relative to the control dentifrice , for both stabilized SnF2 dentifrices . However , these differences were not statistically significant at p=0.05 . The stabilized SnF2 dentifrices were not significantly different from the control dentifrice in their effects on supragingival plaque . No significant differences in adverse oral soft tissue effects were observed between the test and control groups . As expected , accumulation of extrinsic tooth stain increased in the stabilized SnF2 groups . However , the difficulty in removing accumulated dental stain was similar between the control and stabilized SnF2 dentifrices . Since use of SnF2 dentifrices has been reported to produce tooth stain , gingivitis examinations were done with and without custom-made tooth covers to evaluate the potential for examiner bias . Comparable gingivitis and gingival bleeding benefits were observed when the evaluations were conducted with or without the tooth covers . Results from this study support that 0.454 % stabilized stannous fluoride dentifrices can provide an important adjunct to the prevention and control of gingivitis when used in combination with regular personal oral hygiene procedures and professional care PURPOSE S To compare the oral malodor protection efficacy of a 0.454 % stannous fluoride dentifrice versus a negative control ( 0.243 % sodium fluoride ) using a sulfide monitor ( halimeter ) as the measurement . A secondary objective was to assess the effects of tongue brushing . METHODS This was a four-treatment , five-period , examiner-blinded , crossover , r and omized study . Healthy subjects who met the entrance criteria were enrolled into the study . A 5-day acclimation period , in which subjects brushed twice daily in their customary manner with a st and ard sodium fluoride dentifrice , occurred prior to baseline . After baseline halimeter measurements , subjects were r and omly assigned to one of four treatments ( SnF2 dentifrice groups , with or without tongue brushing ; negative control dentifrice groups , with or without tongue brushing ) based on baseline halimeter scores , age , and gender . Test products were used three times a day . Breath measurements were taken 24 hours after baseline ( after three product uses ) . Subjects then brushed again with the product treatment . Final breath measurements were taken 4 hours later , 28 hours after baseline . A 5-day washout separated each treatment period . RESULTS 33 subjects were enrolled and completed the study . The adjusted mean volatile sulfur compound ( VSC ) levels were significantly lower in the SnF2 groups than the NaF groups , at both 24 ( P < 0.01 ) and 28 ( P < 0.001 ) hours post baseline time points . Tongue brushing did not provide additional statistically significant breath benefits when compared to toothbrushing alone . Both dentifrices were well tolerated This r and omized and controlled , examiner blind , parallel group study was undertaken to evaluate the efficacy of three commercial dentifrices on breath malodor . A total of 384 healthy adult subjects with oral malodor were r and omized to one of four brushing groups , using either an antimicrobial dentifrice containing 0.45 % stannous fluoride , an antitartar dentifrice containing 0.243 % sodium fluoride and 5 % pyrophosphate , an antimicrobial dentifrice containing 0.24 % sodium fluoride and 0.30 % triclosan/copolymer , or bottled distilled water which served as the negative experimental control . Breath quality was evaluated over a five-day period by second-person organoleptic grading and measurement of volatile sulfur levels . Following treatment , adjusted mean organoleptic scores and volatile sulfur levels were lowest for the stannous fluoride dentifrice group , with this group exhibiting superior breath quality compared to the negative control at three hours after a single brushing , and again at all cumulative use time points . While all test dentifrices showed some activity , only stannous fluoride had a second-person breath benefit . Breath effects for the other two dentifrices were limited to reductions in volatile sulfur levels at hours 99 and 104 for the antitartar sodium fluoride pyrophosphate dentifrice , and at hour 99 only for the antimicrobial sodium fluoride triclosan/copolymer dentifrice . This research establishes the comparative breath efficacy of three commercial dentifrices in a study model that may prove relevant for other dentifrice clinical trials OBJECTIVE To compare the plaque inhibition benefits of a control 0.454 % stannous fluoride/sodium hexametaphosphate/sodium fluoride dentifrice ( SnF2/SHMP with 1450 ppm F ) to a chlorhexidine digluconate ( 0.05 % ) , aluminum lactate ( 0.8 % ) , and aluminum fluoride ( AlF3/Chx with 1400 ppm F ) dentifrice . METHODS Twenty-nine subjects were r and omized to a two-period , two-treatment , double-blind crossover sequence using blend-a-med EXPERT GUMS PROTECTION toothpaste ( SnF2/SHMP ) and Lacalut Aktiv toothpaste ( AlF3/Chx ) . Each treatment was used along with a st and ard manual toothbrush ( Oral-B P35 Indicator ) for 17 days . Digital plaque image analysis ( DPIA ) was used at the end of each period for three consecutive days to evaluate plaque levels ; a ) overnight ( A.M. pre-brush ) ; b ) following 40 seconds of brushing with the test product ( A.M. post-brush ) ; and c ) mid-afternoon ( P.M. ) . Images were analyzed using an objective computer algorithm to calculate the total area of visible plaque . A four-day washout period was instituted for the crossover phase . RESULTS Twenty-seven subjects completed the study . The SnF2/SHMP dentifrice provided a statistically significant lower level of plaque area coverage compared to the AlF3/Chx dentifrice at all time points . For the SnF2/SHMP dentifrice , plaque coverage was 19.4 % lower ( p = 0.0043 ) at the A.M. pre-brush , 25.6 % lower ( p = 0.0014 ) at the A.M. post-brush , and 19.8 % lower ( p = 0.0057 ) at the P.M. measure relative to the AlF3/Chx dentifrice . CONCLUSION The blend-a-med EXPERT GUMS PROTECTION toothpaste inhibits plaque regrowth , both overnight and during the day , to a significantly greater degree than Lacalut Aktiv . Additionally , immediately after brushing with blend-a-med EXPERT GUMS PROTECTION , subjects had significantly less plaque than after brushing with Lacalut Aktiv PURPOSE The primary objective of this study was to investigate the staining profile of an experimental test dentifrice containing 0.454 % w/w stannous fluoride compared to that of a marketed control dentifrice containing 0.76 % w/w sodium monofluorophosphate ( Colgate Cavity Protection ) following regular and repeat use , with twice daily brushing over 8 weeks . As an exploratory objective , the staining profile of the test dentifrice was compared to that of a marketed comparator dentifrice containing 0.454 % w/w stannous fluoride ( Crest Pro-Health - Clean Mint ) . METHODS This was a single-center , examiner-blind , r and omized , three arm , parallel group study , stratified by pre-baseline stain score [ total Lobene Stain Index ( LSI ) ( area x intensity ) score < 31 , > or = 31 ] and smoking status . Following initial screening , 137 healthy subjects , aged 18 years and above , with 12 gradable anterior teeth returned for baseline assessment s. At the baseline visit , subjects received an oral soft tissue ( OST ) examination and an assessment of extrinsic dental stain using the LSI on the facial and lingual surfaces of the 12 anterior teeth , LSI area , LSI intensity and LSI area x intensity ( the LSI area x intensity score was termed the pre-baseline LSI score ) . Subjects who met study requirements received a dental prophylaxis of the anterior teeth to remove all visible stain from their tooth surfaces such that an LSI ( area x intensity ) score of 0 was achieved . R and omized subjects brushed with their assigned dentifrice at home twice daily for 1 timed minute and returned after 4 and 8 weeks for an OST examination and dental stain assessment of the anterior teeth using LSI . RESULTS There were no statistically significant differences in dental stain build-up between the test dentifrice containing 0.454 % w/w stannous fluoride and a marketed control dentifrice ( Colgate Cavity Protection ) , after 4 and 8 weeks of twice daily brushing , in terms of LSI area x intensity , LSI area or LSI intensity scores . Exploratory analysis indicated that the marketed stannous fluoride dentifrice ( Crest Pro-Health ) exhibited more dental stain build-up at 4 and /or 8 weeks compared to the other two study dentifrices . However , post-hoc analysis revealed an imbalance in LSI baseline stain levels between the treatment groups , with higher stain levels in the marketed comparator group , which made it difficult to draw robust conclusions from the exploratory data . This imbalance was not considered to impact the other study analyses . Study treatments were well tolerated OBJECTIVES To determine the effectiveness of a novel sonic toothbrush in reducing plaque and in maintenance of gingival health when compared to a st and ard manual brush . METHODS This study was a block-r and omized , examiner-blind , two-treatment , parallel group , single centre clinical investigation . A total of 84 subjects were enrolled and r and omly assigned to receive either the Panasonic EW-DL90 or an American Dental Association-endorsed manual toothbrush . Subjects were instructed to follow a twice-daily brushing regimen without flossing . Plaque levels and gingival health were assessed at baseline and after 1 and 3 weeks of treatment using the Turesky Modification of the Quigley-Hein Plaque Index and the Papillary Bleeding Score . RESULTS Subjects assigned to the EW-DL90 group had significantly lower plaque levels after 1 and 3 weeks of treatment than those in the manual group ( P = 0.003 and 0.0035 , respectively ) . Both groups showed a reduction in plaque levels at Week 3 relative to baseline . The EW-DL90 group had significantly lower gingival inflammation scores after 1 week of treatment ( P = 0.0293 ) , but there was no difference between groups after 3 weeks of treatment . CONCLUSION The EW-DL90 toothbrush safely and effectively removes more plaque than a st and ard manual toothbrush . Improvement in gingival inflammation was observed after 1 week of treatment . There was no difference in Papillary Bleeding Score between the two groups after 3 weeks of treatment . CLINICAL SIGNIFICANCE The newly developed sonic brush ( Panasonic EW-DL90 ) tested in this study was found to be more effective than a manual toothbrush at plaque removal . The papillary bleeding scores were significantly lower in the sonic brush group after 1 week of product use . After 3 weeks of product use , both treatment groups had similar papillary bleeding scores almost returning to baseline values PURPOSE To evaluate the extrinsic stain profiles of two experimental stannous-containing dentifrice prototypes compared to two marketed control dentifrices . METHODS This was a 5-week , r and omized , four-treatment , parallel group , double-blind clinical trial of healthy adults . Following a baseline Lobene Stain Index evaluation , subjects received a prophylaxis limited to the 12 anterior teeth to remove surface stain and calculus . They were r and omly assigned based on stain scores to one of the four treatment groups : one of two experimental stannous-containing sodium fluoride dentifrices ; a non-staining marketed triclosan dentifrice ( Colgate Total ) ; or a 0.454 % stannous fluoride dentifrice ( Crest Gum Care ) . Subjects brushed for 1 minute twice daily at home with their assigned dentifrice . Stain examinations were repeated at Week 3 and Week 5 to assess treatment differences . RESULTS For the 96 subjects completing the study , Lobene stain composite mean scores -- as well as extent ( area ) and intensity average scores -- were significantly lower in the two experimental stannous-containing dentifrice groups and the Colgate Total group when compared to Crest Gum Care ( P < 0.0001 ) at both Weeks 3 and 5 . There were no statistically significant differences ( P > 0.145 ) in stain accumulation at either time point between the experimental stannous groups and the Colgate Total group by any Lobene stain measure ( composite , extent , intensity ) . All dentifrices were well-tolerated 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 BACKGROUND Rinsing with the combined use of an oxygenating-agent ( OA ) and chlorhexidine ( CHX ) in addition to mechanical oral hygiene could improve and /or maintain good gingival health over a long period . METHODS This study had an examiner-blinded , r and omized , six-group parallel design consisting of two-phases : a 3-week treatment phase and a subsequent 12-month experimental phase . A total of 267 subjects in good general health ( ≥18 years ) , without periodontitis , with at least five teeth per quadrant , and with moderate to advanced gingivitis were enrolled . A 3-week treatment phase was initiated to improve gingival health . Subjects were assigned to one of the six groups : two basic oral hygiene groups ( Control I & II ) , one professional oral hygiene instruction group ( OHI ) , one professional prophylaxis group ( PP ) , an OA&CHX rinse group and a group receiving a combination of all regimens ( COMBI group ) , being OHI + PP + OA&CHX . Dental plaque , gingival bleeding and staining assessment s were performed at the start of the treatment phase , at baseline and at 4 , 7 , 10 , and 12 months . RESULTS There was a significant reduction in dental plaque-scores for the OA&CHX and COMBI-group ( 0.51 [ SD = 0.37 ] , 0.38 [ SD = 0.33 ] respectively ) and a significant reduction in gingivitis scores for the OA&CHX and COMBI group ( 6.9 % [ SD = 14.0 ] , 13.4 % [ SD = 13.4 ] respectively ) from the start of the treatment phase to baseline . No clinical ly relevant changes were observed for the other four groups . After baseline , bleeding and plaque-scores increased back to a non-significant level between groups , and this level remained throughout the study . CONCLUSION OA&CHX and COMBI-group showed a clinical ly relevant improvement after the treatment phase in terms of dental plaque and gingival bleeding levels . At the 4-month clinical assessment , there was no longer a significant difference between groups OBJECTIVE To compare the anti-plaque efficacy of a stabilized 0.454 % stannous fluoride ( referred to as SnF2 ) dentifrice versus a 0.3 % triclosan dentifrice formulated with a copolymer and sodium fluoride ( referred to as triclosan ) . METHODS The study had a r and omized , double-blind , two-treatment , parallel-group design , and compared plaque reduction from baseline after both three and six weeks of treatment with either the SnF2 or triclosan dentifrices using a manual toothbrush . Subjects brushed their teeth using their assigned treatment dentifrices according to the manufacturer 's instructions . Following overnight plaque accumulation , levels of plaque were assessed by an experienced examiner using the Rustogi , et al. Modified Navy Plaque Index at the start of the study ( baseline ) , and after three and six weeks of regular brushing . Groups were compared using analysis of covariance separately for Weeks 3 and 6 , and by repeated measures for Weeks 3 and 6 combined . RESULTS One-hundred and twenty subjects were r and omized to treatment and 114 subjects completed the study . Both treatment groups showed a statistically significant reduction from baseline in mean plaque values for all three tooth areas ( whole mouth , gingival margin , interproximal ) at both Weeks 3 and 6 ( p < 0.02 for all comparisons ) . Analysis of covariance showed a statistically significantly ( p < 0.0001 ) lower adjusted mean plaque level for the SnF2 group compared to the triclosan group for all three tooth areas at both Weeks 3 and 6 , and for Weeks 3 and 6 combined . Weeks 3 and 6 combined adjusted mean plaque was 36.5 % lower for whole mouth for the SnF2 group versus the triclosan group . Weeks 3 and 6 combined adjusted mean plaque reduction from baseline was three times greater for the SnF2 group relative to the triclosan group . CONCLUSION Both dentifrices showed statistically significant reductions from baseline in whole mouth , gumline , and interproximal accumulated overnight plaque after three and six weeks of brushing , but the SnF2 dentifrice showed statistically significantly greater plaque reductions versus the triclosan dentifrice OBJECTIVES This study was conducted to assess anti-plaque and anti-gingivitis benefits of a stabilized stannous fluoride ( SnF(2))/sodium hexametaphosphate ( SHMP ) dentifrice versus a negative control . MATERIAL AND METHODS This was a r and omized , 6-month , stratified , single-centre , double-blind , parallel group , clinical study conducted in harmony with the guidelines for evaluating chemotherapeutic products for the control of gingivitis outlined by the American Dental Association . A stabilized 0.454 % SnF(2)/SHMP dentifrice was tested against a commercially available negative control dentifrice . Following baseline measurements , subjects received a dental prophylaxis . Subjects were instructed to brush twice daily for 60 s using their assigned product . Efficacy measurements were obtained at baseline , 3 and 6 months post treatment using the Modified Gingival Index , Gingival Bleeding Index and the Turesky Modified Quigley-Hein Plaque Index . Oral tissue examinations were performed at all visits . RESULTS A total of 140 subjects were enroled and 128 completed the study . RESULTS after 6 months showed the SnF(2 ) dentifrice delivered a 16.9 % reduction in gingivitis ( p<0.001 ) , a 40.8 % reduction ( p<0.001 ) in gingival bleeding , and an 8.5 % reduction in plaque ( p=0.001 ) versus the negative control . Both treatments were well tolerated . CONCLUSIONS Twice daily use of the SnF(2)/SHMP dentifrice over 6 months provided statistically significant anti-plaque and anti-gingivitis benefits relative to a negative control INTRODUCTION This study was undertaken to test the hypothesis that male , non-smokers , aged 25 - 50 years , with a proven track record of developing gingivitis would provide suitable subjects for experimental gingivitis studies because the inter-subject variation would be greatly reduced . MATERIAL S AND METHODS Subjects were required to be men aged between 25 and 50 years , in good general health with at least four sound teeth in one posterior quadrant of the m and ible . Subjects who were smokers , taking antibiotics , anti-inflammatory drugs or had any other medical , surgical or social condition making participation in the study inadvisable , were excluded . Subjects had previously participated in a 21-day experimental gingivitis study . Subjects with the most gingivitis at the end of the previous study were invited to participate first , moving down the list until the required number of subjects had been achieved . Subjects were r and omly assigned to one of three toothpastes : Crest Gum Care , Mentadent P or a placebo ( UK Signal ) . Subjects were asked to brush their teeth twice daily for 1 min . , with the tooth-shield in place and containing 1 ml of their assigned toothpaste . RESULTS Thirty-five subjects completed the study using the placebo , 36 used Mentadent P and 39 completed the study using Crest Gum Care . Both toothpastes containing active gum health ingredients ( Triclosan and Zinc Citrate in Mentadent P and Stannous Fluoride in Crest Gum Care ) result ed in statistically significant reductions in gingival bleeding and inflammation . Although a directional reduction , there was no statistically significant reduction in plaque scores . No significant differences between the two active groups were established . CONCLUSION The factors that were controlled or measured and analyzed in these studies were : gender , smoking status , age and chronic gingivitis level . The results add support to the hypothesis that male subjects show less variation , however there is limited evidence linking the female menstrual cycles to variations in gingivitis status . Further research in this area is required before definitive conclusions can be made . Selecting a subject population in order to decrease variation must be undertaken with caution . A subject population selected for particular attributes can be extremely valuable when assessing the anti-gingivitis potential of new agents , but this population would be as biased if used for large efficacy clinical trials . The data obtained will not necessarily be able to be generalized , that is , applicable to the whole population . However there is sufficient evidence to justify balancing for ( or excluding ) smokers from subject population s in experimental gingivitis studies This parallel-group , double-blind , placebo-controlled clinical trial directly compared the efficacy of two antimicrobial dentifrice formulations for the control of plaque , gingivitis and gingival bleeding during six months of use following a pre-test r and omization period . Test antimicrobial dentifrices for the study included : a stabilized stannous fluoride formulation ( Crest Plus Gum Care-currently marketed in U.S. ) comprised of 0.454 % SnF2 in a stabilized silica abrasive base ; and a formulation containing triclosan ( Colgate Total , currently marketed outside the U.S. in numerous countries ) comprised of 0.30 % triclosan . 2.0 % Gantrez co-polymer and 0.243 % NaF in a silica abrasive base . The control dentifrice was a conventional fluoride dentifrice comprised of 0.243 % NaF in a silica abrasive base . Clinical evaluations included Turesky et al. plaque , Löe-Silness gingivitis and gingival bleeding , and Meckel stain . The stabilized stannous fluoride dentifrice exhibited significant efficacy in the reduction of both gingivitis ( 20.5 % ) and gingival bleeding ( 33.4 % ) after six months relative to the placebo control ( p < 0.05 ) . In direct comparison , the stabilized stannous fluoride dentifrice reduced gingivitis and gingival bleeding significantly relative to the triclosan/copolymer dentifrice ( p < 0.05 ) . These results establish : 1 ) the superior clinical efficacy of a stabilized stannous fluoride dentifrice relative to a triclosan/copolymer dentifrice in the chemotherapeutic control of gingivitis and gingival bleeding ; 2 ) the important contribution of clinical test design /sensitivity in assessing the therapeutic efficacy of antimicrobial agents ; and 3 ) the value of head-to-head comparative studies in establishing the therapeutic relevance of clinical effects of formulations for the reduction of gingivitis OBJECTIVE The objective of these three clinical trials was to compare the impact of two commercial products , Colgate Total and Crest Pro-Health , on the formation of dental plaque over a 24-hour period of time . The studies utilized the Modified Gingival Margin Plaque Index ( MGMPI ) , a vali date d and reliable clinical method for assessing the efficacy of products in reducing plaque build-up . METHODS Colgate Total and Crest Pro-Health were the test products for all three clinical trials . Colgate Great Regular Flavor ( CR ) was used as the universal washout product . Colgate Total , as the only toothpaste approved by the FDA under an NDA for antiplaque , antigingivitis , and anticaries benefits , contains 0.3 % triclosan/2.0 % PVM/MA copolymer for antigingivitis and antiplaque , as well as 0.243 % sodium fluoride ( NaF ) for anticaries . Crest Pro-Health contains 0.454 % stannous fluoride ( SnF2 ) as both a monographed anticaries agent and a monographed antigingivitis agent , along with sodium hexametaphosphate and zinc lactate . Twenty-five healthy subjects meeting all study criteria were included into each of the double-blind studies . Product assignment was r and omized and a crossover design was implemented . Informed consent was obtained from all subjects prior to commencement of each of the studies . The studies followed published MGMPI procedures , which require subjects to receive a dental scaling/prophylaxis followed by a one-week washout period prior to use of test products . A baseline MGMPI score was calculated following use of the test products in the dental clinic . Subjects refrained from all oral hygiene for 24 hours following use of each test product , and returned to the clinic for a 24-hour MGMPI score . Following a washout period , subjects repeated the procedure with the other test product as per the crossover design . The differences ( delta ) between baseline plaque scores and 24-hour plaque scores were independently calculated for each study , and the delta values were compared for the two test products in each of the studies . RESULTS In all three clinical trials , Colgate Total significantly reduced plaque regrowth over a 24-hour time period ( p < or = 0.05 ) compared to Crest Pro-Health . Existing differences were determined via a paired t-test , which confirmed that Colgate Total was statistically significantly different from Crest Pro-Health . CONCLUSION These in vivo data support the antiplaque benefit of the 0.3 % triclosan/2.0 % PVM/MA copolymer/0.243 % sodium fluoride dentifrice . Additionally , the results support that Colgate Total provides superior efficacy in inhibiting the formation of dental plaque compared to Crest Pro-Health A partial mouth experimental gingivitis model was employed to establish the potential efficacy of a dentifrice containing a zinc salt and the antimicrobial agent Triclosan to prevent or delay the development of gingivitis over a period of 28 days . Initially , gingival health was established in 34 subjects following a 6-week period of professional tooth cleaning and oral hygiene instruction . A toothshield was constructed to fit 4 posterior m and ibular teeth . Undiluted test or placebo dentifrice was applied to the experimental teeth via the toothshield , which also prevented plaque removal from these teeth during habitual brushing of the remainder of the dentition . The presence of plaque , bleeding after probing and visual signs of inflammation were independently assessed . Plaque accumulated rapidly and gingivitis developed in both groups . At the 2-wk assessment s , lower mean plaque scores were recorded for the group using the test dentifrice . At the 4-wk assessment a significantly lower level of gingivitis was recorded for the test group . It is concluded that ( a ) the model can be used to establish the potential efficacy of a dentifrice to maintain gingival health , ( b ) the dentifrice containing zinc citrate and Triclosan was efficacious and ( c ) the Gingival Index possibly overestimates the proportion of healthy gingival sites Several triclosan and stannous fluoride toothpastes have been shown to have plaque inhibitory and more particularly gingival health benefits when compared to minus active controls . There have been relatively few studies to compare such products with conventional fluoride toothpastes in home use . The aim of this study was to compare the relative gingival health benefits of a triclosan/zinc citrate , triclosan/copolymer , stannous fluoride and conventional fluoride toothpastes in a home use study . The study was a double blind , parallel design with a total 143 healthy dentate volunteers ( 41 male , 102 female ) who toothbrushed 2x daily with 1 of 4 toothpastes over an 18 week period . At the beginning of the trial , each volunteer was scored for plaque and gingivitis and then received a thorough prophylaxis . Each volunteer was allocated a toothpaste according to a predetermined r and omisation scheme . The volunteers were then re-examined after 6 , 12 and 18 weeks . No other oral hygiene products were used during this period . The results showed no statistically significant treatment differences between products for the gingival index throughout the 18 week-trial . No statistically significant treatment effects between products for plaque index were found at 6 or 18 weeks . However , a small but statistically significant treatment effect for plaque index was seen at 12 weeks in favour of the triclosan/copolymer toothpaste compared to the stannous fluoride and conventional fluoride toothpastes , this difference had disappeared by the 18 week examination . All volunteers oral hygiene and gingivitis scores improved after the baseline examination , and this improvement continued throughout the trial . This is a feature of nearly all toothbrushing studies and can be attributed to the initial prophylaxis and the Hawthorne phenomenon . Such phenomena , noted in home use clinical trials , may mask the efficacy of proven antiplaque formulations PURPOSE To evaluate the effects of a highly bioavailable 0.454 % stannous fluoride dentifrice on established gingival bleeding over a 3-month period . MATERIAL S AND METHODS A r and omized controlled clinical trial was conducted . In total , 100 adults with mild-to-moderate gingivitis and an average of 15 bleeding sites were assigned to either the stannous fluoride or regular control pastes for at-home use . Of these , 99 received study treatment and 97 completed the study . RESULTS The stannous fluoride group experienced 50 % to 74 % reductions in bleeding sites relative to baseline or the control , differing significantly ( P < 0.001 ) at all time points . Most subjects in the stannous fluoride group ( 94 % ) had measured improvements in bleeding , and nearly one half completed treatment with one or no bleeding sites . CONCLUSION These study results suggest that incorporation of this 0.454 % stannous fluoride dentifrice into daily oral hygiene maybe expected to yield less gingival bleeding at subsequent dental check-ups , and therefore reduce the risk of progressive periodontal disease |
13,986 | 32,204,501 | Mineral trioxide aggregate ( MTA ) , Biodentine and ferric sulphate yielded good clinical results over time and might be safely used in the pulpotomies of primary molars .
Among agents , MTA seemed to be the material of choice .
On the contrary , calcium hydroxide showed the worst clinical performance .
Although clinical ly successful , formocreosol should be replaced by other material s , due to its potential cytotoxicity and carcinogenicity .
Conclusion : MTA seemed to be the gold st and ard material in the pulpotomy of primary teeth .
Promising results were also provided by calcium silicate-based cements . | Background : Pulpotomy of primary teeth provides favorable clinical results over time ; however , to date , there is still not a consensus on an ideal pulp dressing material .
Therefore , the aim of the present systematic review was to compare pulpotomy agents to establish a preferred material to use . | BACKGROUND Considering formocresol 's toxicity , Ca(OH)(2 ) partial pulpotomy ( PP ) was studied as a treatment alternative . AIM To compare success rates of Ca(OH)(2 ) PP versus formocresol pulpotomy ( FP ) treatment of pulpally exposed lower primary molars . DESIGN A total of 84 lower primary molars , which met study criteria , from 56 child patients were r and omly assigned for each treatment . After treatment , blinded clinical and radiographic evaluation with 96.9 % and 90 % reliability was performed at 6-month intervals to determine treatment success/failure . Chi-squared test was used to compare success rates between the two treatments . RESULTS The success rates from 6 to 36 months for PP ranged from 95.03 % to 75 % , whereas for FP , it was 92.7 - 74.2 % . The success rates for the two treatments at each 6-month interval were not different ( P ≥ 0.05 ) . The most frequent failure was internal resorption , affecting five FP teeth and three PP teeth . The resorption was arrested in five of the teeth and was replaced by a radiopaque calcified tissue in one case . CONCLUSION Considering the favourable clinical and radiographic success rate of PP and the potentially toxic effects of formocresol leads us to recommend the use of PP instead of FP in primary teeth with deep carious lesions Aim To compare the clinical and radiographic success rates of three different pulpotomy agents in primary molars after 18 months . Methods The study was carried out with 51 primary molars of children aged 5–9 years old . The teeth were r and omly assigned to the experimental or control groups . After coronal pulp removal and haemostasis , the remaining pulp tissue was covered with Biodentine ® or mineral trioxide aggregate in the experimental groups . In the control group , formocresol was placed with a cotton pellet over the pulp tissue for 5 min and after removal the pulp tissue was covered with zinc oxide – eugenol ( ZOE ) paste . All teeth were immediately restored with reinforced ZOE base and resin modified glass-ionomer cement , and later with pre-formed metal crowns . Follow-up assessment s were carried out after 3 , 6 , 12 and 18 months . Results Forty-five teeth were available for follow up at the end of 18 months . All of the available teeth for mineral trioxide aggregate and Biodentine ® were clinical ly successful , as were 73.3 % of the FC group . Radiographic success rate for the formocresol group at 18 months follow up was 73.3 , 100 % for mineral trioxide aggregate and 86.6 % for Biodentine ® group . Conclusion Mineral Trioxide aggregate and Biodentine ® showed more favourable results than formocresol PURPOSE The purpose of this study was to investigate the outcomes of vital primary molar pulpotomy when there is no direct contact between eugenol and the vital pulp . Four pulpotomy techniques were compared : ( 1 ) ferric sulfate ( FS ) pulpotomy ; ( 2 ) eugenol-free FS pulpotomy ; ( 3 ) mineral trioxide aggregate ( MTA ) pulpotomy ; and ( 4 ) FS/MTA pulpotomy . METHODS The pulpotomy technique assigned to each molar was determined by r and om selection . Two blinded , disinterested raters classified each molar into 1 of 3 radiographic outcomes : ( 1 ) N = normal molar without pathologic change ; ( 2 ) Po = pathologic change present , follow-up recommended ; ( 3 ) Px = pathologic change present , extract . RESULTS A total of 92 patients with 227 pulpotomy-treated molars returned for at least 1 recall examination . Median follow-up for molars was 24 months ( range=12 - 38 months ) . MTA molars demonstrated significantly fewer Px radiographic outcomes than FS molars ( P=.002 , chi-square test ) . Eugenol-free FS molars demonstrated significantly more Px radiographic outcomes than MTA ( P<.001 , chi-square test ) or FS/MTA ( P=.002 , chi-square test ) molars . Significantly lower survival was demonstrated for eugenol-free FS molars compared to MTA molars ( P=.02 , log-rank test ) over 6 to 38 months . CONCLUSIONS Outcomes for mineral trioxide aggregate pulpotomy were superior to ferric sulfate and eugenol-free ferric sulfate pulpotomy after a median follow-up of 2 years Introduction : This trial was design ed to evaluate the clinical and radiographic success rates of calcium-enriched mixture ( CEM ) cement with and without low level laser therapy ( LLLT ) and compare them to that of formocresol ( FC ) and ferric sulfate ( FS ) in primary molar pulpotomies . Methods and Material s : This r and omized clinical trial was conducted on a total of 160 teeth selected from 40 patients aged 3 - 9 years . Patients with at least four primary molars needing pulpotomy , were included in order to have each tooth assigned r and omly in one of the four following groups ; FC , FS , CEM , and LLLT/CEM . Six- and twelve-month follow-up periods were conducted in order to enable a clinical and radiographic evaluation of the treated teeth . Collected data were analyzed using Cochran Q Tests . Results : The 12-month clinical success rate for each technique was : FC=100 % , FS=95 % , CEM=97.5 % and LLLT/CEM=100 % with no significant differences ( P>0.05 ) . Furthermore , 12-month radiographic success rate for each technique was : FC=100 % , FS=92.5 % , CEM=95 % and LLLT/CEM=100 % with no significant differences ( P>0.05 ) . Conclusion : Favorable outcomes of four treatment techniques in pulpotomy of primary molar teeth were comparable . CEM with/without LLLT may be considered as a safe and successful pulpotomy treatment modality compared to current conventional methods Introduction : Pulpotomy technique is most widely accepted clinical procedure for treating primary teeth with coronal pulp inflammation caused by caries with no involvement of the radicular pulp . Aim and Objective : The aim of the study was to evaluate the success and efficacy of mineral trioxide aggregate ( MTA ) and antioxidant mix as pulpotomy agents both clinical ly and radiographically . Material s and Methods : A total of forty primary molars in children aged between 6 and 9 years , requiring for pulpotomy procedures , were selected . R and om sample s distribution was done , antioxidant mix ( n = 20 ) and MTA ( n = 20 ) both were used as pulpotomy agent . Under rubber dam isolation , pulpotomy procedure was performed in all sample s followed by restoration with stainless steel crowns . Later , the patients were recalled after 6 and 12 months for clinical and radiographic evaluation . The data were evaluated using Fisher 's exact test . Results : Statistically analysis shows no significant difference between the two groups ( P > 0.05 ) with respect to clinical and radiographic success rate , but antioxidant mix showed more efficient result than MTA . Conclusion : Antioxidant mix pulpotomy is more biocompatible and cost effective than any other commercially available medicament Purpose The aim of this study was to compare the effect of white mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomised primary molars . Methods In this clinical trial study , 60 lower second primary molars of 46 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) and FC ( control ) groups by r and om numbered table . Following removal of the coronal pulp and haemostasis , the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps . The teeth of both groups were restored with stainless steel crowns . Children arrived for clinical and radiographic follow-up evaluation after 6 , 12 and 24 months . Results The treated teeth in FC group ( n = 18 ) were clinical ly and radiographically successful after 24 months . The radiographic follow-up evaluation revealed one failure ( furcation involvement ) in 18 molars treated with MTA after 24 months . The treated teeth in MTA group were clinical ly successful 24 months postoperatively . Pulp canal obliteration was observed in one of the teeth treated with MTA and four of the teeth treated with FC . Conclusion MTA could be used as a safe medicament for pulpotomy in cariously exposed primary molars and could be a substitute for FC The aim of this study was to compare the effect of ferric sulfate ( FS ) to that of dilute formocresol ( DFC ) as pulp dressing agents in pulpotomized primary molars . Ninety-six primary molars in 72 children were treated by a conventional pulpotomy technique . Fifty-eight teeth were treated by a FS solution for 15 sec , rinsed , and covered by zinc oxide-eugenol paste ( ZOE ) . In another 38 teeth , a cotton pellet moistened with 20 % DFC was placed for 5 min , removed , and the pulp stumps were covered by ZOE paste . The teeth of both groups were sealed by a second layer of intermediate restorative material ( IRM ) and restored with a stainless steel crown . This is a report of the clinical and radiographic examination of 55 teeth dressed with FS and 37 teeth fixed with DFC , that have been treated 6 to 34 months previously ( mean 20.5 months ) . Four teeth were excluded from the study due to failure of the patient to present for recall . Success rates of 92.7 % for the FS , and of 83.8 % for the DFC were not significantly different . Four teeth ( 7.2 % ) of the FS group and two ( 5.4 % ) of the DFC group presented internal resorption . Inter-radicular radiolucencies were observed in two teeth of the FS group and three teeth of the DFC group . The latter also presented periapical lesions . Success rates of both groups were similar to those of previous studies utilizing the traditional Buckley 's formocresol OBJECTIVES The aim of the present study was to conduct a clinical and radiographic long-term evaluation of pulpotomy in temporary molars performed with Grey and White Mineral Trioxide Aggregate ( MTA ) and compare the results of Grey and White MTA pulpotomies in a sample of 233 primary molars with a maximum follow-up period of 84 months . METHODS The sample was selected from patients treated at the Department of Pediatric Dentistry , Faculty of Dentistry , Complutense University of Madrid , Spain . This prospect i ve study included first and second primary molars treated with pulpotomy with Grey or White MTA , controlled for a maximum follow-up period of 84 months . Statistical analysis of clinical and radiographic findings was completed using ANOVA ( P<0.05 ) . RESULTS Follow-up evaluations , performed every 6 months , revealed that only 2 molars treated with White MTA presented abscess and pathological mobility . Radiographic examination of the 210 molars revealed unfavourable pulp response in only 6 molars ( internal or furcation root resorption ) , without statistically significant differences between Grey and White MTA . Two radiological findings were noticed : dentine bridge formation and partial or total root canal stenosis . Grey MTA induced a higher percentage of dentine bridges with statistically significant differences ( P<0.05 ) , and a higher percentage of pulp canal stenosis , without a statistically significant difference . CONCLUSIONS Grey and White MTA presented high levels of clinical and radiographic success . Although the present study showed evidence of a very good biologic response with both types of MTA , Grey MTA showed significantly higher number of dentine bridge formation than White MTA AIM To compare the treatment outcomes of calcium-enriched mixture ( CEM ) cement and mineral trioxide aggregate ( MTA ) as pulp dressing bio material s in vital pulpotomy of carious primary molars . STUDY DESIGN split-mouth r and omised clinical trial . MATERIAL S AND METHODS Forty children aged 4 - 8 years with 2 carious teeth requiring pulpotomy were selected and r and omly assigned to MTA ( n = 40 ) or CEM ( n = 40 ) groups . After coronal pulp removal , the remaining radicular pulp was covered with an appropriate bio material ; the teeth were then permanently restored . Clinical /radiographic success/failures were blindly evaluated at 6- , 12- and 24-month follow-ups . STATISTICS the recorded data were analyzed with McNemar test and GEE . RESULTS A total of 36 , 33 and 35 patients were available for 6- , 12- and 24-month follow-ups , respectively . At the 12-month follow-up only one and three teeth in the CEM and MTA groups had pathologic external root resorption , respectively . The resorbed teeth were then missed due to extraction /exfoliation at the 24-month follow-up ; all other treated teeth were sign/symptom-free . Overall , clinical and radiographic outcomes in both MTA/CEM groups were comparable at the three follow-ups without significant differences . Time had no significant effect on the success . CONCLUSION MTA and CEM demonstrated favourable treatment outcomes for pulpotomy of carious primary molars ; CEM may be an effective pulp dressing bio material PURPOSE The objective of this study was to assess the effect of mineral trioxide aggregate ( MTA ) as pulp dressing material following pulpotomy in primary molars with carious pulp exposure and compare them to those of formocresol ( FC ) . METHODS Of 33 children , primary molars treated via a conventional pulpotomy technique were r and omly assigned to the MTA group ( 33 teeth ) or FC group ( 29 teeth ) . Clinical and radiographic follow-up ranged between 4 and 74 months . The mean follow-up time was 38 months , with no difference between the groups . Twenty-nine teeth were followed until uneventful shedding ( mean=33 months ) . Failures were detected after a mean period of 16 months ( range=4 to 30 ) . RESULTS The success rate of pulpotomy was 97 % for MTA ( 1 failure ) and 83 % for FC ( 5 failures ) . Eight teeth presented internal resorption . In 4 of them ( 2 of each group ) , progress of the resorption process stopped and the pulp tissue was replaced by a radioopaque calcified tissue . Pulp canal obliteration was observed in 58 % of the MTA group and in 52 % of the FC group ( total=55 % ) . CONCLUSIONS MTA showed a higher ( though not statistically significant ) long-term clinical and radiographic success rate than formocresol , and can be recommended as its replacement as , unlike FC , MTA does not induce undesirable responses Aim To compare the clinical , radiographic and histological responses of the pulp to mineral trioxide aggregate ( MTA ) , calcium hydroxide ( CH ) and Portl and cement ( PC ) when used as a pulpotomy agent in human primary teeth . Study design Forty-five m and ibular primary molar teeth were r and omly assigned to CH , MTA or PC groups and treated by pulpotomy technique . Methods The teeth were treated by conventional pulpotomy technique , differing only in the capping material for each group . Clinical and radiographic evaluations were recorded at 6- , 12- and 24-month follow-up . Teeth in the regular exfoliation period were further processed for histologic analysis .Statistics Data were tested using parametric tests at a significance level of 5 % . The histological results were expressed descriptively . Results Clinical ly and radiographically , the MTA and PC groups showed 100 % success rates at 6 , 12 and 24 months . In CH group , several teeth presented clinical and radiographic failures detected throughout the follow-up period , and internal resorption was a frequent radiographic finding . Histologic analysis revealed the presence of dentine-like mineralised material deposition obliterating the root canal in the PC and MTA groups . CH group presented , in most of the sections , necrotic areas in the root canals . Conclusions MTA and PC may serve as effective material s for pulpotomies of primary teeth as compared to CH . Although our results are very encouraging , further studies and longer follow-up assessment s are needed in order to determine the safe clinical indication of Portl and cement Objective This study examined the effects of MTA and Biodentine on the clinical and radiographic success rates of pulpotomies performed on primary teeth with carious pulp exposures . Material s and methods This study was conducted with 44 m and ibular primary molars requiring vital pulpotomy . Carious dentin surrounding the exposure site was used as the inclusion criteria for all teeth , which were r and omly divided into two groups according to pulpotomy material [ MTA group ( n = 24 ) , Biodentine group ( n = 20 ) ] . Treatment was followed up clinical ly and radiologically for 24 months . Pulp canal obliteration was not regarded as a failure . Results Clinical and radiographic success rates at the end of 24 months were 100 % for the MTA group and 89.4 % for the Biodentine group . Success rates did not vary significantly between the groups ( p = 0.646 ) . Pulp canal obliteration was observed in two teeth ( 8.3 % ) in the MTA group at 6 months , but the teeth were found to be stabilized by 24 months . Conclusion The long-term clinical and radiographic success rates obtained in this study indicate that both MTA and Biodentine are appropriate options for pulpotomy treatment of primary teeth with carious exposure in patients whose teeth should be retained for long periods of time . Clinical relevance The etiology of exposure determines pulpal response , making it crucial to distinguish between mechanical and carious exposures . The carious exposure is presumed to be accompanied by severe inflammation , which makes the prognosis of treatment unpredictable . Bio material s can be used especially in cases with carious pulp exposures Purpose . The purpose of this study was to evaluate clinical and radiographic findings of treatments using a new hemostatic agent ( Ankaferd blood stopper ( ABS ) ) , as compared to ferric sulfate ( FS ) , when used as a pulpotomy medicament in primary teeth . Material s and Methods . The primary molars ( 70 ) were selected from 35 children aged 4 to 6 years . The teeth were r and omized into two groups for pulpotomy with the ABS ( n = 35 ) and the FS ( n = 35 ) agents . The patients were recalled for clinical and radiographic evaluation at 3- , 6- , 9- , and 12-month intervals . Results . At the 3- and 6-month clinical and radiographic evaluations , total success rates of 100 % were observed in each group . In ABS and FS groups , the clinical success rates , however , reduced to 90.9 % and 93.9 % at the 9-month examination and 84,8 % and 90.9 % at the 12-month examination , respectively . Similarly , the teeth in the ABS and FS groups had radiographic success rates of 90.9 % and 93.9 % at 9 months and 84.8 % and 87.8 % at 12 moths , respectively . Conclusion . Although the findings indicated that ABS agents may be useful agents for pulpotomy medicament , further long-term and comprehensive histological investigations of ABS treatments are necessary Aims Despite various advents in technology , the present era marks a shift to phytotherapeutics and alternative modalities to conventional endodontic treatments . Newer endodontic modalities have been developed inculcating the ancient system of medicine . The present study was done to compare and evaluate the clinical pulp response and radiographic signs after pulpotomy in four groups of primary molar teeth treated with formocresol ( control ) , propolis extract , turmeric gel , and calcium hydroxide respectively . Material s and methods Following ethical clearance , 90 primary molar teeth in 45 pediatric patients , aged between 4 and 9 years , were selected for pulpotomy . These were then r and omly divided by split-mouth technique into two groups as experimental ( propolis extract/turmeric gel/calcium hydroxide ) and control ( formocresol ) groups . The patients were followed up for 6 months for clinical and radiographic signs and symptoms to evaluate the success of treatment . Results A comparable clinical and radiographic success rate was seen with all experimental groups as compared to the control ( formocresol ) group . Conclusion With concerns about the safety of formocresol appearing in the dental and medical literature for more than 20 years , the material s used in this study can be considered as promising alternatives for formocresol in pediatric endodontic treatment . How to cite this article Hugar SM , Kukreja P , Hugar SS , Gokhale N , Assudani H. Comparative Evaluation of Clinical and Radiographic Success of Formocresol , Propolis , Turmeric Gel , and Calcium Hydroxide on Pulpotomized Primary Molars : A Preliminary Study . Int J Clin Pediatr Dent 2017;10(1):18 - 23 ABSTRACT Background : Vital pulpotomy is a single-stage procedure of surgical amputation of the coronal portion of exposed vital pulp , usually as a means of preserving the vitality and function of the remaining radicular portion . Aims and objectives : The aim of this study was to compare the clinical and radiographic success rates for ferric sulfate ( FS ) , electrosurgery ( ES ) and laser pulpotomy in human primary molars . Material s and methods : In a r and omized clinical trial , 30 primary molars indicated for pulpotomy in children aged 4 to 10 years were treated using either a FS ( 10 teeth ) , ES technique ( 10 teeth ) and laser ( 10 teeth ) . Following the pulpotomy , the teeth were evaluated for clinical and radiographic success at 3 , 6 , 9 and 12 months on the basis of the presence of pain , sinus , mobility , internal and external resorption , periapical radiolucency , calcification in the canal and bone loss . Statistical analysis : The data were assessed with Chi-square test . Results : After 12 months of follow-up , both clinical and radiographic success rates were 100 % in the laser group but only 80 % in both ES and FS groups . There was statistically significant difference between the success rates of three groups ( p < 0.05 ) . Conclusion : Laser pulpotomy showed better clinical as well as radiographical results than ES and FS pulpotomy . Laser pulpotomy was also found superior in terms of operating time , patient cooperation , ease of use and pain . Although results of the study showed the failure rates for electrosurgical pulpotomy to be equal to those for FS pulpotomy , electrosurgical pulpotomy being a nonpharmacological technique considered more favorable . Further studies using larger sample size and longer evaluation periods are suggested . How to cite this article : Gupta G , Rana V , Srivastava N , Ch and na P. Laser Pulpotomy – An Effective Alternative to Conventional Techniques : A 12 Months Clinicoradiographic Study . Int J Clin Pediatr Dent 2015;8(1):18 - 21 PURPOSE The purpose of this study was to compare outcomes and survival of ferric sulfate with mineral trioxide aggregate ( FS+MTA ) pulpotomy and root canal therapy ( RCT ) in carious vital primary maxillary incisors . METHODS In this parallel group noninferiority trial , asymptomatic carious vital primary incisors with pulp exposure in healthy 18- to 46-month-olds were allocated r and omly to receive FS+MTA pulpotomy or RCT between September 2010 and September 2012 . Each incisor was classified into one of the following radiographic outcomes : N ( incisor without pathologic change ) ; Po ( pathologic change present , follow-up recommended ) ; Px ( pathologic change present , extract . ) Clinical findings and incisor survival were secondary outcomes . RESULTS Seventy subjects were enrolled with a total of 172 incisors . Twelve- and 18-month radiographic outcomes demonstrated no statistical difference between FS+MTA pulpotomy and RCT incisors for Px outcomes ( P=0.38 ; odds ratio equals 0.60 ; 95 percent confidence interval equals 0.19 to 1.89 ; chi-square test ) . There was no statistical differences in clinical outcomes for FS+MTA pulpotomy and RCT at 12 and 18 months ( P=0.51 ; Fisher 's exact test ) or survival for FS+MTA pulpotomy and RCT incisors ( P=0.11 ; log-rank test ) . CONCLUSIONS Ferric Sulfate with Mineral Trioxide Aggregate ( FS+MTA ) is an alternative to RCT for vital primary incisors Objective The aim of this study was to evaluate and compare , both clinical ly and radiographically , the effects of calcium silicate-based material s ( i.e. , ProRoot MTA [ PR-MTA ] , MTA-Plus [ MTA-P ] , and Biodentine [ BD ] ) and ferric sulfate [ FS ] in pulpotomy of primary molars . Material s and Methods In this r and omized clinical trial , 29 healthy 5- to 7-year-old children with at least four carious primary molars with no clinical or radiographic evidence of pulp degeneration were enrolled . The pulpotomy agents were assigned as follows : Group 1 : BD ; Group 2 : MTA-P ; Group 3 : PR-MTA ; and Group 4 : FS . Clinical and radiographic evaluations were performed at 6 , 12 , and 24 months . Data were analyzed using chi-square tests . Results Total success rates at 24 months were 82.75 % , 86.2 % , 93.1 % , and 75.86 % , respectively . No statistically significant differences in total success rates were observed among the groups at 6- , 12- , and 24-month follow-ups . When the groups were compared according to follow-up times , the success rates in each group did not vary significantly among the 6–12-month , 6–24-month , or 12–24-month periods ( p > 0.05 ) . Conclusion Although the success rates of BD , MTA-P , MTA-PR , and FS did not differ significantly , calcium silicate-based material s appeared to be more appropriate than FS in clinical practice PURPOSE The purpose of this prospect i ve study was to compare light-cured calcium hydroxide ( Ca(OH)2 ) with diluted formocresol ( FC ) for its success as a primary molar pulpotomy medicament METHODS Selection criteria included at least 2 matching , asymptomatic , contralateral primary molars requiring vital pulpotomies . Matched teeth in each patient were r and omized to receive either Ca(OH)2 or FC as a pulpotomy medicament . All teeth were restored with prefabricated metal crowns . Twenty patients ( 34 pairs of teeth ) were followed clinical ly and radiographically for > or = 1 year . Two blinded , st and ardized , and calibrated examiners evaluated and scored each radiograph for signs of pathology , based upon a modified scale previously proposed . RESULTS Findings were grouped in : ( a ) 0 - 6 ; ( b ) 7 - 12 ; and ( c ) 13 - 24 month intervals . Radiographic scoring favored the FC group of the 7- to 12- and 13- to 24-month intervals ( P<.05 ) . Clinical success was similar for Ca(OH)2 ( 94 % ) and FC ( 97 % ) at 12 months or less . Beyond 12 months , clinical success varied more ( Ca(OH)2=84 % , FC=97 % ) , but not significantly ( P=.08 ) . Combined success rates were lower for Ca(OH)2 ( 56 % ) than FC ( 94 % ) . CONCLUSIONS Light-cured calcium hydroxide does not appear to be a viable alternative to diluted formocresol as a pulpotomy agent Background The medicament formocresol ( FC ) used for pulpotomy in primary teeth has great concerns regarding its toxicity due to one of its constituent formaldehyde which acts by tissue fixation . Therefore , new medicaments were introduced which cl aim ed preservation and regeneration of pulp . Aim The present study is aim ed to compare and evaluate the clinical and radiographic success of FC , pulpotec , mineral trioxide aggregate ( MTA ) , and emdogain ( EMD ) as pulpotomy medicaments in human primary molars . Design A sample of 21 patients with 84 teeth were selected . All the patients have at least four teeth eligible for pulpotomy according to selection criteria . In each mouth , the teeth selected were r and omly allocated into four groups with 21 each . Results After 24 months of follow-up , the clinical success rates were FC ( 94 % ) , pulpotec ( 94 % ) , MTA ( 100 % ) , and EMD ( 83 % ) and radiographically FC ( 88 % ) , pulpotec ( 83 % ) , MTA ( 94 % ) , and EMD ( 72 % ) , which were statistically not significant ( p > 0.05 ) . Conclusion The outcome of this study demonstrates MTA has a high success rate compared with FC , pulpotec , and EMD as pulpotomy agent . In addition , MTA , pulpotec , and EMD can be considered as alternatives to FC as pulpotomy agent . How to cite this article Sunitha B , Puppala R , Kethineni B , Mallela MK , Peddi R , Tarasingh P. Clinical and Radiographic Evaluation of Four Different Pulpotomy Agents in Primary Molars : A Longitudinal Study . Int J Clin Pediatr Dent 2017;10(3):240 - 244 PURPOSE The purpose of this study was to compare the outcome of primary tooth pulpotomies using two different white mineral trioxide aggregate ( MTA ) cements and calcium hydroxide ( CH ) . METHODS Primary molars ( N=139 ) from three- to nine-year-old children were r and omly assigned to be treated using either ProRoot MTA ( N=46 ) , MTA Angelus ( N=45 ) , or CH paste ( N=48 ) as pulpotomy medicaments . All pulpotomized teeth received a Class I amalgam as a final restoration . Recall examinations were carried out at one , three , six , 12 , 18 , and 24 months . RESULTS The 24-month cumulative clinical success rates for ProRoot MTA , MTA Angelus , and CH were approximately 98 percent , 96 percent , and 77 percent , respectively . The cumulative radiographic success rates for ProRoot MTA , MTA Angelus , and CH were approximately 98 percent , 91 percent , and 45 percent , respectively . For all parameters evaluated , the MTA cements showed similar clinical and radiographic outcomes ( P>.05 ) , which were significantly better than those of CH ( P<.05 ) . The two-year clinical and radiographic survival probabilities for ProRoot MTA and MTA Angelus were comparable ( P=.62 and P=.20 , respectively ) and superior to calcium hydroxide ( all P>.05 ) . CONCLUSIONS ProRoot MTA and MTA Angelus showed similar and favorable success rates as pulpotomy material s in primary molars OBJECTIVE This study was conducted to compare the efficacy of 3Mixtatin ( a combination of simvastatin and 3Mix antibiotic ) with MTA and Formocresol for the pulpotomy of primary molars . STUDY DESIGN 114 children aged 3 - 6 years old with 150 primary molars were r and omly allocated to three groups . MTA , Formocresol or 3Mixtatin were used for Pulpotomies . Hard setting zinc oxide eugenol was used to cover these material s. The teeth were restored with amalgam . Blinded radiographic and clinical examinations were conducted at 6 , 12 and 24 months after treatment for the presence of pain , tenderness to palpation and percussion , sinus tract , swelling , presence of internal or external root resorption , inter-radicular radiolucency , and periapical lesion . RESULTS 122 teeth were available for 24-month follow-up study . The overall success rate was 78.9 % for FC , 90.5 % for 3Mixtatin and 88.1 % for MTA group . There was no significant difference in overall success rate among the groups after 24-month follow-up ( X2=2.43 , df = 2 , P = 0.27 ) . CONCLUSION Our findings demonstrated remarkable results of 3Mixtatin in pulpotomy of primary teeth at the 24-month follow-up . Therefore , 3Mixtatin may be considered as an effective material in pulpotomy of primary teeth because of its successful results Introduction Direct pulp capping treatment is intended to preserve pulp vitality , to avoid or retard root canal treatment , and , in cases with an open apex , to allow continued root development . Historically , calcium hydroxide ( CH ) was the gold st and ard material , but nowadays calcium silicate material s ( CSMs ) are displacing CH because of their high bioactivity , biocompatibility , sealing ability , and mechanical properties . However , more r and omized clinical trials are needed to confirm the appropriateness of CSMs as replacement material s for CH in direct pulp capping procedures . Methods A r and omized clinical trial was conducted that included 169 patients ( mean age , 11.3 years ) from the Maipo district ( Chile ) . The inclusion criterion was patients with 1 carious permanent tooth with pulpal exposure , a c and i date for a direct pulp capping procedure . The patients were r and omly allocated to one of the experimental groups ( CH , Biodentine , or mineral trioxide aggregate [ MTA ] ) . Clinical follow‐up examinations were performed at 1 week , 3 months , 6 months , and 1 year . The Fisher exact test was performed . Results At the follow‐up examination at 1 week , the patients showed 100 % clinical success . At 3 months , there was 1 failure in the CH group . At 6 months , there were 4 new failures ( 1 in the CH group and 3 in the MTA group ) . At 1 year , there was another failure in the CH group . There were no statistically significant differences among the experimental groups . Conclusions CSMs appear to be suitable material s to replace CH . Although no significant differences were found among the material s studied , Biodentine and MTA offered some advantages over CH . HighlightsThis trial compared the efficacy of calcium hydroxide , MTA , and Biodentine as pulp capping material s in young permanent molars . MTA and Biodentine are suitable material s to replace calcium hydroxide in pulp capping procedures .Pulp capping in carious teeth is a successful treatment when done under good clinical protocol PURPOSE This manuscript presents evidence -based guidance on the use of vital pulp therapies for treatment of deep caries lesions in children . A guideline panel convened by the American Academy of Pediatric Dentistry formulated evidence -based recommendations on three vital pulp therapies : indirect pulp treatment ( IPT ; also known as indirect pulp cap ) , direct pulp cap ( DPC ) , and pulpotomy . METHODS The basis of the guideline 's recommendations was evidence from " Primary Tooth Vital Pulp Therapy : A Systematic Review and Meta- Analysis . " ( Pediatr Dent 2017;15;39[1]:16 - 23 . ) A systematic search was conducted in PubMed ® / MEDLINE , Embase ® , Cochrane Central Register of Controlled Trials , and trial data bases to identify r and omized controlled trials and systematic review s addressing peripheral issues of vital pulp therapies such as patient preferences of treatment and impact of cost . Quality of the evidence was assessed through the Grading of Recommendations Assessment , Development , and Evaluation approach ; the evidence -to-decision framework was used to formulate a recommendation . RESULTS The panel was unable to make a recommendation on superiority of any particular type of vital pulp therapy owing to lack of studies directly comparing these interventions . The panel recommends use of mineral trioxide aggregate ( MTA ) and formocresol in pulpotomy treatments ; these are recommendations based on moderate- quality evidence at 24 months . The panel made weak recommendations regarding choice of medicament in both IPT ( moderate- quality evidence [ 24 months ] , low quality evidence [ 48 months ] ) and DPC ( very-low quality evidence [ 24 months ] ) . Success of both treatments was independent of type of medicament used . The panel also recommends use of ferric sulfate ( low- quality evidence ) , lasers ( low- quality evidence ) , sodium hypochlorite ( very low- quality evidence ) , and tricalcium silicate ( very low- quality evidence ) in pulpotomies ; these are weak recommendations based on low- quality evidence . The panel recommended against the use of calcium hydroxide as pulpotomy medicament in primary teeth with deep caries lesions . Conclusions and practical implication s : The guideline intends to inform the clinical practice s with evidence -based recommendations on vital pulp therapies in primary teeth with deep caries lesions . These recommendations are based upon the best available evidence to- date Introduction An ideal pulpotomy agent for primary molars has been sought for many years . Recently , new material s that allow regeneration of residual pulp tissue have been developed . In this study , we compared the preliminary clinical results obtained using Biodentine and mineral trioxide aggregate ( MTA ) as pulp-dressing agents in pulpotomies of primary molars . Methods A r and omized clinical study was performed in children aged 4–9 years with at least one primary tooth with decay or caries requiring pulp treatment . A total of 90 primary molars requiring pulpotomy were r and omly allocated to the MTA or Biodentine group , and 84 pulpotomies were performed . Clinical and radiographic evaluations were undertaken 6 and 12 months after treatment . All teeth were restored with a reinforced zinc oxide – eugenol base and stainless steel crowns . Statistical analysis using Fisher ’s exact test was performed to determine the significant differences between the groups . Results A total of four clinical failures were observed ; all involved gingival inflammation . The clinical success rate in the MTA Group after 12 months was 92 % ( 36/39 ) , whereas the Biodentine Group obtained 97 % ( 38/39 ) ( p = 0.346 ) . All radiographic failures were observed at the 12-month follow-up evaluation . One molar from MTA Group showed internal resorption obtaining a radiographic success rate of 97 % ( 38/39 ) . Two molars from the Biodentine Group showed radiographic failure ( 1 internal resorption and 1 periradicular radiolucency ) obtaining a radiographic success rate of 95 % ( 37/39 ) . Conclusions Biodentine showed similar clinical results as MTA with comparable success rates when used for pulpotomies of primary molars . However , longer follow-up studies are required to confirm our findings . Clinical relevance This article demonstrates the effectiveness of Biodentine as a primary teeth pulpotomy material , performing similar results as MTA at 12-months evaluation AIM The aim of the present study was to clinical ly and radiographically evaluate Mineral Trioxide Aggregate ( MTA ) as an agent for pulpotomy in primary teeth and to compare it with that of Formocresol ( FC ) pulpotomy . METHOD Seventy first and second primary m and ibular molars of children were chosen on patients who required minimum two pulpotomies in either arch or same arch . After the st and ardized technique of Pulpotomy with MTA and Formocresol , all molars were treated with a thick mix of Zinc oxide Eugenol cement into the coronal pulp chamber followed by preformed stainless steel crown . The children were followed up for clinical and radio graphical examination after 6 , 12 and 24 month for Pain , Swelling , Sinus/fistula , Periapical changes , Furcation radiolucency and internal resorption . RESULTS MTA represents 97 % clinical success rate in comparison to Formocresol with 85 % success . Radiographically also MTA showed more promising results with 88.6 % success in comparison to Formocresol with 54.3 % . CONCLUSIONS Thus , MTA pulpotomy has emerged as an easier line of treatment to save the premature loss of primary teeth due to caries or trauma Background : Considering the biological concerns of calcium hydroxide ( CH ) as a pulpotomy agent , an alternative silicate based dentin substitute i.e. Biodentine ( Ca3SiO5 ) was evaluated clinical ly and radiographically . Aims : To evaluate the effectiveness of dentin substitute ( Biodentine ) in regenerative pulpotomy of vital primary teeth that would giv a biological base to its use in forming reactive dentin bridge and overcoming the drawbacks of calcium hydroxide . Material and Methods : R and omised clinical trial on 40 bilateral carious primary molars in 20 participant children ( aged 5 - 10 years ) was carried out by same operator using Ca3SiO5(group-1 ) and CH ( group-2 ) as vital pulpotomy agents . Blinded clinical and radiographic outcomes were observed at 3 , 6 and 12 months interval . Results : Clinical outcomes of both protocol s were analysed using Pearson 's chi-square test applied at P < 0.05 . Descriptive statistics were expressed as mean increase in dentin bridge formation in mms from two reference points in st and ardized radiographs using paired ' t'- test at baseline and 12 months and found to be statistically significant ( P < 0.05 ) in group-1 when compared with group-2 . Conclusion : Group-1 revealed statistically favourable regenerative potential along with clinical success compared to group 2 thereby sharing both indications and mode of action with CH , but without its drawbacks of physical and clinical properties Objectives : Pulpotomy is the common therapy for cariously exposed pulps in symptom-free primary molar teeth . For many years , research ers have search ed for an ideal material that allows regeneration of the residual pulp . The purpose of this study was to evaluate the efficacy of mineral trioxide aggregate ( MTA ) , Biodentine as a pulpotomy medicament in primary teeth , both clinical ly and radiographically . Material s and Methods : A total of 25 children ( 50 human primary molar teeth ) aged between 5 and 9 years were selected in this r and omized clinical study . The patients were r and omly assigned to receive the pulpotomy medicaments in either [ Group 1 ] : MTA or [ Group 2 ] : Biodentine . All pulpotomized teeth were restored with stainless steel crowns and evaluated clinical ly and radiologically at 1 , 3 , 6 and 12 months . Statistical analysis using Mann – Whitney U test and Fisher 's exact test , and chi-square test was performed to determine the significant differences between the groups . Results : Clinical and radiological success rates were 96 and 80 % in Group 1 and 96 and 60 % in Group 2 , respectively . There were no significant differences between the groups ( P > 0.05 ) . The radiographic success rates decreased in the controls , but there were no significant differences . Conclusion : Biodentine showed similar clinical and radiographic results as MTA in the 12-month evaluation and can be safely used as a pulpotomy medicament PURPOSE The aim of this study was to compare the effect of mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomized primary molars with carious pulp exposure . METHODS Forty-five primary molars of 26 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) or FC ( control ) group by a toss of a coin . Following removal of the coronal pulp and hemostasis the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps for 5 minutes and removed ; the pulp stumps were then covered by zinc oxide-eugenol ( ZOE ) paste . The teeth of both groups were restored with stainless steel crowns . Eighteen children with 32 teeth arrived for clinical and radiographic follow-up evaluation ranging from 6 to 30 months . RESULTS The follow-up evaluations revealed only one failure ( internal resorption detected at a 17 months postoperative evaluation ) in a molar treated with formocresol . None of the MTA-treated teeth showed any clinical or radiographic pathology . Pulp canal obliteration was observed in 9 of 32 ( 28 % ) evaluated molars . This finding was detected in 2 out of the 15 teeth treated with FC ( 13 % ) and in 7 out of the 17 treated with MTA ( 41 % ) . CONCLUSION MTA showed clinical and radiographic success as a dressing material following pulpotomy in primary teeth and seems to be a suitable replacement for formocresol in primary teeth PURPOSE This study 's purpose was to assess clinical and radiographic outcomes of Copaifera langsdorffii oil resin ( CLOR ) as a pulpotomy medicament compared with one-minute full-strength formocresol ( FC ) and white mineral trioxide aggregate ( WMTA ) . METHODS Determined by a power analysis , 152 primary molars of 64 four- to eight-year-olds with at least two asymptomatic molars requiring vital pulpotomies were recruited , r and omly assigned to receive CLOR , WMTA , or FC , and restored with prefabricated metal crowns . At the 12-month follow-up , recordings of 59 children with 142 treated teeth were taken for clinical and radiographic symptoms . Clinical evaluation was performed by a blinded calibrated evaluator , whereas four evaluators scored each radiograph for pathologies based upon a modified scale previously proposed . The data were statistically analyzed . RESULTS At 12 months , 100 percent clinical success was observed with all groups . CLOR had the highest frequency of pathologic radiolucencies at 12 months . The radiographic success at 12 months was 76 percent , 90.91 percent , and 88.23 percent for the CLOR , FC , and WMTA groups , respectively ( P=0.10 ) . CONCLUSION Copaifera langsdorffii oil resin can be suggested as a pulpotomy agent for primary teeth up to one year . However , further clinical studies with long-term follow-ups are needed to test its efficacy as a pulpotomy medicament PURPOSE The purpose of this study was to compare the clinical and radiographic success of Biodentine ™ and mineral trioxide aggregate ( MTA ) pulpotomy in primary molars . METHODS Thirty-two four- to nine-year-olds were included in this study . The primary molars were r and omly assigned to the Biodentine ™ and MTA groups . After coronal pulp removal and hemostasis , the remaining pulp tissue was covered with Biodentine ™ or MTA . All teeth were restored with stainless steel crowns . Clinical and radiographic successes and failures were recorded at six- , 12- , 18- and 24-month follow-ups . Data were statistically analyzed using Mann-Whitney U and Wilcoxon tests . RESULTS The 24-month follow-up evaluations revealed that the clinical success rates were 96.8 percent ( 30 out of 31 ) for both Biodentine ™ and MTA . The radiographic success rates at 24 months were 93.6 percent ( 29 out of 31 ) for Biodentine ™ and 87.1 percent ( 27 out of 31 ) for MTA . No significant differences were found among the groups at all follow-up appointments ( P>0.05 ) Conclusion : Biodentine ™ and mineral trioxide aggregate did not differ significantly in combined clinical and radiographic success after 24 months Objective This study compared the clinical and radiographic effectiveness of mineral trioxide aggregate ( MTA ) and Portl and cement ( PC ) as pulp dressing agents in carious primary teeth . Methodology Thirty carious primary m and ibular molars of children aged 5 - 9 years old were r and omly assigned to MTA or PC groups , and treated by a conventional pulpotomy technique . The teeth were restored with resin modified glass ionomer cement . Clinical and radiographic successes and failures were recorded at 6 , 12 , 18 and 24-month follow-up . Results All pulpotomised teeth were clinical ly and radiographically successful at all follow-up appointments . Six out of 15 teeth in the PC group and five out of 14 teeth in the MTA group exfoliated throughout the follow-up period . No statistically significant difference regarding dentine bridge formation was found between both groups throughout the follow-up period . As far as pulp canal obliteration is concerned , a statistically significant difference was detected at 6-month follow-up ( p < 0.05 ) , since the beginning of mineralised material deposition could be radiographically detected in 100 % and 57.14 % of the teeth treated with PC and MTA , respectively . Conclusions PC may serve as an effective and less expensive MTA substitute in primary molar pulpotomies . Further studies and longer follow-up assessment s are needed AIMS This in vivo study aim ed to assess and compare the relative clinical and radiographic success of formocresol , glutaraldehyde and ferric sulphate as medicaments following pulpotomies in primary molars at three-monthly intervals over one year . METHODS The study was carried out on 90 primary molars in 54 children aged from 3 to 9 years . Selected teeth were equally distributed and r and omly assigned to formocresol , glutaraldehyde and ferric sulphate pulpotomy medicament groups ( 30 in each group ) . The teeth were then evaluated clinical ly and radiographically at three-monthly intervals over one year . The result ing data were tabulated and statistically analysed using the chi-square test . RESULTS After one year , the clinical success rate was 100 % with glutaraldehyde , 96.7 % with ferric sulphate , and 86.7 % with formocresol . The radiological success rate gradually decreased over the year in all pulpotomy medicament groups . Radiological success rates in formocresol , glutaraldehyde , and ferric sulphate groups were 56.7 % , 83.3 % , and 63.3 % , respectively . CONCLUSION Two per cent glutaraldehyde may be recommended as a more effective alternative to formocresol and ferric sulphate as a pulpotomy medicament Pulpotomy is the accepted therapy for the management of cariously exposed pulps in symptom-free primary molars ; however , evidence is lacking about the most appropriate technique . The aim of this study was to compare the relative effectiveness of the Er : YAG laser , calcium hydroxide , and ferric sulfate techniques with that of dilute formocresol in retaining such molars symptom-free . Two hundred primary molars in 107 healthy children were included and r and omly allocated to one of the techniques . The treated teeth were blindly re-evaluated after 6 , 12 , 18 , and 24 months . Descriptive data analysis and logistic regression analysis , accounting for each patient ’s effect by a generalized estimating equation ( GEE ) , were used . After 24 months , the following total and clinical success rates were determined ( % ) : formocresol 85 ( 96 ) , laser 78 ( 93 ) , calcium hydroxide 53 ( 87 ) , and ferric sulfate 86 ( 100 ) . Only calcium hydroxide performed significantly worse than formocresol ( p = 0.001 , odds ratio = 5.6 , 95 % confidence interval 2.0–15.5 ) . In conclusion , calcium hydroxide is less appropriate for pulpotomies than is formocresol A pulpotomy is the therapy for management of pulp exposures due to caries in symptom-free primary molars . The aim was to longitudinally compare the relative effectiveness of the Er : YAG laser , calcium hydroxide and ferric sulphate techniques with dilute formocresol in retaining symptom-free molars . Two hundred primary molars in 107 healthy children were included and r and omly allocated to one technique . The treated teeth were blindly reevaluated after 6 , 12 , 18 , 24 and 36 months . Descriptive data analysis and logistic regression analysis accounting for multiple observations per patient by generalised estimating equation were used . Additionally , various influences including tooth type , upper and lower jaws , type of anaesthesia , operator and the final restoration on treatment success were evaluated ( Wald chi-square test ) . After 36 months , the following total ( considering clinical and clinical ly symptom-free radiographic failures ) and clinical success rates were determined ( in percent ) : Formocresol 72 ( 92 ) , laser 73 ( 89 ) , calcium hydroxide 46 ( 75 ) , ferric sulphate 76 ( 97 ) . No significant differences were detected between formocresol and any other technique after 36 months . However , the odds ratio of failure appeared to be three times higher for calcium hydroxide than for formocresol . No significant differences in total success rates were seen regarding the aforementioned influencing clinical parameters . The correct diagnosis of the pulpal status , bleeding control and the specific technique are highly important for long-term success of pulpotomies in primary molars . According to the presented long-term data , pulpotomies using ferric sulphate revealed the best treatment outcome among the used techniques , while calcium hydroxide result ed in the lowest success rates after 3 years . Therefore , we can recommend ferric sulphate for easy and successful treatment of primary molars with caries-exposed pulps PURPOSE The purpose of this multisite , multioperator , prospect i ve , r and omized , controlled clinical trial was to evaluate 2-year outcomes of diluted formocresol ( DFC ) compared to gray mineral trioxide aggregate ( GMTA ) as pulpotomy medicaments . METHODS Following the st and ard pulpotomy procedure , the pulp stumps of 252 primary molars in 168 healthy children were r and omly covered with GMTA or DFC . Pulp chambers were filled with Intermediate Restorative Material ( IRM ( ® ) ) and teeth were restored with stainless steel crowns . At each follow-up appointment , the clinical status of the treated tooth was assessed and radiographs were taken . A total of 694 clinical and radiographic evaluations were analyzed . RESULTS Gender , study site , arch type , and tooth type did not influence treatment outcome . At the combined 6- to 24-month follow-up , clinical success in the DFC group was no different than for the GMTA group . Radiographically , a significantly lower success rate was found in the DFC group vs the MTA group at all time points ( P<.01 ) . Dentin bridge formation was observed at a significantly higher frequency among the GMTA group ( P<.01 ) , while internal root resorption was observed at a higher frequency in the DFC group ( P<.01 ) . CONCLUSION At the combined 6- to 24-month follow-up , gray mineral trioxide aggregate demonstrated significantly better radiographic outcomes vs diluted formocresol as pulpotomy medicaments OBJECTIVES The aim of this study was to determine the clinical efficacy of the newly developed OrthoMTA and RetroMTA , compared to conventionally used ProRoot MTA , for pulpotomy in primary teeth . MATERIAL AND METHODS In this r and omized clinical trial , 151 molars from 102 children , who met the inclusion criteria and were 3 - 10 years old , were enrolled . Ultimately , 143 teeth were divided in a r and omized , single-blind manner into three groups according to the planned treatment : RetroMTA ( n = 49 teeth ) , OrthoMTA ( n = 47 teeth ) or ProRoot MTA ( n = 47 teeth ) . Clinical and radiographic follow-up examinations were conducted at 3 , 6 and 12 months postoperatively . RESULTS By the end of the study period , 109 teeth were evaluated at 12 months . The radiographic success rates in these three groups were 100 % , 94.7 % and 94.7 % , respectively ; the corresponding clinical success rates were 100 % , 97.4 % and 100 % . The Kaplan-Meier survival function curves relative to clinical and radiographic cumulative survival rates did not differ significantly between the three groups . CONCLUSIONS The success rates of RetroMTA , OrthoMTA and ProRoot MTA are indistinguishable , indicating that pulpotomy can be carried out successfully in primary molars with the newly developed material Background : The purpose of this study was to compare the clinical and radiographic outcomes of fresh Aloe vera barbadensis plant extract and mineral trioxide aggregate ( MTA ) as pulpotomy agents in primary molar teeth . Material s and Methods : Pulpotomy procedure was performed in sixty primary molar teeth which were r and omly allocated to two groups , i.e. , Aloe vera pulpotomy ( Group A ) and MTA pulpotomy ( Group B ) . All the pulpotomized teeth were evaluated clinical ly and radiographically at 1 , 3 , 6 , 9 , and 12 months of time interval using predetermined criteria . Results : The success rates between Groups A and B at the end of the 1st month were 24.1 % and 96.4 % , at the end of 3rd month were 57.1 % and 100 % , at the end of 6th month were 75 % and 100 % , at the end of 9th month were 66.6 % and 100 % , and at the end of 12 months were 100 % and 100 % respectively . The overall success rates at the end of 12-month follow-up period were 6.9 % and 71.4 % , respectively , after taking dropout patients into consideration , and the difference was statistically significant ( P < 0.001 ) . Conclusions : MTA pulpotomy was found to be superior when compared to fresh A. barbadensis plant extract pulpotomy in primary molars PURPOSE The purpose of this study was to test the hypothesis that there is no significant difference in the clinical and radiographic outcomes of diluted formocresol ( DFC ) compared to gray mineral trioxide aggregate ( GMTA ) pulpotomy in human primary molars . METHODS A total of 152 children with 252 primary molars met selection criteria . Of those , 119 and 133 teeth were r and omly assigned to the GMTA and DFC groups , respectively . Periapical radiographs , taken pre- and /or postoperatively and at each 6-month follow-up , were digitized and evaluated by three blinded and calibrated examiners . RESULTS Over a 42-month period , a total of 865 clinical and radiographic evaluations were conducted . There was no significant difference in clinical success , with the cumulative proportion of GMTA-treated teeth surviving at 0.98 vs DFC-treated teeth at 0.95 ( P>.05 ) . Radiographic success , however , was significantly greater for GMTA vs DFC , with the cumulative proportion of GMTA-treated teeth surviving at 0.90 vs DFC-treated teeth at 0.47 ( P<.001 ) . Overall , DFC-treated teeth were 5.1 times more likely to fail than GMTA-treated teeth . Radiographic pathologies were observed more frequently in the DFC-treated teeth ( P<.05 ) . CONCLUSION Gray mineral trioxide aggregate can be considered an acceptable replacement for diluted formocresol when used as a medicament for primary molar pulpotomies Seventy primary molar teeth , carious exposed , symptom free , without any sign of root resorption in children aged from 3 to 6 years ( main age 4.3 yr ) were treated with conventional pulpotomy procedures . Ferric sulfate 15.5 % solution ( applied for 15 second for 35 teeth ) and formocresol solution ( five minute procedure of Buckley 's formula for next 35 teeth ) have been used as pulpotomy agents . In both groups , pulp stumps were covered with zinc-oxide eugenol paste . Permanent restorations were stainless steel crowns . Clinical check up was every three-months and radiographic follow-up time was six and twenty months after treatment . Our results within this period revealed 100 % clinical success rate in both groups . Radiographic success rate was in both groups 97.2 % , while in 2.8 % cases has shown internal root resorption . On the basis of these results , we can recommend ferric sulfate as a pulpotomy agent in primary teeth in substitution for formocresol at the moment AIM To compare the clinical and radiographic efficacy of Biodentine ™ , ProRoot ® White Mineral Trioxide Aggregate ( WMTA ) and Tempophore ™ as pulpotomy medicaments in the treatment of carious primary molars . METHODOLOGY A parallel- design , r and omized controlled trial was developed . Patients above 3 years of age with carious primary teeth with vital pulps without spontaneous pain or history of swelling were included . Fifty-eight patients ( 82 teeth ) with a mean age of 4.79 ± 1.23 years were included . The teeth were r and omized , blinded and allocated to one of the three groups ( Biodentine ™ , ProRoot ® WMTA or Tempophore ™ ) for pulpotomy treatment . All teeth were followed up clinical ly and radiographically ( after 6 , 12 and 18 months ) by two blinded calibrated investigators . A generalized estimating equation ( GEE ) , Wald chi-square test and an intention-to-treat analysis ( ITT ) with ' last carried forward ' approach were performed using Statistical Package for Social Sciences v 21.0 ( IBM Corp. , Armonk , NK , USA ) . RESULTS Forty-six patients and 69 teeth were available for follow-up after 18 months . Clinical success ( radiographic success in parenthesis ) was 95.24 % ( 94.4 % ) , 100 % ( 90.9 % ) and 95.65 % ( 82.4 % ) in the Biodentine ™ , ProRoot ® WMTA and Tempophore ™ groups , respectively , but the difference was not significant . Pulp canal obliteration was significantly different amongst the experimental groups as the Biodentine ™ group exhibited significantly more pulp canal obliteration when compared to the ProRoot ® WMTA group at 6 months ( P = 0.008 ) and 18 months ( P = 0.003 ) . CONCLUSIONS After 18-month follow-up , there was no significant difference between Biodentine ™ in comparison with ProRoot ® WMTA or Tempophore ™ PURPOSE The aim of this study was to use clinical , radiographic , and histologic examinations to compare the relative success of gray mineral trioxide aggregate ( MTA ) , white MTA , and formocresol as pulp dressings in pulpotomized primary teeth . METHODS Twenty-four children , each with at least 3 primary molars requiring pulpotomy , were selected for this study 's clinical and radiographic portion . An additional 15 carious primary teeth planned for serial extraction were selected for this study 's histologic portion . All selected teeth were evenly divided into 3 test groups and treated with pulpotomies . Gray MTA was used as the pulp dressing for one third of the teeth , white MTA was the dressing for one third , and the remaining one third were treated with formocresol . The treated teeth selected for the clinical and radiographic evaluations were monitored periodically for 12 months . The treated teeth selected for histologic study were monitored periodically and extracted 6 months postoperatively . RESULTS Four children with 12 pulpotomized teeth failed to return for any follow-up evaluations in the clinical and radiographic study . Of the remaining 60 teeth in 20 patients , 1 tooth ( gray MTA ) exfoliated normally and 6 teeth ( 4 white MTA and 2 formocresol ) failed due to abscesses . The remaining 53 teeth appeared to be clinical ly and radiographically successful 12 months postoperatively . Pulp canal obliteration was a radiographic finding in 11 teeth treated with gray MTA and 1 tooth treated with white MTA . In the histologic study , both types of MTA successfully induced thick dentin bridge formation at the amputation sites , while formocresol induced thin , poorly calcified dentin . Teeth treated with gray MTA demonstrated pulp architecture nearest to normal pulp by preserving the odontoblastic layer and delicate fibrocellular matrix , yet few inflammatory cells or isolated calcified bodies were seen . Teeth treated with white MTA showed a denser fibrotic pattern , with more isolated calcifications in the pulp tissue along with secondary dentin formation . CONCLUSIONS Gray MTA appears to be superior to white MTA and formocresol as a pulp dressing for pulpotomized primary teeth PURPOSE The purpose of this study was to evaluate the total success rates of mineral trioxide aggregate ( MTA ) , ferric sulfate ( FS ) , and formocresol ( FC ) as pulpotomy agents in primary molars . METHODS A r and omized , split-mouth study design was used in 32 healthy 5- to 7-year-old children with 128 carious primary molars without clinical or radiographic evidence of pulp degeneration . The pulpotomy agents were assigned as follows : Group 1=MTA ; Group 2=FS ; Group 3=1:5 diluted Buckley 's FC ; and Group 4=zinc oxide eugenol ( ZOE ) base . Clinical and radiographic follow-up at 6 , 12 , and 24 months used the following criteria : pain ; swelling ; sinus tract ; mobility ; internal root resorption ; and furcation and /or periapical bone destruction . The data were analyzed using chi-square . RESULTS No significant differences in success rates were found among the groups at 6 and 12 months . Success rates in groups 1 to 4 at 24 months were 96 % , 88 % , 88 % , and 68 % respectively . There was a significant difference ( P<.001 ) between the MTA and ZOE groups at 24 months . CONCLUSIONS ZOE , as the only pulpotomy medicament , had a significantly lower success rate than MTA . No significant differences were observed , among the 3 experimental material s ( MTA , FC , and FS ) at 2 years follow-up AIM To evaluate and compare mineral trioxide aggregate ( MTA ) and formocresol as pulpotomy medicaments by clinical and radiographic assessment s and to assess the histological features of both pulpotomy medicaments in deciduous teeth . MATERIAL S AND METHODS This study was performed on 100 m and ibular deciduous molar teeth requiring pulpotomy treatment . Children between age four and six years were r and omly selected and divided into formocresol or MTA group . The patients were recalled after 3 , 6 , 9 , 12 months respectively and evaluated clinical ly and radiographically . Histological assessment was done on lower deciduous canine teeth , which were undergoing serial extraction for interceptive orthodontic purpose . Pulpotomy was done on four teeth with formocresol and another four teeth with MTA . The teeth were extracted after six months following pulpotomy procedure and histologically evaluated . Two freshly extracted carious teeth were taken as controls . RESULTS Clinical and radiographic criteria were laid and Chi analysis revealed significant difference in mobility ( P≤0.05 ) , periodontal ligament widening ( P≤0.01 level ) and inter - radicular radiolucency ( P≤0.02 level ) between two groups at the end of 12 months . Histologically , in MTA group , a layer of new dentine formation with less dentinal tubules at the pulpotomized site was found . In formocresol group , increased inflammatory cells , a zone of atrophy , were noted in radicular portion of pulp . CONCLUSION MTA is superior to formocresol clinical ly , radiographically . Histological analysis showed better reparative ability with hard tissue barrier formation with MTA compared to formocresol INTRODUCTION Inspite of latest advances in the material s and techniques practice d for the treatment of pulpally infected teeth with better reported success rate , still the question arises for safety and effectiveness of these medicaments . AIM The objective of the present study was to compare the effectiveness of the Low Level Laser Therapy to Mineral Trioxide Aggregate ( MTA ) when used for pulpotomy in vital human primary molars . MATERIAL S AND METHODS The sample consisted of 40 primary molars from 29 children aged four to seven years . The teeth were selected based on clinical , radiographic criteria and r and omly allocated to two groups . All the 40 primary molars were subjected to st and ard pulpotomy procedure , where in 20 molars received MTA ( Group I ) and 20 molars received LLLT ( Group II ) pulpotomy . Children were recalled at 3 , 6 and 12 months intervals and pulpotomised molars were examined clinical ly and radiographically . Data was analysed using chi-square test . RESULTS MTA showed 94.7 % success rate at all the three intervals , where as LLLT showed a success of 95 % at three months , which decreased gradually to 85 % at six months and 80 % at 12 months . Intergroup comparisons were not significant . CONCLUSION Low level laser therapy can be considered for primary teeth pulpotomy and its success is comparable to MTA pulpotomy technique BACKGROUND Pulpotomy is the common therapy for cariously exposed pulps in symptom-free primary molar teeth . Formocresol ( FC ) is considered the gold st and ard dressing agent for pulpotomy , but concerns have been raised over the years about its safety . Other alternative pulpotomy agents have been investigated and suggested . OBJECTIVE The objective was to evaluate and compare the clinical and radiographic response of FC and white mineral trioxide aggregate ( MTA ) as pulpotomy material s on primary molars . MATERIAL S AND METHODS Fifty primary molars , with deep carious lesion that exposed a vital but asymptomatic pulp , in 37 children aged 4 - 7 years were treated with conventional pulpotomy procedure . The teeth were divided r and omly into two groups . Group I ( FC ) and group II ( MTA ) . The treated teeth were evaluated clinical ly and radiographically and were followed-up for 12 months . RESULTS At the end of the 12 months follow-up , the clinical success rates for FC and MTA were 81 % and 100 % , respectively . There was a statistically significant difference ( P = 0.04 ) between the clinical success rates of FC and MTA . While the radiographic success rates for FC and MTA were 81 % and 96 % , respectively , there was no statistically significant difference between the radiographic success of MTA and FC . CONCLUSION White MTA showed a higher clinical and radiographic success rate when compared to FC as a pulpotomy agent in vital primary molars , and it has a potential to become a replacement for FC in primary molars This study utilized clinical and radiographic examinations to compare the effectiveness of calcium hydroxide paste and mineral trioxide aggregate ( MTA ) for pulpotomies of primary molars in children . Ninety primary molars that showed clinical and radiographic indications for pulpotomy treatment were selected . The pulpotomies were performed in two sessions , using a corticosteroid/antibiotic solution as therapeutic dressing . The sample was divided into two groups of 45 teeth , in which the pulpal remains were protected with either calcium hydroxide paste ( Group 1 ) or MTA ( Group 2 ) . Radiographs were taken immediately and at 3- , 6- , and 12-month follow-up appointments . Three teeth in Group 1 failed after three months , while two cases failed after six months and one more failed at one year . Two failures were found in Group 2 at the 12-month follow-up . These results indicate that both material s may be utilized for pulpotomies in primary teeth PURPOSE This study 's purpose was to evaluate the success of calcium hydroxide ( CH ) and mineral trioxide aggregate ( MTA ) pulpotomies following the use of five percent sodium hypochlorite ( NaOCl ) as an antibacterial agent to clean the chamber prior to application of the pulpotomy agent . METHODS A total of 128 teeth were r and omly divided into two pulpotomy groups ( CH or MTA ) . The teeth in each pulpotomy group , CH and MTA , were further r and omly divided into subgroups to receive either the NaOCl ( experimental ) or saline ( control ) cleaning agent prior to applying the pulpotomy agent . The treatments were followed clinical ly and radiographically for 12 months . RESULTS The radiographic success rates were 84 percent for CH NaOCl , 74 percent for CH saline control , 97 percent for MTA NaOCl , and 100 percent for MTA saline control . There were no significant differences between the radiographic success rates in the CH and MTA subgroups ( CH NaOCl-CH control and MTA NaOCl-MTA control ) ; no significant differences were observed when comparing the CH NaOCl-MTA NaOCl groups and the CH NaOCl-MTA control groups . CONCLUSION Use of sodium hypochlorite as an antibacterial agent prior to application of the pulpotomy agent improved the success of calcium hydroxide pulpotomies to equal the success of mineral trioxide aggregate pulpotomies for observation up to 12 months Aim : The aim of the study was to provide a comparative evaluation of the clinical and radiographic success of Ankaferd blood stopper ( ABS ) , formocresol ( FC ) , and ferric sulfate ( FS ) as pulpotomy agent in primary teeth . Setting s and Design : This is a clinical study . Material s and Methods : A total of 45 primary m and ibular molar teeth in 26 children aged 6–9 were selected for the study . Teeth were r and omly divided into three groups according to the pulpotomy agents ( ABS , FC , FS ) . Following treatment , for 24 months , teeth were clinical ly and radiographically evaluated once every 3 and 6 months respectively . Statistical Analysis Used : SPSS version 15 software was used in data analysis . Kaplan– Meier , Log Rank and Fisher 's exact tests were used to analysis . Results : After follow-up periods ranging from 6 to 24 months ( average 20.8±0.56 ) , the clinical success rates for ABS , FC , and FS were 87 % , 87 % , and 100 % respectively . The overall radiographic success was 87 % , 80 % , and 87 % . When success rates of the ABS were compared with other agents , there were no significant differences between groups ( P > 0.05 ) . Conclusion : Similar success was achieved in the pulpotomy treatment of primary teeth that using ABS , FC , and FS . ABS would be considered a suitable agent for pulpotomy treatment and can be used as an alternative to other agents UNLABELLED The aim of the present study was to compare , clinical ly and radiographically , the mineral trioxide aggregate ( MTA ) to formocresol ( FC ) when used as medicaments in pulpotomized vital human primary molars . METHODS The sample consisted of 120 primary molars , all teeth were treated with the same conventional pulpotomy technique . Sixty molars received FC and 60 received MTA throughout a r and om selection technique . RESULTS At the end of 24-month evaluation period , 74 molars ( 36 FC , 38 MTA ) were available for clinical and radiographic evaluation . None of the MTA treated teeth showed any clinical or radiographic pathology , while the FC group showed a success rate of 86.8 % radiographically and 98.6 % clinical ly . The difference between the two groups in the radiographic outcomes was statistically significant . It was concluded that MTA treated molars demonstrated significantly greater success . MTA seems to be a suitable replacement for formocresol in pulpotomized primary teeth BACKGROUND Although multiple material s have been suggested for pulpotomized primary molars , there is no reliable evidence of the superiority of one particular type . AIM To compare the effectiveness of formocresol ( FC ) , mineral trioxide aggregate ( MTA ) , ferric sulphate , and sodium hypochlorite ( NaOCl ) as pulp dressing agents in primary molars after 2 years . DESIGN One hundred primary molars requiring pulp treatment were allocated r and omly to the control ( FC ) and experimental groups ( MTA , ferric sulphate , and NaOCl ) . Clinical and radiographic evaluations were performed at 6 , 12 , 18 , and 24 months . Statistical analysis using Fischer 's exact test was performed to determine the significant differences between groups . RESULTS In the FC and MTA groups , 100 % of the available teeth were clinical ly successful at all follow-up appointments . In the NaOCl group , one clinical failure was found at 18 months , and two clinical failures in the ferric sulphate group were noted at 12 and 24 months , but no significant differences were found among the groups ( P = 0.41 ) . No significant differences in radiographic success were found among all the groups at 24 months of follow-up ( P = 0.303 ) . CONCLUSIONS No statistically significant differences among the four material s were found at 24 months suggesting that NaOCl may be an appropriate substitute for FC OBJECTIVE The purpose of this study was to investigate whether a diode laser pulpotomy with mineral trioxide aggregate ( MTA ) sealing could be an acceptable alternative to the conventional formocresol pulpotomy and zinc oxide eugenol ( ZOE ) sealing in human primary teeth . METHODS A r and omized , single-blind , split-mouth study was used with a sample of 16 children aged from 3 to 8 years ( mean age=5.10 years ) . A total of 26 pairs of teeth from these 16 patients were selected based on clinical and radiographic criteria . One tooth from each pair was r and omly assigned to either the laser-MTA pulpotomy group or the formocresol-ZOE pulpotomy group . All teeth were followed up clinical ly and radiographically at 2.3 , 5.2 , 9.5 and 15.7 months . All extracted failures were sectioned and photographed to assess possible reasons for this . RESULTS A total of seven laser-MTA-treated teeth were deemed to be radiographic failures ( mean time until failure=9.1 months ) compared to three formocresol-ZOE treated teeth ( mean time until failure=12.5 months ) . These results were not significant using Fisher 's exact test ( P>0.05 ) . Six of the laser-MTA failures and all three formocresol-ZOE failures exhibited furcal and /or periapical radiolucencies with or without pathologic root resorption . One of the laser-MTA failures displayed premature root resorption and is being observed for exfoliation . Analysis of photographs of teeth available for extraction revealed errors in clinical technique in addition to expected signs of a disease process such as the presence of granulation tissue and areas of pathologic root resorption . CONCLUSIONS The laser-MTA pulpotomy showed reduced radiographic success rates compared to the formocresol-ZOE pulpotomy at 15.7 months ; however , these results were not statistically significant . Improved success rates among a larger patient sample and a longer follow-up period would be required for the laser-MTA pulpotomy to be considered a routine alternative to the conventional formocresol-ZOE procedure . Meticulous restorative techniques must be followed to ensure the success of laser-MTA pulpotomies PURPOSE The purpose of this study was to evaluate the clinical and radiographic success rates of mineral trioxide aggregate partial pulpotomy ( PP ) compared to formocresol pulpotomy ( FP ) in human primary molars . METHODS In this r and omized , controlled , split-mouth , clinical trial , 25 healthy five- to eight-year-olds , with 50 carious primary m and ibular second molars lacking clinical and radiographic evidence of pulp pathology , were selected . The selected teeth were r and omly assigned into two groups , PP and FP , for vital pulp therapy . Stainless steel crowns were placed as final restorations for both groups . Clinical and radiographic evaluation at six , 12 , and 24 months used the following criteria for failure : pain ; swelling ; sinus tract ; mobility ; internal or external root resorption ; furcation or periapical radiolucency ; and widening of periodontal ligament space . The data were analyzed using a binary logistic generalized estimating equation model . RESULTS At the 12-month and 24-month follow-ups , one child and three children , respectively , were lost to follow-up . At the 24-month follow-up , the clinical , radiographic , and overall success rates of PP were 90.9 percent , 90.5 percent , and 81.8 percent versus FP success of 100 percent , 95.2 percent , and 95.2 percent , respectively . CONCLUSION There were no significant differences between clinical , radiographic , and overall success rate of mineral trioxide aggregate partial pulpotomy and formocresol pulpotomy overall 24 months OBJECTIVE To compare the effects of mineral trioxide aggregate ( MTA ) and calcium hydroxide ( CH ) for pulpotomy in primary molars . METHODS A r and omised , bilateral self-controlled clinical trial was design ed to compare the clinical effect of MTA and CH in pulpotomies in primary molars in 4- to 9-year-old children . Children with two similar-sized cavities on bilateral primary molar counterparts requiring pulpotomies were included . The two contralateral molars in each patient were r and omly assigned to MTA or CH treatment . Clinical and radiographic examinations were performed to evaluate the treatment results at post-treatment recall . RESULTS Seventeen pairs of self-controlled contralateral teeth were available for follow-up evaluations . The success rate of MTA was 94.1 % ( 16/17 ) , while the success rate of CH was 64.7 % ( 11/17 ) . Internal root resorption was the most frequent reason for failure in the CH group . Crown discolouration was common in the MTA-treated group . CONCLUSION MTA was more successful than CH for pulpotomies in primary molar teeth , and may be a suitable replacement for CH in primary molar pulpotomies PURPOSE This study 's purpose was to compare the clinical and radiographic success rates of 5.25 percent Sodium Hypochlorite ( NaOCl ) pulpotomies to Formocresol ( FC ) and Ferric Sulfate ( FS ) in decayed primary molars . METHODS Eighty-one primary molars , r and omly divided into three groups , were treated with one of three different pulpotomy material s ; NaOCl , FC and FS . The outcomes of the different groups were assessed clinical ly and radiographically every six months over 18 months . Chi-square test was used to detect differences in outcome measures in all groups . RESULTS At six months , clinical and radiographic success rates were 100 percent for each group ( 27/27 ) . At 12 months , clinical success was 100 percent ( 24/24 ) , 96 percent ( 24/25 ) , and 95.7 percent ( 22/23 ) for NaOCl , FC , and FS respectively . The radiographic success was 95.8 percent ( 23/24 ) for NaOCl group , and 100 percent for FC ( 25/25 ) , and FS ( 23/23 ) . At 18 months , the clinical success was 83.3 percent ( 20/24 ) , 96 percent ( 24/25 ) , and 87 percent ( 20/23 ) for NaOCL , FC , and FS respectively . The 18 month radiographic success was 91.7 percent ( 22/24 ) , 100 percent ( 25/25 ) , and 95.7 percent ( 22/23 ) for NaOCl , FC , and FS respectively . No significant differences were found in clinical or radiographic outcomes between the three groups at six , 12 and 18 months . CONCLUSION The three pulpotomy medicaments yielded similar outcomes The aim of this study was to evaluate the clinical , radiographic and histological outcomes of the dentin-pulp complex from primary molars after pulpotomy with mineral trioxide aggregate ( MTA ) and 15.5 % ferric sulfate ( FS ) . Thirty-one primary molars were r and omly allocated into MTA or FS groups . Clinical and radiographic evaluations were recorded at 3- , 6- , 12- and 18-month follow-up . Teeth at the regular exfoliation period were extracted and processed for histological analysis . Clinical and radiographic data were tested by statistical analysis ( p≤0.01 ) . Histological outcomes were analyzed descriptively . All of the treated teeth presented clinical success over the experimental periods . Both groups exhibited 100 % of radiographic success at 3 , 6 and 12 months . At the 18-month follow-up , one tooth from FS group presented inter-radicular radiolucency ( p>0.01 ) . Histologically , the treated teeth presented pulp vitality and absence of inflammatory infiltrate into the connective tissue . Only MTA group showed hard tissue barrier surrounded by odontoblasts over the pulp stumps . Both MTA and 15.5 % FS are effective for pulpotomies of primary teeth . Although MTA is considered the first-choice material , FS may be a suitable alternative when treatment cost is an issue Aim : The present study is an attempt to compare and evaluate postoperative assessment of diode laser zinc oxide eugenol ( ZOE ) pulpotomy and diode laser mineral trioxide aggregate ( MTA ) pulpotomy procedures in children . Material s and Methods : Forty carious primary molars indicated for pulpotomy within the age group of 4–9 years were selected and divided into two groups of 20 each using simple r and omization , Group 1 : Diode laser MTA and Group 2 : Diode laser ZOE pulpotomy . The teeth were evaluated clinical ly for 1 year at 3 , 6 , and 12 months interval and radiologically for 6 and 12 months . Results : Clinical ly and radiographically , 100 % teeth treated with diode laser MTA and 94 % treated with diode laser ZOE were considered successful after 12-month follow-up interval . No significant difference was seen between two groups . Conclusion : Despite the success rate , the cost factor of diode laser and MTA could be the limiting factor in its judicious use in pulpotomy procedure Background The objective of this clinical study was to prospect ively compare the clinical and radiographic success rates of BiodentineTM pulpotomies versus formocresol pulpotomies in children vital primary molars . Methods A r and omized , split – mouth study design was used with a sample of 37 healthy children aged 4– to 8–year – old . A total of 56 pairs ( 112 teeth ) of carious primary teeth , 1 pair per child , were selected for treatment . One tooth from each pair was r and omly assigned to either the BiodentineTM pulpotomy group or the formocresol pulpotomy group . Children were followed – up at 3 , 6 and 12 months for clinical evaluation and at 6 and 12 months for radiographic evaluation . Data were collected , tabulated and analyzed using Fisher exact and McNemar tests . The level of significance was set at P < 0.05 . Results At 12 months , the clinical success rates of both BiodentineTM and formocresol groups were 100 % , while the radiographic success rates for BiodentineTM and formocresol groups were 100 % and 98.1 % , respectively . There was no statistically significant difference between both groups ( P=1 ) . The only observed radiographic failure was furcal radiolucency in the formocresol group at 12–month interval . Pulp canal obliteration was radiographically observed in 10/56 ( 17.9 % ) and 7/56 ( 12.5 % ) cases in the BiodentineTM and formocresol groups , respectively . Conclusions Both BiodentineTM and formocresol pulpotomy techniques demonstrated favorable clinical and radiographic outcomes over a 12-month period without any significant difference . Trial registration Registered on NCT03779698 . Date of Registration : 18 December 2018 Objective : To evaluate the clinical and radiographical success of primary molar pulpotomies which used 15.5 % ferric sulfate ( FS ) or 1.25 % sodium hypochlorite ( NaOCl ) for hemostasis and zinc oxide – eugenol ( ZOE ) and calcium hydroxide ( CH ) pastes as base material s. Methods : In 29 healthy children , 80 primary molars were r and omly allocated to one of the study groups : Group 1 : FS-ZOE , Group 2 : FS-CH , Group 3 : NaOCl-ZOE , and Group 4 : NaOCl-CH . After hemostasis with the respective solutions , pulp stumps and floor of the pulp chambers were covered with either ZOE or CH pastes . All teeth were restored with stainless steel crowns . Follow-up examinations were carried out at 1 , 3 , 6 , and 12 months . Results : One tooth in Group 1 and two teeth in Group 4 were extracted because of pain and periapial pathosis at sixth month . After 12 months , clinical success rates of pulpotomies in Groups 1–4 were 95 % , 100 % , 100 % , and 89.5 % , respectively . The differences were not significant ( P = 0.548 ) . Radiographic success rates for Groups 1–4 were 80 % , 88.9 % , 78.9 % , and 84.2 % , respectively . No statistically significant difference was found ( P = 0.968 ) . Pain on percussion was the most observed clinical finding . However , internal root resorption was the most common radiological finding and it was observed significantly more in m and ibular primary molars ( P < 0.05 ) . Conclusion : Both ZOE and CH can be preferred as base material s after hemostasis achieved by the use of 15.5 % FS or 1.25 % NaOCl in primary tooth pulpotomy Purpose : The purpose of this study was to compare the success of pulpotomies in primary molars using a new type of mineral trioxide aggregate ( MTA ; NeoMTA Plus ) with a conventional MTA ( ProRoot MTA ) as a pulpotomy medicament in primary molars . Methods : Eighty primary teeth in 28 patients were divided r and omly , with 40 teeth in a control group ( ProRoot MTA ) and 40 teeth in an experimental group ( NeoMTA Plus ) . A st and ardized pulpotomy technique was performed for each tooth . Clinical and radiographic follow-up examinations were conducted at three , six , and 12 months . Results : At 12 months , the clinical success for ProRoot MTA was 97.4 percent ( 38 out of 39 ) and the radiographic success was 94.9 percent ( 37 out of 39 ) ; for NeoMTA Plus , the clinical success was 100 percent ( 40 out of 40 ) and the radiographic success was 97.5 percent ( 39 out of 40 ) . No significant differences were found between the two groups at all follow-up evaluations . Conclusions : NeoMTA Plus showed a high percent success , similar to that of ProRoot MTA . NeoMTA Plus is a potential pulpotomy medicament for primary teeth AIM To compare the effectiveness of mineral trioxide aggregate ( MTA ) , calcium hydroxide ( CH ) and formocresol ( FC ) as pulp dressing agents in carious primary teeth . METHODOLOGY Forty-five primary m and ibular molars with dental caries in 23 children [ AUTHOR QUERY : How many children ? ] between 5 and 9 years old were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the experimental ( CH or MTA ) or control ( FC ) groups . After coronal pulp removal and haemostasis , remaining pulp tissue was covered with MTA paste or CH powder in the experimental groups . In the control group , diluted FC was placed with a cotton pellet over the pulp tissue for 5 min and removed ; the pulp tissue was then covered with zinc oxide-eugenol ( ZOE ) paste . All teeth were restored with reinforced ZOE base and resin modified glass-ionomer cement . Clinical and radiographic successes and failures were recorded at 3 , 6 , 12 , 18 and 24 month follow-up . RESULTS Forty-three teeth were available for follow-up . In the FC and MTA groups , 100 % of the available teeth were clinical ly and radiographically successful at all follow-up appointments ; dentine bridge formation could be detected in 29 % of the teeth treated with MTA . In the CH group , 64 % of the teeth presented clinical and radiographic failures detected throughout the follow-up period , and internal resorption was a frequent radiographic finding . CONCLUSIONS Mineral trioxide aggregate was superior to CH and equally as effective as FC as a pulpotomy dressing in primary m and ibular molars . Internal resorption was the most common radiographic finding up to 24 month after pulpotomies performed with CH |
13,987 | 28,320,362 | Early Dynamic Ultrasound ( DUS ) is consistently described as a reliable assessment of NIH .
Conclusions In the context of increased prevalence of DDH in rural Australia , contemporary evidence suggests that introduction of early DUS could provide rural infants with more effective screening than clinical examination alone .
Targeted early advice about posturing and simple removable supports to abduct infant hips could prevent some cases of DDH in rural Australia | Background Neonatal instability of the hip ( NIH ) , where the femoral head can move away from the acetabulum , in the first weeks of life , is an important risk factor for developmental dysplasia of the hip ( DDH ) .
In rural areas in Australia , there is a recent trend to increased late diagnosis of DDH .
Clinical screening of infant hips , a common practice in Australia , is experience dependent .
Best practice early screening techniques are still debated with different techniques and timing used internationally .
This systematic review examines early dynamic ultrasound ( eDUS ) screening for hip instability in the first 6 weeks after birth , and the early interventions informed by these findings and considers the findings for the context of rural Australia . | Fifty patients with clinical suspicion of hip dislocation were investigated prospect ively with a dynamic ultrasound stress test . A posterior force was applied to hips in flexion and any movement between the femoral head and the acetabulum was measured . The results of this test showed that posterior movement ranged from 0 to 13.0 mm . Hips that were clinical ly normal had a mean movement of 1.4 mm , hips with minor clinical instability had a mean movement of 0.6 mm , hips with moderate instability had a mean movement of 4.5 mm , and those with major instability had a mean movement of 5.1 mm . This was statistically significant to a 1 % confidence interval . We propose two groups of ultrasound-detected movement : group A < 5.0 mm representing physiologic laxity , and group B ° 5.0 mm being pathological and requiring treatment Objectives The authors report the results of a selective ultrasound screening programme for congenital dislocation of the hip ( CDH ) over a period of 20 years , with the aim of defining the rate of screening , conservative treatment and late presentation requiring surgery . Methods All neonates born from June 1988 to December 2008 ( inclusive ) were included in the prospect i ve cohort , with a minimum follow-up of 12 months . All underwent an early clinical examination of the hips and those with clinical instability were referred for ultrasound at 2 weeks ; those with risk factors were sonographically examined at 6 weeks . Risk factors were defined as breech presentation , family history or foot deformity . Results 107 440 live births were clinical ly examined , 20 344 ( 18.9 % ) were referred for ultrasound assessment at either 2 weeks ( due to clinical signs ) or 6 weeks ( due to risk factors ) . 774 ( 3.8 % ) were diagnosed with dysplasia with a crude overall treatment rate of 7.2 per 1000 live births . 37 ( 0.34 per 1000 ) presented late , that is , after 12 weeks of age ; none had detectable clinical signs or risk factors . There were no false negatives . Conclusion Elective screening for developmental dysplasia of the hip in association with one stop treatment and monitoring is an effective programme . The number of infants referred increased statistically significantly year on year over the study period and generated more activity . Pavlik harness treatment rates remained acceptable and steady over the period , despite the increase in referrals . The incidence of late presenting cases ranged from 0 to 4 per year , with no secular trend and there were no ultrasound false negatives OBJECTIVE : We conducted a blinded , r and omized , controlled trial to examine whether mildly dysplastic but stable or instable hips would benefit from early treatment , as compared with watchful waiting . PATIENTS AND METHODS : A total of 128 newborns with mild hip dysplasia ( sonographic inclination angle [ α angle ] of 43 ° –49 ° ) and stable or instable but not dislocatable hips were r and omly assigned to receive either 6 weeks of abduction treatment ( immediate-treatment group ) or follow-up alone ( active-sonographic-surveillance group ) . The main outcome measurement was the acetabular inclination angle , measured by radiograph , at 1 year of age . RESULTS : Both groups included 64 newborns , and there was no loss to follow-up . With the exception of a small but statistically significant excess of girls in the active-sonographic-surveillance group , there were no statistically significant differences in baseline characteristics between the 2 groups . The mean inclination angle at 12 months was 24.2 ° for both groups ( difference : 0.1 [ 95 % confidence interval ( CI ) : −0.8 to 0.9 ] ) , and all children had improved and were without treatment . The mean α angle was 59.7 ° in the treatment group and 57.1 ° in the active-surveillance group for a difference of 2.6 ° evaluated after 1.5 and 3 months ( 95 % CI : 1.8 to 3.4 ; P < .001 ) . At 1.5 months of age , the hips had improved in all treated children but not in 5 children under active surveillance ( P = .06 ) . Among the sonographic-surveillance group , 47 % received treatment after the initial surveillance period of 1.5 months . CONCLUSIONS : Active-sonographic-surveillance halved the number of children requiring treatment , did not increase the duration of treatment , and yielded similar results at 1-year follow-up . Given a reported prevalence of 1.3 % for mildly dysplastic but stable hips , a strategy of active surveillance would reduce the overall treatment rate by 0.6 % . Our results may have important implication s for families as well as for health care costs Background : Ultrasound is increasingly being used to complement the clinical examination in assessing neonatal hip instability . The clinical examination , although highly sensitive in detecting hip instability , can lead to considerable overtreatment . Purpose : To compare anterior dynamic ultrasound and clinical examination in the assessment of neonatal hip instability and regarding treatment rates . Material and Methods : 536 newborn infants ( out of a population of 18,031 ) were selected , on the basis of a combination of risk factors , clinical signs of hip instability or ambiguous clinical findings , to undergo an anterior dynamic ultrasound examination of the hip , by a method developed by our group . This examination , performed by one out of seven experienced examiners , was compared with the st and ard clinical hip examination conducted by one of four pediatric orthopedic surgeons . The clinical examination was carried out both prior to and within a few hours after the ultrasound examination . Results : The clinical examination diagnosed 81.7 % of the hips as normal , 14.5 % as unstable , and 3.8 % as dislocatable or dislocated . With the dynamic ultrasound method , the corresponding figures were 87.8 % , 10.4 % , and 1.8 % , respectively . Use of the criteria of the clinical examination result ed in treatment of 147 infants . Using the dynamic ultrasound examination as a criterion meant that 87 infants would receive treatment . The calculated treatment rate was 0.85 % when based on the clinical stress test and 0.49 % when based on the dynamic ultrasound . Conclusion : The dynamic ultrasound results reduced the treatment rate by over 40 % when used as a basis for the decision regarding treatment Objective : To evaluate the quality of the routine examination of the newborn as carried out by senior house officers ( SHOs ) and midwives . Design : R and omised controlled trial set in a district general hospital in Southeast Engl and . Eligible babies were r and omised to a midwife ( 11 ) or an SHO ( 8) who were then video recorded undertaking the routine newborn examination . Main outcome measures : Quality of 62 observed technical and communication components of the newborn examination , as agreed between independent consultant paediatrician and senior midwife raters . Results : Major differences were found in the rated quality of examinations between midwives and SHOs for the examinations of the heart and lungs , for the overall quality of the examination , and in areas of communication skills . Quality of examination of the hips was assessed as poor for both professional groups . Where there were significant differences between examiners , the quality of the midwives ' examinations was higher . Inter-rater agreement between the consultant paediatricians and senior midwives ranged from excellent to poor for different items of the examination with a mean kappa value of 0.42 across all items indicating moderate agreement . Conclusions : The quality of midwife examinations exceeded that of SHOs . All midwives who examine receive formalised training in the examination of the newborn ; SHOs may benefit from similar specific training . Training for both professional groups may need to be review ed , particularly in relation to agreement on ' gold st and ards ' for the screening of developmental dysplasia of the hip The aim of this study was to evaluate whether universal ( all neonates ) or selective ( neonates belonging to the risk groups ) ultrasound screening of the hips should be recommended at birth . We carried out a prospect i ve , r and omised trial between 1988 and 1992 , including all newborn infants at our hospital . A total of 15 529 infants was r and omised to either clinical screening and ultrasound examination of all hips or clinical screening of all hips and ultrasound examination only of those at risk . The effect of the screening was assessed by the rate of late detection of congenital or developmental hip dysplasia in the two groups . During follow-up of between six and 11 years , only one late-detected hip dysplasia was seen in the universal group , compared with five in the subjective group , representing a rate of 0.13 and 0.65 per 1,000 , respectively . The difference in late detection between the two groups was not statistically significant ( p = 0.22 ) . When clinical screening is of high quality , as in our study , the effect of an additional ultrasound examination , measured as late-presenting hip dysplasia , is marginal . Under such circumstances , we consider that universal ultrasound screening is not necessary , but recommend selective ultrasound screening for neonates with abnormal or suspicious clinical findings and those with risk factors for hip dysplasia BACKGROUND Clinical screening aims to identify and treat neonatal hip instability associated with increased risk of hip displacement , but risks failures of diagnosis and treatment ( abduction splinting ) , iatrogenic effects , and costs to parents and health services . Our objectives were to assess clinical effectiveness and net cost of ultrasonography compared with clinical assessment alone , to provide guidance for management of infants with clinical hip instability . METHODS Infants with clinical hip instability were recruited from 33 centres in UK and Irel and and r and omised to either ultrasonographic hip examination ( n=314 ) or clinical assessment alone ( n=315 ) . The primary outcome was appearance on hip radiographs by 2 years . Secondary outcomes included surgical treatment , abduction splinting , level of mobility , re source use , and costs . Analysis was by intention to treat . FINDINGS Protocol compliance was high , and radiographic information was available for 91 % of children by 12 - 14 months and 85 % by 2 years . By age 2 years , subluxation , dislocation , or acetabular dysplasia were identified by radiography on one or both hips of 21 children in each of the groups ( relative risk 1.00 ; 95 % CI 0.56 - 1.80 ) . Fewer children in the ultrasonography group had abduction splinting in the first 2 years than did those in the no-ultrasonography group ( 0.78 ; 0.65 - 0.94 ; p=0.01 ) . Surgical treatment was required by 21 infants in the ultrasonography group ( 6.7 % ) and 25 ( 7.9 % ) in the no-ultrasonography group ( 0.84 ; 0.48 - 1.47 ) . One child from the ultrasonography group and four from the no-ultrasonography group were not walking by 2 years ( 0.25 ; 0.03 - 2.53 ; p=0.37 ) . Infants in the ultrasonography group incurred significantly higher ultrasound costs over the first 2 years ( pound 42 vs pound 23 , mean difference pound 19 , 95 % CI 11 - 27 ) ; total hospital costs were lower for those infants , but the difference was not significant . INTERPRETATION The use of ultrasonography in infants with screen-detected clinical hip instability allows abduction splinting rates to be reduced , and is not associated with an increase in abnormal hip development , higher rates of surgical treatment by 2 years of age , or significantly higher health-service costs We evaluated risk factors for neonatal hip instability ( NHI ) at birth using ultrasonography and assessed the reliability of our ultrasound method by means of an interobserver study . The hips of 4,459 newborns were examined by ultrasound from 1988 to 1990 . The ultrasound evaluation was based mainly on measurement of femoral head coverage ( FHC ) by the bony acetabular roof . The mean FHC was 56 % in boys and 54 % in girls ( a significant difference ) . Fifty-five newborns with unstable hips had a mean FHC of 37 % , which was significantly lower than that of the normal hips . Known risk factors for NHI were confirmed ( breech position , family history of hip dysplasia , increased birth weight ) , but no new risk factors were detected . The interobserver study included 200 hips . The 95 % confidence limit for interobserver variation in FHC ( ±2 SD ) was ±8 % . Because of this moderate interobserver variation , and because the incidence of late-detected hip dysplasia was low ( 0.2 per 1,000 ) , we conclude that our method for ultrasound examination is sufficiently reliable for screening of hips in newborns INTRODUCTION Developmental dysplasia of the hip ( DDH ) can result in chronic pain , gait abnormalities and degenerative arthritis . Infants with a family history , Breech delivery or unstable/"clicking " of the hip on examination are at higher risk . The goal is to detect cases early enough for normal hip development and function by the end of adolescence , but clinical examination alone is ineffective . MATERIAL S AND METHODS All infants born at the West Middlesex University Hospital , Isle-worth , U.K. , between 3/3/2005 and 21/10/2006 underwent prospect i ve clinical screening to reveal risk factors of unstable hip on examination , family history of DDH and Breech delivery . Infants with risk factors underwent static and dynamic ultrasound of the hips ( Harke 's method with Terjesen measurements ) , performed by a consultant radiologist or sonographer . The infant was then examined by an Orthopaedic Surgeon who was blinded to the ultrasound findings until after creating a management plan . RESULTS 5772 infants were born during the study period . 200 ( 3.5 % ) at-risk infants were identified , result ing in 400 hip ultrasounds . Following review of ultrasound findings , the majority of cases ( 163/200 , 81.5 % ) lead to no change in management . Change in timing or type of clinical follow up occurred in 31 cases with normal ultrasounds and 20 cases with abnormal ( immature hip ) ultrasounds . Dysplasia was demonstrated in 6 infants ( 3 % ) on ultrasound , who were treated with Parvlik Harness . Of these , only 5 were detected on examination . Therefore , the ultrasound findings lead to 1 intervention with Parvlik Harness which would have otherwise gone undiagnosed from clinical examination . CONCLUSION Whereas type and timing of follow up was adjusted in 18.5 % of the at-risk infants , targeted screening of at-risk with ultrasound lead to only one intervention . This encourages discussion on the re source implication and viability of ultrasound screening , as only one from two hundred lead to an intervention In the management of a newborn 's hips , ultrasonography has proven to be useful . The progression of measurements at different ages in normal hips has not been thoroughly investigated . The purpose of this prospect i ve study was to assess the longitudinal development of clinical ly stable hips . Forty newborns ( 80 hips ) were assessed by ultrasonography at birth and at 6 and 12 weeks of age . Femoral head coverage ( FHC ) , alpha angles , and beta angles were measured . The results showed a significant change in values between the three points in time for all measurements ( P < 0.001 ) . The mean FHC progressed from 58.4 % to 65.6 % to 69.3 % , the mean alpha angle from 70.2 ° to 76.8 ° to 80.3 ° , and the mean beta angle from 52.1 ° to 45.7 ° to 42.9 ° . In clinical ly stable hips , the FHC and alpha and beta angles change significantly over time ; therefore , it is important to consider the child 's age when interpreting ultrasound images The relationship between ultrasonographic findings at birth and risk factors for developmental dysplasia of the hip have not been prospect ively evaluated . Since implementing a routine screening programme for all new-born babies in 1989 we have collected 48 000 sets of data , including family history , birth presentation , mode of delivery and birth weight . Of the 92 babies ( three per 1000 live births ) with persistent ultrasonographic abnormality at 6 weeks only 20 % displayed evidence of clinical instability at the original examination . Female babies without the additional risks of breech birth or positive family history were quantitatively the most significant group , accounting for 75 % of cases treated . The majority of babies requiring intervention would not have been identified utilizing present criteria for selective ultrasound screening |
13,988 | 27,274,333 | CONCLUSION Internet interventions are superior to other broad reach cessation interventions ( ie , print material s ) , equivalent to other currently recommended treatment modes ( telephone and in-person counseling ) , and they have an important role to play in the arsenal of tobacco-dependence treatments | BACKGROUND The aim of this systematic review was to determine the effectiveness of Internet interventions in promoting smoking cessation among adult tobacco users relative to other forms of intervention recommended in treatment guidelines . | Eligible smokers ( N = 6,451 ) visiting the American Cancer Society 's Internet site offering cessation assistance were , with informed consent , r and omized to receive access either to a static Internet site with quitting advice or to one of five interactive sites provided by cooperating research partners . Three-month follow-up surveys were conducted via online survey with E-mail prompts , or telephone calls , to assess quitting success ; 54 % of participants provided follow-up data . Results showed no significant overall difference in cessation rates among participants assigned to the interactive or static sites . We found large differences in the utilization of the five interactive sites . When sites were grouped by level of use , a significantly higher reported 3-month cessation rate was observed among participants assigned to the more highly utilized sites than among those assigned to the less utilized sites ( 12.2 % vs. 10.2 % of all r and omized participants , 26.0 % vs. 22.1 % of followed participants ) . These findings show that interactive Internet sites yielding high levels of utilization can increase quitting success among smokers seeking assistance via the Internet Background Web-based and mobile health interventions ( also called “ Internet interventions ” or " eHealth/mHealth interventions ") are tools or treatments , typically behaviorally based , that are operationalized and transformed for delivery via the Internet or mobile platforms . These include electronic tools for patients , informal caregivers , healthy consumers , and health care providers . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the suboptimal reporting of r and omized controlled trials ( RCTs ) . While the CONSORT statement can be applied to provide broad guidance on how eHealth and mHealth trials should be reported , RCTs of web-based interventions pose very specific issues and challenges , in particular related to reporting sufficient details of the intervention to allow replication and theory-building . Objective To develop a checklist , dubbed CONSORT-EHEALTH ( Consoli date d St and ards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth ) , as an extension of the CONSORT statement that provides guidance for authors of eHealth and mHealth interventions . Methods A literature review was conducted , followed by a survey among eHealth experts and a workshop . Results A checklist instrument was constructed as an extension of the CONSORT statement . The instrument has been adopted by the Journal of Medical Internet Research ( JMIR ) and authors of eHealth RCTs are required to su bmi t an electronic checklist explaining how they addressed each subitem . Conclusions CONSORT-EHEALTH has the potential to improve reporting and provides a basis for evaluating the validity and applicability of eHealth trials . Subitems describing how the intervention should be reported can also be used for non- RCT evaluation reports . As part of the development process , an evaluation component is essential ; therefore , feedback from authors will be solicited , and a before-after study will evaluate whether reporting has been improved Background Studies suggest that tailored material s are superior to nontailored material s in supporting health behavioral change . Several trials on tailored Internet-based interventions for smoking cessation have shown good effects . There have , however , been few attempts to isolate the effect of the tailoring component of an Internet-based intervention for smoking cessation and to compare it with the effectiveness of the other components . Objective The study aim was to isolate the effect of tailored emails in an Internet-based intervention for smoking cessation by comparing two versions of the intervention , with and without tailored content . Methods We conducted a two-arm , r and omized controlled trial of the open and free Norwegian 12-month follow-up , fully automated Internet-based intervention for smoking cessation , slutta.no . We collected information online on demographics , smoking , self-efficacy , use of the website , and participant evaluation at enrollment and subsequently at 1 , 3 , and 12 months . Altogether , 2298 self-selected participants aged 16 years or older registered at the website between August 15 , 2006 and December 7 , 2007 and were r and omly assigned to either a multicomponent , nontailored Internet-based intervention for smoking cessation ( control ) or a version of the same Internet-based intervention with tailored content delivered on the website and via email . Results Of the r and omly assigned participants , 116 ( of 419 , response rate = 27.7 % ) in the intervention group and 128 ( of 428 , response rate = 29.9 % ) in the control group had participated over the 12 months and responded at the end of follow-up . The 7-day intention-to-treat abstinence rate at 1 month was 15.2 % ( 149/982 ) among those receiving the tailored intervention , compared with 9.4 % ( 94/999 ) among those who received the nontailored intervention ( P < .001 ) . The corresponding figures at 3 months were 13.5 % ( 122/902 ) and 9.4 % ( 84/896 , P = .006 ) and at 12 months were 11.2 % ( 47/419 ) and 11.7 % ( 50/428 , P = .91 ) . Likewise , the intervention group had higher self-efficacy and perceived tailoring at 1 and 3 months . Self-efficacy was found to partially mediate the effect of the intervention . Conclusion Tailoring an Internet-based intervention for smoking cessation seems to increase the success rates in the short term , but not in the long term Background Although many smokers seek Internet-based cessation assistance , few studies have experimentally evaluated long-term cessation rates among cigarette smokers who receive Internet assistance in quitting . Objective The purpose of this study is to describe long-term smoking cessation rates associated with 6 different Internet-based cessation services and the variation among them , to test the hypothesis that interactive and tailored Internet services yield higher long-term quit rates than more static Web-posted assistance , and to explore the possible effects of level of site utilization and a self-reported indicator of depression on long-term cessation rates . Method In 2004 - 05 , a link was placed on the American Cancer Society ( ACS ) website for smokers who wanted help in quitting via the Internet . The link led smokers to the QuitLink study website , where they could answer eligibility questions , provide informed consent , and complete the baseline survey . Enrolled participants were r and omly assigned to receive emailed access to one of five tailored interactive sites provided by cooperating research partners or to a targeted , minimally interactive ACS site with text , photographs , and graphics providing stage-based quitting advice and peer modeling . Results 6451 of the visitors met eligibility requirements and completed consent procedures and the baseline survey . All of these smokers were r and omly assigned to one of the six experimental groups . Follow-up surveys done online and via telephone interviews at approximately 13 months after r and omization yielded 2468 respondents ( 38 % ) and found no significant overall quit rate differences among those assigned to the different websites ( P = .15 ) . At baseline , 1961 participants ( 30 % ) reported an indicator of depression . Post hoc analyses found that this group had significantly lower 13-month quit rates than those who did not report the indicator ( all enrolled , 8 % vs 12 % , P < .001 ; followed only , 25 % vs 31 % , P = .003 ) . When the 4490 participants ( 70 % ) who did not report an indicator of depression at baseline were separated for analysis , the more interactive , tailored sites , as a whole , were associated with higher quitting rates than the less interactive ACS site : 13 % vs 10 % ( P = .04 ) among 4490 enrolled and 32 % vs 26 % ( P = .06 ) among 1798 followed . Conclusions These findings show that Internet assistance is attractive and potentially cost-effective and suggest that tailored , interactive websites may help cigarette smokers who do not report an indicator of depression at baseline to quit and maintain cessation Background Web-based computer-tailored approaches have the potential to be successful in supporting smoking cessation . However , the potential effects of such approaches for relapse prevention and the value of incorporating action planning strategies to effectively prevent smoking relapse have not been fully explored . The Stay Quit for You ( SQ4U ) study compared two Web-based computer-tailored smoking relapse prevention programs with different types of planning strategies versus a control group . Objectives To assess the efficacy of two Web-based computer-tailored programs in preventing smoking relapse compared with a control group . The action planning ( AP ) program provided tailored feedback at baseline and invited respondents to do 6 preparatory and coping planning assignments ( the first 3 assignments prior to quit date and the final 3 assignments after quit date ) . The action planning plus ( AP+ ) program was an extended version of the AP program that also provided tailored feedback at 11 time points after the quit attempt . Respondents in the control group only filled out question naires . The study also assessed possible dose – response relationships between abstinence and adherence to the programs . Methods The study was a r and omized controlled trial with three conditions : the control group , the AP program , and the AP+ program . Respondents were daily smokers ( N = 2031 ) , aged 18 to 65 years , who were motivated and willing to quit smoking within 1 month . The primary outcome was self-reported continued abstinence 12 months after baseline . Logistic regression analyses were conducted using three sample s : ( 1 ) all respondents as r and omly assigned , ( 2 ) a modified sample that excluded respondents who did not make a quit attempt in conformance with the program protocol , and ( 3 ) a minimum dose sample that also excluded respondents who did not adhere to at least one of the intervention elements . Observed case analyses and conservative analyses were conducted . Results In the observed case analysis of the r and omized sample , abstinence rates were 22 % ( 45/202 ) in the control group versus 33 % ( 63/190 ) in the AP program and 31 % ( 53/174 ) in the AP+ program . The AP program ( odds ratio 1.95 , P = .005 ) and the AP+ program ( odds ratio 1.61 , P = .049 ) were significantly more effective than the control condition . Abstinence rates and effects differed per sample . Finally , the results suggest a dose – response relationship between abstinence and the number of program elements completed by the respondents . Conclusion Despite the differences in results caused by the variation in our analysis approaches , we can conclude that Web-based computer-tailored programs combined with planning strategy assignments and feedback after the quit attempt can be effective in preventing relapse 12 months after baseline . However , adherence to the intervention seems critical for effectiveness . Finally , our results also suggest that more research is needed to assess the optimum intervention dose . Trial Registration Dutch Trial Register : NTR1892 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1892 ( Archived by WebCite at http://www.webcitation.org/693S6uuPM Background Online computer-tailored smoking cessation programs have not yet been compared directly . Objective To compare the efficacy of two Internet-based , computer-tailored smoking cessation programs . Methods R and omized controlled trial conducted in 2003 - 2004 . Visitors to a smoking cessation website were r and omly assigned to either an original online , interactive smoking cessation program or to a modified program . Both programs consisted of tailored , personalized counseling letters based on participants ' characteristics , followed by monthly email reminders . The original program was based on psychological and addiction theory , and on preliminary research conducted in the same population . The modified program was shorter and contained more information on nicotine replacement therapy and nicotine dependence , and less information on health risks and coping strategies . In both programs , 1 month and 2 months after entering the study , participants were invited by email to answer the same tailoring question naire again in order to receive a second counseling letter . Participants in both programs obtained , on average , 1.2 feedback counseling letters over 2.5 months , and 84 % received only 1 feedback letter . The outcome was self-reported smoking abstinence ( no puff of tobacco in the previous 7 days ) , assessed 2.5 months after entry in the program . We report results from intention-to-treat ( ITT ) analyses , where all non-respondents at follow-up were counted as smokers . Results The baseline question naire was answered by a total of 11969 current ( 74 % ) and former ( 26 % ) smokers , and the follow-up survey by 4237 people ( 35 % ) . In an ITT analysis , abstinence rates in baseline current smokers were respectively 10.9 % and 8.9 % ( odds ratio [OR]=1.24 , 95 % confidence interval [CI]1.08 - 1.43 , P=.003 ) in the original and modified programs , and 25.2 % and 15.7 % ( OR=1.81 , CI 1.51 - 2.16 , P<.001 ) in baseline former smokers . While we found statistically significant differences in quit rates in smokers in the contemplation stage favoring the original program ( OR=1.54 , CI 1.18 - 2.02 , P=.002 ) , no between-group differences in quit rates were observed in smokers in the precontemplation ( OR=1.07 , CI 0.36 - 3.14 , P=.91 ) and preparation ( OR=1.15 , CI 0.97 - 1.37 , P=.10 ) stages of change . Conclusions In smokers in the contemplation stage of change and in former smokers , the original program produced higher smoking abstinence rates than the modified program OBJECTIVES To examine the feasibility , acceptability , and potential effectiveness of an online intervention targeting college smokers . The incentives involved discounted or free goods and services from businesses proximal to each campus . METHODS A r and omized controlled trial was conducted with 122 current smokers recruited from 2 Southeastern US universities . The intervention involved health behavior monitoring , targeted messaging , and incentives for healthy goods and services versus the American Cancer Society 's Guide to Quitting Smoking online . RESULTS The intervention achieved greater adherence and utilization ( p 's < .001 ) . Overall , 55.6 % learned about a local business through this program . At end-of-treatment , intervention participants less frequently attempted to quit ( p = .02 ) but smoked fewer cigarettes/day ( p = .05 ) . Both groups demonstrated significant end-of-treatment cessation rates . CONCLUSIONS This intervention demonstrated feasibility and acceptability INTRODUCTION Identifying successful smoking treatment interventions and methods of delivery is critical given the smoking rates among HIV-positive population s and the medical implication s of smoking in this population . This study compared the efficacy of 3 smoking cessation interventions provided in HIV clinical treatment setting s. METHODS Following a baseline assessment , 209 HIV-positive smokers were r and omly assigned to 1 of 3 conditions in a parallel group design . Treatment conditions were individual counseling plus nicotine replacement treatment ( NRT ) , a computer-based Internet smoking treatment plus NRT , and self-help plus NRT . Smoking status was determined at follow-up assessment s completed at 12 , 24 , 36 , and 52 weeks following treatment initiation . RESULTS Cessation rates ranged from 15 % to 29 % ; however , no statistically significant differences in abstinence were found among the treatment conditions over time . Those employed , those who reported a greater desire to quit , or those with lower mood disturbance scores were more likely to achieve abstinence ( p < .01 ) . The number of cigarettes participants reported smoking in the 24hr prior to each assessment significantly declined over time ( p < .001 ) . CONCLUSIONS Although we found no differences in abstinence rates across groups , the results indicate that integration of smoking cessation interventions is feasible in HIV clinical treatment setting s , and cessation results are promising . The overall abstinence rates we report are comparable to those found in similar treatment studies across multiple population s. Further research is warranted Objective : To evaluate the feasibility and preliminary efficacy of a Web-based tobacco treatment for persons living with HIV ( PLWH ) . Design : Prospect i ve , r and omized controlled trial . Setting : HIV-care center in the Bronx , New York . Subjects : Eligibility criteria included HIV infection , current tobacco usage , interest in quitting , and access to a computer with internet . One hundred thirty-eight subjects enrolled , and 134 completed the study . Intervention : Positively Smoke Free on the Web ( PSFW ) , an 8-session , 7-week targeted tobacco treatment program for PLWH , was compared with st and ard care ( brief advice to quit and self-help brochure ) . All subjects were offered nicotine patches . Main Outcome Measures : The main feasibility outcomes were number of sessions logged into , number of Web pages visited , number of interactive clicks , and total time logged in . The main efficacy outcome was biochemically verified , 7-day point prevalence abstinence 3 months after intervention . Results : PSFW subjects logged into a mean of 5.5 of 8 sessions and 26.2 of 41 pages . They executed a mean of 10 interactive clicks during a mean total of 59.8 minutes logged in . Most required reminder phone calls to complete the sessions . Educational level , anxiety score , and home access of the Web site were associated with Web site usage . Ten percent of the PSFW group vs. 4.3 % of controls achieved the abstinence end point . Among those who completed all 8 sessions , 17.9 % were abstinent , and among women completers , 30.8 % were abstinent . Conclusions : Web-based treatment is a feasible strategy for PLWH smokers , and preliminary findings suggest therapeutic efficacy Background Dem and for online information and help exceeds most other forms of self-help . Web-assisted tobacco interventions ( WATIs ) offer a potentially low-cost way to reach millions of smokers who wish to quit smoking and to test various forms of online assistance for use/utilization and user satisfaction . Objectives Our primary aim was to determine the utilization of and satisfaction with 2 versions of a smoking cessation website ( smokefree.gov ) , one of which included an asynchronous bulletin board ( BB condition ) . A secondary goal was to measure changes in smoking behavior 3 months after enrollment in the study . Methods All participants were adult federal employees or contractors to the federal government who responded to an email and indicated a willingness to quit smoking in 30 days . We r and omly assigned participants to either the BB condition or the publicly available version — usual care (UC)— and then assessed the number of minutes of website use and satisfaction with each condition as well as changes in smoking behavior . Results Among the 1375 participants , 684 were r and omized to the BB intervention , and 691 to the control UC condition . A total of 39.7 % returned a follow-up question naire after 3 months , with similar rates across the two groups ( UC : n=279 , 40.3 % ; BB : n=267 , 39.0 % ) . Among those respondents assigned to the BB condition , only 81 participants ( 11.8 % ) elected to view the bulletin board or post a message , limiting our ability to analyze the impact of bulletin board use on cessation . Satisfaction with the website was high and did not differ significantly between conditions ( UC : 90.2 % , BB : 84.9 % , P= .08 ) . Utilization , or minutes spent on the website , was significantly longer for the BB than the UC condition ( 18.0 vs 11.1 , P = .01 ) and was nearly double for those who remained in the study ( 21.2 ) than for those lost to follow-up ( 9.6 , P < .001 ) . Similar differences were observed between those who made a serious quit attempt versus those who did not ( 22.4 vs 10.4 , P= .02 ) and between those with a quit date on or a few days prior to the enrollment date versus those with a later quit date ( 29.4 vs 12.5 , P = .001 ) . There were no statistically significant differences in quit rates between the BB and UC group , both in intent-to-treat analysis ( ITT ) and in analyzing the adherence subgroup ( respondents ) only . Combined across the UC and BB groups , 7-day abstinence was 6.8 % with ITT and 17.6 % using only participants in the follow-up ( adherence ) . For participants who attempted to quit within a few days of study entry ( vs 30 days ) , quit rates were 29.6 % ( ITT ) and 44.4 % ( adherence ) . Conclusions Quit rates for participants were similar to other WATIs , with the most favorable outcomes demonstrated by smokers ready to quit at the time of enrolling in the trial and smokers using pharmacotherapy . Utilization of the asynchronous bulletin board was lower than expected , and did not have an impact on outcomes ( quit rates ) . Given the dem and for credible online re sources for smoking cessation , future studies should continue to evaluate use of and satisfaction with Web features and to clarify results in terms of time since last cigarette as well as use of pharmacotherapy . Trial Registration Clinical trials.gov NCT00245076 ; http:// clinical trials.gov/ct2/show/NCT00245076 ( Archived by WebCite at http://www.webcitation.org/5dBuBASA0 Background Distributing a multiple computer-tailored smoking cessation intervention through the Internet has several advantages for both provider and receiver . Most important , a large audience of smokers can be reached while a highly individualized and personal form of feedback can be maintained . However , such a smoking cessation program has yet to be developed and implemented in the Netherl and s. Objective To investigate the effects of a Web-based multiple computer-tailored smoking cessation program on smoking cessation outcomes in a sample of Dutch adult smokers . Methods Smokers were recruited from December 2009 to June 2010 by advertising our study in the mass media and on the Internet . Those interested and motivated to quit smoking within 6 months ( N = 1123 ) were r and omly assigned to either the experimental ( n = 552 ) or control group ( n = 571 ) . Respondents in the experimental group received the fully automated Web-based smoking cessation program , while respondents in the control group received no intervention . After 6 weeks and after 6 months , we assessed the effect of the intervention on self-reported 24-hour point prevalence abstinence , 7-day point prevalence abstinence , and prolonged abstinence using logistic regression analyses . Results Of the 1123 respondents , 449 ( 40.0 % ) completed the 6-week follow-up question naire and 291 ( 25.9 % ) completed the 6-month follow-up question naire . We used a negative scenario to replace missing values . That is , we considered respondents lost to follow-up to still be smoking . The computer-tailored program appeared to have significantly increased 24-hour point prevalence abstinence ( odds ratio [ OR ] 1.85 , 95 % confidence interval [ CI ] 1.30–2.65 ) , 7-day point prevalence abstinence ( OR 2.17 , 95 % CI 1.44–3.27 ) , and prolonged abstinence ( OR 1.99 , 95 % CI 1.28–3.09 ) rates reported after 6 weeks . After 6 months , however , no intervention effects could be identified . Results from complete-case analyses were similar . Conclusions The results presented suggest that the Web-based computer-tailored smoking cessation program had a significant effect on abstinence reported after a 6-week period . At the 6-month follow-up , however , no intervention effects could be identified . This might be explained by the replacement of missing values on the primary outcome measures due to attrition using a negative scenario . While results were similar when using a less conservative scenario ( ie , complete-case analyses ) , the results should still be interpreted with caution . Further research should aim at identifying strategies that will prevent high attrition in the first place and , subsequently , to identify the best strategies for dealing with missing data when studies have high attrition rates . Trial Registration Dutch Trial Register NTR1351 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1351 ( Archived by WebCite at http://www.webcitation.org/67egSTWrz Background Happy Ending ( HE ) is an intense 1-year smoking cessation program delivered via the Internet and cell phone . HE consists of more than 400 contacts by email , Web pages , interactive voice response , and short message service technology . HE includes a craving helpline and a relapse prevention system , providing just-in-time therapy . All the components of the program are fully automated . Objective The objectives were to describe the rationale for the design of HE , to assess the 12-month efficacy of HE in a sample of smokers willing to attempt to quit without the use of nicotine replacement therapy , and to explore the potential effect of HE on coping planning and self-efficacy ( prior to quitting ) and whether coping planning and self-efficacy mediate treatment effect . Methods A two-arm r and omized controlled trial was used . Subjects were recruited via Internet advertisements and r and omly assigned to condition . Inclusion criteria were willingness to quit on a prescribed day without using nicotine replacement and being aged 18 years or older . The intervention group received HE , and the control group received a 44-page self-help booklet . Abstinence was defined as “ not even a puff of smoke , for the last seven days ” and was assessed by means of Internet surveys or telephone interviews 1 , 3 , 6 , and 12 months postcessation . The main outcome was repeated point abstinence ( ie , abstinence at all four time points ) . Coping planning and self-efficacy were measured at baseline and at the end of the preparation phase ( ie , after 2 weeks of treatment , but prior to cessation day ) . Results A total of 290 participants received either the HE intervention ( n=144 ) or the control booklet ( n=146 ) . Using intent-to-treat analysis , participants in the intervention group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants ( 20 % versus 7 % , odds ratio [ OR ] = 3.43 , 95 % CI = 1.60 - 7.34 , P = .002 ) . Although no differences were observed at baseline , by the end of the preparation phase , significantly higher levels of coping planning ( t 261 = 3.07 , P = .002 ) and precessation self-efficacy ( t 261 = 2.63 , P = .01 ) were observed in the intervention group compared with the control group . However , neither coping planning nor self-efficacy mediated long-term treatment effect . For point abstinence 1 month after quitting , however , coping planning and self-efficacy showed a partial mediation of the treatment effect . Conclusions This 12-month trial documents a long-term treatment effect of a fully automated smoking cessation intervention without the use of nicotine replacement therapy . The study adds to the promise of using digital media in supporting behavior change The aim was to compare the effectiveness of untailored text messages for smoking cessation to tailored text messages delivered at a higher frequency . From February 2007 to August 2009 , 2030 users of an internet-based smoking cessation program with optional text message support aged 15 - 25 years were consecutively r and omized to versions of the program that offered either tailored or untailored text messages . Thirty-day point abstinence from smoking was measured self-reportedly at 12-months follow-up . Response rates were 36.3 % and 38.1 % in the tailored and untailored group , respectively . We analyzed the entire study population , as well as those opting for text messages ( n = 1619 ) . In intention-to-treat analysis with multiple imputation of missing data , the odds ratio for 30-day point abstinence was 1.28 ( 95 % CI 0.91 - 2.08 ) for the tailored compared with untailored messages . When restricting the analysis to those who had chosen to receive text messages , the corresponding odds ratio was 1.45 ( 95 % CI 1.01 - 2.08 ) . The higher long-term quit rates in the group receiving the tailored text messages compared with untailored text messages in the restricted analysis indicated that tailoring and higher frequency of text messages increases quit rates among young smokers Background People with low education and /or income are more likely to smoke , less likely to quit , and experience disparately poor health outcomes compared to those with education and income advantage . Cost-effective strategies are needed to inform and engage this group into effective cessation treatments . We developed a novel , web-based , motivational , decision-support system that was design ed to engage disadvantaged smokers into tobacco cessation treatment . We piloted the system among smokers in a primary care safety net clinic . Methods Thirty-nine eligible subjects were assessed at baseline and used the decision-support system ; 38 were assessed 2 months later . Chi-square or Fisher ’s exact tests were used to assess whether participants who used the program were more likely to use cessation treatment than a r and omly selected group of 60 clinic patients . Results Thirty-nine percent of smokers initiated cessation treatment after using the decision-support system , compared to 3 percent of the comparison group ( Fisher ’s exact = 21.2 ; p = 0.000 ) . Over 10 percent achieved continuous abstinence over the 2-month follow-up . Users were satisfied with the program – 100 percent stated they would recommend it to a friend . Conclusions Our data indicate that this web-based , motivational , decision-support system is feasible , satisfactory , and promising in its ability to engage smokers into cessation treatment in a primary care safety net clinic . Further evaluation research is warranted Background Although experts cl aim that computer-tailored interventions provided over the Internet have great potential to promote health behavior change , few studies have tested the efficacy of computer-tailored lifestyle interventions online-delivered over the Internet . Purpose To evaluate the short-term ( 1 month ) efficacy of an Internet-delivered , computer-tailored lifestyle intervention targeting saturated fat intake , physical activity ( PA ) , and smoking cessation , and to evaluate exposure to the intervention . Methods A pretest – posttest r and omized controlled trial with an intervention group and a no intervention waiting list control group was conducted . Self-reported behavior and determinants were assessed at baseline and 1 month follow-up . Exposure to the intervention was monitored through server registration s. The data were analyzed using multiple linear and logistic regression analysis . Results The intervention result ed in a significantly lower self-reported saturated fat intake ( b = −0.76 , p < 0.01 ) and a higher likelihood of meeting the PA guidelines among respondents who were insufficiently active at baseline ( OR = 1.34 , 95%CI = 1.001–1.80 ) . No significant intervention effects were found for self-reported smoking status . Of the participants , 81 % actually visited the website . Conclusions The Internet-delivered , computer-tailored lifestyle intervention was effective in reducing self-reported saturated fat intake and in increasing self-reported PA among participants who completed the study AIMS To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention . DESIGN Two-arm r and omized control trial ( RCT ) . Setting World Wide Web ( WWW ) study based in Norway . PARTICIPANTS Subjects ( n = 396 ) were recruited via internet advertisements and assigned r and omly to conditions . Inclusion criteria were willingness to quit smoking and being aged 18 years or older . INTERVENTION The treatment group received the internet- and cell-phone-based Happy Ending intervention . The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail , web-pages , interactive voice response ( IVR ) and short message service ( SMS ) technology . The control group received a self-help booklet . Additionally , both groups were offered free nicotine replacement therapy ( NRT ) . MEASUREMENTS Abstinence was defined as ' not even a puff of smoke , for the last 7 days ' , and assessed by means of internet surveys or telephone interviews . The main outcome was repeated point abstinence at 1 , 3 , 6 and 12 months following cessation . FINDINGS Participants in the treatment group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants [ 22.3 % versus 13.1 % ; odds ratio ( OR ) = 1.91 , 95 % confidence interval ( CI ) : 1.12 - 3.26 , P = 0.02 ; intent-to-treat ) . Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group . CONCLUSIONS As the first RCT documenting the long-term treatment effects of such an intervention , this study adds to the promise of digital media in supporting behaviour change Background Preliminary findings suggest that Web-based interventions may be effective in achieving significant smoking cessation . To date , very few findings are available for primary care patients , and especially for the involvement of general practitioners . Objective Our goal was to examine the short-term effectiveness of a fully automated Web-based coaching program in combination with accompanied telephone counseling in smoking cessation in a primary care setting . Methods The study was an unblinded cluster-r and omized trial with an observation period of 12 weeks . Individuals recruited by general practitioners r and omized to the intervention group participated in a Web-based coaching program based on education , motivation , exercise guidance , daily short message service ( SMS ) reminding , weekly feedback through Internet , and active monitoring by general practitioners . All components of the program are fully automated . Participants in the control group received usual care and advice from their practitioner without the Web-based coaching program . The main outcome was the biochemically confirmed smoking status after 12 weeks . Results We recruited 168 participants ( 86 intervention group , 82 control group ) into the study . For 51 participants from the intervention group and 70 participants from the control group , follow-up data were available both at baseline and 12 weeks . Very few patients ( 9.8 % , 5/51 ) from the intervention group and from the control group ( 8.6 % , 6/70 ) successfully managed smoking cessation ( OR 0.86 , 95 % CI 0.25 - 3.0 ; P=.816 ) . Similar results were found within the intent-to-treat analysis : 5.8 % ( 5/86 ) of the intervention group and 7.3 % ( 6/82 ) of the control group ( OR 1.28 , 95 % CI 0.38 - 4.36 ; P=.694 ) . The number of smoked cigarettes per day decreased on average by 9.3 in the intervention group and by 6.6 in the control group ( 2.7 mean difference ; 95 % CI -5.33 to -0.58 ; P=.045 ) . After adjustment for the baseline value , age , gender , and height , this significance decreases ( mean difference 2.2 ; 95 % CI -4.7 to 0.3 ; P=.080 ) . Conclusions This trial did not show that the tested Web-based intervention was effective for achieving smoking cessation compared to usual care . The limited statistical power and the high drop-out rate may have reduced the study ’s ability to detect significant differences between the groups . Further r and omized controlled trials are needed in larger population s and to investigate the long-term outcome . Trial Registration German Register for Clinical Trials , registration number DRKS00003067 ; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL _ ID = DRKS00003067 ( Archived by WebCite at http://www.webcitation.org/6Sff1YZpx ) Background Web-based computer-tailored interventions for multiple health behaviors can have a significant public health impact . Yet , few r and omized controlled trials have tested this assumption . Objective The objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors . Methods A r and omized controlled trial was conducted with 3 tailoring conditions ( ie , sequential , simultaneous , and control conditions ) in the Netherl and s in 2009 - 2012 . Follow-up measurements took place after 12 and 24 months . The intervention content was based on the I-Change model . In a health risk appraisal , all respondents ( N=5055 ) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity , vegetable consumption , fruit consumption , alcohol intake , and smoking . Participants in the sequential ( n=1736 ) and simultaneous ( n=1638 ) conditions received tailored motivational feedback to change unhealthy behaviors one at a time ( sequential ) or all at the same time ( simultaneous ) . Mixed model analyses were performed as primary analyses ; regression analyses were done as sensitivity analyses . An overall risk score was used as outcome measure , then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention . Results Both tailoring strategies were associated with small self-reported behavioral changes . The sequential condition had the most significant effects compared to the control condition after 12 months ( T1 , effect size=0.28 ) . After 24 months ( T2 ) , the simultaneous condition was most effective ( effect size=0.18 ) . All 5 individual lifestyle behaviors changed over time , but few effects differed significantly between the conditions . At both follow-ups , the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition ( T1 effect size=0.31 ; T2 effect size=0.41 ) . The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months ( effect size=0.27 ) . Change was predicted by the amount of exposure to the intervention ( total visiting time : beta=–.06 ; P=.01 ; total number of visits : beta=–.11 ; P<.001 ) . Both interventions were appreciated well by respondents without significant differences between conditions . Conclusions Although evidence was found for the effectiveness of both programs , no simple conclusive finding could be drawn about which intervention mode was more effective . The best kind of intervention may depend on the behavior that is targeted or on personal preferences and motivation . Further research is needed to identify moderators of intervention effectiveness . The results need to be interpreted in view of the high and selective dropout rates , multiple comparisons , and modest effect sizes . However , a large number of people were reached at low cost and behavioral change was achieved after 2 years . Trial Registration Nederl and s Trial Register : NTR 2168 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2168 ( Archived by WebCite at http://www.webcitation.org/6MbUqttYB ) Background Tobacco smoking leads to death or disability and a drain on national re sources . The literature suggests that cigarette smoking continues to be a major modifiable risk factor for a variety of diseases and that smokers aged 18 - 30 years are relatively resistant to antismoking messages due to their widely held belief that they will not be lifelong smokers . Objective To conduct a r and omized controlled trial ( RCT ) of a computer-generated photoaging intervention to promote smoking cessation among young adult smokers within a community pharmacy setting . Methods A trial was design ed with 80 % power based on the effect size observed in a published pilot study ; 160 subjects were recruited ( 80 allocated to the control group and 80 to the intervention group ) from 8 metropolitan community pharmacies located around Perth city center in Western Australia . All participants received st and ardized smoking cessation advice . The intervention group participants were also digitally photoaged by using the Internet-based APRIL Face Aging software so they could p review images of themselves as a lifelong smoker and as a nonsmoker . Due to the nature of the intervention , the participants and research er could not be blinded to the study . The main outcome measure was quit attempts at 6-month follow-up , both self-reported and biochemically vali date d through testing for carbon monoxide ( CO ) , and nicotine dependence assessed via the Fagerström scale . Results At 6-month follow-up , 5 of 80 control group participants ( 6.3 % ) suggested they had quit smoking , but only 1 of 80 control group participants ( 1.3 % ) consented to , and was confirmed by , CO validation . In the intervention group , 22 of 80 participants ( 27.5 % ) reported quitting , with 11 of 80 participants ( 13.8 % ) confirmed by CO testing . This difference in biochemically confirmed quit attempts was statistically significant ( χ2 1=9.0 , P=.003 ) . A repeated measures analysis suggested the average intervention group smoking dependence score had also significantly dropped compared to control participants ( P<.001 ) . These differences remained statistically significant after adjustment for small differences in gender distribution and nicotine dependence between the groups . The mean cost of implementing the intervention was estimated at AU $ 5.79 per participant . The incremental cost-effectiveness ratio was AU $ 46 per additional quitter . The mean cost that participants indicated they were willing to pay for the digital aging service was AU $ 20.25 ( SD 15.32 ) . Conclusions Demonstrating the detrimental effects on facial physical appearance by using a computer-generated simulation may be both effective and cost-effective at persuading young adult smokers to quit . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12609000885291 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12609000885291 ( Archived by WebCite at http://www.webcitation.org/6F2kMt3kC Background Smoking is one of the largest contributors to the global burden of disease . Internet interventions have been shown to reduce smoking rates successfully . However , improved methods of evaluating effectiveness need to be developed for large-scale Internet intervention trials . Objective To illustrate a method to interpret outcomes of large-scale , fully automated , worldwide Internet intervention trials . Methods A fully automated , international , Internet-based smoking cessation r and omized controlled trial was conducted in Spanish and English , with 16,430 smokers from 165 countries . The r and omized controlled trial replicated a published efficacy trial in which , to reduce follow-up attrition , 1000 smokers were followed up by phone if they did not provide online follow-up data . Results The 7-day self-reported abstinence rates ranged from 36.18 % ( 2239/6189 ) at 1 month to 41.34 % ( 1361/3292 ) at 12 months based on observed data . Given high rates of attrition in this fully automated trial , when participants unreachable at follow-up were presumed to be smoking , the abstinence rates ranged from 13.63 % ( 2239/16.430 ) at 1 month to 8.28 % ( 1361/16,430 ) at 12 months . We address the problem of interpreting results with high follow-up attrition rates and propose a solution based on a smaller study with intensive phone follow-up . Conclusions Internet-based smoking cessation interventions can help large numbers of smokers quit . Large-scale international outcome studies can be successfully implemented using automated Internet sites . Interpretation of the studies ’ results can be aided by extrapolating from results obtained from sub sample s that are followed up by phone or similar cohort maintenance methods . Trial Registration Clinical Trials.gov NCT00721786 ; http:// clinical trials.gov/ct2/show/NCT00721786 ( Archived by WebCite at http://www.webcitation.org/63mhoXYPw Background Smoking tobacco is one of the most preventable causes of illness and death . Web-based tailored smoking cessation interventions have shown to be effective . Although these interventions have the potential to reach a large number of smokers , they often face high attrition rates , especially among lower educated smokers . A possible reason for the high attrition rates in the latter group is that computer-tailored smoking cessation interventions may not be attractive enough as they are mainly text-based . Video-based messages might be more effective in attracting attention and stimulating comprehension in people with a lower educational level and could therefore reduce attrition rates . Objective The objective of the present study was to investigate whether differences exist in message-processing mechanisms ( attention , comprehension , self-reference , appreciation , processing ) and future adherence ( intention to visit/use the website again , recommend the website to others ) , according to delivery strategy ( video or text based messages ) and educational level , to a Dutch computer-tailored smoking cessation program . Methods Smokers who were motivated to quit within the following 6 months and who were aged over 16 were included in the program . Participants were r and omly assigned to one of two conditions ( video/text CT ) . The sample was stratified into 2 categories : lower and higher educated participants . In total , 139 participants completed the first session of the web-based tailored intervention and were subsequently asked to fill out a question naire assessing message-processing mechanisms and future adherence . ANOVAs and regression analyses were conducted to investigate the differences in message-processing mechanisms and future adherence with regard to delivery strategy and education . Results No interaction effects were found between delivery strategy ( video vs text ) and educational level on message-processing mechanisms and future adherence . Delivery strategy had no effect on future adherence and processing mechanisms . However , in both groups results indicated that lower educated participants showed higher attention ( F 1,138=3.97 ; P=.05 ) and processing levels ( F 1,138=4.58 ; P=.04 ) . Results revealed also that lower educated participants were more inclined to visit the computer-tailored intervention website again ( F 1,138=4.43 ; P=.04 ) . Conclusions Computer-tailored programs have the potential to positively influence lower educated groups as they might be more involved in the computer-tailored intervention than higher educated smokers . Longitudinal studies with a larger sample are needed to gain more insight into the role of delivery strategy in tailored information and to investigate whether the intention to visit the intervention website again results in the ultimate goal of behavior change . Trial Registration Netherl and s Trial Register ( NTR3102 ) OBJECTIVE To test the feasibility and efficacy of an internet program for smoking cessation during and after inpatient treatment in rehabilitation centers . METHODS A total of 7574 consecutively admitted in patients from three German rehabilitation centers were assessed for smoking status . Daily smokers or former daily smokers who regularly used the internet and e-mail were proactively invited for study participation . Out of 749 eligible patients , 477 ( 64 % ) participated in the study and were r and omly assigned to an intervention or an assessment only control group based on the calendar week of admission . Patients of the intervention group had the possibility to use an internet program for smoking cessation for a period of six months . The program provided at least one but up to seven individual counseling sessions through a computer expert system , informational websites and a message board . RESULTS At six-months follow-up , seven-day point prevalence smoking abstinence was twice as high in the intervention group as in the control group ( OR=2.0 ; CI 1.1 - 3.8 ; p=.02 ) . CONCLUSIONS Proactive recruitment of smokers in combination with the provision of an internet program for smoking cessation allow for an inexpensive and effective smoking cessation support during and after inpatient rehabilitation treatment Internet interventions for smoking cessation are ubiquitous . Yet , to date , there are few r and omized clinical trials that gauge their efficacy . This study is a r and omized clinical trial ( N= 284 , n= 140 in the treatment group , n= 144 in the control group ) of an Internet smoking cessation intervention . Smokers were r and omly assigned to receive either bupropion plus counseling alone , or bupropion and counseling in addition to 12 weeks of access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention ( CHESS SCRP ; a Web site which provided information on smoking cessation as well as support ) . We found that access to CHESS SCRP was not significantly related to abstinence at the end of the treatment period ( OR= 1.13 , 95 % CI 0.66 - 2.62 ) or at 6 months postquit ( OR= 1.48 , 95 % CI 0.66 - 2.62 ) . However , the number of times participants used CHESS SCRP per week was related to abstinence at both end of treatment ( OR= 1.79 , 95 % CI 1.25 - 2.56 ) and at the 6-month follow-up ( OR= 1.59 , 95 % CI 1.06 - 2.38 ) . Participants with access to CHESS SCRP logged in an average of 33.64 times ( SD=30.76 ) over the 90-day period of access . Rates of CHESS SCRP use did not differ by ethnicity , level of education or gender ( all p>.05 ) . In sum , results suggest that participants used CHESS SCRP frequently , CHESS SCRP use was related to success , but the effects in general did not yield intergroup effects Background Smoking cessation remains a significant public health problem . Innovative interventions that use the Internet have begun to emerge that offer great promise in reaching large numbers of participants and encouraging widespread behavior change . To date , the relatively few controlled trials of Web-based smoking cessation programs have been limited by short follow-up intervals . Objective We describe the 6-month follow-up results of a r and omized controlled trial in which participants recruited online were r and omly assigned to either a Web-based smoking cessation program ( Quit Smoking Network ; QSN ) or a Web-based exercise enhancement program ( Active Lives ) adapted somewhat to encourage smoking cessation . Methods The study was a two-arm r and omized controlled trial that compared two Web-based smoking cessation programs : ( 1 ) the QSN intervention condition presented cognitive-behavioral strategies , and ( 2 ) the Active Lives control condition provided participants with guidance in developing a physical activity program to assist them with quitting . The QSN condition provided smoking cessation information and behavior change strategies while the Active Lives condition provided participants with physical activity recommendations and goal setting . The QSN condition was design ed to be more engaging ( eg , it included multimedia components ) and to present much greater content than is typically found in smoking cessation programs . Results Contrary to our hypotheses , no between-condition differences in smoking abstinence were found at 3- and 6-month follow-up assessment s. While participants in the QSN intervention condition spent more time than controls visiting the online program , the median number of 1.0 visit in each condition and the substantial attrition ( 60.8 % at the 6-month follow-up ) indicate that participants were not as engaged as we had expected . Conclusions Contrary to our hypothesis , our test of two Web-based smoking cessation conditions , an intervention and an attention placebo control , failed to show differences at 3- and 6-month assessment s. We explored possible reasons for this finding , including limited engagement of participants and simplifying program content and architecture . Future research needs to address methods to improve participant engagement in online smoking cessation programs . Possible approaches in this regard can include new informed consent procedures that better explain the roles and responsibilities of being a research participant , new program design s that add more vitality ( changing content from visit to visit ) , and new types of reminders pushed out to participants to encourage return visits . Simplifying program content through a combination of enhanced tailoring and information architecture also merits further research attention BACKGROUND Health promotion efforts encourage smokers to quit and to use effective cessation treatments . R and omized controlled trials demonstrate that medications and behavioral treatments improve cessation rates , but retrospective surveys have been inconsistent . This study assessed frequency of quit attempts , use of treatments for cessation , and abstinence rates among treatment users and non-users . METHODS Data were analyzed from the 2003 Tobacco Use Special Cessation Supplement to the Current Population Survey . Participants included 29,537 U.S. smokers aged > or = 18 years who smoked daily 12 months before the survey . Outcome measures included past-year quit attempts ; use of behavioral , pharmacologic , and alternative treatments ; receipt of social support ; and abstinence for > or = 4 weeks at time of survey . RESULTS Approximately 43.5 % of smokers reported a quit attempt in the preceding year : 64.2 % of attempters used no cessation treatments ; 8.8 % used behavioral treatment ; 32.2 % used medication ; and 14.1 % used more than one treatment . Social support was reported to have been received by 24.1 % . More nicotine-dependent smokers were more likely to use medications ( OR=3.58 ; 95 % CI=3.04 - 4.20 ) . At the time of the survey , 19.3 % of attempters were abstinent > or = 4 weeks . Smokers who sought treatment were less likely to be abstinent ( OR=0.75 ; 95 % CI=0.67 - 0.84 ) , and those who sought multiple treatments were even less likely to be abstinent . CONCLUSIONS Many U.S. smokers make quit attempts , but most do not use behavioral or pharmacologic treatments . More nicotine-dependent smokers were more likely to seek treatment . Smokers who sought treatment were less likely to report abstinence , probably due to biased self- selection and recall . Retrospective survey data are not well-suited to assess the effectiveness of treatment Background Novel interventions tailored to blue collar workers are needed to reduce the disparities in smoking rates among occupational groups . Objective The main objective of this study was to evaluate the efficacy and usage of the Web-enhanced “ Tobacco Tactics ” intervention targeting operating engineers ( heavy equipment operators ) compared to the “ 1 - 800-QUIT-NOW ” telephone line . Methods Operating engineers ( N=145 ) attending one of 25 safety training sessions from 2010 through 2012 were r and omized to either the Tobacco Tactics website with nurse counseling by phone and access to nicotine replacement therapy ( NRT ) or to the 1 - 800-QUIT-NOW telephone line , which provided an equal number of phone calls and NRT . The primary outcome was self-reported 7-day abstinence at 30-day and 6-month follow-up . The outcomes were compared using chi-square tests , t tests , generalized mixed models , and logistic regression models . Results The average age was 42 years and most were male ( 115/145 , 79.3 % ) and white ( 125/145 , 86.2 % ) . Using an intent-to-treat analysis , the Tobacco Tactics website group showed significantly higher quit rates ( 18/67 , 27 % ) than the 1 - 800-QUIT NOW group ( 6/78 , 8 % ) at 30-day follow-up ( P=.003 ) , but this difference was no longer significant at 6-month follow-up . There were significantly more positive changes in harm reduction measures ( quit attempts , number of cigarettes smoked per day , and nicotine dependence ) at both 30-day and 6-month follow-up in the Tobacco Tactics group compared to the 1 - 800-QUIT-NOW group . Compared to participants in the 1 - 800-QUIT NOW group , significantly more of those in the Tobacco Tactics website group participated in the interventions , received phone calls and NRT , and found the intervention helpful . Conclusions The Web-enhanced Tobacco Tactics website with telephone support showed higher efficacy and reach than the 1 - 800-QUIT-NOW intervention . Longer counseling sessions may be needed to improve 6-month cessation rates . Trial Registration Clinical trials.gov NCT01124110 ; http:// clinical trials.gov/ct2/show/NCT01124110 ( Archived by WebCite at http://www.webcitation.org/6TfKN5iNL ) Background Digital interventions provide effective and potentially cost-effective models for improving health outcomes as they deliver health information and services that are widely disseminated , confidential , and can be tailored to needs of the individual user . Digital interventions have been used successfully for health promotion , mental health , and for enabling self-management of long-term conditions . However , their effectiveness is limited by low usage rates , with non-engagement a major challenge . Hence , it is crucial to find effective strategies to increase user engagement with digital interventions . Objective This systematic review will aim to evaluate the effectiveness of technology-based strategies to promote engagement with digital interventions . Methods We will follow Cochrane Collaboration guidelines on systematic review methodology . The search strategy will be executed across seven e- data bases ( including MEDLINE , EMBASE , PsycINFO , CINAHL ) using the concepts “ digital intervention ” and “ engagement ” , limited by study type ( r and omized controlled trial ) . Grey literature and reference lists of included studies will be search ed . Titles and abstract s will be independently screened by 2 authors . Then the full text of potentially eligible papers will be obtained and double screened . Data from eligible papers will be extracted by 1 author and checked for accuracy by another author . Bias will be assessed using the Cochrane bias assessment tool . Narrative synthesis will report on all included studies , and where appropriate , data will be pooled using meta- analysis . All findings will be reported according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses guidelines . Sources of heterogeneity will be further investigated if required . Results Our research is in progress . The final draft of the systematic review is being written and will be su bmi tted before the end of 2015 . Conclusions The review findings will inform research ers and digital intervention providers about optimal use of technology-based strategies to promote engagement with digital interventions . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42014010164 ; http://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42014010164#.VTZmmiFViko ( Archived by WebCite at http://www.webcitation.org/6XxQC8fT8 ) BACKGROUND This study aim ed to determine the relative effect of Internet and Internet plus telephone treatment for smoking cessation on smoking abstinence among US adults . A priori hypotheses were that Internet enhanced with tailored content and social support would outperform basic Internet ( BI ) and that enhanced Internet ( EI ) plus proactive telephone counseling would outperform the other conditions . METHODS The Quit Using Internet and Telephone Treatment ( iQUITT ) study used a 3-group r and omized controlled design comparing BI , EI , and EI and telephone combined ( EI+P ) . The trial was conducted from March 8 , 2005 , through November 30 , 2008 . Current adult smokers in the United States who smoked 5 or more cigarettes per day were recruited via search engines . Characteristics of the 2005 participants include mean ( SD ) age of 35.9 ( 10.8 ) years , 51.1 % women , and 86.5 % white . The follow-up assessment rate at 18 months was 68.2 % . The main outcome measure was 30-day point prevalence abstinence measured at 3 , 6 , 12 , and 18 months after r and omization using intent-to-treat analysis . RESULTS At 18 months , the 30-day multiple point prevalence abstinence rate across all follow-up intervals was 3.5 % ( BI ) , 4.5 % ( EI ) , and 7.7 % ( EI+P ) , with EI+P significantly outperforming BI and EI . At 18 months , 30-day single point prevalence abstinence rates were 19.0 % ( BI ) , 17.4 % ( EI ) , and 19.6 % ( EI+P ) and did not differ among the groups . CONCLUSIONS Combined Internet and telephone treatment outperforms static and dynamic Internet interventions . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00282009 The lack of promising smoking cessation interventions targeting young adults is a recognized public health problem . This study was design ed to determine the feasibility of a young-adult-oriented program , the X-Pack Program , when administered to college student smokers , and to estimate its effect on smoking cessation . Participants ( N = 83 ) were r and omized after enrollment to receive either a moderately intensive , E-mail-based , young-adult intervention ( the X-Pack group ) or a less-intensive program aim ed at a general adult audience ( the Clearing the Air group ) . Participants were assessed at baseline and at 3 and 6 months after enrollment . Participants in the X-Pack group rated their treatment more favorably overall , were more engaged in program activities , and quit for more consecutive days at the 3- and 6-month follow-ups , compared with the Clearing the Air group . Differences in quit rates favored the X-Pack group at the two follow-ups , but the differences were not significant . These findings offer some support for the X-Pack Program when administered to college smokers The aim was to better underst and structural factors associated with uptake of automated tailored interventions for smoking cessation . In a prospect i ve r and omized controlled trial with interventions only offered , not m and ated , participants were r and omized based on the following : web-based expert system ( QuitCoach ) ; text messaging program ( onQ ) ; both as an integrated package ; the choice of using either or both ; or a control condition informed of a static website ( not considered here ) . Participants were 3530 smokers or recent quitters recruited from two sources ; those seeking smoking cessation information , mostly recruited over the phone , and a cold-contacted group recruited from an Internet panel . More participants ( 60.1 % ) initially accepted the intervention they had been offered than used it ( 42.5 % ) . Uptake of each intervention differed substantially by both recruitment source and modality ( phone or web ) . onQ was a little more popular overall , especially in the information seeker sample . Highest overall intervention uptake occurred in the choice condition . A web-based intervention is most attractive if the offer to use is made by web , whereas a phone-based intervention is more likely to be used if the offer is made over the phone . Providing automated interventions on multiple platforms allows for maximal choice and greatest overall use of some form of help Background Smoking among cancer survivors increases the risk of late effects and second cancers . This article reports on Partnership for Health-2 (PFH-2)—an effort to develop an effective and scalable version of Partnership for Health ( PFH ) , which was a previously tested peer-delivered telephone counseling program that doubled smoking cessation rates among childhood cancer survivors who smoke . Objective This paper presents results from a r and omized controlled trial evaluating the effectiveness of PFH-2 in targeted and tailored Web-based versus print formats . The overall goal was to determine whether the intervention outcomes in these self-guided scalable formats approximate what was found in a more intensive telephone counseling program . Methods This study was a r and omized controlled trial with a 15-month follow-up that included 374 smokers who were survivors of childhood or young adult cancers , recruited from five survivorship clinics . Participants were r and omly assigned to a Web-based or print format of the PFH intervention ; all had access to free pharmacotherapy . The website was design ed to provide new content at each log-on , and a peer counselor moderated a forum/chat feature . The primary outcome was smoking status at 15 months post r and omization . Results In total , 58.3 % ( 77/132 ) of Web participants logged on at least once ( mean visits 3.25 ) . Using multiple imputation methods for missing data , there were similar rates of cessation in the two arms ( print : 20/128 , 15.6 % ; Web : 33/201 , 6.4 % ) , and no differences in quit attempts or readiness to quit . The quit rates were equivalent to those found in our previous telephone counseling intervention . There were high rates of satisfaction with both of the PFH-2 interventions . Conclusions The print and Web formats yielded equivalent levels of success to those found with our telephone-delivered intervention and are comparable to other Internet treatment studies . This study provides important options for survivorship programs that may not have re sources for interpersonal forms of cessation counseling . Efforts to increase patient use of the interventions may result in higher cessation rates . Trial Registration Clinical trials.gov NCT00588107 ; http:// clinical trials.gov/ct2/show/NCT00588107 ( Archived by WebCite at http://www.webcitation.org/6K1gJtFEC ) Background Although effective smoking cessation interventions exist , information is limited about their cost-effectiveness and cost-utility . Objective To assess the cost-effectiveness and cost-utility of an Internet-based multiple computer-tailored smoking cessation program and tailored counseling by practice nurses working in Dutch general practice s compared with an Internet-based multiple computer-tailored program only and care as usual . Methods The economic evaluation was embedded in a r and omized controlled trial , for which 91 practice nurses recruited 414 eligible smokers . Smokers were r and omized to receive multiple tailoring and counseling ( n=163 ) , multiple tailoring only ( n=132 ) , or usual care ( n=119 ) . Self-reported cost and quality of life were assessed during a 12-month follow-up period . Prolonged abstinence and 24-hour and 7-day point prevalence abstinence were assessed at 12-month follow-up . The trial-based economic evaluation was conducted from a societal perspective . Uncertainty was accounted for by bootstrapping ( 1000 times ) and sensitivity analyses . Results No significant differences were found between the intervention arms with regard to baseline characteristics or effects on abstinence , quality of life , and addiction level . However , participants in the multiple tailoring and counseling group reported significantly more annual health care – related costs than participants in the usual care group . Cost-effectiveness analysis , using prolonged abstinence as the outcome measure , showed that the mere multiple computer-tailored program had the highest probability of being cost-effective . Compared with usual care , in this group € 5100 had to be paid for each additional abstinent participant . With regard to cost-utility analyses , using quality of life as the outcome measure , usual care was probably most efficient . Conclusions To our knowledge , this was the first study to determine the cost-effectiveness and cost-utility of an Internet-based smoking cessation program with and without counseling by a practice nurse . Although the Internet-based multiple computer-tailored program seemed to be the most cost-effective treatment , the cost-utility was probably highest for care as usual . However , to ease the interpretation of cost-effectiveness results , future research should aim at identifying an acceptable cutoff point for the willingness to pay per abstinent participant CONTEXT Young adult smokers have the highest smoking prevalence among all US age groups but are least likely to use evidence -based cessation counseling or medication to quit . OBJECTIVE Use and effectiveness of nicotine patch were explored in a r and omized trial evaluating smoking cessation interventions with this population . PARTICIPANTS Smokers aged 18 to 30 ( n = 3094 ) were recruited through online and off-line methods and from telephone quit lines and analyzed . DESIGN Smokers were enrolled in a pretest-posttest trial , and r and omized to 1 of 3 cessation services . SETTING Trial delivering counseling services by self-help booklet , telephone quit lines , or online expert system in the 48 continental United States . INTERVENTION Smokers could request a free 2-week course of nicotine replacement therapy ( NRT ) patches from the project . MAIN OUTCOME MEASURE Follow-up surveys at 12 and 26 weeks assessed smoking abstinence , use of NRT , counseling , and other cessation medications , and smoking-related variables . RESULTS Overall , 69.0 % of smokers reported using NRT ( M = 3.2 weeks ) at 12 weeks and 74.8 % ( M = 3.3 weeks ) at 26 weeks . More smokers who were sent the free nicotine patches ( n = 1695 ; 54.8 % ) reported using NRT than those who did not receive them ( 12 weeks : 84.3 % vs 41.9 % , P < .001 ; 26 weeks : 87.6 % vs 51.1 % , P < .001 ) . The use of NRT was associated with greater smoking abstinence at 12 weeks ( P < .001 ) and 26 weeks ( P < .05 ) , especially if used for more than 2 weeks ( P < .001 ) . Smokers assigned to a self-help booklet or cessation Web site and heavier smokers were most likely to use NRT ( P < .05 ) , whereas those reporting marijuana use and binge drinking used NRT less ( P < .05 ) . CONCLUSIONS Many young adults were willing to try NRT , and it appeared to help them quit in the context of community-based cessation services . Strategies should be developed to make NRT available to this age group and support them in using it to prevent lifelong smoking AIM To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation material s among nicotine patch users . DESIGN Two-group r and omized controlled trial . SETTING World Wide Web in Engl and and Republic of Irel and . PARTICIPANTS A total of 3971 subjects who purchased a particular br and of nicotine patch and logged-on to use a free web-based behavioral support program . INTERVENTION Web-based tailored behavioral smoking cessation material s or web-based non-tailored material s. MEASUREMENTS Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up . FINDINGS Using three approaches to the analyses of 6- and 12-week outcomes , participants in the tailored condition reported clinical ly and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition . In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once , continuous abstinence rates at 6 weeks were 29.0 % in the tailored condition versus 23.9 % in the non-tailored condition ( OR = 1.30 ; P = 0.0006 ) ; at 12 weeks continuous abstinence rates were 22.8 % versus 18.1 % , respectively ( OR = 1.34 ; P = 0.0006 ) . Moreover , satisfaction with the program was significantly higher in the tailored than in the non-tailored condition . CONCLUSIONS The results of this study demonstrate a benefit of the web-based tailored behavioral support material s used in conjunction with nicotine replacement therapy . A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program The aim of this study was to examine moderating and mediating factors of the efficacy of World Wide Web-based tailored behavioral smoking cessation material s. The design was a two-group r and omized controlled trial in Engl and and the Republic of Irel and . Participants were 3971 subjects who purchased a particular br and of nicotine patch and logged on to use a free Web-based behavioral support program . The intervention was Web-based tailored behavioral smoking cessation material s or Web-based nontailored material s. The 10-week continuous abstinence rate was assessed by Internet-based survey at 12-week follow-up . Potential treatment moderators were examined using subgroups of established or possible predictors of smoking cessation . Treatment mediators examined included 6-week follow-up measures of program relevance and amount of the Web-based material s read . Within all subgroups examined , subjects in the Web-based tailored intervention were more likely to report 10-week continuous abstinence at 12-week follow-up . Significant moderators , indicating a significant difference in program efficacy between subgroups , included presence of a tobacco-related illness ( larger treatment-control differences among subjects with a tobacco-related illness ) , presence of nonsmoking children in the household ( larger treatment-control differences among subjects with nonsmoking children in the household ) , and frequent alcohol consumption ( larger treatment-control differences among subjects with higher alcohol consumption ) . Perceived program relevance at 6-week follow-up was a mediator of cessation at 12-week follow-up . Robust results of the tailored program may be explained by the tailoring strategies utilized in the treatment conditions . Moderating variables may be particularly useful to address in tailored messaging . The mediating factor of perceived message relevance may provide a partial mechanism of effective program tailoring OBJECTIVE College represents a window of opportunity to reach the sizeable number of cigarette smokers who are vulnerable to lifelong smoking . The underutilization of typical cessation programs suggests the need for novel and more engaging approaches for reaching college smokers . The aim of the present study was to test the efficacy of a dissonance-enhancing , Web-based experiential intervention for increasing smoking cessation motivation and behavior . METHOD We used a 4-arm , r and omized design to examine the efficacy of a Web-based , experiential smoking intervention ( Web-Smoke ) . The control conditions included a didactic smoking intervention ( Didactic ) , a group-based experiential intervention ( Group ) , and a Web-based nutrition experiential intervention ( Web-Nutrition ) . We recruited 341 college smokers . Primary outcomes were motivation to quit , assessed immediately postintervention , and smoking abstinence at 1 and 6 months following the intervention . RESULTS As hypothesized , the Web-Smoke intervention was more effective than control groups in increasing motivation to quit . At 6-month follow-up , the Web-Smoke intervention produced higher rates of smoking cessation than the Web-Nutrition control intervention . Daily smoking moderated intervention outcomes . Among daily smokers , the Web-Smoke intervention produced greater abstinence rates than both the Web-Nutrition and Didactic control conditions . CONCLUSION Findings demonstrate the efficacy of a theory-based intervention delivered over the Internet for increasing motivation to quit and smoking abstinence among college smokers . The intervention has potential for translation and implementation as a secondary prevention strategy for college-aged smokers . ( PsycINFO Data base Record ( c ) 2013 APA , all rights reserved ) BACKGROUND Review s state that there is a room for improvements of smoking cessation ( SC ) intervention in general practice . METHODS In 2005 , all 61 general practitioners ( GPs ) in four municipalities in Copenhagen , Denmark , were invited to participate . Twenty-four GPs accepted and were cluster r and omized to one of three groups : Group A , referral to group-based SC counselling ( national model ) , n = 10 ; Group B , referral to internet-based SC programme ( newly developed ) , n = 8 ; or Group C , no referral ( ' do as usual ' ) , n = 6 . A total of 1518/1914 smokers were included , and 760 returned a question naire at 1-year follow-up . RESULTS The participating GPs reported significantly more SC counselling than GPs who refused participation ( P = 0.04 ) . Self-reported point abstinence was 6.7 % ( 40/600 ) , 5.9 % ( 28/476 ) and 5.7 % ( 25/442 ) in Groups A , B and C , respectively . Only 40 smokers attended group-based SC counselling , and 75 logged in at the internet-based SC programme . In cluster analyses , we found no significant additional effect of referral to group-based ( OR : 1.05 ; 95 % CI : 0.6 - 1.8 ) or internet-based SC programmes ( OR : 0.91 ; 95 % CI : 0.6 - 1.4 ) . CONCLUSIONS We found no additional effect on cessation rates of GPs ' referring to group-based SC counselling or internet-based SC programme . This finding might , to some degree , be explained by the short time used by the GPs on SC counselling and the selection of the participating doctors BACKGROUND Interventions using sustained aerobic exercise programs to aid smoking cessation have result ed in modest , short-term cessation rates comparable to conventional cessation methods . No smoking cessation trial to date has prescribed intermittent bouts of exercise in response to nicotine cravings . OBJECTIVES This pilot r and omized controlled trial examined the feasibility and efficacy of an Internet-based smoking cessation program alone ( CON ) vs. the same Internet-based program + intermittent exercise in response to cigarette cravings ( EX ) . STUDY POPULATION Participants ( N = 38 ; mean age = 43.6 [ SD = 11.5 ] ; 60.5 % women ) were generally healthy , inactive adult smokers who desired to quit . RESULTS The overall retention rate was 60.5 % ( n = 23 ) , and no significant retention rate differences were found between groups ( EX vs. CON ) . Although retained participants achieved a higher cessation rate ( 26.1 % ) than all enrolled participants ( 15.8 % ) , adjusted intent-to-treat and per- protocol binary logistic regression analyses revealed no significant cessation rate differences between EX and CON groups . Linear regression results indicated that additional days of self-reported exercise on the study website during the intervention phase predicted significantly higher reduction rates among EX group participants , F(2 , 16 ) = 31.08 , p < .001 . CONCLUSIONS Results were mixed with regard to the incremental benefit of exercise in the presence of the apparently valuable Internet-based smoking cessation program . The results support findings from related research and underscore the need for additional investigation into both the mechanisms underlying the effect of exercise on cigarette cravings and the challenges of poor adherence in the context of exercise-based smoking cessation interventions AIMS To determine whether web-based tailored cessation advice , based on social cognitive theory and the perspectives on change model , was more effective in aiding a quit attempt than broadly similar web-based advice that was not tailored . DESIGN Participants were allocated r and omly to one of two groups , to receive either a cessation advice report and progress report that were tailored to individual-level characteristics or a cessation advice report that presented st and ardized ( non-tailored ) content . Tailoring was based on smoking-related beliefs , personal characteristics and smoking patterns , self-efficacy and outcome expectations . SETTING Participant enrolment and baseline assessment s were conducted remotely online via the study website , with the advice reports presented by the same website . PARTICIPANTS Participants ( n = 1758 ) were visitors to the QUIT website who were based in the United Kingdom , aged 18 years or over and who smoked cigarettes or h and -rolled tobacco . MEASUREMENTS Follow-up assessment s were made at 6 months by telephone interview . The primary outcome measure was self-reported 3 months prolonged abstinence , and secondary outcomes were 1 month prolonged abstinence , 7-day and 24-hour point prevalence abstinence . FINDINGS The intervention group did not differ from the control group on the primary outcome ( 9.1 % versus 9.3 % ; odds ratio = 1.02 95 % confidence interval 0.73 - 1.42 ) or on any of the secondary outcomes . Intervention participants gave more positive evaluations of the material s than control participants . CONCLUSIONS A web-based intervention that tailored content according to smoking-related beliefs , personal characteristics and smoking patterns , self-efficacy and outcome expectations , was not more effective than web-based material s presenting broadly similar non-tailored information Aims To estimate the short-term effectiveness , feasibility and acceptability of a smoking cessation intervention ( the iQuit system ) that consists of tailored printed and Short Message Service ( SMS ) text message self-help delivered as an adjunct to cessation support in primary care to inform the design of a definitive trial . Design A stratified two parallel-group r and omized controlled trial comparing usual care ( control ) with usual care plus the iQuit system ( intervention ) , delivered by primary care nurses/healthcare assistants who were blinded to the allocation sequence . Setting Thirty-two general practice ( GP ) surgeries in Engl and , UK . Participants A total of 602 smokers initiating smoking cessation support from their local GP surgery were r and omized ( control n = 303 , intervention n = 299 ) . Measurements Primary outcome was self-reported 2-week point prevalence abstinence at 8 weeks follow-up . Secondary smoking outcomes and feasibility and acceptability measures were collected at 4 weeks after quit date , 8 weeks and 6 months follow-up . Findings There were no significant between-group differences in the primary outcome [ control 40.3 % , iQuit 45.2 % ; odds ratio ( OR ) = 1.22 , 95 % confidence interval ( CI ) = 0.88–1.69 ] or in secondary short-term smoking outcomes . Six-month prolonged abstinence was significantly higher in the iQuit arm ( control 8.9 % , iQuit 15.1 % ; OR = 1.81 , 95 % CI = 1.09–3.01 ) . iQuit support took on average 7.7 minutes ( st and ard deviation = 4.0 ) to deliver and 18.9 % ( 95 % CI = 14.8–23.7 % ) of intervention participants discontinued the text message support during the programme . Conclusions Tailored printed and text message self-help delivered alongside routine smoking cessation support in primary care does not significantly increase short-term abstinence , but may increase long-term abstinence and demonstrated feasibility and acceptability compared with routine cessation support alone BACKGROUND Smoking remains the primary preventable cause of death and illness in the U.S. Effective , convenient treatment programs are needed to reduce smoking prevalence . PURPOSE This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline . METHODS Current treatment-seeking smokers ( n=1202 ) were recruited from a large healthcare organization between October 2006 and October 2007 . Eligible participants were r and omized to one of three smoking-cessation interventions : web-based counseling ( n=401 ) ; proactive telephone-based counseling ( PTC ; n=402 ) ; or combined PTC and web counseling ( n=399 ) . All participants received a st and ard 12-week FDA -approved course of varenicline . Self-report determined the primary outcomes ( 7-day point prevalent abstinence at 3- and 6-month follow-ups ) ; the number of days varenicline was taken ; and treatment-related symptoms . Behavioral measures determined utilization of both the web- and Phone-based counseling . RESULTS Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months ( 38.9 % , 48.5 % , 43.4 % ) and at 6 months ( 30.7 % , 34.3 % , 33.8 % ) for the web , PTC , and PTC-web groups , respectively . The PTC group had a significantly higher percentage of abstinence than the web group at 3 months ( OR=1.48 , 95 % CI=1.12 , 1.96 ) , but no between-group differences in abstinence outcomes were seen at 6 months . CONCLUSIONS Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence , but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline OBJECTIVE This study was design ed to compare the initial efficacy of Motivational Interviewing ( MI ) , Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention ( HRI ) on four health risk factors ( inactivity , BMI , stress and smoking ) in a worksite sample . METHOD A r and omized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments . The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months . At the initial post-treatment assessment at 6 months , groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks . RESULTS Compared to the HRI only group , the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months . MI and TTM group outcomes were not different . CONCLUSION This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes . Future research will examine the long-term impacts of each treatment , their cost effectiveness , effects on productivity and quality of life and process variables mediating outcomes INTRODUCTION Smoking is quite prevalent among Korean Americans ( KAs ) . Quitting is Winning was developed using community-based participatory research principles as an online self-help smoking cessation program for KAs in response to feedback from our community partner who felt that most KAs prefer to quit " on their own . " METHODS A r and omized controlled trial was used to evaluate this cognitive-behavioral program . The main outcome was the proportion of participants who had quit for at least 30 days , 50 weeks after enrollment , among those r and omized into the Internet intervention compared with those receiving a similar program via booklet . The study had 11 online surveys administered every 5 weeks . RESULTS The study took place between September 2005 and April 2009 and had a final enrollment of 1,112 . Based on the outcome assessed at 50 weeks , there was no significant difference in 30-day smoking cessation between the Internet ( 11 % ) and booklet ( 13 % ) groups ( intent-to-treat [ ITT ] difference = -2 % , 95 % CI = -6 % to 2 % ) . In post-hoc analysis , quitting was higher among participants in the Internet intervention ( n = 562 ) who completed the online program : 26 % quit compared with 10 % who did not complete the program ( ITT difference = 16 % , 95 % CI = 3%-29 % ) . CONCLUSIONS The Internet self-help smoking cessation program appears to help KA smokers quit , although not more than a similar program delivered via booklet . If we can get people engaged , online cessation programs have potential to reach smokers who would not or can not participate in more traditional interventions Objective : The objective of this project was to test the short term ( 90 days ) efficacy of an automated behavioural intervention for smoking cessation , the “ 1 - 2 - 3 Smokefree ” programme , delivered via an internet website . Design : R and omised control trial . Subjects surveyed at baseline , immediately post-intervention , and 90 days later . Setting s : The study and the intervention occurred entirely via the internet site . Subjects were recruited primarily via worksites , which referred potential subjects to the website . Subjects : The 351 qualifying subjects were notified of the study via their worksite and required to have internet access . Additionally , subjects were required to be over 18 years of age , smoke cigarettes , and be interested in quitting smoking in the next 30 days . Eligible subjects were r and omly assigned individually to treatment or control condition by computer algorithm . Intervention : The intervention consisted of a video based internet site that presented current strategies for smoking cessation and motivational material s tailored to the user ’s race/ethnicity , sex , and age . Control subjects received nothing for 90 days and were then allowed access to the programme . Main outcome measures : The primary outcome measure was abstinence from smoking at 90 day follow up . Results : At follow up , the cessation rate at 90 days was 24.1 % ( n = 21 ) for the treatment group and 8.2 % ( n = 9 ) for the control group ( p = 0.002 ) . Using an intent-to-treat model , 12.3 % ( n = 21 ) of the treatment group were abstinent , compared to 5.0 % ( n = 9 ) in the control group ( p = 0.015 ) . Conclusions : These evaluation results suggest that a smoking cessation programme , with at least short term efficacy , can be successfully delivered via the internet BACKGROUND PAS ( Personal Advice in Stopping smoking ) combines two of the most effective smoking cessation interventions : multiple computer tailoring and tailored counselling by a practice nurse in the general practice . METHODS / DESIGN Since May 2009 , practice nurses are recruiting smoking patients . Each practice nurse is asked to recruit 15 adult smokers who are willing to quit within 6months and have access to the Internet . Smokers can sign up for PAS through the PAS website and are then r and omized into one of three groups receiving multiple tailoring and counselling ( MTC ) , multiple tailoring ( MT ) or usual care ( UC ) , respectively . All groups receive question naires at baseline , 2days after a set quit date and at 6weeks , 6months and 12months follow-up . The MT group receives tailored , iterative feedback letters at the first four measurements points . At 12months follow-up biochemical validation will take place amongst respondents reporting to have quit . The three groups will be compared with regard to quit attempt rate , point prevalence abstinence and continued abstinence by means of logistic multilevel regression analyses . Linear multilevel regression analyses will be used to compare the three groups regarding smoking related beliefs . DISCUSSION The present paper provides an extensive description of the development of PAS and of the design of the study towards its effectiveness . This might provide insight into PAS ' potentially effective working mechanisms . The results concerning effectiveness may contribute to knowledge about the effectiveness of smoking cessation interventions aim ed at smoking adults . TRIAL REGISTRATION Dutch Trial Register NTR1351 This study reports the outcome of a r and omized controlled trial testing a computer-tailored smoking cessation intervention based on the transtheoretical model in a general population setting in Germany . Participants of the smoking intervention study were recruited from an existing general population health examination survey in a university hospital . The sample consisted of 611 current and former smokers at baseline , and of 485 participants in the core group of baseline daily cigarette smokers . Follow-ups were conducted 6 , 12 , 18 , and 24 months after baseline . The intervention was design ed for both current and former smokers , involved up to three individualized feedback letters , and was created using expert-system technology . Based on 7-day point-prevalence abstinence and 6-month prolonged abstinence as the outcome measures , the study identified no significant differences between the intervention and control groups . Modeling the full longitudinal data in generalized estimation equation analyses , using different nonresponse procedures , and adjusting for covariates did not alter the results . We conclude that the computer-tailored transtheoretical model-based smoking cessation intervention , as delivered in this study and in this special setting , was ineffective OBJECTIVES To determine the efficacy of providing online cessation intervention for college smokers . METHODS This is a two-group r and omized controlled trial . The intervention group received $ 10 weekly incentives to visit an online college life magazine that provided personalized smoking cessation messages and peer email support . Evaluation assessment s occurred at baseline and 8 , 20 , and 30 weeks after enrollment . The primary outcome is self-reported 30-day abstinence at week 30 . Carbon monoxide ( CO ) breath testing was performed for participants reporting 30-day abstinence at week 30 . RESULTS Five-hundred and seventeen college smokers at the University of Minnesota were enrolled via internet health screening ( control=260 , intervention=257 ) in the fall of 2004 . Intervention participants completed an average of 18.9 ( SD 2.5 ) of 20 weekly website visits over the course of the study . The rate of 30-day abstinence at week 30 was higher for the intervention compared to the control group ( 41 % vs. 23 % , p<0.001 ) . CO testing showed low rates of under-reporting . There was no difference in self-reported 6-month prolonged abstinence measured at week 30 . CONCLUSION Providing personalized smoking cessation messages as part of a general interest online college life magazine increased 30-day abstinence by the end of this two semester intervention INTRODUCTION There are 1.1 billion smokers worldwide . Traditional smoking cessation methods , such as nicotine replacement therapy and smoking cessation groups , yield between 14 % and 27 % abstinence rates at 6 months . Evidence -based Internet interventions with comparable abstinence rates could be a powerful global tool to reduce tobacco-related morbidity and mortality . METHODS We report a r and omized control trial in which 500 Spanish-speaking and 500 English-speaking adult Internet users , smoking at least 5 cigarettes/day and intending to quit in the next month , were recruited online from 68 countries . Consenting participants who completed baseline measures , logged cigarettes smoked on 3 days within a week , and set a quit date were r and omized to four conditions . Each condition added new elements : Condition 1 was the " Guía Para Dejar de Fumar , " a static National Cancer Institute evidence -based stop smoking guide ; Condition 2 consisted of Condition 1 plus E-mail reminders to return to the site ; Condition 3 consisted of Condition 2 plus mood management lessons ; and Condition 4 consisted of Condition 3 plus a " virtual group " ( an asynchronous bulletin board ) . Main outcome measures were 7-day point prevalence abstinence at 1 , 3 , 6 , and 12 months after initial quit date . RESULTS There were no significant differences among the four conditions . The overall 12-month 7-day abstinence rates were 20.2 % for Spanish speakers and 21.0 % for English speakers when those with missing data were assumed to be smoking . DISCUSSION Internet smoking cessation interventions with such abstinence rates provided globally in additional language s could contribute substantially to tobacco control efforts Background Web-based programs for health promotion , disease prevention , and disease management often experience high rates of attrition . There are 3 questions which are particularly relevant to this issue . First , does engagement with program content predict long-term outcomes ? Second , which users are most likely to drop out or disengage from the program ? Third , do particular intervention strategies enhance engagement ? Objective To determine : ( 1 ) whether engagement ( defined by the number of Web sections opened ) in a Web-based smoking cessation intervention predicts 6-month abstinence , ( 2 ) whether particular sociodemographic and psychographic groups are more likely to have lower engagement , and ( 3 ) whether particular components of a Web-based smoking cessation program influence engagement . Methods A r and omized trial of 1866 smokers was used to examine the efficacy of 5 different treatment components of a Web-based smoking cessation intervention . The components were : high- versus low-personalized message source , high- versus low-tailored outcome expectation , efficacy expectation , and success story messages . Moreover , the timing of exposure to these sections was manipulated , with participants r and omized to either a single unified Web program with all sections available at once , or sequential exposure to each section over a 5-week period of time . Participants from 2 large health plans enrolled to receive the online behavioral smoking cessation program and a free course of nicotine replacement therapy ( patch ) . The program included : an introduction section , a section focusing on outcome expectations , 2 sections focusing on efficacy expectations , and a section with a narrative success story ( 5 sections altogether , each with multiple screens ) . Most of the analyses were conducted with a stratification of the 2 exposure types . Measures included : sociodemographic and psychosocial characteristics , Web sections opened , perceived message relevance , and smoking cessation 6-months following quit date . Results The total number of Web sections opened was related to subsequent smoking cessation . Participants who were younger , were male , or had less formal education were more likely to disengage from the Web-based cessation program , particularly when the program sections were delivered sequentially over time . More personalized source and high-depth tailored self-efficacy components were related to a greater number of Web sections opened . A path analysis model suggested that the impact of high-depth message tailoring on engagement in the sequentially delivered Web program was mediated by perceived message relevance . Conclusions Results of this study suggest that one of the mechanisms underlying the impact of Web-based smoking cessation interventions is engagement with the program . The source of the message , the degree of message tailoring , and the timing of exposure appear to influence Web-based program engagement To address health problems that have a major impact on global health requires research design s that go beyond r and omized controlled trials . One such design , the participant preference trial , provides additional information in an ecologically valid manner , once intervention efficacy has been demonstrated . The current study presents illustrative data from a participant preference trial of an internet-based smoking cessation intervention . Participants ( N=7763 ) from 124 countries accessed the intervention and were allowed to choose from nine different site components to aid their quit attempt . Of consenting participants , 36.7 % completed at least one follow-up assessment . Individuals with depression were more likely to choose a mood management module and participants who smoked a higher number of cigarettes were more likely to choose a cigarette counter and a nicotine replacement therapy guide . Furthermore , depressed participants selecting the mood management component were more likely to report at least one successful 7 day quit ( 37.2 % vs. 22.2 % ) in the 12 months following the intervention . Thus , participants with depressive symptoms appear to make choices on the basis of their needs and to benefit from these decisions . This suggests that providing the ability to customize previously vali date d re sources may be a successful way to widely disseminate interventions To assess and compare the impact on quit attempts of online computer-tailored smoking cessation counseling reports and untailored reports , we performed a r and omized controlled trial on a smoking cessation website in 2007–2008 . After answering a question naire , current and former smokers were r and omly assigned to immediately receiving either an online , individually tailored counseling report or a personalized but untailored generic report . Participants were invited by e-mail to report any smoking in the previous 24 hours , 48 hours after baseline . We used an intention-to-treat analysis , where nonrespondents at follow-up were counted as smokers . There were 2,872 participants at baseline and 2,226 at follow-up ( 78 % ) . At baseline , there were 76 % of current smokers ( mean = 18 cigarettes/day ) and 24 % of recent quitters ( median = 7 days of abstinence ) . The same proportion of smokers in both study groups had made a 24-hour quit attempt at follow-up ( 12.1 % , P = 1.0 ) . In baseline recent quitters , lapse/relapse rates at follow-up were similar in both groups ( tailored : 25.1 % , untailored : 23.5 % , P = 0.64 ) . We conclude that untailored reports were as effective as tailored reports in the short term . Even though these particular computer-tailored reports were not more effective than untailored reports , meta-analyses show that computer-tailored documents are in general more effective than untailored ones ABSTRACT Little is known about the relative , additive , and interactive effects of different population -based treatments for smoking cessation . The goal of this study was to evaluate the main and interactive effects of five different smoking interventions . Using the multiphase optimization strategy ( MOST ) , 1,034 smokers who entered a Web site for smokers ( smokefree.gov ) were r and omly assigned to the “ on ” and “ off ” conditions of five smoking cessation interventions : the National Cancer Institute ’s ( NCI ) Web site ( www.smokefree.gov vs a “ lite ” Web site ) , telephone quitline counseling ( vs none ) , a smoking cessation brochure ( vs a lite brochure ) , motivational e-mail messages ( vs none ) , and mini-lozenge nicotine replacement therapy ( NRT vs none ) . Analyses showed that the NCI Web site and NRT both increased abstinence ; however , the former increased abstinence significantly only when it was not used with the e-mail messaging intervention ( messaging decreased Web site use ) . The other interventions showed little evidence of effectiveness . There was evidence that mailed nicotine mini-lozenges and the NCI Web site ( www.smokefree.gov ) provide benefit as population -based smoking interventions INTRODUCTION Quit rates for smoking cessation attempts are maximized by using counseling with medication . Internet-based counseling might be a suitable replacement for in-person counseling . METHODS Patients in a military medical system in the active phase of quitting presented for study intake . They were r and omized to in-person counseling ( n = 44 ) or Internet counseling ( n = 173 ) . In-person counseling consisted of four 1.5 hour classes based on the American Cancer Society 's Freshstart program . Internet counseling consisted of daily e-mails with recommended activities through Pfizer 's GetQuit program . Both groups were concomitantly treated with st and ard dose varenicline . The primary outcome was the quit rate at 12 weeks , defined as abstinence and an exhaled carbon monoxide level < 10 ppm at the 12-week visit . All those lost to follow-up were considered persistent smokers . RESULTS 217 smokers were r and omized , of which 43 % returned for the 12-week follow-up visit . Quit rates between the two groups were similar ( Internet group : 21 % , n = 36/173 ; in-person group : 18 % , n = 8/44 , p = 0.7 ) . CONCLUSIONS Internet-based counseling might be equivalent to in-person counseling for smoking cessation in patients taking varenicline . Additional studies with more complete and longer-term ( ≥1 year ) follow-up are needed to confirm these findings The Internet provides a medium to administer and evaluate evidence -based interventions for highly prevalent public health problems worldwide . The authors report a series of four Internet smoking cessation studies conducted in English and Spanish . These studies examined both outcome ( self-reported 7-day abstinence ) and mechanisms related to outcome ( the impact of major depressive episodes [ MDEs ] on the likelihood of quitting ) . Over 4,000 smokers from 74 countries entered the studies . Studies 1 and 2 evaluated a st and ard smoking cessation guide ( the " Guía " ) . Studies 3 and 4 were r and omized trials comparing the Guía+ITEMs ( individually timed educational messages ) to the Guía+ITEMs+a mood management course . ITEMs were E-mails inviting participants back to the site at specific times . Online follow-up assessment s result ed in completion rates of 44%-54 % at 1 month and 26%-30 % at 6 months in studies 1 and 2 . Incentives and follow-up phone calls increased these rates to 70 % , 66 % , 65 % , and 62 % at 1 , 3 , 6 , and 12 months in study 4 . At 6 months , self-reported 7-day abstinence rates using missing = smoking data were 6 % in studies 1 and 2 , 10%-14 % in study 3 , and 20%-26 % in study 4 . The Guía+ITEMs condition tended to have higher quit rates , which reached significance at the 12-month follow-up in study 3 and at the 3-month follow-up in study 4 . Smokers with past ( but not current ) MDEs tended to be the most likely to abstain and those with current MDEs the least likely . This trend reached significance in studies 1 and 4 OBJECTIVE Web-based smoking cessation interventions have high reach , but low effectiveness . To address this problem , we conducted a pilot r and omized controlled trial of the first web-based acceptance and commitment therapy ( ACT ) intervention for smoking cessation . The aims were to determine design feasibility , user receptivity , effect on 30-day point prevalence quit rate at 3 months post-r and omization , and mediation by ACT theory-based processes of acceptance . METHODS Adult participants were recruited nationally into the double-blind r and omized controlled pilot trial ( N = 222 ) , which compared web-based ACT for smoking cessation ( WebQuit.org ) with the National Cancer Institute 's Smokefree.gov-the U.S. national st and ard for web-based smoking cessation interventions . RESULTS We recruited 222 participants in 10 weeks . Participants spent significantly longer on the ACT WebQuit.org site per login ( 18.98 vs. 10.72 min ; p = .001 ) and were more satisfied with the site ( 74 % vs. 42 % ; p = .002 ) . Using available follow-up data , more than double the fraction of participants in the ACT WebQuit.org arm had quit smoking at the 3-month follow-up ( 23 % vs. 10 % ; OR = 3.05 ; 95 % CI = 1.01 - 9.32 ; p = .050 ) . Eighty percent of this effect was mediated by ACT theory-based increases in total acceptance of physical , cognitive , and emotional cues to smoke ( p < .001 ) . CONCLUSIONS The trial design was feasible . Compared with Smokefree.gov , ACT had higher user receptivity and short-term cessation , and strong evidence of theory-based mechanisms of change . While results were promising , they were limited by the pilot design ( e.g. , limited follow-up ) , and thus a full-scale efficacy trial is now being conducted Health care and health care services are increasingly being delivered over the Internet . There is a strong argument that interventions delivered online should also be evaluated online to maximize the trial ’s external validity . Conducting a trial online can help reduce research costs and improve some aspects of internal validity . To date , there are relatively few trials of health interventions that have been conducted entirely online . In this paper we describe the major method ological issues that arise in trials ( recruitment , r and omization , fidelity of the intervention , retention , and data quality ) , consider how the online context affects these issues , and use our experience of one online trial evaluating an intervention to help hazardous drinkers drink less ( DownYourDrink ) to illustrate potential solutions . Further work is needed to develop online trial methodology We describe a r and omized controlled trial , the Lakota Oyate Wicozani Pi Kte ( LOWPK ) trial , which was design ed to determine whether a Web-based diabetes and nutritional intervention can improve risk factors related to cardiovascular disease ( CVD ) among a group of remote reservation – dwelling adult American Indian men and women with type 2 diabetes who are at high risk for CVD . Enrollment on a rolling basis of 180 planned participants began during 2009 ; an average 18-month follow-up was completed by June 2011 . The primary outcome variable is change in glycosylated hemoglobin level after an average 18-month follow-up period . Secondary outcome variables include changes in low-density lipoprotein cholesterol , systolic blood pressure , body mass index , and smoking status , as well as an evaluation of intervention cost-effectiveness . If effective , the LOWPK trial may serve as a guide for future chronic disease intervention trials in remote , technologically challenged setting Background The Internet is an optimal setting to provide massive access to tobacco treatments . To evaluate open-access Web-based smoking cessation programs in a real-world setting , adherence and retention data should be taken into account as much as abstinence rate . Objective The objective was to analyze the usage and effectiveness of a fully automated , open-access , Web-based smoking cessation program by comparing interactive versus noninteractive versions . Methods Participants were r and omly assigned either to the interactive or noninteractive version of the program , both with identical content divided into 4 interdependent modules . At baseline , we collected demographic , psychological , and smoking characteristics of the smokers self-enrolled in the Web-based program of Universidad Nacional de Educación a Distancia ( National Distance Education University ; UNED ) in Madrid , Spain . The following question naires were administered : the anxiety and depression subscales from the Symptom Checklist-90-Revised , the 4-item Perceived Stress Scale , and the Heaviness of Smoking Index . At 3 months , we analyzed dropout rates , module completion , user satisfaction , follow-up response rate , and self-assessed smoking abstinence . Results A total of 23,213 smokers were registered , 50.06 % ( 11,620/23,213 ) women and 49.94 % ( 11,593/23,213 ) men , with a mean age of 39.5 years ( SD 10.3 ) . Of these , 46.10 % ( 10,701/23,213 ) were married and 34.43 % ( 7992/23,213 ) were single , 46.03 % ( 10,686/23,213 ) had university education , and 78.73 % ( 18,275/23,213 ) were employed . Participants smoked an average of 19.4 cigarettes per day ( SD 10.3 ) . Of the 11,861 smokers r and omly assigned to the interactive version , 2720 ( 22.93 % ) completed the first module , 1052 ( 8.87 % ) the second , 624 ( 5.26 % ) the third , and 355 ( 2.99 % ) the fourth . Completion data was not available for the noninteractive version ( no way to record it automatically ) . The 3-month follow-up question naire was completed by 1085 of 23,213 enrolled smokers ( 4.67 % ) . Among them , 406 ( 37.42 % ) self-reported not smoking . No difference between groups was found . Assuming missing respondents continued to smoke , the abstinence rate was 1.74 % ( 406/23,213 ) , in which 22,678 were missing respondents . Among follow-up respondents , completing the 4 modules of the intervention increased the chances of smoking cessation ( OR 1.95 , 95 % CI 1.27 - 2.97 , P<.001 ) , as did smoking 30 minutes ( OR 1.58 , 95 % CI 1.04 - 2.39 , P=.003 ) or 1 hour after waking ( OR 1.93 , 95 % CI 1.27 - 2.93 , P<.001 ) compared to smoking within the first 5 minutes after waking . Conclusions The findings suggest that the UNED Web-based smoking cessation program was very accessible , but a high level of attrition was confirmed . This could be related to the ease of enrollment , its free character , and the absence of direct contact with professionals . It is concluded that , in practice , the greater the accessibility to the program , the lower the adherence and retention . Professional support from health services and the payment of a reimbursable fee could prevent high rates of attrition BACKGROUND Initial trials of web-based smoking-cessation programs have generally been promising . The active components of these programs , however , are not well understood . This study aim ed to ( 1 ) identify active psychosocial and communication components of a web-based smoking-cessation intervention and ( 2 ) examine the impact of increasing the tailoring depth on smoking cessation . DESIGN R and omized fractional factorial design . SETTING Two HMOs : Group Health in Washington State and Henry Ford Health System in Michigan . PARTICIPANTS 1866 smokers . INTERVENTION A web-based smoking-cessation program plus nicotine patch . Five components of the intervention were r and omized using a fractional factorial design : high- versus low-depth tailored success story , outcome expectation , and efficacy expectation messages ; high- versus low-personalized source ; and multiple versus single exposure to the intervention components . MEASUREMENTS Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up . FINDINGS Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source . The cumulative assignment of the three tailoring depth factors also result ed in increasing the rates of 6-month cessation , demonstrating an effect of tailoring depth . CONCLUSIONS The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions . The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs . Finally , the use of a novel fractional factorial design allowed efficient examination of the study aims . The rapidly changing interfaces , software , and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery OBJECTIVE To examine the influence of positive affect and mood-management in the completion and success of an Internet-based smoking cessation intervention . METHODS Participants were recruited online ( n = 1000 ) and r and omized to 4 different interventions . Half of the participants received a mood-management tool . RESULTS Retention was predicted by positive affect at 3 and 12 months . There was a higher 12-month abstinence rate among those who were assigned to the mood-management intervention and had initial low positive affect . CONCLUSIONS The study supports the inclusion of mood-management tools in smoking cessation interventions and indicates that positive affect increases persistence to quit smoking INTRODUCTION Research needs to systematic ally identify which components increase online intervention effectiveness ( i.e. , active ingredients ) . This study explores the effects of 4 potentially important design features in an Internet-based , population -level smoking intervention . METHODS Smokers ( n = 1,865 ) were recruited from a large health care organization , regardless of readiness to quit . Using a full factorial design , participants were r and omized to 1 of the 2 levels of each experimental factor ( message tone [ prescriptive vs. motivational ] , navigation autonomy [ dictated vs. not ] , e-mail reminders [ yes vs. no ] , and receipt of personally tailored testimonials [ yes vs. no ] ) and provided access to the online intervention . Primary outcomes were self-reported 7-day point-prevalent smoking abstinence and confirmed utilization of adjunct treatment ( pharmacotherapy or phone counseling ) available through the health plan at 1 year . Outcomes were also assessed at 2 and 6 months and were examined among all enrolled participants ( intent-to-treat [ ITT ] ) and all who viewed the intervention ( modified ITT ) . RESULTS At 1 year , 13.7 % were abstinent and 26.0 % utilized adjunct treatment . None of the contrasting factor levels differentially influenced abstinence or treatment utilization at 12 months . In the modified ITT sample , smokers receiving testimonials were less likely to use adjunct treatment at 6 months ( odds ratio = 0.54 , 95 % confidence interval = 0.30 - 0.98 , p = .04 ) . CONCLUSIONS None of the design features enhanced treatment outcome . The negative effect observed for testimonials is provocative , but it should be viewed with caution . This study offers a model for future research testing the " active ingredients " of online interventions BACKGROUND Young adulthood is a critical transition period for the development of health behaviors . We present here the results of a r and omized controlled trial of an online avatar-hosted personal health makeover program design ed for young adult smokers . METHODS We conducted a three-group r and omized trial comparing delivery of general lifestyle content ( Tx1 ) , personally tailored health information ( Tx2 ) , and personally tailored health information plus online video-based peer coaching ( Tx3 ) as part of a 6-week online health program . Participants were asked to set weekly goals around eating breakfast , exercise , alcohol use , and cigarette smoking . Eligibility criteria included age ( 18 - 30 years ) and smoking status ( any cigarette use in the previous 30 days ) . The primary outcome was self-reported 30-day abstinence measured 12 weeks postenrollment . RESULTS Participant ( n = 1698 ) characteristics were balanced across the groups ( 72 % women , mean age 24 , 26 % nonwhite , 32 % high school education or less , and 50 % daily smokers ) . Considering intention to treat , 30-day smoking abstinence rates were statistically significantly higher in the intervention groups ( Tx1 = 11 % , Tx2 = 23 % , Tx3 = 31 % , P < .001 ) . Participants in the intervention groups were also more likely to reduce their number of days spent on binge drinking and increase their number of days eating breakfast and exercising . Overall , intervention group participants were much more likely to make positive changes in at least three or four of the target behaviors ( Tx1 = 19 % , Tx2 = 39 % , Tx3 = 41 % , P < .001 ) . CONCLUSIONS This online avatar-hosted personal health makeover " show " increased smoking abstinence and induced positive changes in multiple related health behaviors . Addition of the online video-based peer coaching further improved behavioral outcomes Background Although evidence exists for the effectiveness of web-based smoking cessation interventions , information about the cost-effectiveness of these interventions is limited . Objective The study investigated the cost-effectiveness and cost-utility of two web-based computer-tailored ( CT ) smoking cessation interventions ( video- vs. text-based CT ) compared to a control condition that received general text-based advice . Methods In a r and omized controlled trial , respondents were allocated to the video-based condition ( N = 670 ) , the text-based condition ( N = 708 ) or the control condition ( N = 721 ) . Societal costs , smoking status , and quality -adjusted life years ( QALYs ; EQ-5D-3L ) were assessed at baseline , six- and twelve-month follow-up . The incremental costs per abstinent respondent and per QALYs gained were calculated . To account for uncertainty , bootstrapping techniques and sensitivity analyses were carried out . Results No significant differences were found in the three conditions regarding demographics , baseline values of outcomes and societal costs over the three months prior to baseline . Analyses using prolonged abstinence as outcome measure indicated that from a willingness to pay of € 1,500 , the video-based intervention was likely to be the most cost-effective treatment , whereas from a willingness to pay of € 50,400 , the text-based intervention was likely to be the most cost-effective . With regard to cost-utilities , when quality of life was used as outcome measure , the control condition had the highest probability of being the most preferable treatment . Sensitivity analyses yielded comparable results . Conclusion The video-based CT smoking cessation intervention was the most cost-effective treatment for smoking abstinence after twelve months , varying the willingness to pay per abstinent respondent from € 0 up to € 80,000 . With regard to cost-utility , the control condition seemed to be the most preferable treatment . Probably , more time will be required to assess changes in quality of life . Future studies with longer follow-up periods are needed to investigate whether cost-utility results regarding quality of life may change in the long run . Trial Registration Nederl and s Trial Register AIMS To test the population impact of offering automated smoking cessation interventions via the internet and /or by mobile phone . DESIGN Pragmatic r and omized controlled trial with five conditions : offer of ( i ) minimal intervention control ; ( ii ) QuitCoach personalized tailored internet-delivered advice program ; ( iii ) onQ , an interactive automated text-messaging program ; ( iv ) an integration of both QuitCoach and onQ ; and ( v ) a choice of either alone or the combined program . SETTING Australia , via a mix of internet and telephone contacts . PARTICIPANTS A total of 3530 smokers or recent quitters recruited from those interested in quitting , and seeking self-help re sources ( n = 1335 ) or cold-contacted from internet panels ( n = 2195 ) . MEASUREMENTS The primary outcome was self-report of 6 months sustained abstinence at 7 months post-recruitment . FINDINGS Only 42.5 % of those offered one of the interventions took it up to a minimal level . The intervention groups combined had a non-significantly higher 6-month sustained abstinence rate than the control [ odds ratio ( OR ) = 1.48 ; 95 % confidence interval ( CI ) : 0.98 - 2.24 ] ( missing cases treated as smokers ) , with no differences between the interventions . Among those who used an intervention , there was a significant overall increase in abstinence ( OR = 1.95 ; CI : 1.04 - 3.67 ) , but not clearly so when analysing only cases with reported outcomes . Success rates were greater among those recruited after seeking information compared to those cold-contacted . CONCLUSIONS Smokers interested in quitting who were assigned r and omly to an offer of either the QuitCoach internet-based support program and /or the interactive automated text-messaging program had non-significantly greater odds of quitting for at least 6 months than those r and omized to an offer of a simple information website Objective : Smokers with depressive symptoms have more difficulty quitting smoking than the general population of smokers . The present study examines a web-based treatment using acceptance and commitment therapy ( ACT ) for smokers with depressive symptoms . The study aim ed to determine participant receptivity to the intervention and its effects on smoking cessation , acceptance of internal cues , and depressive symptoms . Methods : Smokers who had positive screening results for depressive symptoms at baseline ( n = 94 ) were selected from a r and omized controlled trial ( N = 222 ) comparing web-based ACT for smoking cessation ( WebQuit.org ) with Smokefree.gov . Forty-five participants ( 48 % ) completed the three-month follow-up . Results : Compared to Smokefree.gov , WebQuit participants spent significantly more time on site ( p = .001 ) and had higher acceptance of physical cravings ( p = .033 ) . While not significant , WebQuit participants were more engaged and satisfied with their program and were more accepting of internal cues overall . There was preliminary evidence that WebQuit participants had higher quit rates ( 20 % versus 12 % ) and lower depressive symptoms at follow-up ( 45 % versus 56 % ) than those in Smokefree.gov . Conclusions : This was the first study of web-based ACT for smoking cessation among smokers with depressive symptoms , with promising evidence of receptivity , efficacy , impact on a theory-based change process , and possible secondary effects on depression . A fully powered trial of the ACT WebQuit.org intervention specifically for depressed smokers is needed . This was part of a clinical trial registered as NCT#01166334 at www . clinical trials.gov Background Internet programs for smoking cessation are widely available but few controlled studies demonstrate long-term efficacy . Purpose To determine the 13-month effectiveness of an Internet program presenting a set sequence of interactive steps , and the role of depressed affect . Methods In a r and omized controlled trial sponsored by the American Cancer Society , a treatment condition ( n = 1,106 ) was compared to a control site ( n = 1,047 ) . Results More treatment condition participants were abstinent ( 30-day point prevalence ) than control site participants ( 12.9 % vs. 10.1 % , p < .05 ) at 13 months . This effect was greater among participants not reporting depressed affect ( 15.0 % vs. 10.1 % , p < .01 ) . Among smokers who reported depressed affect , there was no difference in abstinence between the treatment and control conditions . Conclusions Data support the long-term efficacy of an Internet intervention for cessation modeled on a structured , in-person treatment approach , especially for participants not experiencing daily depressed affect |
13,989 | 29,235,205 | Surface treatment in Y-TZP improved the values of SBS between the Y-TZP and veneer ceramic .
The associations between two or more treatments also showed positive effect on the bond strength due the cumulative effect of the treatments | PURPOSE The objective of this systematic review with meta- analysis was to evaluate surface treatment in yttria-stabilized tetragonal zirconia polycrystal ceramic ( Y-TZP ) on the shear bond strength ( SBS ) values between Y-TZP ( core ceramic ) and veneer ceramic , compared to untreated specimens . | OBJECTIVE The aim of this study was to evaluate the effect of different surface treatments : s and blasting , liners , and different laser irradiations on shear bond strength ( SBS ) of pre-sintered zirconia to veneer ceramic . BACKGROUND DATA The SBS between veneering porcelain and zirconium oxide ( ZrO2 ) substructure was weak . Various surface treatment methods have been suggested for zirconia to obtain high bond strength to veneering porcelain . There is no study that evaluated the bond strength between veneering porcelain and the different surface treatments on pre-sintered ZrO2 substructure . METHODS Two hundred specimens with 7 mm diameter and 3 mm height pre-sintered zirconia blocks were fabricated . Specimens were r and omly divided into 10 groups ( n=20 ) according to surface treatments applied . Group C , untreated ( Control ) ; Group E , erbium : yttrium-aluminum-garnet ( Er : YAG ) laser irradiated ; Group N , neodymium : yttrium-aluminum-garnet ( Nd : YAG ) laser irradiated ; Group SB , s and blasted ; Group L , liner applied ; Group NL , Nd : YAG laser irradiated+liner applied ; Group EL , Er : YAG laser irradiated+liner applied ; Group SN , s and blasted+Nd : YAG laser irradiated ; Group SE , s and blasted+Er : YAG laser irradiated ; and Group SL , s and blasted+liner applied . The disks were then veneered with veneering porcelain . Before the experiment , specimens were steeped in 37 ° C distilled water for 24 h. All specimens were thermocycled for 5000 cycles between 5 ° C and 55 ° C with a 30 sec dwell time . Shear bond strength test was performed at a crosshead speed of 1 mm/min . The fractured specimens were examined under a stereomicroscope to evaluate the fracture pattern . RESULTS Surface treatments significantly changing the topography of the yttrium-stabilized tetragonal zirconia ( Y-TZP ) ceramic according to scanning electron microscopic ( SEM ) images . The highest mean bond strength value was obtained in Group SE , and the lowest bond strength value was observed in NL group . Bond strength values of the other groups were similar to each other . CONCLUSIONS This study shows that s and blasting+Er : YAG , s and blasting , Er : YAG+liner , s and blasting+Nd : YAG , and Er : YAG laser treatment on pre-sintered ZrO2 substructure increased the bond strength to veneering porcelain , compared with other surface treatments . After different surface treatments , there was no difference in surface roughness of pre-sintered zirconia to compare after sintering ; sintering enhanced the bond strength within the limitations of present study OBJECTIVE This study investigated the mechanism of action at the interface between a commercially available Y-TZP and its veneering ceramic after final firing . Particular attention was paid , from a microstructural point of view , to evaluating the effects of different surface treatments carried out on the zirconia . METHODS In total , 32 specimens of presintered zirconia Y-TZP ( LavaFrame , 3 M ESPE , Germany ) were cut with a low-speed diamond blade . The specimens were divided in two major groups , for testing after fracture or after mirror finishing , and were sintered following the manufacturer 's instructions . Each major group was then r and omly divided into four subgroups , according to using or not using the dedicated framework modifier , with or without a preliminary silica coating ( CoJet , 3 M ESPE ) . A suitable veneering ceramic was used for each group ( Lava Ceram Overlay Porcelain , 3 M ESPE ) . A detailed microstructural study of the interfaces of the zirconia-veneering ceramic was performed using a scanning electron microscope equipped with an energy-dispersive X-ray spectrometer to evaluate chemical variation at the interfaces . RESULTS When the framework modifier was not applied on the Y-TZP surface , microdetachments , porosities , and openings in the ceramic layer were observed at the interlayers . A degree of diffusion of different elements through the interfaces from both the zirconia and veneering layers was detected . CONCLUSIONS Application of the framework modifier can increase the wettability of the zirconia surfaces , allowing a continuous contact with the veneering layer . The micro- analysis performed showed the presence of a reaction area at the interface between the different material s. CLINICAL SIGNIFICANCE the increase of the wettability of the zirconia surface could improve the adhesion at interface with the veneering ceramic and reduce the clinical failure as chipping or delamination OBJECTIVES The aim of this study was to compare the effects of three different surface treatments in enhancing porcelain zirconia bonding . METHODS Totally , 160 densely sintered zirconia specimens were prepared and r and omly divided into four study groups : control ( no treatment , Group C ) , s and blasting ( Group S ) , s and blasting followed by regeneration firing ( Group SH ) , and laser irradiation ( pulse mode ) on a CO₂ laser system ( Group L ) . After surface treatment , porcelain powders were veneered on zirconia surface . Half of the specimens in each group were evaluated without aging ( initial shear bond strength - initial SBS ) , and the other half was tested after being stored in water for one month ( aging SBS ) . X-ray diffractometry ( XRD ) was used to observe any crystallographic transformation at zirconia surface . Results were statistically analyzed using analysis of variance ( ANOVA ) and Turkey test ( = 0.05 ) . RESULTS The initial average SBS values of Group S , Group SH , and Group L were 31.3 ± 5.7 MPa , 29.2 ± 7.0 MPa and 32.1 ± 7.5 MPa , respectively . The differences among these three groups were not significant . The control group had significantly lower value , 24.8 ± 6.7 MPa , than those of Group S and Group L. Furthermore , there was no significant difference between initial and aging values in each group . XRD analysis showed that s and blasting caused tetragonal to monoclinic phase transformation . Regeneration firing reversed such a transformation . However , crystallographic transformation could not be detected in laser treated specimens . SIGNIFICANCE Both s and blasting and laser irradiation increased porcelain zirconia bond strength . The presented new modified laser pre-treatment might be an alternative way to s and blasting for improving zirconia/porcelain integration |
13,990 | 27,574,585 | The data for SBRT show encouraging and comparable results in terms of freedom from biochemical failure ( > 90 % for low and intermediate risk at 5 - 7 years ) and acute and late toxicity ( < 6 % grade 3 - 4 late toxicities ) .
At this time , neither SBRT device is recommended over the other for all patients ; however , gantry-based SBRT machines have the abilities of treating larger volumes with conventional fractionation , shorter treatment time per fraction ( ~15 minutes for gantry vs ~45 minutes for robotic arm ) , and the ability to achieve better plans among obese patients ( since they are able to use energies > 6 MV ) .
Finally , SBRT ( particularly on a gantry ) may also be more cost-effective than conventionally fractionated external-beam radiation therapy . | Prostate cancer is the most prevalent cancer diagnosed in men in the United States besides skin cancer .
Stereotactic body radiation therapy ( SBRT ; 6 - 15 Gy per fraction , up to 45 minutes per fraction , delivered in five fractions or less , over the course of approximately 2 weeks ) is emerging as a popular treatment option for prostate cancer .
The American Society for Radiation Oncology now recognizes SBRT for select low- and intermediate-risk prostate cancer patients .
SBRT grew from the notion that high doses of radiation typical of brachytherapy could be delivered noninvasively using modern external-beam radiation therapy planning and delivery methods .
SBRT is most commonly delivered using either a traditional gantry-mounted linear accelerator or a robotic arm-mounted linear accelerator .
In this systematic review article , we compare and contrast the current clinical evidence supporting a gantry vs robotic arm SBRT for prostate cancer . | PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity Background To evaluate the daily total error shift patterns on post-prostatectomy patients undergoing image guided radiotherapy ( IGRT ) with a diagnostic quality computer tomography ( CT ) on rails system . Methods A total of 17 consecutive post-prostatectomy patients receiving adjuvant or salvage IMRT using CT-on-rails IGRT were analyzed . The prostate bed 's daily total error shifts were evaluated for a total of 661 CT scans . Results In the right-left , cranial-caudal , and posterior-anterior directions , 11.5 % , 9.2 % , and 6.5 % of the 661 scans required no position adjustments ; 75.3 % , 66.1 % , and 56.8 % required a shift of 1 - 5 mm ; 11.5 % , 20.9 % , and 31.2 % required a shift of 6 - 10 mm ; and 1.7 % , 3.8 % , and 5.5 % required a shift of more than 10 mm , respectively . There was evidence of correlation between the x and y , x and z , and y and z axes in 3 , 3 , and 3 of 17 patients , respectively . Univariate ( ANOVA ) analysis showed that the total error pattern was r and om in the x , y , and z axis for 10 , 5 , and 2 of 17 patients , respectively , and systematic for the rest . Multivariate ( MANOVA ) analysis showed that the ( x , y ) , ( x , z ) , ( y , z ) , and ( x , y , z ) total error pattern was r and om in 5 , 1 , 1 , and 1 of 17 patients , respectively , and systematic for the rest . Conclusions The overall daily total error shift pattern for these 17 patients simulated with an empty bladder , and treated with CT on rails IGRT was predominantly systematic . Despite this , the temporal vector trends showed complex behaviors and unpredictable changes in magnitude and direction . These findings highlight the importance of using daily IGRT in post-prostatectomy patients The National Cancer Institute of Canada ( NCIC ) Clinical Trials Group PR.3/Medical Research Council PR07/ Intergroup T94 - 0110 ( 1 ) was a r and omized controlled trial ( RCT ) of radiation therapy ( RT ) and and rogen deprivation therapy ( ADT ) vs. ADT alone , for men with locally advanced prostate cancer . The authors defined locally advanced as : ( I ) T3 - 4 , N0/X , M0 ; or ( II ) T1 - 2 with prostate specific antigen ( PSA ) > 40 ng/mL ; or ( III ) PSA 20 - 40 ng/mL and Gleason 8 - 10 . Men were r and omized to lifelong ADT vs. ADT + RT , 65 - 69 Gy in 1.8 Gy fractions , using 3D conformal RT , to the prostate and pelvis or prostate alone . Of the 1,205 patients treated between 1995 and 2005 , 602 received ADT alone and 603 received ADT + RT . Overall survival ( OS ) was significantly improved in the patients allocated to ADT + RT [ hazard ratio ( HR ) = 0.70 ; 95 % CI , 0.57 - 0.85 ; P<0.001 ] . Prostate cancer specific mortality ( CSM ) was improved in the patients allocated to ADT + RT ( HR = 0.46 ; 95 % CI , 0.34 - 0.61 ; P<0.001 ) . Although patients on ADT + RT arm reported a higher rate of gastrointestinal ( GI ) toxicity , only 2 of 589 patients had grade 3 or greater diarrhea at 24 months after RT Objectives : Freedom from biochemical failure ( FFBF ) is a common primary outcome of r and omized-controlled trials of prostate cancer ( PCa ) . We aim ed to determine how increasing the PCa biologically equivalent dose ( BED ) of external radiation therapy ( RT ) is correlated with FFBF and overall patient outcomes : overall survival ( OS ) , distant metastasis ( DM ) , and cancer-specific mortality ( CSM ) ; as well as genitourinary ( GU ) , and gastrointestinal toxicities . Material s and Methods : We performed a meta- analysis of 6884 PCa patients from 12 r and omized-controlled trials of external beam RT . Mixed effects regression models were used to estimate weighted linear relationships between BED and observed percentages of 5- and 10-year outcomes . For toxicities , a subset analysis of using 3-dimensional conformal RT ( 3D-CRT ) versus intensity-modulated RT ( IMRT ) was performed . Results : Increasing BED correlated with improved FFBF : 10-year absolute improvement of 9.6 % and 7.2 % for low-risk and intermediate-risk patients , respectively ( P<0.05 ) ; but not with improvement of OS , DM , or CSM at either time point . BED escalation was not correlated with increased acute toxicities ; it was correlated with increased late gastrointestinal toxicities in patients treated with 3D-CRT ( 1.5 % increase over BED range , P<0.01 ) . IMRT patients had significantly fewer late toxicities , despite being treated at higher BED . Conclusions : RT BED escalation has result ed in significantly improved PCa FFBF at up to 10 years ; but not with improvement in OS , DM , or CSM . Thus , FFBF is a poor surrogate of overall patient outcomes for trials of RT . Late toxicities were less frequent with IMRT than with 3D-CRT , even at higher BED Objectives : Stereotactic body radiation therapy ( SBRT ) takes advantage of the prostate ’s low α/β ratio to deliver a large radiation dose in few fractions . Initial studies on small groups of low-risk patients support SBRT ’s potential for clinical efficacy while limiting treatment-related morbidity and maintained quality of life . This prospect i ve study exp and s upon prior studies to further evaluate SBRT efficacy for a large patient population with organ confined , low- and intermediate-risk prostate cancer patients . Methods : Four hundred seventy-seven patients with prostate cancer received CyberKnife SBRT . The median age was 68.6 years and the median PSA was 5.3 ng/mL. Three hundred twenty-four patients were low-risk ( PSA < 10 ng/mL and Gleason < 7 ) , 153 were intermediate-risk ( PSA 10–20 ng/mL or Gleason = 7 ) . And rogen deprivation therapy was administered to 51 patients for up to 6 months . One hundred fifty-four patients received 35 Gy delivered in five daily fractions ; the remaining patients received a total dose of 36.25 Gy in five daily fractions . Biochemical failure was assessed using the phoenix criterion . Results : Median follow-up was 72 months . The median PSA at 7 years was 0.11 ng/mL. Biochemical failures occurred for 11 low-risk patients ( 2 locally ) , 14 intermediate-risk patients ( 3 locally ) . The actuarial 7-year freedom from biochemical failure was 95.6 and 89.6 % for low- and intermediate-risk groups , respectively ( p < 0.012 ) . Among patients with intermediate-risk disease , those considered to have low intermediate-risk ( Gleason 6 with PSA > 10 , or Gleason 3 + 4 with PSA < 10 ; n = 106 ) had a significantly higher bDFS than patients with high intermediate-risk ( Gleason 3 + 4 with PSA 10–20 or Gleason 4 + 3 ; n = 47 ) , with bDFS of 93.5 vs. 79.3 % , respectively . For the low-risk and low intermediate-risk groups , there was no difference in median PSA nadir or biochemical disease control between doses of 35 and 36.25 Gy . Conclusion : CyberKnife SBRT produces excellent biochemical control rates . Median PSA levels compare favorably with other radiation modalities and strongly suggest durability of response . These results also strongly suggest that 35 Gy is as effective as 36.25 Gy for low- and intermediate-risk patients PURPOSE Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology . The results of a prospect i ve trial of stereotactic body radiotherapy ( SBRT ) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented . METHODS AND MATERIAL S From 2003 through 2009 , 67 patients with clinical ly localized low-risk prostate cancer were enrolled . Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology . No patient received hormone therapy . Patient self-reported bladder and rectal toxicities were grade d on the Radiation Therapy Oncology Group scale ( RTOG ) . RESULTS Median follow-up was 2.7 years . There were no grade 4 toxicities . Radiation Therapy Oncology Group Grade 3 , 2 , and 1 bladder toxicities were seen in 3 % ( 2 patients ) , 5 % ( 3 patients ) , and 23 % ( 13 patients ) respectively . Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity . Urinary incontinence , complete obstruction , or persistent hematuria was not observed . Rectal Grade 3 , 2 , and 1 toxicities were seen in 0 , 2 % ( 1 patient ) , and 12.5 % ( 7 patients ) , respectively . Persistent rectal bleeding was not observed . Low- grade toxicities were substantially less frequent with QOD vs. QD dose regimen ( p = 0.001 for gastrointestinal and p = 0.007 for genitourinary ) . There were two prostate-specific antigen ( PSA ) , biopsy-proven failures with negative metastatic workup . Median PSA at follow-up was 0.5 ± 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94 % ( 95 % confidence interval , 85%-102 % ) . CONCLUSION Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent . PSA relapse-free survival compares favorably with other definitive treatments . The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer PURPOSE Report of clinical cancer control outcomes on Radiation Therapy Oncology Group ( RTOG ) 9406 , a three-dimensional conformal radiation therapy ( 3D-CRT ) dose escalation trial for localized adenocarcinoma of the prostate . METHODS AND MATERIAL S RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer . Patients were registered on five sequential dose levels : 68.4 Gy , 73.8 Gy , 79.2 Gy , 74 Gy , and 78 Gy with 1.8 Gy/day ( levels I-III ) or 2.0 Gy/day ( levels IV and V ) . Neoadjuvant hormone therapy ( NHT ) from 2 to 6 months was allowed . Protocol -specific , American Society for Therapeutic Radiation Oncology ( ASTRO ) , and Phoenix biochemical failure definitions are reported . RESULTS Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable . Median follow-up for levels I , II , III , IV , and V was 11.7 , 10.4 , 11.8 , 10.4 , and 9.2 years , respectively . Thirty-six percent of patients received NHT . The 5-year overall survival was 90 % , 87 % , 88 % , 89 % , and 88 % for dose levels I-V , respectively . The 5-year clinical disease-free survival ( excluding protocol prostate-specific antigen definition ) for levels I-V is 84 % , 78 % , 81 % , 82 % , and 82 % , respectively . By ASTRO definition , the 5-year disease-free survivals were 57 % , 59 % , 52 % , 64 % and 75 % ( low risk ) ; 46 % , 52 % , 54 % , 56 % , and 63 % ( intermediate risk ) ; and 50 % , 34 % , 46 % , 34 % , and 61 % ( high risk ) for levels I-V , respectively . By the Phoenix definition , the 5-year disease-free survivals were 68 % , 73 % , 67 % , 84 % , and 80 % ( low risk ) ; 70 % , 62 % , 70 % , 74 % , and 69 % ( intermediate risk ) ; and 42 % , 62 % , 68 % , 54 % , and 67 % ( high risk ) for levels I-V , respectively . CONCLUSION Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer . This multi-institutional experience allows comparison to other experiences with modern radiation therapy BACKGROUND AND PURPOSE Biological dose escalation through stereotactic ablative radiotherapy ( SABR ) holds promise of improved patient convenience , system capacity and tumor control with decreased cost and side effects . The objectives are to report the toxicities , biochemical and pathologic outcomes of this prospect i ve study . MATERIAL S AND METHODS A phase I/II study was performed where low risk localized prostate cancer received SABR 35 Gy in 5 fractions , once weekly on st and ard linear accelerators . Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group late morbidity scores were used to assess acute and late toxicities , respectively . Biochemical control ( BC ) was defined by the Phoenix definition . RESULTS As of May 2012 , 84 patients have completed treatment with a median follow-up of 55 months ( range 13 - 68 months ) . Median age was 67 years and median PSA was 5.3 ng/ml . The following toxicities were observed : acute grade 3 + : 0 % gastrointestinal ( GI ) , 1 % genitourinary ( GU ) , 0 % fatigue ; late grade 3 + : 1 % GI , 1 % GU . Ninety-six percent were biopsy negative post-treatment . The 5-year BC was 98 % . CONCLUSIONS This novel technique employing st and ard linear accelerators to deliver an extreme hypofractionated schedule of radiotherapy is feasible , well tolerated and shows excellent pathologic and biochemical control Background Patients with large prostate volumes have been shown to have higher rates of genitourinary and gastrointestinal toxicities after conventional radiation therapy for prostate cancer . The efficacy and toxicity of stereotactic body radiation therapy ( SBRT ) , which delivers fewer high-dose fractions of radiation treatment , is unknown for large prostate volume prostate cancer patients . We report our early experience using SBRT for localized prostate cancer in patients with large prostate volumes . Methods 57 patients with prostate volumes ≥50 cm3 prior to treatment with SBRT for localized prostate carcinoma and with a minimum follow up of two years were included in this retrospective review of prospect ively collected data . Treatment was delivered using Cyberknife ( Accuray ) with doses of 35 - 36.25 Gy in 5 fractions . Biochemical control was assessed using the Phoenix definition . Toxicities were scored using the CTCAE v.4 . Quality of life was assessed using the American Urological Association ( AUA ) Symptom Score and the Exp and ed Prostate Cancer Index Composite (EPIC)-26 . Results 57 patients ( 23 low- , 25 intermediate- and 9 high-risk according to the D’Amico classification ) at a median age of 69 years ( range , 54 - 83 years ) received SBRT with a median follow-up of 2.9 years . The median prostate size was 62.9 cm3 ( range 50 - 138.7 cm3 ) . 33.3 % of patients received ADT . The median pre-treatment prostate-specific antigen ( PSA ) was 6.5 ng/ml and decreased to a median PSA of 0.4 ng/ml by 2 years ( p < 0.0001 ) . A mean baseline AUA symptom score of 7.5 significantly increased to 13 at 1 month ( p = 0.001 ) and returned to baseline by 3 months ( p = 0.21 ) . 23 % of patients experienced a late transient urinary symptom flare in the first two years following treatment . Mean baseline EPIC bowel scores of 95.8 decreased to 78.1 at 1 month ( p < 0.0001 ) , but subsequently improved to 93.5 three months ( p = 0.08 ) . The 2-year actuarial incidence rates of GU and GI toxicity ≥ grade 2 were 49.1 % and 1.8 % , respectively . Two patients ( 3.5 % ) experienced grade 3 urinary toxicity , and no patient experienced grade 3 gastrointestinal toxicity . Conclusions SBRT for clinical ly localized prostate cancer was well tolerated in men with large prostate volumes PURPOSE To up date the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 669 patients with localized prostate cancer were r and omly assigned to receive 68 or 78 Gy . The patients were stratified by age , institution , use of neoadjuvant or adjuvant hormonal therapy , and treatment group . The primary endpoint was freedom from failure ( FFF ) , with failure defined as clinical or biochemical failure . Two definitions of biochemical failure were used : the American Society for Therapeutic Radiology and Oncology definition ( three consecutive increases in prostate-specific antigen level ) and the Phoenix definition ( nadir plus 2 microe secondary endpoints were freedom from clinical failure , overall survival , and genitourinary and gastrointestinal toxicity . RESULTS After a median follow-up of 70 months , the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm ( 7-year FFF rate , 54 % vs. 47 % , respectively ; p = 0.04 ) . The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm ( 7-year FFF rate , 56 % vs. 45 % , respectively ; p = 0.03 ) . However , no differences in freedom from clinical failure or overall survival were observed . The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms ( 40 % and 41 % at 7 years ; p = 0.6 ) . However , the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm ( 35 % vs. 25 % at 7 years ; p = 0.04 ) . CONCLUSION The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity Background Radiotherapy is an increasingly preferred treatment option for localized prostate cancer , and stereotactic body radiation therapy ( SBRT ) a relatively established modality of therapeutic irradiation . The present study analyzes the toxicity and biochemical efficacy of SBRT in 100 consecutive prostate cancer patients treated with CyberKnife Robotic Radiosurgery System . Methods One hundred patients were treated with SBRT at the Radiation Oncology department of San Bortolo Hospital , Vicenza , Italy . All patients included in this IRB-approved protocol -driven prospect i ve study had biopsy-proven prostate cancer . Risk category was low in 41 , intermediate in 42 , and high in 17 patients . The patients were treated with CyberKnife-SBRT ( CK-SBRT ) , the prescription dose was 35 Gy in five fractions , corresponding to 92 Gy in 2-Gy fractions ( α/β = 1.5 Gy ) ; 29 patients also received and rogen deprivation therapy ( ADT ) . Results Median follow-up was 36 months ( range , 6–76 months ) . Acute Grade 2 genitourinary and gastrointestinal toxicity occurred in respectively 12 % and 18 % of the patients ; there were no Grade 3 or higher acute toxicities . Late Grade 1 , 2 , and 3 genitourinary toxicities occurred in 4 % , 3 % , and 1 % of the patients , respectively ; late Grade 1 gastrointestinal toxicity occurred in two patients and Grade 2 toxicity in one patient ; no late gastrointestinal toxicities of grade 3 or 4 were observed . Median PSA nadir was 0.45 ng/ml at 36 months for all patients . In the SBRT-monotherapy group , the median PSA nadir at 36 months was 0.62 ng/ml ; in the ADT-SBRT group , it was 0.18 ng/ml . Four patients had clinical recurrence : one local , two lymph nodes , and one to the bone . Ninety-six patients had no evidence of biochemical or clinical recurrence . A benign PSA bounce of median 1.08 ng/ml occurred in 12 % of the 71 SBRT monotherapy patients at a mean 23 months ( range , 18–30 months ) . Conclusions In this study CK-SBRT has provided promising outcomes in localized prostate cancer with good PSA response , minimal toxicity and patient inconvenience PURPOSE To evaluate the tolerability of escalating doses of stereotactic body radiation therapy in the treatment of localized prostate cancer . PATIENTS AND METHODS Eligible patients included those with Gleason score 2 to 6 with prostate-specific antigen ( PSA ) ≤ 20 , Gleason score 7 with PSA ≤ 15 , ≤ T2b , prostate size ≤ 60 cm(3 ) , and American Urological Association ( AUA ) score ≤ 15 . Pretreatment preparation required an enema and placement of a rectal balloon . Dose-limiting toxicity ( DLT ) was defined as grade 3 or worse GI/genitourinary ( GU ) toxicity by Common Terminology Criteria of Adverse Events ( version 3 ) . Patients completed quality -of-life question naires at defined intervals . RESULTS Groups of 15 patients received 45 Gy , 47.5 Gy , and 50 Gy in five fractions ( 45 total patients ) . The median follow-up is 30 months ( range , 3 to 36 months ) , 18 months ( range , 0 to 30 months ) , and 12 months ( range , 3 to 18 months ) for the 45 Gy , 47.5 Gy , and 50 Gy groups , respectively . For all patients , GI grade ≥ 2 and grade ≥ 3 toxicity occurred in 18 % and 2 % , respectively , and GU grade ≥ 2 and grade ≥ 3 toxicity occurred in 31 % and 4 % , respectively . Mean AUA scores increased significantly from baseline in the 47.5-Gy dose level ( P = .002 ) as compared with the other dose levels , where mean values returned to baseline . Rectal quality -of-life scores ( Exp and ed Prostate Cancer Index Composite ) fell from baseline up to 12 months but trended back at 18 months . In all patients , PSA control is 100 % by the nadir + 2 ng/mL failure definition . CONCLUSION Dose escalation to 50 Gy has been completed without DLT . A multicenter phase II trial is underway treating patients to 50 Gy in five fractions to further evaluate this experimental therapy Purpose Modern radiotherapy has achieved substantial improvement in tumour control and toxicity rates by escalating the total dose to the target volume while sparing surrounding normal tissues . It has therefore become necessary to precisely track tumour position in order to minimise geometrical uncertainties due to setup errors and organ motion . We conducted this prospect i ve evaluation of prostate cancer patients treated with image-guided conformal radiation therapy at our institution . We implanted three fiducial markers ( gold seeds ) within the prostatic gl and in order to quantify daily target displacements and to generate specific margins around the clinical target volume ( CTV ) to create an appropriate planned target volume ( PTV ) . Material s and methods Between April and December 2009 , ten patients affected with localised prostate cancer were transrectally implanted with three radio-opaque markers . Each patient underwent a computed tomography ( CT ) scan for planning purpose s following proper bladder and rectum preparation . During treatment two orthogonal images were acquired daily and compared with previously generated digitally reconstructed radiographs . After manual localisation , comparison between the position of the gold seeds on the portal and reference images was carried out , and a set of extrapolated lateral-lateral ( LL ) , anterior-posterior ( AP ) and cranial-caudal ( CC ) shift corrections was calculated and recorded . Couch corrections were applied with a threshold of 3 mm displacement . Results Systematic and r and om errors for each direction were calculated either as measured according to displacement of the gold seeds prior to any couch movement and after couch position correction according to the radio-opaque markers . For skin marks , mean systematic and r and om errors were 0.12 + 2.94 mm for LL , 1.04 + 3.37 mm for AP , −1.14 + 2.71 mm for CC , whereas for seed markers , mean and systematic errors were 0.6 + 1.5 mm for LL , 0.51 + 2.45 mm for AP and −0.25 + 2.51 mm for CC . A scatter plot generated on all measurements after couch repositioning according to gold-seed displacement suggested a confidence range of shift distributions within 5 mm for LL , 8 mm for CC , and 7 mm for AP . The total systematic and r and om components were then used to calculate proper PTV in patients receiving conventional treatment ( 7 mm for LL and 9 mm for both AP and CC ) . Conclusions Prostate positional variability during a course of radiation treatment is strongly influenced by setup and organ motion . Organ tracking through fiducial markers and electronic portal imaging is able to reduce the spread of displacements , significantly contributing to improve the ballistic precision of radiation delivery . RiassuntoObiettivoLa moderna radioterapia ha raggiunto traguardi considerevoli in termini di controllo tumorale e riduzione dei tassi di tossicità associati al trattamento , con la possibilità di erogare dosi importanti al volume bersaglio , risparmi and o contemporaneamente i tessuti sani . Risulta , pertanto , focale la caratterizzazione precisa della posizione della lesione neoplastica per minimizzare le incertezze geometriche dovute agli errori di posizionamento ed al movimento d’organo . Abbiamo intrapreso una valutazione prospettica dei pazienti trattati mediante radioterapia conformazionale gui data dalle immagini per carcinoma prostatico , utilizz and o tre reperi fiduciali ( semi d’oro ) impiantati all’interno della prostata per quantificare gli scostamenti giornalieri del volume bersaglio e generare margini specifici attorno al volume bersaglio clinico ( CTV ) cre and o un appropriato volume bersaglio di pianificazione ( PTV ) . Material i e metodiTra aprile e dicembre 2009 , 10 pazienti affetti da adenocarcinoma prostatico organo-confinato sono stati sottoposti ad impianto trans-rettale sotto guida ecografica di 3 reperi fiduciali radio-opachi . Ogni paziente è stato sottoposto a tomografia computerizzata ( CT ) di pianificazione con una adeguata preparazione vescicale e rettale ; ad ogni seduta di trattamento , sono state acquisite 2 immagini ortogonali e poi confrontate con immagini radiografiche a ricostruzione digitale . è stata effettuata una localizzazione manuale confront and o la posizione dei reperi fiduciali nelle immagini portali con quella nelle immagini di riferimento . Sono stati estrapolati e registrati gli scostamenti nelle direzioni latero-laterale ( LL ) , anteroposteriore ( AP ) e cranio-caudale ( CC ) . La correzione della posizione del lettino di trattamento è stata effettuata con una soglia di 3 mm . RisultatiSono stati calcolati l’errore st and ard e sistematico per ogni direzione , misur and o gli scostamenti dei semi d’oro prima del movimento del lettino di trattamento e dopo aver applicato gli spostamenti secondo i reperi fiduciali . Per i reperi cutanei , l’errore sistematico e casuale medio sono stati 0,12±2,94 mm per la direzione LL , 1,04±3,37 mm per la direzione AP e −1,14±2,71 mm per la direzione CC ; per i reperi fiduciali , l’errore sistematico e casuale medio sono stati 0,6±1,5 mm per la direzione LL , 0,51±2,45 mm per la direzione AP e −0,25±2,51 mm per la direzione CC . è stato creato un diagramma di distribuzione di tutte le misure ottenute dopo il riposizionamento del lettino in funzione degli scostamenti registrati mediante i reperi fiduciali ; l’ambito di confidenza della distribuzione degli spostamenti si trova entro i 5 mm per la direzione LL , entro i 6 mm per la direzione CC ed entro i 7 mm per la direzione AP . L’errore sistematico e l’errore casuale totale sono stati utilizzati per generare margini per ottenere il PTV nei pazienti trattati convenzionalmente ( 7 mm per la direzione LL ; 9 mm sia per la direzione AP che per la direzione CC ) . Conclusion iLa variabilità della posizione della ghi and ola prostatica durante un trattamento radiante è influenzata in modo importante dal posizionamento e dal movimento d’organo . Il monitoraggio della posizione della prostata mediante reperi fiduciali ed immagini portali è in grado di ridurre la dispersione degli scostamenti rispetto all’atteso , contribuendo in maniera significativa al miglioramento della precisione balistica della radioterapia PURPOSE To evaluate the early and late health-related quality of life ( QOL ) outcomes among prostate cancer patients following stereotactic body radiation therapy ( SBRT ) . METHODS AND MATERIAL S Patient self-reported QOL was prospect ively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer . Data from the Exp and ed Prostate Cancer Index Composite ( EPIC ) instrument were obtained at baseline and at regular intervals up to 6 years . SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions . A short course of and rogen deprivation therapy was given to 14 % of patients . RESULTS Median follow-up was 3 years and 194 patients remained evaluable at 5 years . A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years . The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities . Sexual QOL decline was predominantly observed within the first 9 months , a pattern not altered by the use of and rogen deprivation therapy or patient age . CONCLUSION Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL . A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels . With a large number of patients evaluable up to 5 years following SBRT , it is unlikely that unexpected late adverse effects will manifest themselves PURPOSE To evaluate the feasibility and toxicity of stereotactic hypofractionated accurate radiotherapy ( SHARP ) for localized prostate cancer . METHODS AND MATERIAL S A Phase I/II trial of SHARP performed for localized prostate cancer using 33.5 Gy in 5 fractions , calculated to be biologically equivalent to 78 Gy in 2 Gy fractions ( alpha/beta ratio of 1.5 Gy ) . Noncoplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment . Genitourinary ( GU ) and gastrointestinal ( GI ) toxicity were evaluated by American Urologic Association ( AUA ) score and Common Toxicity Criteria ( CTC ) . Prostate-specific antigen ( PSA ) values and self-reported sexual function were recorded at specified follow-up intervals . RESULTS The study includes 40 patients . The median follow-up is 41 months ( range , 21 - 60 months ) . Acute toxicity Grade 1 - 2 was 48.5 % ( GU ) and 39 % ( GI ) ; 1 acute Grade 3 GU toxicity . Late Grade 1 - 2 toxicity was 45 % ( GU ) and 37 % ( GI ) . No late Grade 3 or higher toxicity was reported . Twenty-six patients reported potency before therapy ; 6 ( 23 % ) have developed impotence . Median time to PSA nadir was 18 months with the majority of nadirs less than 1.0 ng/mL. The actuarial 48-month biochemical freedom from relapse is 70 % for the American Society for Therapeutic Radiology and Oncology definition and 90 % by the alternative nadir + 2 ng/mL failure definition . CONCLUSIONS SHARP for localized prostate cancer is feasible with minimal acute or late toxicity . Dose escalation should be possible PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes . PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen < /= 15 ng/mL were r and omly assigned to a total dose of either 70.2 Gray equivalents ( GyE ; conventional ) or 79.2 GyE ( high ) . No patient received and rogen suppression therapy with radiation . Local failure ( LF ) , biochemical failure ( BF ) , and overall survival ( OS ) were outcomes . Results A total of 393 men were r and omly assigned , and median follow-up was 8.9 years . Men receiving high-dose radiation therapy were significantly less likely to have LF , with a hazard ratio of 0.57 . The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4 % for conventional-dose and 16.7 % for high-dose radiation therapy ( P < .0001 ) . This difference held when only those with low-risk disease ( n = 227 ; 58 % of total ) were examined : 28.2 % for conventional and 7.1 % for high dose ( P < .0001 ) . There was a strong trend in the same direction for the intermediate-risk patients ( n = 144 ; 37 % of total ; 42.1 % v 30.4 % , P = .06 ) . Eleven percent of patients subsequently required and rogen deprivation for recurrence after conventional dose compared with 6 % after high dose ( P = .047 ) . There remains no difference in OS rates between the treatment arms ( 78.4 % v 83.4 % ; P = .41 ) . Two percent of patients in both arms experienced late grade > /= 3 genitourinary toxicity , and 1 % of patients in the high-dose arm experienced late grade > /= 3 GI toxicity . CONCLUSION This r and omized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation . This was achieved without an increase in grade > /= 3 late urinary or rectal morbidity PURPOSE To report the long-term results of a r and omized radiotherapy dose escalation trial for prostate cancer . METHODS AND MATERIAL S From 1993 to 1998 , a total of 301 patients with stage T1b to T3 prostate cancer were accrued to a r and omized external beam dose escalation trial using 70 Gy versus 78 Gy . The median follow-up is now 8.7 years . Kaplan-Meier analysis was used to compute rates of prostate-specific antigen ( PSA ) failure ( nadir + 2 ) , clinical failure , distant metastasis , disease-specific , and overall survival as well as complication rates at 8 years post-treatment . RESULTS For all patients , freedom from biochemical or clinical failure ( FFF ) was superior for the 78-Gy arm , 78 % , as compared with 59 % for the 70-Gy arm ( p = 0.004 , and an even greater benefit was seen in patients with initial PSA > 10 ng/ml ( 78 % vs. 39 % , p = 0.001 ) . The clinical failure rate was significantly reduced in the 78-Gy arm as well ( 7 % vs. 15 % , p = 0.014 ) . Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm . Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients ( 26 % vs. 13 % ) , although genitourinary toxicity of grade 2 or greater was less ( 13 % vs. 8 % ) and not statistically significantly different . Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum . CONCLUSIONS Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA > 10 ng/ml Stereotactic body radiotherapy ( SBRT ) boost following external beam radiation therapy ( EBRT ) for advanced localized prostate cancer may reduce toxicity while escalating the dose . We present preliminary biochemical control and urinary , rectal and sexual toxicities for 73 patients treated with SBRT as a boost to EBRT . Forty-one intermediate- and 32 high-risk localized prostate cancer patients received 45 Gy EBRT with SBRT boost . Twenty-eight patients ( 38.3 % ) received a total SBRT boost dose of 18 Gy ( 3 fractions of 6 Gy ) , 28 patients ( 38.3 % ) received 19.5 Gy ( 3 fractions of 6.5 Gy ) , and 17 patients ( 23.2 % ) received 21 Gy ( 3 fractions of 7 Gy ) . Toxicity was assessed using the Radiation Therapy Oncology Group urinary and rectal toxicity scale . Biochemical failure was assessed using the Phoenix definition . The median follow-up was 33 months ( range , 22 − 43 months ) . Less than 7 % Grade II and no higher grade acute toxicities occurred . To date , one Grade III and no Grade IV late toxicities occurred . For the 97 % of patients with 24 months minimum follow-up , 71.8 % achieved a PSA nadir threshold of 0.5 ng/mL. Three intermediate-risk and seven high-risk biochemical failures occurred ; one high-risk patient died of his cancer . Three-year actuarial biochemical control rates were 89.5 % and 77.7 % for intermediate- and high-risk patients , respectively . SBRT boost for prostate cancer treatment is safe and feasible with minimal acute toxicity . At 33 months late toxicity and biochemical control are promising . Long-term durability of these findings remains to be established PURPOSE The effectiveness of stereotactic body radiotherapy ( SBRT ) for localized prostate cancer is tested . METHODS AND MATERIAL S A total of 1100 patients with clinical ly localized prostate cancer were enrolled in separate prospect i ve phase 2 clinical trials of SBRT from 8 institutions during 2003 - 11 and pooled for analysis . SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4 - 5 fractions . Patients were low-risk ( 58 % ) , intermediate-risk ( 30 % ) and high-risk ( 11 % ) . A short-course of and rogen deprivation therapy ( ADT ) was given to 14 % . PSA relapse defined as a rise > 2ng/ml above nadir was analyzed with the Kaplan Meier method . RESULTS With a median follow-up of 36months there were 49 patients with PSA failure ( 4.5 % ) , 9 of whom were subsequently determined to be benign PSA bounces . The 5-year biochemical relapse free survival ( bRFS ) rate was 93 % for all patients ; 95 % , 83 % and 78 % for GS ⩽6 , 7 and ⩾8 , respectively ( p=0.001 ) , and 95 % , 84 % and 81 % for low- , intermediate- and high-risk patients , respectively ( p<0.001 ) . No differences were observed with ADT ( p=0.71 ) or as a function of total dose ( p=0.17 ) . A PSA bounce of > 0.2ng/ml was noted among 16 % of patients . For 135 patients possessing a minimum of 5years follow-up , the 5-year bRFS rate for low- and intermediate-risk patients was 99 % and 93 % , respectively . CONCLUSION PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients . The current evidence supports consideration of SBRT among the therapeutic options for these patients BACKGROUND In men with localised prostate cancer , conformal radiotherapy ( CFRT ) could deliver higher doses of radiation than does st and ard-dose conventional radical external-beam radiotherapy , and could improve long-term efficacy , potentially at the cost of increased toxicity . We aim ed to present the first analyses of effectiveness from the MRC RT01 r and omised controlled trial . METHODS The MRC RT01 trial included 843 men with localised prostate cancer who were r and omly assigned to st and ard-dose CFRT or escalated-dose CFRT , both administered with neoadjuvant and rogen suppression . Primary endpoints were biochemical-progression-free survival ( bPFS ) , freedom from local progression , metastases-free survival , overall survival , and late toxicity scores . The toxicity scores were measured with question naires for physicians and patients that included the Radiation Therapy Oncology Group ( RTOG ) , the Late Effects on Normal Tissue : Subjective/ Objective /Management ( LENT/SOM ) scales , and the University of California , Los Angeles Prostate Cancer Index ( UCLA PCI ) scales . Analysis was done by intention to treat . This trial is registered at the Current Controlled Trials website http://www.controlled-trials.com/IS RCT N47772397 . FINDINGS Between January , 1998 , and December , 2002 , 843 men were r and omly assigned to escalated-dose CFRT ( n=422 ) or st and ard-dose CFRT ( n=421 ) . In the escalated group , the hazard ratio ( HR ) for bPFS was 0.67 ( 95 % CI 0.53 - 0.85 , p=0.0007 ) . We noted 71 % bPFS ( 108 cumulative events ) and 60 % bPFS ( 149 cumulative events ) by 5 years in the escalated and st and ard groups , respectively . HR for clinical progression-free survival was 0.69 ( 0.47 - 1.02 ; p=0.064 ) ; local control was 0.65 ( 0.36 - 1.18 ; p=0.16 ) ; freedom from salvage and rogen suppression was 0.78 ( 0.57 - 1.07 ; p=0.12 ) ; and metastases-free survival was 0.74 ( 0.47 - 1.18 ; p=0.21 ) . HR for late bowel toxicity in the escalated group was 1.47 ( 1.12 - 1.92 ) according to the RTOG ( grade > /=2 ) scale ; 1.44 ( 1.16 - 1.80 ) according to the LENT/SOM ( grade > /=2 ) scales ; and 1.28 ( 1.03 - 1.60 ) according to the UCLA PCI ( score > /=30 ) scale . 33 % of the escalated and 24 % of the st and ard group reported late bowel toxicity within 5 years of starting treatment . HR for late bladder toxicity according to the RTOG ( grade > /=2 ) scale was 1.36 ( 0.90 - 2.06 ) , but this finding was not supported by the LENT/SOM ( grade > /=2 ) scales ( HR 1.07 [ 0.90 - 1.29 ] ) , nor the UCLA PCI ( score > /=30 ) scale ( HR 1.05 [ 0.81 - 1.36 ] ) . INTERPRETATION Escalated-dose CFRT with neoadjuvant and rogen suppression seems clinical ly worthwhile in terms of bPFS , progression-free survival , and decreased use of salvage and rogen suppression . This additional efficacy is offset by an increased incidence of longer term adverse events Purpose Single-institution single-arm prospect i ve study . Endpoint : To assess whether there are more than 5 % of men having grade 3 GU or any grade 3 GI acute toxicity during stereotactic body radiation therapy ( SBRT ) for prostate cancer using helical tomotherapy . Methods Since May 2012 , 17 prostate cancer patients were treated with helical tomotherapy . The exclusion criteria used are the following : Gleason score ≥8 , PSA > 20 ng/ml , cT3b-4 , IPSS ≥20 and history of acute urinary retention . CTV included the prostate gl and and 1 cm of seminal vesicles in the low-risk group ( LR ) or the seminal vesicles completely in the intermediate ( IR ) and high-risk ( HR ) NCCN groups . CTV margins ranged from 2 to 8 mm , while PTV margins were 2 to 9 mm . Patients received eight fractions of 5.48 Gy ( LR ) or 5.65 Gy ( IR , HR ) on alternate days . Total equivalent doses at 2 Gy per fraction are 87.4 for LR and 92.3 Gy for IR – HR using an α/β value of 1.5 . Correspondent figures for a α/β of 3 are 74.3 Gy and 78.2 Gy , respectively . Megavoltage CT ( MVCT ) for on-line correction was taken before every fraction . Results The patient distribution by risk group is 29 , 47 and 24 % for LR , IR and HR , respectively . 82 % received neoadjuvant-concomitant hormonal therapy . Acute GU toxicity grade 1 , 2 and 3 was found in 70 , 6 and 0 % of men . GI toxicity was observed in 50 , 0 and 0 . After 136 MVCT , the st and ard deviation of the mean individual corrections in the anterior – posterior direction was 2.5 mm . ConclusionS BRT for prostate cancer using helical tomotherapy is feasible . Initial results show an early toxicity profile no worse than SBRT delivered with robotic radiosurgery or conventionally fractionated radiotherapy Recent reports using extreme hypofractionated regimens in the treatment of low‐risk prostate adenocarcinoma have been encouraging . Here , the authors report on their own multi‐institutional experience with extreme hypofractionated stereotactic radiotherapy for early stage disease R and omized controlled trials ( RCTs ) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment . For many patients , cancer is a chronic illness ; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making , as “ concrete ” patient outcomes ( eg , survival ) will likely be excellent independent of the intervention , and detecting a difference between trial arms may be impossible . In this commentary , we articulate 9 recommendations that we hope future clinical trialists and funding agencies ( including those under the National Cancer Institute ) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making , based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men , that is , prostate cancer . We recommend routinely reporting : ( 1 ) race ; ( 2 ) medical comorbidities ; ( 3 ) psychiatric comorbidities ; ( 4 ) insurance status ; ( 5 ) education ; ( 6 ) marital status ; ( 7 ) income ; ( 8) sexual orientation ; and ( 9 ) facility-related characteristics ( eg , number of centers involved , type of facilities , yearly hospital volumes ) . We discuss how these factors independently affect patient outcomes and toxicities ; future clinicians and governing organizations should consider this information to plan RCTs accordingly ( to maximize patient accrual and total n ) , select appropriate endpoints ( eg , toxicity , quality of life , sexual function ) , actively monitor RCTs , and report results so as to identify the optimal treatment among sub population BACKGROUND We tested our ability to approximate the dose ( 38 Gy ) , fractionation ( four fractions ) , and distribution of high-dose-rate ( HDR ) brachytherapy for prostate cancer with CyberKnife ( CK ) stereotactic body radiotherapy ( SBRT ) plans . We also report early clinical observations of CK SBRT treatment . METHODS AND MATERIAL S Ten patients were treated with CK . For each CK SBRT plan , an HDR plan was design ed using common contour sets and simulated HDR catheters . Planning target volume coverage , intraprostatic dose escalation , and urethra , rectum , and bladder exposure were compared . RESULTS Planning target volume coverage by the prescription dose was similar for CK SBRT and HDR plans , whereas percent of volume of interest receiving 125 % of prescribed radiation dose ( V125 ) and V150 values were higher for HDR , reflecting higher doses near HDR source dwell positions . Urethra dose comparisons were lower for CK SBRT in 9 of 10 cases , suggesting that CK SBRT may more effectively limit urethra dose . Bladder maximum point doses were higher with HDR , but bladder dose falloff beyond the maximum dose region was more rapid with HDR . Maximum rectal wall doses were similar , but CK SBRT created sharper rectal dose falloff beyond the maximum dose region . Second CK SBRT plans , constructed by equating urethra radiation dose received by point of maximum exposure of volume of interest to the HDR plan , significantly increased V125 and V150 . Clinical ly , 4-month post-CK SBRT median prostate-specific antigen levels decreased 86 % from baseline . Acute toxicity was primarily urologic and returned to baseline by 2 months . Acute rectal morbidity was minimal and transient . CONCLUSIONS It is possible to construct CK SBRT plans that closely recapitulate HDR dosimetry and deliver the plans noninvasively |
13,991 | 29,025,740 | FCR improved complete remission , PFS and overall survival vs the comparator ; median PFS was not reached in the subgroup of CLL patients with mutated IGHV | In chronic lymphocytic leukemia ( CLL ) patients with mutated IGHV , 3 recent studies have demonstrated prolonged progression-free survival ( PFS ) after treatment with fludarabine-cyclophosphamide-rituximab ( FCR ) chemoimmunotherapy . | BACKGROUND Chemoimmunotherapy with fludarabine , cyclophosphamide , and rituximab is the st and ard therapy for physically fit patients with advanced chronic lymphocytic leukaemia . This international phase 3 study compared the efficacy and tolerance of the st and ard therapy with a potentially less toxic combination consisting of bendamustine and rituximab . METHODS Treatment-naive fit patients with chronic lymphocytic leukaemia ( aged 33 - 81 years ) without del(17p ) were enrolled after undergoing a central screening process . Patients were r and omly assigned ( 1:1 ) with a computer-generated r and omisation list using r and omly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage . Patients were allocated to receive six cycles of intravenous fludarabine ( 25 mg/m(2 ) per day ) and cyclophosphamide ( 250 mg/m(2 ) per day ) for the first 3 days or to intravenous bendamustine ( 90 mg/m(2 ) per day ) for the first 2 days of each cycle . Rituximab 375 mg/m(2 ) was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m(2 ) during the next five cycles on day 1 . The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the st and ard therapy . We aim ed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5 % or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio ( HR ) based on the 90·4 % CI . The final analysis was done by intention to treat . The study is registered with Clinical Trials.gov , number NCT%2000769522 . FINDINGS 688 patients were recruited between Oct 2 , 2008 , and July 11 , 2011 , of which 564 patients who met inclusion criteria were r and omly assigned . 561 patients were included in the intention-to-treat population : 282 patients in the fludarabine , cyclophosphamide , and rituximab group and 279 in the bendamustine and rituximab group . After a median observation time of 37·1 months ( IQR 31·0 - 45·5 ) median progression-free survival was 41·7 months ( 95 % CI 34·9 - 45·3 ) with bendamustine and rituximab and 55·2 months ( 95 % CI not evaluable ) with fludarabine , cyclophosphamide , and rituximab ( HR 1·643 , 90·4 % CI 1·308 - 2·064 ) . As the upper limit of the 90·4 % CI was greater than 1·388 the null hypothesis for the corresponding non-inferiority hypothesis was not rejected . Severe neutropenia and infections were more frequently observed with fludarabine , cyclophosphamide , and rituximab ( 235 [ 84 % ] of 279 vs 164 [ 59 % ] of 278 , and 109 [ 39 % ] vs 69 [ 25 % ] , respectively ) during the study . The increased frequency of infectious complications with fludarabine , cyclophosphamide , and rituximab was more pronounced in patients older than 65 years . INTERPRETATION The combination of fludarabine , cyclophosphamide , and rituximab remains the st and ard front-line therapy in fit patients with chronic lymphocytic leukaemia , but bendamustine and rituximab is associated with less toxic effects . FUNDING Roche Pharma AG , Mundipharma , German Federal Ministry of Education and Research Summary Background Uncontrolled studies comparing pentostatin ( P ) , cyclophosphamide ( C ) , and rituximab ( R ) ( PCR ) to fludarabine plus C+R ( FCR ) suggest similar efficacy with fewer infectious complications with PCR . We compared FCR and PCR in previously-untreated or minimally-treated B-cell chronic lymphocytic leukemia ( CLL ) . Treatment FCR ( F 20 mg/m2 Days 1–5 , C 600 mg/m2 Day 1 , R 375 mg/m2 Day 1 ) ( 28-day cycles ) or PCR ( P 4 mg/m2 Day 1 , C 600 mg/m2 Day 1 , R 375 mg/m2 Day 1 ) ( 21-day cycles ) . Dose 1 of R : 100 mg/m2 was given on Day 8 Cycle 1 and the remainder on Day 9 ; in subsequent cycles the entire dose was given on Day 1 . Results Ninety-two patients were r and omly assigned to each group ( N = 184 ) . Groups were balanced ; ~20 % had received prior chemotherapy . The infection rate ( FCR/PCR ) was 31%/36 % , the infective event rate was 38%/45 % ; 30 (35%)/37 ( 44 % ) patients were hospitalized ; total hospitalization days was 271/404 . 12 (14%)/6 ( 7 % ) patients achieved complete remissions ( CR ) ; the overall response rate ( ORR ) including CR+nodular PR (nPR)+PR was 59%/49 % . Grade 3–4 treatment related AEs : neutropenia ( 69%/57 % ) , leukopenia ( 34%/17 % ) , thrombocytopenia ( 13%/6 % ) . Grade 3–4 infections : febrile neutropenia ( 8%/6 % ) , fever ( 2%/6 % ) , infection ( 1%/3 % ) , urinary tract infection ( 1%/0 % ) , pneumonia ( 3%/1 % ) , and sepsis ( 1%/2 % ) ; 5 deaths ( 1 FCR/4 PCR ) were treatment-related . Conclusions PCR and FCR have significant activity in CLL and can be given safely in the community setting despite significant toxicity . ORRs were lower than expected ; the CR rate was higher ( NS ) with FCR . This trial did not demonstrate a lower infection rate with PCR The high complete remission rate with first-line combined fludarabine , cyclophosphamide , and rituximab ( FCR ) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point . We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR . MRD was prospect ively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment . After course 3 and at final response assessment , 17 % and 43 % of patients were MRD negative in bone marrow , respectively . A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses ( MVAs ) . MRD-negative status was independently associated with significantly longer progression-free survival ( PFS ) and overall survival ( OS ) in MVA ( P = .03 and .02 , respectively ) . This association was confirmed also on l and mark MVA at the time of MRD assessment ( P = .04 and .05 , respectively ) . MRD-negative patients had comparable PFS and OS , independent of the number of courses received or interim staging . Early MRD eradication may be a desirable goal , prompting consideration of early discontinuation of treatment . This trial was registered at www . clinical trials.gov as # NCT00759798 BACKGROUND Chronic lymphocytic leukemia ( CLL ) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression . We conducted an international , open-label , r and omized phase 3 trial to compare two oral agents , ibrutinib and chlorambucil , in previously untreated older patients with CLL or small lymphocytic lymphoma . METHODS We r and omly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil . The primary end point was progression-free survival as assessed by an independent review committee . RESULTS The median age of the patients was 73 years . During a median follow-up period of 18.4 months , ibrutinib result ed in significantly longer progression-free survival than did chlorambucil ( median , not reached vs. 18.9 months ) , with a risk of progression or death that was 84 % lower with ibrutinib than that with chlorambucil ( hazard ratio , 0.16 ; P<0.001 ) . Ibrutinib significantly prolonged overall survival ; the estimated survival rate at 24 months was 98 % with ibrutinib versus 85 % with chlorambucil , with a relative risk of death that was 84 % lower in the ibrutinib group than in the chlorambucil group ( hazard ratio , 0.16 ; P=0.001 ) . The overall response rate was higher with ibrutinib than with chlorambucil ( 86 % vs. 35 % , P<0.001 ) . The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib . Adverse events of any grade that occurred in at least 20 % of the patients receiving ibrutinib included diarrhea , fatigue , cough , and nausea ; adverse events occurring in at least 20 % of those receiving chlorambucil included nausea , fatigue , neutropenia , anemia , and vomiting . In the ibrutinib group , four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage . A total of 87 % of the patients in the ibrutinib group are continuing to take ibrutinib . CONCLUSIONS Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma , as assessed by progression-free survival , overall survival , response rate , and improvement in hematologic variables . ( Funded by Pharmacyclics and others ; RESONATE-2 Clinical Trials.gov number , NCT01722487 . ) Despite promising results with targeted drugs , chemoimmunotherapy with fludarabine , cyclophosphamide ( FC ) , and rituximab ( R ) remains the st and ard therapy for fit patients with untreated chronic lymphocytic leukemia ( CLL ) . Herein , we present the long-term follow-up of the r and omized CLL8 trial reporting safety and efficacy of FC and FCR treatment of 817 treatment-naïve patients with CLL . The primary end point was progression-free survival ( PFS ) . With a median follow-up of 5.9 years , median PFS were 56.8 and 32.9 months for the FCR and FC group ( hazard ratio [ HR ] , 0.59 ; 95 % confidence interval [ CI ] , 0.50 - 0.69 , P < .001 ) . Median overall survival ( OS ) was not reached for the FCR group and was 86.0 months for the FC group ( HR , 0.68 ; 95 % CI , 0.54 - 0.89 , P = .001 ) . In patients with mutated IGHV ( IGHV MUT ) , FCR improved PFS and OS compared with FC ( PFS : HR , 0.47 ; 95 % CI , 0.33 - 0.68 , P < .001 ; OS : HR , 0.62 ; 95 % CI , 0.34 - 1.11 , P = .1 ) . This improvement remained applicable for all cytogenetic subgroups other than del(17p ) . Long-term safety analyses showed that FCR had a higher rate of prolonged neutropenia during the first year after treatment ( 16.6 % vs 8.8 % ; P = .007 ) . Secondary malignancies including Richter 's transformation occurred in 13.1 % in the FCR group and in 17.4 % in the FC group ( P = .1 ) . First-line chemoimmunotherapy with FCR induces long-term remissions and highly relevant improvement in OS in specific genetic subgroups of fit patients with CLL , in particular those with IGHV MUT . This trial was registered at www . clinical trials.gov as # NCT00281918 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 Early results of the fludarabine , cyclophosphamide , and rituximab ( FCR ) regimen in 224 patients showed that it was highly active as initial therapy of chronic lymphocytic leukemia . In this report , we present the final results of all 300 study patients at a median follow up of 6 years . The overall response rate was 95 % , with complete remission in 72 % , nodular partial remission in 10 % , partial remission due to cytopenia in 7 % , and partial remission due to residual disease in 6 % . Two patients ( < 1 % ) died within 3 months of starting therapy . Six-year overall and failure-free survival were 77 % and 51 % , respectively . Median time to progression was 80 months . Pretreatment characteristics independently associated with inferior response were age 70 years or older , beta2-microglobulin twice the upper limit of normal ( 2N ) or more , white cell count 150 x 10(9)/L or more , abnormal chromosome 17 , and lactate dehydrogenase 2N or more . No pretreatment characteristic was independently associated with decreased complete remission duration . The risk of late infection was 10 % and 4 % for the first and second years of remission , respectively , and less than 1.5 % per year for the third year onward . In a multivariate analysis of patients receiving fludarabine-based therapy at our center , FCR therapy emerged as the strongest independent determinant of survival Combination chemotherapy with fludarabine plus cyclophosphamide ( FC ) was compared with the st and ard regimen of fludarabine monotherapy in first-line treatment of younger patients with chronic lymphocytic leukemia ( CLL ) . Between 1999 and 2003 , a total of 375 patients younger than 66 years who predominantly had advanced CLL were r and omly assigned to receive either fludarabine ( 25 mg/m(2 ) for 5 days intravenously , repeated every 28 days ) or FC combination therapy ( fludarabine 30 mg/m(2 ) plus cyclophosphamide 250 mg/m(2 ) for 3 days intravenously , repeated every 28 days ) . Both regimens were administered to a maximum of 6 courses . FC combination chemotherapy result ed in significantly higher complete remission rate ( 24 % ) and overall response rate ( 94 % ) compared with fludarabine alone ( 7 % and 83 % ; P < .001 and P = .001 ) . FC treatment also result ed in longer median progression-free survival ( 48 vs 20 months ; P = .001 ) and longer treatment-free survival ( 37 vs 25 months ; P < .001 ) . Thus far , no difference in median overall survival has been observed . FC caused significantly more thrombocytopenia and leukocytopenia but did not increase the number of severe infections . In summary , first-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL ADMIRE was a multicenter , r and omized-controlled , open , phase IIB superiority trial in previously untreated chronic lymphocytic leukemia . Conventional front-line therapy in fit patients is fludarabine , cyclophosphamide and rituximab ( FCR ) . Initial evidence from non-r and omized phase II trials suggested that the addition of mitoxantrone to FCR ( FCM-R ) improved remission rates . Two hundred and fifteen patients were recruited to assess the primary end point of complete remission ( CR ) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria . Secondary end points were progression-free survival ( PFS ) , overall survival ( OS ) , overall response rate , minimal residual disease ( MRD ) negativity and safety . At final analysis , CR rates were 69.8 FCR vs 69.3 % FCM-R ( adjusted odds ratio ( OR ) : 0.97 ; 95 % confidence interval ( CI ) : ( 0.53–1.79 ) , P=0.932 ) . MRD-negativity rates were 59.3 FCR vs 50.5 % FCM-R ( adjusted OR : 0.70 ; 95 % CI : ( 0.39–1.26 ) , P=0.231 ) . During treatment , 60.0 % ( n=129 ) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia , a lower proportion on FCR compared with FCM-R ( 56.1 vs 63.9 % ) . The toxicity of both regimens was acceptable . There are no significant differences between the treatment groups for PFS and OS . The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response . Oral FCR was well tolerated and result ed in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy PURPOSE To determine the clinical significance of flow cytometric minimal residual disease ( MRD ) quantification in chronic lymphocytic leukemia ( CLL ) in addition to pretherapeutic risk factors and to compare the prognostic impact of MRD between the arms of the German CLL Study Group CLL8 trial . PATIENTS AND METHODS MRD levels were prospect ively quantified in 1,775 blood and bone marrow sample s from 493 patients r and omly assigned to receive fludarabine and cyclophosphamide ( FC ) or FC plus rituximab ( FCR ) . Patients were categorized by MRD into low- ( < 10(-4 ) ) , intermediate- ( ≥ 10(-4 ) to < 10(-2 ) ) , and high-level ( ≥ 10(-2 ) ) groups . RESULTS Low MRD levels during and after therapy were associated with longer progression-free survival ( PFS ) and overall survival ( OS ; P < .0001 ) . Median PFS is estimated at 68.7 , 40.5 , and 15.4 months for low , intermediate , and high MRD levels , respectively , when assessed 2 months after therapy . Compared with patients with low MRD , greater risks of disease progression were associated with intermediate and high MRD levels ( hazard ratios , 2.49 and 14.7 , respectively ; both P < .0001 ) . Median OS was 48.4 months in patients with high MRD and was not reached for lower MRD levels . MRD remained predictive for OS and PFS in multivariate analyses that included the most important pretherapeutic risk markers in CLL . PFS and OS did not differ between treatment arms within each MRD category . However , FCR induced low MRD levels more frequently than FC . CONCLUSION MRD levels independently predict OS and PFS in CLL . Therefore , MRD quantification might serve as a surrogate marker to assess treatment efficacy in r and omized trials before clinical end points can be evaluated BACKGROUND On the basis of promising results that were reported in several phase 2 trials , we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia . METHODS Treatment-naive , physically fit patients ( aged 30 - 81 years ) with CD20-positive chronic lymphocytic leukaemia were r and omly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine ( 25 mg/m(2 ) per day ) and cyclophosphamide ( 250 mg/m(2 ) per day ) for the first 3 days of each 28-day treatment course with or without rituximab ( 375 mg/m(2 ) on day 0 of first course , and 500 mg/m(2 ) on day 1 of second to sixth courses ) in 190 centres in 11 countries . Investigators and patients were not masked to the computer-generated treatment assignment . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00281918 . FINDINGS 408 patients were assigned to fludarabine , cyclophosphamide , and rituximab ( chemoimmunotherapy group ) and 409 to fludarabine and cyclophosphamide ( chemotherapy group ) ; all patients were analysed . At 3 years after r and omisation , 65 % of patients in the chemoimmunotherapy group were free of progression compared with 45 % in the chemotherapy group ( hazard ratio 0·56 [ 95 % CI 0·46 - 0·69 ] , p<0·0001 ) ; 87 % were alive versus 83 % , respectively ( 0·67 [ 0·48 - 0·92 ] ; p=0·01 ) . Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia ( 136 [ 34 % ] of 404 vs 83 [ 21 % ] of 396 ; p<0·0001 ) and leucocytopenia ( 97 [ 24 % ] vs 48 [ 12 % ] ; p<0·0001 ) . Other side-effects , including severe infections , were not increased . There were eight ( 2 % ) treatment-related deaths in the chemoimmunotherapy group compared with ten ( 3 % ) in the chemotherapy group . INTERPRETATION Chemoimmunotherapy with fludarabine , cyclophosphamide , and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia . Moreover , the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia . FUNDING F Hoffmann-La Roche PURPOSE Fludarabine and cyclophosphamide ( FC ) , which are active in treatment of chronic lymphocytic leukemia ( CLL ) , are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines . A chemoimmunotherapy program consisting of fludarabine , cyclophosphamide , and rituximab ( FCR ) was developed with the goal of increasing the complete remission ( CR ) rate in previously untreated CLL patients to > /= 50 % . PATIENTS AND METHODS We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL . Flow cytometry was used to measure residual disease . Results and safety were compared with a previous regimen using FC . RESULTS The median age was 58 years ; 75 patients ( 33 % ) had Rai stage III to IV disease . The CR rate was 70 % ( 95 % CI , 63 % to 76 % ) , the nodular partial remission rate was 10 % , and the partial remission rate was 15 % , for an overall response rate of 95 % ( 95 % CI , 92 % to 98 % ) . Two thirds of patients evaluated with flow cytometry had less than 1 % CD5- and CD19-coexpressing cells in bone marrow after therapy . Grade 3 to 4 neutropenia occurred during 52 % of courses ; major and minor infections were seen in 2.6 % and 10 % of courses , respectively . One third of the 224 patients had > /= one episode of infection , and 10 % had a fever of unknown origin . CONCLUSION FCR produced a high CR rate in previously untreated CLL . Most patients had no detectable disease on flow cytometry at the end of therapy . Time to treatment failure analysis showed that 69 % of patients were projected to be failure free at 4 years ( 95 % CI , 57 % to 81 % ) This study aim ed to assess the frequency of and the contributing factors for second primary malignancies ( SPMs ) and Richter ’s transformations ( RTs ) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine ( F ) vs F+cyclophosphamide ( FC ) , chlorambucil vs F , FC without or with rituximab , and bendamustine+R ( BR ) . Among 1458 patients , 239 ( 16.4 % ) experienced either an SPM ( N=191 ) or a RT ( N=75 ) . Solid tumors ( N=115 ; 43.2 % of all second neoplasias ) appeared most frequently , followed by RTs ( N=75 ; 28.2 % ) . Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry . Age>65 ( hazard ratio ( HR ) 2.1 ; P<0.001 ) , male sex ( HR 1.7 ; P=0.01 ) , co-morbidities ( HR 1.6 ; P=0.01 ) and number of subsequent treatments⩾1 ( HR 12.1 ; P<0.001 ) showed an independent adverse prognostic impact on SPM-free survival . Serum thymidine kinase>10 U/l at trial enrollment ( HR 3.9 ; P=0.02 ) , non-response to first-line treatment ( HR 3.6 ; P<0.001 ) and number of subsequent treatments⩾1 ( HR 30.2 ; P<0.001 ) were independently associated with increased risk for RT BACKGROUND Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil . We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia . METHODS Between 1990 and 1994 , we r and omly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments : fludarabine ( 25 mg per square meter of body-surface area , administered intravenously daily for 5 days every 28 days ) , chlorambucil ( 40 mg per square meter , given orally every 28 days ) , or fludarabine ( 20 mg per square meter per day for 5 days every 28 days ) plus chlorambucil ( 20 mg per square meter every 28 days ) . Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles . RESULTS Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone . Among the other two groups , the response rate was significantly higher for fludarabine alone than for chlorambucil alone . Among 170 patients treated with fludarabine , 20 percent had a complete remission , and 43 percent had a partial remission . The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent ( P < 0.001 for both comparisons ) . The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months , respectively , whereas both values were 14 months in the chlorambucil group ( P<0.001 for both comparisons ) . The median overall survival among patients treated with fludarabine was 66 months , which was not significantly different from the overall survival in the other two groups ( 56 months with chlorambucil and 55 months with combined treatment ) . Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil ( P=0.08 ) , although , overall , toxic effects were tolerable with the two single-drug regimens . CONCLUSIONS When used as the initial treatment for chronic lymphocytic leukemia , fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil Mutations in TP53 , NOTCH1 , and SF3B1 were analyzed in the CLL8 study evaluating first-line therapy with fludarabine and cyclophosphamide ( FC ) or FC with rituximab ( FCR ) among patients with untreated chronic lymphocytic leukemia ( CLL ) . TP53 , NOTCH1 , and SF3B1 were mutated in 11.5 % , 10.0 % , and 18.4 % of patients , respectively . NOTCH1(mut ) and SF3B1(mut ) virtually showed mutual exclusivity ( 0.6 % concurrence ) , but TP53(mut ) was frequently found in NOTCH1(mut ) ( 16.1 % ) and in SF3B1(mut ) ( 14.0 % ) patients . There were few significant associations with clinical and laboratory characteristics , but genetic markers had a strong influence on response and survival . In multivariable analyses , an independent prognostic impact was found for FCR , thymidine kinase ( TK ) ≥10 U/L , unmutated IGHV , 11q deletion , 17p deletion , TP53(mut ) , and SF3B1(mut ) on progression-free survival ; and for FCR , age ≥65 years , Eastern Cooperative Oncology Group performance status ≥1 , β2-microglobulin ≥3.5 mg/L , TK ≥10 U/L , unmutated IGHV , 17p deletion , and TP53(mut ) on overall survival . Notably , predictive marker analysis identified an interaction of NOTCH1 mutational status and treatment in that rituximab failed to improve response and survival in patients with NOTCH1(mut ) . In conclusion , TP53 and SF3B1 mutations appear among the strongest prognostic markers in CLL patients receiving current-st and ard first-line therapy . NOTCH1(mut ) was identified as a predictive marker for decreased benefit from the addition of rituximab to FC . This study is registered at www . clinical trials.gov as # NCT00281918 A French and Belgian multicenter phase 3 trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia . Of 178 patients enrolled in the study , 165 were r and omly assigned to receive 6 courses of oral fludarabine and cyclophosphamide ( FC ) in combination with rituximab ( FCR ; 375 mg/m(2 ) in cycle one , 500 mg/m(2 ) in all subsequent cycles ) or alemtuzumab ( FCCam ; 30 mg subcutaneously injected on cycle days 1 - 3 ) ; each cycle was 28 days . Recruitment was halted prematurely because of excess toxicity ; 8 patients died in the FCCam group , 3 from lymphoma and 5 from in-fection . Overall response rates were 91 % with FCR and 90 % with FCCam ( P = .79 ) . Complete remission rates were 33.75 % with FCR and 19.2 % with FCCam ( P = .04 ) . Three-year progression-free survival was 82.6 % with FCR and 72.5 % with FCCam ( P = .21 ) . Three-year overall survival was similar between the 2 arms at 90.1 % in the FCR arm and 86.4 % in the FCCam arm ( P = .27 ) . These results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile , representing a significant limitation of its use . This study is registered with www . clinical trials.gov as number NCT00564512 Fludarabine , cyclophosphamide , and rituximab ( FCR ) has represented a significant treatment advancement in chronic lymphocytic leukemia ( CLL ) . In the new scenario of targeted agents , there is an increasing interest in identifying patients who gain the maximum benefit from FCR . In this observational multicenter retrospective analysis of 404 CLL patients receiving frontline FCR , the combination of three biomarkers that are widely tested before treatment ( IGHV mutation status , 11q deletion and 17p deletion ; available in 80 % of the study cohort ) allowed to identify a very low-risk category of patients carrying mutated IGHV genes but neither 11q or 17p deletion that accounted for 28 % of all cases . The majority of very low-risk patients ( 71 % ) remained free of progression after treatment and their hazard of relapse decreased after 4 years from FCR . The life expectancy of very low-risk patients ( 91 % at 5 years ) was superimposable to that observed in the matched normal general population , indicating that neither the disease nor complications of its treatment affected survival in this favorable CLL group . These findings need a prospect i ve validation and may be helpful for the design of clinical trials aim ed at comparing FCR to new targeted treatments of CLL , and , possibly , for optimized disease management Purpose Therapeutic targeting of Bruton tyrosine kinase ( BTK ) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy , and relapse has been uncommon with current follow-up . Acquired mutations in BTK and PLCG2 can cause relapse , but data regarding the prevalence and natural history of these mutations are limited . Patients and Methods Patients accrued to four sequential studies of ibrutinib were included in these analyses . Deep sequencing for BTK and PLCG2 was performed retrospectively on patients who experienced relapse and prospect ively on a screening population . Results With a median follow-up time of 3.4 years , the estimated cumulative incidence of progression at 4 years is 19 % ( 95 % CI , 14 % to 24 % ) . Baseline karyotypic complexity , presence of del(17)(p13.1 ) , and age less than 65 years were risk factors for progression . Among patients who experienced relapse , acquired mutations of BTK or PLCG2 were found in 85 % ( 95 % CI , 71 % to 94 % ) , and these mutations were detected an estimated median of 9.3 months ( 95 % CI , 7.6 to 11.7 months ) before relapse . Of a group of 112 patients examined prospect ively , eight patients have experienced relapse , and all of these patients had acquired resistance mutations before relapse . A resistance mutation was detected in an additional eight patients who have not yet met criteria for clinical relapse . Conclusion Relapse of chronic lymphocytic leukemia after ibrutinib is an issue of increasing clinical significance . We show that mutations in BTK and PLCG2 appear early and have the potential to be used as a biomarker for future relapse , suggesting an opportunity for intervention |
13,992 | 24,952,308 | Grip strength in various grip types ( power grip , key pinch , precision pinch and tripod pinch ) was found to improve by h and exercise therapy without having adverse effects on pain or disease activity .
Adaptations in the range of motion in response to h and exercise therapy were less pronounced .
There appears to be some transfer from the improvements on the body functioning level to the level of daily functioning , with the largest improvements found on grip ability .
With regard to the intervention content , there was some evidence in favour of a longer therapy duration and a higher therapy intensity .
No conclusions could be drawn on the effectiveness of the different types of exercises . | H and exercises are often part of the treatment of h and rheumatoid arthritis ; however , it is still unclear whether and what type of exercises is effective in the treatment of this condition .
Therefore , a systematic review into the effectiveness of h and exercises in the treatment of h and rheumatoid arthritis has been performed . | & NA ; Physical therapists seeking to use evidence to guide their practice may have limited time to read research reports . One way to reduce the time required to identify and read about the research that is relevant to a particular clinical question is to read a systematic review that summarizes multiple studies . This paper explains the process that is used to conduct systematic review s , which includes the establishment of a protocol , comprehensive search ing , appraisal of the quality of the included studies , data extraction and meta analysis , and consideration of the clinical and research implication s of the findings . We also consider how the reader of a systematic review can determine whether the review is likely to provide an unbiased ( believable ) estimate of the treatment effect . A systematic review of r and omized trials of a cardiopulmonary physical therapy intervention is used as an example . The issue of appraisal of quality is then discussed further , with a demonstration of how one vali date d tool for quality appraisal ‐‐the PEDro scale‐‐can be used to evaluate a r and omized trial in cardiopulmonary physical therapy Rheumatoid arthritis ( RA ) is a systemic inflammatory and chronic disease of joints , which may result in irreversible deformities . To evaluate the effects of an exercise programme aim ed at improving the h and strength in individuals with h and deformities result ing from RA and to analyse the impact these exercises have on functionality . Twenty women with RA h and deformities participated in the study . They were r and omly divided into two groups as follows : Group 1 ( n = 13 ) had women participating in the exercise programme aim ed at improving h and grip ( HS ) and pinch strengths ( PS ) as well as the motor coordination of the h and ; Group 2 ( n = 7 ) had women with RA who received no treatment for their h and s ( control ) . The treatment programme for h and s consisted of 20 sessions , twice a week and at-home exercises . Both groups were su bmi tted to Health Assessment Question naire ( HAQ ) and evaluation of HS and PS by means of dynamometry . Re-evaluations were performed after 10 and 20 sessions in Group 1 and after 2 months in Group 2 . After 20 sessions of physiotherapy , Group 1 had a significant gain in HS and PS ( p < 0.05 ) in addition to the improvement of functionality as assessed by HAQ ( p = 0.016 ) . For Group 2 , no difference was found between the variables analysed ( p > 0.05 ) . The strengthening exercises for individuals with RA h and deformity are beneficial to improve h and grip and pinch strengths as well as functionality OBJECTIVE To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the h and s and feet in patients with rheumatoid arthritis ( RA ) . METHODS Data of the 281 completers of a 2 year r and omised controlled trial comparing the effects of usual care physical therapy ( UC ) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage ( Larsen score ) of the h and s and feet . Potential determinants of outcome were defined : disease activity , use of drugs , change in physical capacity and in bone mineral density , and attendance rate at exercise sessions . RESULTS After 2 years , the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC . The mean ( SD ) increase in damage was 3.5 ( 7.9 ) in the exercise group and 5.7 ( 10.2 ) in the UC group , p = 0.045 . Separate analysis of the damage to the h and s and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the h and s. The rate of damage was independently associated with less disease activity , less frequent use of glucocorticoids , and with an improvement in aerobic fitness . CONCLUSION The progression of radiological joint damage of the h and s and feet in patients with RA is not increased by long term high intensity weightbearing exercises . These exercises may have a protective effect on the joints of the feet OBJECTIVE To investigate the effects of a 21-week concurrent strength and endurance training protocol on physical fitness profile in women with early or longst and ing rheumatoid arthritis ( RA ) compared with healthy subjects . METHODS Twenty-three female patients with RA volunteered for the study . Twelve had early RA and eleven had longst and ing RA . Twelve healthy women served as controls . Maximal strength of different muscle groups was measured by dynamometers , walking speed with light cells , and vertical squat jump on the force platform to mirror explosive force . Maximal oxygen uptake was measured by gas analyzer . Six training sessions ( 3 strength training and 3 endurance training ) were carried out in a 2-week period for 21 weeks . RESULTS The training led to large gains in maximal strength both in women with RA and in healthy women ( P < 0.043 - 0.001 ) . The strength gains were accompanied by increases in walking speed ( P < 0.034 - 0.001 ) and vertical squat jump ( P < 0.034 - 0.001 ) . Significant improvements also occurred in maximal aerobic capacity in all groups ( P < 0.023 - 0.014 ) . CONCLUSIONS Both early and longst and ing RA patients with stable disease can safely improve all characteristics of their physical fitness profile using a progressive concurrent strength and endurance training protocol OBJECTIVE To evaluate the effectiveness of three different physiotherapeutic approaches in the management of the rheumatoid h and . METHODS In a r and omized controlled trial , participants with rheumatoid arthritis ( RA ) recruited from a rheumatology department in Mid-Staffordshire , UK ( February 1999 to January 2001 ) were r and omized to three groups . All received joint protection ( JP ) information delivered by a therapist at baseline . Group 1 participants received a set of additional h and -strengthening and mobilizing home exercises , group 2 a different set of additional h and -stretching exercises and group 3 the JP information alone . The primary outcome was the Arthritis Impact Measurement Scales II ( AIMS II ) ( upper limb ; h and and finger function subscales ) . Outcomes were assessed at baseline and 1 , 3 and 6 months . Analysis was by intention to treat . RESULTS Sixty-seven participants ( mean age 59.6 yr ) were recruited : group 1 n = 21 , group 2 n = 24 and group 3 n = 22 . A 78 % follow-up was achieved at 6 months . There was a mean fall ( SD ) in AIMS II upper limb function 0 - 6 month change scores in group 1 of 1.00 ( 1.07 ) . In groups 2 and 3 there was a mean increase in AIMS II scores of 0.18 ( 1.54 ) and 0.30 ( 1.22 ) , respectively . The differences in AIMS change scores between group 1 and groups 2 and 3 were statistically significant ( P = 0.007 ) and remained so after adjustment for multiple testing ( P = 0.012 ) . CONCLUSION Statistically significant improvements in arm function have been demonstrated following a programme of home-strengthening h and exercises in RA patients compared with simple stretches or advice alone 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 . A series of experiments showed that , on exercise of the inflamed human knee , intra-articular pressure rises above synovial capillary perfusion pressure , causing intra-articular hypoxia ; and that , on cessation of exercise , there is oxidative damage to lipids and IgG within the joint . These findings are consistent with the hypothesis that persistence of synovial inflammation can be due to exercise-induced hypoxic-reperfusion injury mediated by reactive oxygen species The primary objective of our study was to evaluate the effect of 6-week-long isotonic and isometric h and exercises on pain , h and functions , dexterity and quality of life in women diagnosed as rheumatoid arthritis ( RA ) . Our secondary objective was to assess the changes in h and grip strength and disease activity . This r and omized , parallel , single-blinded 6-week intervention study enrolled 52 female patients between 40 and 70 years of age , who were diagnosed with RA according to American College of Rheumatology criteria , had disease duration of at least 1 year and had a stage 1–3 disease according to Steinbrocker ’s functional evaluation scale . Patients were r and omized into isotonics and isometrics groups . Exercises were performed on sixth week . All patients were applied wax therapy in the first 2 weeks . Their pain was assessed with visual analog scale ( VAS ) , their h and functions with Duruöz H and Index ( DHI ) , dexterity with nine hole peg test ( NHPT ) and quality of life with Rheumatoid Arthritis Quality of Life question naire ( RAQoL ) . Dominant and non-dominant h and grip strengths ( HS ) were measured . Disease activity was determined by disease activity score ( DAS 28 ) . We evaluated the difference in the above parameters between baseline and 6 weeks by Wilcoxon paired t test . The study was completed with 47 patients ( isotonics n = 23 ; isometrics n = 24 ) . VAS , DHI , NHPT , and RAQoL scores significantly improved in both groups by the end of 6th week compared to the baseline scores of the study ( for isotonics p = 0.036 , p = 0.002 ; p = 0.0001 , p = 0.003 ; for isometrics p = 0.021 , p = 0.002 , p = 0.005 , p = 0.01 , respectively ) . DAS 28 scores decreased in both exercise groups ( p = 0.002 ; p = 0.0001 , respectively ) , while isometrics showed a significant increase in dominant HS ( p = 0.029 ) , and isotonics showed a significant increase in non-dominant HS ( p = 0.013 ) . This study showed that isometric and isotonic h and exercises decrease pain and disease activity and improve h and functions , dexterity and quality of life as well as mildly increasing muscle strength in patients diagnosed as RA OBJECTIVE To study the short-term effects of physical therapy ( ice massage or wax packs , thermal baths , and faradic h and baths ) and exercise therapy on the rheumatoid h and . METHODS The effect of individual physical therapy and exercise therapy programs was evaluated in 50 r and omly selected rheumatoid arthritis in patients ( 38 women and 12 men ) . Mean patient age ( + /- SD ) was 47.94 + /- 11.22 years , and mean disease duration was 5.04 + /- 4.80 years . The control group consisted of 50 r and omly selected rheumatoid arthritis out patients ( 37 women and 13 men ; mean age 48.46 + /- 10.65 years , mean duration of disease 5.23 + /- 4.89 years ) who at the time of the investigation were not receiving any physical or exercise therapy . The clinical indices used for evaluation of inflammation included erythrocyte sedimentation rate ( ESR ) , pain intensity , proximal interphalangeal ( PIP ) joint size , and Ritchie articular index . H and grip strength , palmar tip-to-tip and key pinch finger strength , finger range of motion , and activities of daily living ( ADL ) were the parameters used to assess the functional h and status . The study was single-blinded and of 3 weeks duration . RESULTS In the physical therapy treated group , there was an improvement for most of the observed indices from baseline parameters that achieved statistical significance ( P < 0.01 and P < 0.005 ) after the 3-week study period . ESR and PIP joint size improved clinical ly but failed to reach statistical significance . Patients had a more significant improvement in h and pain , joint tenderness , and ADL score ( P < 0.005 ) than in range of motion ( P < 0.01 ) . All parameters in the control group slightly deteriorated over the study period . CONCLUSION At least in the short term , physical and , particularly , exercise therapy produce a favorable improvement in the functional status of the rheumatoid h and |
13,993 | 18,843,621 | There is one high quality trial comparing the different alternating pressure devices for pressure ulcer prevention which suggests that alternating pressure mattresses may be more cost effective than alternating pressure overlays .
A study of Accident & Emergency trolley overlays did not identify a reduction in pressure ulcer incidence .
There are tentative indications that foot waffle heel elevators , a particular low air loss hydrotherapy mattress and two types of operating theatre overlays are harmful .
The relative merits of higher-tech constant low pressure and alternating pressure for prevention are unclear but alternating pressure mattresses may be more cost effective than alternating pressure overlays .
Medical grade sheepskins are associated with a decrease in pressure ulcer development . | BACKGROUND Pressure ulcers ( also known as bedsores , pressure sores , decubitus ulcers ) are areas of localised damage to the skin and underlying tissue due to pressure , shear or friction .
They are common in the elderly and immobile and costly in financial and human terms .
Pressure-relieving beds , mattresses and seat cushions are widely used as aids to prevention in both institutional and non-institutional setting s. OBJECTIVES This systematic review seeks to answer the following questions : ( 1 ) to what extent do pressure-relieving cushions , beds , mattress overlays and mattress replacements reduce the incidence of pressure ulcers compared with st and ard support surfaces?(2 ) how effective are different pressure-relieving surfaces in preventing pressure ulcers , compared to one another ? | on admission to hospital and a further 22 % subsequently developed them at some time during their stay . The average length of time the patients suffered from sores was three-fifths of their total length of stay and ranged from one day to more than six months . Contrary to popular opinion , they were not always a terminal event ( 31 % of these patients were eventually discharged ) , but even in those patients who died the average duration of the sores before death was 3.1 weeks . In a small work study conducted in the geriatric wards ( to be published ) the average nursing-time per patient was shown to be increased by 50 % in patients with pressure sores compared with that of equally ill patients without sores . A large amount of this STUDY OBJECTIVES We hypothesized that continuous , automatic turning utilizing a patient-friendly , low air loss surface would reduce the incidence of early ICU pneumonia in selected groups of critically ill medical patients . DESIGN Prospect i ve , r and omized , controlled clinical trial . SETTING Medical ICU of a large community teaching hospital . PATIENTS One hundred twenty-four critically ill new admissions to the medical ICU at Charity Hospital in New Orleans . INTERVENTIONS Patients were prospect ively r and omized within one of five diagnosis-related groups (DRG)--sepsis ( SEPSIS ) , obstructive airways disease ( OAD ) , metabolic coma , drug overdose , and stroke -- to either routine turning on a st and ard ICU bed or to continuous turning on an oscillating air-flotation bed for a total of five days . MEASUREMENTS AND RESULTS Patients were monitored daily during the treatment period for the development of pneumonia . The incidence of pneumonia during the first five ICU days was 22 percent in patients r and omized to the st and ard ICU bed vs 9 percent for the oscillating bed ( p = 0.05 ) . This treatment effect was greatest in the SEPSIS DRG ( 23 percent vs 3 percent , p = 0.04 ) . Continuous automatic oscillation did not significantly change the number of days of required mechanical ventilation , ICU stay , hospital stay , or hospital mortality overall or within any of the DRGs . CONCLUSIONS We conclude that air-supported automated turning during the first five ICU days reduces the incidence of early ICU pneumonia in selected DRGs ; however , this form of automated turning does not reduce other measured clinical outcome parameters A comparison of pressure reducing properties of alternating air , static air , and water mattress overlays was conducted with 57 patients in a surgical intensive care unit . Sacral and heel pressures in both recumbent and semi-Fowler 's positions were tested for each surface using a repeated measures design . Mean pressures for the alternating air mattress were significantly higher than pressures with other surfaces , regardless of position or site . There were significant main effects for position and site , with higher pressures in the semi-Fowler 's position and at the sacral site . A significant interaction between surface , site , and position was found . Pressure sores developed in eight patients , but the incidence was not significantly different across groups . A pressure measuring device constructed from available clinical material s proved to be both sensitive and reliable . The findings suggest alternating air overlays should be avoided , and that positioning and periodic position change to reduce sacral pressures for patients requiring prolonged upper body elevation is important OBJECTIVE To estimate the effectiveness of a new high-performance Australian medical sheepskin ( meeting Australian St and ard 4480.1 - 1998 ) in preventing pressure ulcers in a general hospital population at low to moderate risk of these ulcers . DESIGN Open-label r and omised controlled clinical trial . SETTING A large metropolitan teaching hospital in Melbourne , Victoria , in 2000 . PARTICIPANTS 441 patients aged over 18 years admitted between 12 June and 30 November 2000 , with expected length of stay over 2 days and assessed as at low to moderate risk of developing pressure ulcers . INTERVENTION Patients were r and omly allocated to receive a sheepskin mattress overlay for the duration of their hospital stay ( 218 patients ) or usual treatment , as determined by ward staff ( referent group , 223 patients ) . MAIN OUTCOME MEASURES Incidence rate and cumulative incidence of pressure ulcers , assessed daily throughout hospital stay . RESULTS 58 patients developed pressure ulcers ( sheepskin group , 21 ; referent group , 37 ) . Cumulative incidence risk was 9.6 % in the sheepskin group ( 95 % CI , 6.1%-14.3 % ) versus 16.6 % in the referent group ( 95 % CI , 12.0%-22.1 % ) . Patients in the sheepskin group developed new pressure ulcers at a rate less than half that of referent patients ( rate ratio , 0.42 ; 95 % CI , 0.26 - 0.67 ) . CONCLUSIONS The Australian Medical Sheepskin is effective in reducing the incidence of pressure ulcers in general hospital in patients at low to moderate risk of these ulcers There is limited research related to pressure ulcers in the ICU patient population and even less has focused on patients who have undergone cardiovascular surgery and IABP support . The objective of this article was to determine the incidence of pressure ulcers in the postoperative CVS patient with IABP support and to determine if LAL therapy was more effective in the prevention of pressure ulcers in this patient population . In a quasiexperimental design , a convenience sample of 36 adults was used . Patients who were placed on IABP support the day of surgery were enrolled into the study within 24 hours of admission to the cardiovascular recovery room . Data collection was daily for 4 days and continued if the patient developed a pressure ulcer . Final measurements were obtained on the day of hospital discharge . Instruments used were demographic data form , APACHE II , Patient Identification for Rotation Therapy , and the Braden Scale . The most common surgical patient in this pilot underwent aortocoronary bypass with IABP support . Pressure ulcers developed in 9 of 36 ( 25 % ) patients for a total of 17 ulcers . Patients who developed pressure ulcers were generally older , had a history of cerebrovascular disease , renal insufficiency , a higher APACHE II score , and Braden score of 9 on POD 1 . In addition , these patients generally had a lower hemoglobin level , higher serum creatinine level , and an altered level of consciousness on POD 1 . The results suggest that LAL therapy does make a difference in the prevention of pressure ulcers in the aortocoronary bypass patient with IABP support Intensive care wards have a high incidence of pressure sores . This trial , in an eight-bed unit , aim ed to compare the cost-effectiveness of constant-low-pressure and alternating-pressure support systems for preventing pressure sores . Patients without sores with a Norton risk score of < 13 were allocated to either alternating- or constant-low-pressure supports according to their hospital number . The cheapest supports were used initially , and changed for more sophisticated types if the patient 's pressure areas deteriorated . None of the 23 patients using low-cost alternating-pressure supports developed open sores and only one had to be transferred to a more sophisticated mattress because of persistent erythema . Eleven out of 20 patients on constant-low-pressure mattresses or overlays developed either persistent erythema ( three ) or sores ( eight ) . Ten were transferred to more expensive support systems . The mean cost of supports per patient in the alternating-pressure group was 44.50 pounds and in the constant-low-pressure group 86.20 pounds Pressure sores are a problem , especially in elderly patients . Our study was design ed to determine the effectiveness in pressure-sore prevention of a new interface-pressure decreasing mattress . In a prospect i ve r and omised controlled clinical trial we tested the Comfortex DeCube mattress ( Comfortex , Winona , USA ) against our st and ard hospital mattress in 44 patients with femoral-neck fracture and concomitant high pressure-sore risk score . In addition both groups were treated according to the Dutch consensus protocol for the prevention of pressure sores . On admission and 1 and 2 weeks after admission , pressure sores were grade d. The two groups were similar in patient characteristics and pressure-sore risk factors . At 1 week , 25 % of the patients nursed on the DeCube mattress and 64 % of the patients nursed on the st and ard mattress had clinical ly relevant pressure sores ( grade 2 or more ) . At 2 weeks the figures were 24 % and 68 % , respectively . The maximum score over the several body regions of the pressure-sore grading , measured on a 5-point sale , was significantly different in favour of the DeCube mattress at 1 week ( p = 0.0043 ) and 2 weeks ( p = 0.0067 ) postoperatively . We show that the occurrence of pressure sores and their severity can be significantly reduced when patients at risk are nursed on an interface-pressure decreasing mattress This study had three aims : to investigate if visco-elastic foam mattresses are more effective than st and ard hospital mattresses in reducing the incidence of pressure ulcers in patients with hip fractures ; to compare pressure ulcer grade and location and documented nursing prevention and treatment interventions in patients using the two types of mattresses ; to identify possible predictors of pressure ulcer development . Using a prospect i ve r and omised controlled trial design 101 patients ( mean age : 84 years ) were r and omly allocated either a visco-elastic foam mattress or a st and ard mattress . There was no significant difference in the incidence of pressure ulcers between the two groups , but patients on st and ard mattresses tended to develop more severe pressure ulcers . Furthermore , according to the documentation , patients with grade I pressure ulcers who were allocated a st and ard mattress received more preventive interventions , which may have reduced the differences in outcomes between the two groups . The research ers concluded that the results support the use of the test mattress . Significant predictors of pressure ulcer development were long waiting times for surgery and low haemoglobin levels at hospital admission The Pegasus Airwave mattress has been used for many years in the Eastbourne NHS Trust and has proven its efficiency in the prevention of pressure sores . Pegasus has now produced a new , improved , model : the Cairwave Therapy System . This article looks at criteria that may be used to determine whether the new model is suitable for patient care . The evaluation took the form of a r and omized controlled study in which 12 mattresses were r and omly allocated to patients --six Airwave mattresses and six Cairwave Therapy Systems -- over a 4-month period . The results of the evaluation showed that patients found the mattress comfortable . An encompassing cover reduced the risk of cross-infection , rehabilitation was supported by the firm edges of the bed and patient movement was easier due to the soft cover . During the trial all patients remained free from pressure sores & NA ; In a r and omized clinical trial , 187 adult patients with chronic neurologic conditions who were at a high risk of developing pressure sores were assigned for 3 months to either an alternating air ( AA ) mattress overlay or a silicore ( S ) mattress overlay . Costs associated with each overlay were calculated and compared by adding depreciation and yearly expenses related to maintenance , operation , and repair for 148 patients who completed the trial . Acceptability was measured by question naires and interviews involving 45 of the patients ’ primary nurses and a sample of 40 patients ( 20 from each overlay group ) . The annual cost of the AA overlay was 54 % more than that of the S overlay . Although most nurses ( more than 74 % ) believed that both overlays helped prevent pressure sores and deter their progression , many ( more than 56 % ) would not recommend either type to other facilities or to patients at home due to specific negative features . Implication s for manufacturers , investigators , clinicians , and administrators are identified Specialised beds which are design ed to prevent unacceptably high levels of pressure loads on skin surfaces are frequently used in the management of patients with , or at risk of developing , pressure sores . This study compares the intersurface pressure on ' at risk ' body sites of six subjects on a new design of water bed with those obtained from resting on a King 's Fund bed . The findings show flotation on the water bed offers more effective support to body tissue than that provided by the King 's Fund bed This experimental study was design ed to identify the etiology of pressure ulcers in a surgical sample and to evaluate a special OR mattress overlay in preventing pressure ulcer development . Surgical patients ( N = 413 ) were r and omized to receive " usual perioperative care " or the new mattress overlay . Over six postoperative days , 89 patients ( 21.5 % ) developed pressure ulcers , primarily stage I. Only 2 % developed stage II or IV ulcers . Patients with ulcers were statistically older , had diabetes , were smaller in body mass , had lower Braden Scale scores on admission , and used the new mattress overlay ( P < .02 ) . Pressure ulcers that presented as " burns " or ecchymosis did not deteriorate to stage III or IV ulcers during the study . The mattress overlay was not effective in preventing pressure ulcer development Abstract Objective To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital . Design Cost effectiveness analysis carried out alongside the pressure relieving support surfaces ( PRESSURE ) trial ; a multicentre UK based pragmatic r and omised controlled trial . Setting 11 hospitals in six UK NHS trusts . Participants Intention to treat population comprising 1971 participants . Main outcome measures Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital . Results Alternating pressure mattresses were associated with lower overall costs ( £ 283.6 per patient on average , 95 % confidence interval - £ 377.59 to £ 976.79 ) mainly due to reduced length of stay in hospital , and greater benefits ( a delay in time to ulceration of 10.64 days on average , - 24.40 to 3.09 ) . The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant ; however , a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80 % probability of being cost saving . Conclusion Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays OBJECTIVE To investigate the relation between pressure ulcer incidence and buttock-wheelchair seat cushion interface pressure measurements . DESIGN Secondary analysis of data from a r and omized clinical trial . SETTING Skilled nursing facility . PATIENTS Thirty-two elderly patients ( age , > or = 65 yr ) , with Braden score < or = 18 and Braden mobility and activity subscale score < or = 5 , who used wheelchairs > or = 6 hr/d , were free of existing sitting-induced pressure ulcers , and weighed < or = 250 lb . INTERVENTIONS Generic foam seat cushion or pressure-reducing seat cushion . MAIN OUTCOME MEASURES The incidence of sitting-induced pressure ulcers over a 1- to 12-month period was compared with pressure measured between patients ' buttocks and wheelchair seat cushions . A flexible pad with a 15 x 15 pressure sensor array was used to measure interface pressure . RESULTS Interface pressure measured on wheelchair seat cushions was higher ( p < or = .01 for both peak pressure and average of highest 4 pressures ) for patients who developed sitting-acquired pressure ulcers compared with those patients who did not . CONCLUSIONS Results indicated that higher interface pressure measurements are associated with a higher incidence of sitting-acquired pressure ulcers for high-risk elderly people who use wheelchairs Thirty-two chronic neurologic patients between 19 and 60 years of age were r and omly assigned , for a period of three months , to either an alternating air mattress or a silicore mattress to test the preventive qualities of special mattresses in the occurrence of decubitus ulcers . The two groups were comparable on the variables of age , weight , diagnoses , history of disease process , history of being wheelchair bound , history of previous pressures , and mean scores on Norton 's scale of risk , which is based on the subject 's physical condition , mental alertness , ambulation , mobility and incontinence . No significant differences were observed in the preventive qualities of the two types of special mattresses in terms of the incidence , location , severity , or healing duration of the subjects ' decubitus ulcers . Improved studies of common special mattresses are suggested Patients with chronic neurological diseases who were at high risk of decubitus ulcers were r and omly assigned to alternating air on silicore mattress overlays for a period of 3 months . Of 148 subjects who completed the trial , more than 50 % in each group developed one or more ulcers . No statistically significant differences between groups were found in the incidence , severity , healing duration or the location of the ulcers ; with the exception of a significant difference ( p less than 0.001 ) in the categorical location of the trochanters This paper details the follow up clinical evaluation of a pressure reducing foam mattress ( PRFM ) three years after a r and omised controlled trial . The PRFMs involved in the 1993 r and omised controlled trial were used constantly for three years and recalled in 1996 . In the original trial the control group had consisted of 18 st and ard NHS mattresses . In 1996 none of these mattresses were still in use which made it impossible to replicate the 1993 r and omised controlled trial . Instead a clinical evaluation using the 1993 methods was carried out using the PRFMs only . Recruitment to the evaluation proved difficult because changes in clinical practice between the two studies had result ed in shorter lengths of stay in hospital for the target population . Comparison of the two outcome measures namely pressure sore incidence and the subjects ' perception of comfort showed no statistically significant change between 1993 and 1996 . With the exception of two damaged mattress covers all of the original foam components and covers remained in working order in 1996 . During the time between the two studies , a pressure sore prevention programme was implemented within the research area . This programme has result ed in a year by year drop in the Directorate incidence rate . It is therefore not possible to attribute the low pressure sore incidence rate to the PRFMs alone . The results obtained suggest that the PRFMs appear to be providing a similar level of performance after three years of use By means of a scientific method , st and ard hospital mattresses were evaluated for pressure-relieving properties and patient comfort . Vendors ' written material s and product demonstrations led to the initial selection of seven mattresses . On the basis of findings from a survey of staff nurses and environmental services and pressure readings obtained with three healthy volunteers , three mattresses were selected for intensive evaluation . Eighteen mattresses ( six of each type ) were placed in six clinical care units ; at 2-week intervals , interface pressure readings ( occipital , sacral , and heel ) were performed on patients by means of a computerized measurement system . Caregiver and patient question naires ( n = 100 ) were analyzed for clinical significance and patients ' responses . We conclude that there are no significant differences among the three mattresses tested in pressure-reducing capabilities , nursing functions , or patient comfort AIMS AND OBJECTIVES In this experimental study , a 4-cm thermoactive viscoelastic foam overlay and a heating source on the operating room table was compared with the st and ard operating room table with a heating source for the effect on the postoperative pressure ulcer incidence in cardiac surgery patients . BACKGROUND Pressure ulcer incidence in the cardiac surgery population is reported to be up to 29.5 % . The prolonged compressive forces from lying on the operating room table are one source of pressure ulcer development in this population . Pressure-reducing devices on the operating room (OR)-table should reduce the patients ' interface pressure and thus the hazard of skin breakdown . METHODS A r and omized controlled trial was performed to test the effect of a 4-cm thermoactive viscoelastic foam overlay with a water-filled warming mattress on the OR-table ( test OR-table ) compared with the st and ard OR-table ( a water-filled warming mattress , no pressure-reducing device ) on the postoperative pressure ulcer incidence in cardiac surgery patients . INSTRUMENTS The pressure ulcer classification system of the European Pressure Ulcer Advisory Panel ( EPUAP ) was used for pressure ulcer grading . RESULTS The results show that patients lying on the 4-cm thermoactive viscoelastic foam overlay suffer slightly more pressure ulcer ( 17.6 % ) than patients on the st and ard OR-table without the foam overlay ( 11.1 % ) . Because of the clinical relevance of the results , the r and omized controlled trial was terminated after 175 patients at the interim analysis although the power calculation stated 350 patients . CONCLUSIONS The combination of a 4-cm viscoelastic foam overlay and a warming source can not be recommended for pressure ulcer prevention on the operating room table . RELEVANCE TO CLINICAL PRACTICE Foam overlays are used to prevent pressure ulcers in patients . It is necessary to use such devices according to patient safety and use of re sources This r and omised controlled trial of two dry-flotation pressure-reducing surfaces evaluates pressure sore incidence , patient comfort and the appropriate use of equipment in 100 orthopaedic patients . The trial involved five full Roho mattresses , five Sofflex mattresses and 10 Roho Quatro cushions to be used to complement the beds . Given the low rate of pressure sore incidence in this high-risk group it is not possible to determine whether there is any difference in effectiveness between the two mattresses . Both appear to provide similar levels of comfort , with the majority of patients finding them either comfortable or very comfortable . The initial setting of the equipment was , however , unsatisfactory Abstract Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers , healing of existing pressure ulcers , and patient acceptability . Design Pragmatic , open , multicentre , r and omised controlled trial . Setting 11 hospitals in six NHS trusts . Participants 1972 people admitted to hospital as acute or elective patients . Interventions Participants were r and omised to an alternating pressure mattress ( n = 982 ) or an alternating pressure overlay ( n = 990 ) . Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse ; time to development of new pressure ulcers ; proportions of participants developing a new ulcer within 30 days ; healing of existing pressure ulcers ; and patient acceptability . Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse ( 10.7 % overlay patients , 10.3 % mattress patients ; difference 0.4 % , 95 % confidence interval - 2.3 % to 3.1 % , P = 0.75 ) . More overlay patients requested change owing to dissatisfaction ( 23.3 % ) than mattress patients ( 18.9 % , P = 0.02 ) . Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer . Trial registration IS RCT N This paper summarizes the results of the trial of the Beaufort Bead Bed system design ed to reduce the incidence and severity of pressure sores . Elderly orthopaedic admissions were allocated alternately to the Beaufort system and to the usual trolley , table and bed surfaces , and followed from admission to hospital until separation . The incidence of pressure sores was 15.6 % in the 32 ' trial ' patients , which was significantly less than the 48.8 % in the 43 ' control ' patients , as was the mean maximum diameter of the pressure sores incurred : 6.4 mm for the ' trials ' as against 29.5 mm for the ' controls ' . In particular the trial group were free from pressure lesions to the heel , which affected 32.6 % of the control group . The groups were well matched on a variety of criteria on admission , and we conclude that the Beaufort system successfully reduces the incidence and severity of pressure sores for elderly orthopaedic patients . The system -- renamed recently the ' Neumark-Macclesfield Support System'--is now in regular and satisfactory use Because critical care nurses recognize that many of their patients are at risk for pressure ulcer development , they provide them with support surfaces that can reduce this risk . Few reported studies , however , are available to help these nurses choose these surfaces wisely . This project was a new-product evaluation that compared the clinical effectiveness of three types of support surfaces : two dynamic mattress replacement surfaces and a static foam mattress replacement . Members of a convenience sample of 110 patients admitted to a surgical intensive care unit each used one of the three support surfaces . When each patient was placed on one of the three surfaces , the evaluators rated likelihood of pressure ulcer development ( Braden Scale score ) and assessed the skin for pressure ulcers . The evaluators repeated the Braden Scale score weekly and the skin assessment three times each week . Nine patients ( 8 % ) , three patients on each support surface , acquired pressure ulcers . The log-rank test did not find a statistically significant difference between the three types of support surfaces with respect to the risk of pressure ulcer development . Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer , the averaged total Braden Scale score , and the averaged score for the sensory perception subscale of the Braden Scale . Although these three surfaces were comparable in effectiveness , they were not comparable in cost . Both dynamic mattress replacement surfaces cost approximately $ 2000 each , whereas the cost of the static foam mattress replacement was only $ 240 each . The results of this product evaluation should encourage other nurses to evaluate patient care products carefully before making recommendations OBJECTIVES Despite the diversity of wheelchair cushions currently in clinical use , pressure on bony prominences continues to be a major problem for wheelchair-bound patients , and the incidence of pressure ulcers remains high . No static surface has been reported to reduce resting pressure under the ischial tuberosities to below that of capillary pressure , which may well be the threshold for inducing tissue damage . An entirely new form of seating was design ed to decrease absolute pressure using a prosthetic fitting technique analogous to a below-the-knee prosthesis . DESIGN A repeated measures r and omized design was used to test differences between the experimental ( TCS ) and three other st and ard cushions . SETTING A Veterans Medical Center outpatient service . PATIENTS Wheelchair-bound volunteer subjects , n = 47 , were selected who weighed more than 60 kg . MAIN OUTCOME MEASURES Pressures were measured by a st and ard air pressure pad and also by a computer-linked array of pressure transducers . The grid was st and ardized and used to generate topographic maps for each site over time . These data were used to measure the seating interface pressures . RESULTS There was a significant main effect of cushion over site , F = 131 for left ischial tuberosity . Pressure were lowest while patients sat on the experimental seat and differences were significant at all time points . Using 1psi as presumed capillary pressure , frequency of success at achieving this pressure threshold was greatest for the experimental seat , p < .001 . This difference persisted throughout the 30 minutes of testing . CONCLUSIONS A computerized pressure grid was developed that allowed evaluation of anatomically localized pressures . The prosthetically design ed TCS displays lower seating pressures than any other cushion tested . Consistent and sustained pressures were below the postulated threshold for tissue damage OBJECTIVE To compare the effectiveness of a high-specification foam mattress ( control ) with a high-tech ( Duo2 , Hill Rom ) alternating/continuous low-pressure mattress ( treatment ) in the prevention of pressure ulceration . The study also evaluated if there is a difference in performance between the two working modalities ( alternating and continuous low pressure ) of the high-tech mattress in a comparable sample of patients . METHOD Thirty-three patients were observed for two weeks in the control group . In the treatment group , 86 patients were r and omised to receive alternating low pressure and 84 continuous low pressure . Incidence of pressure ulcers in both arms was recorded . Student 's t-test was used to compare all Braden scores , and the chi-square test and Fisher 's exact test to evaluate differences between groups . RESULTS There was a high difference in the number of new pressure ulcers in the control group when compared with the treatment group . There was no difference in performance between the alternating and continuous low-pressure modes . However , the sample size is too small to prove or disprove a statistically significant difference between the two modalities . CONCLUSION The high-tech mattress was markedly more effective than the high-specification foam mattress in preventing the onset of pressure ulcers . Initial data suggest that the use of alternating or continuous low pressure made little or no difference to the results This study compared the sacral interface pressures obtained in four mattresses ( all supplied by the same manufacturer ) , in two positions adopted for surgical procedures , to determine the similarities and differences between them . The mattresses were all variations of the st and ard product used in operating departments . The null hypotheses were that there are no differences in interface pressures between the mattresses or between the two surgical positions , and that measurements are not influenced by subject body mass index . The measurement technology was also tested for reliability and suitability for intra-operative use . Sacral interface pressures of 25 healthy volunteers were recorded using each of the four mattresses ( order individually r and omised ) in both the supine and the Lloyd Davies positions . A pressure-sensitive mat was used and one-way analysis of variance was the main statistical approach . Statistical significance was determined by p-values of < or = 0.05 . One mattress recorded significantly lower interface pressures than the others and all pressures were influenced by body mass index . Surgical position was a significant factor , measurements in the Lloyd Davies position being 9.5 - 14.2 % higher than in the supine position . The pressure measurement technique has proved to be reliable and easy to calibrate , position and use . Indications are that it can be used safely and effectively in operating departments . These results have implication s for research ers and clinicians Pressure redistributing ( PR ) support surfaces are positioned by manufacturers against different levels of patient vulnerability to developing pressure ulcers . However , there is no agreed method through which such linkage between a patient and an appropriate support surface can be made . This lack of clarity leads to new devices being positioned in a manner not representative of their eventual use in clinical practice . Using a data hierarchy approach , three str and s of evidence ( interface pressure , a pilot national survey and a r and omized controlled trial ) are presented to illustrate , and support , the repositioning of the Viaclin dynamic mattress overlay ( formerly the Pegasus Overture ) from use with medium-risk patients to use with higher-risk patients . The need for amendment is seen most strikingly in the two clinical studies featured in this article , during which 87 % of all patients nursed on the Viaclin dynamic mattress overlay were at high- to very high-risk of developing ulcers Underst and ing the efficacy of patient support surfaces is essential if pressure sore management is to be both efficient and effective . However , laboratory and clinical studies in this area are fraught with well recognized problems . This investigation reports a combination of laboratory , r and omized controlled trial ( efficacy data ) and measures of effectiveness to illustrate the beneficial role of a new dynamic integrated mattress and seat cushion system : the Pegasus Trinova . Successful prevention of sores among a vulnerable patient population , along with positive comments regarding the system 's comfort and ' user-friendliness ' are supported by laboratory measures of interface pressure to provide a hierarchy of data . Such an approach may present one solution to the lack of timeliness of most mattress clinical trials , thus allowing decisions regarding new support surfaces to be made upon the basis of evidence , not on anecdote or solely upon marketing cl aims This study determines the effectiveness of a new low-unit-cost support system in patients at very high risk of developing pressure sores . In a prospect i ve r and omised controlled trial , a low-pressure inflatable mattress and cushion system ( Repose ) was compared to a dynamic support mattress ( Nimbus II ) used in conjunction with an alternating-pressure cushion ( Alpha TranCell ) in 80 patients with fractured neck of femur and high scores on a pressure sore risk assessment scale . All patients received best st and ard care , including turning at regular intervals . Skin condition was assessed in 17 locations on admission , preoperatively , and seven and 14 days postoperatively . No difference was found between the groups in skin condition or the occurrence and severity of pressure sores at any time point The aim of this investigation was to determine which positions result ed in the lowest pressures to the skin of persons lying in bed . Pressures were recorded in 10 different lying positions on 2 mattresses in 62 healthy volunteers . The study revealed that the 30 degrees semi-Fowler position and the prone position result ed in the lowest interface pressures . The 30 degrees laterally inclined position had lower pressure readings than the 90 degrees side lying position ; 90 degrees side lying position gives the highest pressure readings and thus should be avoided . A Tempur polyethylene-urethane mattress reduces interface pressures by 20 to 30 % in comparison to a st and ard hospital mattress ( 12-cm-thick cold foam ) Most st and ard hospital beds are flat based with a pull-out backrest , result ing in a tendency for the patient to slide down the bed . This study aim ed to compare the outcome for patients at high risk of developing pressure ulcers nursed on either this type of bed or an electrically operated , multi-sectioned profiling bed . A total of 100 patients were r and omly assigned either to the profiling bed with a pressure-reducing foam mattress ( experimental group ) or a flat-based bed with an appropriate pressure-redistributing mattress ( control group ) for a maximum of 10 days . Risk status and pressure damage were assessed daily . Both a patient and a nurse question naire were completed . Data from 70 patients who participated in the study for five days or more were included in the analysis . Pressure ulcer incidence was 0 % in both groups . All patients ( 35 ) in the experimental group were able to maintain a sitting position compared with only 12/35 in the control group ( p = 0.0001 ) . While the question naire results suggest there were significant differences in postural control and ease of transfer between patients in the two groups , it was not possible to map this to pressure ulcer formation . Poor recruitment into the study was due to the ' blocking ' of electric beds by heavily dependent patients who did not meet the inclusion criteria , precluding a significant result in terms of pressure ulcer outcomes . This nurse-led use of the profiling beds was examined alongside the main study to investigate why they were allocated in this way A clinical evaluation of eight base foam pressure-reducing mattresses was undertaken at Addenbrooke 's NHS Trust , Cambridge . Data were collected on the medical and nutritional status , skin condition , medication , weight and Waterlow score for each patient , together with ratings on mattress comfort . At the beginning and end of the study , mattresses were assessed for interface pressures and the general condition of each mattress and its cover was evaluated OBJECTIVE To determine whether a viscoelastic polymer ( energy absorbing ) foam mattress was superior to a st and ard hospital mattress for pressure ulcer prevention and to analyze the cost-effectiveness in comparison with st and ard hospital mattresses . DESIGN Unblinded , r and omized , prospect i ve trial SETTING Elderly acute care , rehabilitation , and orthopedic wards at 3 hospitals in the United Kingdom PARTICIPANTS 1168 patients at risk of developing pressure ulcers ( Waterlow score , 15 to 20 ) , with a median age of 83 years ( 25th to 75th percentile range , 79–87 ) . INTERVENTIONS Participants were allocated to either the experimental equipment ( CONFOR-Med mattress/cushion combination ) or a st and ard mattress/cushion combination ; all were given st and ard nursing care . Pressure areas were observed daily . MAIN OUTCOME MEASURE Development of nonblanching erythema RESULTS A significant decrease in the incidence of blanching erythema ( 26.3 % to 19.9 % ; P = .004 ) and a nonsignificant decrease in the incidence of nonblanching erythema occurred in participants allocated to the experimental equipment . However , when the survival curve plots were analyzed at 7 days , both categories showed statistically significant decreases ( P = .0015 and P = .042 , respectively ) . Participants on st and ard equipment had a relative odds ratio of 1.36 ( 95 % confidence interval [ CI ] , 1.10–1.69 ) for developing blanching erythema or worse and 1.46 ( 95 % CI , 0.90–1.82 ) for developing nonblanching erythema or worse . To prevent nonblanching erythema , the number needed to treat ( NNT ) was 41.9 ( 95 % CI , −82.6–15.3 ) . To prevent any erythema ( blanching or nonblanching ) , the NNT was 11.5 ( 95 % CI , 41.6–9.3 ) . Participants with blanching or nonblanching erythema were significantly less mobile than participants with normal skin and more likely to have worsening mobility ( P < .001 ) . For participants with similar pressure ulcer status , mattress type was not associated with difference in mobility . CONCLUSIONS Regardless of prevention routine , pressure ulcers occur . In this study , the experimental equipment showed statistical significance to st and ard equipment for prevention of blanching erythema ; significance was not achieved for nonblanching erythema . Trend and survival analysis show that a larger study is required to determine whether this nonsignificant difference is genuine OBJECTIVE To determine if the use of pressure-reducing wheelchair cushions for elderly nursing home resident wheelchair users who are at high risk for developing sitting-acquired pressure ulcers would result in a lower incidence rate of pressure ulcers , a greater number of days until ulceration , and lower peak interface pressures compared with the use of convoluted foam cushions over a 12-month period . To determine the feasibility of conducting a subsequent full-scale definitive trial to evaluate the use of pressure-reducing seat cushions for elderly nursing home resident wheelchair users . DESIGN R and omized control trial SETTING 2200-bed skilled nursing facilities ( 1 suburban and 1 urban academic medical center ) PATIENTS 32 male and female at-risk nursing home residents who were wheelchair users > or = 65 years of age . Participants had Braden Scale scores < or = 18 , Braden Activity and Mobilitysubscale scores < or = 5 , no sitting surface pressure ulcers , and a daily wheelchair sitting tolerance of more than 6 hours . All met criteria for using the ETAC Twin wheelchair . INTERVENTIONS Seating evaluation with pressure-mapping and subsequent seating prescription . Subjects were assigned to either a foam ( n=17 ) or pressure-reducing cushion ( n=15 ) group and weekly assessment s of skin and pressure ulcer risk were made . MAIN OUTCOME MEASURES Incidence of pressure ulcers , days to ulceration , and peak interface pressure . MAIN RESULTS At a 95 % confidence interval , a 2-tailed analysis showed no differences between the FOAM and pressure-reducing cushion groups for pressure ulcer incidence , total days to pressure ulcer , or initial peak interface pressure . Pressure-reducing cushions were more effective in preventing sitting-acquired ( ischial ) pressure ulcers ( P<.005 ) . Higher interface pressures were associated with a higher incidence of pressure ulcers ( P<.001 ) . CONCLUSIONS A definitive r and omized control multicenter cushion trial is feasible with a sample size of 50 to 100 per study group . In the definitive trial , the definition of sitting-acquired pressure ulcers should be limited to lesions occurring over the ischial tuberosities The purchase , cleaning and maintenance of air mattresses can be an expensive part of pressure sore prevention and repositioning of patients can be time consuming and costly in terms of possible nursing injuries . The King 's Fund bed has been a friend to the health service for many years but the time has come to look for an alternative system that will support patient comfort and independence , will assist nurses in implementation of a no-lifting policy and aid pressure sore prevention policies . This article describes a study that was undertaken in two medical wards to assess the value of electrically controlled beds in relation to the prevention of pressure sores , implementation of a no-lifting policy and quality of patient care . A total of 782 patients took part in the study over a 6-month period and 726 replies were obtained from nurses . The ward had similar profiles of patients ' medical conditions and age ; they were being medically managed by the same consultants . Results showed that patients experienced greater comfort on beds with the electric facility , produced less pressure sores , mobilized easily and pressure sore prevention costs could be reduced . There is a need to be proactive in prevention of pressure sores and not reactive to a pressure sore that is already developing An innovative approach using a multiple- study research programme that incorporated five individual projects , each of which can be interpreted independently or as an integral part of the Four hundred and forty-six general , vascular and gynaecological surgical patients were recruited to a two centre , double triangular sequential r and omised controlled trial to compare the post-operative pressure sore incidence in patients positioned on the st and ard operating table mattress with those positioned on the dry visco-elastic polymer pad ( Action Products Inc. ) . Two hundred and twenty two patients were r and omised to the experimental group and 224 to the st and ard mattress . The main endpoint failure rate ( a pressure sore ) was found to be 11 % ( 22/205 ) for patients allocated to the dry visco-elastic polymer pad and 20 % ( 43/211 ) for patients allocated to the st and ard operating table mattress . There was a significant reduction in the odds of developing a pressure sore on the dry visco-elastic polymer pad as compared to the st and ard , [ symbol see text ] = 0.46 with 95 % confidence interval of ( 0.26 , 0.82 ) , P = 0.010 . The adjusted point estimates of the probability of developing a pressure sore on the dry visco-elastic polymer pad and the st and ard operating table mattress were 0.11 and 0.21 respectively OBJECTIVE To determine whether low airloss hydrotherapy reduces the incidence of new skin lesions associated with incontinence in hospitalized patients and results in more rapid healing of existing pressure sores compared with st and ard care . To assess subjectively patient and nursing satisfaction related to using low airloss hydrotherapy beds . DESIGN R and omized , prospect i ve , unblinded study . SETTING Acute and chronic hospital wards . PARTICIPANTS A total of 116 newly admitted , incontinent , hospitalized patients with and without existing pressure sores . INTERVENTION Low airloss hydrotherapy compared with treatment on hospital beds and mattresses ordered by the patient 's attending physician . MEASUREMENTS Incidence rates of new skin lesion development , e.g. , pressure sores , c and idiasis , and chemical irritation ; improvement in existing pressure sore size , volume , and status ; subjective assessment of patient and nursing satisfaction . RESULTS Possible hypothermia was identified in two patients during the first week of the study , and patient and nursing dissatisfaction with low airloss hydrotherapy remained high throughout the first months of the study . Therefore , two major modifications in the initial protocol were made : ( 1 ) increased patient temperature monitoring for hypothermia was initiated in Week 2 of the study and ( 2 ) increased staff re sources for in-service training on bed use began in Week 18 of the study . After the latter change , 58 subjects were r and omized to low airloss hydrotherapy and 58 to st and ard care . Subjects were old ( median age > or = 80 years ) , and almost all were bedbound or nonambulatory . The median ( range ) length of follow-up for subjects in the treatment group was significantly shorter than for those in the control group ( 4 ( 1 - 60 ) days versus 6 ( 1 - 62 ) days , respectively , P = .017 ) because there were more dropouts from the treatment group ( 24 ( 36 % ) of 58 versus 2 ( 3 % ) of 58 , P = .0001 ) . The major reasons dropout occurred were patient or family dissatisfaction ( 12 ( 21 % ) ) , new or worsened skin lesions thought to be related to bed use ( 4 ( 7 % ) ) , and hypothermia < 97 degrees F ( 4 ( 7 % ) ) . The total cumulative incidence of new truncal skin lesions within 9 days of enrollment was greater in the treatment than in the control group ( 48 % versus 14 % , respectively , P < 0.01 ) . Too few patients with existing pressure sores were treated for too short a period of time to assess the effect of low airloss hydrotherapy on pressure sore healing . Because only 10 patients treated on low airloss hydrotherapy beds were able to complete satisfaction surveys meaningfully , interpretation of these data is difficult . Only nine ( 21 % ) of 44 nurses subjectively reported overall satisfaction using the low airloss hydrotherapy bed . CONCLUSIONS This study shows the value of a rigorously design ed clinical ly based evaluation of a new product developed for older patients . The results of the study led to re-engineering of the prototype low airloss hydrotherapy bed as well as a change in marketing strategy . Studies of products targeted to the prevention and treatment of pressure sores in older patients should be undertaken before generalized marketing begins OBJECTIVE To compare 3 pressure-reduction devices for effectiveness in prevention of heel ulcers in moderate-risk to high-risk patients . DESIGN A prospect i ve quasi-experimental 3-group design was used . SETTING AND SUBJECTS A sample of 338 “ moderate-risk to high-risk ” adult in patients , ages 18 to 97 , at 2 medical centers in South Texas were studied . INSTRUMENTS The Braden Scale for Pressure Ulcer Risk and investigator-developed history and skin assessment tools were used . METHODS Subjects were r and omly assigned to the High-Cushion Kodel Heel Protector ( bunny boot ) , Egg Crate Heel Lift Positioner ( egg crate ) , or EHOB Foot Waffle Air Cushion ( foot waffle ) . Data are demographics , Braden scores , comorbidities , skin assessment s , lengths of stay , and costs of devices . Analyses were Chi-square , analysis of variance , and regression . RESULTS Of 240 subjects with complete data , 77 ( 32 % ) were assigned to the bunny boot group , 87 ( 36.3 % ) to the egg crate , and 76 ( 31.7 % ) to the foot waffle . Twelve ulcers developed in 240 subjects ( 5 % incidence ) . Six subjects had only 1 foot . Eleven ulcers were Stage I ( nonblanchable erythema ) , and 1 was Stage II ( partial thickness ) . Overall incidence was 3.9 % for the bunny boot , 4.6 % for the egg crate , and 6.6 % for the foot waffle ( not significantly different among groups ) . The bunny boot with pillows was most cost effective ( F[3 ] , N = 240 ) = 1.342 , p ≤ .001 ) . CONCLUSIONS In this study , the bunny boot was as effective as higher-tech devices . The results , however , were confounded by nurses adding pillows to the bunny boot group Abstract The effectiveness of a new method of preventing pressure sores , the ' Air Wave System ' ( AWS ) , has been compared with that of the conventional large-cell ripple mattress . 31 matched pairs of patients at high risk of sores developing took part in the trial . The AWS was significantly more effective in preventing and reducing the severity of pressure sores and in promoting recovery from existing sores . Moreover , it was reliable and free from mechanical breakdown during the trial Abstract Background : Pressure ulcers are a frequent complication of bed rest . The development of an efficient and low cost pressure relieving system for the prevention of bed-sores would be of considerable hospital health and economic interest . Our study was design ed to determine the effectiveness in pressure-sore prevention of an interface pressure-decreasing mattress , the Kliniplot ® mattress , used in our institution since 1978 . Methods : In a prospect i ve r and omised controlled 7-month clinical trial we compared the Kliniplot ® mattress with our st and ard hospital mattress in 1729 patients admitted to medical and surgical departments ( neurology , cardiology , oncology-haematology , neurosurgery , thoracic surgery and orthopaedic surgery ) . Two groups ( Klinipot ® mattress and st and ard hospital mattress ) were monitored for the prevention of pressure sores . The patients were evaluated on a daily basis from their admission until the eventual occurrence of a bed-sore . Patients ’ characteristics and pressure-sore risk factors were similar at the baseline in both groups . Patients presenting with a pressure sore at the time of admission were excluded . Results : Forty-two of the 1729 patients ( 2.4 % ) who entered the study developed at least one pressure sore . Twenty-one of the 657 patients ( 3.2 % ) nursed on the Kliniplot ® mattress , and 21 of the 1072 patients ( 1.9 % ) on the st and ard mattress developed bed-sores ( p = 0.154 ) . The median time for the occurrence of pressure sores was 31 days ( range 687 ) with the Kliniplot ® mattress and 18 days ( range 2 to 38 ) with the st and ard mattress ( p < 0.001 ) . The risk categories for developing bed-sores using the modified Ek ’s scale were no different at the baseline between both groups ( p = 0.764 ) . The severity of the pressure sores was no different between both groups ( p = 0.918 ) . Conclusions : Our results show that the occurrence of pressure sores is not reduced but is delayed when patients are nursed on a Kliniplot ® pressure-decreasing mattress Pressure sores are a potential complication of intensive care . Modern methods of pressure sore prevention centre around the use of pressure‐relieving devices . Few studies exist that confirm the effectiveness of these devices . This study evaluates the effectiveness of two devices , the Hill‐Rom Duo ® mattress and the KCI TheraPulse ® . High‐risk patients were r and omly assigned to receive one of two devices . We excluded those patients who had pressure sores upon admission . Those patients that did develop a pressure sore had their wound digitally photographed and grade d by two independent tissue viability nurses . Sixty‐two patients were included ( 30 TheraPulse ® , 32 Duo ® ) . Nine developed a pressure sore ( 6 Duo ® , 3 TheraPulse ® ) . No statistical differences between the two devices could be found . The longer a patient was nursed on a device , the greater the risk of pressure sore development . Despite the use of these devices , pressure sores can still develop in the Intensive Care patient population BACKGROUND studies of the effectiveness of alternating pressure air mattresses ( APAMs ) for the prevention of pressure ulcers are scarce and in conflict . OBJECTIVE evaluating whether an APAM is more or equally effective as the st and ard prevention . DESIGN r and omised controlled trial . SETTING AND SUBJECTS patients admitted to 19 surgical , internal , or geriatric wards in seven Belgian hospitals were included if they were in need of prevention of pressure ulcers . To define this need , two methods were used r and omly : the Braden Scale or the presence of non-blanchable erythema ( NBE ) . METHODS 447 patients were r and omised into either an experimental or a control group . In the experimental group , 222 patients were lying on an APAM ( Alpha-X-Cell , Huntleigh Healthcare , UK ) . In the control group , 225 patients were lying on a visco-elastic foam mattress ( Tempur , Tempur-World Inc. , USA ) in combination with turning every 4 hours . Both groups had identical sitting protocol s. RESULTS there was no significant difference in incidence of pressure ulcers ( grade 2 - 4 ) between the experimental ( 15.6 % ) and control group ( 15.3 % ) ( P = 1 ) . There were significantly more heel pressure ulcers in the control group ( P = 0.006 ) . There was an interaction effect between the risk assessment method and preventive measures for the development of all pressure ulcers and sacral pressure ulcers . CONCLUSION fewer patients developed heel pressure ulcers on an APAM . Patients identified as being in need of prevention based on the presence of NBE had a tendency to develop fewer pressure ulcers on an APAM . Patients identified as being in need of prevention , based on the Braden Scale , appeared to develop more sacral pressure ulcers on an APAM BACKGROUND Turning is considered to be an effective way of preventing pressure ulcers , however almost no research has been undertaken on this method . AIM The aim of the study was to investigate the effect of four different preventative regimes involving either frequent turning ( 2 , 3 hourly ) or the use of a pressure-reducing mattress in combination with less frequent turning ( 4 , 6 hourly ) . SUBJECTS 838 geriatric nursing home patients participated in the study . METHODS During 28 days , four different turning schemes were used : turning every 2 h on a st and ard institutional ( SI ) mattress ( n = 65 ) , turning every 3 h on a SI mattress ( n = 65 ) , turning every 4 h on a viscoelastic foam ( VE ) mattress ( n = 67 ) , and turning every 6h on a VE mattress ( n = 65 ) . The remaining patients ( n = 576 ) received st and ard preventive care . MAIN RESULTS The incidence of non-blanchable erythema ( 34.8 - 38.1 % ) was not different between the groups . The incidence of grade II and higher pressure ulcers in the 4h interval group was 3.0 % , compared with incidence figures in the other groups varying between 14.3 % and 24.1 % . CONCLUSIONS Turning every 4 h on a VE mattress result ed in a significant reduction in the number of pressure ulcer lesions and makes turning a feasible preventive method in terms of effort and cost Comparisons were made between body-support pressures obtained when 15 male paraplegics laid on waterbed , foam , and st and ard mattresses . The variables examined were mattress , bone prominence , and time . The major findings were that the waterbed , in comparisons with the other mattresses , yielded significantly lower occipital , scapular , and sacral pressures at 5 , 20 , and 35 minutes The risk of nosocomial pneumonia and atelectasis is high among critically ill immobilized patients . We hypothesized that continuous turning on the kinetic treatment table would reduce their incidence . Sixty-five critically ill patients , immobilized because of head injury or traction , were prospect ively r and omized for treatment in a conventional bed ( n = 38 ) or the kinetic treatment table ( n = 27 ) . Patients were well matched for baseline demographic and pulmonary risk factors . Patients in the conventional bed group had a higher incidence of cigarette smoking . The combined incidence of significant atelectasis or pneumonia was higher ( 66 % ) in the conventional vs. kinetic treatment table ( 33 % ) groups ( p less than .01 ) . Atelectasis , pneumonia , adult respiratory distress syndrome , requirements for ventilator treatment , for PEEP , and for an FIO2 greater than 0.50 were not significantly different , but tended to be higher in the control group . Survival and the incidence of decubitus ulcers were similar Comfort is particularly important for patients with terminal illness where the priority is to maximize quality of life . Equally important is effective pressure area care , as such patients are at high risk of developing pressure sores because of their poor general condition ( Bale and Regnard , 1995 ) . The present r and omized controlled study set in a hospice focused on the development of methodology for assessing patient comfort and quality of sleep and used this to compare two widely used , alternating air pressure mattresses ( the Nimbus II and the Pegasus Airwave ) . The Nimbus II mattress performed consistently better than the Pegasus Airwave in terms of patient comfort and quality of sleep . Features of the Nimbus II that may explain its better performance include less extreme changes in pressure , lower peak inflation pressures and the ability to automatically vary the pressure to suit the patient 's position and weight The purpose of this study was to compare the incidence of pressure ulcers in 40 newly admitted at-risk ( Braden Scale score < 18 ) skilled-nursing-facility residents , r and omly assigned to Iris 3000 ( Bio Clinic of Sunrise Medical Corp , Ontario , CA ) foam mattress overlays ( n = 20 ) or a MAXIFLOAT ( BG Industries , Northridge , CA ) foam mattress replacements ( n = 20 ) . Head-to-toe skin assessment s were done 3 times weekly for a maximum of 21 days , using Bergstrom Skin Assessment Tool . Subjects on MAXIFLOAT had fewer pressure ulcers ( chi 2[1 , N = 40 ] = 5.013 , p = .025 ) despite heavier body mass ( t[35 ] = 2.60 , p = .013 ) and more days on the surface ( t[38 ] = 2.24 , p = .03 ) . MAXIFLOAT proved to be more effective in preventing pressure ulcers in an at-risk skilled-care population and was cost-effective . Research findings on efficacy , adequate feedback from nursing staff , residents , and ancillary staff regarding issues of patient comfort , ease of use , and cost are important factors in decision-making when considering product changes Nurses caring for elderly patients often need to select support surfaces that reduce the likelihood of pressure ulcers , but there is little information about the effectiveness of different support surfaces . This r and omized trial compared two support surfaces and investigated patient attributes related to the risk of developing a pressure ulcer . Eighty-four elderly patients were nursed on a convoluted or solid foam overlay and assessed three times a week for pressure ulcers . Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer and the variables mobility and type of support surface |
13,994 | 20,675,643 | The two moderate-strength recommendations include the suggestions for early postoperative protective weight bearing and for the use of protective devices that allow for postoperative mobilization | null | null |
13,995 | 23,881,651 | There is insufficient evidence to exclude an increased risk of bleeding when NSAIDs are used in paediatric tonsillectomy .
They do however confer the benefit of a reduction in vomiting | BACKGROUND Nonsteroidal anti-inflammatory drugs ( NSAIDs ) are used for pain relief following tonsillectomy in children .
However , as they inhibit platelet aggregation and prolong bleeding time they could cause increased perioperative bleeding .
The overall risk remains unclear .
This review was originally published in 2005 and was up date d in 2010 and in 2012 .
OBJECTIVES The primary objective of this review was to assess the effects of NSAIDs on bleeding with paediatric tonsillectomy .
Our secondary outcome was to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia . | BACKGROUND In this prospect i ve r and omized double-blind study , we compared the incidence of emesis and 48-h recovery profiles after a single dose of ketorolac vs fentanyl in dexamethasone-pretreated children undergoing ambulatory adenoidectomy and laser-assisted tonsillectomy ( ADLAT ) . We evaluated the hypothesis that avoiding the use of opioids and replacing them with an equianalgesic dose of ketorolac , a nonsteroidal anti-inflammatory drug , would reduce the incidence of postoperative nausea and vomiting ( PONV ) . METHODS Fifty-seven ASA I and II children aged 1.710 years who underwent ADLAT were r and omized to receive either intravenous ketorolac ( 1 mg.kg(-1 ) ) or fentanyl ( 2 microg.kg(-1 ) ) for pain control during a st and ardized general anaesthetic with propofol infusion . The early ( postanaesthesia care unit , day surgical area ) and late postoperative courses were compared between the groups . RESULTS The incidence of PONV was low and equal in both groups . Postoperative pain scores were equal at all stages of followup . Agitation scores in the postanaesthesia care unit were significantly higher in the ketorolac group , but this had no effect on the late variables of behaviour studied . CONCLUSIONS Ketorolac showed no advantage over fentanyl in reducing the incidence of PONV in children undergoing ADLAT Investigators from Bristol described a fentanyl‐ and diclofenac‐based analgesic technique for tonsillectomy with low postoperative nausea and vomiting rates and low pain scores . This study compared the effectiveness of a modified Bristol technique with a codeine‐based regimen with respect to PONV and analgesia . Sixty‐five children , ASA 1‐2 , were r and omly assigned to either the Bristol group ( fentanyl 1–2 μg.kg−1 and diclofenac 1–2 mg.kg−1 ) or codeine group ( codeine 1.5 mg.kg−1 ) . All children received paracetamol 15 mg.kg−1 and dexamethasone 0.1 mg.kg−1 . Postoperative nausea and vomiting and pain scores were recorded hourly , and fitness for discharge was assessed at 4 h. The overall incidence of postoperative nausea and vomiting was 21 % with no difference between groups ( Bristol group 8/30 , codeine group 5/32 , p = 0.29 ) . Children in the Bristol group required analgesia earlier than those in the codeine group ( p < 0.005 ) , but maximum pain scores were not different ( Bristol group median ( IQR [ range ) 4.5 ( 3‐5 [ 0‐5 ] ) , codeine group 4.0 ( 2‐5 [ 1‐5 ] ) , p = 0.15 ) . Twenty‐three per cent of children were assessed as not fit for discharge at 4 h. The codeine‐based regimen may have a small advantage over the Bristol regimen , but neither technique seems ideally suited for a day‐case service without a longer period of observation & NA ; The efficacy of ketorolac , a non‐steroidal anti‐inflammatory drug , in the management of moderate to severe pain in adults , has led us to conduct a trial of this analgesic in children following tonsillectomy . Children were r and omized to receive intramuscular ( i.m . ) ketorolac ( 1 mg/kg , EXP group , n = 45 ) or saline ( CTL group , n = 42 ) at the completion of surgery . Intravenous ( i.v . ) fentanyl ( 0.5 & mgr;g/kg/dose ) was administered in repeated doses postoperatively . Pain intensity was measured using both the Oucher and the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) to allow for comparison between self‐report and behavioral measures of pain intensity . Severity of postoperative bleeding was measured using a 4‐point rating scale . The EXP group had a significant reduction in total fentanyl dose ( mean : 35.9 & mgr;g ) compared to the CTL group ( mean : 48.3 & mgr;g , t = −2.21 , P < 0.03 ) . There was a statistically significant decrease in pre‐fentanyl CHEOPS scores in the Post‐Anesthesia Care Unit ( PACU ) in the ketorolac group ( F ( 2,30 ) = 5.34 , P < 0.01 ) , but not in the saline group ( F ( 2.24 ) = 2.46 , P > 0.05 ) . In the first hour postoperatively , the CHEOPS demonstrated significant decreases in pain intensity scores in response to opioids , in both groups . In the PACU , children were unable to provide a self‐report of pain intensity potentially due to a variety of factors ( e.g. , emergence delirium , agitation , excitement , sedation , and /or pain ) . However , during the remainder of the postoperative stay , the photographic scale of the Oucher was a more valid measure of pain intensity than the CHEOPS . There were no differences between the 2 groups in the severity of postoperative bleeding . Children in the EXP group were discharged significantly earlier ( i.e. , 30 min , t = −2.22 , P < 0.03 ) . Our data demonstrate that i.m . administration of ketorolac , at the end of surgery , significantly reduces opioid requirements and shortens length of stay without any evidence of increased bleeding . In addition , our data suggest that the patient 's altered level of consciousness and attention span may diminish the utility of self‐report measures of pain intensity in the immediate postoperative period Purpose To compare the incidence of vomiting following codeine or ketorolac for tonsillectomy in children . Methods We had planned to enrol 240 patients , aged 2–12 yr undergoing elective tonsillectomy into a r and omized , single-blind study in University Children ’s Hospital . The study was terminated , after 64 patients because interim analysis of the data by a blinded non- study scientist concluded that the patients were at undue risk of excessive perioperative bleeding . After induction of anaesthesia by inhalation with N2O/halothane or with propofol 2.5−3.5 mg · kg−1 iv , the children were administered 150 μg · kg−1 ondansetron and 50 μg · kg−1 midazolam . Maintenance of anaesthesia was with N2O and halothane in O2 . Subjects were administered either 1.5 mg · kg−1 codeine i m or 1 mg · kg−1 ketorolac iv before the commencement of surgery . Intraoperative blood loss was measured with a Baxter Medi-Vac ® Universal Critical Measurement Unit . Postoperative management of vomiting and pain was st and ardized . Vomiting was recorded for 24 hr after anaesthesia . Data were compared with ANOVA , Chi-Square analysis and Fisher Exact Test . Results Thirty-five subjects received ketorolac . Demographic data were similar . The incidence of vomiting during the postoperative period was 31 % in the codeine-group and 40 % in the ketorolac-group . Intraoperative blood losses was 1.3 ± 0.8 ml · kg−1 after codeine and 2.2 ± 1.9 ml · kg−1 after ketorolac ( mean ± SD ) P < 0.05 . Five ketorolac-treated patients had bleeding which led to unscheduled admission to hospital , P < 0.05 , Exact Test . Conclusion Preoperative ketorolac increases perioperative bleeding among children undergoing tonsillectomy without beneficial effects . RésuméObjectifComparer l’incidence des vomissements après l’analgésie au kétorolac et à la codéine chez les amygdalectomisés . MéthodesLes auteurs prévoyaient inclure 240 patients âgés de 2 à 12 ans programmés pour une amygdalectomie réglée dans cette étude aléatoire en simple aveugle . L’étude a été terminée après 64 patients après qu’une analyse intérimaire des données par un scientifique sans implication dans l’étude eût montré que les patients étaient soumis à un risque excessif de saignement postopératoire . Après l’induction de l’anesthésie à l’halothane/N2O et au propofol 2,5 - 3,5 mg · kg−1 iv , les enfants ont reçu 150 μg · kg−1 d’ondensetron et 50 μg · kg−1 de midazolam . L’anesthésie a été entretenue avec du N2O et de l’halothane en O2 . Les sujets ont ensuite reçu soit de la codéine 1,5 mg·kg−1 i m soit du kétorolac 1 mg · kg−1 iv avant la chirurgie . La perte sanguine peropératoire a été déterminée avec une dispositif de mesure Baxter Medi-Vac ® . Le traitement postopératoire des vomissements et de la douleur a été uniforme . Les vomissements ont été enregistrés pendant 24 heures après l’anesthésie . Les données ont été comparées par ANOVA , l’analyse du Chi2 et le test d’exactitude de Fisher . RésultatsTrente-cinq enfants ont reçu du kétorolac . Les données démographiques étaient identiques . L’incidence des vomissements en postopératoire a été de 31 % dans le groupe codéine et de 40 % dans le groupe kétorolac . Les pertes sanguines peropératoires ont été de 1,3 ± 0,8 ml · kg−1 après la codéine et de 2,2 ± 1,9 ml · kg−1 après le kétorolac ( moyenne ± ET ) , P < 0,05 . Cinq patients traités au kétorolac ont eu des saignements qui ont nécessité une réadmission à l’hôpital , P < 0,05 . Conclusion Le kétorolac administré en préopératoire augmente sans effets bénéfiques les saignements périopératoires chez les enfants amygdalectomisés The efficacy of benzydamine hydrochloride ( Difflam ) spray to relieve pain from postoperative tonsillectomy was assessed , but it was found that it did not relieve the symptoms after operation when compared to matching placebo 127 children scheduled for elective tonsillectomy or adenotonsillectomy were studied . Anaesthesia was induced with propofol and maintained with a volatile agent . At induction the child received either rectal diclofenac 1 mg.kg-1 with or without fentanyl 0.75 microgram.kg-1 i.v . , or intravenous tenoxicam 0.4 mg.kg-1 with or without fentanyl 0.75 microgram.kg-1 i.v . Blood loss was measured peroperatively . Nausea and vomiting scores , sedation scores and pain scores were recorded in the recovery room , at one , two , four and eight h postoperatively and at discharge . There were no significant differences in blood loss between the groups or between nausea and vomiting scores . Pain scores in the tenoxicam without fentanyl group were significantly higher in recovery ( P < 0.05 ) than the diclofenac group without fentanyl and both fentanyl groups . This group required supplemental analgesia earlier although this was not significant . The pain scores in the diclofenac with fentanyl group were significantly lower at one h and four h than the group receiving diclofenac alone ( P = 0.008 and 0.02 respectively ) BACKGROUND We investigated the effect of preincisional rectal diclofenac on pain scores and postoperative morphine requirements of children undergoing tonsillectomy after remifentanil-propofol anaesthesia in a r and omized clinical trial . METHODS Induction and maintenance of anaesthesia were with remifentanil and propofol . Forty children were r and omly assigned into two groups before incision . The diclofenac group ( n=20 ) received diclofenac suppositories ( approximately 1 mg x kg(-1 ) ) and the control group ( n=20 ) received no treatment . Following discontinuation of remifentanil , patient-controlled analgesia ( PCA ) with morphine ( a loading dose 50 micro g x kg(-1 ) , a background infusion 4 micro g x kg(-1 ) x h(-1 ) and a dem and dose 20 micro g x kg(-1 ) with 5-min intervals ) was started . We assessed pain score [ verbal analogue scales ( VAS ) , 0 - 10 ] and sedation level at 5-min intervals and recorded the total morphine consumption of the first hour in the PACU . Patients were discharged to the ward with a new PCA morphine programme ( a dem and dose 20 micro g.kg-1 with a lockout time of 30 min , for 4 h ) , and total morphine consumption was recorded . RESULTS The mean VAS score of the diclofenac group was significantly lower than the control group on arrival in the PACU ( 2.85 + /- 0.77 , 7.60 + /- 0.83 , respectively , P < 0.01 ) and it remained significantly lower in the PACU stay of the children . The mean total morphine consumption of the diclofenac group was less than the control group in the PACU ( 130.33 + /- 11.26 and 169.92 + /- 9.22 , respectively , P=0.012 ) and the ward ( 50.80 + /- 11.38 and 87.77 + /- 10.55 , respectively , P=0.021 ) . CONCLUSIONS Preemptive diclofenac given rectally reduced pain intensity and morphine requirements of children anaesthetized with remifentanil for tonsillectomy OBJECTIVES /HYPOTHESIS To identify the main risk factors associated with postoperative hemorrhage following tonsillectomy . STUDY DESIGN Prospect i ve multicenter observational study . METHODS The Surgical Instrument Surveillance Programme ( SISP ) was established in 2003 to monitor tonsil and adenoid surgery and the associated complications in all hospitals in Wales . Data were examined between April 1 , 2003 , and June 30 , 2008 , by using binary logistic regression , for risk factors that may contribute to primary ( R1 ) or secondary ( R2 ) postoperative hemorrhage of a severity sufficient to require a return to the operating theater . RESULTS A total of 17,480 procedures were included . Patients aged ≥12 years were 1.5 ( 1.0 - 2.1 ; P < .05 ) and 3 times ( 2.2 - 4.9 ; P < .0001 ) more likely to experience R1 and R2 complications , respectively . There were 2.5 times as many females as males aged ≥12 years who underwent tonsillectomy , but males were almost twice as likely to experience R1 ( 1.4 - 2.8 ) , P < .0001 , or R2 ( 1.2 - 2.5 ) , P < .001 , postoperative hemorrhage . There was a 1.9-fold increased likelihood of R1 ( 1.1 - 3.3 ) , P < .05 , with the most junior surgeon , and no relationship with R2 . All techniques that used heat had a significantly greater adjusted odds of R2 as compared with cold dissection , with odds ranging from 2.7 ( 1.5 - 4.7 ) , P < .001 , for dissection plus bipolar diathermy and ties , to 13.0 ( 5.8 - 29.1 ) , P < .0001 , with coblation when used with other techniques . No additional risk was associated with specified single-use instruments . CONCLUSIONS Patient age and sex and operative technique were the most significant factors affecting the risk and timing of serious postoperative hemorrhage , with no additional risk associated with the use of specified single-use instruments We have compared the analgesic and opioid sparing effect of three i.v . non-steroidal anti-inflammatory drugs with placebo in a r and omized , double-blind , placebo-controlled study in 80 adult patients after elective tonsillectomy . A st and ard anaesthetic was used . After induction of anaesthesia , patients received ketoprofen 100 mg , diclofenac 75 mg or ketorolac 30 mg by i.v . infusion over 30 min . Patients in the placebo group received saline . Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic . Patients in the ketoprofen group requested 32 % less opioid and patients in the diclofenac and ketorolac groups 42 % less opioid than those in the placebo group ( P < 0.05 ) . There were one , two and six patients in the placebo , diclofenac and ketorolac groups , respectively , but none in the ketoprofen group , who did not request opioid analgesia during the study ( P < 0.05 , ketorolac vs placebo and ketoprofen ) . Visual analogue pain scores were similar in all groups . Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group . The incidence of nausea was 44 - 54 % . There were no differences in the incidence of other adverse reactions . We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy Ketorolac tromethamine ( KT ) is a nonsteroidal , antiinflammatory analgesic . Its nonsedating property makes it an attractive analgesic for sleep apnea patients undergoing uvulopharyngopalatoplasty , but its antiplatelet activity makes the potential for postoperative hemorrhage a concern . A prospect i ve , r and omized , double-blind study was design ed to evaluate the bleeding risk of KT using adult tonsillectomy patients as the model . Patients were r and omized into two groups receiving Meperidine ( MP ) ( controls ) or KT for the first postoperative day . Posttonsillectomy bleeding rates of 7 % ( 3/43 ) in the MP group and 18.9 % ( 7/37 ) in the KT group were demonstrated , but this difference was not statistically significant . The number of KT doses administered had no effect on the incidence of bleeding or the number of cases requiring return to the operative suite for hemostasis . Although this study did not attain statistical significance , the trend towards increased hemorrhage with KT is worrisome . This study and other reports in the literature support the manufacturer 's warning that the use of KT is contraindicated in major surgery We have compared the effect of peritonsillar infiltration with tenoxicam 5 mg and placebo on postoperative pain after tonsillectomy . Fifty patients undergoing bilateral elective tonsillectomy under general anaesthesia were allocated r and omly to receive peritonsillar infiltration with tenoxicam 5 mg in 8 ml of normal saline ( 4 ml per tonsil ) or normal saline only , before tracheal extubation . Median time to first request for morphine ( 30 min in each group , P = 0.83 ) , cumulative morphine requirements from 0 to 2 h after surgery ( two and one doses , P = 0.50 ) , and from 2 to 24 h after surgery ( one dose in each group , P = 0.17 ) were similar . There were no significant differences between groups in VAS scores at rest or when drinking 100 ml of water at any time . The power of detecting a reduction in VAS scores of 20 mm was 90 % at the 5 % significance level OBJECTIVES The treatment of postoperative pain after uvulopalatopharyngoplasty ( UPPP ) and tonsillectomy presents a challenge . Opioids can cause sedation and respiratory depression . Nonsteroidal antiinflammatory drugs can increase postoperative bleeding . The authors have evaluated the severity of postoperative pain and the consumption of opioid in 53 adult patients undergoing either UPPP or tonsillectomy . STUDY DESIGN A prospect i ve , parallel-groups study . METHODS A general endotracheal anesthesia was used in each patient . After surgery patients received ketoprofen 1 mg/kg as an intravenous bolus , followed by a continuous infusion of 4 mg/kg during 24 hours . For rescue analgesia patient-controlled intravenous fentanyl was used . RESULTS Both UPPP and tonsillectomy are associated with intense postoperative pain . More than 40 % of the patients had high pain scores during the first 24 postoperative hours . Postoperative pain after UPPP was more severe and the difference was significant during swallowing ( P < .05 ) . The need for fentanyl in the UPPP group was twice that of the tonsillectomy group ( P < .01 ) . There was a high interindividual scatter in the patient-controlled fentanyl attempts in both groups . The patients in the UPPP group needed significantly more oxygen supply during recovery ( P = .007 ) . No serious adverse effects occurred and none of the patients experienced postoperative bleeding that required any intervention . CONCLUSION Individually tailored analgesic treatment protocol is essential for patients undergoing UPPP and tonsillectomy to ensure safe and effective pain alleviation BACKGROUND Tonsillectomy is a common pediatric surgical procedure result ing in significant postoperative pain . There is ongoing controversy as to the most satisfactory analgesic regimen . Nonsteroidal antiinflammatory drugs ( NSAIDs ) are an alternative to opioids in this setting . NSAID use in tonsillectomy has been shown to be opioid sparing in the recovery period and to have similar analgesic effects to opioids in pediatric patients . Because of their nonspecific action on the enzyme cyclo-oxygenase there is potential for increased bleeding which has led many practitioners to avoid NSAIDs completely in this patient population potentially result ing in suboptimal pain control . Our aim in this study was to assess the effect of preoperatively administered diclofenac on the blood clot strength in children undergoing ( adeno- ) tonsillectomy . METHODS Twenty patients undergoing ( adeno- ) tonsillectomy were recruited into this prospect i ve observational study . All patients received 2 mg.kg(-1 ) of diclofenac rectally immediately preoperatively . Blood was taken for thromboelastograph analysis pre-diclofenac and 1 and 4 h post-diclofenac administration . RESULTS There was a statistically significant increase in maximal clot strength ( MA ) at 1 and 4 h after diclofenac . Similarly there was a statistically significant reduction in time to initial fibrin formation ( R time ) post-diclofenac . There was no primary or secondary hemorrhage . CONCLUSIONS Diclofenac when given preoperatively does not adversely affect clot strength in the immediate postoperative period when the risk of primary hemorrhage is greatest We evaluated the effects of a single dose of diclofenac ( 75 mg ) or indomethacin ( 50 mg ) on intraoperative events and on the early recovery phase . The study was performed in a r and omised , double‐blind , placebo‐controlled fashion in 63 adult patients scheduled for elective tonsillectomy . Study infusions started intravenously immediately after the induction of general anaesthesia with thiopentone ; maintenance was with N2O/O2 and halothane . After intubation with the aid of suxamethonium , the patients breathed spontaneously via a Bain coaxial system . Perioperative events ( bleeding tendency , bleeding , need for pain medication , physical recovery ) were recorded with the aid of a question naire applied to the anaesthesia nurses and estimation of vigilance , attention , concentration , short‐term memory , and simple motor speed during recovery was with the aid of three neuropsychological tests ( thumb tapping test , digit span test and homogenic interference test ) . No significant differences between the three groups were found in systolic and diastolic arterial pressures , the results of the question naire , and those of the neuropsychological tests . The ability to keep the head elevated for at least 5 s recovered significantly later ( P < 0.05 ) and heart rate levels in the indomethacin group were significantly lower ( P < 0.001 ) than in the other two groups . No enhanced bleeding during the perioperative period was observed . Diclofenac and indomethacin in the doses used in our study have only a marginal effect on the patient 's emergence from anaesthesia BACKGROUND Pain following tonsillectomy is often intense . Nonsteroidal anti-inflammatory drugs and opioids are effective , but both can cause adverse effects . Tramadol may be a viable alternative for post-tonsillectomy pain . This study was design ed to compare the analgesic effects of ketoprofen and tramadol during the early recovery period after tonsillectomy . METHODS Forty-five ASA class I children ( 9 - 15 years ) were r and omized to receive either saline , ketoprofen ( 2 mg.kg(-1 ) ) or tramadol ( 1 mg.kg(-1 ) ) after induction of anesthesia . Upon completion of surgery , the study treatment was continued as a 6 h intravenous ( i.v . ) infusion of another dose of saline , ketoprofen ( 2 mg.kg(-1 ) ) or tramadol ( 1 mg.kg(-1 ) ) . Postoperatively , each patient received rescue analgesia with patient-controlled analgesia ( PCA ) device programmed to deliver 0.5 microg.kg(-1 ) bolus doses of fentanyl . Postoperative pain was assessed using Visual Analog Scale ( VAS ) during swallowing . Intraoperative blood loss was measured . RESULTS The total number of requests of PCA-fentanyl was significantly less in ketoprofen group compared with tramadol and placebo groups ( P = 0.035 and P = 0.049 , respectively , in pairwise comparisons ) and the VAS scores for pain were significantly lower in ketoprofen group compared with tramadol ( P = 0.044 ) or placebo groups ( P = 0.018 ) during the first six postoperative hours . Measured intraoperative blood loss was greater in ketoprofen-treated patients than in those receiving placebo ( P = 0.029 ) . CONCLUSION A dose of 4 mg.kg(-1 ) of i.v . ketoprofen provided good pain relief with moderate supplemental PCA-fentanyl requirements during the first six postoperative hours after tonsillectomy in children whereas the effects of 2 mg.kg(-1 ) of i.v . tramadol did not differ from those of placebo In a prospect i ve r and omized clinical study the incidence of post-tonsillectomy haemorrhage was studied in 832 patients receiving either acetylsalicylic acid or paracetamol as postoperative analgesic ( 423 and 409 patients , respectively ) . Of 27 patients experiencing 1 or more bleeding episodes postoperatively , 18 received acetylsalicylic acid and 9 paracetamol . No difference was found regarding the incidence of bleeding within the first 24 h but , later on , a significantly lower incidence of secondary bleeding occurred in the paracetamol group ( 0.5 % ) compared with the acetylsalicylic acid group ( 3.1 % ) . We conclude that acetylsalicylic acid is not the optimum postoperative analgesic following tonsillectomy and that other alternatives must be sought OBJECTIVE To evaluate recovery after tonsillectomy in children , and to determine the safety and efficacy of ketoprofen in pain treatment after discharge . STUDY DESIGN A prospect i ve , longitudinal study in 102 children undergoing tonsillectomy . METHODS All children underwent tonsillectomy under a same general anesthesia . At discharge , all patients were prescribed ketoprofen capsules at a dose of 3 - 5 mg(-1 ) kg(-1 ) per 24 h for postoperative pain control at home , with paracetamol or paracetamol-codeine tablets for rescue analgesia . At home , the patients recorded pain and analgesic consumption each day for the first week after surgery . At 3 weeks , patients recorded the total analgesic requirement , duration of pain , and all adverse events during recovery and return to normal daily activities . RESULTS The median of pain cessation was 9 days ( range 1 - 20 days ) and the median duration of analgesic treatment was 10 days ( 4 - 19 days ) . More than 50 % of the patients needed rescue analgesic daily during the first week after tonsillectomy . Ketoprofen combined with paracetamol or paracetamol-codeine provided sufficient analgesia for most children . However , the analgesic action of drugs was too short to achieve pain relief , which allow undisturbed sleep during the first postoperative nights . A return back to normal daily activities took place after 9 days ( 2 - 26 days ) . The influence of age for pain pattern was negligible . Five patients needed electrocautery to stop postoperative bleeding . No other serious adverse-events occurred . CONCLUSIONS The main problem after tonsillectomy is significant pain that may last 9 days or longer after surgery . Ketoprofen combined with paracetamol-codeine seems to provide a sufficient analgesia , but before ketoprofen may be recommended for children during tonsillectomy a larger study is needed to show whether or not ketoprofen increases the hemorrhage rate Nonsteroidal anti-inflammatory drugs ( NSAIDs ) have been shown to be as effective as opioid analgesia following tonsillectomy in children . Opioids are still frequently used but tonsillectomy is associated with a high incidence of vomiting . This study has attempted to assess postoperative analgesic consumption and nausea and vomiting after general anaesthesia for tonsillectomy using either paracetamol premedication , paracetamol plus a NSAID or intravenous morphine to provide postoperative analgesia . Some children required a rescue dose of morphine in the recovery room , including some who had received intravenous morphine at induction . Least supplementary morphine was required by those who had received paracetamol plus ketorolac . Postoperative nausea and vomiting was significantly less in the two groups which were not given intraoperative morphine . The number of vomiting incidents was also much less . We conclude that the preoperative administration of paracetamol alone provides satisfactory analgesia in many children but that supplementary analgesia is still required for some INTRODUCTION Tonsillectomy is frequently associated with postoperative pain of considerable duration , which is usually accompanied by the substantial consumption of both opioid and non-opioid analgesic such as NSAIDs and local anaesthetics . OBJECTIVE The aim of this study was to evaluate the efficacy between 2 % viscous lignocaine and sodium diclofenac based upon the visual analogue scores ( VASs ) , consumption of pethidine 0.5mgkg(-1 ) as the rescue drug postoperatively and time taken to resume feeding . METHODS 130 patients aged between 5 and 12 years old were r and omly allocated into 2 groups to be given either 2 % viscous lignocaine 4mgkg(-1 ) body weight topically post-tonsillectomy or sodium diclofenac 1mgkg(-1 ) per-rectal post-induction of anaesthesia . Postoperatively visual analogues score was done for 24h , the amount of pethidine given and time when the patient start taking oral feeding of clear fluid , soft diet and normal diet were documented . RESULTS There was no significant difference in the visual analogue scores in both groups , however the requirement of pethidine as the rescue drug postoperatively was significant 2h post-tonsillectomy ( p=0.023 ) in viscous lignocaine group compared to sodium diclofenac . The time taken to resume oral feeding and soft diet was also significant in viscous lignocaine group ( p=0.016 and p=0.007 ) whereas there was no significant in taking normal diet . CONCLUSION We concluded that 2 % viscous lignocaine applied topically post-tonsillectomy is comparable to sodium diclofenac per-rectal in providing analgesia and faster oral feeding BACKGROUND The analgesics used for paediatric tonsillectomy may be associated with side-effects such as sedation , respiratory depression and vomiting ( opioids ) or increased bleeding [ non-steroidal anti-inflammatory drugs ( NSAIDs ) ] . In our institution , we employ a combination of paracetamol , NSAID and opioid , although there is no published evidence of analgesic benefit from adding NSAIDs to paracetamol in children . METHODS This r and omized , double-blinded clinical study examined the analgesic effectiveness of combining paracetamol ( 20 mg kg(-1 ) ) with rofecoxib ( 0.625 mg kg(-1 ) ) , ibuprofen ( 5 mg kg(-1 ) ) or placebo as premedication for (adeno)tonsillectomy ( n=98 ) in children aged 3 - 15 yr . Intravenous fentanyl 1 - 2 microg kg(-1 ) was given intraoperatively . Regular oral paracetamol ( 15 mg kg(-1 ) , 4 hourly ) was given after operation and could be supplemented on request from the child with oral ibuprofen 5 mg kg(-1 ) or oral codeine 1 mg kg(-1 ) . The primary outcome variable was need for early supplementary analgesia ( within 2 h after surgery ) . RESULTS The addition of ibuprofen to paracetamol reduced the need for early analgesia from 72 % to 38 % of children ( difference 34 % ; 95 % confidence interval 4 - 64 % ) . The addition of rofecoxib to paracetamol did not significantly alter the need for early analgesia ( 68 vs 72 % ) . Pain scores were higher in those children who required early analgesia . There were no differences between the groups in operative blood loss or complications , total 24-h analgesic consumption , pain scores at 4 and 8 h , vomiting or antiemetic use . CONCLUSION This study provides evidence to support the combination of ibuprofen ( but not rofecoxib ) with paracetamol for perioperative analgesia in children OBJECTIVE : To evaluate the efficacy and safety of celecoxib and ketoprofen in pain management during tonsillectomy in 120 patients . STUDY DESIGN AND SETTING : The study was r and omized , double-blind , and placebo-controlled with parallel groups . Sixty minutes before anesthesia induction and 12 hours after , the patients received a 200-mg celecoxib , a 100-mg ketoprofen , or a placebo capsule . After discharge , patients were prescribed either celecoxib or ketoprofen capsules to be taken every 12 hours . RESULTS : During the first 24 hours , the need for rescue analgesic was less in the ketoprofen-group ( 5 ( 1 - 9 ) ) doses ( median ( range ) ) than in the placebogroup ( 6 ( 1 - 13 ) ) ( P = 0.021 ) , but similar to the cele-coxib-group ( 5 ( 2 - 14 ) ) . After discharge , the cessation of pain during eating occurred earlier in the celecoxib-treated patients , after 10 ( 1 - 17 ) days , than in the ketoprofen-treated patients , after 12 ( 1 - 21 ) days , ( P = 0.008 ) . One celecoxib-treated patient and 6 ketoprofen-treated patients ( P = 0.013 ) needed electrocautery to stop postoperative bleeding . CONCLUSION : Ketoprofen provided a better initial analgesic efficacy but after discharge the recovery with celecoxib was faster and the incidence of secondary hemorrhages was lower . SIGNIFICANCE : Celecoxib seems to be more effective and safe than ketoprofen for pain management after discharge in patients with tonsillectomy BACKGROUND Tonsillectomy is one of the most common pediatric procedures in the United States . An optimal perioperative pain control regimen remains a challenge . Intravenous ibuprofen administered at induction of anesthesia may be a safe and efficacious option for postoperative tonsillectomy pain . OBJECTIVES To determine whether preoperative administration of intravenous ibuprofen ( IV-ibuprofen ) can significantly decrease the number of doses of postoperative fentanyl when compared with placebo in pediatric tonsillectomy surgical patients . METHODS This was a multicenter , r and omized , double-blind placebo-controlled trial conducted at six hospitals in the United States . A total of 161 pediatric patients aged 6 - 17 years undergoing tonsillectomy were r and omized to receive either a single preoperative dose of 10 mg·kg(-1 ) IV-ibuprofen or placebo ( normal saline ) . Postoperative pain was managed with intravenous fentanyl ( 0.5 μg·kg(-1 ) ) on an as needed basis when the visual analog scale ( VAS ) was > 30 mm and deemed appropriate by recovery room nurse/physician . The primary endpoint was the number of doses and amount of postoperative fentanyl administered postoperatively for rescue analgesia . RESULTS There was a significant reduction in the number of postoperative doses and the amount of fentanyl administered after surgery in the IV-ibuprofen group compared with the placebo group ( P = 0.021 ) . There were no differences in the time to first analgesia request or the number of patients who required postoperative analgesia . There were no significant differences in the incidence of serious adverse events , surgical blood loss ( P = 0.662 ) , incidence of postoperative bleeding , or a need for surgical re-exploration between the treatment groups . CONCLUSION Administration of IV-ibuprofen , 10 mg·kg(-1 ) , significantly reduced fentanyl use in pediatric tonsillectomy patients A controlled investigation was conducted to compare the effectiveness of diclofenac and papaveretum in the prevention of pain and restlessness after tonsillectomy in children . Sixty children between 3 and 13 years of age were r and omly allocated to receive rectal diclofenac 2 mg/kg , intramuscular papaveretum 0.2 mg/kg or no medication immediately after induction of anaesthesia . Pain and appearance were assessed 1 , 3 and 6 hours postoperatively , and the following morning . The assessment s were double‐blind and performed by the same observer . No significant differences in postoperative pain were found between the groups at any time . The use of diclofenac was associated with a significantly more rapid return to calm wakefulness and had significantly less effect upon respiratory rate . Consumption of paracetamol on the day of operation was significantly less in the diclofenac group . Diclofenac may offer advantages compared to papaveretum with regard to safety and convenience for use in the treatment of pain after tonsillectomy in children OBJECTIVE To evaluate the effect of ketamine , as an adjunct to fentanyl , on postoperative analgesia and duration of Postoperative Care Unit ( PACU ) stay , in children undergoing tonsillectomy . BACKGROUND Ketamine , as an N-methyl-d-aspartate antagonist , has been recognized to have an opioid sparing effect . In addition , it does not depress respiration or affect airway tone . Hence , addition of ketamine could be potentially beneficial in children undergoing tonsillectomy , due to the high incidence of sleep apnea in these patients . METHODS In a double blinded , r and omized trial , 60 ASA status I and II children between 2 and 7 years of age , scheduled to undergo elective tonsillectomy were recruited . They were r and omly assigned to one of four groups to receive fentanyl 1 mcg·kg(-1 ) ( F1 group ) , fentanyl 2 mcg·kg(-1 ) ( F2 group ) , ketamine 0.5 mg·kg(-1 ) ( K group ) , or fentanyl 1 mcg·kg(-1 ) plus ketamine 0.5 mg·kg(-1 ) ( FK group ) pre-incision . Postoperative pain was scored on arrival to the PACU and at 30 , 60 , and 90 min thereafter . Any incidence of nausea/vomiting and time to discharge from the PACU were also recorded . RESULTS Important predictors found for postoperative pain on arrival to the recovery room are the group ( P = 0.02 ) and duration of surgery ( P = 0.02 ) . Least square means and st and ard errors of pain scores on PACU arrival were 4.87±0.69 , 3.04±0.68 , 2.10±0.68 and 2.03±0.69 for F1 , F2 , K and FK groups , respectively . On group-wise comparison adjusted for surgical time , significant difference was detected between F1 and K ( P = 0.02 ) , and F1 and FK ( P = 0.0048 ) groups . Marginal significance was detected in duration of PACU stay among groups ( P = 0.08 ) ; F2 and FK group had a shorter PACU stay than F1 ( P = 0.05 and 0.04 respectively ) . No significant difference was detected in the need for supplemental analgesia . CONCLUSION We conclude that the administration of ketamine 0.5 mg·kg(-1 ) with 1 mcg·kg(-1 ) fentanyl in children undergoing tonsillectomy may improve postoperative pain control without delaying home discharge Background : Diclofenac and paracetamol have different mechanisms and sites of action . Therefore , we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values Background : In order to establish an effective drug regimen , we compared the analgesic efficacy of oral diclofenac and high‐dose acetaminophen on pain after tonsillectomy One hundred and ninety‐eight children , aged 3 to 12 years , who were scheduled for tonsillectomy were r and omly allocated to receive either diclofenac 1.0 mg.kg−1 or papaveretum 0.2 mg.kg−1 by intramuscular injection after induction of anaesthesia . There were no significant differences between the treatment groups in operating theatre blood loss , the frequency of bleeding on the ward , or the need for operative haemostasis . However , the incidence of above average bleeding in the recovery room was significantly higher in the diclofenac group ( p < 0.05 ) . Similarly , marked restlessness in the recovery room was more frequent in the diclofenac group ( p < 0.01 ) . In both treatment groups there was an association between bleeding and restlessness during recovery so the increased bleeding in the diclofenac group may not be a direct effect OBJECTIVE To compare the analgesic efficacy of oral tramadol hydrochloride and oral diclofenac sodium for posttonsillectomy pain management . DESIGN Single-blind ( surgeon and research team members ) , prospect i ve , r and omized , controlled clinical trial . PATIENTS AND METHODS Sixty-four patients 11 years and older undergoing bipolar electrocautery tonsillectomy were r and omized to either the oral tramadol or the oral diclofenac postoperative pain group . Patients recorded pain levels twice daily for 14 days using a visual analogue scale . RESULTS Pain scores for the 14 days were not significantly different between the oral tramadol and oral diclofenac groups . There were no significant differences in the incidence of postoperative hemorrhage and hospital readmission for uncontrolled pain . CONCLUSION Oral tramadol can deliver the same analgesic efficacy as oral diclofenac for posttonsillectomy pain relief , which might be beneficial for avoiding the adverse effects of nonsteroidal anti-inflammatory drug therapy Background and objective Nonsteroidal anti-inflammatory drugs are effective analgesics but their use during tonsillectomy is controversial because of the risk of postoperative bleeding . The aim of this study was to compare the analgesic efficacy and safety of nimesulide , a preferential cyclo-oxygenase type-2 inhibitor , with ibuprofen in the treatment of pain after tonsillectomy . Study design A prospect i ve , double-blind , r and omised clinical trial . Patients and methods A total of 80 consenting generally healthy patients , aged 14–58 years , undergoing tonsillectomy were r and omly assigned to receive either nimesulide 100 mg or ibuprofen 800 mg orally 60 minutes before surgery . Subsequent doses of the same study medication were administered at 12-hour intervals for the first 7 days , and thereafter when needed . During the first 24 postoperative hours in hospital oxycodone was used for rescue analgesia , and after discharge patients were allowed to use a paracetamol-codeine combination for breakthrough pain . Recovery was recorded up to 3 weeks after surgery . Results The need for rescue analgesia during the first 24 hours was similar in the two study groups ; 0–7 doses ( mean ± SD 3.3 ± 1.7 doses ) in the nimesulide group and 0–11 doses ( 3.3 ± 2.4 doses ) in the ibuprofen group . After discharge significant differences were found between the two study groups in favour of the nimesulide-treated patients . Cessation of significant pain while swallowing occurred after 3–19 ( 10.9 ± 3.8 ) days in the nimesulide group versus 7–20 ( 12.9 ± 3.3 ) days in the ibuprofen group ( p = 0.041 ) , and return to normal daily activities occurred after 3–21 ( 10.3 ± 4.9 ) days in the nimesulide group versus after 3–19 ( 12.7 ± 4.2 ) days in the ibuprofen group ( p = 0.048 ) . At 3 weeks , six of 33 patients in the nimesulide group versus 15 of 37 patients in the ibuprofen group had pain during swallowing ( p = 0.049 ) . One patient ( 3 % ) in the nimesulide group and five patients ( 12 % ) [ p = 0.22 ] in the ibuprofen group needed electrocautery to stop postoperative bleeding . Conclusion Oral nimesulide was as effective as ibuprofen in pain management after tonsillectomy , and nimesulide improved the recovery after discharge The efficacy and tolerability of diclofenac suppositories given pre and /or post-operatively were investigated in a r and omized double-blind study on 99 patients undergoing tonsillectomy . In one group , 50 mg diclofenac was given 1 h preoperatively , followed by 50 mg directly after the operation . In another group , diclofenac 100 mg was given only immediately post-operatively . A significantly lower consumption of rescue analgesics ( paracetamol and /or pethidine ) was found in the group treated preoperatively with diclofenac and the average time until first dem and of rescue analgesics was significantly longer compared to the group given diclofenac post-operatively only . The tolerance was good and no serious bleeding complications occurred in either group . In the treatment of post-operative pain after tonsillectomy , the combination of pre and post-operative administration of diclofenac suppositories result ed in significantly lower consumption of rescue analgesics and is thus preferable to administration solely post-operatively Diclofenac sodium was assessed as an analgesic for postoperative pain following paediatric tonsillectomy in a r and omised double blind trial . In a comparison made with both a pethidine and a control group diclofenac was shown to be an effective analgesic . No significant difference in analgesic efficacy was demonstrated between the two drugs , although patients who received diclofenac tended to be less drowsy postoperatively than those who received pethidine . There were no significant differences between the two drugs in respect of time to awaken from anaesthesia or incidence of postoperative vomiting The anxiety and pain‐relieving effect of paracetamol 10 mg/kg or a combination of aminophenazone 4 mg/kg and diazepam 0.2 mg/kg suppositories was studied in 82 children after tonsillectomy in a double‐blind study . Both suppositories were studied after halothane or enflurane anaesthesia . At 30 min after administration of coded suppositories , 88–90 % of the children in various groups needed extra analgesics , and received pethidine 0.5 mg/kg i.v . Thereafter , the anxiety and pain relief was satisfactory in all groups . There was no significant difference between the effects caused by the drugs . No bleeding occurred from the operation site in any of the study groups . The results suggest that both paracetamol and a combination of aminophenazone and diazepam in the doses used here were weak analgesics for throat pain after tonsillectomy in children during the early postoperative period Objectives : We evaluated the analgesic efficacy and the opioid-sparing effect of oral rofecoxib compared with intramuscular ( IM ) ketoprofen in tonsillectomy . Methods : Seventy-seven adult patients were r and omized into 2 groups : group R ( n = 39 ) , which received a single oral preoperative dose of rofecoxib 50 mg , and group K ( n = 38 ) , which received 2 IM doses of ketoprofen 100 mg ( before surgery and after 12 hours ) . In both groups , additional IM meperidine hydrochloride 1 mg/kg was given . All patients received general anesthesia . A pain score ( visual analog scale , 0 to 100 ) was assessed both at rest and during swallowing at 30 minutes and at 4 , 8 , 12 , 16 , and 24 hours after operation . If the pain score exceeded 40 , patients were given meperidine as rescue analgesia . Results : The pain scores during rest and swallowing in group R were significantly lower ( p > .05 ) than those of group K at 4 , 8 , and 12 hours after operation . Meperidine was given as rescue medication in significantly more patients of group K ( 76 % ) than of group R ( 38 % ; p > .05 ) . Conclusions : Oral premedication with rofecoxib seems to be more effective than use of ketoprofen in decreasing postoperative pain and the need for opioid rescue medication after elective tonsillectomy . Both drugs seem to be relatively safe as far as postoperative bleeding is concerned We design ed a prospect i ve , r and omized , double-blind study to test the efficacy and safety of ibuprofen compared with acetaminophen with codeine for pediatric posttonsillectomy/adenotonsillectomy patients . Twenty-seven children , aged 6 to 16 years , were enrolled . We collected information on pain control , return to normal sleep pattern , return to normal diet , and duration for which medication was required . Coagulation profiles were measured before surgery and on postoperative day 3 . Acetaminophen with codeine was more effective in controlling pain on days 1 and 3 ( p = 0.0475 and 0.0328 , respectively ) . However , we detected no difference between the treatment groups ( p = 0.2216 ) with regard to pain control on day 5 . The ibuprofen group required medication for a longer period ( p = 0.0464 ) . We detected no statistically significant differences between groups with regard to return to normal diet ( p = 0.2346 ) and return to normal sleep pattern ( p = 0.9554 ) . The postoperative hemorrhage rate was 0 % in the acetaminophen-with-codeine group and 12.5 % in the ibuprofen group . The ibuprofen group demonstrated a mean increase in bleeding time of 2.07 minutes on the third postoperative day ( p = 0.0379 ) . The mean change in postoperative bleeding time between the two groups was statistically significant ( p = 0.0140 ) . We found no statistically significant differences in prothrombin time and partial thromboplastin time between groups . On the basis of the findings of this pilot study , we conclude that acetaminophen with codeine is safer and more efficacious than ibuprofen in the management of posttonsillectomy/adenotonsillectomy pain in children We have evaluated the safety and efficacy of ketoprofen during tonsillectomy in 106 adults receiving st and ardized anaesthesia . Forty-one patients received ketoprofen 0.5 mg kg(-1 ) at induction ( ' pre ' ketoprofen group ) and 40 patients after surgery ( ' post ' ketoprofen group ) , in both cases followed by a continuous ketoprofen infusion of 3 mg kg(-1 ) over 24 h ; 25 patients received normal saline ( placebo group ) . Oxycodone was used for rescue analgesia . Patients in the ketoprofen groups experienced less pain than those in the placebo group . There was no difference between the study groups in the proportion of patients who were given oxycodone during the first 4 h after surgery . However , during the next 20 h , significantly more patients in the placebo group ( 96 % ) received oxycodone compared with patients in the ' pre ' ketoprofen group ( 66 % ) and the ' post ' ketoprofen group ( 55 % ) ( P=0.002 ) . Patients in the placebo group received significantly more oxycodone doses than patients in the two ketoprofen groups ( P=0.001 ) . Two patients ( 5 % ) in the ' pre ' ketoprofen group and one ( 3 % ) in the ' post ' ketoprofen group had post-operative bleeding between 4 and 14 h. All three patients required electrocautery BACKGROUND Tonsillectomy is commonly performed in children , but unfortunately it is associated with intense postoperative pain . The use and optimal timing of nonsteroidal anti-inflammatory drugs ( e.g. ketoprofen ) during tonsillectomy is controversial . METHODS We evaluated the safety and efficacy of ketoprofen in 109 children , aged 3 - 16 years , during and after tonsillectomy in 1998 - 2000 . St and ardized anaesthesia was used . Forty-seven children received ketoprofen 0.5 mg.kg-1 at induction ( preketoprofen group ) and 42 children after surgery ( postketoprofen group ) , followed by continuous ketoprofen infusion of 3 mg.kg-1 over 24 h in both groups ; 20 children received normal saline ( placebo group ) . Oxycodone was used for rescue analgesia . RESULTS Pre- and postketoprofen groups did not differ in experienced pain or in opioid consumption in the first 24 h after surgery ; demonstrating that ketoprofen did not have a pre-emptive effect . Patients in the placebo group received 30 more oxycodone doses than did patients in the ketoprofen groups , but the difference was not significant ( P=0.074 ) . Two patients ( 5 ) in the postketoprofen group had postoperative bleeding at 4 h and 26 h , respectively . Both patients required electrocautery to stop bleeding . Neither the incidence nor the severity of adverse events differed between study groups . CONCLUSIONS This study demonstrates that ketoprofen did not have a preemptive effect and , at the dose used , did not perform statistically significantly better than placebo OBJECTIVE To compare the use of ibuprofen with the use of acetaminophen with codeine for posttonsillectomy management . BACKGROUND We were not satisfied with our traditional pain-management practice for tonsillectomy patients . We hoped to find a new approach for improved patient comfort and avoid scheduled , abusable drugs such as codeine . DESIGN Intervention , prospect i ve , r and omized control trial . Follow-up was 1 month . SETTING University referral center ; institutional pediatric practice , ambulatory . PATIENTS 110 children undergoing tonsillectomy with or without other procedures . Consecutive patients were offered participation . Enrollees were r and omly assigned to one of two classes and analyzed with the initial assignment . No patients withdrew for adverse effects , although 12 in group 2 used codeine and 5 of those used acetaminophen , whereas 2 in group 1 received ibuprofen . INTERVENTIONS Patients received either acetaminophen with codeine ( group 1 ) or ibuprofen ( group 2 ) for postoperative pain control . MAIN OUTCOME MEASURES The main outcomes , determined before initiation of the study , were assessment of ( 1 ) postoperative bleeding , ( 2 ) pain , ( 3 ) efficacy of relief of pain by drug , ( 4 ) nausea , ( 5 ) emesis , ( 6 ) readmission to hospital , ( 7 ) average temperature , and ( 8) highest temperature after surgery . RESULTS The only statistically significant difference is less nausea in patients receiving ibuprofen ( p = 0.0049 ) . Of note , no difference existed in postoperative bleeding , pain , or temperature control . CONCLUSIONS Ibuprofen is at least as effective as acetaminophen with codeine for postoperative pain control in children after tonsillectomy Post-tonsillectomy analgesia from ibuprofen , aspirin and placebo is compared in a double-blind study . The results are reported showing ibuprofen to have greater therapeutic benefit than placebo whereas aspirin did not . Methods of providing pain relief after tonsillectomy and the relative clinical merits of ibuprofen and aspirin are discussed Background : Tonsillectomy is a common procedure in childhood result ing in significant morbidity due to pain . The aim of this study was to evaluate the analgesic efficacy and safety of a single dose of ketorolac i.v . given before or after tonsillectomy , compared to placebo The study was design ed to compare intravenous ketorolac to rectal acetaminophen for analgesia and bleeding in pediatric patients undergoing tonsillectomy . We studied 50 patients , aged 2 - 15 yr undergoing tonsillectomy with or without adenoidectomy . In a r and omized , prospect i ve double-blind fashion , patients were assigned to receive either ketorolac ( 1 mg/kg ) or rectal acetaminophen ( 35 mg/kg ) . Bleeding was evaluated by measuring intraoperative blood loss and noting extra measures required to obtain hemostasis . Bleeding times were also measured before and during surgery . Pain was evaluated using a st and ard objective pain score for the first 3 h. Persistent pain was treated with morphine , acetaminophen , and codeine and recorded for 24 h. Blood for determination of acetaminophen levels was drawn at 20 and 40 min after the administration of study drugs . Pain scores were not significantly different between the ketorolac and acetaminophen groups . The majority of patients in both groups required additional opioid in the postoperative period . Acetaminophen levels were all less than the therapeutic range . Intraoperative bleeding times were normal in all patients , but blood loss was significantly higher in the ketorolac group ( 2.67 mL/kg ) compared to the acetaminophen group ( 1.44 mL/kg ) , P = 0.025 . Significantly more measures to achieve hemostasis were required in the ketorolac group ( P = 0.012 ) . We conclude that ketorolac is no more effective than high-dose rectal acetaminophen for analgesia in the patient undergoing tonsillectomy . Hemostasis during tonsillectomy was significantly more difficult to achieve in patients receiving ketorolac . ( Anesth Analg 1995;80:226 - 9 Summary The efficacy and tolerability of nimesulide were assessed and compared with those of paracetamol in the treatment of 35 children with pain and inflammation following adenotonsillectomy . The antipyretic and analgesic efficacy of the 2 drugs was similar , although more patients had complete remission of pain after 4 days of treatment with nimesulide . Both drugs were well tolerated , even though occasional elevation of transaminase enzymes and alkaline phosphatase was noted in the nimesulide-treated group . It is postulated that this effect may have been attributable to the volatile anaesthetics used during surgery The charts of 258 patients undergoing tonsillectomy with or without adenoidectomy between June 1991 and June 1993 were review ed . One hundred sixty-nine of these patients received ketorolac tromethamine during the perioperative period as a nonnarcotic alternative for postoperative pain management . The incidence of postoperative hemorrhage among patients who received ketorolac tromethamine was 10.1 % , compared to 2.2 % in those patients who received narcotic analgesia only . The average time to adequate oral intake and discharge was evaluated . Ketorolac appeared to moderately decrease the time to adequate oral intake . The use of ketorolac did not significantly alter the time to discharge . The increased incidence of postoperative hemorrhage in patients receiving ketorolac should be considered before this medication is used in the perioperative period . The risk/benefit ratio of ketorolac use as a postoperative analgesic may be better demonstrated in a prospect i ve study Ninety-six children received morphine 0.1 mg/kg ( n = 47 ) or ketorolac 1 mg/kg ( n = 49 ) intravenously ( IV ) in a prospect i ve , r and omized , double-blind fashion , after tonsillectomy . Recovery variables and complications were recorded while subjects were in the hospital and parent(s ) were contacted 24 h and 14 days after surgery . There were no differences in demographics , surgical management , awakening time , oxygen requirements , or time to readiness for postanesthesia care unit ( PACU ) discharge or discharge home between the two groups . Ketorolac subjects had fewer emetic episodes than morphine subjects ( median 1 vs 3 ; P = 0.006 ) and were less likely to have more than two episodes of emesis after PACU discharge ( 9/49 vs 22/47 ; P = 0.007 ) . Ketorolac subjects had more major bleeding ( bleeding requiring intervention ; 5/49 vs 0/47 , one-tailed P = 0.03 ) and more bleeding episodes ( 0.22 episodes/subject vs 0.04 episodes/subject , P < 0.05 ) in the first 24 h after surgery , but no greater overall incidence of bleeding than the morphine subjects . In children having tonsillectomy , ketorolac , compared to morphine , reduced the number of emetic episodes after PACU discharge , but did not hasten awakening , readiness for PACU discharge or discharge home , and increased the likelihood of major bleeding in the first 24 h after surgery . ( Anesth Analg 1995;81:1136 - 41 Background : Diclofenac is widely used for postoperative analgesia but the perioperative safety of this drug is controversial because of its effect on platelet aggregation , which might increase blood loss . In a prospect i ve investigator‐blinded study the effects of diclofenac and paracetamol on pain and blood loss were compared in patients undergoing tonsillectomy The efficacy of diclofenac suppositories was estimated in a two-centre , double-blind , placebo-controlled study comprising 97 patients ( 47 in the diclofenac group and 50 in the placebo group ) . The series from the two centres and patients in the two treatment groups were comparable . Immediately postoperatively , the patients received 100 mg diclofenac , followed by 50 mg in the evening and 50 mg in the morning after the operation , or placebo suppositories . The efficacy was assessed both by the patients and by the staff by marking on a visual analogue scale . Statistical analyses showed that diclofenac has a significant ( p less than 0.001 ) effect on the pain associated with swallowing and on the general condition of the patients . The therapeutic gain was calculated to 50 % . As a consequence of this study , treatment with diclofenac has been introduced in both ENT departments A double blind trial was conducted to evaluate the analgesic efficacy of intramuscular tenoxicam for pain relief following tonsillectomy in children . Fifty children , aged 3 - 10 years , were r and omly allocated to receive intramuscular tenoxicam 0.75 mg.kg-1 or intramuscular morphine sulphate 0.2 mg.kg-1 after induction of anaesthesia . Although the tenoxicam group required significantly more postoperative morphine.(mean 57.8 micrograms.kg-1 compared with 26.9 micrograms.kg-1 , P = 0.025 ) , the total morphine dose was significantly reduced after tenoxicam ( 57.8 micrograms.kg-1 compared with 226.9 micrograms.kg-1 , P < 0.0001 ) . There was no difference between the quality of analgesia after discharge from recovery . The incidence of postoperative vomiting was significantly reduced after tenoxicam ( 20 % ) compared with morphine ( 71 % ) A wide variety of surgical and pharmacological methods have been described in an attempt to reduce pain after tonsillectomy , with conflicting results . Opiates are still widely used , despite unwanted side-effects . Recently the non-steroidal anti-inflammatory drugs have been shown to be effective against a variety of post-operative pains . Diclofenac is effective in both children and adults in the relief of pain after tonsillectomy when administered rectally , but absorption is variable , and suppositories are not widely accepted in the UK . The present double-blind study compared a single intramuscular dose of diclofenac with papaveretum in adults undergoing tonsillectomy . Post-operatively , the patients who received diclofenac had less pain and started drinking significantly sooner than the control group . There were no undesirable side-effects . Intramuscular diclofenac is superior to papaveretum in the relief of pain in adults undergoing tonsillectomy BACKGROUND The primary aim of this study was to determine whether the combination of i.v . ketoprofen and i.v . paracetamol provides superior postoperative analgesia in children undergoing adenoidectomy or tonsillotomy compared to either drug alone . The secondary goal was to assess the time until rescue analgesia was needed , propofol requirements and the incidence of vomiting and time of discharge from the postanaesthesia recovery unit ( PARU ) . METHODS This double-blinded study included 120 children ( aged 3 - 13 years ) scheduled for elective tonsillectomy , adenoidectomy or adenotonsillectomy . The children were r and omly assigned to one of 3 groups of 40 children each , using the sealed envelope method . The children received i.v . ketoprofen 2 mg/kgBW ( group 1 ) or paracetamol 15 mg/kgBW ( group 2 ) or the combination of these 2 drugs ( group 3 ) after induction of anaesthesia . St and ardized general anaesthesia consisted of sevoflurane and fentanyl at a dose of 2 - 3 μg/kgBW . Pain was assessed using a 5-point scoring system based on the Smiley scale . The Smiley scale shows various faces from a laughing face which corresponds to the state of no pain to a very unhappy face which corresponds to the situation of worst pain ( 1 : no pain , 2 : mild pain , 3 : moderate pain , 4 : severe pain , 5 : worst pain ) . Pain was assessed at 30 min , 1 h , 2 h , 3 h and 4 h after arriving in the PACU . If the pain score exceeded 2 an i.v . dose of 0.1 mg/kgBW morphine was administered as rescue analgesia . RESULTS During the stay in the PACU the children in the combination group required significantly less supplementary rescue analgesia than children in the ketoprofen and paracetamol groups ( 17.5 % versus 30.8 % versus 45 % , respectively , χ(2 ) analysis < 0.05 ) . Pain scoring was highest after paracetamol , however , this difference was only significant when compared to the group receiving the combination of paracetamol and ketoprofen ( U-test p<0.05 ) . Rescue analgesia was administered earliest in group 2 ( paracetamol ) reaching statistical significance , however , only when compared to group 3 ( logrank test p<0.05 ) . Propofol requirements and time to discharge from the PACU did not differ significantly between the 3 groups ( χ(2 ) analysis ; U-test ; p>0.05 ) . The overall incidence of vomiting was very low in this study with 6.4 % ( 9/139 ) . Significantly more children in the paracetamol group compared to ketoprofen group and combination group suffered from vomiting ( 17.5 % versus 2.6 % versus 2.5 % ; χ(2 ) analysis ; p<0.05 ) . The time to discharge from PACU did not differ significantly between the 3 groups ( U-test : p>0.05 ) . CONCLUSION The combination of i.v . paracetamol and i.v . ketoprofen provides superior postoperative analgesia compared to the single use of paracetamol Purpose Dexmedetomidine , a selective α2 adrenoreceptor agonist , has analgesic and sedative properties , minimal impact on respiratory parameters , and reportedly decreases analgesic requirements after surgery . Given its pharmacodynamic profile , dexmedetomidine might have a role for postoperative pain control in children undergoing tonsillectomy . In this study , we hypothesized that dexmedetomidine would delay and decrease opioid requirements after tonsillectomy . Methods In a double-blind controlled trial , participants undergoing tonsillectomy were r and omized to receive one intravenous dose of fentanyl ( 1 μg·kg−1 or 2 μg·kg−1 ) or dexmedetomidine ( 2 μg·kg−1 or 4 μg·kg−1 ) immediately after endotracheal intubation . Primary outcomes included requirement for rescue morphine in the initial postoperative period . Results One hundred and one children were enrolled . During the postoperative period , dexmedetomidine ( 2 and 4 μg·kg−1 groups combined ) significantly prolonged the opioid-free interval of children who underwent tonsillectomy compared with fentanyl ( 1 and 2 μg·kg−1 groups combined ) ( P < 0.001 ) . Children treated with dexmedetomidine 2 μg·kg−1vs dexmedetomidine 4 μg·kg−1 had similar cumulative incidence curves for time to morphine rescue , whereas there was a small difference in time to first morphine rescue administration when comparing fentanyl 1 μg·kg−1vs fentanyl 2 μg·kg−1 . Furthermore , length of stay in the postanesthesia care unit was significantly longer for children treated with dexmedetomidine vs children treated with fentanyl ( P = 0.0016 ) . Conclusions High-dose dexmedetomidine decreases opioid requirements , prolongs the opioid-free interval after tonsillectomy , and prolongs length of stay in the postanesthesia care unit . It is conceivable that these early opioid-sparing effects could benefit patients at risk for respiratory complications early in the postoperative course after tonsillectomy ( e.g. , patients with obstructive sleep apnea ) . ( Clinical Trials.gov number , NCT00654511).RésuméObjectifLa dexmédétomidine , un agoniste sélectif des récepteurs adrénergiques α2 , a des propriétés analgésiques et sédatives ainsi qu’un impact minimal sur les paramètres respiratoires . De plus , elle semble réduire les besoins analgésiques après une chirurgie . Étant donné son profil pharmacodynamique , la dexmédétomidine pourrait jouer un rôle sur le contrôle de la douleur postopératoire chez les enfants subissant une amygdalectomie . Dans cette étude , nous avons émis l’hypothèse que la dexmédétomidine retarderait et réduirait les besoins en opioïdes après une amygdalectomie . MéthodeDans une étude contrôlée à double insu , les participants devant subir une amygdalectomie ont été r and omisés à recevoir une dose intraveineuse de fentanyl ( 1 μg·kg−1 ou 2 μg·kg−1 ) ou de dexmédétomidine ( 2 μg·kg−1 ou 4 μg·kg−1 ) immédiatement après l’intubation endotrachéale . Le critère d’évaluation principal était le besoin en analgésie morphinique de secours dans la période postopératoire initiale . RésultatsCent-un enfants ont été recrutés . Pendant la période postopératoire , la dexmédétomidine ( groupes 2 et 4 μg·kg−1 combinés ) a prolongé de façon significative l’intervalle sans opioïde chez les enfants subissant une amygdalectomie par rapport au fentanyl ( groupes 1 et 2 μg·kg−1 combinés ) ( P < 0,0001 ) . Les enfants traités avec de la dexmédétomidine 2 μg·kg−1vs de la dexmédétomidine 4 μg·kg−1 ont affiché des courbes d’incidence cumulative semblables au niveau du temps jusqu’à administration d’une analgésie morphinique de secours . En revanche , une légère différence a été observée dans les temps jusqu’à la première administration de morphine de secours lors de la comparaison de fentanyl 1 μg·kg−1 et de fentanyl 2 μg·kg−1 . De plus , la durée de séjour en salle de réveil était significativement plus longue pour les enfants traités avec de la dexmédétomidine que pour les enfants traités avec du fentanyl ( P = 0,0016 ) . Conclusion La dexmédétomidine en forte dose réduit les besoins en opioïdes , prolonge l’intervalle sans opioïde après une amygdalectomie , et prolonge également la durée de séjour en salle de réveil . On peut imaginer que ces effets précoces de réduction des besoins en opioïdes pourraient être avantageux pour les patients présentant un risque de complications respiratoires en période postopératoire après une amygdalectomie ( par ex . les patients souffrant d’apnée obstructive du sommeil ) . ( Numéro de Clinical Trials.gov , NCT00654511 ) |
13,996 | 30,656,147 | Visual analogue scale pain intensity ratings and the number of myofascial trigger points present in the neck and shoulder/axillary area of participants significantly decreased in the exercise group compared to those in the control group .
Pain pressure thresholds significantly increased in muscle areas of the cervical spine in the water exercise group .
Aerobic exercise presents a potential treatment modality for managing myofascial pain . | Myofascial pain is prevalent chronic pain disorder that is comorbid with many conditions .
Strengthening and stretching exercises are capable of inducing hypoalgesic effects in people with myofascial pain syndrome .
The goal of this systematic review was to summarize the effects of aerobic exercise on the management of myofascial pain . | OBJECTIVES To determine the immediate effects of modified Proprioceptive Neuromuscular Facilitation ( PNF ) stretching ( group I ) versus Myofascial Trigger Point ( MTrP ) therapy plus modified PNF stretching ( group II ) in comparison to a control group receiving no treatment . DESIGN R and omized , assessor-blind , ( 3 x 4 ) mixed-model repeated measures . SETTING University laboratory . PARTICIPANTS Thirty physically active males with tight hamstrings and at least one latent MTrP on muscles innervated by the lumbosacral , sciatic , tibial and common peroneal nerves . MAIN OUTCOME MEASURES Knee range of motion ( ROM ) , stretch perception , pressure pain threshold ( PPT ) and subjective pain intensity . Outcomes were evaluated at baseline , immediately after treatment , at 10 and 30 min . RESULTS Significant changes over time occurred for group II in all outcomes ( p < or = 0.001 ) . Group II also showed lower pain intensity scores than group I immediately post-treatment ( p = 0.045 ) and a strong clinical effect over group I in ROM at all follow-ups ( effect sizes = 0.9 - 1.0 , p < or = 0.05 ) . Other differences were found between both stretching groups as compared to the control group ( p < or = 0.05 ) . CONCLUSION The results indicate immediate pre- to post-treatment benefits from MTrP therapy combined with modified PNF stretching in young and physically active males with latent MTrPs OBJECTIVE To evaluate the effects of an 8-week water physical therapy program on cervical and shoulder pain , pressure sensitivity , and the presence of trigger points ( TrPs ) in breast cancer survivors . DESIGN R and omized , controlled trial . SETTING To date , no study has investigated effects of water therapy in breast cancer . PATIENTS Sixty-six breast cancer survivors were r and omly assigned into two groups : WATER group , who received a water exercise program or CONTROL group who received the usual care treatment for breast cancer . INTERVENTIONS The WATER therapy program consisted of 24 sessions ( 3 times/week over 8 weeks ) of low-intensity exercises in a warm pool ( 32 ° C ) . Each session included 10-minute warm-up period ; 35 minutes of aerobic , low-intensity endurance , and core stability training ; and a 15-minute cool-down period ( stretching and relaxation ) . OUTCOMES Neck and shoulder pain ( visual analog scale , 0 - 100 mm ) , pressure pain thresholds ( PPTs ) over C5-C6 zygapophyseal joints , deltoid muscles , second metacarpal , and tibialis anterior muscles , and the presence of TrPs in cervical-shoulder muscles were assessed at baseline and after the 8-week program by an assessor blinded to treatment allocation . RESULTS The WATER group demonstrated a between-group improvement for neck pain of -31 mm ( 95 % confidence interval [CI]-49 to -22 , P < 0.001 ; effect size 1.1 , 0.81 - 1.75 ) and for shoulder-axillary of -19 mm ( -40 to -04 , P = 0.046 ; effect size 0.70 , 0.14 - 1.40 ) . Improvements were also noted for PPT levels over C5-C6 joints ( between-group differences , affected side : 27.7 kPa , 95 % CI 3.9 - 50.4 ; unaffected : 18.1 kPa , 95 % CI 6.1 - 52.2 ) . No between-group differences for PPT over the remaining points were observed ( P > 0.05 ) . Finally , patients in the WATER program showed a greater reduction of active TrPs as compared with the CONTROL group ( P < 0.05 ) . CONCLUSIONS An 8-week water therapy program was effective for improving neck and shoulder/axillary pain , and reducing the presence of TrPs in breast cancer survivors as compared with usual care ; however , no significant changes in widespread pressure pain hyperalgesia were found Background : High insulin and insulin-like growth factor-I ( IGF-I ) levels may be associated with an increased breast cancer risk and /or death . Given the need to identify modifiable factors that decrease insulin , IGF-I , and breast cancer risk and death , we investigated the effects of a 6-month r and omized controlled aerobic exercise intervention versus usual care on fasting insulin , IGF-I , and its binding protein ( IGFBP-3 ) in postmenopausal breast cancer survivors . Methods : Seventy-five postmenopausal breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and r and omly assigned to an exercise ( n = 37 ) or usual care ( n = 38 ) group . The exercise group participated in 150 minutes per week of moderate-intensity aerobic exercise . The usual care group was instructed to maintain their current physical activity level . A fasting blood sample was collected on each study participant at baseline and 6 months . Blood levels of insulin and IGF were measured with ELISA . Results : On average , exercisers increased aerobic exercise by 129 minutes per week compared with 45 minutes per week among usual care participants ( P < 0.001 ) . Women r and omized to exercise experienced decreases in insulin , IGF-I , and IGFBP-3 , whereas women r and omized to usual care had increases in these hormones . Between-group differences in insulin , IGF-I , and IGFBP-3 were 20.7 % ( P = 0.089 ) , 8.9 % ( P = 0.026 ) , and 7.9 % ( P = 0.006 ) , respectively . Conclusions : Moderate-intensity aerobic exercise , such as brisk walking , decreases IGF-I and IGFBP-3 . The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer . ( Cancer Epidemiol Biomarkers Prev 2009;18(1):306–13 The aim of this study was to evaluate the effects of scapular stabilization exercise ( SSE ) on pain intensity , pressure pain threshold ( PPT ) , muscle tension and anxiety in patients with scapulocostal syndrome ( SCS ) . Thirty-six patients were r and omly assigned to receive a 30-minute session of either SSE or control ( relaxed by lying supine quietly ) for 12 sessions over a period of 4 weeks . Pain intensity , PPT , muscle tension and anxiety were assessed before and after a 4-week intervention period and 2 weeks after the intervention period . The adverse effects were evaluated after completion of the intervention period . Results indicated that the SSE group showed a significant improvement in all parameters after the intervention period and at 2 weeks after the intervention period ( p < 0.05 ) . For all outcomes , similar changes were not found in the control group . The adjusted post-test mean values of each assessment time point for pain intensity , muscle tension and anxiety were significantly lower in the SSE group than those of the control group ( p < 0.05 ) . Moreover , the values for PPT were significantly higher in the SSE group ( p > 0.05 ) . There were no reports of adverse effects in either group . We therefore conclude that SSE can improve pain related parameters and could be an effective intervention for SCS 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 Summary Cold pressor pain and exercise causes multisegmental increases in pressure pain thresholds . Exercise is dominated by local manifestations of hypoalgesia , whereas cold pressor pain results generally in remote hypoalgesia . ABSTRACT Pain inhibitory mechanisms are often assessed by paradigms of exercise‐induced hypoalgesia ( EIH ) and conditioned pain modulation ( CPM ) . In this study it was hypothesized that the spatial and temporal manifestations of EIH and CPM were comparable . The participants were 80 healthy subjects ( 40 females ) , between 18 and 65 years of age in this r and omized , repeated‐ measures cross‐over trial that involved data collection on 2 different days . CPM was assessed by 2 different cold pressor tests ( h and and foot ) . EIH was assessed by 2 intensities of aerobic bicycling exercises and 2 intensities of isometric muscle contraction exercises ( arm and leg ) . Pressure pain thresholds ( PPTs ) were recorded before , during , after , and 15 minutes after conditioning/exercise at sites local to and remote from the extremity used for cold pressor stimulation and exercise . PPTs increased at local as well as at remote sites during both cold pressor tests and after all of the exercise conditions except low‐intensity bicycling . EIH after bicycling was higher in women than in men . CPM and the EIH responses after isometric exercises were comparable in men and women and were not affected by age . The EIH response was larger in the exercising body part compared with nonexercising body parts for all exercise conditions . High‐intensity exercise produced greater EIH responses than did low‐intensity exercise . The change in PPTs during cold pressor tests and the change in PPTs after exercises were not correlated . The CPM response was not dominated by local manifestations , and the effect was seen only during the stimulation , whereas exercise had larger local manifestations , and the effects were also found after exercise OBJECTIVE This prospect i ve study examined circulating cytokines in patients with fibromyalgia ( FM ) over 6 months rather than at only one timepoint , and investigated correlations between serum cytokine concentrations and pain intensity in FM patients receiving multidisciplinary pain therapy . METHODS Serum concentrations of proinflammatory cytokines interleukin 6 ( IL-6 ) , IL-8 , and tumor necrosis factor-alpha ( TNF-alpha ) and antiinflammatory cytokines IL-4 and IL-10 were measured ( Bio-Plex system ) in 20 FM patients and 80 healthy subjects on admission and 10 , 21 , and 180 days after initiation of treatment and correlated to pain intensity . RESULTS On admission , serum levels of IL-8 ( p < 0.001 ) and TNF-alpha ( p < 0.001 ) , but not IL-6 , were elevated in patients with FM . No significant difference in IL-4 and IL-10 was found between FM patients and controls . High IL-8 levels remained consistent during the followup , but TNF-alpha was already reduced after 10 days and until 6 months after therapy . After 6 months ' treatment with multidisciplinary pain therapy , IL-8 and TNF-alpha levels were significantly lower than at the beginning ( p < 0.05 for IL-8 , p < 0.001 for TNF-alpha ) . IL-8 but not TNF-alpha serum levels were correlated with pain intensity ( r = -0.782 , p = 0.001 ) in FM patients after 6 months ' multidisciplinary pain therapy . CONCLUSION Our results suggest that proinflammatory cytokines TNF-alpha and IL-8 are involved in FM , but they do not apparently provoke the pain of FM directly . Multidisciplinary pain therapy modified the cytokine profile in patients with FM during the observation period OBJECTIVES The purpose of this study was to investigate the effects of electrotherapy and exercise on pain intensity and mobility of connective tissue in patients with myofascial pain syndrome ( MPS ) in their cervical region . METHODS 60 patients were divided into 3 groups using a r and om allocation programme method . A hotpack was applied , and ultrasound was carried out on the patients in the treatment group who were also given exercise training . Exercise training was only given to the exercise group while the control group was given two weeks rest . The demographic characteristics , autonomic symptoms , and other MPS-associated symptoms of patients were recorded . The Short-Form McGill Pain Question naire was used to evaluate the intensity and quality of pain , and a skin-roll test was used to evaluate connective tissue mobility . RESULTS There was a statistically significant difference between treatment and control group on the sensory pain , total pain , and Visual Analog Scale measurements ( p < 0.05 ) . There was a decrease in connective tissue sensitivity measurements in the treatment and control groups . The connective tissue tension measurements were also decreased after treatment in the treatment and exercise groups . CONCLUSION We concluded that combined treatment was more effective to decrease pain intensity , and increase connective tissue mobility |
13,997 | 31,011,880 | Conclusion DOACs peri-cardioversion in patients with AF appears safe from both a bleeding and thromboembolic risk perspective .
Available evidence supports the use of DOACs as st and ard of care peri-cardioversion in patients with AF | Background Clinical guidelines recommend peri-cardioversion anticoagulation in patients with atrial fibrillation ( AF ) .
We performed a systematic review and meta- analysis to compare the safety and efficacy of direct oral anticoagulants ( DOACs ) versus vitamin K antagonists ( VKAs ) in patients with AF undergoing cardioversion . | Aims R and omized trials showed non-inferior or superior results of the non-vitamin-K-antagonist oral anticoagulants ( NOACs ) compared with warfarin . The aim of this study was to assess the effectiveness and safety of dabigatran ( direct thrombin inhibitor ) vs. acenocoumarol ( vitamin K antagonist ) in patients with atrial fibrillation ( AF ) in daily clinical practice . Methods and results In this observational study , we evaluated all consecutive patients who started anticoagulation because of AF in our outpatient clinic from 2010 to 2013 . Data were collected from electronic patient charts . Primary outcomes were stroke or systemic embolism and major bleeding . Propensity score matching was applied to address the non-r and omized design . In total , 920 consecutive AF patients were enrolled ( 442 dabigatran , 478 acenocoumarol ) , of which 2 × 383 were available for analysis after propensity score matching . Mean follow-up duration was 1.5 ± 0.56 year . The mean calculated stroke risk according to the CHA2DS2-VASc score was 3.5%/year in dabigatran vs. 3.7%/year acenocoumarol-treated patients . The actual incidence rate of stroke or systemic embolism was 0.8%/year [ 95 % confidence interval ( CI ) : 0.2–2.1 ] vs. 1.0%/year ( 95 % CI : 0.4–2.1 ) , respectively . Multivariable analysis confirmed this lower but non-significant risk in dabigatran vs. acenocoumarol after adjustment for the CHA2DS2-VASc score [ hazard ratio (HR)dabigatran = 0.72 , 95 % CI : 0.20–2.63 , P = 0.61 ] . According to the HAS-BLED score , the mean calculated bleeding risk was 1.7%/year in both groups . Actual incidence rate of major bleeding was 2.1%/year ( 95 % CI : 1.0–3.8 ) in the dabigatran vs. 4.3%/year ( 95 % CI : 2.9–6.2 ) in acenocoumarol . This over 50 % reduction remained significant after adjustment for the HAS-BLED score ( HRdabigatran = 0.45 , 95 % CI : 0.22–0.93 , P = 0.031 ) . Conclusion In ‘ real-world ’ patients with AF , dabigatran appears to be as effective , but significantly safer than acenocoumarol Background — Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism ( VTE ) in a previous trial . We undertook this study to extend those findings . Methods and Results — In a r and omized , double-blind , double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days , we compared dabigatran 150 mg twice daily with warfarin . The primary outcome , recurrent symptomatic , objective ly confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients ( 2.3 % ) compared with 28 of the 1289 warfarin patients ( 2.2 % ; hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.64–1.80 ; absolute risk difference , 0.2 % ; 95 % CI , −1.0 to 1.3 ; P<0.001 for the prespecified noninferiority margin for both criteria ) . The safety end point , major bleeding , occurred in 15 patients receiving dabigatran ( 1.2 % ) and in 22 receiving warfarin ( 1.7 % ; hazard ratio , 0.69 ; 95 % CI , 0.36–1.32 ) . Any bleeding occurred in 200 dabigatran ( 15.6 % ) and 285 warfarin ( 22.1 % ; hazard ratio , 0.67 ; 95 % CI , 0.56–0.81 ) patients . Deaths , adverse events , and acute coronary syndromes were similar in both groups . Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 ( 95 % CI , 0.76–1.57 ) , for major bleeding of 0.73 ( 95 % CI , 0.48–1.11 ) , and for any bleeding of 0.70 ( 95 % CI , 0.61–0.79 ) . Conclusion — Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE . Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifiers : NCT00680186 and NCT00291330 Background — The R and omized Evaluation of Long-Term Anticoagulation Therapy ( RE-LY ) trial compared dabigatran 110 mg BID ( D110 ) and 150 mg BID ( D150 ) with warfarin for stroke prevention in 18 113 patients with nonvalvular atrial fibrillation . Methods and Results — Cardioversion on r and omized treatment was permitted . Precardioversion transesophageal echocardiography was encouraged , particularly in dabigatran-assigned patients . Data from before , during , and 30 days after cardioversion were analyzed . A total of 1983 cardioversions were performed in 1270 patients : 647 , 672 , and 664 in the D110 , D150 , and warfarin groups , respectively . For D110 , D150 , and warfarin , transesophageal echocardiography was performed before 25.5 % , 24.1 % , and 13.3 % of cardioversions , of which 1.8 % , 1.2 % , and 1.1 % were positive for left atrial thrombi . Continuous treatment with study drug for ≥3 weeks before cardioversion was lower in D110 ( 76.4 % ) and D150 ( 79.2 % ) compared with warfarin ( 85.5 % ; P<0.01 for both ) . Stroke and systemic embolism rates at 30 days were 0.8 % , 0.3 % , and 0.6 % ( D110 versus warfarin , P=0.71 ; D150 versus warfarin , P=0.40 ) and similar in patients with and without transesophageal echocardiography . Major bleeding rates were 1.7 % , 0.6 % , and 0.6 % ( D110 versus warfarin , P=0.06 ; D150 versus warfarin , P=0.99 ) . Conclusions — This study is the largest cardioversion experience to date and the first to evaluate a novel anticoagulant in this setting . The frequencies of stroke and major bleeding within 30 days of cardioversion on the 2 doses of dabigatran were low and comparable to those on warfarin with or without transesophageal echocardiography guidance . Dabigatran is a reasonable alternative to warfarin in patients requiring cardioversion . Clinical Trial Registration — URL : http://www . Clinical Trials.gov . Unique identifier : NCT00262600 Abstract Aims In patients with atrial fibrillation ( AF ) pharmacological or electrical cardioversion may be performed to restore sinus rhythm . The procedure is associated with an increased risk of thromboembolic events , which can be significantly reduced by adequate anticoagulation ( OAC ) . Our aim was to create a partly prospect i ve , partly retrospective cardioversion registry , particularly focusing on OAC strategies in different European countries , and on emerging choice of OAC over time . Methods From September 2014 to October 2015 , cardioversions due to AF performed in six European city hospitals in five European countries ( Hungary : Budapest-1 and -2 ; Italy : Bari and Pisa ; France : Amiens ; Spain : Madrid ; and Lithuania : Kaunas ) were recorded in the registry . Results A total of 1101 patients ( retrospective/ prospect i ve : 679/422 , male/female : 742/359 , mean age : 67.3 years ± 11.2 ) were registered . Most of the cardioversions were electrical ( 97 % ) . Oral anticoagulants were administered in 87 % of the patient , the usage of non-VKA oral anticoagulants ( NOACs ) vs Vitamin K antagonists ( VKA ) was 31.5 % vs 68.5 % , respectively . Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure , and 86 % more than 4 weeks after the procedure . When using VKA , international normalized ratio ( INR ) at cardioversion was above 2.0 in 76 % of the cases . A decline in VKA usage ( P = 0.033 ) in elective cardioversion over approximately 1 year was observed . During the observation period , there was an increase in apixaban ( P < 0.001 ) , a slight increase in rivaroxaban ( P = 0.028 ) and no changes in dabigatran ( P = 0.34 ) usage for elective cardioversion . There were differences in use of OAC between the countries : Spain used most VKA ( 89 % ) , while France used least VKA ( 39 % , P < 0.001 ) . Conclusion According to current AF guidelines , NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion . Our results indicate that NOAC use is increasing and there is a significant decrease in VKA use Abstract Aim The primary objective was to compare apixaban to heparin/vitamin K antagonist ( VKA ) in patients with atrial fibrillation ( AF ) and ≤48 h anticoagulation prior to r and omization undergoing cardioversion . Methods One thous and five hundred patients were r and omized . The apixaban dose of 5 mg b.i.d . was reduced to 2.5 mg b.i.d . in patients with two of the following : age ≥ 80 years , weight ≤ 60 kg , or serum creatinine ≥ 133 µmol/L. To expedite cardioversion , at the discretion of the investigator , imaging and /or a loading dose of 10 mg ( down-titrated to 5 mg ) was allowed . The endpoints for efficacy were stroke , systemic embolism ( SE ) , and death . The endpoints for safety were major bleeding and clinical ly relevant non-major ( CRNM ) bleeding . Results There were 1038 active and 300 spontaneous cardioversions ; 162 patients were not cardioverted . Imaging was performed in 855 patients , and 342 received a loading dose of apixaban . Comparing apixaban to heparin/VKA in the full analysis set , there were 0/753 vs. 6/747 strokes [ relative risk ( RR ) 0 ; 95 % confidence interval ( 95 % CI ) 0–0.64 ; nominal P = 0.015 ] , no SE , and 2 vs. 1 deaths ( RR 1.98 ; 95 % CI 0.19–54.00 ; nominal P > 0.999 ) . In the safety population , there were 3/735 vs. 6/721 major ( RR 0.49 ; 95 % CI 0.10–2.07 ; nominal P = 0.338 ) and 11 vs. 13 CRNM bleeding events ( RR 0.83 ; 95 % CI 0.34–1.89 ; nominal P = 0.685 ) . On imaging , 60/61 with thrombi continued r and omized treatment ; all ( 61 ) were without outcome events . Conclusions Rates of strokes , systemic emboli , deaths , and bleeds were low for both apixaban and heparin/VKA treated AF patients undergoing cardioversion . Clinical Trials.gov number 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 Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) AIMS We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation ( AF ) . METHODS AND RESULTS In ARISTOTLE , 18 201 patients were r and omized to apixaban 5 mg twice daily or warfarin . Concomitant aspirin use was left to the discretion of the treating physician . In this predefined analysis , simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use . Outcome measures included stroke or systemic embolism , ischaemic stroke , myocardial infa rct ion , mortality , major bleeding , haemorrhagic stroke , major or clinical ly relevant non-major bleeding , and any bleeding . On Day 1 , 4434 ( 24 % ) patients were taking aspirin . Irrespective of concomitant aspirin use , apixaban reduced stroke or systemic embolism [ with aspirin : apixaban 1.12 % vs. warfarin 1.91 % , hazard ratio ( HR ) 0.58 , 95 % confidence interval ( CI ) 0.39 - 0.85 vs. without aspirin : apixaban 1.11 % vs. warfarin 1.32 % , HR 0.84 , 95 % CI 0.66 - 1.07 ; P interaction = 0.10 ] and caused less major bleeding than warfarin ( with aspirin : apixaban 3.10 % vs. warfarin 3.92 % , HR 0.77 , 95 % CI 0.60 - 0.99 vs. without aspirin : apixaban 1.82 % vs. warfarin 2.78 % , HR without aspirin 0.65 , 95 % CI 0.55 - 0.78 ; P interaction = 0.29 ) . Similar results were seen in the subgroups of patients with and without arterial vascular disease . CONCLUSION Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin , irrespective of concomitant aspirin use BACKGROUND [ corrected ] Atrial fibrillation is an important risk factor for ischaemic stroke . Anticoagulation treatment with warfarin can substantially reduce the risk of stroke in people with atrial fibrillation but concerns about their side-effects have limited their use in clinical practice . However there has been little population -based research on the comorbidity associated with atrial fibrillation and on the prevalence of potential contraindications to anticoagulantion treatment among these patients . AIM To determine the prevalence of known risk factors for ischaemic stroke and possible contraindications to anticoagulant treatment among patients with atrial fibrillation . METHOD One-year prospect i ve cohort study in 60 general practice s in Engl and and Wales with a total population of 502,493 people . Age and sex specific prevalence rates and relative risks of risk factors for ischaemic stroke and possible contraindications to antithrombotic treatment were calculated . RESULTS The number of patients who had a diagnosis of atrial fibrillation during the year was 1,414 ( 0.3 % ) patients . The prevalence of other nsk factors for ischaemic stroke in patients with atrial fibrillation increased with age in men , from 48 % ( relative risk [ RR ] = 3.78 , 95 % confidence interval [ 95 % CI ] = 3.23 - 4.41 ) at 45 to 64 years to 64 % ( RR = 2.21 , 95 % CI = 2.00 - 2.44 ) at 75years and over A similar increase of 50 % ( RR = 4.36 , 95 % CI = 3.54 - 5.38 ) to 60 % ( RR = 2.07 , 95 % CI = 1.91 - 2.23 ) was seen in women . The percentage of men with atrial fibrillation with at least one contraindication to antithrombotic treatment was 5 % at 45 to 64 years and 14 % at 75 years and over . Among women with atrial fibrillation , 7 % had a contraindication at 45 to 64 years and 16 % at 75 years and over . The all-ages relative risk of a contraindication was 1.17 ( 95 % CI = 0.92 - 1.48 ) in men and 1.53 ( 95 % CI = 1.28 - 1.83 ) in women . Forty per cent ( 575 ) of patients with atrial fibrillation had at least one risk factor for ischaemic stroke and no contraindications to antithrombotic treatment . CONCLUSION Atrial fibrillation is associated with a substantial increase in the prevalence of risk factors for ischaemic stroke . By contrast , potential contraindications for antithrombotic treatment are more evenly distributed among patients with and without atrial fibrillation . Around 40 % of patients with atrial fibrillation in primary care are at high risk of stroke and have no contraindicationsfor antithrombotic treatment BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment . Rivaroxaban , an oral factor Xa inhibitor , may provide more consistent and predictable anticoagulation than warfarin . METHODS In a double-blind trial , we r and omly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban ( at a daily dose of 20 mg ) or dose-adjusted warfarin . The per- protocol , as-treated primary analysis was design ed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism . RESULTS In the primary analysis , the primary end point occurred in 188 patients in the rivaroxaban group ( 1.7 % per year ) and in 241 in the warfarin group ( 2.2 % per year ) ( hazard ratio in the rivaroxaban group , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.96 ; P<0.001 for noninferiority ) . In the intention-to-treat analysis , the primary end point occurred in 269 patients in the rivaroxaban group ( 2.1 % per year ) and in 306 patients in the warfarin group ( 2.4 % per year ) ( hazard ratio , 0.88 ; 95 % CI , 0.74 to 1.03 ; P<0.001 for noninferiority ; P=0.12 for superiority ) . Major and nonmajor clinical ly relevant bleeding occurred in 1475 patients in the rivaroxaban group ( 14.9 % per year ) and in 1449 in the warfarin group ( 14.5 % per year ) ( hazard ratio , 1.03 ; 95 % CI , 0.96 to 1.11 ; P=0.44 ) , with significant reductions in intracranial hemorrhage ( 0.5 % vs. 0.7 % , P=0.02 ) and fatal bleeding ( 0.2 % vs. 0.5 % , P=0.003 ) in the rivaroxaban group . CONCLUSIONS In patients with atrial fibrillation , rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism . There was no significant between-group difference in the risk of major bleeding , although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group . ( Funded by Johnson & Johnson and Bayer ; ROCKET AF Clinical Trials.gov number , NCT00403767 . ) BACKGROUND Edoxaban , an oral factor Xa inhibitor , is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy . Few safety data about edoxaban in patients undergoing electrical cardioversion are available . METHODS We did a multicentre , prospect i ve , r and omised , open-label , blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin-warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation . The dose of edoxaban was reduced to 30 mg per day if one or more factors ( creatinine clearance 15 - 50 mL/min , low bodyweight [ ≤60 kg ] , or concomitant use of P-glycoprotein inhibitors ) were present . Block r and omisation ( block size four)-stratified by cardioversion approach ( transoesophageal echocardiography [ TEE ] or not ) , anticoagulant experience , selected edoxaban dose , and region-was done through a voice-web system . The primary efficacy endpoint was a composite of stroke , systemic embolic event , myocardial infa rct ion , and cardiovascular mortality , analysed by intention to treat . The primary safety endpoint was major and clinical ly relevant non-major ( CRNM ) bleeding in patients who received at least one dose of study drug . Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety . This trial is registered with Clinical Trials.gov , number NCT02072434 . FINDINGS Between March 25 , 2014 , and Oct 28 , 2015 , 2199 patients were enrolled and r and omly assigned to receive edoxaban ( n=1095 ) or enoxaparin-warfarin ( n=1104 ) . The mean age was 64 years ( SD 10·54 ) and mean CHA2DS2-VASc score was 2·6 ( SD 1·4 ) . Mean time in therapeutic range on warfarin was 70·8 % ( SD 27·4 ) . The primary efficacy endpoint occurred in five ( < 1 % ) patients in the edoxaban group versus 11 ( 1 % ) in the enoxaparin-warfarin group ( odds ratio [ OR ] 0·46 , 95 % CI 0·12 - 1·43 ) . The primary safety endpoint occurred in 16 ( 1 % ) of 1067 patients given edoxaban versus 11 ( 1 % ) of 1082 patients given enoxaparin-warfarin ( OR 1·48 , 95 % CI 0·64 - 3·55 ) . The results were independent of the TEE-guided strategy and anticoagulation status . INTERPRETATION ENSURE-AF is the largest prospect i ve r and omised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation . Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups . FUNDING Daiichi Sankyo provided financial support for the study INTRODUCTION Every year about 2500 patients in Sweden undergo surgery due to heart valve disease . A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding . Treatment quality with warfarin is crucial for patients with mechanical valve prostheses . It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group . TTR ( Time in Therapeutic Range ) on warfarin has been shown to affect the risk of complications in atrial fibrillation , but has not been studied in patients with mechanical heart valves . Our aim is to evaluate the impact of TTR on the risk of complications in this patient group . MATERIAL S AND METHODS A non-r and omized , prospect i ve study of 534 adults with mechanical heart valve prostheses from Malmö and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011 . Quartiles regarding individual TTR levels were compared regarding risk of complications . RESULTS The risk of complications was significantly higher at lower TTR levels for all complications ( p=0.005 ) , bleeding ( p=0.01 ) and death ( p=0.018 ) but not for thromboembolism . In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism . CONCLUSION Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death . A TTR of 83 % or higher at the individual level should be obtained for best outcome Three post‐hoc analyses from warfarin‐controlled trials of non – vitamin K oral anticoagulants in patients with atrial fibrillation (AF)1 and 1 prospect i ve study 2 comparing rivaroxaban and warfarin in 1504 patients have shown low and comparable rates of thromboembolic events and hemorrhagic complications in patients undergoing electrical cardioversion . We compared outcomes with edoxaban vs warfarin in the Effective Anticoagulation With Factor Xa Next Generation ( ENGAGE ) AF‐TIMI 48 trial among patients who underwent a first electrical cardioversion while on study Direct oral anticoagulants ( DOACs ) are effective for stroke prevention in nonvalvular atrial fibrillation ( AF ) . Cardioversion ( CV ) is frequently performed in patients with AF or flutter . To further explore the safety profile of DOACs in the context of CV , we sought to assess the prevalence of intracardiac thrombi under DOAC therapy in comparison with treatment with vitamin K antagonists . A total of 672 transesophageal echocardiograms performed in 643 patients with a history of nonvalvular AF were analyzed . The median CHA2DS2-VASc score was 4 . Cases were stratified according to anticoagulation with dabigatran ( n = 79 ) , rivaroxaban ( n = 122 ) , phenprocoumon ( n = 180 ) , or bridging therapy ( n = 287 ) . In a subgroup analysis , only patients receiving phenprocoumon with an international normalized ratio ≥2 on the day of the investigation or on DOAC therapy for ≥3 weeks were considered . The prevalence of intracardiac thrombi under phenprocoumon was significantly higher than under DOACs ( phenprocoumon , 17.8 % ; all DOACs , 3.9 % ; dabigatran , 3.8 % ; rivaroxaban , 4.1 % ) and showed no significant difference to bridging therapy ( 12.5 % ) . In patients with sufficient short-term anticoagulation , similar differences between DOAC and phenprocoumon groups were observed ( phenprocoumon , 18.4 % ; all DOACs , 3.8 % ; dabigatran , 0 % ; rivaroxaban , 6.6 % ) . The influence of anticoagulation medication on thrombus rates was confirmed after adjusting for baseline intergroup differences regarding left atrial size and CHA2DS2-VASc score . In conclusion , the prevalence of intracardiac thrombi was lower under DOAC therapy than under phenprocoumon in this high-risk patient cohort . Safety of CV during DOAC treatment requires further prospect i ve evaluation BACKGROUND Rivaroxaban , an oral factor Xa inhibitor , may provide a simple , fixed-dose regimen for treating acute deep-vein thrombosis ( DVT ) and for continued treatment , without the need for laboratory monitoring . METHODS We conducted an open-label , r and omized , event-driven , noninferiority study that compared oral rivaroxaban alone ( 15 mg twice daily for 3 weeks , followed by 20 mg once daily ) with subcutaneous enoxaparin followed by a vitamin K antagonist ( either warfarin or acenocoumarol ) for 3 , 6 , or 12 months in patients with acute , symptomatic DVT . In parallel , we carried out a double-blind , r and omized , event-driven superiority study that compared rivaroxaban alone ( 20 mg once daily ) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism . The primary efficacy outcome for both studies was recurrent venous thromboembolism . The principal safety outcome was major bleeding or clinical ly relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study . RESULTS The study of rivaroxaban for acute DVT included 3449 patients : 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist . Rivaroxaban had noninferior efficacy with respect to the primary outcome ( 36 events [ 2.1 % ] , vs. 51 events with enoxaparin-vitamin K antagonist [ 3.0 % ] ; hazard ratio , 0.68 ; 95 % confidence interval [ CI ] , 0.44 to 1.04 ; P<0.001 ) . The principal safety outcome occurred in 8.1 % of the patients in each group . In the continued-treatment study , which included 602 patients in the rivaroxaban group and 594 in the placebo group , rivaroxaban had superior efficacy ( 8 events [ 1.3 % ] , vs. 42 with placebo [ 7.1 % ] ; hazard ratio , 0.18 ; 95 % CI , 0.09 to 0.39 ; P<0.001 ) . Four patients in the rivaroxaban group had nonfatal major bleeding ( 0.7 % ) , versus none in the placebo group ( P=0.11 ) . CONCLUSIONS Rivaroxaban offers a simple , single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation . ( Funded by Bayer Schering Pharma and Ortho-McNeil ; Clinical Trials.gov numbers , NCT00440193 and NCT00439725 . ) AIMS X-VeRT is the first prospect i ve r and omized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion . METHODS AND RESULTS We assigned 1504 patients to rivaroxaban ( 20 mg once daily , 15 mg if creatinine clearance was between 30 and 49 mL/min ) or dose-adjusted vitamin K antagonists ( VKAs ) in a 2:1 ratio . Investigators selected either an early ( target period of 1 - 5 days after r and omization ) or delayed ( 3 - 8 weeks ) cardioversion strategy . The primary efficacy outcome was the composite of stroke , transient ischaemic attack , peripheral embolism , myocardial infa rct ion , and cardiovascular death . The primary safety outcome was major bleeding . The primary efficacy outcome occurred in 5 ( two strokes ) of 978 patients ( 0.51 % ) in the rivaroxaban group and in 5 ( two strokes ) of 492 patients ( 1.02 % ) in the VKA group [ risk ratio 0.50 ; 95 % confidence interval ( CI ) 0.15 - 1.73 ] . In the rivaroxaban group , four patients experienced primary efficacy events following early cardioversion ( 0.71 % ) and one following delayed cardioversion ( 0.24 % ) . In the VKA group , three patients had primary efficacy events following early cardioversion ( 1.08 % ) and two following delayed cardioversion ( 0.93 % ) . Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs ( P < 0.001 ) . Major bleeding occurred in six patients ( 0.6 % ) in the rivaroxaban group and four patients ( 0.8 % ) in the VKA group ( risk ratio 0.76 ; 95 % CI 0.21 - 2.67 ) . CONCLUSION Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion . NAME OF THE TRIAL REGISTRY Clinical trials.gov ; TRIAL REGISTRATION NUMBER NCT01674647 |
13,998 | 31,490,989 | The most expensive clinical events were related to renal failure , while TIA was the least expensive event .
Generally , there was substantial variation in reported cost estimates for T2DM-related events . | BACKGROUND Type 2 diabetes mellitus ( T2DM ) is an established risk factor for cardiovascular and nephropathic events .
In the Netherl and s , prevalence of T2DM is expected to be as high as 8 % by 2025 .
This will result in significant clinical and economic impact , highlighting the need for well-informed reimbursement decisions for new treatments .
However , availability and consistent use of costing method ologies is limited . | Background and Purpose — Surgical decompression reduces mortality and increases the probability of a favorable functional outcome after space-occupying hemispheric infa rct ion . Its cost-effectiveness is uncertain . Methods — We assessed clinical outcomes , costs , and cost-effectiveness for the first 3 years in patients who were r and omized to surgical decompression or best medical treatment within 48 hours after symptom onset in the Hemicraniectomy After Middle Cerebral Artery Infa rct ion With Life-Threatening Edema Trial ( HAMLET ) . Data on medical consumption were derived from case record files , hospital charts , and general practitioners . We calculated costs per quality -adjusted life year ( QALY ) . Uncertainty was assessed with bootstrapping . A Markov model was constructed to estimate costs and health outcomes after 3 years . Results — Of 39 patients enrolled within 48 hours , 21 were r and omized to surgical decompression . After 3 years , 5 surgical ( 24 % ) and 14 medical patients ( 78 % ) had died . In the first 3 years after enrollment , operated patients had more QALYs than medically treated patients ( mean difference , 1.0 QALY [ 95 % confidence interval , 0.6–1.4 ] ) , but at higher costs ( mean difference , & OV0556;127 000 [ 95 % confidence interval , 73 100–181 000 ] ) , indicating incremental costs of & OV0556;127 000 per QALY gained . Ninety-eight percent of incremental cost-effectiveness ratios replicated by bootstrapping were > & OV0556;80 000 per QALY gained . Markov modeling suggested costs of ≈&OV0556;60 000 per QALY gained for a patient ’s lifetime . Conclusions — Surgical decompression for space-occupying infa rct ion results in an increase in QALYs , but at very high costs . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N94237756 PURPOSE To assess the effectiveness and cost-effectiveness of state-of-the-art noninvasive diagnostic imaging strategies in patients with a transient ischemic attack ( TIA ) or minor stroke who are suspected of having carotid artery stenosis ( CAS ) . MATERIAL S AND METHODS All prospect ively evaluated patients provided informed consent , and the local ethics committee approved this study . Diagnostic performance , treatment , long-term events , quality of life , and costs result ing from strategies employing duplex ultrasonography ( US ) , computed tomographic ( CT ) angiography , contrast material -enhanced magnetic resonance ( MR ) angiography , and combinations of these modalities were modeled in a decision tree and Markov model . Data sources included a prospect i ve diagnostic cohort study , a meta- analysis , and a review of the literature . Outcomes were costs , quality -adjusted life-years ( QALYs ) , incremental cost-effectiveness ratios , and net health benefits ( QALY-equivalents ) , with a willingness-to-pay threshold of euro 50,000 per QALY and a societal perspective . The strategy with the highest net health benefit was considered the most cost effective . Extensive one-way , two-way , and probabilistic sensitivity analyses to explore the effect of varying parameter values were performed . The reference case analysis assumed that patients underwent surgery 2 - 4 weeks after the first symptoms , and the effect of earlier intervention was explored . RESULTS The reference case analysis showed that duplex US combined with CT angiography and surgery for 70%-99 % stenoses was the most cost-effective strategy , with a net health benefit of 13.587 and 15.542 QALY-equivalents in men and women , respectively . In men , the CT angiography strategy with a 70%-99 % cutoff yielded slightly more QALYs , at an incremental cost of euro 71,419 per QALY , compared with duplex US combined with CT angiography . In patients with a high-risk profile , in patients with a high prior probability of disease , and when patients could be treated within 2 weeks after the first symptoms , the CT angiography strategy with surgery for 50%-99 % stenoses was the most cost-effective strategy . CONCLUSION In diagnosing CAS , duplex US should be the initial test , and , if its results are positive , CT angiography should be performed ; patients with 70%-99 % stenoses should then undergo carotid endarterectomy . In patients with a high-risk profile , a high probability of CAS , or who can undergo surgery without delay , immediate CT angiography and surgery for 50%-99 % stenoses is indicated BACKGROUND Statins are lipid-lowering drugs that reduce the risk of cardiovascular events in patients with diabetes . OBJECTIVES The objective of this study was to determine whether statin treatment for primary prevention in newly diagnosed type 2 diabetes is cost-effective , taking nonadherence , baseline risk , and age into account . METHODS A cost-effectiveness analysis was performed by using a Markov model with a time horizon of 10 years . The baseline 10-year cardiovascular risk was estimated in a Dutch population of primary prevention patients with newly diagnosed diabetes from the Groningen Initiative to Analyse Type 2 Diabetes Treatment ( GIANTT ) data base , using the United Kingdom Prospect i ve Diabetes Study risk engine . Statin adherence was measured as pill days covered in the IADB.nl pharmacy research data base . Cost-effectiveness was measured in costs per quality -adjusted life-year ( QALY ) from the health care payers ' perspective . RESULTS For an average patient aged 60 years , the base case , statin treatment was highly cost-effective at € 2245 per QALY . Favorable cost-effectiveness was robust in sensitivity analysis . Differences in age and 10-year cardiovascular risk showed large differences in cost-effectiveness from almost € 100,000 per QALY to almost being cost saving . Treating all patients younger than 45 years at diabetes diagnosis was not cost-effective ( weighted cost-effectiveness of almost € 60,000 per QALY ) . CONCLUSIONS Despite the nonadherence levels observed in actual practice , statin treatment is cost-effective for primary prevention in patients newly diagnosed with type 2 diabetes . Because of large differences in cost-effectiveness according to different risk and age groups , the efficiency of the treatment could be increased by targeting patients with relatively higher cardiovascular risk and higher ages Objective : To evaluate the safety and cost-effectiveness of short-stay intensive care ( SSIC ) treatment for low-risk coronary artery bypass patients . Design : R and omized clinical equivalence trial . Setting : University Hospital Maastricht , the Netherl and s. Patients : Low-risk coronary artery bypass patients . Interventions : A total of 600 patients were r and omly assigned to undergo either SSIC treatment ( 8 hrs of intensive care treatment ) or control treatment ( care as usual , overnight intensive care treatment ) . Measurements : The primary outcome measures were intensive care readmissions and total hospital stay . The secondary outcome measures were total hospital costs , quality of life , postoperative morbidity , and mortality . Hospital costs consisted of the cost of hospital admission or admissions and outpatient costs . Main Results : The difference in intensive care readmission between the two groups of 1.13 % was very small and not significantly different ( p = .241 ; 95 % confidence interval , −0.9 % to 2.9 % ) . The total hospital stay ( p = .807 ; 95 % confidence interval , 1.2 to −0.4 ) and postoperative morbidity were comparable between the groups . The SSIC group 's quality of life improved more compared with the control group 's quality of life ( p = .0238 ; 95 % confidence interval , 0.0012 to 0.0464 ) . The total hospital costs for SSIC were significantly lower ( 95 % confidence interval , & U20AC;−1,581 to & U20AC;−174 ) compared with those for the control group ( & U20AC;4,625 and & U20AC;5,441 , respectively ) . The estimated incremental cost-effectiveness ratio ( cost/delta quality -adjusted life months ) thus showed the dominance of SSIC . Bootstrap and sensitivity analyses confirm the robustness of the study findings . Conclusions : Compared with usual care , SSIC is a safe and cost-effective approach . SSIC can be considered as an alternative for conventional postoperative intensive care treatment for low-risk coronary artery bypass graft patients Objective This study aims to systematic ally evaluate available evidence regarding direct medical costs of treating cardiovascular ( CV ) events in Germany after 2003 on an individual patient basis and from a payer perspective . The CV events of interest were myocardial infa rct ion ( MI ) , unstable angina , heart failure ( HF ) , stroke , and peripheral artery disease ( PAD ) . Method A systematic literature search was performed in the following data bases according to Preferred Reporting Items for Systematic Review s and Meta- Analysis ( PRISMA ) guidelines - Medline , Embase , Centre for Review s and Dissemination , TIBORDER , and German dissertation data base from January 2003 to October 2013 . Both observational studies and r and omized clinical trials were considered for the review . All values stated in € are inflation adjusted to 2014 € unless stated otherwise . Result This review included 13 articles . For newly occurred MI patients , the average hospitalization costs during the acute phase were reported to be between € 6790 and € 8918 per admission . In the first year after a MI event , direct medical costs were € 13,838–14,792 per patient . Direct medical costs of chronic HF patients were found to be between € 3417 and 5576 per patient per year . Treatment costs increase with disease progression . The average treatment costs for hospitalized PAD in the acute phase were reported to be € 4963 per admission , € 2535 per patient during month 1–6 after the initial hospitalization , € 1601 in month 7–12 , and € 1390 in month 13–18 . For stroke of all types , total direct medical costs in the 1st year after an event were reported to be € 13,273 per patient . Total direct medical costs during the 1st year after an ischemic stroke event were € 17,399–21,954 per patient , € 6260 in month 13–18 , and € 6496 per year in the subsequent 4 years . Conclusion MI , unstable angina , HF , stroke and PAD have a high financial impact on the German health care system . Treatment costs of these diseases are mostly incurred during the acute phase of events and tend to decrease over time . Hospitalization and rehabilitation costs were two major cost drivers . Medication costs was one of the smallest cost component reported BACKGROUND Despite the growing interest in haemodiafiltration ( HDF ) , there is no information on the costs and cost-utility of this dialysis modality yet . It was therefore our objective to study the cost-utility of HDF versus haemodialysis ( HD ) . METHODS A cost-utility analysis was performed using a Markov model . It included data from the Convective Transport Study ( CONTRAST ) , a r and omized controlled trial that compared online HDF with low-flux HD . Costs were estimated using a societal perspective . Probabilistic sensitivity analyses were performed to study uncertainty . RESULTS Total annual costs for HDF and HD were € 88 622±19,272 and € 86,086±15,945 , respectively ( in 2009 euros ) . When modelled over a 5-year period , the incremental cost per quality -adjusted life year ( QALY ) of HDF versus HD was € 287,679 . Sensitivity analyses revealed that this amount will not fall below € 140,000 , even under the most favourable assumptions like a high-convection volume ( > 20.3 L ) . CONCLUSIONS Based on accepted societal willingness-to-pay thresholds , HDF can not be considered a cost-effective treatment for patients with end-stage renal disease at present . Apparently , minor additional costs of HDF are not counterbalanced by a relevant QALY gain Background Economic evaluation of stroke services indicates that such services may lead to improved quality of life at affordable cost . The present study assesses lifetime health impact and cost consequences of stroke in an integrated service setting . Methods The EDISSE study is a prospect i ve non-r and omized controlled cluster trial that compared stroke services ( n = 151 patients ) to usual care ( n = 187 patients ) . Health status and cost trial- data were entered in multi-dimensional stroke life-tables . The tables distinguish four levels of disability which are defined by the modified Rankin scale . Quality -of-life scores ( EuroQoL-5D ) , transition and survival probabilities are based on concurrent Dutch follow-up studies . Outcomes are quality -adjusted life years lived and lifetime medical cost by disability category . An economic analysis compares outcomes from a successful stroke service to usual care , by bootstrapping individual costs and effects data from patients in each arm . Results Lifetime costs and QALYs after stroke depend on age-of-onset of first-ever stroke . Lifetime QALYs after stroke are 2.42 ( 90 % CI - 0.49 - 2.75 ) for male patients in usual care and 2.75 ( -0.61 ; 6.26 ) for females . Lifetime costs for men in the usual care setting are € 39,335 ( 15,951 ; 79,837 ) and € 42,944 ( 14,081 ; 95,944 ) for women . A comparison with the stroke service results in an ICER of € 11,685 saved per QALY gained ( € 14,211 and € 7,745 for men and women respectively ) . This stroke service is with 90 % certainty cost-effective . Conclusions Our analysis shows the potential of large health benefits and cost savings of stroke services , taking a lifetime perspective , also in other European setting The aim of this study was to determine whether between-country variations in hospital costs are larger than within-country variations and , furthermore , to explore reasons for this variability . For this purpose , we chose the primary treatment of patients with acute myocardial infa rct ion ( AMI ) as an episode of care . We obtained hospitalisation costs and reimbursement rates from 45 hospitals in nine different EU member states ( i.e. Denmark , Engl and , France , Germany , Hungary , Italy , Netherl and s , Pol and , and Spain ) for the year 2005 . To further analyse the variations in hospital costs , we employed a hierarchical r and om effects model based on treatment and hospital characteristics and using purchasing power parities ( PPPs ) as a proxy for country-specific price levels . The between-country st and ard error was estimated at 2473 euros , whereas the within-country st and ard error was estimated at 1242 euros . Our regression analysis showed that percutaneous coronary intervention was associated with significantly increased hospitals costs compared to other treatment strategies . We were able to distinguish between three groups of countries with different cost levels based on the number of hospitals that were able to provide these services ( i.e. percutaneous transluminal coronary angioplasty ( PTCA ) with intracoronary stenting ) . Excluding Hungary , Pol and , and Spain , where none of the participating hospitals were able to provide these procedures , the between-country st and ard error decreased to 1632 euros , whereas the within-country st and ard error increased to 1416 euros . Finally , we observed exogenous price-level effects between countries and within countries for hospitals located in urban areas BACKGROUND In the Netherl and s a program on quality assurance in medical care has started in 1996 . Clinical professionals , patient organizations and health services research ers formulate evidence based guidelines with a concomitant cost-effectiveness analysis . OBJECTIVES To examine the cost-effectiveness of guideline recommendations for prevention of nephropathy in diabetes mellitus type 1 and 2 . RESEARCH DESIGN A semi-Markov compartment model was developed . Data from international publications on epidemiological surveys and r and omized trials , together with national data on health care use and costs , were used to feed the model . A cohort of diabetes patients without renal disease enters the model . MEASURES Complication ( end-stage renal disease ) free years , QALY 's , and life-time medical costs per patient treated according to guideline recommendations or current anti-diabetic strategy . RESULTS Guideline treatment for type 1 diabetes yields 4.2 complication free life years , at a cost-effectiveness ratio of 13 500 ( Dutch guilders ) NLG per QALY . Type 2 diabetes patients gain 0.2 complication free life years at a cost-effectiveness ratio of 31 000 NLG per QALY . CONCLUSION Guideline development for diabetes nephropathy , with concomitant cost-effectiveness calculations , has result ed in a transparent guideline with explicit information on long-term cost and effects . The project has brought health care providers and health services research ers together Background — Percutaneous coronary intervention ( PCI ) in a day-case setting might reduce logistic constraints on hospital re sources , but data on safety are limited . We evaluated the safety and feasibility of same-day discharge after PCI . Methods and Results — Eight hundred consecutive patients scheduled for elective PCI by femoral approach were r and omized to same-day discharge or overnight hospital stay . Four hours after PCI , patients were triaged as suitable for early discharge or not . Suitable patients were discharged immediately or kept overnight , according to r and omization . Patients with an indication for extended hospital stay were not discharged regardless of r and omization . Primary end points were death , myocardial infa rct ion , coronary artery bypass graft surgery , repeat PCI , or puncture-related complications occurring within 24 hours after PCI . A total of 403 patients were assigned to same-day discharge , of whom 77 ( 19 % ) were identified for extended observation ; 397 patients were assigned to overnight stay , of whom 85 ( 21 % ) were identified for extended observation . Among all patients , the composite primary end point occurred in 9 ( 2.2 % ) same-day discharge patients and in 17 ( 4.2 % ) overnight stay patients ( risk difference , −0.020 ; 95 % CI , −0.045 to −0.004 ; P for noninferiority < 0.0001 ) . Among patients deemed suitable for early discharge , the composite end point occurred in 1 of 326 ( 0.3 % ) same-day discharge patients and 2 of 312 ( 0.6 % ) overnight-stay patients ( risk difference , −0.003 ; 95 % CI , −0.014 to 0.007 ; P for noninferiority < 0.0001 ) . The last 3 events were related to puncture site . Conclusions — Same-day discharge after elective PCI is feasible and safe in the majority ( 80 % ) of patients selected for day-case PCI . Same-day discharge does not lead to additional complications compared with overnight stay BACKGROUND Coronary revascularisation by means of surgery or percutaneous intervention plays an important role in the management of patients with ischaemic heart disease . Coronary bypass surgery without cardiopulmonary bypass ( off-pump surgery ) has been reintroduced into clinical practice to avoid complications related to the use of cardiopulmonary bypass . It is unknown whether off-pump surgery can match the outcomes of bypass surgery with cardiopulmonary bypass ( on-pump surgery ) or intracoronary stent implantation . METHODS The Octopus study comprised two multicentre r and omised trials . In the Octopump trial , on-pump surgery was compared with off-pump surgery ( 139 vs. 142 patients ) . In the Octostent trial stent implantation was compared with off-pump surgery ( 138 vs. 142 patients ) . The primary cardiac endpoint was survival free from the following cardiovascular events : stroke , myocardial infa rct ion and repeated coronary revascularisation . Secondary endpoints included quality of life and cost-effectiveness . The uncertainty surrounding the cost-effectiveness analysis was addressed by bootstrapping . RESULTS Octopump trial : at one year , event-free survival in the on-pump group was 90.6 % and in the off-pump group 88.0 % ( difference 2.6 % , 95 % CI-4.6 to 9.8 ) . Quality -adjusted years of life were 0.83 and 0.82 ( p=0.81 ) , respectively . On-pump surgery was associated with € 2089 ( 14.1 % ) additional direct medical costs per patient ( p<0.01 ) . Off-pump was more cost-effective than on-pump surgery in 95 % of bootstrap estimates . Octostent trial : at one year , event-free survival in the stent group was 85.5 % and in the off-pump surgery group 91.5 % ( difference -6.0 % , 95 % CI -13.5 to 1.4 ) . Quality -adjusted years of life were 0.82 and 0.79 ( p=0.09 ) , respectively . Stent implantation reduced direct medical costs by € 2813 ( 26.0 % ) per patient ( p=0.01 ) . Stent implantation was more cost-effective in 95 % of bootstrap estimates . CONCLUSION In selected patients eligible for bypass surgery , there was no difference in cardiac outcome between on-pump and off-pump surgery . Off-pump surgery , however , was more cost-effective than on-pump surgery and may be preferred from an economic perspective . In selected patients eligible for percutaneous coronary intervention , stent implantation was more cost-effective than off-pump surgery while maintaining comparable cardiac outcome . Therefore , stent implantation rather than off-pump surgery can be recommended as a first-choice revascularisation strategy PURPOSE To assess the cost-effectiveness of noninvasive imaging strategies in patients who have had a transient ischemic attack ( TIA ) or minor stroke and are suspected of having significant carotid artery stenosis . MATERIAL S AND METHODS From 1997 through 2000 , 350 patients were included in a multicenter blinded consecutive cohort study . The sensitivities and specificities of duplex ultrasonography ( US ) , magnetic resonance ( MR ) angiography , and these two examinations combined were estimated by using digital subtraction angiography ( DSA ) as the reference st and ard . The actual costs ( from a societal perspective ) of performing imaging and endarterectomy were estimated . The survival , quality of life , and costs associated with stroke were based on data reported in the literature . Markov modeling was used to predict long-term outcomes . Subsequently , a decision model was used to calculate costs , quality -adjusted life-years ( QALYs ) , and incremental costs per QALY gained for 62 examination-treatment strategies . Extensive sensitivity analyses were performed . RESULTS Duplex US had 88 % sensitivity and 76 % specificity with use of conventional cutoff criteria . MR angiography had comparable values : 92 % sensitivity and 76 % specificity . Combined concordant duplex US and MR angiography had superior diagnostic performance : 96 % sensitivity and 80 % specificity . Duplex US alone was the most efficient strategy . Adding MR angiography led to a marginal increase in QALYs gained but at prohibitive costs ( cost-effectiveness ratio > 1 500 000 per QALY gained ) . Performing DSA owing to discordant duplex US and MR angiographic findings and to confirm duplex US and MR angiographic findings led to extra costs and QALY loss owing to complications . Sensitivity analyses revealed that duplex US as a st and -alone examination remained the preferred strategy while estimates and assumptions were varied across plausible ranges . CONCLUSION Duplex US performed without additional imaging is cost-effective in the selection of symptomatic patients suitable for endarterectomy . Adding MR angiography increases effectiveness slightly at disproportionately high costs , whereas DSA is inferior because of associated complications Summary We examined the incremental cost – effectiveness of telemonitoring ( TM ) versus usual care ( UC ) in patients with congestive heart failure ( CHF ) . In one university and two general hospitals , 382 patients were r and omised to usual care or telemonitoring and followed for 1 year . Hospital-related and home costs were estimated , based on re source use multiplied by the appropriate unit prices . Effectiveness was expressed as QALYs gained . Information was gathered , using 3 monthly costs diaries and question naires . The mean age of the patients was 71 years ( range 32–93 ) , 59 % were male and 64 % lived with a partner . Health related quality of life improved by 0.07 points for the usual care and 0.1 points for the telemonitoring group , but the difference between groups was not significant . There were no significant differences in annual costs per patient between groups . At a threshold of € 50,000 the probability of telemonitoring being cost-effective was 48 % . The cost effectiveness analysis showed a high level of decision uncertainty , probably caused by the divergence between the participating institutions . It is therefore premature to draw an unambiguous conclusion regarding cost-effectiveness for the whole group BACKGROUND R and omized trials have shown that integrating services for acute stroke care may lead to organizational improvements , higher efficiency and better patient outcomes in the acute phase . AIM To compare the costs and effects of stroke services in an experimental group of patients compared to a group of patients receiving conventional care . DESIGN Prospect i ve non-r and omized controlled trial . METHODS We compared all consecutively hospitalized stroke patients in three experimental stroke service setting s ( Delft , Haarlem and Nijmegen , n = 411 ) with concurrent patients receiving conventional stroke care ( n = 187 ) over 6 months follow-up . Main end-points were total costs per patient and total health-adjusted days per 100 patients as measured by the EuroQol-5D score during follow-up . RESULTS Mean total costs per patient were 16,000 Euro ( 95%CI 14,670 Euro-16,930 Euro ) : 13,160 Euro in Delft , 16,790 Euro in Haarlem , 20,230 Euro in Nijmegen , and 13,810 Euro in the control regions . Early discharge in Delft saved about 2500 Euro hospital costs per patient . General patient health in Delft was significantly better than in the control regions ; Haarlem and Nijmegen showed no difference in health . DISCUSSION Our study confirms the potential to improve stroke outcomes in a cost-effective way in Dutch setting s. This was seen in the group of patients in Delft , a complete and relatively simple stroke service , but not in two other regions with more complex stroke services . Important factors are reduction of hospital days and , most likely , adequate multidisciplinary rehabilitation Despite the importance of hemodialysis vascular access , the cost of vascular access care has not been studied in detail . A prospect i ve cost analysis was performed among incident hemodialysis patients to determine the cost of vascular access care overall and on the basis of access type . Detailed clinical and demographic information , as well as data on access type , was collected for all local incident hemodialysis patients between July 1 , 1999 , and November 1 , 2001 . A comprehensive measure of total vascular access costs , including surgery , radiology , hospitalization for access complications , physician costs , costs for management of outpatient bacteremia , and vascular access monitoring costs , was obtained . Costs are reported in 2002 Canadian dollars ( 1 CAN dollar = 0.69 US dollar ) . A total of 239 consecutive incident hemodialysis patients were identified , 49 , 157 , and 33 of whom were dialyzed exclusively with a catheter or had a native arteriovenous fistula or synthetic graft attempted , respectively . In year 1 , 18.4 % of all hospital admissions were for vascular access-related complications . The mean cost of all vascular access care in year 1 was 6890 CAN dollars(median 4020 dollars ; interquartile range [ IQR ] 2440 dollars to 7540 dollars ) . The mean cost of access care per patient-year at risk for maintaining a catheter exclusively , attempting an arteriovenous fistula , or attempting a graft was 9180 dollars ( median 3812 dollars ; IQR 2250 dollars to 7762 dollars ) , 7989 dollars ( median 4641 dollars ; IQR 3035 dollars to 8832 dollars ) , and 11,685 dollars ( median 8152 dollars ; IQR 3395 dollars to 12,908 dollars ) , respectively ( P = 0.01 ) . Vascular access care is responsible for a significant proportion of health care costs in the first year of hemodialysis . These results support clinical practice guidelines that recommend preferential placement of a native fistula BACKGROUND The multicentre , r and omised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina , with one or more de-novo lesions , less than 18 mm long , in vessels of diameter 3 mm or more . METHODS 827 patients were r and omly assigned stent implantation ( 414 patients ) or st and ard balloon angioplasty ( 413 patients ) . The primary clinical endpoint was event-free survival at 6 months , including death , myocardial infa rct ion , and the need for revascularisation . The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months . There was also one-to-one subr and omisation to either clinical and angiographic follow-up or clinical follow-up alone . Analyses were by intention to treat . FINDINGS Four patients ( one stent group , three angioplasty group ) were excluded from analysis since no lesion was found . At 6 months , a primary clinical endpoint had occurred in 53 ( 12.8 % ) of 413 patients in the stent group and 79 ( 19.3 % ) of 410 in the angioplasty group ( p=0.013 ) . This significant difference in clinical outcome was maintained at 12 months . In the subgroup assigned angiographic follow-up , the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group , ( 1.89 [ SD 0.65 ] vs 1.66 [ 0.57 ] mm , p=0.0002 ) , which corresponds to restenosis rates ( diameter stenosis > or = 50 % ) of 16 % and 31 % ( p=0.0008 ) . In the group assigned clinical follow-up alone , event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group ( 0.89 vs 0.79 , p=0.004 ) at a cost of an additional 2085 Dutch guilders ( US$ 1020 ) per patient . INTERPRETATION Over 12-month follow-up , a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty Aims Recent cost-effectiveness analyses of percutaneous coronary intervention ( PCI ) versus coronary artery bypass grafting ( CABG ) have been limited by a short time horizon or were restricted to the US healthcare perspective . We , therefore , used individual patient-level data from the SYNTAX trial to evaluate the cost-effectiveness of PCI versus CABG from a European ( Dutch ) perspective . Methods and results Between 2005 and 2007 , 1800 patients with three-vessel or left main coronary artery disease were r and omised to either CABG ( n=897 ) or PCI with drug-eluting stents ( DES ; n=903 ) . Costs were estimated for all patients based on observed healthcare re source usage over 5 years of follow-up . Health state utilities were evaluated with the EuroQOL question naire . A patient-level microsimulation model based on Dutch life-tables was used to extrapolate the 5-year in-trial data to a lifetime horizon . Although initial procedural costs were lower for CABG , total initial hospitalisation costs per patient were higher ( € 17 506 vs € 14 037 , p<0.001 ) . PCI was more costly during the next 5 years of follow-up , due to more frequent hospitalisations , repeat revascularisation procedures and higher medication costs . Nevertheless , total 5-year costs remained € 2465/patient higher with CABG . When the in-trial results were extrapolated to a lifetime horizon , CABG was projected to be economically attractive relative to DES-PCI , with gains in both life expectancy and quality -adjusted life expectancy . The incremental cost-effectiveness ratio ( ICER ) ( € 5390/ quality -adjusted life year ( QALY ) gained ) was favourable and remained < € 80 000/QALY in > 90 % of the bootstrap replicates . Outcomes were similar when incorporating the prognostic impact of non-fatal myocardial infa rct ion and stroke , as well as across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs . However , DES-PCI was economically dominant compared with CABG in patients with a SYNTAX Score ≤22 or in those with left main disease . In patients for whom the SYNTAX Score II favoured PCI based on lower predicted 4-year mortality , PCI was also economically dominant , whereas in those patients for whom the SYNTAX Score II favoured surgery , CABG was highly economically attractive ( ICER range , € 2967 to € 3737/QALY gained ) . Conclusions For the broad population with three-vessel or left main disease who are c and i date s for either CABG or PCI , we found that CABG is a clinical ly and economically attractive revascularisation strategy compared with DES-PCI from a Dutch healthcare perspective . The cost-effectiveness of CABG versus PCI differed according to several anatomic factors , however . The newly developed SYNTAX Score II provides enhanced prognostic discrimination in this population , and may be a useful tool to guide re source allocation as well . Trial registration number Clinical trial unique identifier : NCT00114972 ( http://www . clinical -trials.gov Background and Objective Many patients with type 2 diabetes mellitus ( T2DM ) on insulin therapy have inadequate glycaemic control . In such cases , Dutch guidelines recommend unlimited up-titration of insulin , yet in practice many patients never reach their glycaemic target . Clinical evidence shows that dapagliflozin — a highly selective sodium – glucose cotransporter 2 inhibitor — meets a need for these patients , i.e. by reducing glycated haemoglobin levels and bodyweight . We estimated the cost effectiveness and cost utility of adding dapagliflozin to insulin compared with not adding dapagliflozin in patients with T2DM who have inadequate glycaemic control while on insulin . Methods The cost effectiveness of dapagliflozin was estimated using the Cardiff Diabetes Model , using direct comparative efficacy data from a r and omized placebo-controlled trial ( Clinical Trials.gov identifier NCT00673231 ) . In this trial , up-titration of insulin was allowed in case of severe glycaemic imbalance . Risk factor progression and the occurrence of future vascular events were estimated using the United Kingdom Prospect i ve Diabetes Study 68 risk equations . Costs and utilities were derived from the literature . The analysis was conducted from the societal perspective , simulating the remaining lifetime of the patients . Results The overall incidence of macro- and microvascular complications was lower , and life expectancy was greater ( 19.43 versus 19.35 life-years [ LYs ] ) in patients receiving dapagliflozin than in those not receiving dapagliflozin . Patients in the dapagliflozin arm obtained an incremental benefit of 0.42 quality -adjusted life-years ( QALYs ) . The lifetime incremental cost per patient in the dapagliflozin arm was € 2,293 , result ing in an incremental cost-effectiveness ratio of € 27,779 per LY gained and an incremental cost – utility ratio of € 5,502 per QALY gained . Sensitivity and scenario analyses showed that the results were insensitive to variations in modelling assumptions and input variables . Conclusion Dapagliflozin in combination with insulin was estimated to be a cost-effective treatment option for patients with T2DM whose insulin treatment regimen does not provide adequate glycaemic control in a Dutch healthcare setting |
13,999 | 32,222,797 | Application of the OKR can rule out knee fracture and thus avoid unnecessary radiography .
These results also translate to improved efficiency , lower medical costs and reduced waiting times .
• The Ottawa Knee Rule helps clinicians to rule out fracture in adults with an acute knee injury .
• The rule allows a reduction in radiography requests , patient waiting time in the emergency department and healthcare costs | This systematic review and meta- analysis aim ed to evaluate the current evidence on the diagnostic accuracy of the Ottawa Knee Rule ( OKR ) for acute knee injuries in adults . | Background This study was design ed to determine the accuracy of the Ottawa Knee Rule ( OKR ) when applied to patients with acute knee injury in the Iranian population of the Imam Hospital Emergency Department ( ED ) at . Methods This prospect i ve cohort validation study included a convenience sample of all patients with a blunt knee injury sustained in the preceding 7 days presenting to the ED of a tertiary care teaching hospital during the study period . Patients were assessed for the five variables comprising the OKR , and a st and ardised data form was completed for each patient . St and ard knee radiographs were ordered on all patients irrespective of the determination of the rule . The rules were interpreted by the primary investigator on the basis of the data sheet and the final orthopaedist radiograph reading . Outcome measures of this study were : sensitivity , specificity , positive predictive value and negative predictive value of the OKR . Results A total of 283 patients were enrolled in the study . 22 fractures ( 7.77 % ) were detected . The decision rule had a sensitivity of 0.95 ( 95 % CI 0.77 to 0.99 ) , and a specificity of 0.44 ( 95 % CI 0.37 to 0.50 ) . The potential reduction in use of radiography was estimated to be 41 % . The OKR missed only one fracture . Conclusion Prospect i ve validation has shown that the OKR is a highly sensitive tool for detecting knee fractures and has the potential to reduce the number of radiographs in patients with acute knee injuries OBJECTIVE To determine interobserver agreement between triage registered nurses ( RNs ) and emergency physicians ( EPs ) regarding indication for knee radiographs by applying the Ottawa knee rule ( OKR ) and individual components of the rule . METHODS This was a prospect i ve , observational study in a suburban , teaching emergency department . The study enrolled a convenience sample of patients aged > 17 years with traumatic knee injuries less than one week old . Patients with prior knee surgery or distracting conditions were excluded . Before study initiation , the RNs and EPs were in-serviced in the OKR . Nurses and EPs independently examined each patient for OKR criteria , blinded to the other 's assessment . Knee radiographs were ordered at the discretion of the EP and were interpreted by board-certified radiologists . All patients received follow-up with a structured telephone interview to identify any undetected fractures . Kappa was calculated for each component and the overall application of the OKR to assess interobserver agreement . RESULTS Ninety-six patients were enrolled . The mean age was 39.6 + /- 18.7 years ; 50 % were male . Eight patients ( 8 % ) had knee fractures . Interobserver agreements between the RNs and EPs for individual components of the OKR were : age > or = 55 years ( kappa = 0.97 ) ; inability to weight bear ( kappa = 0.51 ) ; inability to bend knee to 90 degrees ( kappa = 0.52 ) ; fibular head tenderness ( kappa = 0.45 ) ; and isolated patellar tenderness ( kappa = 0.40 ) . The EPs and RNs agreed with OKR criteria for x-ray 71 % of the time ( kappa = 0.41 ) . CONCLUSIONS The only criterion that result ed in almost perfect agreement between the RNs and EPs was patient age ; agreement for the other four criteria and the overall decision to order x-rays was moderate OBJECTIVE To vali date a previously derived decision rule for the use of radiography in patients with acute knee injury . DESIGN Prospect ively administered survey . SETTING Emergency departments of two university hospitals serving adults . PATIENTS Convenience sample of 1096 of 1251 eligible adults with acute knee injuries ; 124 patients were examined by two physicians . MAIN OUTCOME MEASURES Attending emergency physicians assessed each patient for st and ardized clinical variables and determined the need for radiography according to the decision rule . Patients who did not have radiography underwent a structured telephone interview at day 14 to determine the possibility of a fracture . The rule was assessed for ability to correctly identify the criterion st and ard , fracture of the knee . An attempt was made to refine the rule by means of univariate and recursive partitioning analyses . RESULTS The decision rule had a sensitivity of 1.0 ( 95 % confidence interval [ CI ] , 0.94 to 1.0 ) for identifying 63 clinical ly important fractures . Physicians correctly interpreted the rule in 96 % of cases , and the k value for interpretation was 0.77 ( 95 % CI , 0.65 to 0.89 ) . The potential relative reduction in use of radiography was estimated to be 28 % . The probability of fracture , if the decision rule were " negative , " is estimated to be 0 % ( 95 % CI , 0 % to 0.4 % ) . Attempts to refine the rule led to a model with improved specificity but with an unacceptable loss of sensitivity . CONCLUSION Prospect i ve validation has shown this decision rule to be 100 % sensitive for identifying fractures of the knee , to be reliable and acceptable , and to have the potential to allow physicians to reduce the use of radiography in patients with acute knee injury Abstract . Our objective was to determine the value of the Ottawa knee rules when applied by users with different levels of clinical training . We used a prospect i ve patient survey by the medical students and surgery residents of a European university trauma centre . The study group consisted of 261 eligible patients who presented with acute knee trauma during a 6-month period . Radiography or follow-up was obtained for each patient . Data were separately analysed according to the degree of qualification of the initial examiner . The Ottawa knee rules had a sensitivity and a negative predictive value of 1.00 . Variable degree of medical competence of the users did not alter the accuracy of the rules . Application of the rules would have reduced knee radiography requests by 25 % . The Ottawa knee rules remain highly sensitive when applied by medical users with different levels of qualification , such as encountered in a teaching setting STUDY OBJECTIVE To derive a highly sensitive decision rule for the selective use of radiography in acute knee injuries . DESIGN Prospect ively administered survey . SETTING Emergency departments of two university hospitals . PARTICIPANTS Convenience sample of 1,047 adults with acute knee injuries . RESULTS Attending emergency physicians assessed each patient for 23 st and ardized clinical findings , which were recorded on data collection forms . A total of 127 patients was examined independently by two physicians to determine interobserver agreement . The outcome measure was fracture of the knee . Any patients who did not have ED radiography underwent a structured telephone interview to determine the possibility of a missed fracture . Those variables found to be both reliable ( highest kappa values ) and strongly associated with a fracture ( highest chi 2 values ) were further analyzed by a recursive-partitioning multivariate technique . The derived decision rule included the following variables : ( 1 ) age 55 years or older , ( 2 ) tenderness at the head of the fibula , ( 3 ) isolated tenderness of the patella , ( 4 ) inability to flex to 90 degrees , and ( 5 ) inability to bear weight both immediately and in the ED ( four steps ) . The presence of one or more of these findings would have identified the 68 fractures in the study population with a sensitivity of 1.0 ( 95 % confidence interval [ Cl ] , .95 to 1.0 ) and a specificity of .54 ( 95 % Cl , .51 to .57 ) . Application of the rule would have led to a 28.0 % relative reduction in the use of radiography from 68.6 % to 49.4 % in the study population . CONCLUSION A practical , highly sensitive , and reliable decision rule for the use of radiography in acute knee injuries has been derived . Clinical application should await prospect i ve validation of the rule OBJECTIVES To study : 1 ) the efficiency of the current use of radiography in acute knee injuries , 2 ) the judgments and attitudes of experienced clinicians in their use of knee radiography , and 3 ) the potential for decision rules to improve efficiency . METHODS This two-stage study of adults with acute knee injuries involved : 1 ) a retrospective review of all 1,967 patients seen over a 12-month period in the EDs of one community and two teaching hospital , and 2 ) a prospect i ve survey of another 1,040 patients seen by attending emergency physicians . The prospect i ve survey assessed each clinician 's estimate of the probability of a knee or patella fracture ; 120 patients were independently assessed by two physicians . RESULTS Of the 1,967 patients seen in the first stage , 74.1 % underwent radiography but only 5.2 % were found to have fractures . Of the 1,727 knee and patella radiographic series ordered , 92.4 % were negative for fracture . In the second stage , experienced physicians predicted the probability of fracture to be 0 or 0.1 for 75.6 % of the patients . The kappa value for this response was 0.51 ( 95 % CI 0.34 to 0.68 ) . The physicians also indicated that they would have been comfortable or very comfortable in not ordering radiography for 55.5 % of the patients . The area under the receiver operating characteristics curve for the physicians ' prediction of fracture was 0.87 ( 95 % CI 0.82 to 0.91 ) , reflecting good discrimination between fracture and nonfracture cases . Likelihood ratios for the physicians ' prediction ranged from 0.09 at the 0 level to 42.9 at the 0.9 - 1.0 level . CONCLUSIONS Emergency physicians order radiography for most patients with acute knee injuries , even though they can accurately discriminate between fracture and nonfracture cases and expect most of the radiographs to be normal . These findings suggest great potential for more efficient use of knee radiography , possibly through the use of a clinical decision rule We design ed a prospect i ve observational study to attempt to vali date two recently described clinical decision rules for knee radiography . Consecutive patients aged > or = 15 yr with acute knee injuries occurring less than 1 wk prior to presentation were included for study . Patients with distracting conditions , open knee injuries , or previous surgery were excluded . Each patient was assessed for 7 historical and 15 physical examination criteria that were recorded on a st and ardized data collection instrument . Radiographs were ordered at the discretion of the attending physician and were read by two board-certified radiologists . When radiographs were not ordered , structured telephone follow-up was performed after 3 wk . The main outcome parameter was the presence or absence of a clinical ly significant fracture . There were 351 patients in the study ; 26 ( 7 % ) had knee fractures . Fractures were significantly associated with an increased prevalence for two of the three criteria in the rule derived by Bauer : inability to weight bear immediately or in the emergency department ( ED ; 76.9 % of patients with a fracture vs. 29.8 % of patients without a fracture ) and effusion ( 53.8 % vs. 28.9 % , respectively ) . Ecchymosis was not significantly associated with fracture ( 19.2 % with fracture vs. 9 % with no fracture ) . Use of the Bauer rule would have led to a radiographic evaluation of 22 of the 26 patients with knee fractures ( sensitivity = 84.6 % , specificity = 48.9 % ) . Fractures were associated with a significantly increased prevalence for three of the five criteria in the decision rule proposed by Stiell : isolated patella tenderness ( 30.8 % with fracture vs. 14.5 % with no fracture ) , inability to flex the knee to 90 degrees ( 42.3 % vs. 19.7 % , respectively ) , and inability to weight bear immediately and in the ED ( 57.7 % vs. 18.8 % , respectively ) . Age > or = 55 yr ( 23.1 % vs. 12.0 % , respectively ) and fibula head tenderness ( 11.5 % vs. 5.5 % , respectively ) were not significantly associated with fracture . Use of the Stiell rule would have led to radiographic evaluation of 22 of the 26 patients with knee fractures ( sensitivity = 84.6 % , specificity = 49.8 % ) . We conclude that neither clinical decision rule is 100 % sensitive . Further refinement will be necessary to identify all patients with knee fractures CONTEXT The Ottawa Knee Rule is a previously vali date d clinical decision rule that was developed to allow physicians to be more selective and efficient in their use of plain radiography for patients with acute knee injuries . OBJECTIVE To assess the impact on clinical practice of implementing the Ottawa Knee Rule . DESIGN Controlled clinical trial with before-after and concurrent controls . SETTING Emergency departments of 2 teaching and 2 community hospitals . PATIENTS All 3907 consecutive eligible adults seen with acute knee injuries during two 12-month periods before and after the intervention . INTERVENTION During the after period in the 2 intervention hospitals , the Ottawa Knee Rule was taught to all house staff and attending physicians who were encouraged to order knee radiography according to the rule . MAIN OUTCOME MEASURES Referral for knee radiography , accuracy and reliability of the rule , mean time in emergency department , and mean charges . RESULTS There was a relative reduction of 26.4 % in the proportion of patients referred for knee radiography in the intervention group ( 77.6 % vs 57.1 % ; P<.001 ) , but a relative reduction of only 1.3 % in the control group ( 76.9 % vs 75.9 % ; P=.60 ) . These changes over time were significant when the intervention and control groups were compared ( P<.001 ) . The rule was found to have a sensitivity of 1.0 ( 95 % confidence interval [ CI ] , 0.94 - 1.0 ) for detecting 58 knee fractures . The K coefficient for interpretation of the rule was 0.91 ( 95 % CI , 0.82 - 1.0 ) . Compared with nonfracture patients who underwent radiography during the after-intervention period , those discharged without radiography spent less time in the emergency department ( 85.7 minutes vs 118.8 minutes ) and incurred lower estimated total medical charges for physician visits and radiography ( US $ 80 vs US $ 183 ) . CONCLUSIONS Implementation of the Ottawa Knee Rule led to a decrease in use of knee radiography without patient dissatisfaction or missed fractures and was associated with reduced waiting times and costs . Widespread use of the rule could lead to important health care savings without jeopardizing patient care STUDY OBJECTIVE We sought to vali date the Ottawa Knee Rules for determining the need for radiography in patients with acute knee injury . METHODS A prospect i ve cohort study was performed in emergency departments of 11 hospitals of the Osakidetza-Basque Country Health Service . The patient population was composed of a convenience sample of 1,522 eligible adults of 2,315 patients with acute knee injuries . The attending emergency physicians assessed each patient for st and ardized clinical variables and determined the need for radiography according to the decision rule . Radiography was performed in each patient , irrespective of the determination of the rule , after clinical evaluation findings were recorded . The rule was assessed for the ability to correctly identify fracture of the knee . RESULTS The decision rule had a sensitivity of 1.0 ( 95 % confidence interval [ CI ] 0.96 to 1.0 ) , identifying 89 patients with clinical ly important fractures . The potential reduction in use of radiography was estimated to be 49 % . The probability of fracture , if the decision rules were negative , is estimated to be 0 % ( 95 % CI 0 % to 0.5 % ) . CONCLUSION Prospect i ve validation has shown the Ottawa Knee Rules to be 100 % sensitive for identifying fractures of the knee and to have the potential to allow physicians to reduce the use of radiography in patients with acute knee injuries OBJECTIVE To determine whether triage nurses can successfully interpret the Ottawa Knee Rule ( OKR ) and order knee radiographs according to the OKR . METHODS This was a prospect i ve implementation trial of a clinical decision rule , set in a suburban , community emergency department ( ED ) , evaluating a convenience sample of ED patients aged > 17 years with acute knee injuries . Patients were excluded for altered mental status , distracting injuries , and knee lacerations . Triage nurses and attending emergency physicians ( EPs ) were trained in appropriate use of the OKR . The triage nurses evaluated eligible patients and radiographs were ordered according to their interpretation of the OKR . EPs who were initially blinded to the triage assessment s also evaluated the patients . EPs could add an x-ray order if , according to their assessment of the OKR , one was indicated and a radiograph had not been ordered by the nurse . Nurses and EPs recorded their blinded assessment s on st and ardized data collection instruments . Kappa values were calculated to assess interobserver agreement ( IOA ) between nurses and EPs ; sensitivity , specificity , negative predictive value ( NPV ) , and positive predictive value ( PPV ) were calculated as appropriate . RESULTS One hundred three patients were enrolled ; 53 % were female ; 10 fractures were identified ( 9.7 % ) . The IOAs between the nurses and EPs for each of the criteria were moderate to almost perfect : age-0.94 ; fibular head tenderness-0.4 ; isolated patellar tenderness-0.68 ; inability to bend knee to 90 degrees-0.73 ; inability to bear weight-0.76 . The IOA was moderate ( 0.52 ) for the overall interpretation of the OKR by nurses and EPs . Sensitivity of nurse interpretation of the OKR for fracture was 70 % , specificity 33 % , NPV 91 % , PPV 10 % . Sensitivity of EP interpretation of the OKR for fracture was 100 % , specificity 25 % , NPV 100 % , PPV 13 % . CONCLUSIONS Triage nurses showed fair to good ability to appropriately apply the OKR to pre-order knee radiographs OBJECTIVE We evaluated the Ottawa knee rules in a high-volume teaching hospital in the United States to determine whether the rules could be safely used to decide whether patients with acute blunt knee trauma should undergo radiography . SUBJECTS AND METHODS During a 13-month period , 378 patients with acute blunt knee trauma were prospect ively examined using the Ottawa knee rules . Data collected included the presence or absence of fracture predictors and the results of radiography . RESULTS A fracture was seen in 43 ( 11 % ) of the 378 patients who met inclusion criteria . The knee rules predicted 42 of the 43 fractures ; sensitivity was 98 % , and specificity was 19 % . Radiography of 65 patients ( 17 % ) who had no predictors for fracture could have been avoided if the knee rules had been used to screen for radiography . CONCLUSION The Ottawa knee rules are highly sensitive for fracture in this setting and may safely be used to decide whether patients with acute blunt knee trauma should undergo radiography |
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