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13,400 | 29,885,907 | CONCLUSION Nurse-initiated analgesia was associated with safe , timely and effective pain relief | AIM This paper reports a systematic literature review evaluating the impact and quality of pain management associated with nurse initiated analgesia in patients presenting to the emergency department ( ED ) .
BACKGROUND Pain is a major presenting complaint for individuals attending the ED .
Timely access to effective analgesia continues to be a global concern in the ED setting ; emergency nurses are optimally positioned to improve detection and management of pain . | Background : Pain is the most common reason due to which patients come to the emergency department ( ED ) . Aim : The purpose of this study was to measure the correlation , if any , between pain reduction and the level of satisfaction in patients who presented to the ED with pain as their chief complaint . Material s and Methods : This study used a r and omly selected group of patients who presented to the ED with pain of 4 or more on the Visual Analogue Pain Scale ( VAS ) as their chief complaint to a level one adult and pediatric trauma center . Instruments that were used in this study were the VAS , Brief Pain Inventory ( BPI ) , and the Medical Interview Satisfaction Scale ( MISS ) . They were administered to patients by research fellows in the treatment rooms . Statistical analysis included frequencies , descriptive , and linear regression . This study was approved by the Internal Review Board . Results : A total of 159 patients were enrolled in the study . All patients were given some type of treatment for their pain upon arrival to the ED . A logistic regression showed a significant relationship to reduction in pain by 40 % or more and customer service questions . Conclusions : A reduction in perceived pain levels does directly relate to several indicators of customer service . Patients who experienced pain relief during their stay in the ED had significant increases in distress relief , rapport with their doctor , and intent to comply with given instructions OBJECTIVES The objectives of this study were : ( i ) to measure the analgesic efficacy and frequency of adverse events following autonomous nurse-initiated intravenous morphine in patients presenting with acute pain , awaiting medical assessment ; and ( ii ) to determine whether such a process would improve the time to analgesia . METHODS A prospect i ve convenience sample of patients presenting in acute pain received titrated intravenous morphine by experienced emergency nurses . Pain scores on a 10.0 cm visual analogue scale and predetermined adverse events defined by physiological parameters were measured at regular intervals over the following 60 min . Demographic , diagnostic and waiting time data were also recorded . RESULTS Three hundred and forty nine patients were enrolled over a 12-month period . The median initial pain score was 8.5 cm , with a reduction to 4.0 cm at 1 h. Respiratory rate , oxygen saturation , heart rate and blood pressure all showed small but statistically significant reductions over 60 min . There were 15 predefined adverse events , 10 episodes of hypotension and five episodes of oxygen desaturation . No intervention other than supplemental oxygen was required . There were no episodes of bradycardia , bradypnoea or reduced level of consciousness . The median time to narcotic was 18 min and the median time to be seen by a doctor was 52 min . CONCLUSION Experienced emergency nurses can initiate effective intravenous narcotic analgesia for patients in acute pain awaiting medical assessment , with minimal change in physiological parameters . This process can improve the time to analgesia for patients in acute pain INTRODUCTION Timely and appropriate pain management is an important quality indicator of ED performance . Emergency health care workers are well positioned to become active leaders and innovatively responsive in reducing human suffering . A pain management audit was conducted to determine Australia practice patterns . METHODS A 12-month retrospective descriptive cohort audit was undertaken . Through the r and omization process a medical record audit tool was completed for each record identified . Ethical approval for the study was obtained . RESULTS Seventy-four hospitals agreed to conduct the audit , 36 ( 48 % ) provided data . The total number of patient notes review ed was 2,066 . Ninety-five percent ( 1,966 ) of patients arrived by ambulance . Of the patients ( n=547 ; 56.4 % ) with a documented triage pain score the majority arrived in severe pain ( n=300 ; 41.3 % ) . Of the total number of patients ( 1,966 ) documented arriving in pain 1,473 ( 74.9 % ) received an analgesic . Six hundred and forty-four ( 32.7 % ) patients received an opioid . From time of emergency department arrival , the median time for analgesic administration was 70 minutes ( IQR 58 minutes to 92 minutes ) . Twenty-five emergency departments ( 69.4 % ) had pain management policies that enabled nurses to initiate a pharmacological analgesia without medical consultation . DISCUSSION The Australian pain management audit highlighted current practice s and potential areas for further research . While the audit demonstrated that nurse initiated pain management interventions promoted better analgesic response , greater consistency of triage pain assessment , code allocation , and documentation of pain scores may go some way to improving the timeliness of analgesia STUDY OBJECTIVE Emergency department ( ED ) crowding is a common and complicated problem challenging EDs worldwide . Nurse-initiated protocol s , diagnostics , or treatments implemented by nurses before patients are treated by a physician or nurse practitioner have been suggested as a potential strategy to improve patient flow . METHODS This is a computer-r and omized , pragmatic , controlled evaluation of 6 nurse-initiated protocol s in a busy , crowded , inner-city ED . The primary outcomes included time to diagnostic test , time to treatment , time to consultation , or ED length of stay . RESULTS Protocol s decreased the median time to acetaminophen for patients presenting with pain or fever by 186 minutes ( 95 % confidence interval [ CI ] 76 to 296 minutes ) and the median time to troponin for patients presenting with suspected ischemic chest pain by 79 minutes ( 95 % CI 21 to 179 minutes ) . Median ED length of stay was reduced by 224 minutes ( 95 % CI -19 to 467 minutes ) by implementing a suspected fractured hip protocol . A vaginal bleeding during pregnancy protocol reduced median ED length of stay by 232 minutes ( 95 % CI 26 to 438 minutes ) . CONCLUSION Targeting specific patient groups with carefully written protocol s can result in improved time to test or medication and , in some cases , reduce ED length of stay . A cooperative and collaborative interdisciplinary group is essential to success AIM The purpose of this prospect i ve observational study was to characterise patients occupying the ambulance bay and to determine the ensuing nursing workload . BACKGROUND The number of patients presenting to ED by ambulance is increasing . During periods of peak dem and and access block in the ED , patients with ongoing care needs , requiring continual assessment and symptom management by emergency nurses can remain in the ambulance bay for extended periods of time . The profile of these patients and on the related nursing workload is not well known . METHODS A prospect i ve observational study design based upon a convenience sample of patients was conducted over a r and omly selected four-week period . Nursing workload was assessing using the Jones Dependency Tool . A modified Work Observation Method By Activity Timing technique was used to estimate direct nursing care time . RESULTS Of 4068 presentations to ED , 640 ( 16 % ) occupied the ambulance bay following triage , of which the majority ( n=408 ; 64 % ) had arrived by ambulance . Of those occupying the ambulance bay 205 ( 32 % ) were evaluated using the JDT . The majority of patients had potentially life-threatening symptoms ( ATS 3 , n=424 ; 66 % ) , were moderately dependent ( n=134 ; 65 % ) , and consumed approximately 152.1h of direct nursing care time . A large proportion of direct nursing care time was spent on patient re assessment ( 60.4h ) and pain management ( 29.6h ) . Patients occupying the ambulance bay had an average ED length of stay of 5.6h ( 4.6h ) , of which 1.8h ( SD 1.8h ) was spent delayed in the ambulance bay . CONCLUSION Early detailed assessment and symptom management of patients occupying the ambulance bay is extensively undertaken by emergency nurses . The frequency and number of patients off-loaded into non- clinical areas is not currently monitored or reported upon . This study has demonstrated that patients managed in the ambulance bay consume large amounts of nursing re sources , commonly require acute level care and hospital admission OBJECTIVES The aims of this study were to 1 ) estimate differences in pain management process and patient-reported outcomes , pre- and postimplementation of analgesic protocol s for adults with sickle cell disease ( SCD ) , and 2 ) examine the effects of site and visit frequency on changes in pain scores and time to analgesic . METHODS A multicenter , prospect i ve , longitudinal study enrolled patients from three academic medical centers between October 2007 and September 2009 . All ED patients 18 years or older with a chief complaint of a sickle cell pain episode were enrolled . Sites formed a SCD quality improvement ( QI ) team and implemented st and ard nurse-initiated emergency department ( ED ) analgesic protocol s ; outcomes were compared between study periods defined as pre- and postimplementation of protocol s. Medical record review was conducted to measure time to administration of initial analgesic , opioids used , route of opioid administration , the change in pain scores from arrival to discharge ( negative numbers reflect a decrease in pain scores ) , and the number of ED visits per individual patient during the study period at each site . On day 7 after the ED visit , a follow-up phone interview was conducted . Patients were queried about their ED pain management using a scale from 1 to 10 ( 1 = outst and ing , 10 = worst ) . Descriptive statistics are used to report the results . Ordinary least-squares regression models were constructed to measure the effect of time period , site , and number of visits per patient on change in pain score . RESULTS During the study period , 342 unique patients ( 57 % female , mean ± SD age = 32 ± 11 years ) were enrolled and had a total of 2,934 visits . There was no difference in time to administration of the initial analgesic between study periods . Overall , there was a significant decrease in pain scores from arrival to discharge between the pre- and postintervention study periods : the average difference in arrival to discharge pain scores ( cm ) was greater during the postimplementation period than during the preintervention period ( -4.1 vs. -3.6 , t = 2.6 , p < 0.01 ) . Site 1 had significant improvement between study periods ( mean difference = -0.87 , t = 2.63 , p < 0.01 ; F = 14.3 , p < 0.01 ) . Patients with few ED visits ( one to six annual visits , mean difference = -1.55 , t = 2.1 , p = 0.04 ) and those with frequent ED visits ( 7 to 19 annual visits , mean difference = -1.65 , t = 3.52 , p < 0.01 ) had a significant decrease in pain scores compared to patients with very frequent ED visits ( > 19 visits ) . There was an overall decrease in the use of morphine sulfate ( MS ) and increase in the use of hydromorphone ( χ(2 ) = 105.67 , p < 0.001 ) between study periods and a significant increase in the use of oral ( PO ) and subcutaneous ( SC ) routes , with a corresponding decrease in the intravenous ( IV ) route ( χ(2 ) = 13.67 , p < 0.001 ) . There were no statistically significant differences in patient-reported satisfaction with the attempt to manage pain in the ED between study periods ( p = 0.54 ) . CONCLUSIONS While the use of a learning collaborative and implementation of nurse-initiated analgesic protocol s was not associated with improvement in time to administration of the initial analgesic , improvements in the decrease in the arrival to discharge pain score and increased use of hydromorphone and the SC route were noted in adults with SCD in the ED PURPOSE S This study was design ed to evaluate the ability of a triage pain protocol to improve frequency and time to delivery of analgesia for musculoskeletal injuries in the emergency department ( ED ) . BASIC PROCEDURES Frequency and time to analgesic administration were measured before and after use of a triage pain protocol . The protocol allowed analgesic medications to be given at the time of triage . MAIN FINDINGS Time to medication administration was 76 minutes ( 95 % confidence interval [ CI ] , 68 - 84 minutes ) before and 40 minutes ( 95 % CI , 32 - 47 minutes ) after the protocol . Five hundred fifty-nine ( 70 % ) of 800 patients received analgesics using the protocol compared with 212 of 471 ( 45 % ) patients prior . PRINCIPAL CONCLUSIONS Use of a triage pain protocol increased the number of patients with musculoskeletal injury who received pain medication in the ED . Use of the protocol also result ed in a decrease in the time to analgesic medication administration INTRODUCTION This study describes an innovative pain management strategy that aim ed to improve the efficiency and effectiveness of timely analgesia for those patients in moderate pain and who experienced significant delay prior to medical assessment . METHOD A 12-week prospect i ve exploratory study was conducted to evaluate the introduction of a triage nurse initiated schedule 4 drug . A panadeine forte policy was developed and a data tool formulated to evaluate the effectiveness and frequency of nurse initiated panadeine forte . RESULTS The average pre-pain score reported by patients was 68 mm and the median was 70 mm . The average post-pain score was 37 mm and the median was 35 mm . The average post-pain score reduced by 31 mm demonstrating a clinical ly significant change . A statistically significant ( Wilcoxon signed rank test < 0.001 ) reduction in post-pain scores was also identified . CONCLUSION We identified a statistically and clinical ly significant reduction in post-analgesic pain scores for patients . Improving pain management can have a positive impact on patients in moderate pain who experience extended waiting times prior to medical assessment While acute musculoskeletal pain is a frequent complaint , its management is often neglected . An implementation of a nurse-initiated pain protocol based on the algorithm of a Dutch pain management guideline in the emergency department might improve this . A pre-post intervention study was performed as part of the prospect i ve PROTACT follow-up study . During the pre- ( 15 months , n = 504 ) and post-period ( 6 months , n = 156 ) patients ' self-reported pain intensity and pain treatment were registered . Analgesic provision in patients with moderate to severe pain ( NRS ≥4 ) improved from 46.8 % to 68.0 % . Over 10 % of the patients refused analgesics , result ing into an actual analgesic administration increase from 36.3 % to 46.1 % . Median time to analgesic decreased from 10 to 7 min ( P < 0.05 ) , whereas time to opioids decreased from 37 to 15 min ( P < 0.01 ) . Mean pain relief significantly increased to 1.56 NRS-points , in patients who received analgesic treatment even up to 2.02 points . The protocol appeared to lead to an increase in analgesic administration , shorter time to analgesics and a higher clinical ly relevant pain relief . Despite improvements , suffering moderate to severe pain at ED discharge was still common . Protocol adherence needs to be studied in order to optimize pain management |
13,401 | 30,323,313 | No significant association was observed in the combined effect analysis of CYP3A4 * 1 G and CYP3A5 * 3 with three significant SNPs in the POR gene .
Age , post-transplant duration , and the use of sirolimus were identified as the most important factors that influenced the TAC concentrations .
A meta- analysis of four studies results and our cohort indicated that compared with recipients carrying the CT or TT genotypes , recipients carrying the CC genotypes of POR*28 showed significantly higher TAC concentrations .
Our study suggested the positive influence of mutations in the POR gene on TAC exposure at 3 months after kidney transplantation | The P450 oxidoreductase ( POR ) and peroxisome proliferator-activated receptor alpha ( PPARA ) genes are associated with the activity of cytochrome P450 enzymes in vivo .
We aim ed to investigate the impact of single nucleotide polymorphisms ( SNPs ) in the POR and PPARA genes on the pharmacokinetics of tacrolimus ( TAC ) in renal transplant recipients . | Background Most of the previous studies reported that tacrolimus ( TAC ) with sirolimus ( SRL ) was associated with worse post-transplant outcomes in kidney transplantation , compared with TAC with mycophenolate mofetil ( MMF ) . These might be attributable to high-dose SRL . However , outcomes using low-dose SRL with TAC for kidney transplantation are uncertain . The aim of this study was to assess the efficacy and safety of low-dose SRL with extended-release tacrolimus ( ER-TAC ) versus MMF with ER-TAC . Methods We r and omly assigned 158 renal transplant patients to receive low-dose SRL or MMF in combination with ER-TAC and corticosteroid . The primary endpoint was the composite efficacy failure rate , including biopsy-proven acute rejection ( BPAR ) , graft loss , death or loss to follow-up , within 12 months post-transplantation . This trial is registered with Clinical Trial.gov ( number NCT01680952 ) . Results The efficacy failure rate was 6.6 % in the low-dose SRL group and 13.3 % in the MMF group in the intention-to-treat population ( absolute difference , 6.8 % ; 95 % confidence interval , -2.8 % to 16.3 % ) . The incidence of BPAR within 12 months post-transplantation was 5.3 % in the low-dose SRL group and 13.3 % in the MMF group ( P = 0.09 ) . The mean estimated glomerular filtration rate at 12 months post-transplantation was 53.2 mL/min/1.73 m2 in the low-dose SRL group and 52.4 mL/min/1.73 m2 in the MMF group ( P = 0.76 ) . The incidences of adverse events and serious adverse events were similar between groups . Conclusion Low-dose SRL with ER-TAC was not inferior to MMF with ER-TAC with respect to efficacy and safety . When used for immunosuppression in kidney transplantation , low-dose SRL with ER-TAC can effectively prevent acute rejection and preserve renal function Background : The P450 oxidoreductase (POR)*28 variant allele has been associated with altered cytochrome P450 3A enzyme activities . Both CYP3A5 and CYP3A4 are involved in the metabolism of calcineurin inhibitors and recent data show that POR*28 may explain part of the variability observed in tacrolimus ( Tac ) pharmacokinetics . The aim of this study was to investigate the impact of the POR*28 allele on Tac and cyclosporine A ( CsA ) immunosuppressive therapies . Methods : Kidney transplant recipients receiving either Tac ( n = 184 ) or CsA ( n = 174 ) , participating in a prospect i ve multicenter trial , were genotyped for POR*28 , CYP3A4 * 22 , and CYP3A5 * 3 . Results : CYP3A5 expressers that were carriers of at least 1 POR*28 allele had a 16.9 % decrease in dose-adjusted predose concentrations when compared CYP3A5 expressers that carried the POR*1/*1 genotype ( P = 0.03 ) , indicating an increased CYP3A5 activity for POR*28 carriers . In CYP3A5 , nonexpressers carrying 2 POR*28 alleles , a 24.1 % ( confidence interval95 % = −39.4 % to −4.9 % ; P = 0.02 ) decrease in dose-adjusted predose concentrations was observed for Tac , suggesting higher CYP3A4 activity . For CsA , POR*28/*28 patients not expressing CYP3A5 and not carrying the CYP3A4 * 22 decrease-of-function allele showed 15 % lower CsA dose-adjusted predose concentrations ( P = 0.01 ) , indicating also increased CYP3A4 activity . In both cohorts ( ie , Tac and CsA ) , the POR*28 allele was neither associated with the incidence of delayed graft function nor with biopsy-proven acute rejection . These results were further confirmed in 2 independent cohorts . Conclusions : Our results show that the POR*28 allele is associated with increased in vivo CYP3A5 activity for Tac in CYP3A5 expressers , whereas POR*28 homozygosity was associated with a significant higher CYP3A4 activity in CYP3A5 nonexpressers for both Tac and Aim In a cohort of 298 de-novo renal recipients treated with a st and ard tacrolimus loading dose of 0.2 mg/kg , the combined effects of the CYP3A5 * 1 , POR*28 , and CYP3A4 * 22 genotypes on early tacrolimus exposure ( C 0 ) , dose requirements , and achievement of the therapeutic target , C 0 , were examined . The incidence of clinical events ( e.g. acute rejection , diabetes mellitus ) was compared between genotypes . Results Fast metabolizers ( CYP3A5 * 1/POR*28 T carriers ) had two-fold to three-fold higher tacrolimus dose requirements compared with slow metabolizers ( CYP3A5 * 3/*3/CYP3A4 * 22 carriers ) and needed significantly more time to achieve the target tacrolimus C 0 of a minimum 10 ng/ml ( 3.3±1.7 vs. 1.34±0.75 days ; P<0.0001 ) . No differences in acute rejection incidence and time to first rejection were observed . Slow metabolizers more frequently had tacrolimus C 0 above the target range early after transplantation ( 70 vs. 13 % on day 3 ) ; however , this did not translate into a higher incidence of post-transplantation diabetes mellitus or graft dysfunction . Multivariate analyses identified the CYP3A5 * 1/POR*28/CYP3A4 * 22 genotype combination as the single strongest determinant of tacrolimus dose requirements throughout the first year , explaining between 24–40 % of its variability , whereas recipient age , hematocrit , and delayed graft function were additional nongenetic determinants of tacrolimus dose . Conclusion Combining the CYP3A5 * 1 , POR*28 and CYP3A4 * 22 genotypes allows partial differentiation of early tacrolimus dose requirements and the time to reach therapeutic target concentrations after transplantation , but without obvious clinical implication s. Larger prospect i ve studies need to address the clinical relevance of early combined genotype-based tacrolimus dosing in de-novo renal recipients Left ventricular hypertrophy ( LVH ) regression after kidney transplantation may be influenced by immunosuppression . In a 24-month open-label , multicenter , phase-IV study , 71 kidney allograft recipients without previous acute rejection , showing eGFR > 40 ml/min and proteinuria < 500 mg/day and between 6 months and 3 years post-transplantation , were r and omized to receive everolimus ( EVR ) + mycophenolic acid ( MPA ) or were maintained on tacrolimus ( TAC ) + MPA . The aim was to assess whether the conversion to EVR could reduce left ventricular mass index ( LVMi ) at month-24 . LVMi at month-24 decreased without differences between groups ( TAC : 54.0 vs. 48.2 g/m2.7 ; EVR : 53.4 vs. 49.4 g/m2.7 ) . The LVH prevalence at baseline and month-24 was 59.4 % and 40.6 % in TAC group and 57.1 % and 50.0 % in EVR group . EVR conversion was associated with nearly disappearance of concentric LVH and concentric remodeling pattern . The procollagen type I N-terminal propeptide at month-24 showed greater reduction in EVR group ( 51.6 vs. 58.2 mg/l ; P = 0.004 ) . Conversion from TAC to EVR was associated with a significant improvement of eGFR ( P = 0.0315 , ancova ) . Adverse events were similar between groups without rejection episode or graft loss . Conversion from TAC to EVR did not further reduce LVMi after 24 months , although its effect on concentric LVH deserves further investigation ( NCT01169701 ) Background : POR*28 is a recently newly described allelic variant of the cytochrome P450 oxidoreductase ( POR ) , which might be associated with an increased metabolic activity of P450 cytochromes ( CYP ) 3A5 and 3A4 . Consequently , carriers of at least 1 allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations ( C0 ) . The objective of this study was to test whether the allelic variant of POR , which is associated with an increased metabolic activity of CYP3A , impacts tacrolimus ( Tac ) pharmacokinetics . Methods : We tested this hypothesis in a population of 229 kidney transplant recipients ( KTR ) from a large , multicenter , prospect i ve and r and omized study . We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration ( Tac C0 ) 10 days after transplantation . We have also measured the association between POR*28 and the Tac C0 , and adjusted Tac C0 ( Tac C0/Tac dose ) over time using generalized mixed linear models . Results : Ten days after transplantation , there was no difference of frequencies of KTR within the target range of Tac C0 ( C0 10–15 ng/mL ) according to the POR*28 genotype ( P = 0.8 ) . The mean Tac C0 at day 10 in the POR*1/*1 group was 15.3 ± 9.7 ng/mL compared with 15.7 ± 7.8 ng/mL in the POR*1/*28 group and 14.2 ± 6.8 ng/mL , in the POR*28/*28 group , P = 0.8 . The adjusted Tac C0 was not associated with POR*28 genotype over time ( r and om effects model , P = 0.9 ) . When restricted to KTR expressing CYP3A5 , POR*28 genotype did not impact the proportion of individuals within the Tac C0 target range neither the adjusted Tac C0 ( r and om effects model , P = 0.1 ) . Conclusions : POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR . This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target C0 |
13,402 | 31,662,383 | Disability was also statistically significantly reduced by LLLT .
LLLT reduces pain and disability in KOA at 4 - 8 J with 785 - 860 nm wavelength and at 1 - 3 J with 904 nm wavelength per treatment spot . | OBJECTIVES Low-level laser therapy ( LLLT ) is not recommended in major knee osteoarthritis ( KOA ) treatment guidelines .
We investigated whether a LLLT dose-response relationship exists in KOA . | BACKGROUND The aim of the study was to estimate the influence of various laser therapy methods on knee joint pain and function in patients with knee osteoarthritis . MATERIAL AND METHODS 125 patients were r and omly assigned to 4 groups : • group I received one-wave laser irradiation ( wave length 810 nm , dose 8 J/point ) • group II received two-wave MLS laser irradiation ( power 1100 mW , frequency 2000 Hz , dose 12.4 J/point ) • group III received a similar regimen of two-wave MLS laser irradiation , but at a dose of 6.6 J per point • group IV was a placebo group where laser therapy procedures were simulated without actual irradiation . The effectiveness of the therapy was evaluated by means of Lequesne 's scale , a modified Laitinen question naire and a visual analogue scale ( VAS ) . Statistical analysis utilised non-parametric Wilcoxon 's and Mann-Whitney 's tests . Calculations were carried out with MedCalc v. 11.6.1.0 . RESULTS Statistically significant improvements in knee joint function and pain relief were seen in all groups ( I , II and III ) . When groups I , II and III were compared , the largest improvement was found in group II ( MLS laser , dose 12.4 J/point ) . The degrees of improvement in groups I and III were similar . CONCLUSIONS One-wave laser irradiation at a dose of 8 J per point and two-wave laser irradiation with doses of 12.4 J and 6.6 J per point significantly improved knee joint function and relieved knee pain in patients with osteoarthritis BACKGROUND AND OBJECTIVES A prospect i ve , double-blind , r and omized , and controlled trial was conducted in patients with knee osteoarthritis ( OA ) to evaluate the efficacy of infrared low-power Gallium-Arsenide ( Ga-As ) laser therapy ( LPLT ) and compared two different laser therapy regimes . STUDY DESIGN / MATERIAL S AND METHODS Ninety patients were r and omly assigned to three treatment groups by one of the nontreating authors by drawing 1 of 90 envelopes labeled ' A ' ( Group I : actual LPLT consisted of 5 minutes , 3 J total dose + exercise ; 30 patients ) , ' B ' ( Group II : actual LPLT consisted of 3 minutes , 2 J total dose + exercise ; 30 patients ) , and ' C ' ( Group III : placebo laser group + exercise ; 30 patients ) . All patients received a total of 10 treatments , and exercise therapy program was continued during study ( 14 weeks ) . Subjects , physician , and data analysts were unaware of the code for active or placebo laser until the data analysis was complete . All patients were evaluated with respect to pain , degree of active knee flexion , duration of morning stiffness , painless walking distance and duration , and the Western Ontario and Mc Master Universities Osteoarthritis Index ( WOMAC ) at week 0 , 6 , 10 , and 14 . RESULTS Statistically significant improvements were indicated in respect to all parameters such as pain , function , and quality of life ( QoL ) measures in the post-therapy period compared to pre-therapy in both active laser groups ( P < 0.01 ) . Improvements in all parameters of the Group I and in parameters , such as pain and WOMAC of the Group II , were more statistically significant when compared with placebo laser group ( P < 0.05 ) . CONCLUSIONS Our study demonstrated that applications of LPLT in different dose and duration have not affected results and both therapy regimes were a safe and effective method in treatment of knee OA Objectives : To estimate the effects of low level laser therapy in combination with a programme of exercises on pain , functionality , range of motion , muscular strength and quality of life in patients with osteoarthritis of the knee . Design : A r and omized double-blind placebo-controlled trial with sequential allocation of patients to different treatment groups . Setting : Special Rehabilitation Services . Subjects : Forty participants with knee osteoarthritis , 2–4 osteoarthritis degree , aged between 50 and 75 years and both genders . Intervention : Participants were r and omized into one of two groups : the laser group ( low level laser therapy dose of 3 J and exercises ) or placebo group ( placebo laser and exercises ) . Main measures : Pain was assessed using a visual analogue scale ( VAS ) , functionality using the Lequesne question naire , range of motion with a universal goniometer , muscular strength using a dynamometer , and activity using the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) question naire at three time points : ( T1 ) baseline , ( T2 ) after the end of laser therapy ( three weeks ) and ( T3 ) the end of the exercises ( 11 weeks ) . Results : When comparing groups , significant differences in the activity were also found ( P = 0.03 ) . No other significant differences ( P > 0.05 ) were observed in other variables . In intragroup analysis , participants in the laser group had significant improvement , relative to baseline , on pain ( P = 0.001 ) , range of motion ( P = 0.01 ) , functionality ( P = 0.001 ) and activity ( P < 0.001 ) . No significant improvement was seen in the placebo group . Conclusion : Our findings suggest that low level laser therapy when associated with exercises is effective in yielding pain relief , function and activity on patients with osteoarthritis of the knees Objective The aim of this study was to evaluate the effects of an exercise training protocol and low-level laser therapy ( and the association of both treatments ) on musculoskeletal atrophy using an experimental model of knee osteoarthritis ( OA ) . Design Fifty male Wistar rats were r and omly divided into five groups : control group , knee OA control group , OA plus exercise training group , OA plus low-level laser therapy group , and OA plus exercise training associated with low-level laser therapy group . The exercise training and the laser irradiation started 4 wks after the surgery , 3 days per week for 8 wks . The exercise was performed at a speed of 16 m/min , 3 days per week , 50 mins per day , for 8 wks . Laser irradiation was applied at two points of the left knee joint ( medial and lateral ) , for 24 sessions . Results The results showed that both trained groups ( irradiated or not ) presented a significant increase in the muscle cross-sectional area and a decrease in muscle fiber density compared with the knee OA control group . Moreover , both trained and laser-irradiated groups demonstrated decreased muscle-specific ring-finger protein 1 and atrogin-1 immunoexpression . Conclusions These results suggest that exercise training and low-level laser therapy were effective in preventing musculoskeletal alterations related to atrophy caused by the degenerative process induced by knee OA Background Osteoarthritis is a chronic disease with a multifactor etiology involving changes in bone alignment , cartilage , and other structures necessary to joint stability . There is a need to investigate therapeutic re sources that combine different wavelengths as well as different light sources ( low-level laser therapy and light-emitting diode therapy ) in the same apparatus for the treatment of osteoarthritis . The aim of the proposed study is to analyze the effect of the incorporation of phototherapy into a therapeutic exercise program for individuals with osteoarthritis of the knee . Methods / Design A double-blind , controlled , r and omized clinical trial will be conducted involving patients with osteoarthritis of the knee . Evaluations will be performed using functional question naires before and after the treatment protocol s , in a reserved room with only the evaluator and participant present , and no time constraints placed on the answers or evaluations . The following functional tests will also be performed : stabilometry ( balance assessment ) , dynamometry ( muscle strength of gluteus medius and quadriceps ) , algometry ( pain threshold ) , fleximeter ( range of motion ) , timed up- and -go test ( functional mobility ) , and the functional reach test . The participants will then be allocated to three groups through a r and omization process using opaque envelopes : exercise program , exercise program + phototherapy , or exercise program + placebo phototherapy , all of which will last for eight weeks . Discussion The purpose of this r and omized clinical trial is to analyze the effect of the incorporation of phototherapy into a therapeutic exercise program for osteoarthritis of the knee . The study will support the practice based on evidence to the use of phototherapy in individuals with a diagnosis of osteoarthritis of the knee . Data will be published after the study is completed . Trial registration The protocol for this study has been su bmi tted to Clinical Trials , registration number NCT02102347 , on 29 March 2014 IMPORTANCE There is debate about benefits of acupuncture for knee pain . OBJECTIVE To determine the efficacy of laser and needle acupuncture for chronic knee pain . DESIGN , SETTING , AND PARTICIPANTS Zelen- design clinical trial ( r and omization occurred before informed consent ) , in Victoria , Australia ( February 2010-December 2012 ) . Community volunteers ( 282 patients aged ≥50 years with chronic knee pain ) were treated by family physician acupuncturists . INTERVENTIONS No acupuncture ( control group , n = 71 ) and needle ( n = 70 ) , laser ( n = 71 ) , and sham laser ( n = 70 ) acupuncture . Treatments were delivered for 12 weeks . Participants and acupuncturists were blinded to laser and sham laser acupuncture . Control participants were unaware of the trial . MAIN OUTCOMES AND MEASURES Primary outcomes were average knee pain ( numeric rating scale , 0 [ no pain ] to 10 [ worst pain possible ] ; minimal clinical ly important difference [ MCID ] , 1.8 units ) and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index , 0 [ no difficulty ] to 68 [ extreme difficulty ] ; MCID , 6 units ) at 12 weeks . Secondary outcomes included other pain and function measures , quality of life , global change , and 1-year follow-up . Analyses were by intention-to-treat using multiple imputation for missing outcome data . RESULTS At 12 weeks and 1 year , 26 ( 9 % ) and 50 ( 18 % ) participants were lost to follow-up , respectively . Analyses showed neither needle nor laser acupuncture significantly improved pain ( mean difference ; -0.4 units ; 95 % CI , -1.2 to 0.4 , and -0.1 ; 95 % CI , -0.9 to 0.7 , respectively ) or function ( -1.7 ; 95 % CI , -6.1 to 2.6 , and 0.5 ; 95 % CI , -3.4 to 4.4 , respectively ) compared with sham at 12 weeks . Compared with control , needle and laser acupuncture result ed in modest improvements in pain ( -1.1 ; 95 % CI , -1.8 to -0.4 , and -0.8 ; 95 % CI , -1.5 to -0.1 , respectively ) at 12 weeks , but not at 1 year . Needle acupuncture result ed in modest improvement in function compared with control at 12 weeks ( -3.9 ; 95 % CI , -7.7 to -0.2 ) but was not significantly different from sham ( -1.7 ; 95 % CI , -6.1 to 2.6 ) and was not maintained at 1 year . There were no differences for most secondary outcomes and no serious adverse events . CONCLUSIONS AND RELEVANCE In patients older than 50 years with moderate or severe chronic knee pain , neither laser nor needle acupuncture conferred benefit over sham for pain or function . Our findings do not support acupuncture for these patients . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12609001001280 Inflammation of synovial membrane and degeneration of articular cartilage in osteoarthritis ( OA ) lead to major changes in joint space width ( JSW ) and biochemical components such as collagen-II telopeptide ( CTX-II ) and matrix metallo protineases ( MMP-3 , 8 , and 13 ) . Low-level laser therapy ( LLLT ) is thought to have an analgesic effect as well as biomodulatory effect on microcirculation and cartilage regeneration in animal studies . The objective of this study was to examine the analgesic and biochemical effect of LLLT in patients with knee osteoarthritis . Subjects ( n = 34 ) who fulfilled the selection criteria were r and omly divided into active group ( n = 17 ) and placebo group . Subjects in active group were irradiated laser with the frequency of 3 days per week for 4 weeks with the specific parameters on 8 different points on the joint at 1.5 J per point for 60 s for 8 points for a total dose of 12 J in a skin contact method . The placebo group was treated with the same probe with minimum emission of energy . Visual analog scale for pain intensity , joint space width , collagen-II telopeptide , and matrix metallo protinease-3 , 8 , and 13 was measured before treatment and at 4 and 8 weeks following treatment . Data are analyzed with mean values and st and ard deviation with p < 0.05 . Baseline values of all outcome measures show insignificant difference ( p > 0.05 ) in both groups which shows homogeneity . After 4- and 8-week treatment , active laser group shows more significant difference ( p < 0.001 ) in all the parameters than the placebo laser group ( p > 0.05 ) . Our results show that low-level laser therapy was more efficient in reducing pain and improving cartilage thickness through biochemical changes Objective : This study was design ed to evaluate the short-term efficacy of low-level laser therapy ( LLLT ) for improving pain and function in patients with knee osteoarthritis . Methods : Forty-seven patients with knee osteoarthritis ( 79 knees ) , of both genders , participated in this r and omized controlled double-blind clinical trial . They were r and omly allocated to two groups : laser group with 25 patients ( 41 knees ) and placebo group with 22 patients ( 38 knees ) . LLLT was performed three times a week , totaling nine sessions , using a AsGa 904 nm laser with mean power of 60 mW and beam area of 0.5 cm2 . Nine points were irradiated on the knee , with energy of 3.0 J/point . The placebo group was treated with the same laser device , but with a sealed probe . Evaluations using Lequesne , visual numerical scale ( VNS ) , Timed Up and Go ( TUG ) , goniometry and dynamometry were conducted before the treatment started and after the nine sessions of LLLT . Results : A significant improvement in pain and function was found in all the assessment s applied to the laser group . On comparing the laser group with the placebo group , significant differences were found in the VNS-resting and Lequesne evaluations . Conclusion : Treatment with LLLT improves pain and function over the short term in patients with knee osteoarthritis OBJECTIVE The aim of this study was to evaluate the effectiveness of an interferential pattern generated by two identical and independent lasers in the relief of knee pain . BACKGROUND DATA Low-level laser therapy ( LLLT ) is generally applied by a single probe . MATERIAL S AND METHODS A double-blind controlled clinical trial was performed on 152 patients with knee pain who were r and omly assigned into two different groups . Group I patients ( n = 76 ) received interferential laser therapy generated by two identical laser probes located opposite each other on the knee joint . Group II patients ( n = 76 ) received one live probe in conventional laser therapy and one dummy probe . The device used in both groups was an AlGaAs laser ( wavelength 810 nm , power 100 mW , in continuous mode ) . Fifteen laser sessions were applied transcutaneously on 5 knee points ( 6 J/point ) per session . In addition , patients in both groups received a quadriceps strength program based on isometric exercises . A visual analogue scale ( VAS ) was used for pain evaluation in different situations , such as in st and ing , in knee flexion/extension , and when going up and down stairs . VAS pain scores were evaluated before , in the middle of , and after treatment . RESULTS ANOVA results showed no significant differences between groups for all VAS scores or in the interaction with the sessions ( p > 0.05 ) . The VAS score results showed a statistically significant pain reduction throughout all sessions ( p = 0.000 ) . CONCLUSIONS Interferential laser therapy is safe and effective in reducing knee pain . However , the results of the study indicate that it is not superior to the use of a single conventional laser The aim of this study was to investigate the analgesic efficacy of low power laser therapy in patients with knee osteoarthritis ( OA ) . The study design was r and omised , placebo-controlled and single blinded . Sixty patients with knee OA according to the American College of Rheumatology criteria were included and r and omly assigned to three treatment groups : active laser with dosage of 3 J/per painful point , active laser with a dosage of 1.5/J per painful point and placebo laser treatment groups . A Gal-Al-As diode laser device was used as a source of low power laser with a power output of 50 mW and a wavelength of 830 nm . The patients were treated 5 times weekly with 10 treatments in all . The clinical assessment s included Western Ontario and McMaster Universities osteoarthritis index ( WOMAC ) pain , stiffness and physical function subscales . In addition , the intensity of pain at rest and on activation was evaluated on a visual analogue scale . Compared to baseline , at week 3 and at month 6 , no significant improvement was observed within the groups . Similarly , no significant differences were found among the treatment groups at any time . With the chosen laser type and dose regimen the results that we obtained in this study , suggest that low-level laser therapy has no effect on pain in patients with knee OA OBJECTIVE To explore the effects of combined laser on patients with knee osteoarthritis ( OA ) of yang deficiency and cold coagulation type . METHODS Forty-one cases with knee OA of yang deficiency and cold coagulation type were r and omly divided into a combined laser group ( n = 22 ) and a red light group ( n = 19 ) , with combined laser and red light irradiation on Dubi ( ST 35 ) and Neixiyan ( EX-LE 4 ) , respectively . They were treated for 6 weeks . The scores of Western Ontario and McMaster Universities ' Osteoarthritis Index ( WOMAC VA3 . 1 ) were used for assessment of therapeutic effects . RESULTS After treatment for 2 weeks and 6 weeks , the WOMAC scores significantly decreased in the two groups as compared with those before treatment ( P < 0.05 , P < 0.01 and P < 0.001 ) . The mean improvement rate of WOMAC scores in the combined laser group was better than those in the red light group . CONCLUSION Combined laser irradiation can improve the pain , stiffness and functional limitation of patients with knee OA of yang deficiency and cold coagulation type AIM to compare the effectiveness of active laser acupuncture with placebo on reducing pain intensity and improving functional outcome in geriatric patients with knee osteoarthritis ( OA ) . METHODS a double-blind r and omized controlled trial was conducted in geriatrics with knee OA at Medical Acupuncture Outpatient Clinic , Integrated Geriatric Outpatient Clinic , Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital , Jakarta , during May to October 2015 . Sixty two patients with knee OA were r and omly assigned into two groups : active laser acupuncture group or placebo laser acupuncture group . Interventions were carried out using a gallium aluminum arsenide laser device at the ST35 Dubi , ST36 Zusanli , SP9 Yinlingquan , GB34 Yanglingquan and EX - LE - 4 Neixiyan acupuncture points on the affected knee for ten sessions of treatment , i.e. twice a week . Patients were assessed using a visual analogue scale ( VAS ) and Lequesne index at baseline , after four sessions , after nine sessions and at 2 weeks after the treatment had been stopped . RESULTS the VAS scores were significantly improved in the active laser acupuncture group compared to the placebo group . The evaluation of VAS scores was carried out after four treatment sessions ( mean difference : 0.39 ; p<0.001 ) , after nine treatment sessions ( mean difference : 37.48 ; p<0.001 ) and at 2 weeks post intervention ( mean difference : 39.15 ; p<0.001 ) . The evaluation also showed significant improvement of Lequesne index after four treatment sessions ( mean difference : 4.68 ; p<0.001 ) , after nine treatment sessions ( mean difference : 5.90 ; p<0.001 ) and at 2 weeks post intervention ( mean difference : 6.48 ; p<0.001 ) . CONCLUSION active laser acupuncture is effective in reducing pain Phototherapy with low-level laser therapy ( LLLT ) and light-emitting diode therapy ( LEDT ) has arisen as an interesting alternative to drugs in treatments of musculoskeletal disorders . However , there is a lack of studies investigating the effects of combined use of different wavelengths from different light sources like lasers and light-emitting diodes ( LEDs ) in skeletal muscle disorders . With this perspective in mind , this study aim ed to investigate the effects of phototherapy with combination of different light sources on nonspecific knee pain . It was performed a r and omized , placebo-controlled , double-blinded clinical trial . Eighty-six patients rated 30 or greater on the pain visual analogue scale ( VAS ) were recruited and included in study . Patients of LLLT group received 12 treatments with active phototherapy ( with 905 nm super-pulsed laser and 875 and 640 nm LEDs , Manufactured by Multi Radiance Medical , Solon , OH , USA ) and conventional treatment ( physical therapy or chiropractic care ) , and patients of placebo group were treated at same way but with placebo phototherapy device . Pain assessment s ( VAS ) were performed at baseline , 4th , 7th , and 10th treatments , after the completion of treatments and at 1-month follow-up visit . Quality of life assessment s ( SF-36 ® ) were performed at baseline , after the completion of treatments and at 1-month follow-up visit . Our results demonstrate that phototherapy significantly decreased pain ( p < 0.05 ) from 10th treatment to follow-up assessment s and significantly improved ( p < 0.05 ) SF-36 ® physical component summary at posttreatments and follow-up assessment s compared to placebo . We conclude that combination of super-pulsed laser , red and infrared LEDs is effective to decrease pain and improve quality of life in patients with knee pain The aim of this double-blind study was to evaluate the effect of low power Ga-Al-As laser treatment on chronic pain related to osteoarthritis of the knee with periarticular tender points . Twenty-nine out- patients with uni- or bilateral osteoarthritis of the knee were included and r and omly assigned to treatment with either laser or placebo laser . Fourteen patients received active laser treatment and all patients included completed the study . The effect variables were daily levels of pain , analgesic requirements , palpation tenderness and isokinetic quadriceps strength . Each patient participated in the study for 9 weeks and registered daily level of pain and consumption of analgesics . In weeks 4 , 5 and 6 the patients received a total of nine treatments , each of 15 min and administered to periarticular tender points . The dose per treatment was 22.5 joule . No significant differences in any of the effect variables were found between the two groups before , during or after treatment . With regard to the patients ' overall assessment there was a clearly demonstrable positive effect of treatment in both groups . This is likely to be due to a placebo effect BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) are widely used to treat osteoarthritis ( OA ) , though their long-term efficacy is uncertain . We report a comparison of the symptomatic responses to therapy with tiaprofenic acid , indomethacin and placebo over 5 yr . METHODS A parallel-group , r and omized , single-blind trial of patients with knee OA recruited 812 patients from 20 centres ; 307 patients received tiaprofenic acid ( 300 mg b.d . ) , 202 indomethacin ( 25 mg t.d.s . ) and 303 matching placebo for up to 5 yr . At the end of the parallel-group study , patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo , both given for 2 weeks . Assessment s were at baseline , 4 weeks , then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study . They comprised pain scores , duration of morning stiffness , patients ' global assessment s , paracetamol consumption , adverse reactions , withdrawals and functional outcomes . RESULTS There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase . Thereafter there were no advantages favouring active therapy . In the cross-over phase , pain scores were significantly lower in patients receiving tiaprofenic acid than placebo . Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa . Adverse events were reported by 61 % of patients receiving tiaprofenic acid , 63 % on indomethacin and 51 % on placebo . Potentially severe side-effects were rare ; for example , there were only three cases of gastrointestinal bleeding on NSAIDs . The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study ; at 48 weeks 53 % of the patients remained on tiaprofenic acid , 50 % on indomethacin and 54 % on placebo . CONCLUSIONS NSAIDs significantly reduce overall pain over 4 weeks . This short-term responsiveness is retained , and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo . Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy Our objective was to assess the efficacy and safety of combined 10.6 μm and 650 nm laser irradiation on patients with knee osteoarthritis ( OA ) . Forty patients with OA were r and omly allocated to an active laser group or to a placebo laser group ( 20 per group ) . They either received active or sham laser treatment at acupoint Dubi ( ST 35 ) in a total of 12 sessions . There was significant difference between the two groups in the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index pain score change from baseline after 2 weeks of treatment ( P = 0.047 ) . The pain reduction of the active laser treatment group was 49 % , whereas that of the placebo control group was only 13 % . However , due to the high patient drop-out rate , the 4-week assessment could not be analyzed . Combined laser treatment seems beneficial to patients with knee OA . However , due to the small sample size and the high drop-out rate of patients in the placebo group , a large sample -size clinical trial is warranted to determine further the therapeutic efficacy of the device The aim of this study was to investigate the effect of low-level laser therapy ( LLLT ) on short-term and long-term joint pain , synovitis , anabolic , and catabolic factors in the cartilage of a rabbit model with progressive osteoarthritis ( OA ) induced by anterior cruciate ligament transection ( ACLT ) . A total of 160 New Zeal and white rabbits were r and omly assigned into two groups ( ACLT group and LLLT group ) . All rabbits received ACLT surgery , and 2- , 4- , 6- , and 8-week treatment after the surgery , with 20 rabbits being tested biweekly over every study period . The LLLT group received LLLT with a helium – neon ( He – Ne ) laser ( 830 nm ) of 1.5 J/cm2 three times per week , and the ACLT group received placebo LLLT with the equipment switched off . Long-term and short-term pain was tested via weight-bearing asymmetry ; synovitis was assessed histologically ; and knee joint cartilage was evaluated by gross morphology , histology , and gene expression analysis of anabolic and catabolic factors . The histological assessment of pain and synovitis showed that at least 6-week intermittent irradiation of LLLT could relief knee pain and control synovium inflammation . Gross morphologic inspection and histological evaluation showed that 6 weeks of LLLT could decrease cartilage damage of medical femoral condyle and 8 weeks of LLLT could decrease cartilage damage of medical and lateral femoral condyles and medical tibial plateau . Gene expression analysis revealed two results : At least 6 weeks of LLLT could decrease production of catabolic factors , for example , interleukin 1β ( IL-1β ) , inducible nitric oxide synthase ( iNOS ) , and MMP-3 , and slow down the loss of anabolic factors , mainly TIMP-1 . Eight weeks of LLLT treatment could slow down the loss of collagen II , aggrecan , and anabolic factors , mainly transforming growth factor beta ( TGF-β ) . The study suggests that LLLT plays a protective role against cartilage degradation and synovitis in rabbits with progressive OA by virtue of the regulation of catabolic and anabolic factors in the cartilage OBJECTIVE The goals of the present study were to evaluate the effect and safety of combined 10.6 microm and 650 nm laser acupuncture-moxibustion on patients with knee osteoarthritis ( OA ) and to vali date a nonacupoint sham control for assessing the effect of point specificity on the treatment . MATERIAL S AND METHODS A r and omized , sham-controlled clinical trial was conducted in an outpatient clinical setting on patients with knee OA ( n = 40 ) . Laser irradiation was performed on acupoint Dubi ( ST35 ) and a sham point three times a week for 4 wk . Outcome measurements were performed at baseline and at wk 2 and 4 using Western Ontario and McMaster Universities ' Osteoarthritis Index ( WOMAC ) . RESULTS At the 2-wk assessment , i.e. , after 6 treatments , improvement in the WOMAC pain score of the acupoint group was significantly greater than that of the control group ( 49.21 % vs. 11.99 % , respectively ; p = 0.021 ) . However , there were no significant differences between the two groups in the WOMAC physical function score ( p = 0.129 ) or joint stiffness score ( p = 0.705 ) . No side effects were found during the trial . CONCLUSIONS Combined 10.6-mum-650-nm laser acupuncture-moxibustion on acupoint ST35 is safe to use and was effective after 2-wk treatment , but not at the 4-wk assessment , in relieving knee OA pain compared to a nonacupoint sham control . A larger clinical trial to verify our findings is warranted The aim of this study was to investigate the effect of low-level laser therapy ( LLLT ) on pain relief and functional performance in patients with chronic knee osteoarthritis ( OA ) . Forty patients with knee OA were r and omly assigned into active laser group ( n = 20 ) and placebo laser group ( n = 20 ) . The LLLT device used was a Ga – As diode laser with a power output of 50 mW , a wavelength of 850 nm , and a diameter beam of 1 mm . Eight points were irradiated and received dosage of 6 J/point for 60 s , with a total dosage of 48 J/cm2 in each session . The placebo group was identical but treated without emission of energy . LLLT was applied two times per week over the period of 4 weeks . Outcome measurements included pain intensity at rest and at movement on visual analog scale , knee function using Western Ontario McMaster Universities Osteoarthritis Index scale , and ambulation duration . These measurements were collected at baseline and post-intervention . The results showed significant improvements in all assessment parameters in both groups compared to baseline . Active laser group showed significant differences in pain intensity at rest and movement , knee function , and ambulation duration when compared with the placebo group . Therefore , LLLT seemed to be an effective modality for short-term pain relief and function improvement in patients with chronic knee OA Background Osteoarthritis ( OA ) is one of the most common joint disorders in the elderly which could be associated with considerable physical disability . Patients and methods In a descriptive , prospect i ve study , 33 patients enrolled in the study from which 15 people were excluded due to incomplete course of treatment , leaving the total number of 18 patients with knee osteoarthritis . Gal-Al-As diode laser device was used as a source of low-power laser . Patients were performed laser therapy with a probe of LO7 with a wavelength of 810 nm and 50 mW output power in pulse radiation mode ( F = 3,000 , peak power = 80 W , Δt = 200 ns , density = 0.05 W/cm2 , dose = 6 J/cm2 , area = 1 cm2 ) and also a probe of MLO1 K with a power output of 30 mW and a wavelength of 890 nm in pulse radiation mode ( F = 3,000 Hz , peak power = 50 W , Δt = 200 ns , density = 0.017 W/cm2 , total dose = 10 J/cm2 ) , and were given low-level laser therapy ( LLLT ) three times a week with a total number of 12 sessions . Data were analyzed using SPSS ver . 15 , and the obtained data were reported as mean ± SD and frequency ( % ) . To analyze the data , repeated measurement and marginal homogeneity approaches were used . Results In the current study , a significant reduction was observed regarding the nocturnal pain , pain on walking and ascending the steps , knee circumference , distance between the hip and heel , and knee to horizontal hip to heel distance at the end of the treatment course . Conclusions In brief , the current study focuses on the fact that LLLT is effective in reducing pain in knee osteoarthritis OBJECTIVE To evaluate the efficacy of low-level laser therapy ( LLLT ) applied to acupuncture points on the knee joint in combination with exercise and advice in patients with knee osteoarthritis . DESIGN R and omised , double-blind , comparative clinical trial . PARTICIPANTS Forty-nine patients with knee osteoarthritis were assigned at r and om into two groups : active laser group ( n=26 ) and placebo laser group ( n=23 ) . INTERVENTION Using a gallium aluminium arsenide laser device , patients received either active or placebo LLLT at five acupuncture points on the affected knee during nine sessions . OUTCOME MEASURES Patients were assessed using a visual analogue scale ( VAS ) and the Saudi Knee Function Scale ( SKFS ) at baseline , the fifth treatment session , the last treatment session , 6 weeks post intervention and 6 months post intervention . RESULTS VAS scores showed a significant improvement in the active laser group compared with the placebo laser group at 6 weeks post intervention [ mean difference -1.3 , 95 % confidence interval ( CI ) of the difference -2.4 to -0.3 ; P=0.014 ] and 6 months post intervention ( mean difference -1.8 , 95 % CI of the difference -3.0 to -0.7 ; P=0.003 ) using the independent sample s test . SKFS scores also showed a significant improvement in the active laser group compared with the placebo laser group at the last treatment session ( median difference -15 , 95 % CI of the difference -27 to -2 ; P=0.035 ) and 6 months post intervention ( median difference -21 , 95 % CI of the difference -34 to -7 ; P=0.006 ) using the Mann-Whitney U test . CONCLUSIONS The results demonstrate that short-term application of LLLT to specific acupuncture points in association with exercise and advice is effective in reducing pain and improving quality of life in patients with knee osteoarthritis Objectives : To assess the long-term effects of low-level laser therapy ( LLLT ) , in combination with strengthening exercises in patients with osteoarthritis of the knee . Design : Follow-up results at three and six months in a previously published r and omized , double-blind , placebo-controlled trial . Setting : Specialist Rehabilitation Services . Subjects : Forty participants of both genders , aged 50–75 years with knee osteoarthritis grade 2–4 on Kellgren – Lawrence scale . Intervention : The LLLT group received 10 LLLT treatments with invisible infrared laser ( 904 nm , 3 Joules/point ) over three weeks followed by an eight-week supervised strengthening exercise program . The placebo LLLT group received identical treatment , but the infrared laser output was disabled . Main measures : Pain on a visual analogue scale , paracetamol consumption , and osteoarthritis severity measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and Lequesne Index . Results : The new data obtained during the follow-up period showed that all outcomes remained stable and there were no significant differences between the groups at three and six months . However , daily consumption of rescue analgesics ( paracetamol ) was significantly lower in the LLLT group throughout the follow-up period , ending at a group difference of 0.45 vs. 3.40 units ( P < 0.001 ) at six months follow-up . We conclude that within the limitations of this small study , the previously reported improvement after LLLT plus exercise was maintained for a period of six months . Conclusion : We find that the immediate post-intervention improvements from LLLT plus strengthening exercises were maintained for six months OBJECTIVE / BACKGROUND Efficacy in osteoarthritis ( OA ) is principally measured using subjective visual analogue ( VAS ) and /or Likert scale responses . The relationship between these two scales and their relative precision in discriminating active from placebo treatment in OA patients was determined . DESIGN / METHODS Patient overall pain assessment , and patient and investigator global assessment s were each measured on a 100 mm VAS and on a 0 to 4 point Likert scale in a 6-week OA study of rofecoxib vs placebo . The relationship between the VAS and Likert responses was examined graphically and via summary statistics . Analysis of variance was used to assess consistency of the VAS/Likert relationship over time and across the different endpoints . Precision was compared using effect size , and normality of VAS scale of measurement was assessed using the Shapiro-Wilk test . RESULTS Mean VAS scores and changes from baseline at individual time points were generally highly correlated with corresponding Likert responses ( r-values generally approximately 0.7 - 0.8 ) . The magnitude of VAS values and changes varied depending on endpoint , on the associated magnitude of increment of Likert score , and on the Likert baseline value ( i.e. , where on the Likert scale the change was occurring ) . Precision of VAS and Likert responses to detect difference between treatments was generally similar with effect sizes approximately 1 . Normality and homogeneity of variance of VAS scores was most closely approximated by actual changes in comparison to percent change or log-transformed measures . CONCLUSIONS VAS and Likert responses are highly correlated and yield similar precision for discriminating treatments in OA patients . Since Likert responses are easier to administer and interpret , they may be preferable to measure OA response INTRODUCTION Low-level laser therapy ( LLLT ) is thought to have an analgesic effect as well as a biomodulatory effect on microcirculation . This study was design ed to examine the pain-relieving effect of LLLT and possible microcirculatory changes measured by thermography in patients with knee osteoarthritis ( KOA ) . MATERIAL S AND METHODS Patients with mild or moderate KOA were r and omized to receive either LLLT or placebo LLLT . Treatments were delivered twice a week over a period of 4 wk with a diode laser ( wavelength 830 nm , continuous wave , power 50 mW ) in skin contact at a dose of 6 J/point . The placebo control group was treated with an ineffective probe ( power 0.5 mW ) of the same appearance . Before examinations and immediately , 2 wk , and 2 mo after completing the therapy , thermography was performed ( bilateral comparative thermograph by AGA infrared camera ) ; joint flexion , circumference , and pressure sensitivity were measured ; and the visual analogue scale was recorded . RESULTS In the group treated with active LLLT , a significant improvement was found in pain ( before treatment [ BT ] : 5.75 ; 2 mo after treatment : 1.18 ) ; circumference ( BT : 40.45 ; AT : 39.86 ) ; pressure sensitivity ( BT : 2.33 ; AT : 0.77 ) ; and flexion ( BT : 105.83 ; AT : 122.94 ) . In the placebo group , changes in joint flexion and pain were not significant . Thermographic measurements showed at least a 0.5 degrees C increase in temperature-- and thus an improvement in circulation compared to the initial values . In the placebo group , these changes did not occur . CONCLUSION Our results show that LLLT reduces pain in KOA and improves microcirculation in the irradiated area BACKGROUND In clinical trials , at the group level , results are usually reported as mean and st and ard deviation of the change in score , which is not meaningful for most readers . OBJECTIVE To determine the minimal clinical ly important improvement ( MCII ) of pain , patient 's global assessment of disease activity , and functional impairment in patients with knee and hip osteoarthritis ( OA ) . METHODS A prospect i ve multicentre 4 week cohort study involving 1362 out patients with knee or hip OA was carried out . Data on assessment of pain and patient 's global assessment , measured on visual analogue scales , and functional impairment , measured on the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) function subscale , were collected at baseline and final visits . Patients assessed their response to treatment on a five point Likert scale at the final visit . An anchoring method based on the patient 's opinion was used . The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA , 211 with hip OA ) . RESULTS For knee and hip OA , MCII for absolute ( and relative ) changes were , respectively , ( a ) -19.9 mm ( -40.8 % ) and -15.3 mm ( -32.0 % ) for pain ; ( b ) -18.3 mm ( -39.0 % ) and -15.2 mm ( -32.6 % ) for patient 's global assessment ; ( c ) -9.1 ( -26.0 % ) and -7.9 ( -21.1 % ) for WOMAC function subscale score . The MCII is affected by the initial degree of severity of the symptoms but not by age , disease duration , or sex . CONCLUSION Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients OBJECTIVE The purpose of this study was to investigate the effects and minimum effective dose of laser acupuncture in knee osteoarthritis ( KOA ) , and to determine if it is superior to placebo treatment ( sham ) in the evaluation of clinical -functional outcome and quality of life . METHODS In this r and omized , placebo-controlled study , patients with grade 2 and 3 primary KOA were selected . Group I ( n = 27 ) received 904-nm low-level laser irradiation with 10 mW/cm(2 ) power density , 4 mW output power , 0.4 cm(2 ) spot size , 0.48 J dose per session , and 120-sec treatment time on the medial side of the knee to the acupuncture point Sp9 . Group II ( n = 25 ) received placebo-laser therapy at the same place on the same point . Patients in both of the groups had treatment 5 days per week ( total duration of therapy was 10 days ) and 20 min per day . The study was comprised of a 2-week ( 10-session ) intervention . Participants were evaluated before treatment ( baseline ) , after treatment ( 2nd week ) , and at the 12th week . In this double-blind study , a blind examiner carried out all outcome assessment s. The main outcome measures were as follows : pain on movement ( pVAS ) , 50-foot walking time ( 50 foot w ) , knee circumference ( KC ) , medial tenderness score ( MTS ) , Western Ontario and McMaster Universities osteoarthritis index ( WOMAC ) , and Nottingham Health Profile ( NHP ) . RESULTS Statistically significant improvement was observed in PVAS , 50 foot w , and KC in group 1 . In Group II , statistically significant improvement was observed in PVAS , 50 foot w , and WOMAC . When groups were compared with each other , the improvement observed in KC was superior in Group I at the 2(nd ) week ( p = 0.005 ) . CONCLUSION Laser acupuncture was found to be effective only in reducing periarticular swelling when compared with placebo laser OBJECTIVE To evaluate the effects of low-power light therapy on pain and disability in elderly patients with degenerative osteoarthritis of the knee . DESIGN Partially double-blinded , fully r and omized trial comparing red , infrared , and placebo light emitters . PATIENTS Fifty patients with degenerative osteoarthritis of both knees were r and omly assigned to three treatment groups : red ( 15 patients ) , infrared ( 18 patients ) , and placebo ( 17 patients ) . Infrared and placebo emitters were double-blinded . INTERVENTIONS Self-applied treatment to both sides of the knee for 15 minutes twice a day for 10 days . MAIN OUTCOME MEASURES Short-Form McGill Pain Question naire , Present Pain Intensity , and Visual Analogue Scale for pain and Disability Index Question naire for disability were used . We evaluated pain and disability before and on the tenth day of therapy . The period from the end of the treatment until the patient 's request to be retreated was summed up 1 year after the trial . RESULTS Pain and disability before treatment did not show statistically significant differences between the three groups . Pain reduction in the red and infrared groups after the treatment was more than 50 % in all scoring methods ( P less than 0.05 ) . There was no significant pain improvement in the placebo group . We observed significant functional improvement in red- and infrared-treated groups ( p less than 0.05 ) , but not in the placebo group . The period from the end of treatment until the patients required treatment was longer for red and infrared groups than for the placebo group ( 4.2 + /- 3.0 , 6.1 + /- 3.2 , and 0.53 + /- 0.62 months , for red , infrared , and placebo , respectively ) . CONCLUSIONS Low-power light therapy is effective in relieving pain and disability in degenerative osteoarthritis of the knee INTRODUCTION Osteoarthritis ( OA ) is a common degenerative joint disease particularly in older subjects . It is usually associated with pain , restricted range of motion , muscle weakness , difficulties in daily living activities and impaired quality of life . To determine the effects of adding two different intensities of low-level laser therapy ( LLLT ) to exercise training program on pain severity , joint stiffness , physical function , isometric muscle strength , range of motion of the knee , and quality of life in older subjects with knee OA . METHODS Patients were r and omly assigned into three groups . They received 16 sessions , 2 sessions/week for 8 weeks . Group-I : 18 patients were treated with a laser dose of 6 J/cm(2 ) with a total dose of 48 J. Group-II : 18 patients were treated with a laser dose of 3 J/cm(2 ) with a total dose of 27 J. Group-III : 15 patients were treated with laser without emission as a placebo . All patients received same exercise training program including stretching and strengthening exercises . Patients were evaluated before and after intervention by visual analogue scale ( VAS ) , the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index for quality of life , h and held dynamometer and universal goniometer . RESULTS T test revealed that there was a significant reduction in VAS and pain intensity , an increase in isometric muscle strength and range of motion of the knee as well as increase in physical functional ability in three treatment groups . Also analysis of variance ( ANOVA ) proved significant differences among them and the post hoc tests ( LSD ) test showed the best improvements for patients of the first group . CONCLUSION It can be concluded that addition of LLLT to exercise training program is more effective than exercise training alone in the treatment of older patients with chronic knee OA and the rate of improvement may be dose dependent , as with 6 J/cm(2 ) or 3 J/cm(2 ) The aim of this r and omized controlled study was to compare the effects of low-level laser therapy ( LLLT ) and high-intensity laser therapy ( HILT ) on pain relief and functional improvement in patients with knee osteoarthritis ( KOA ) . A total of 53 male patients participated in this study , with a mean ( SD ) age of 54.6 ( 8.49 ) years . Patients were r and omly assigned into three groups and treated with HILT and exercise ( HILT + EX ) , LLLT and exercise ( LLLT + EX ) , and placebo laser plus exercise ( PL + EX ) in groups 1 , 2 , and 3 , respectively . The outcomes measured were pain level measured by visual analog scale ( VAS ) and knee function measured by Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Statistical analyses were performed to compare the differences between baseline and posttreatment measurements . The level of statistical significance was set as P < 0.05 . The result showed that HILT and LLLT combined with exercise were effective treatment modalities in decreasing the VAS and WOMAC scores after 6 weeks of treatment . HILT combined with exercises was more effective than LLLT combined with exercises , and both treatment modalities were better than exercises alone in the treatment of patients with KOA |
13,403 | 23,884,963 | None of the included studies reported congenital abnormalities .
AUTHORS ' CONCLUSIONS Results from RCTs do not support the clinical use of IMSI .
There is no evidence of effect on live birth or miscarriage and the evidence that IMSI improves clinical pregnancy is of very low quality .
There is no indication that IMSI increases congenital abnormalities . | BACKGROUND Subfertility is a condition found in up to 15 % of couples of reproductive age .
Gamete micromanipulation , such as intracytoplasmic sperm injection ( ICSI ) , is very useful for treating couples with compromised sperm parameters .
Recently a new method of sperm selection named ' motile sperm organelle morphology examination ' ( MSOME ) has been described and the spermatozoa selected under high magnification ( over 6000x ) used for ICSI .
This new technique , named intracytoplasmic morphologically selected sperm injection ( IMSI ) , has a theoretical potential to improve reproductive outcomes among couples undergoing assisted reproduction techniques ( ART ) .
OBJECTIVES To compare the effectiveness and safety of IMSI and ICSI in couples undergoing ART . | In previous studies , a new IVF method of intracytoplasmic morphologically selected sperm injection ( IMSI ) was introduced , based on motile sperm organellar morphology examination ( MSOME ) . It was concluded that microinjection of morphologically selected sperm cells with strictly normal nucleus , defined by MSOME , improves IVF-ICSI outcome . The aim of the present study was to confirm this conclusion in new , enlarged study groups . Comparison between 80 couples , who underwent an IVF-IMSI trial , with matched couples , who underwent a st and ard IVF-ICSI procedure , confirmed that pregnancy rate following IVF-IMSI was significantly higher , and abortion rate significantly lower than in the routine IVF-ICSI ( 60.0 versus 25.0 % , and 14 versus 40 % respectively , P < or= 0.05 ) . Another comparison was performed between matched IMSI groups , where embryos were obtained from microinjection by spermatozoa with a morphologically normal nucleus ( ' best ' group , n = 70 ) and a ' second best ' group was selected , where embryos were obtained from microinjection of spermatozoa with minimal morphological impairment , since no other sperm cells were available . It was confirmed that microinjection by ' second best ' spermatozoa result in significantly lower pregnancy and delivery rates and significantly higher abortion rates than microinjection with ' best ' spermatozoa ( 25.7 versus 58.2 % , P < or= 0.01 ; 17.1 versus 52.8 % , P < or= 0.01 , and 33.3 versus 9.7 % , P < or= 0.02 respectively ) . The present study has strengthened previous conclusions STUDY QUESTION Does high-magnification sperm selection influence oocyte fertilization and further embryo development ? SUMMARY ANSWER The present study did not show a difference in oocyte fertilization rate , nor in embryo development between high-magnification intracytoplasmic morphologically selected sperm injection ( IMSI ) and conventional ICSI . WHAT IS KNOWN ALREADY The presence of nuclear vacuoles in sperm seems to influence embryo development and more specifically blastocyst formation . The use of high magnification for morphological sperm selection prior to ICSI has been associated with higher pregnancy rates and lower miscarriage rates . STUDY DESIGN , SIZE , DURATION A prospect i ve sibling-oocyte study was conducted , including 350 ICSI cycles to alleviate male infertility . Cycles were included from March 2010 to November 2011 . PARTICIPANTS / MATERIAL S , SETTING , METHODS On the day of treatment , a high-magnification sperm morphology was assessed on at least 200 spermatozoa . Primary endpoints were oocyte fertilization rate and embryo development . Because embryo transfers were not r and omized , the clinical outcome ( clinical pregnancy rate per transfer cycle ) was descriptive . However , the embryologist selecting the embryos for transfer was blinded for the sperm selection procedure . MAIN RESULTS AND THE ROLE OF CHANCE IMSI morphology was assessed in 330 semen sample s , result ing in the following distribution : 18.1 ± 14.8 % Grade I , 15.2 ± 10.3 % Grade II , 12.3 ± 9.1 % Grade III and 54.4 ± 23.2 % Grade IV . Oocyte fertilization rate was 79.1 and 77.3 % after IMSI and ICSI , respectively ( NS , paired t-test ) . Embryo development was similar in both treatment groups up to Day 5 of preimplantation development . Comparable numbers of IMSI-only ( n = 125 ) and ICSI-only ( n = 139 ) embryo transfers were performed . Clinical pregnancies with fetal heart beat were equally distributed over transfers with embryos from IMSI-only ( 34.4 % ) or ICSI-only treatment ( 36.7 % ) . LIMITATIONS , REASONS FOR CAUTION The clinical outcome remains descriptive . No firm conclusions could be drawn on cycle rank as a possible indication for IMSI . WIDER IMPLICATION S OF THE FINDINGS The prevalence of vacuoles in normal-shaped spermatozoa is as low as 27.5 % . A routine application of IMSI in unselected artificial reproductive technology patients can not be advocated . STUDY FUNDING /COMPETING INTEREST(S ) None BACKGROUND Our preceding studies have already demonstrated the advantage of intracytoplasmic morphologically selected sperm injection ( IMSI ) over the conventional IVF-ICSI procedure in terms of pregnancy rate . This study was undertaken to determine whether the increased pregnancy outcome was attributable to the preferred nuclear morphology of the selected spermatozoa , and not to the special sperm preparation technique modified by IMSI . METHODS Comparison between two matched IMSI groups , i.e. negative comprising 38 cycles , where no spermatozoa with intact nuclei were available for microinjection ; and positive , involving ovum microinjection by spermatozoa with strictly defined morphologically normal nuclei . RESULTS Implantation and pregnancy rates were significantly higher , and abortion rates significantly lower , in the positive group compared with the negative group ( 25.0+/-25.9 versus 5.9+/-12.9 % , F=15.8 , P < or = 0.01 ; 52.6 versus 18.4 % , chi2=9.7 , P < or = 0.01 ; and 10.0 versus 57.1 % , chi2=7.1 , P < or = 0.02 , respectively ) . CONCLUSIONS Implantation and pregnancy by ICSI is associated with morphological nuclear normalcy of sperm . Sperm with a morphologically abnormal nucleus usually have low fertility potential , but some with certain nuclear abnormalities may still be able to produce pregnancy following ICSI OBJECTIVE To examine the effect of sperm morphology on embryo development at the chromosomal level . DESIGN Prospect i ve study . SETTING Assisted fertilization center . PATIENT(S ) Couples who underwent IVF-PGS cycle , as a result of advanced maternal age , were r and omly allocated into two groups : intracytoplasmic sperm injection ( ICSI ; n = 60 ) or intracytoplasmic morphologically selected sperm injection ( IMSI ; n = 60 ) . INTERVENTION(S ) IVF in conjunction with preimplantation genetic screening ( PGS ) . MAIN OUTCOME MEASURE(S ) Sperm nuclear morphology at high-magnification ICSI and incidence of aneuploidy in derived embryo . RESULT ( S ) There was a significantly increased incidence for sex chromosome aneuploidy in ICSI embryos when compared with IMSI embryos ( 23.5 % vs. 15.0 % , respectively ) . High-magnification sperm selection was associated with a significantly lower risk of sex chromosome abnormalities ( odds ratio [ OR ] , 0.57 ; confidence interval [ CI ] , 0.37 - 0.90 ) . The incidence of chaotic embryos was also significantly higher with the ICSI procedure ( 27.5 % vs. 18.8 % ) , while the IMSI procedure was associated with a significantly lower risk of chaotic embryos ( OR , 0.64 ; CI , 0.43 - 0.96 ) . Moreover , the cycle cancellation rate was significantly higher in ICSI cycles ( 11.8 % vs. 2.5 % ) . High-magnification sperm selection was a significant predictor of the likelihood of cycle cancellation ( OR , 0.26 ; CI , 0.11 - 0.62 ) . CONCLUSION ( S ) Spermatozoa free of nuclear morphological malformations were found to be significantly associated with the lower incidence of aneuploidy in derived embryos , result ing in lower rates of cycle cancellation OBJECTIVE To verify whether microinjection into retrieved oocytes of motile spermatozoa with morphologically normal nuclei , strictly defined by high power light microscopy ( x > 6000 ) , improves the IVF/intracytoplasmic sperm injection ( ICSI ) pregnancy rate in couples with repeated ICSI failures . DESIGN Comparative prospect i ve study testing routine IVF/ICSI outcome parameters against those of modified ICSI based on morphological selection of spermatozoa with normal nuclei . SETTING Male factor fertility laboratory and IVF center . PATIENT(S ) Sixty-two couples , with at least two previous consequent pregnancy failed ICSI cycles , underwent a single ICSI trial preceded by morphological selection of spermatozoa with normal nuclei . Fifty of these couples were matched with couples who underwent a routine ICSI procedure at the same IVF center and exhibited the same number of previous ICSI failures . INTERVENTION(S ) St and ard ICSI and modified ICSI . MAIN OUTCOME MEASURE(S ) ICSI pregnancy rate . RESULT ( S ) The matching study revealed that pregnancy rate after modified ICSI was significantly higher than that of the routine ICSI procedure ( 66.0 % vs. 30.0 % ) . CONCLUSION ( S ) Microinjection into retrieved oocytes of selected spermatozoa with strictly defined morphologically normal nuclei improves significantly the incidence of pregnancy in couples with previous ICSI failures Background The purpose of this study was to compare laboratory and clinical outcomes of intracytoplasmic morphologically selected sperm injection ( IMSI ) and conventional intracytoplasmic sperm injection ( ICSI ) in couples with repeated implantation failures . Methods A total of 200 couples with at least two prior unsuccessful ICSI cycles were enrolled : 100 couples were su bmi tted to IMSI and 100 were su bmi tted to routine ICSI . For IMSI , spermatozoa were selected at 8400 × magnification using an inverted microscope equipped with Nomarski ( differential interference contrast ) optics . For conventional ICSI , spermatozoa were selected at 400 × magnification . Clinical outcomes were evaluated between the two groups . Results Study patients were comparable in age , number of treatment failures , aetiology of infertility , percentage of normal form assessed by MSOME ( motile sperm organelle morphology examination ) , semen parameters , total number of oocytes collected , number of mature oocytes collected , total number of embryos transferred and number of high- quality embryos transferred . No statistically significant differences between the two groups were observed with regard to rates of fertilisation , implantation and pregnancy/cycle . Although not statistically significant , rates of miscarriage ( IMSI:15.3 % vs ICSI:31.7 % ) , ongoing pregnancy ( IMSI:22 % vs ICSI:13 % ) and live births ( IMSI:21 % vs ICSI:12 % ) showed a trend towards better outcomes in the IMSI group . In addition , analysis of sub population s with or without male factor showed similar results . Conclusions Our results suggest that IMSI does not provide a significant improvement in clinical outcome compared to ICSI , at least in couples with repeated implantation failures after conventional ICSI . However , it should be noted that there were clear trends for lower miscarriage rates ( ≈50 % reduced ) and higher rates of ongoing pregnancy and live births ( both nearly doubled ) within the IMSI group . Further confirmation as well as r and omized large-scale trials are needed to confirm the beneficial effects of IMSI in couples with poor reproductive prognoses This prospect i ve r and omized study investigated whether intracytoplasmic sperm injection ( ICSI ) outcome can be improved with sperm pre selection under ×6000 magnification and intracytoplasmic morphologically selected sperm injection ( IMSI ) in patients with teratozoospermia and characterized embryo development and quality regarding sperm morphology and presence of head vacuoles . Couples with isolated teratozoospermia were divided into two groups : IMSI group ( n=52 ) and ICSI group ( n=70 ) and fertilization , blastocyst and clinical pregnancy rates were compared . Oocytes from 30 r and omly chosen patients from the IMSI group were injected with spermatozoa that had been previously classified under ×6000 magnification into four classes according to the number and size of vacuoles in the head and then cultured separately . Pronuclear morphology , embryo development and blastomere viability were estimated to investigate the influence of sperm morphology , especially vacuoles , on embryo developmental capacity . A significantly higher clinical pregnancy rate was achieved in the IMSI group compared with the ICSI group ( 48 % versus 24 % , P<0.05 ) . Fertilization with spermatozoa without head vacuoles yielded higher number of morphologically normal zygotes , higher blastocyst rate and smaller proportion of arrested embryos than spermatozoa with vacuoles and other head defects . IMSI is a method of choice in patients with teratozoospermia Background Sperm of poor quality can negatively affect embryo development to the blastocyst stage . The aim of this comparative prospect i ve r and omized study was to evaluate the role of an intracytoplasmic morphologically selected sperm injection ( IMSI ) in the same infertile couples included in the programme of intracytoplasmic sperm injection ( ICSI ) due to their indications of male infertility which had result ed in all arrested embryos following a prolonged 5-day culture in previous ICSI cycles . Methods Couples exhibiting poor semen quality and with all arrested embryos following a prolonged 5-day culture in previous ICSI cycles were divided into two groups : Group 1 : IMSI group ( n = 20 ) with IMSI performed in a current attempt and Group 2 : ICSI group ( n = 37 ) with a conventional ICSI procedure performed in a current attempt of in vitro fertilization . Fertilization rate , embryo development , implantation , pregnancy and abortion rates were compared between current IMSI and conventional ICSI procedures , and with previous ICSI attempts . Results The IMSI group was characterized by a higher number of blastocysts per cycle than the ICSI group ( 0.80 vs. 0.65 ) after a prolonged 5-day embryo culture . There was a significantly lower number of cycles with all arrested embryos and cycles with no embryo transfer in the IMSI group versus the ICSI group ( 0 % vs. 27.0 % , p = 0.048 ) . After the transfer of embryos at the blastocyst or morula stage ( on luteal day 5 ) a tendency toward higher implantation and pregnancy rates per cycle was achieved in the IMSI group compared to the ICSI group ( 17.1 % vs. 6.8 % ; 25.0 % vs. 8.1 % , respectively ) , although not statistically significant . After IMSI , all pregnancies achieved by the blastocyst transfer were normally on-going , whereas after ICSI , two of three pregnancies ended in spontaneous abortion . After IMSI , two pregnancies were also achieved by the morula stage embryos , whereas after the conventional ICSI procedure , embryos at the morula stage did not implant . Conclusions The IMSI procedure improved embryo development and the laboratory and clinical outcomes of sperm microinjection in the same infertile couples with male infertility and poor embryo development over the previous ICSI attempts The aim of this prospect i ve r and omized study was to determine if the use of intracytoplasmic morphologically selected sperm injection ( IMSI ) is associated with gender incidence . Couples who underwent IVF-preimplantation genetic screening ( PGS ) cycles , as a result of advanced maternal age , were r and omly allocated into two groups : intracytoplasmic sperm injection ( ICSI ; n=80 ) or intracytoplasmic morphologically selected sperm injection ( IMSI ; n=80 ) . The incidences of genders were compared between ICSI- and IMSI-derived embryos . Considering all the biopsied embryos were characterized as normal for sex chromosome , the results showed that IMSI results in a significantly higher incidence of female embryos as compared with ICSI ( 65.1 % versus 54.0 % , respectively , P=0.0277 ) . After analysing only euploid embryos for the eight selected chromosomes , a significantly higher incidence of XX embryos derived from IMSI was also observed compared with ICSI cycles ( 66.9 % versus 52.5 % , respectively , P=0.0322 ) . This result was confirmed by logistic regression , which demonstrated a nearly 2-fold increase in euploid XX embryos derived from spermatozoa selected by high magnification ( OR 1.83 , 95 % CI 1.05 - 3.35 , P=0.032 ) . A higher proportion of morphologically normal spermatozoa analysed under high magnification seem to carry the X chromosome . The aim of this study was to determine if the use of intracytoplasmic morphologically selected sperm injection ( IMSI ) is associated with gender incidence . Couples who underwent IVF with preimplantation genetic screening , as a result of advanced maternal age , were r and omly allocated into two groups : intracytoplasmic sperm injection ( ICSI ; n=80 ) or intracytoplasmic morphologically selected sperm injection ( IMSI ; n=80 ) . The incidences of genders were compared between ICSI- and IMSI-derived embryos . Our results showed that a significantly higher incidence of female embryos derived from IMSI compared with ICSI cycles ( 66.9 % versus 52.5 % , respectively , P=0.0322 ) . This result was confirmed by logistic regression , which demonstrated a nearly 2-fold increase in female embryos derived from sperm selected by high magnification ( OR 1.83 , 95 % CI 1.05 - 3.35 , P=0.032 ) . A higher proportion of morphologically normal spermatozoa analysed under high magnification seem to carry the X chromosome Recent evidence shows that the selection of spermatozoa based on the analysis of morphology under high magnification ( ×6000 ) may have a positive impact on embryo development in cases with severe male factor infertility and /or previous implantation failures . The objective of this prospect i ve r and omized study was to compare the clinical outcome of 87 intracytoplasmic morphologically selected sperm injection ( IMSI ) cycles with 81 conventional intracytoplasmic sperm injection ( ICSI ) cycles in an unselected infertile population . IMSI did not provide a significant improvement in the clinical outcome compared with ICSI although there were trends for higher implantation ( 28.9 % versus 19.5 % ) , clinical pregnancy ( 54.0 % versus 44.4 % ) and live birth rates ( 43.7 % versus 38.3 % ) in the IMSI group . However , severe male factor patients benefited from the IMSI procedure as shown by significantly higher implantation rates compared with their counterparts in the ICSI group ( 29.6 % versus 15.2 % , P=0.01 ) . These results suggest that IMSI may improve IVF success rates in a selected group of patients with male factor infertility . New technological developments enable the real time examination of motile spermatozoa with an inverted light microscope equipped with high-power differential interference contrast optics , enhanced by digital imaging . High magnification ( over ×6000 ) provides the identification of spermatozoa with a normal nucleus and nuclear content . Intracytoplasmic injection of spermatozoa selected according to fine nuclear morphology under high magnification may improve the clinical outcome in cases with severe male factor infertility The aim of the present prospect i ve study was to determine whether subtle sperm morphological characteristics affect the outcome of intracytoplasmic sperm injection ( ICSI ) , and if so , to identify those that are relevant . For this purpose , we developed a new method , the motile sperm organelle morphology examination ( MSOME ) . The examination is performed in real time using an inverted light microscope equipped with high-power Nomarski optics enhanced by digital imaging to achieve a magnification up to 6300x . MSOME was applied to the leftover sperm fraction selected for microinjection in 100 r and om couples referred for ICSI treatment at 3 major in vitro fertilization centers . We found that the morphological normalcy of the entire sperm cell , according to MSOME criteria , was positively associated with ICSI fertilization rate ( area under the receiver operating characteristics [ ROC ] curve , 88 % ) but not with pregnancy outcome . The morphological normalcy of the sperm nucleus , defined by MSOME , was significantly and positively associated with both fertilization rate and pregnancy outcome ( areas under the ROC curve , 72 % and 74 % , respectively ) . These findings indicate that ICSI-associated pregnancy rate may be affected by subtle morphological malformations of the sperm nucleus , which may remain undetected by the embryologist during the routine selection procedure Intracytoplasmic morphologically selected sperm injection ( IMSI ) , by selecting spermatozoa at high magnification improves the outcome of intracytoplasmic sperm injection ( ICSI ) mainly after several failures . However , only few monocentric r and omized studies are available and they do not analyse results as a function of sperm characteristics . In 255 couples attempting their first assisted reproductive technology ( ART ) attempt for male infertility ( motile sperm count < 1 × 106 after sperm selection , but at least 3 × 106 spermatozoa per ejaculate to allow a detailed analysis of sperm characteristics ) , a prospect i ve r and omized trial was performed to compare the clinical outcomes of IMSI and ICSI and to evaluate the influence of sperm characteristics on these outcomes . IMSI did not provide any significant improvement in the clinical outcomes compared with ICSI neither for implantation ( 24 % vs. 23 % ) , nor clinical pregnancy ( 31 % vs. 33 % ) nor live birth rates ( 27 % vs. 30 % ) . Moreover , the results of IMSI were similar to the ICSI ones whatever the degree of sperm DNA fragmentation , nuclear immaturity and sperm morphology . These results show that IMSI instead of ICSI has no advantage in the first ART attempts . However , this does not rule out IMSI completely and more r and omized trials must be performed especially regarding patients carrying severe teratozoospermia , or high sperm DNA fragmentation levels or having previous ICSI failures Purpose We used computer assisted sperm selection ( MSOME ) during cycles of intracytoplasmic sperm injection to test whether this technique improves results over traditional ICSI protocol s. We also used the TUNEL assay to test whether MSOME could deselect physiologically abnormal spermatozoa . Methods Individual spermatozoa were examined with MSOME . Normal and abnormal spermatozoa were tested for the level of DNA fragmentation using TUNEL assay . In a prospect i ve , r and omized trial , patients were selected for st and ard ICSI , or IMSI techniques . We tested the two groups for biological and clinical parameters . Results 64.8 % of spermatozoa , otherwise selectable for ICSI , were characterized by abnormalities after computer-assisted sperm analysis . These sperm were also characterized by an increase in the level of DNA fragmentation . We noted an increase in embryo quality , pregnancy and implantation rates after computerized sperm selection during ICSI procedures . Conclusions Computerised selection of spermatozoa during ICSI procedures deselects physiological abnormal spermatozoa and improves clinical results The aim of this prospect i ve r and omized study was to assess the advantages of a new modified intracytoplasmic sperm injection ( ICSI ) technique called intracytoplasmic morphologically selected sperm injection ( IMSI ) over the conventional ICSI procedure in the treatment of patients with severe oligoasthenoteratozoospermia . The new procedure consisted of IMSI based on a preliminary motile sperm organellar morphology examination under x6600 high magnification . A total of 446 couples with at least two previous diagnoses of severe oligoasthenoteratozoospermia , 3 years of primary infertility , the woman aged 35 years or younger , and an undetected female factor were r and omized to IVF micro-insemination treatments : ICSI ( n = 219 ; group 1 ) and IMSI ( n = 227 ; group 2 ) . A comparison between the two different techniques was made in terms of pregnancy , miscarriage and implantation rates . The data showed that IMSI result ed in a higher clinical pregnancy rate ( 39.2 % versus 26.5 % ; P = 0.004 ) than ICSI when applied to severe male infertility cases . Despite their initial poor reproductive prognosis , patients with two or more previous failed attempts benefited the most from IMSI in terms of pregnancy ( 29.8 % versus 12.9 % ; P = 0.017 ) and miscarriage rates ( 17.4 % versus 37.5 % ) . At present , 35 healthy babies have been born following the introduction of this promising technique in daily IVF practice OBJECTIVE To evaluate advanced maternal age as a rationale for performing intracytoplasmic morphologically selected sperm injection ( IMSI ) . STUDY DESIGN This study included couples undergoing intracytoplasmic sperm injection ( ICSI ) as a result of advanced maternal age ( ≥37 years old ) . Sample size calculations were based on the assumption that a 15 % difference in implantation rate would mean a clinical ly significant difference . To achieve this difference , 33 cycles would be needed in each treatment arm ( with a significance level of 5 % and power of 85 % ) . Couples were r and omly allocated to one of two sperm selection procedures ( ICSI , n=33 ; or IMSI , n=33 ) . Sperm selection in the ICSI group was analyzed under a magnification of 400 × . Sperm selection in the IMSI group was analyzed under high magnification of 6600 × . The groups were compared with regard to the outcome of the cycles . RESULTS IMSI cycles showed significantly higher implantation ( 4/33 , 12.1 % vs. 18/47 , 38.3 % , p=0.026 ) and pregnancy ( 4/29 , 13.8 vs. 18/30 , 60.0 % , p<0.001 ) rates . The IMSI procedure positively influenced the blastocyst formation rate ( RC : 15.00 , R2 : 49.9 % , p=0.001 ) and implantation rate ( RC : 24.04 , R2 : 9.6 , p=0.027 ) , and was determinant to the increased odds of pregnancy ( OR : 9.0 , CI : 2.17 - 37.38 , p=0.001 ) . CONCLUSION It seems that the injection of a morphologically normal spermatozoon overcomes the low oocyte quality in older women , result ing in improved embryo quality and in a 9-fold increase in the clinical pregnancy rate in couples with advanced maternal age OBJECTIVE To evaluate whether intracytoplasmic morphologically selected sperm injection ( IMSI ) could influence early paternal effects by observing embryo quality at day 2 . STUDY DESIGN The study included 30 couples with at least one of the following criteria : male factor infertility , at least 2 previous failures of implantation or previous miscarriages after IVF/ICSI . Sibling oocytes of each patient were r and omly assigned to either the ICSI group or the IMSI group . For IMSI , spermatozoa were selected at 8400x magnification through an inverted microscope equipped with Nomarski differential interference contrast optics , Uplan Apo 100x oil/1.35 objective lens and variable zoom lens . For conventional ICSI , spermatozoa were selected at 400x magnification . An embryo was defined as top quality if there were four identical blastomeres on day 2 with no fragments or multinucleation of blastomeres . Data were analysed using the Wilcoxon and chi-squared tests . The significance level was set at P<0.05 . The variables were analysed in relation to the general population and the sub population s with or without male factor . RESULTS A total of 331 MII oocytes ( 30 oocyte retrievals ) were selected and injected by the ICSI ( n : 172 ) or IMSI ( n : 159 ) procedure . For IMSI , only spermatozoa classified as morphologically normal at high magnification were used . No differences ( P>0.05 ) in fertilisation rate ( ICSI : 70.9 % ; IMSI : 70.4 % ) , early embryo cleavage rate ( ICSI : 66.9 % ; IMSI : 60.4 % ) or cleavage rate ( ICSI : 99.2 % ; IMSI : 99.1 % ) were observed . On day 2 , as compared to ICSI , IMSI provided a similar proportion of top quality embryos ( ICSI : 57.8 % ; IMSI : 52.2 % ; P>0.05 ) . These results were not influenced by the presence or absence of male factor . CONCLUSION In terms of embryo quality at day 2 , IMSI had the same performance as conventional ICSI . However , we can not exclude the possibility that IMSI effects occur only as a positive later paternal effect PURPOSE To determine if isolation of sperm by nuclear characteristics using high magnification offers any advantage over the normal morphologic methods when performing intracytoplasmic sperm injection ( ICSI ) in refractory cases in which the male partner had an abnormal DNA fragmentation index . MATERIAL S AND METHODS Women aged < or = 39 with failure to have a successful conception after three consecutive embryo transfers whose male partner had a DNA fragmentation index > 30 % were r and omly assigned to isolation of sperm for ICSI by a new high magnification procedure to evaluate nuclear morphology and the usual method with normal magnification where nuclear characteristics were not seen . Women 40 - 43 were not r and omized and were given the option after hearing pros and cons . RESULTS Overall the live delivered pregnancy rates were similar in the high vs normal magnification groups ( 33.3 % vs 36.3 % ) . CONCLUSIONS Isolation of sperm with normal nuclei with high magnification does not offer any advantage over conventional IVF for refractory cases where the male partner has a high DNA fragmentation index |
13,404 | 32,061,651 | Consistent with clinical trials , real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients | BACKGROUND AND AIMS Glecaprevir/pibrentasvir is approved for treating adults infected with hepatitis C virus ( HCV ) genotypes 1 - 6 .
In clinical trials , glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment Week 12 ( SVR12 ) and was well tolerated .
A systematic review and meta- analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken . | BACKGROUND Chronic hepatitis C virus ( HCV ) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease . Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end‐stage renal disease than those who have chronic kidney disease without HCV infection . Patients with both HCV infection and advanced chronic kidney disease have limited treatment options . METHODS We conducted a multicenter , open‐label , phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1 , 2 , 3 , 4 , 5 , or 6 infection and also had compensated liver disease ( with or without cirrhosis ) with severe renal impairment , dependence on dialysis , or both . Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon , ribavirin , sofosbuvir , or a combination of these medications . The primary end point was a sustained virologic response 12 weeks after the end of treatment . RESULTS Among the 104 patients enrolled in the trial , 52 % had genotype 1 infection , 16 % had genotype 2 infection , 11 % had genotype 3 infection , 19 % had genotype 4 infection , and 2 % had genotype 5 or 6 infection . The sustained virologic response rate was 98 % ( 102 of 104 patients ; 95 % confidence interval , 95 to 100 ) . No patients had virologic failure during treatment , and no patients had a virologic relapse after the end of treatment . Adverse events that were reported in at least 10 % of the patients were pruritus , fatigue , and nausea . Serious adverse events were reported in 24 % of the patients . Four patients discontinued the trial treatment prematurely because of adverse events ; three of these patients had a sustained virologic response . CONCLUSIONS Treatment with glecaprevir and pibrentasvir for 12 weeks result ed in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection . ( Funded by AbbVie ; Clinical Trials.gov number , NCT02651194 . BACKGROUND In our country , the national program for hepatitis C virus treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir was approved for patients with stage four of liver fibrosis and stage three associated with specific comorbidities . Our aim was to analyze the characteristics associated with the presence of adverse events in patients receiving this antiviral regimen , with ribavirin in cirrhotic patients . METHODS We prospect ively studied a cohort of adults with hepatitis C virus infection with Child A cirrhosis , treated for 12 weeks with ombitasvir/paritaprevir/ritonavir/dasabuvir and ribavirin , which have been followed in an infectious diseases tertiary-care hospital . RESULTS We included 137 adult patients diagnosed with compensated cirrhosis , hepatitis C virus genotype 1b infected , 82 ( 60 % ) previously treated . We recorded 201 adverse events in 98 ( 71.5 % ) patients , with a median number of events per patient of one . The intensity of adverse events was classified as mild , moderate and severe in 50 % , 36 % and 14 % of cases , respectively . Forty-five ( 22 % ) episodes required medical intervention . The most frequently reported adverse events were pruritus 34(35 % ) , asthenia 22(22 % ) and insomnia 15(15 % ) . The presence of severe adverse events was associated with the presence of comorbidities ( p = 0.01 , OR : 9.5 , 95 % CI : 1.2 - 74.3 ) and with the presence of associated medication ( p = 0.02 , OR : 3.9 , 95 % CI : 1.08 - 14.2 ) . At the end of current treatment , 136 ( 99.2 % ) patients had undetectable viral load . CONCLUSION We found a high number of adverse events , but most of them were mild or moderate and only one quarter of them required medical intervention . Only severe adverse events were associated with comorbidities and associated medication Well‐tolerated , ribavirin‐free , pangenotypic hepatitis C virus ( HCV ) treatments for transplant recipients remain a high priority . Once‐daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response at 12 weeks posttreatment ( SVR12 ) across all major HCV genotypes ( GTs ) . This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1‐6 infection who had received a liver or kidney transplant . MAGELLAN‐2 was a phase 3 , open‐label trial conducted in patients who were ≥3 months posttransplant . Patients without cirrhosis who were HCV treatment‐naive ( GT1‐6 ) or treatment‐experienced ( GT1 , 2 , 4‐6 ; with interferon‐based therapy with or without sofosbuvir , or sofosbuvir plus ribavirin ) received glecaprevir/pibrentasvir ( 300/120 mg ) once daily for 12 weeks . The primary endpoint compared the percentage of patients receiving glecaprevir/pibrentasvir with SVR12 to a historic SVR12 rate based on the st and ard of care . Safety of glecaprevir/pibrentasvir was assessed . In total , 80 liver transplant and 20 kidney transplant patients participated in the trial . Most patients had no or minimal fibrosis ( 80 % had fibrosis scores F0‐F1 ) and were infected with HCV GT1 ( 57 % ) or GT3 ( 24 % ) . The overall SVR12 was 98 % ( n/N = 98/100 ; 95 % confidence interval , 95.3%–100 % ) , which exceeded the prespecified historic st and ard‐of‐care SVR12 threshold of 94 % . One patient experienced virologic failure . One patient discontinued because of an adverse event considered to be unrelated to treatment ; this patient achieved SVR12 . Adverse events were mostly mild in severity , and laboratory abnormalities were infrequent . Conclusion : Once‐daily glecaprevir/pibrentasvir for 12 weeks is a well‐tolerated and efficacious , ribavirin‐free treatment for patients with chronic HCV GT1‐6 infection who have received a liver or kidney transplant . ( Clinical Trials.gov NCT02692703 . ) ( Hepatology 2018 ; 00:000‐000 ) The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus ( HCV ) genotype 4-infected patients with METAVIR F0-F4 fibrosis . Sixty-three patients ( 33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced ) enrolled in a partly r and omized , open-label , multicentre , phase IIa study . Patients with F0-F3 fibrosis were r and omized ( 1:1 ) into two groups ( A1 and A2 ) , stratified according to treatment experience and METAVIR score , to receive either eight weeks ( Group A1 , n=20 ) or 12 weeks ( Group A2 , n=20 ) of treatment . Patients with compensated cirrhosis ( METAVIR F4 ) received 12 weeks of treatment ( Group B , n=23 ) . Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily . The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment ( SVR12 ) . Safety and tolerability were assessed throughout . Overall , 92 % ( 95 % CI : 82 - 97 ) of patients achieved SVR12 ; 75 % ( 15/20 ) in Group A1 and 100 % in groups A2 and B. Patients who did not achieve SVR12 ( n=5 ) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders . The most commonly reported treatment-emergent adverse events ( TEAEs ) were asymptomatic lipase increase ( 14 % ) , pruritus ( 14 % ) , headache ( 13 % ) and hyperbilirubinaemia ( 11 % ) . No patients discontinued due to TEAEs . In conclusion , simeprevir plus sofosbuvir for 12 weeks achieved a 100 % SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis ( Clinical Trials.gov : NCT02278419 ) . The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens BACKGROUND Injection drug use is the primary mode of transmission for hepatitis C virus ( HCV ) , and treatment guidelines recommend treating HCV-infected people who use drugs ; however , concerns about adherence , effectiveness , and reinfection have impeded treatment uptake . METHODS Data were pooled from seven phase III trials that evaluated the efficacy and safety of 8 or 12 weeks of glecaprevir/pibrentasvir ( G/P ) in patients chronically infected with HCV genotypes 1 - 6 . Patients had compensated liver disease , with or without cirrhosis , and were HCV treatment-naïve or -experienced with interferon or pegylated interferon ± ribavirin , or sofosbuvir plus ribavirin ± pegylated interferon . Patients were grouped into recent drug users ( injection drug use ≤12 months before screening , positive urine drug screen [ UDS ] , and /or drug-related adverse event ) , former drug users ( > 12 months before screening and negative UDS ) , or non-drug users . Assessment s included sustained virologic response at 12 weeks posttreatment ( SVR12 ) , treatment adherence , and safety . RESULTS Among 1819 patients , 5 % , 34 % , and 61 % were recent , former , and non-drug users , respectively . Treatment adherence and completion were high ( ≥96 % ) regardless of drug use status . SVR12 was achieved by 93 % ( n/N = 91/98 ) , 97 % ( n/N = 591/610 ) , and > 99 % ( n/N = 1106/1111 ) of recent , former , and non-drug users , respectively ( intention-to-treat analysis ) . The overall rates of virologic failure were ≤1.5 % across all three sub population s , with no HCV reinfections among recent drug users . Drug-related serious adverse events and adverse events leading to treatment discontinuation were experienced by ≤1 % of patients . CONCLUSIONS G/P is a well-tolerated and efficacious pangenotypic regimen for chronic HCV-infected people with recent or active drug use Screening and treatment for hepatitis C virus ( HCV ) infection were not prioritised in psychiatric patients due to adverse neuropsychiatric effects of interferon therapy despite reports of high prevalence . However , with the safe new antiviral drugs , HCV eradication has become a reality in these patients . The aim of this study was to report HCV seroprevalence , risk factors and treatment model in an Australian cohort . This prospect i ve study involved patients admitted to four inpatient psychiatric units , from December 2016 to December 2017 . After pretest counselling and consent , HCV testing was done ; information on risk factors collected . A total of 260 patients ( 70 % male ) , median age 44 years ( IQR 24 ) , were studied . The HCV seroprevalence was 10.8 % ( 28/260 ) with 95 % CI 7 - 15 . Independent predictors of HCV positivity were injection drug use ( P < 0.001 , OR 44.05 , 95 % CI 7.9 - 245.5 ) , exposure to custodial stay ( P = 0.011 , OR 7.34 , 95 % CI 1.6 - 33.9 ) and age ( P = 0.011 , OR 1.09 , 95 % CI 1.02 - 1.16 ) . Eight of the 16 HCV RNA-positive patients were treated . Hepatitis nurses liaised with community mental health teams for treatment initiation and follow-up under supervision of hepatologists . Seven patients achieved sustained viral response , one achieved end of treatment response . The remaining eight patients were difficult to engage with . In conclusion , HCV prevalence was high in our cohort of psychiatric in patients . Although treatment uptake was achieved only in 50 % patients , it was successfully completed in all , with innovative models of care . These findings highlight the need to integrate HCV screening with treatment linkage in psychiatry practice |
13,405 | 28,210,109 | We found a large treatment effect of adding astragalus-based herbal treatment to st and ard chemotherapy regimens . | BACKGROUND Non-small-cell lung cancer ( NSCLC ) is a leading cause of death .
Interventions to reduce mortality in patients with NSCLC represent a patient-important field of research .
Little is known about interventions used outside the Western world for NSCLC .
One intervention widely used in Asia is astragalus-based herbal preparations . | I SHALL discuss the combination of estimates of relative prevalence or incidence , commonly referred to as relative risk , obtained from retrospective 2 X 2 tables . Barnet Woolf ' described the method in 1954 and J. B. S. Haldane2 introduced some modifications shortly afterward in the Annals of Human Genetics . Figure 1 shows how retrospective case and control data may be classified . There are usually some background classes based on age , sex , race , occupation , and the like . Within each such class , individuals are further classified into a 2 X 2 table according to the presence or absence of the disease being studied and the presence or absence of a defined characteristic of focal interest . For any single 2 X 2 table , Cornfield3 has shown a simple way to estimate the risk of disease among those wvith the characteristic , relative to the risk of disease among those without the characteristic . This is done , as illustrated below Figure 1 , by taking the ratio of diagonal products of the cell frequencies . This is a maximum likelihood estimate of the relative risk of disease in the parent population , provided that it is assumed that the cases and controls have been selected at r and om and that cases comprise a negligible portion of the population . It is also possible to obtain a combined , unconditioned , maximum likelihood estimate of relative risk based on all of the 2 X 2 tables . However , the method is time-consuming , involving the iterative solution of sets of quadratic equations . Unless such a method is programed for the computer , I feel that the less tedious procedure to be described is adequate for most practical purpose s. Strictly speaking , the maximum likelihood estimate just described has infinite bias and it is positively skewed . To help remedy these defects , the number , 1/2 , is added to each cell frequency before obtaining the ratio of diagonal products ; furthermore , the natural logarithm of this ratio is taken . The result ing value is an estimate of natural log relative risk . Woolf pointed out that the logarithmic transformation tends to remove skew and Haldane showed that of all possible numbers which might be added to or subtracted from the cell frequencies , 1/2 is the number which reduces the bias of the estimate to a minimum . This estimate of log relative risk is shown in the first column of Figure 2 . The estimated Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for r and omization and could on those grounds be deemed authentic r and omized controlled trials ( 6.8 % , 95 % confidence interval 5.9–7.7 ) . There was no statistically significant difference in the rate of authenticity between r and omized controlled trials of traditional interventions and those of conventional interventions . R and omized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals ( relative risk 1.58 , 95 % confidence interval 1.18–2.13 , and relative risk 14.42 , 95 % confidence interval 9.40–22.10 , respectively ) . The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals ( relative risk 9.32 , 95 % confidence interval 5.83–14.89 ) . All r and omized controlled trials of pre-market drug clinical trial were authentic by our criteria . Of the trials conducted at university-affiliated hospitals , 56.3 % were authentic ( 95 % confidence interval 32.0–81.0 ) . Conclusion Most reports of r and omized controlled trials published in some Chinese journals lacked an adequate description of r and omization . Similarly , most so called ' r and omized controlled trials ' were not real r and omized controlled trials owing toa lack of adequate underst and ing on the part of the authors of rigorous clinical trial design . All r and omized controlled trials of pre-market drug clinical trial included in this research were authentic . R and omized controlled trials conducted by authors in high level hospitals , especially in hospitals affiliated to medical universities had a higher rate of authenticity . That so many non-r and omized controlled trials were published as r and omized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed OBJECTIVE To determine whether clinical trials originating in certain countries always have positive results . DATA SOURCES Abstract s of trials from Medline ( January 1966-June 1995 ) . STUDY SELECTION Two separate studies were conducted . The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo , no treatment , or a nonacupuncture intervention . In the second study , r and omized or controlled trials of interventions other than acupuncture that were published in China , Japan , Russia/USSR , or Taiwan were compared to those published in Engl and . DATA EXTRACTION Blinded review ers determined inclusion and outcome and separately classified each trial by country of origin . DATA SYNTHESIS In the study of acupuncture trials , 252 of 1085 abstract s met the inclusion criteria . Research conducted in certain countries was uniformly favorable to acupuncture ; all trials originating in China , Japan , Hong Kong , and Taiwan were positive , as were 10 out of 11 of those published in Russia/USSR . In studies that examined interventions other than acupuncture , 405 of 1100 abstract s met the inclusion criteria . Of trials published in Engl and , 75 % gave the test treatment as superior to control . The results for China , Japan , Russia/USSR , and Taiwan were 99 % , 89 % , 97 % , and 95 % , respectively . No trial published in China or Russia/USSR found a test treatment to be ineffective . CONCLUSIONS Some countries publish unusually high proportions of positive results . Publication bias is a possible explanation . Research ers undertaking systematic review s should consider carefully how to manage data from these countries BACKGROUND We conducted a r and omized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer . METHODS A total of 1207 patients with advanced non-small-cell lung cancer were r and omly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens : cisplatin and gemcitabine , cisplatin and docetaxel , or carboplatin and paclitaxel . RESULTS The response rate for all 1155 eligible patients was 19 percent , with a median survival of 7.9 months ( 95 percent confidence interval , 7.3 to 8.5 ) , a 1-year survival rate of 33 percent ( 95 percent confidence interval , 30 to 36 percent ) , and a 2-year survival rate of 11 percent ( 95 percent confidence interval , 8 to 12 percent ) . The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens . Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3 , 4 , or 5 renal toxicity ( in 9 percent of patients , vs. 3 percent of those treated with cisplatin plus paclitaxel ) . Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1 . CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer PURPOSE This r and omized trial was design ed to determine whether paclitaxel plus carboplatin ( PC ) offered a survival advantage over vinorelbine plus cisplatin ( VC ) for patients with advanced non -- small-cell lung cancer . Secondary objectives were to compare toxicity , tolerability , quality of life ( QOL ) , and re source utilization . PATIENTS AND METHODS Two hundred two patients received VC ( vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d , day 1 every 28 days ) and 206 patients received PC ( paclitaxel 225 mg/m(2 ) over 3 hours with carboplatin area under the curve of 6 , day 1 every 21 days ) . Patients completed QOL question naires at baseline , 13 weeks , and 25 weeks . Re source utilization forms were completed at five time points through 24 months . RESULTS Patient characteristics were similar between the groups . The objective response rate was 28 % in the VC arm and 25 % in the PC arm . Median survival was 8 months in both arms , with 1-year survival rates of 36 % and 38 % , respectively . Grade 3 and 4 leukopenia ( P = .002 ) and neutropenia ( P = .008 ) occurred more frequently on the VC arm . Grade 3 nausea and vomiting were higher on the VC arm ( P = .001 , P = .007 ) , and grade 3 peripheral neuropathy was higher on the PC arm ( P < .001 ) . More patients on the VC arm discontinued therapy because of toxicity ( P = .001 ) . No difference in QOL was observed . Overall costs on the PC arm were higher than on the VC arm because of drug costs . CONCLUSION PC is equally efficacious as VC for the treatment of advanced non -- small-cell lung cancer . PC is less toxic and better tolerated but more expensive than VC . New treatment strategies should be pursued OBJECTIVE To observe the clinical therapeutic effect and mechanism of Yiqi Yangyin Jiedu Decoction ( YYJD , a Chinese herbal recipe for strengthening qi , nourishing yin and removing toxic substance , consisting of milkvetch root 30 g , glehnia root 30 g , asparagus root 15 g , lilyturf root 15 g , grossy privet fruit 12 g , spikemoss herb 30 g , Chinese sage herb 30 g , manyleaf paris rhizome 30 g , etc . ) in treating patients with advanced nonsmall cell lung cancer ( NSCLC ) . METHODS Sixty patients with advanced lung cancer of qi-yin deficiency syndrome were r and omized into three groups : the TCM group ( A ) treated with YYJD , the chemotherapy group ( B ) treated by chemotherapy with NP or GP protocol , and the combined treated group ( C ) treated with YYJD and chemotherapy in combination . The efficacy was evaluated after two cycles of treatment . RESULTS The total effective rate for alleviating qi-yin deficiency syndrome in group A was 80 % , significantly higher than that in Group C and B ( 35 % and 20 % , P < 0.01 ) respectively . The KPS increasing and stabilizing rate in Group A and C was 90 % and 85 % respectively , significantly higher than that in Group B ( 75 % ) , and difference between A and B was significant ( P < 0.05 ) . In Group C after treatment , CD(3)+ showed a rising trend ( P = 0.05 ) , different to that in Group A and B ( P < 0.05 and P < 0.01 ) ; CD(4)+ significantly increased ( P < 0.05 ) and CD(4)+/CD(8)+ ratio showed increasing trend ( P = 0.06 ) , while in Group B both were decreased significantly , showed significantly difference ( P < 0.05 ) . CD(8)+ CD(28)+ significantly increased after treatment in Group A and C ( P < 0.01 and P < 0.05 ) , but showed decreasing trend ( P = 0.06 ) in Group B , significant difference was shown between B and C ( P < 0.05 ) . CONCLUSION YYJD can ameliorate the qi-yin deficiency syndrome evidently in advance lung cancer patients ; improve their quality of life , the mechanism might be by way of enhancing T-lymphocyte activity and killer T-cell function , to elevate the T-cell mediated immunity in a round way OBJECTIVE To observe the regulatory effect of Jianpi Wenshen Recipe ( JPWS ) , a Chinese herbal preparation for strengthening Pi and warming Shen , combined with chemotherapy on the level of estradiol ( E2 ) in patients with mid-late non-small cell lung cancer ( NSCLC ) , and to analyse the relationship between the changes of estradiol and tumor size . METHODS Fifty-one NSCLC patients were r and omized into three groups : 16 cases in the JPWS group treated with JPWS alone , 18 cases in the test group treated with combined therapy of JPWS plus chemotherapy , and 17 cases in the chemotherapy group treated with chemotherapy alone , all were treated for 2 months . The changes of blood E2 level and tumor size before and after treatment were compared . RESULTS The disease control rate in the JPWS group and combined therapy group was 53.85 % ( 7/13 ) and 80.00 % ( 8/10 ) , respectively , both were higher than that in the chemotherapy group ( 44.40 % , 4/9 ) , but the difference showed statistical in significance ( P > 0.05 ) . E2 level was significantly lowered after treatment in the former two groups ( all P < 0.05 ) , and the change was in accordance with that of tumor size in 26 out of 31 patients ( P < 0.01 ) . CONCLUSION JPWS combined with chemthherapy can stabilize the tumor size and down-regulate E2 levelo , with the change of E2 correlated with that of tumor size in patients . Hence , decreasing E2 is one of the mechanisms for JPWS in treating lung cancer BACKGROUND To compare the therapeutic effect , adverse reaction and effect on immunity of chemotherapy combined Aidi injection ( AI ) with those of chemotherapy alone in the treatment of advanced non small cell lung cancer ( NSCLC ) . METHODS Ninety eight cases of advanced NSCLC were r and omly divided into two groups , trial group and control group . In the trial group , NP plus AI ( 60 80 ml ) were given intravenously by dissolving in 400 ml of normal saline per day for 8 - 10 days , while in the control group , only NP chemotherapy was given . Navelbine ( 25 mg/m² , d1 , 8) and cisplastin ( 40 mg/m² , d1 - 3 ) were chosen in the chemotherapy . Each patient received at least two cycles of treatment . RESULTS The effective rate in the trial group and the control group was 53.1 % and 44.9 % respectively , without significant difference between the two groups ( P > 0.05 ) . But the rate of progression , adverse reactions in bone marrow and digestive tract , and change of immunity in the trial group were all lower than those in the control group ( P < 0.05 ) , and the improvement in Karnofsky score in the trial group was higher than that in the control group ( P < 0.05 ) . CONCLUSIONS Chemotherapy of NP combined with AI shows benefit in the treatment of advanced NSCLC . AI could decrease the influence on immunity and adverse reaction of chemotherapy , and improve the quality of life in patients with NSCLC OBJECTIVE To assess the method ologic quality of approaches used to allocate participants to comparison groups in r and omized controlled trials from one medical specialty . DESIGN Survey of published , parallel group r and omized controlled trials . DATA SOURCES All 206 reports with allocation described as r and omized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology . MAIN OUTCOME MEASURES Direct and indirect measures of the adequacy of r and omization and baseline comparisons . RESULTS Only 32 % of the reports described an adequate method for generating a sequence of r and om numbers , and only 23 % contained information showing that steps had been taken to conceal assignment until the point of treatment allocation . A mere 9 % described both sequence generation and allocation concealment . In reports of trials that had apparently used unrestricted r and omization , the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance . In reports of trials in which hypothesis tests had been used to compare baseline characteristics , only 2 % of reported test results were statistically significant , lower than the expected rate of 5 % . CONCLUSIONS Proper r and omization is required to generate unbiased comparison groups in controlled trials , yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation . Additional analyses suggest that nonr and om manipulation of comparison groups and selective reporting of baseline comparisons may have occurred PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type |
13,406 | 17,066,630 | CONCLUSIONS Major bone grafting procedures of extremely resorbed m and ibles may not be justified .
Bone substitutes may replace autogenous bone for sinus lift procedures of extremely atrophic sinuses .
Both guided bone regeneration procedures and distraction osteogenesis can be used to augment bone vertically , but it is unclear which is the most efficient .
It is unclear whether augmentation procedures are needed at immediate single implants placed in fresh extraction sockets ; however , sites treated with barrier + Bio-Oss showed a higher position of the gingival margin than sites treated with barriers alone .
More bone was regenerated around fenestrated implants with nonresorbable barriers than without barriers ; however , it remains unclear whether such bone is of benefit to the patient .
Bone morphogenetic proteins may enhance bone formation around implants grafted with Bio-Oss , but there was no reliable evidence supporting the efficacy of other active agents , such as platelet-rich plasma , in conjunction with implant treatment | PURPOSE To test ( a ) whether and when bone augmentation procedures are necessary and ( b ) which is the most effective augmentation technique for specific clinical indications . | The purpose of the present study was to compare the success of and surgical differences between 1- and 2-stage sinus inlay bone grafts and implants after 1 year in function . The individual risk for implant failure in grafted areas among 1-stage patients was about twice the risk in 2-stage patients ( odds ratio 2.3 , CI 0.6 ; 8.5 ) . The risk for implant failure in non-grafted areas was significantly lower ( P < .05 ) than in grafted areas , regardless of the technique used . Forty edentulous patients , selected according to strict inclusion criteria from consecutive referrals , were allocated to one or other of the 2 sinus-inlay procedures . Twenty patients received bone blocks fixed by implants to the residual alveolar crest in a 1-stage procedure ( group 1 ) . In another 20 patients , particulated bone was condensed against the antral floor and left to heal for 6 months before implants were placed ( group 2 ) . An almost equal number of implants was placed in the patients of each group , 76 in the 1-stage procedure and 74 in the 2-stage procedure . Additionally , 72 and 66 implants were placed in the anterior non-grafted regions of group 1 and group 2 patients , respectively . After 1 year in function , a total of 20 implants failed in 1-stage patients , versus 11 in 2-stage patients . Sixteen and 8 implants , respectively , of these were placed in grafted bone . All but one 1-stage patient received the planned fixed prosthetic restorations , but 1 restoration was re design ed after the first year in function because of a functionally unacceptable prosthetic design . At the 1-year follow-up , one 2-stage patient lost her prosthesis as the result of multiple implant failures . Bruxism and postoperative infections were the only parameters that could be related to implant failure , however , depending on the statistical method used To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results The aim of the present clinical study was to test whether or not the addition of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) to a xenogenic bone substitute mineral ( Bio-Oss ) will improve guided bone regeneration therapy regarding bone volume , density and maturation . In 11 partially edentulous patients , 34 Brånemark implants were placed at two different sites in the same jaw ( five maxillae , six m and ibles ) requiring lateral ridge augmentation . The bone defects were r and omly assigned to test and control treatments : the test and the control defects were both augmented with the xenogenic bone substitute and a resorbable collagen membrane ( Bio-Gide ) . At the test sites , the xenogenic bone substitute mineral was coated with rhBMP-2 in a lyophilization process . Following implant insertion ( baseline ) , the peri-implant bone defect height was measured from the implant shoulder to the first implant-bone contact . After an average healing period of 6 months ( SD 0.17 , range 5.7 - 6.2 ) , the residual defects were again measured and trephine burs were used to take 22 bone biopsies from the augmented regions . The healing period was uneventful except for one implant site that showed a wound dehiscence , which spontaneously closed after 4 weeks . Later at reentry , all implants were stable . At baseline , the mean defect height was 7.0 mm ( SD 2.67 , range 3 - 12 mm ) at test and 5.8 mm ( SD 1.81 , range 3 - 8 mm ) at control sites . At reentry , the mean defect height decreased to 0.2 mm ( SD 0.35 , range 0 - 1 mm ) at test sites ( corresponding to 96 % vertical defect fill ) and to 0.4 mm ( SD 0.66 , range 0 - 2 mm ) at the control site ( vertical defect fill of 91 % ) . Reduction in defect height from baseline to reentry for both test and control sites was statistically significant ( Wilcoxon P<0.01 ) . Histomorphometric analysis showed an average area density of 37 % ( SD 11.2 , range 23 - 51 % ) newly formed bone at test sites and 30 % ( SD 8.9 , range 18 - 43 % ) at control sites . The fraction of mineralized bone identified as mature lamellar bone amounted to 76 % ( SD 14.4 , range 47.8 - 94 % ) at test compared to 56 % ( SD 18.3 , range 31.6 - 91.4 % ) at control sites ( paired t-test P<0.05 ) . At BMP-treated sites 57 % ( SD 16.2 , range 29 - 81 % ) and at control sites 30 % ( SD 22.6 , range 0 - 66 % ) of the surface of the bone substitute particles were in direct contact with newly formed bone ( paired t-test P<0.05 ) . It is concluded that the combination of the xenogenic bone substitute mineral with rhBMP-2 can enhance the maturation process of bone regeneration and can increase the graft to bone contact in humans . rhBMP-2 has the potential to predictably improve and accelerate guided bone regeneration therapy The purpose of this clinical investigation was to compare the new resorbable collagen membrane , Bio-Gide , to the conventional exp and ed polytetrafluoroethylene material ( Gore-Tex ) for guided bone regeneration in situations involving exposed implant surfaces . Over a 2-year period , 25 split-mouth patients were treated r and omly : one defect site was treated with Bio-Gide and the other defect site with Gore-Tex ; all 84 defects were filled with Bio-Oss and covered with the respective membrane . The defect types , their dimensions , and their morphology were measured in detail initially and at re-entry to allow for calculation of the exposed implant surface . Changes in defect surface for both types of membranes were statistically significant ( P < .0001 ) ; however , no statistical significance ( P > .94 ) could be detected between the two membranes . The mean average percentage of bone fill was 92 % for Bio-Gide and 78 % for Gore-Tex sites . In the latter group , 44 % wound dehiscences and /or premature membrane removal occurred . The resorbable membrane , Bio-Gide , in combination with a bone graft , can be a useful alternative to the well-established exp and ed polytetrafluoroethylene membranes OBJECTIVES Graft insertion can effectively enhance the regeneration of debilitated bone . The effects of an alloplastic bone-replacing material , beta-tricalcium phosphate ( Cerasorb ) , and of autogenous bone graft were compared . MATERIAL S AND METHODS In 17 edentulous patients , the maxillary sinus floor was extremely atrophied to such an extent that implant placement was impossible . The Schneiderian membrane was surgically elevated bilaterally by insertion of Cerasorb ( experimental side ) and autogenous bone graft ( control side ) . After surgery , the recovery was followed clinical ly and radiologically . After 6 months , 68 bone cylinders were excised from the grafted areas and implants were inserted into their places . The bone sample s were embedded into resin , and the osteointegration of the grafts was studied histologically . Trabecular bone volume ( TBV ) and trabecular bone pattern factor ( TBPf ) were quantified by histomorphometry . RESULTS Cerasorb proved to be an effective bone-replacing material with osteoconductivity ; it was capable of gradual disintegration , thereby providing space for the regenerating bone . The new bone density was not significantly different on the experimental and control sides ( 32.4+/-10.9 % and 34.7+/-11.9 % , respectively ) . However , the graft biodegradation was significantly slower on the experimental side than the control side . The TBPf value was lower on the control side than on the experimental side ( -0.53+/-1.7 and -0.11+/-1.4 mm(-1 ) , respectively ) , but this difference was not significant . CONCLUSIONS Six months after insertion of the grafts , the bone of the augmented sinus floor was strong and suitable for anchorage of dental implants , irrespective of whether autogenous bone or Cerasorb particles had been applied Two techniques of ridge augmentation using onlay bone graft alone or associated with a non-resorbable membrane have been previously described . This prospect i ve , r and omized study compared these two techniques at 6 months , in terms of bone gain , resorption and quality obtained at edentulous sites . Osseous measurements were taken using stents , callipers and CT-scans . Membrane exposure occurred at one site , 4 weeks after placement . Endosseous implants were successfully placed at all grafted sites . The mean graft thickness for all subjects was 4.7 mm ( range : 2.3 - 6.2 mm ) . Overall mean resorption was 1.5 mm ( range : 0 - 4.6 mm ) whereas overall mean width gain was 3.2 mm ( range : 0.8 - 6.2 mm ) . Six months following surgery , the membrane group experienced significantly less bone resorption than the graft alone group ( P<0.01 ) . Width augmentation did not differ significantly between the two groups . In conclusion , combining a membrane with an onlay graft demonstrates less bone resorption with a minimal risk of complications . Longer follow-up is needed to confirm the benefits of using a non-resorbable membrane Lack of bone in localized areas of the jaws frequently poses a problem when placing oral implants . In this clinical study , we have tested an osteopromotive membrane technique for its ability to create bone over buccal fenestrations after fixture installation in the maxilla . 7 patients were selected by the use of CT-scan . Criteria for patient selection were that the alveolar crest should have a vertical height > 13 mm and a facial-palatal concavity , where exposure at the central portion of the fixture could be anticipated . One fenestration , r and omly chosen , in each patient was covered with an e-PTFE ( exp and ed polytetrafluoroethylene ) ( Gore-Tex GTAM ) membrane . Contralateral fenestrations served as controls ( without the placement of a membrane ) . The amount of newly formed bone was calculated by photometric assessment s. The results showed that the fixture fenestrations , treated with the membrane technique , demonstrated a significantly ( p<0.005 ) higher amount of new bone formation compared to the controls , where little or no improvement had taken place at the fenestrations . The study conclusively shows that the membrane technique is a reconstructive technique , able to create new bone at localized bone fenestrations at titanium fixtures . Additionally , the study also demonstrates that the periosteum alone , in adult humans , is not capable of generating new bone at exposed titanium implants PURPOSE The aim of this r and omized study was to evaluate and compare the long-term success rates of cylindric , screw-type titanium implants with a larger diameter ( 5.9 mm ) that were placed in fresh extraction sockets in association with resorbable bone substitutes or a resorbable membrane . MATERIAL S AND METHODS Eighty-three partially edentulous adult patients , selected from among those treated in 1997 and 1998 at the San Raffaele Institute in whom 1 or more implants had been placed into fresh posterior m and ibular or maxillary sockets , were included in the study . A total of 111 implants were placed , 36 in m and ibles and 75 in maxillae . Fifty-six implants were placed in combination with resorbable hydroxyapatite ( HA group ) and 55 with a resorbable membrane ( MR group ) . Intraoral radiographs and follow-up examinations , including verification of implant stability via the Periotest , were carried out at second-stage surgery 3 , 6 , 9 , and 12 months later ; and then annually up to 4 years after placement of the definitive restoration . The radiographic examination was conducted by means of a st and ardized procedure to verify osseointegration . RESULTS There was 100 % attendance at the follow-up examination after 4 years . At second-stage surgery , which was performed after 4 to 6 months ' healing time , none of the implants showed any signs of mobility , peri-implantitis , or bone loss . Two implants failed in the MR group , one at 3 months and one at 9 months after placement ; 1 implant failed in the HA group at 4 months after placement . After 4 years , the implant success rate was 97.3 % ( 108 of 111 implants were considered successful ) . The success rate did not differ significantly between the HA group ( 98.2 % ) and the MR group ( 96.4 % ) . DISCUSSION The use of larger-diameter implants served to minimize the anatomic discrepancies that would have evolved when substituting a molar with a st and ard-diameter implant . According to the accepted criteria for success , the 5-year success rate should be at least 85 % ; therefore both methods may be considered satisfactory . CONCLUSION Implants placed in combination with a resorbable allogeneic material or with a resorbable membrane provided predictable long-term results when restored with a fixed partial denture This 6-month clinical study evaluated the use of a porous bone mineral matrix xenograft ( Bio-Oss ) as an adjunct to a biodegradable barrier membrane ( Bio-Gide ) to support healing following the immediate placement of transmucosal implants into extraction sockets . Twenty adult patients scheduled for tooth replacement with dental implants were accepted for participation . Following implant placement into the extraction site , subjects were assigned to one of two treatment alternatives for the remaining bone defect around the implant : ( 1 ) Bio-Oss + Bio-Gide membrane ( test ) ; or ( 2 ) Bio-Gide membrane ( control ) . The treatment outcome was evaluated after 6 months by the use of clinical and radiographic variables . The null hypothesis of no treatment group differences was tested by ANOVA . At 6 months , the radiographic bone level remained unchanged compared to baseline in the test and control groups . No differences were observed between test and control groups in terms of mean probing attachment level . At proximal sites , the soft tissue margin was located 2.6 mm more coronal than the shoulder of the implant in the test group , compared to 1.3 mm in the control group . The corresponding figures for the lingual aspect were 2.3 mm and 1.1 mm , respectively , and at buccal sites 2.1 mm and 0.9 mm , respectively . The use of deproteinized bovine bone mineral as a membrane support at immediately placed transmucosal implants may offer an advantage in areas with high esthetic dem and s in terms of soft tissue support The efficacy of combinations of membranes and autogenous bone grafts at immediate implants were compared in a prospect i ve study . Sixty-two consecutively treated patients each received an immediate implant for a single tooth replacement at a maxillary anterior or premolar site . Dimensions of the peri-implant defect at the implant collar were measured as follows : vertical defect height ( VDH ) , horizontal defect depth ( HDD ) and horizontal defect width ( HDW ) . Each implant r and omly received one of five augmentation treatments and were submerged with connective tissue grafts : Group 1 (n=12)--exp and ed polytetrafluoroethylene membrane only , Group 2 (n=11)--resorbable polylactide/polyglycolide copolymer membrane only , Group 3 (n=13)--resorbable membrane and autogenous bone graft ; Group 4 (n=14)--autogenous bone graft only , and Group 5 (n=12)--no membrane and no bone graft control . At re-entry , all groups showed significant reduction in VDH , HDD and HDW . Comparisons between groups showed no significant differences for VDH ( mean 75.4 % ) and HDD ( mean 77 % ) reduction . Significant differences were observed between groups for HDW reduction ( range , 34.1 - 67.3 % ) , with membrane-treated Groups 1 , 2 and 3 showing the greatest reduction . In the presence of dehiscence defects of the labial plate , HDW reduction of 66.6 % was achieved with membrane use compared with 37.7 % without membranes . Over 50 % more labial plate resorption occurred in the presence of a dehiscence defect irrespective of the augmentation treatment used . The results indicate that VDH and HDD reduction at defects adjacent to immediate implants may be achieved without the use of membranes and /or bone grafts PURPOSE The aim of this prospect i ve clinical study was to compare the clinical and radiographic results of 3 modes of implant treatment in combination with an overdenture in patients with extremely resorbed m and ibles . The 3 treatment strategies used were a transm and ibular implant , augmentation of the m and ible with an autologous bone graft followed by placement of 4 endosseous implants , and the placement of 4 endosseous implants only . MATERIAL S AND METHODS Sixty edentulous patients met the inclusion criteria and were assigned according to a balanced allocation method to 1 of the 3 groups . Postoperative complications , implant survival , periodontal indices , change in m and ibular bone height , and prosthetic complications were assessed during a 2-year evaluation period . RESULTS During the evaluation period significantly more implants were lost in the transm and ibular implant and the augmentation groups compared to the group with endosseous implants only . Except for the Bleeding Index and the Periotest values , the periodontal parameters did not differ significantly among the groups . In all 3 groups , there was no significant bone loss at most locations . Minimal prosthetic retreatment was necessary . DISCUSSION Although implant loss is a frequently used outcome measure for success , the necessity of retreatment seems to be of more relevance for both the patient and the clinician . CONCLUSIONS The results of this study suggested that patients with extremely resorbed m and ibles can be treated with implants alone in this patient population PURPOSE To evaluate the clinical outcome of implants placed into sites grafted with bioactive glass . MATERIAL S AND METHODS Seventeen consecutively treated patients were referred to a private specialist surgical practice for the repair of dentoalveolar defects , and /or ridge maintenance at the site of extraction sockets , prior to implantation . Bioactive glass available in 1 of 2 forms was utilized as an alloplastic grafting material . Bone cores were trephined out at the time of implantation and processed and examined to evaluate the tissue response under the light microscope . Implant mobility , marginal bone levels , and soft tissue health were all evaluated over a 2- to 3-year follow-up period to determine treatment success . RESULTS A total of 40 Astra Tech dental implants were placed . The overall success rate at the end of the study was 88.6 % for implants that were in function for a mean period of 29.2 months ( 22 to 24 months ) . One patient with 5 successful implants died at 18 months after functional loading . At that time the cumulative success rate was 90 % . Another patient who was diagnosed with cancer of the large bowel lost 3 implants . If this patient were excluded from the data , the cumulative success rate increases to 96.8 % . Mean marginal bone loss measured 0.5 mm mesially and 0.4 mm distally over a maximum follow-up of 36 months . Human histology demonstrated that connective tissue was seen to exist without any inflammatory response , for up to 6 months . Increasing evidence of bone formation was seen in direct relation to the bioactive glass material beyond this time frame . DISCUSSION The need to repair and augment dentoalveolar defects necessitates the use of autogenous bone or a substitute that may be seen to avoid the additional morbidity of a donor site procedure and without risk of cross infection . The use of bioactive glass has been proposed as a viable bone substitute . The current study draws attention to the long healing time required to achieve even a small amount of new bone incorporation into the graft , as seen histologically . However , the high rate of osseointegration and continued medium-term function of implants placed into these grafted sites would indicate that the use of bioactive glass does not prohibit osseointegration . However , it is likely that the initial integration will have derived from those areas in contact with native bone . CONCLUSION Implants will survive for up to 3 years in sites grafted with bioactive glass , even when such grafts appear to only slowly conduct new bone growth PURPOSE This phase II study was design ed to evaluate 2 concentrations of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) for safety and efficacy in inducing adequate bone for endosseous dental implant in patients requiring staged maxillary sinus floor augmentation . MATERIAL S AND METHODS Patients were treated with rhBMP-2 ( via an absorbable collagen sponge [ ACS ] ) , at concentrations of 0.75 mg/mL ( n = 18 ) , 1.50 mg/mL ( n = 17 ) , or with bone graft ( n = 13 ) . Bone induction was assessed by alveolar ridge height , width , and density measurements from computed tomography scans obtained before and 4 months after treatment and 6 months post-functional loading of dental implants ( density only ) . RESULTS Mean increases in alveolar ridge height at 4 months after treatment were similar among the groups ; 11.3 mm , 9.5 mm , and 10.2 mm , respectively , in the bone graft , 0.75 mg/mL , and 1.50 mg/mL rhBMP-2/ACS treatment groups . Mean increases in alveolar ridge width ( buccal to lingual ) at the crest of the ridge were statistically different among the treatment groups ; 4.7 mm , 2.0 mm , and 2.0 mm , respectively , in the bone graft , 0.75 mg/mL , and 1.50 mg/mL treatment groups ( P < or= .01 vs 0.75 mg/mL ; P < .01 vs 1.50 mg/mL ) . At 4 months postoperative new bone density was statistically different among the treatment groups ; 350 mg/cc , 84 mg/cc , and 134 mg/cc for the bone graft , 0.75 mg/mL , and 1.50 mg/mL rhBMP-2/ACS treatment groups , respectively ( P = .003 vs 0.75 mg/mL , P = .0137 vs 1.50 mg/mL , P = .0188 ; 1.50 mg/mL vs 0.75 mg/mL ) . Core bone biopsies obtained at the time of dental implant placement confirmed normal bone formation . The proportion of patients who received dental implants that were functionally loaded and remained functional at 36 months post-functional loading was 62 % , 67 % , and 76 % in the bone graft , 0.75 mg/mL , and 1.50 mg/mL rhBMP-2/ACS treatment groups , respectively . CONCLUSION This study is the first r and omized controlled trial demonstrating de novo organ tissue growth in humans from a recombinant human protein . rhBMP-2/ACS safely induced adequate bone for the placement and functional loading of endosseous dental implants in patients requiring staged maxillary sinus floor augmentation Dental implant surgery produces bone debris which can be used to correct bone defects in the " simultaneous-augmentation " technique . However , this debris is potentially contaminated with oral bacteria . Therefore , this study examined bone debris collected during dental implant surgery in order 1 ) to identify the microbial contaminants and 2 ) to compare the effects of two different aspiration protocol s on the levels of microbial contamination . Twenty-four partially dentate patients were r and omly allocated into two equal groups and underwent bone collection using the Frios Bone Collector during surgery to insert two endosseous dental implants . In group S ( using a stringent aspiration protocol ) , bone collection occurred within the surgical site only . In group NS ( utilizing a non-stringent aspiration protocol ) , bone collection and tissue fluid control was achieved using the same suction tip . Bone sample s were immediately transported for microbial analysis . Colonial and microscopic morphology , gaseous requirements and identification kits were utilized for identification of the isolated microbes . Twenty-eight species were identified including a number associated with disease , in particular , Enterococcus faecalis and Staphylococcus epidermidis as well as the anaerobes Actinomyces odontolyticus , Eubacterium sp. , Prevotella intermedia , Propionibacterium propionicum and Peptostreptococcus asaccharolyticus . In group S ( stringent aspiration protocol ) , significantly fewer organisms were found than in group NS , the non-stringent aspiration protocol ( P=0.001 ) . Gram-positive cocci dominated the isolates from both groups . It is concluded that if bone debris is collected for implantation around dental implants , it should be collected with a stringent aspiration protocol ( within the surgical site only ) to minimize bacterial contaminants PURPOSE To compare the efficacy and complications of 2 different techniques for vertical bone augmentation at implant placement : particulated autogenous bone grafts covered either by resorbable collagen barriers supported by osteo synthesis plates ( test ) or by nonresorbable titanium-reinforced e-polytetrafluoroethylene ( e-PTFE ) barrier ( control ) . MATERIAL S AND METHODS Twenty-two partially edentulous patients requiring vertical bone augmentation were r and omly allocated to 2 treatment groups of 11 patients each . Early implant failures , the amount of vertically regenerated bone measured intrasurgically , and biologic complications were recorded by an independent assessor blinded to the group allocation . The implant site requiring the most vertical bone regeneration was selected in each patient for the bone gain assessment . Patients were followed from implant insertion with simultaneous augmentation procedure to insertion of the provisional restoration . Paired and independent t tests and Fisher exact tests were conducted to compare means and proportions at the .05 level of significance . RESULTS No patient dropped out or was excluded . Both procedures obtained significant bone gain and achieved the desired results , 2.2 mm ( SD 1.5 ; P < .001 ) on average for resorbable barriers and 2.5 mm ( SD 1.1 ) for nonresorbable barriers ( P < .001 ) . There was no statistically significant difference in bone gain between the 2 procedures ( P = .58 ) . Complications occurred in 40 % of the patients . There was no difference in occurrence of complications between the procedures ( P > .99 ) . Three major complications occurred , 2 in the resorbable group and 1 in the nonresorbable group , which determined the complete failure of the augmentation procedure . CONCLUSIONS Both techniques were effective in augmenting bone ; however , both were associated with complications . Clinicians and patients must carefully weigh risks and benefits when considering the use of vertical guided bone regeneration This study evaluated bone regeneration and osseointegration of hydroxyapatite ( HA ) coated and titanium plasma sprayed ( TPS ) implants placed in sockets immediately after extraction in 36 adults , mean age 55.2 years ( range 26 to 81 years ) . Twelve TPS and 10 HA-coated implants in 20 patients were grafted with demineralized freeze-dried bone allograft ( DFDBA ) , covered with a barrier material , and the facial flap coronally positioned to attain primary closure ( experimental ) . The remaining 11 TPS and 10 HA-coated implants were placed similarly , except that no DFDBA was used ( control ) . Osseous structures were measured at the initial placement and 6-month re-entry surgeries . At the 6-month re-entry , all implants placed were clinical ly osseointegrated . Bone resorption at the most coronal socket crest was -1.53 mm for the grafted group and -1.59 mm for the control group . Crestal bone apposition of 1.39 mm was noted at the most apical socket crest ( ASC ) for the grafted group , whereas crestal resorption of -0.11 mm was noted in the ungrafted control group ( P < 0.02 ) . Bone fill from the base of the deepest osseous defect was 5.68 mm for the grafted group and 3.18 mm for the control group ( P < 0.04 ) . Complete resolution of osseous defects occurred at 15 of 22 sites in the grafted group and at 9 of 21 sites in the control group . Clinical exposure of the barrier material and a subsequent inflammatory response at 27 of 43 sites , requires removal of the material prior to the 6-month re-entry and was associated with significantly more bone loss at the ASC sites ( P < 0.01 ) . There was no significant difference for any of the parameters when comparing the TPS with the HA-coated implants The objective of the present study was to analyse the effects of implant supported overdentures on masticatory function in patients with an extremely resorbed m and ible , and to compare the masticatory function in these patients using three differing types of implant treatment protocol s. The m and ibular overdentures were retained by a transm and ibular implant , by four endosseous implants following augmentation of the m and ible , and by four short endosseous implants , respectively . Sixty patients ( 50 women , 10 men , mean age 59.4 years ) were r and omly allocated to one of the three treatment groups . Masticatory function was assessed before and after treatment using a question naire , a masticatory performance test , and a structured interview . The patient-based masticatory function improved significantly . Concerning these parameters there were no significant differences between the three groups before and after treatment . A significant difference existed between the three groups for the laboratory-assessed masticatory function before treatment , but after treatment this difference was no longer significant . From this study it can be concluded that patients with an extremely resorbed m and ible and functional complaints of their lower denture report significant improvement in masticatory function after implant-overdenture treatment . Differences in masticatory function between the three studied modalities were not significant after treatment Xenografts have been used extensively , either alone or in combination with autogenous bone , in sinus floor elevation techniques . However , controversy exists regarding the need to cover the lateral osteotomy site with a membrane . Also , the healing period before loading remains undefined when machined-surface implants are placed . Twenty-nine patients showing reduced bone volume in the posterior maxilla had 61 Brånemark System implants placed in 30 sinuses augmented with a lateral osteotomy approach . Sinuses grafted with Bio-Oss and covered with a collagen membrane Bio-Gide ( M+ ) received 29 implants , while grafted but uncovered sites ( M- ) received 32 implants . An immediate procedure was followed to place 41 implants and a staged procedure was used for 20 implants . Abutment connection was made in 2 distinct postoperative periods : 6 to 9 months and over 9 months . The patients were followed for an average of 22.4 months . The survival rate of the implants was dependent on the postoperative healing time and membrane presence . In case of the immediate procedure and in M- sites , when residual bone height was less than 5 mm , more failures occurred when the loading was done at 6 to 9 months than after 9 months . No failures occurred in the M- series when a staged approach was followed . The overall survival rate was 78.1 % for the M- sites and 93.1 % for the M+ sites . No failures occurred ( 0/35 ) in the control implants placed in adjacent native bone . Implant survival rate was related to the quality of the reconstructed cortical plate and to implant length . The concomitant use of a collagen barrier to cover the osteotomy site , when machined-surface implants were used in sinus grafting , seemed to improve the quality of the graft healing and survival rate of the implants loaded between 6 and 9 months after placement This study was design ed to compare the regenerative potential at dehisced implant sites of the resorbable demineralized laminar bone sheets and non resorbable GTAM membranes . Twenty-six st and ard screw-type fixtures showing buccal dehiscences in 7 patients were treated using the GBR principles and received either laminar bone sheets ( experimental ) or GTAM ( control ) membranes . Twelve experimental and 10 control sites were available for evaluation at second stage surgery carried out 8 months following implant placement . Height and maximum width of the dehiscence defects were measured at the time of implant insertion and at second-stage procedure . Mean percentage of defect fill was 75.17 % in the experimental dehiscences versus 86.70 % in the control defects . A statistically significant difference in the percentage of defect fill could not be evidence d between the two treatment modalities . Complete fill was observed in 25 % of the experimental versus 70 % of the control sites . A significant difference was found in the median Density Index with the GTAM group showing a consistency similar to bone in a larger number of sites . Histologically , material with the same staining features of bone was evidence d inside the GTAM membranes in 3 cases while newly-formed bone was present in all instances under the control GTAM barriers . In the laminar bone-treated sites , the membrane maintained its integrity in almost all cases . Newly formed bone was found underlying the membrane in cases with a Density Index of 5 with no evidence of bony tissue adhering to the laminar sheets BACKGROUND Conventional dentoalveolar osseous reconstruction often involves the use of grafting material s with or without barrier membranes . The purpose of this study was to evaluate the efficacy of bone induction for the placement of dental implants by two concentrations of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) delivered on a bioabsorbable collagen sponge ( ACS ) compared to placebo ( ACS alone ) and no treatment in a human buccal wall defect model following tooth extraction . METHODS Eighty patients requiring local alveolar ridge augmentation for buccal wall defects ( > or = 50 % buccal bone loss of the extraction socket ) of the maxillary teeth ( bicuspids forward ) immediately following tooth extraction were enrolled . Two sequential cohorts of 40 patients each were r and omized in a double-masked manner to receive 0.75 mg/ml or 1.50 mg/ml rhBMP-2/ACS , placebo ( ACS alone ) , or no treatment in a 2:1:1 ratio . Efficacy was assessed by evaluating the amount of bone induction , the adequacy of the alveolar bone volume to support an endosseous dental implant , and the need for a secondary augmentation . RESULTS Assessment of the alveolar bone indicated that patients treated with 1.50 mg/ml rhBMP-2/ACS had significantly greater bone augmentation compared to controls ( P < or = 0.05 ) . The adequacy of bone for the placement of a dental implant was approximately twice as great in the rhBMP-2/ACS groups compared to no treatment or placebo . In addition , bone density and histology revealed no differences between newly induced and native bone . CONCLUSION The data from this r and omized , masked , placebo-controlled multicenter clinical study demonstrated that the novel combination of rhBMP-2 and a commonly utilized collagen sponge had a striking effect on de novo osseous formation for the placement of dental implants The objective of the present report was to study the effect of implant treatment on subjective parameters in edentulous patients with an extremely resorbed m and ible . Three different treatment modalities to support an overdenture were compared : transm and ibular implant according to Bosker , augmentation of the m and ible followed by four endosseous implants , and the insertion of four short endosseous implants . Sixty patients [ 50 women and 10 men , mean ( + /- SD ) age 59 ( + /- 11 ) years ] met the inclusion criteria and were assigned in one of the three treatment groups . Before treatment and 12 months after placement of the new overdentures , denture satisfaction , psychosocial aspects and experiences during the surgical phase were assessed with a battery of question naires . After 1 year , 58 patients were available for evaluation : one patient had died , and one patient had moved out of the region . There was a significant improvement of patient satisfaction and psychosocial functioning in all three treatment groups . At the 1-year evaluation , differences amongst the three groups were not significant . However , in terms of discomfort and pain during the surgical phase as well as the length of this phase ( at least 6 months ) , the augmentation using an autologous bone graft from the iliac crest followed by inserting four endosseous implants 3 months later appeared the least favorite option of the three modalities studied PURPOSE Implant placement in the posterior maxilla may often be contraindicated because of insufficient bone volume and the presence of the maxillary sinus . In these situations , sinus floor lifting and grafting frequently have been proposed as the best treatment . The aim of this study was to compare histologically the use of 100 % autogenous bone versus a combination of autogenous bone and corticocancellous pig bone for maxillary sinus augmentation . MATERIAL S AND METHODS Eighteen patients requiring bilateral maxillary sinus augmentation were selected for this study . Bone for grafting was harvested from the iliac crest . Each patient received 100 % autogenous bone in 1 r and omly selected sinus ( control side ) and a 1:1 mixture of autogenous bone and corticocancellous pig bone particles in the contralateral sinus ( test side ) . Five months after the augmentation procedure , bone biopsy specimens were taken at the time of implant placement . RESULTS No complications were observed during the surgical procedures ; all patients healed uneventfully . No signs or symptoms of maxillary sinus disease were observed during the 5 months after surgery . No significant differences in bone percentages were observed in the bone biopsies from test and control sides . DISCUSSION AND CONCLUSION It could be concluded from this study that corticocancellous pig bone particles can be successfully used in a 1:1 mixture with autogenous bone from the iliac crest for maxillary sinus augmentation in cases of severely atrophic maxilla Successful bone augmentation requires predictable space maintenance and adequate exclusion of those cells that lack osteogenetic potential from the defect area . Natural bone mineral is considered to be osteoconductive and is used as space maker in combination with membrane barrier techniques . The aim of this study was to compare qualitative histological results achieved by using deproteinized bovine bone mineral ( DBBM ) as a space maintainer and a new collagen barrier ( Ossix , test group ) vs. the same bone substitute and the st and ard e-PTFE membrane ( Gore-Tex ) , control group ) . Twenty-eight patients were r and omly assigned to the test or the control group . Seven months after augmentation procedures , biopsies were obtained at reentry and were analysed histomorphometrically . In all , 14 specimens of group I ( test group , Ossix ) and 13 specimens of group II ( controls , PTFE-membranes ) showed close qualitative similarity of their histologies . Histomorphometrically , total mineralized bone area was 42 % + /- 18 % in group I vs. 39 % + /- 15 % in group II . The unmineralized tissue area was 44 % + /- 15 % vs. 46 % + /- 12 % and the area of DBBM remnants 14 % + /- 9 % and 15 % + /- 12 % , respectively . The differences were statistically nonsignificant ( Mann-Whitney test ) . The occurrence of barrier exposure did not interfere with the histological outcome either in the test or in the control group . The new collagen barrier combined with the DBBM provided qualitative bone regeneration comparable to the st and ard e-PTFE material combined with the same mineral OBJECTIVE In a double blind r and omised clinical pilot trial , it was investigated whether low intensity pulsed ultrasound therapy stimulates early bone formation in a distraction gap created in a severely resorbed m and ible . DESIGN Eight patients underwent a m and ibular vertical distraction over an average distance of 6.6+/-1.1 mm . Ultrasound self-therapy or placebo therapy was started on the first day of distraction and continued daily until the implants were inserted . After 31+/-3.8 days of consolidation , the distraction device was removed , a transm and ibular biopsy was taken , and two endosseous implants were inserted . RESULTS All patients complied well with ultrasound therapy . During an average of 30.1+/-4.1 months follow-up , no complications did occur . Microradiographic examination of the biopsies revealed a comparable mean area of mineralised tissue in the distraction gap of 1.9+/-1.7mm(2 ) in the ultrasound treatment group and 1.9+/-1.3mm(2 ) in the placebo treatment group . Histological examination indicated that active woven bone was present within the distraction gap just adjacent to the osteotomy plane , with no apparent differences between the treatment groups . The lamellar bone formation outside the distraction gap appeared to have started as well . CONCLUSION During a 31-day consolidation period , ultrasound treatment does not appear to stimulate bone formation in the severely resorbed vertical distracted m and ible and it seems that this period is too short to evaluate properly if there is an effect . Therefore , a longer consolidation period has to be studied PURPOSE Two different graft material s , beta-tricalcium phosphate ( Cerasorb ) and autogenous bone , were used in the same patient . The objective was to determine whether donor site morbidity could be avoided by using pure-phase beta-tricalcium phosphate ( Cerasorb ) . MATERIAL S AND METHODS Bilateral sinus grafting was performed on 20 selected patients ; Cerasorb was used on the experimental side , and autogenous bone was used on the control side . In each patient , one side was r and omly design ated the experimental side . In 10 of the 20 patients , the maxilla reconstruction included sinus grafting and onlay bone grafting . Implants were placed 6 months after the procedure . In addition to routine panoramic radiographs , in 10 of the 20 patients , 2- and 3-dimensional computerized tomographic examinations were performed pre- and postoperatively and after implantation . Eighty bone biopsy specimens were taken at the time of implant placement . RESULTS Histologically and histomorphometrically , there was no significant difference between the experimental and control grafts in terms of the quantity and rate of ossification . For each histologic sample , the total surface area , the surface area that consisted of bone , and the surface area that consisted of graft material were measured in mm2 , and bone and graft material were analyzed as percentages of the total . The mean percentage bone areas were 36.47 % + /- 6.9 % and 38.34 % + /- 7.4 % , respectively ; the difference was not significant ( P = .25 ) . DISCUSSION AND CONCLUSION Comparisons with other studies reveal that beta-tricalcium phosphate ( Cerasorb ) is a satisfactory graft material , even without autogenous bone Subantral sinus augmentation is often necessary to permit placement of endosseous implants . Recent efforts to improve wound healing have focused on autogenous sources of bioactive mediators , such as platelet-rich plasma ( PRP ) , which offer the potential to enhance the biological activity of bone replacement grafts . The purpose of this r and omized , single-blinded , controlled study was to compare bone formation after subantral maxillary sinus augmentation with freeze-dried bone allograft ( FDBA ) plus PRP versus FDBA plus resorbable membrane . Ten patients underwent bilateral maxillary subantral sinus augmentation , with sites within subjects r and omized to receive FDBA plus PRP or FDBA plus membrane . Core biopsy specimens were obtained 4.5 to 6 months after the grafting procedure at time of implant placement . Histomorphometric analysis revealed a significantly higher percentage of vital tissue in sinuses after treatment with FDBA and PRP ( 78.8 ± 8.3 ) than with FDBA and membrane ( 63.0 ± 15.7 ) . Moreover , the percentage of bone formation in sinuses augmented with the combination of FDBA plus PRP ( 33.3 ± 11.3 ) was nonsignificantly ( P ≤ 0.10 ) higher than in sinuses grafted with FDBA plus membrane ( 26.5 ± 6.8 ) . Residual graft particles constituted a significantly higher percentage of the regenerate in sinuses treated with FDBA plus membrane than in sinuses augmented with FDBA plus PRP ( 37.0 ± 15.7 ) versus ( 21.2 ± 8.3 , respectively ) . When comparing the relative proportion of vital bone to residual graft particles , a significant difference also was observed between sinuses treated with FDBA and membrane compared with sinuses augmented with FDBA and PRP ( 0.98 ± 0.77 versus 1.82 ± 0.88 , respectively ) . The results of this study suggest that the combination of FDBA and PRP enhances the rate of formation of bone compared with FDBA and membrane , when used in subantral sinus augmentation . Future research is needed to determine the clinical significance and the cost- and risk-benefit considerations of the approach The purpose of this prospect i ve study was to compare vertical guided bone regeneration ( GBR ) and vertical distraction osteogenesis ( DO ) for their ability in correcting vertically deficient alveolar ridges and their ability in maintaining over time the vertical bone gain obtained before and after implant placement . Eleven patients ( group 1 ) were treated by means of vertical GBR with autogenous bone and e-PTFE membranes , while 10 patients ( group 2 ) were treated by means of DO . In group 1 , six patients received implants at the time of GBR ( subgroup 1A ) , while five patients had implants placed at the time of membrane removal ( subgroup 1B ) . In group 2 , implants were placed at the time of distraction device removal . A total of 25 implants were placed in group 1 and 34 implants were placed in group 2 patients . Three to 5 months after implant placement , patients were rehabilitated with implant-borne dental prostheses . The following parameters were evaluated : ( a ) bone resorption of the regenerated ridges before and after implant placement ; ( b ) peri-implant clinical parameters 1 , 2 , and 3 years after prosthetic loading of implants ; ( c ) survival and success rates of implants . Bone resorption values before and after implant placement were significantly higher in group 1 . The results suggested that both techniques may improve the deficit of vertically resorbed edentulous ridges , although distraction osteogenesis seems to be more predictable as far as the long-term prognosis of vertical bone gain is concerned . Implant survival rates as well as peri-implant clinical parameters do not differ significantly between the two groups , whereas the success rate of implants placed in group 2 patients was higher than that obtained in group 1 patients BACKGROUND Guided bone regeneration ( GBR ) is a viable treatment for osseous defects surrounding dental implants . Controversy exists regarding the choice of barrier membrane used and the method of membrane fixation to achieve GBR . METHODS This study compared the efficacy of a porcine-derived bioabsorbable collagen membrane and an exp and ed polytetrafluoroethylene ( ePTFE ) membrane ( non-resorbable ) for GBR using a bovine bone xenograft/autograft bone composite in defects surrounding dental implants . The study also examined the effect of primary barrier fixation on GBR . Defect size was recorded at Stage 1 and 2 surgeries ( performed 6 months apart ) . Forty-eight subjects ( 41 % males , 59 % females ) requiring GBR were treated with either collagen ( 23 ) or ePTFE ( 25 ) barriers , respectively . Implants were titanium self-tapping screw-type . In 34 GBR sites , barrier fixation was achieved with polylactic acid resorbable pins . The remaining barriers were secured with the implant cover screw and /or embedded beneath the flaps . RESULTS At 6 months , a decrease in defect width ( collagen barrier 1.95 + /- 0.60 mm , ePTFE barrier 2.65 + /- 0.56 mm ) , length ( collagen barrier 2.65 + /- 0.61 mm , ePTFE barrier 2.26 + /- 0.66 mm ) , and circumference ( degrees ) ( collagen barrier 57.7 + /- 18.7 , ePTFE barrier 80.2 + /- 19.9 ) was observed for both membranes . A significant number ( chi2 , P = 0.041 ) of postoperative complications occurred when barrier fixation was lacking at initial surgery . Furthermore , a significant difference ( P < 0.05 ) in the success of GBR with respect to defect size was observed when barrier fixation was taken into account . CONCLUSIONS In conclusion , both collagen and ePTFE barriers proved suitable for achieving GBR of osseous defects surrounding dental implants . The results of this study stress the importance of barrier fixation at the time of initial surgery The aim of this study was to test the value of the new polydioxanone-membrane ( PDS , Ethicon , Norderstedt , Germany ) in combination with autogenous bone as a spacer for guided bone regeneration of denuded implant surfaces compared to simple augmentation . Forty implants were selected for 20 test cases ( with membrane ) and 20 control cases ( without membrane ) and were distributed r and omly in 19 patients who were treated according to a st and ard protocol and examined . The defects were filled with autogenous bone chips , harvested interforaminally or locally , and were covered by the PDS membrane within the test group ( control group : periosteum ) . The membranes were fixed with Memfix screws and cover screws . Seven membranes became exposed and were removed before reentry . Within the control group , three augments were sequestered . After 6 months , reentry was performed , the healing results were observed clinical ly , and biopsies were taken . The test group , including the seven cases with early removal of the membrane , showed that bone had filled in the defects in 95 % of test cases , compared with 60 % for the control group . The results of this study show that single augmentation of defects exceeding 9 mm2 is not sufficient . The membrane used in this investigation may be helpful for guided bone regeneration ( GBR ) at denuded screw thread sites in implant dentistry |
13,407 | 29,387,640 | Conclusion SE appears to be a very useful diagnostic tool , in particular in tendon pathology .
This is a dynamic examination , provides an immediate evaluation of the tissue elasticity , and may be useful in recognizing tendon abnormalities and in implementing the information available with conventional US . | Background Sonoelastography ( SE ) is a new ultrasound-based method adopted in an increased number of scientific reports to analyse normal and pathological tendons .
The aim of this study is to provide a systematic overview of clinical applications of SE in normal and pathological tendons .
Results There is an increasing interest in the application of SE in the evaluation of healthy and diseased tendons .
Many different tendons are amenable for SE evaluation , such as the Achilles and patellar tendons , rotator cuff , common extensor tendons , quadriceps tendon , and the plantar fascia . | AIM To investigate the feasibility and reproducibility of real-time freeh and ultrasound elastography ( RTE ) of the normal Achilles tendon and to describe its elastographic appearances . MATERIAL S AND METHODS Fifty normal Achilles tendons were prospect ively examined using RTE performed by tissue compression using the h and -held transducer . The information was colour-coded ( red = soft , green = medium , blue = hard ) and superimposed on the B-mode image . Each tendon was examined three times transversely and longitudinally by two radiologists and the ratio between tendon and retro-Achilles fat strain ( strain index ) was calculated . The reproducibility of the elastograms was assessed qualitatively and quantitatively using the strain index inter and intra observer variation coefficient ( intra/inter-CV and intra/inter-CC , respectively ) . RESULTS All tendons were clearly visualized on the elastograms . Nineteen tendons ( 19/50 , 38 % ) appeared homogeneously green/blue ( type 1 ) . Thirty-one tendons ( 31/50 , 62 % ) appeared green with longitudinal red stripes ( type 2 ) . The intra- and inter-CC values of the strain index were lower for the transverse plane than for the longitudinal plane ( 0.43 , 0.45 , 0.41 and 0.78 , 0.66 , 0.51 , respectively ) . The intra-CV and inter-CV values were higher for the transverse than for the longitudinal plane measurements ( 39 % , 37 % , 30 % and 30.50 % , 30.10 % , 29.60 % , respectively ) . CONCLUSION RTE of the normal Achilles tendon is a feasible method . The reproducibility of the strain index is good and higher for longitudinal elastograms . Qualitative assessment enables the discrimination of two distinct elastographic patterns . Further studies are required to assess the clinical value of this method PURPOSE To investigate the differences in viscoelastic properties between normal and pathologic Achilles tendons ( ATs ) by using real-time shear-wave elastography ( SWE ) . MATERIAL S AND METHODS The institutional review board approved this study , and written informed consent was obtained from 25 symptomatic patients and 80 volunteers . One hundred eighty ultrasonographic ( US ) and SWE studies of ATs without tendonopathy and 30 studies of the middle portion of the AT in patients with tendonopathy were assessed prospect ively . Each study included data sets acquired at B-mode US ( tendon morphology and cross-sectional area ) and SWE ( axial and sagittal mean velocity and relative anisotropic coefficient ) for two passively mobilized ankle positions . The presence of AT tears at B-mode US and signal-void areas at SWE were noted . RESULTS Significantly lower mean velocity was shown in tendons with tendonopathy than in normal tendons in the relaxed position at axial SWE ( P < .001 ) and in the stretched position at sagittal ( P < .001 ) and axial ( P = .0026 ) SWE . Tendon softening was a sign of tendonopathy in relaxed ATs when the mean velocity was less than or equal to 4.06 m · sec(-1 ) at axial SWE ( sensitivity , 54.2 % ; 95 % confidence interval [ CI ] : 32.8 , 74.4 ; specificity , 91.5 % ; 95 % CI : 86.3 , 95.1 ) and less than or equal to 5.70 m · sec(-1 ) at sagittal SWE ( sensitivity , 41.7 % ; 95 % CI : 22.1 , 63.3 ; specificity , 81.8 % ; 95 % CI : 75.3 , 87.2 ) and in stretched ATs , when the mean velocity was less than or equal to 4.86 m · sec(-1 ) at axial SWE ( sensitivity , 66.7 % ; 95 % CI : 44.7 , 84.3 ; specificity , 75.6 % ; 95 % CI : 68.5 , 81.7 ) and less than or equal to 14.58 m · sec(-1 ) at sagittal SWE ( sensitivity , 58.3 % ; 95 % CI : 36.7 , 77.9 ; specificity , 83.5 % ; 95 % CI : 77.2 , 88.7 ) . Anisotropic results were not significantly different between normal and pathologic ATs . Six of six ( 100 % ) partial-thickness tears appeared as signal-void areas at SWE . CONCLUSION Whether the AT was relaxed or stretched , SWE helped to confirm and quantify pathologic tendon softening in patients with tendonopathy in the midportion of the AT and did not reveal modifications of viscoelastic anisotropy in the tendon . Tendon softening assessed by using SWE appeared to be highly specific , but sensitivity was relatively low Objective The aim of this study was to investigate whether ultrasound elastography can demonstrate the outcome of the treatment in comparison with gray-scale imaging . Methods Sixteen patients ( mean age , 46.9 years ) with plantar fasciitis were prospect ively enrolled after unsuccessful conservative treatment . Individuals grade d their heel pain on a 100-mm visual analogue scale ( VAS ) and underwent gray-scale ultrasonography and sonoelastography . Collagen was injected in the heels . Fascial thickness and hypoechogenicity , perifascial edema , and plantar fascial elasticity were evaluated . Follow-up sonoelastography and VAS grading were done 3 months after the injection . Statistical analyses were performed by the paired t test and the Fisher exact test . A P < 0.05 was considered statistically significant . Results Mean plantar fascial thickness showed insignificant decrease on follow-up ( from 4.30 [ 1.37 ] to 4.23 [ 1.15 ] mm , P = 0.662 ) . Fascial hypoechogenicity and perifascial edema did not change significantly after treatment . The mean strain ratio of the plantar fascia was significantly increased ( from 0.71 [ 0.24 ] to 1.66 [ 0.72 ] , P = 0.001 ) . Softening of the plantar fascia decreased significantly after injection ( from 12 to 3 ft , P = 0.004 ) . Twelve ( 75 % ) of 16 patients showed significant VAS improvement at the follow-up . Conclusions Sonoelastography revealed a hardening of the plantar fascia after collagen injection treatment and could aid in monitoring the improvement of the symptoms of plantar fasciitis , in cases where gray-scale imaging is inconclusive Purpose To investigate the feasibility of real-time sonoelastography in the assessment of the mechanical tendon properties in small unilateral supraspinatus tears , to describe the sonoelastographic properties of the torn supraspinatus tendons and to correlate real-time sonoelastography findings with clinical results and demographic data . Methods All the patients presenting for a unilateral rotator cuff tear were prospect ively scrutinized . Clinical evaluation included complete physical examination , VAS , Quick DASH , Constant – Murley score , Simple Shoulder Test , ASES score and UCLA score . Radiological evaluation was performed with conventional ultrasounds and real-time sonoelastography ; this is a noninvasive method that uses ultrasounds to evaluate the mechanical properties of tissues , reflecting their quality , that can be semi-quantitatively estimated using the strain index . During the enrolment period , 92 patients were scrutinized , and 50 were included in the study . Results A negative correlation between strain index and VAS for pain , a strong positive correlation between strain index and Constant – Murley score and ASES score were found . Comparable results were observed in male and female patients , but in males , we found a strong positive correlation also for Simple Shoulder Test and UCLA score . Conclusions Real-time sonoelastography was a feasible method applicable in the assessment of tendon quality in small supraspinatus tears , and its findings correlated with the clinical results of the patients . In day-by-day clinical practice , this information is very important because quality of tendons is one of the most important prognostic factors for surgeons performing rotator cuff repair . Level of evidence III Abstract Purpose To evaluate the sonoelastographic features of Achilles tendon healing after percutaneous treatment using real-time sonoelastography , a new tool able to quantify deformation in biological tissues . Methods Patients with atraumatic Achilles tendon ruptures , treated with a percutaneous technique , were assessed . Sonoelastographic evaluations were performed at the myotendinous junction , tendon body/lesion site and osteotendinous junction , both for the operated and contralateral side , at 40 days , 6 months and 1 year after surgery . Using st and ard regions of interest , the “ strain index ” ( SI ) was calculated as an indicator of tendon elasticity . Clinical outcomes were assessed by the ATRS question naire at 6 months and 1 year post-operatively and correlated with sonoelastographic findings . Sixty healthy tendons from 30 volunteers were used to provide a healthy control range . Results Twenty-five patients were recruited for this study . The SI in treated tendons showed progressive stiffening over time , especially at myotendinous junction and at the site of the sutured lesion , result ing in significantly higher stiffness than both the contralateral tendon and healthy volunteers . Peak thickness of treated tendons occurred at 6 months , with a tendency to reduce at 1 year , while never achieving a normal physiological state . Greatest remodelling was seen at the lesion site . The contralateral tendon showed significant thickening at the myotendinous and osteotendinous junctions . The SI of the contralateral tendon was found to be stiffer than physiological values found in the control group . ATRS score improved significantly between 6 months and 1 year , being negatively correlated with the SI ( p < 0.001 ) . Conclusion RTSE showed that operatively treated Achilles tendons become progressively stiffer during follow-up , while the ATRS score improved . From a biomechanical point of view , at 1 year after surgery Achilles tendons did not show a “ restitutio ad integrum ” . Real-time sonoelastography provides more qualitative and quantitative details in the diagnostics and follow-up of Achilles tendon conditions as the post-operative evolution of the repairing tissue . Level of evidence Diagnostic and therapeutic study , Level III RATIONALE AND OBJECTIVES Shear wave elastography ( SWE ) has been shown to be a powerful tool to estimate tissue stiffness . The aim of this study was to compare the diagnostic accuracy of SWE to that of st and ard ultrasound ( US ) ( combined use of B-mode US and power Doppler [ PD ] US ) for diagnosing tendinopathies . MATERIAL S AND METHODS This is a prospect i ve institutional review board-approved study on 112 participants ( mean age 42 ± 13.4 years ) with chronic ( > 6 months ) tendon pain in Achilles , patellar , or epicondylar tendons . Participants were systematic ally examined with US , PD , and SWE using a high-resolution linear 15 MHz probe ( SuperSonic Imagine ) . A semiquantitative analysis of SWE color charts and a quantitative region of interest-based analysis of tendon elasticity were performed . SWE values of symptomatic and healthy tendons were compared by using Student t test . Clinical symptom scores served as the st and ard of reference . US findings were compared to clinical symptom scores by using Spearman correlation . RESULTS At semiquantitative analysis of SWE color charts , symptomatic tendons were rated as " soft " in 80/140 ( 57.1 % ) , as " intermediate " in 54/140 ( 38.6 % ) , and as " rigid " in 6/140 ( 4.3 % ) . Healthy tendons were rated as " soft " in 8/84 ( 10 % ) , as " intermediate " in 31/84 ( 37 % ) , and as " rigid " in 45/84 ( 53 % ) . At quantitative analysis , symptomatic tendons exhibited significantly lower mean SWE values ( 60.3 kPa/4.48 m/s ; range 15.3 - 201.4 kPa/2.26 - 14.18 m/s ) than healthy tendons ( 185 kPa/7.85 m/s ; range 56 - 265 kPa/4.32 - 9.23 m/s ) ( P = 0.0004 ) . SWE values correlated closely with patients ' clinical symptoms obtained by clinical scores ( r = 0.81 ) . Overall sensitivity of conventional US and PD in detecting tendinopathies could be enhanced from 67.1 % ( 94/140 ) to 94.3 % ( 132/140 ) when combined with SWE . CONCLUSIONS SWE is a simple way to estimate tissue stiffness and , by reduced tissue rigidity , to identify tendon pathology . SWE significantly increases the diagnostic accuracy of tendon sonography and may prove to be a sensitive tool to early detect or monitor tendinopathy The objective of this study was to investigate the role of real-time sonoelastography ( RTSE ) in patients with lateral epicondylitis ( LE ) and whether it is associated with clinical parameters . Seventeen patients with unilateral LE were enrolled in the study . The healthy elbows of the participants constituted the control group . Using B-mode ultrasound , color Doppler ultrasound , and RTSE , we prospect ively examined 34 common extensor tendon elbows of 17 patients . Both color scales and strain ratio were used for evaluating RTSE images . Two radiologists evaluated the RTSE images separately . Elbow pain was scored on a 100-mm visual analog scale ( VAS ) . Symptom duration and the presence of nocturnal pain were question ed . Quick disabilities of arm shoulder and h and ( DASH ) Question naire was applied to assess the pain , function , and disability . Nottingham health profile ( NHP ) was used to determine and quantify perceived health problems . Both color scales and strain ratios of the affected tendon portions were significantly different from that of healthy tendons ( p < 0.001 ) . There was no significant association between NHP , VAS , Quick DASH scores , and color scales and strain ratio . Strain ratio of the medial portion of the affected tendon was significantly correlated with symptom duration ( rho = −0.61 p = 0.010 ) and nocturnal pain ( rho = 0.522 p = 0.031 ) . Interobserver agreement was substantial for color scales ( κ = 0.74 , p = 0.001 ) and strain ratio ( ICC = 0.61 , p = 0.031 ) . RTSE may facilitate differentiation between healthy and affected elbows as a feasible and practical supplementary method with substantial interobserver agreement . RTSE was superior to B-mode ultrasound and color Doppler ultrasound in discriminating tendons with LE . Strain ratio of the medial portion of the tendon is associated moderately with nocturnal pain and symptom duration . No other associations were present between RTSE findings and clinical or functional parameters BACKGROUND Highly operator-based injection therapy with vasosclerosing and anesthetic polidocanol is used for tendinopathies . This pilot- study evaluates the topical application of polidocanol gel . METHODS Prospect i ve case series . 39 patients with tendinopathies ( 14 Achilles , 14 patella , 11 wrist extensors ) with a symptom duration > 6 months were included . Polidocanol and static stretching were the therapy in the first 2 weeks , while static stretching was continuously performed for 6 months . Clinical outcome was evaluated with VISA-A , VISA-P and DASH Scores and sonographically with B-Mode ( B-Mode ) , Power Doppler ( PD ) and Shearwave Elastography ( SWE ) . RESULTS 22 patients clinical ly improved ( > + 10 score points ) , 11 patients were without improvement ( < + 10 ) and 1 patient worsened during 6 months . The VISA-A Score increased in average 19 points from 56 to 75 ( p < 0.01 ) , VISA-P Score increased 13 points from 59 to 72 ( p < 0,01 ) and the DASH-Score decreased 20 points from 40 to 20 ( p < 0,01 ) . SWE correlates better than B-Mode or PD with symptom improvement . CONCLUSION The combination of static training and topical polidocanol application seems to be successful in the treatment of tendinopathies . Further RCT studies need to evaluate the efficiency of topical polidocanol application . SWE is a more sensitive tool to describe symptom development than PD or B-Mode . LEVEL OF EVIDENCE IV OBJECTIVE The objective of our study was to investigate the clinical feasibility of ultrasound elastography for assessing patients with lateral epicondylosis and to establish an objective and quantitative method of elastographic measurement in the affected tendon . SUBJECTS AND METHODS A total of 97 symptomatic and 89 asymptomatic common extensor tendons from both elbows of 79 consecutive patients with lateral epicondylosis and 14 healthy participants were prospect ively examined by gray-scale sonography , color Doppler sonography , and compression-based elastography . Real-time color-coded elastography was performed and quantified with two regions of interest : the adjacent subcutis ( S1 ) for a reference area and the common extensor tendon ( S2 ) for the target area . The mean strain ratio ( S1/S2 ) was used for quantitative comparisons . The difference in the mean strain ratio between symptomatic and asymptomatic tendons was assessed with conditional regression analysis . RESULTS In symptomatic elbows , 87 of 97 tendons ( 89.7 % ) showed intratendinous hypoechogenicity , 86 of 97 ( 88.7 % ) showed swelling , and 70 of 97 tendons ( 72.2 % ) showed intratendinous hyperemia . Color-coded elastography revealed a soft area on 73 of 97 tendons ( 75.3 % ) . The mean strain ratio was 1.45 ( SD , 0.45 ) for symptomatic tendons and 2.07 ( SD , 0.70 ) for asymptomatic tendons . The mean strain ratio of the symptomatic tendons was significantly lower than that of asymptomatic tendons ( p < 0.001 ) , indicating that the symptomatic tendons were softer . CONCLUSION Our results revealed that patients with lateral epicondylosis had significantly lower strain ratios in their common extensor tendon origins . Ultrasound elastography using quantitative strain ratio measurements could be a promising supplementary method to evaluate tendon abnormalities in lateral epicondylosis Objective To determine whether there is an association between T2/T2 * mapping and supraspinatus tendon mechanical properties as assessed by shear-wave ultrasound elastography ( SWE ) . Material s and methods This HIPAA-compliant prospect i ve pilot study received approval from our hospital ’s institutional review board . Eight patients ( 3 males/5 females ; age range 44–72 years ) and nine shoulders underwent conventional shoulder MRI , T2/T2 * mapping on a 3-T scanner , and SWE . Two musculoskeletal radiologists review ed the MRI examinations in consensus for evidence of supraspinatus tendon pathology , with tear size measured for full-thickness tears . T2/T2 * values and ultrasound shear-wave velocities ( SWV ) were calculated in three corresponding equidistant regions of interest ( ROIs ) within the insertional 1–2 cm of the supraspinatus tendon ( medial , middle , lateral ) . Pearson correlation coefficients between T2/T2 * values and SWV , as well as among T2 , T2 * , SWV and tear size , were calculated . Results There was a significant negative correlation between T2 * and SWV in the lateral ROI ( r = −0.86 , p = 0.013 ) and overall mean ROI ( r = −0.90 , p = 0.006 ) . There was significant positive correlation between T2 and measures of tear size in the lateral and mean ROIs ( r range 0.71–0.77 , p range 0.016–0.034 ) . There was significant negative correlation between SWV and tear size in the middle and mean ROIs ( r range −0.79–-0.68 , p range 0.011–0.046 ) . Conclusion Our pilot study demonstrated a potential relationship between T2 * values and shear wave velocity values in the supraspinatus tendon , a finding that could lead to an improved , more quantitative evaluation of the rotator cuff tendons Objective Evaluating prospect ively elastosonographyc ( EUS ) findings of distal third of Achilles tendon in asymptomatic volunteers and correlating with subject characteristics and ultrasound ( US ) findings and , subsequently , calculating reproducibility of method . Material s and methods 70 consecutives Achilles tendons were examined with US and EUS in 35 asymptomatic volunteers . Mean age 42.3 years ( ±7.6 ) , 22 were female ( mean age 41 ± 8.7 ) and 13 were male ( mean age 42.5 ± 11.4 ) . Information about population was collected ( anthropometric data , sport activity , taken therapy and associated conditions/pathologies ) . Results Statistically significant correlation was found between BMI and EUS findings ( p = 0.007 ) and between EUS aspect and US diagnosis ( p = 0.039 ) both to the right tendon . Possible influence of smoking ( p = 0.063 to right ) and associated conditions ( p = 0 . 059 to left ) , has been found . The multivariate analysis showed that EUS results are correlated only with BMI ( high BMI corresponds to the best EUS results ) , independently from smoke and associated conditions on right side . No correlations have emerged for the left tendon . The 22.8 % of the volunteers took on chronic therapies , none statistically significant correlation . In the past , 80 % of subjects played sports ( 7.4 % agonistic and 92.6 % non-agonistic ) . The 22.9 % of volunteers played sporadic or no activity . The 60 % of volunteers has played sports that may lead overload of the Achilles tendon . The 61.5 % of subjects with BMI ≥ 25 was active little or nothing ; 63.6 % of the subjects with BMI < 25 is playing sports . US examination showed 57.1 % normal tendons and 42.9 % tendinosic . Rate of tendinosic tendons was similar in both left and right ( 40 and 45.7 % , respectively ) . Statistically significant correlation was found between EUS aspect and US diagnosis on the right tendon but not on the left Correlation between thickness and EUS aspect was calculated : no correlation was found . Interoperator correlation was excellent ( k = 0.89 for left tendon and k = 0.91 for right tendon ) . Conclusions The EUS is an interesting and useful technique , characterised by a high reproducibility . Its results are related to BMI and US appearance of the tendon , and they are probably influenced by the smoke and associated conditions . However , the flexed ankle position , needed to properly examine the distal third by US , alters the elasticity of the tendon and causes false negative results to EUS . Then , for the EUS study of the distal third , it would be appropriate the relaxed position , with a gel pad to optimise the probe adhesion PURPOSE To evaluate the use of axial-strain real-time sonoelastography in patients with plantar fasciitis compared with that in healthy control subjects . MATERIAL S AND METHODS Institutional review board approval and patients ' consent were obtained . Eighty feet of 80 patients ( 43 men , 37 women ; mean age ± st and ard deviation , 46.3 years ± 8.7 ) with plantar fasciitis and 50 feet of 50 asymptomatic volunteers ( 27 men , 23 women ; mean age , 44.3 years ± 8.0 ) were prospect ively evaluated . Individuals grade d heel pain with a visual analogue scale and underwent B-mode ultrasonography ( US ) and real-time sonoelastography . Maximum fascial thickness was measured , and two longitudinal images were recorded with both modalities . Two radiologists who were blinded to clinical symptoms independently review ed images for hypoechoic echotexture and fascial-border blurring at B-mode US and semiquantitative elasticity score at real-time sonoelastography ( blue , 1 ; green , 2 ; red , 3 ) , with the fascia divided into proximal , intermediate , and distal sections . RESULTS No differences were found for sex ( P = .999 ) or age distribution ( P = .144 ) between groups . Fascial thickening , hypoechoic echotexture , and fascial-border blurring at B-mode US were increased in patients versus control subjects ( P < .001 ) , and fascial thickening and hypoechoic echotexture correlated with heel pain score ( r > .475 , P < .001 ) . Plantar fasciae of patients ( median score , 11 ; interquartile interval , 10 - 12 ) were less elastic than those of control subjects ( median score , 7 ; interquartile interval , 6 - 7.25 ) ( P < .001 ) . Image interpretation yielded high interobserver reproducibility ( κ ≥ .80 ) . Pain and real-time sonoelastographic scores correlated significantly ( r = 0.851 , P < .001 ) . Pain was associated with older age ( t = 3.7 , P < .001 ) , fascial thickening ( t = 7.3 [ multiple stepwise regression model ] , P < .001 ) , and total real-time sonoelastographic score ( t = 10.2 , P < .001 ) but not with sex , fascial-border blurring , or hypoechoic echotexture . Accuracy increased from 90.0 % with B-mode US to 95.4 % with real-time sonoelastography ( P = .016 ) . CONCLUSION Real-time sonoelastography can show plantar fasciitis , increase diagnostic performance of B-mode US , and assist in cases of inconclusive B-mode US findings Purpose Our aim was to comparatively investigate the strain ratio and thickness of the Achilles tendon in children with cerebral palsy ( CP ) , and to eluci date whether there is a correlation between biomechanical features of the Achilles tendon and strain ratio . Methods A total of 155 participants ( 72 CP patients and 83 healthy controls ) who underwent real-time elastography of both Achilles tendons were studied . A linear transducer ( 4.8–11.0 MHz ) was used to obtain the images . Correlation analysis between age , length , and thickness of the Achilles tendon , and strain ratio ( SR ) was performed by means of Pearson correlation and Spearman ’s rho tests . Results Comparison of results obtained from CP patients and controls showed that the length of the Achilles tendon was shorter ( p < 0.001 ) and SR was higher ( p < 0.001 ) in CP patients . In CP patients , there was a positive correlation between SR and age and between SR and the thickness and length of the Achilles tendon ( p < 0.001 for all ) . Furthermore , the length of the tendon and age were positively associated ( p < 0.001 ) . ROC analysis revealed that the cut-off value for SR was 1.89 . Conclusion The results of the present study demonstrated that real-time elastography can constitute a simple , practical , and noninvasive method for evaluation of the elasticity of the Achilles tendon in children with CP OBJECTIVES The purpose of our paper was to evaluate by sonoelastography the Achilles tendon of asymptomatic volunteers and of patients referring for chronic overuse-associated pain , also comparing these findings with those obtained with B-mode ultrasound ( US ) . METHODS This study had local Ethics Committee approval ; all patients gave their written informed consent . Twelve patients ( 9 men , 3 women , median age 52.5 years , range 38 - 64 years ) referred for unilateral Achilles tendon pain associated with amateur sporting activities and 18 healthy controls ( 11 men , 7 women , median age 54 years , range 27 - 64 years ) were studied . US/sonoelastography were performed with a Logos EUB8500 system ( Hitachi Ltd. , Tokyo , Japan ) equipped with a 10 - 6 MHz high-resolution broadb and linear array , on 12 symptomatic tendons and 36 controls . The probe was positioned at the calcaneal enthesis , retrocalcaneal bursa , myotendineus juction , and in three different areas of the tendon body . The elastogram colour range was translated to a numeric score and the differences of tendon resilience were compared by the Kruskall-Wallis test . RESULTS On US , symptomatic tendons showed increased tendon thickness ( 12/12 tendons vs. 8/36 controls , p<0.0001 ) , interruption ( 5/12 vs. 0/36 , p=0.0004 ) , and fragmentation ( 5/12 vs. 0/36 , p=0.0004 ) . Disappearance of fibrillar echotexture was comparable in the two groups . Symptomatic tendons were harder , showing a prevalence of blue to green colour ( p<0.0001 ) . Loss of elasticity was associated with both fragmentation ( p=0.0089 ) and loss of fibrillar texture ( p=0.0019 ) , and was inversely correlated with tendon thickness ( p<0.0001 ) . Sonoelastography showed no difference between symptomatic and control tendons at the enthesis and myotendineus junction . CONCLUSIONS Sonoelastography shows increased stiffness in symptomatic enlarged Achilles tendons in comparison to normal ones OBJECTIVES This study aim ed to compare sonoelastographic findings for the quadriceps tendon in patients with chronic renal failure who were in a dialysis program to findings in a control group . METHODS Fifty-three r and omly allocated patients ( mean age , 54.3 years ; range , 27 - 86 years ) with chronic renal failure who were in a dialysis program 3 days a week between January and May 2012 were included . The measurements were performed in both knees of 53 patients undergoing dialysis and 25 individuals in the control group . The tendons were classified as follows : type 1 , very stiff tissue ( blue ) ; type 2 , stiff tissue ( blue-green ) ; and type 3 , intermediate tissue ( green-yellow ) according to color mapping . RESULTS The mean quadriceps tendon thicknesses in the patient group were 4.9 mm ( range , 1.9 - 6.5 mm ) for the right knee and 4.9 mm ( 1.4 - 6.5 mm ) for the left knee ; the values in the control group were 5.4 mm ( 3.6 - 7.0 mm ) for the right knee and 5.4 mm ( 3.4 - 7.0 mm ) for the left knee . The mean elasticity scores in the patient group were 3.14 ( 1.03 - 5.23 ) for the right knee and 3.33 ( 1.29 - 5.00 ) for the left knee ; in the control group , the values were 3.79 ( 1.73 - 5.23 ) and 3.69 ( 1.23 - 5.53 ) for the right and left knees , respectively ( right knee , P = .025 ; left knee , P = .018 ; Mann-Whitney U test ) . The quadriceps tendons were significantly thinner in the patient group ( right knee , P = .054 ; left knee , P = .015 ; Mann-Whitney U test ) . CONCLUSIONS Quadriceps tendons in patients with chronic renal failure are thinner and have lower elasticity scores compared to controls |
13,408 | 27,254,800 | Based on the literature included in this systematic review , psychological and psychiatric problems in children with a history of mTBI were found to be more prevalent when mTBI is associated with hospitalization , when assessment occurs earlier in the recovery period ( that is , resolves over time ) , when there are multiple previous mTBIs , in individuals with preexisting psychiatric illness , when outcomes are based on retrospective recall , and when the comparison group is noninjured healthy children ( as opposed to children with injuries not involving the head ) .
In the absence of true reports of preinjury problems and when ideally comparing mild TBI to non-TBI injured controls , there is little evidence to suggest that psychological , behavioural , and /or psychiatric problems persist beyond the acute and subacute period following an mTBI in children and adolescents | Background : Evidence regarding longer-term psychiatric , psychological , and behavioural outcomes ( for example , anxiety , mood disorders , depression , and attention disorders ) following mild traumatic brain injury ( mTBI ) in children and adolescents has not been previously synthesized .
Objective : To conduct a systematic review of the available evidence examining psychiatric , psychological , and behavioural outcomes following mTBI in children and adolescents . | Background : In a previous prospect i ve study , the risk of concussion and all injury was more than threefold higher among Pee Wee ice hockey players ( ages 11–12 years ) in a league that allows bodychecking than among those in a league that does not . We examined whether two years of bodychecking experience in Pee Wee influenced the risk of concussion and other injury among players in a Bantam league ( ages 13–14 ) compared with Bantam players introduced to bodychecking for the first time at age 13 . Methods : We conducted a prospect i ve cohort study involving hockey players aged 13–14 years in the top 30 % of divisions of play in their leagues . Sixty-eight teams from the province of Alberta ( n = 995 ) , whose players had two years of bodychecking experience in Pee Wee , and 62 teams from the province of Quebec ( n = 976 ) , whose players had no bodychecking experience in Pee Wee , participated . We estimated incidence rate ratios ( IRRs ) for injury and for concussion . Results : There were 272 injuries ( 51 concussions ) among the Bantam hockey players who had bodychecking experience in Pee Wee and 244 injuries ( 49 concussions ) among those without such experience . The adjusted IRRs for game-related injuries and concussion overall between players with bodychecking experience in Pee Wee and those without it were as follows : injury overall 0.85 ( 95 % confidence interval [ CI ] 0.63 to 1.16 ) ; concussion overall 0.84 ( 95 % CI 0.48 to 1.48 ) ; and injury result ing in more than seven days of time loss ( i.e. , time between injury and return to play ) 0.67 ( 95 % CI 0.46 to 0.99 ) . The unadjusted IRR for concussion result ing in more than 10 days of time loss was 0.60 ( 95 % CI 0.26 to 1.41 ) . Interpretation : The risk of injury result ing in more than seven days of time loss from play was reduced by 33 % among Bantam hockey players in a league where bodychecking was allowed two years earlier in Pee Wee compared with Bantam players introduced to bodychecking for the first time at age 13 . In light of the increased risk of concussion and other injury among Pee Wee players in a league where bodychecking is permitted , policy regarding the age at which hockey players are introduced to bodychecking requires further consideration Introduction Persistent postconcussive symptoms ( PCSs ) is the persistence of somatic , cognitive , physical , psychological and /or behavioural changes lasting more than 1 month following concussion . Persistent concussion impacts the quality of life through impaired cognition , memory and attention affecting school performance , mood and social engagement . No large epidemiological studies have determined the true prevalence of persistent concussion symptoms . Vali date d , easy-to-use prognosticators do not exist for clinicians to identify children at highest risk . The goal of Predicting and Preventing Postconcussive Problems in Pediatrics study is to derive a clinical prediction rule for the development of persistent postconcussion symptoms in children and adolescents presenting to emergency department following acute head injury . Methods and analysis This study is a prospect i ve , multicentre cohort study across nine academic Canadian paediatric emergency departments . We will recruit the largest prospect i ve epidemiological cohort of children with concussion . Eligible children will be followed using Post-Concussion Symptom Inventory , a vali date d tool in children as young as 5 years . Patients will follow-up at 1 , 2 , 4 , 8 and 12 weeks postinjury . The main outcome will be the presence/absence of PCSs defined as three or more persistent concussion symptoms 1 month following the injury . 1792 patients provide adequate power to derive a clinical decision rule using multivariate analyses to find predictor variables sensitive for detecting cases of persistent postconcussion symptoms . Ethics and dissemination Results of this large prospect i ve study will enable clinicians to identify children at highest risk , optimise treatment and provide families with realistic and appropriate anticipatory guidance . Ethics has been obtained through the Children 's Hospital of Eastern Ontario Research Ethics Board . Results will be disseminated at international conferences and in four manuscripts to peer- review ed journals . Trial registration This study is registered at Clinical trials.gov through the US National Institute of Health/National Library of Medicine ( NCT01873287 ; http:// clinical trials.gov/ct2/show/NCT01873287 ) BACKGROUND The etiology of schizophrenia is believed to include genetic and nongenetic factors , with the pathogenesis involving abnormal neurodevelopment . We investigated whether mild head injury during brain maturation plays a role in the expression of schizophrenia in multiply affected families . METHODS We compared the history and severity of head injuries in childhood ( age , < or = 10 years ) and through adolescence ( age , < or = 17 years ) in 67 subjects with narrowly defined schizophrenia and 102 of their unaffected siblings from 23 multiply affected families . In subjects with schizophrenia , only head injuries preceding the onset of psychosis were considered . RESULTS Subjects in the schizophrenia group ( n = 16 [ 23.9 % ] ) were more likely than the unaffected siblings group ( n = 12 [ 11.8 % ] ) to have a history of childhood head injury ( P = .04 ; odds ratio , 2.35 [ 95 % confidence interval , 1.03 - 5.36 ] ) . Subjects in the schizophrenia group with a history of childhood head injury had a significantly younger median age at onset of psychosis ( 20 years ) compared with those with no such history ( 25 years ; z = -2.98 ; P = .003 ) . The severity of head injury ranged from minimal to mild , including concussions , but within this narrow range , severity was correlated with younger age at onset ( r(s ) = -0.66 ; P = .005 ) . Head injury occurred a median of 12 years before the onset of psychosis . Results were similar if head injuries during adolescence were included , but did not achieve statistical significance . CONCLUSIONS Mild childhood head injury may play a role in the expression of schizophrenia in families with a strong genetic predisposition . Prospect i ve studies of mild head injury should consider genetic predisposition for possible long-term neurobehavioral sequelae Objectives : The question of whether any adverse cognitive or psychosocial outcomes occur after mild head injury in early childhood has evoked considerable controversy . This study examined mild head injury before age 10 and potential differences in late childhood/early adolescence as a function of severity of mild injury and age at injury . Methods : A fully prospect i ve longitudinal design tracked a large birth cohort of children . Confirmed cases of mild head injury before age 10 were divided on the basis of outpatient medical attention ( n=64–84 ) or inpatient observation ( hospital overnight ; n=26–28 ) and compared with the non-injured remainder of the cohort ( reference group ; n=613–807 ) . A range of pre-injury and post-injury child and family characteristics were used to control for any potential confounds . Outcome after injury before and after age 5 was also assessed . Results : After accounting for several demographic , family , and pre-injury characteristics , the inpatient but not the outpatient group displayed increased hyperactivity/inattention and conduct disorder between ages 10 to 13 , as rated by both mothers and teachers . Psychosocial deficits were more prevalent in the inpatient subgroup injured before age 5 . No clear effects were evident for various cognitive/academic measures , irrespective of severity of mild injury or age at injury . Conclusions : Most cases of mild head injury in young children do not produce any adverse effects , but long term problems in psychosocial function are possible in more severe cases , perhaps especially when this event occurs during the preschool years . The view that all mild head injuries in children are benign events requires revision and more objective measures are required to identify cases at risk A 2 1/4-year prospect i ve study of children suffering head injury is described . Three groups of children were studied : ( a ) 31 children with ' severe ' head injuries result ing in a post-traumatic amnesia ( PTA ) of at least 7 days ; ( b ) an individually matched control group of 28 children with hospital-treated orthopaedic injuries ; and ( c ) 29 children with ' mild ' head injuries result ing in a PTA exceeding 1 hour but less than 1 week . A retrospective assessment of the children 's pre-accident behaviour was obtained by parental interview and teacher question naire immediately after the accident and before the behavioural sequelae of the injury could be known . Further psychiatric assessment s were undertaken 4 months , 1 year and 2 1/4 years after the initial injury . The mild head injury group showed a raised level of behavioural disturbance before the accident but no increase thereafter . It was concluded that head injuries result ing in a PTA of less than 1 week did not appreciably increase the psychiatric risk . By contrast , there was a marked increase in psychiatric disorders following severe head injury . The high rate of new disorders in children with severe head injuries who were without disorder before the accident , together with the finding of a dose-response relationship with the severity of brain injury , indicated a causal relationship . However , the development of psychiatric disorders in children with severe head injuries was also influenced by the children 's pre-accident behaviour , their intellectual level , and their psychosocial circumstances . With the exception of social disinhibition and a slight tendency for the disorders to show greater persistence over time , the disorders attributable to head injury showed no specific features OBJECTIVE The impact of mild head injury or mild traumatic brain injury ( TBI ) in children is variable , and determinants of outcome remain poorly understood . There have been no previous attempts to evaluate the impact of interventions to improve outcome . Results of previous intervention studies in adults have been mixed . This study aim ed to evaluate the impact of providing information on outcome measured in terms of reported symptoms , cognitive performance , and psychological adjustment in children 3 months after injury . METHODS A total of 61 children with mild TBI were assessed 1 week and 3 months after injury , and 58 children with mild TBI were assessed 3 months after injury only . They were compared with 2 control groups ( N = 45 and 47 ) of children with minor injuries not involving the head . Participants completed measures of preinjury behavior and psychological adjustment , postconcussion symptoms , and tests of attention , speed of information processing , and memory . Children with mild TBI seen at 1 week were also given an information booklet outlining symptoms associated with mild TBI and suggested coping strategies . Those seen 3 months after injury only did not receive this booklet . RESULTS Children with mild TBI reported more symptoms than controls at 1 week but demonstrated no impairment on neuropsychological measures . Initial symptoms had resolved for most children by 3 months after injury , but a small group of children who had previous head injury or a history of learning or behavioral difficulties reported ongoing problems . The group not seen at 1 week and not given the information booklet reported more symptoms overall and was more stressed 3 months after injury . CONCLUSIONS Providing an information booklet reduces anxiety and thereby lowers the incidence of ongoing problems The degree to which postinjury posttraumatic stress disorder ( PTSD ) and /or depressive symptoms in adolescents are associated with cognitive and functional impairments at 12 and 24 months after traumatic brain injury ( TBI ) is not yet known . The current study used a prospect i ve cohort design , with baseline assessment and 3- , 12- , and 24-month followup , and recruited a cohort of 228 adolescents ages 14 - 17 years who sustained either a TBI ( n = 189 ) or an isolated arm injury ( n = 39 ) . Linear mixed-effects regression was used to assess differences in depressive and PTSD symptoms between TBI and arm-injured patients and to assess the association between 3-month PTSD and depressive symptoms and cognitive and functional outcomes . Results indicated that patients who sustained a mild TBI without intracranial hemorrhage reported significantly worse PTSD ( Hedges g = 0.49 , p = .01 ; Model R(2 ) = .38 ) symptoms across time as compared to the arm injured control group . Greater levels of PTSD symptoms were associated with poorer school ( η(2 ) = .07 , p = .03 ; Model R(2 ) = .36 ) and physical ( η(2 ) = .11 , p = .01 ; Model R(2 ) = .23 ) functioning , whereas greater depressive symptoms were associated with poorer school ( η(2 ) = .06 , p = .05 ; Model R(2 ) = .39 ) functioning Background Concussion is one of the most commonly occurring injuries in sport today . The Sport Concussion Assessment Tool ( SCAT ) is a commonly used paper neurocognitive tool . To date , little is known about SCAT baseline normative values in youth athletes . Objective The purpose of this study was to determine normative values on the SCAT for male and female youth hockey players . Methods This is a secondary data analysis of pooled data from three prospect i ve cohort studies examining the risk of injury in paediatric ice hockey players aged 9–17 years . A preseason baseline demographic and injury history question naire was completed by each player . Results A total of 4193 players completed SCATs at baseline and were included in the analysis . 781 players ( 18.6 % ) reported a previous history of concussion . Fatigue and low energy followed by headache were the most commonly reported symptoms in all players . The majority of youth players could recite all five words immediately but only three words when delayed . A smaller proportion of the males were able to report the months of the year in reverse order compared with females of a similar age . The median number of digits recited in reverse order was 4 . Conclusions Youth ratings varied between age groups , gender and from previously reported ratings of varsity athletes , possibly reflecting developmental and gender differences . An underst and ing of these differences in youth athletes is important to ensure appropriate performance expectations on the SCAT and when making clinical decisions following a concussion BACKGROUND Improving our knowledge about the natural history and persistence of symptoms following mild traumatic brain injury is a vital step in improving the provision of health care to children with postconcussion syndrome . The purpose s of this study were to ( 1 ) determine the incidence and persistence of symptoms after mild traumatic brain injury and ( 2 ) ascertain whether Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) , symptom criteria for postconcussion syndrome in adults are appropriate for use in children . METHODS A tertiary care pediatric emergency department was the setting for this study . This was a prospect i ve observational follow-up cohort study of children ( ages 2 to 18 years ) with mild traumatic brain injury . Data were collected in person during the acute presentation , and subsequent follow-up was performed by telephone at 7 - 10 days and 1 , 2 , and 3 months postinjury . Postconcussion Symptom Inventory for parents and children was used . The DSM-IV diagnostic criteria for postconcussion syndrome were explored using receiver operating characteristic curve analysis . RESULTS A total of 467 children ( 62.5 % boys , median age 12.04 , range 2.34 - 18.0 ) with mild traumatic brain injury participated . The median time until symptom resolution was 29.0 days ( 95 % confidence intervals : 26.09 - 31.91 ) . Three months after injury , 11.8 % of children with mild traumatic brain injury remained symptomatic . Receiver operating curve characteristic analysis of the postconcussion syndrome criteria successfully classified symptomatic participants at three months postinjury ; the adolescent receiver operating characteristic curve was excellent with the area under the curve being 0.928 ( P < 0.001 , st and ard error 0.019 ) . CONCLUSIONS Consistent with our previous study , 11.8 % of children presenting to the emergency room with a mild traumatic brain injury remain symptomatic at 3 months postinjury . This is the first study to demonstrate stable incidence rates of postconcussion syndrome in children and that modified DSM-IV criteria can be used to successfully classify postconcussion syndrome in children . Although most children report a decay in symptoms over time , 10 % of children develop symptoms even though they initially had a good outcome . Caution should be used when using only parent report as a surrogate for childhood outcomes following a concussion OBJECTIVE To extend findings regarding predictive factors of psychiatric outcome from the first to the second year after traumatic brain injury ( TBI ) in children and adolescents . METHOD Subjects were children aged 6 to 14 years at the time they were hospitalized after TBI . The study used a prospect i ve follow-up design . Assessment s of preinjury psychiatric , behavioral , adaptive functioning , family functioning and family psychiatric history status were conducted . Severity of injury was assessed by st and ard clinical scales and neuroimaging was analyzed . The outcome measure was the presence of a psychiatric disorder , not present before the injury ( " novel " ) , during the second year after TBI . RESULTS Fifty subjects enrolled , and the analyses focused on 42 subjects followed at 24 months . Severity of injury , preinjury family function , and preinjury lifetime psychiatric history predicted the development of a " novel " psychiatric disorder present in the second year . CONCLUSION These data suggest that there are children , identifiable through clinical assessment , at increased risk for " novel " psychiatric disorders in the second year after TBI Background : There is controversy about which children with minor head injury need to undergo computed tomography ( CT ) . We aim ed to develop a highly sensitive clinical decision rule for the use of CT in children with minor head injury . Methods : For this multicentre cohort study , we enrolled consecutive children with blunt head trauma presenting with a score of 13–15 on the Glasgow Coma Scale and loss of consciousness , amnesia , disorientation , persistent vomiting or irritability . For each child , staff in the emergency department completed a st and ardized assessment form before any CT . The main outcomes were need for neurologic intervention and presence of brain injury as determined by CT . We developed a decision rule by using recursive partitioning to combine variables that were both reliable and strongly associated with the outcome measures and thus to find the best combinations of predictor variables that were highly sensitive for detecting the outcome measures with maximal specificity . Results : Among the 3866 patients enrolled ( mean age 9.2 years ) , 95 ( 2.5 % ) had a score of 13 on the Glasgow Coma Scale , 282 ( 7.3 % ) had a score of 14 , and 3489 ( 90.2 % ) had a score of 15 . CT revealed that 159 ( 4.1 % ) had a brain injury , and 24 ( 0.6 % ) underwent neurologic intervention . We derived a decision rule for CT of the head consisting of four high-risk factors ( failure to reach score of 15 on the Glasgow coma scale within two hours , suspicion of open skull fracture , worsening headache and irritability ) and three additional medium-risk factors ( large , boggy hematoma of the scalp ; signs of basal skull fracture ; dangerous mechanism of injury ) . The high-risk factors were 100.0 % sensitive ( 95 % CI 86.2%–100.0 % ) for predicting the need for neurologic intervention and would require that 30.2 % of patients undergo CT . The medium-risk factors result ed in 98.1 % sensitivity ( 95 % CI 94.6%–99.4 % ) for the prediction of brain injury by CT and would require that 52.0 % of patients undergo CT . Interpretation : The decision rule developed in this study identifies children at two levels of risk . Once the decision rule has been prospect ively vali date d , it has the potential to st and ardize and improve the use of CT for children with minor head injury The issue of whether mild head injuries ( HIs ) in children cause behavior problems and poor scholastic performance is controversial . This study included 119 children ( range = 8 - 16 years old ) with HI , 114 with other injuries , and 106 with no injury ( NI ) . Behavioral functioning was assessed with the Child Behavior Checklist ; academic functioning , with school grade s and st and ardized testing . Higher T scores were found for both injury groups versus NI participants on preinjury behavioral status . All 3 groups ' behavioral scores decreased relative to baseline at 1 year . HI and NI groups did not differ in school grade s or achievement testing either pre- or postinjury . These results are consistent with the conclusion that head injury of the mildest type does not increase the probability of new overt behavioral or academic problems OBJECTIVE To demonstrate the similarity of children with a history of traumatic brain injury ( TBI ) , particularly mild TBI , to matched children without such a history , within a child psychiatry outpatient clinic . METHOD This is a chart review of patients presenting to a child psychiatry outpatient clinic over a 3-year period . Children with TBI were matched by age , sex , race , and social class to children with no history of TBI . Axis I and II diagnoses , use of special education services , and IQ scores were compared . RESULTS Seventy-four ( 5.6 % ) of 1,333 consecutive clinic cases had a definite TBI . Of these , 64 were mild . Only 3 of 59 comparisons that were made between TBI and control subjects were significant . A developmental communication disorder cluster was significantly more frequent in the TBI group . Autism and a pervasive developmental disorder cluster were significantly more frequent in the control group . CONCLUSION In a child psychiatry clinic , patients with a history of TBI are virtually indistinguishable from matched children without TBI . Caution should be exercised before attributing the child 's problems , especially long-term problems , to the TBI unless the injury was severe or the child is exhibiting related phobic or posttraumatic stress symptomatology CONTEXT Ice hockey has one of the highest sport participation and injury rates in youth in Canada . Body checking is the predominant mechanism of injury in leagues in which it is permitted . OBJECTIVE To determine if risk of injury and concussion differ for Pee Wee ( ages 11 - 12 years ) ice hockey players in a league in which body checking is permitted ( Alberta , Canada ) vs a league in which body checking is not permitted ( Quebec , Canada ) . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted in Alberta and Quebec during the 2007 - 2008 Pee Wee ice hockey season . Participants ( N = 2154 ) were players from teams in the top 60 % of divisions of play . MAIN OUTCOME MEASURES Incidence rate ratios adjusted for cluster based on Poisson regression for game- and practice -related injury and concussion . RESULTS Seventy-four Pee Wee teams from Alberta ( n = 1108 players ) and 76 Pee Wee teams from Quebec ( n = 1046 players ) completed the study . In total , there were 241 injuries ( 78 concussions ) reported in Alberta ( 85 077 exposure-hours ) and 91 injuries ( 23 concussions ) reported in Quebec ( 82 099 exposure-hours ) . For game-related injuries , the Alberta vs Quebec incidence rate ratio was 3.26 ( 95 % confidence interval [ CI ] , 2.31 - 4.60 [ n = 209 and n = 70 for Alberta and Quebec , respectively ] ) for all injuries , 3.88 ( 95 % CI , 1.91 - 7.89 [ n = 73 and n = 20 ] ) for concussion , 3.30 ( 95 % CI , 1.77 - 6.17 [ n = 51 and n = 16 ] ) for severe injury ( time loss , > 7 days ) , and 3.61 ( 95 % CI , 1.16 - 11.23 [ n=14 and n=4 ] ) for severe concussion ( time loss , > 10 days ) . The estimated absolute risk reduction ( injuries per 1000 player-hours ) that would be achieved if body checking were not permitted in Alberta was 2.84 ( 95 % CI , 2.18 - 3.49 ) for all game-related injuries , 0.72 ( 95 % CI , 0.40 - 1.04 ) for severe injuries , 1.08 ( 95 % CI , 0.70 - 1.46 ) for concussion , and 0.20 ( 95 % CI , 0.04 - 0.37 ) for severe concussion . There was no difference between provinces for practice -related injuries . CONCLUSION Among 11- to 12-year-old ice hockey players , playing in a league in which body checking is permitted compared with playing in a league in which body checking is not permitted was associated with a 3-fold increased risk of all game-related injuries and the categories of concussion , severe injury , and severe concussion OBJECTIVE To determine the incidence of psychiatric illness 3 years after mild traumatic brain injury ( TBI ) in children . DESIGN Prospect i ve cohort study with 3-year follow-up . SETTING Emergency department , hospital , and outpatient clinics in a large health maintenance organization . PARTICIPANTS Children , 14 years old or less ( n=490 ) , who sustained a mild TBI in 1993 . Three TBI unexposed subjects per TBI exposed patient were matched by sex , age , and enrollment at the time of injury ( n=1470 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Computerized records were examined to identify psychiatric diagnoses , psychiatric medication prescription , and utilization of psychiatric services for the year before TBI and 3 years after . Adjusted relative risks for incidence of psychiatric illness were estimated for those with and without a premorbid psychiatric disorder . RESULTS The cumulative incidence estimates for any psychiatric illness in the 3 years after mild TBI were 30 % in children exposed to mild TBI and 20 % in unexposed children ( P=.0001 ) . Cumulative incidence estimates were particularly high in both TBI exposed ( 55 % ) and unexposed children ( 63 % ) who had psychiatric illness in the year before the index TBI ( psychiatric history ) . The exposed and unexposed children with psychiatric history did not have significantly different estimates of incidence during follow-up for any of the studied indicators of psychiatric illness . In those with no psychiatric history , 26 % of exposed and 16 % of unexposed children ( P<.0001 ) had evidence of a psychiatric illness in the 3 years after mild TBI . For those with no psychiatric history , the adjusted relative risk estimate of any psychiatric illness in TBI exposed versus unexposed children , in the first year after TBI , was 2.03 ( 95 % confidence interval [ CI ] , 1.4 - 2.9 ) . Children with mild TBI but no psychiatric history were at higher risk for hyperactivity ( diagnosis of hyperkinetic syndrome of childhood or prescription of psychostimulants ) in the first year after injury ( incidence , 3 % ; first year relative risk , 7.59 ; 95 % CI , 2.7 - 21.6 ) . CONCLUSIONS In the 3 years after mild TBI , children with no evidence of prior-year psychiatric history were at significantly increased risk for psychiatric illness , particularly hyperactivity in the first year after injury . Prior-year psychiatric history conferred a significant independent risk for subsequent psychiatric illness . There was no evidence for an additional increase in risk in the 3-year follow-up that is attributable to mild TBI in children with prior psychiatric history BACKGROUND : Much disagreement exists as to whether postconcussion syndrome ( PCS ) is attributable to brain injury or to other factors such as trauma alone , preexisting psychosocial problems , or medicolegal issues . We investigated the epidemiology and natural history of PCS symptoms in a large cohort of children with a mild traumatic brain injury ( mTBI ) and compared them with children with an extracranial injury ( ECI ) . METHODS : This investigation was a prospect i ve , consecutive controlled-cohort study of 670 children who presented to a tertiary referral emergency department with mTBI and 197 children who presented with ECI . For all participants , data were collected by use of a telephone interview of a parent 7 to 10 days after injury . If a change from preinjury symptoms was reported by a parent , follow-up continued monthly until symptom resolution . Outcomes were measured by using the Post Concussion Symptom Inventory , Rivermead Postconcussion Symptom Question naire , Brief Symptom Inventory , and Family Assessment Device . RESULTS : There was a significant difference between the mTBI and ECI groups in their survival curves for time to symptom resolution ( log rank [ Mantel-Cox ] 11.15 , P < .001 ) . Three months after injury , 11 % of the children in the mTBI group were symptomatic ( 13.7 % of children older than 6 years ) compared with 0.5 % of the children in the ECI group . The prevalence of persistent symptoms at 1 year was 2.3 % in the mTBI group and 0.01 % in the ECI group . Family functioning and maternal adjustment did not differ between groups . CONCLUSIONS : Among school-aged children with mTBI , 13.7 % were symptomatic 3 months after injury . This finding could not be explained by trauma , family dysfunction , or maternal psychological adjustment . The results of this study provide clear support for the validity of the diagnosis of PCS in children OBJECTIVES To estimate the incidence and demographics of concussions in children coming to emergency departments ( EDs ) in the United States and describe the rates of neuroimaging and follow-up instructions in these patients . STUDY DESIGN This is a cross-sectional study of children 0 to 19 years old diagnosed with concussion from the National Hospital Ambulatory Medical Care Survey . National Hospital Ambulatory Medical Care Survey collects data on approximately 25,000 visits annually to 600 r and omly selected hospital emergency and outpatient departments . We examined visits to United States emergency departments between 2002 and 2006 . Simple descriptive statistics were used . RESULTS Of the 50,835 pediatric visits in the 5-year sample , 230 observations , representing 144,000 visits annually , were for concussions . Sixty-nine percent of concussion visits were by males . Thirty percent were sports-related . Sixty-nine percent of patients diagnosed with a concussion had head imaging . Twenty-eight percent of patients were discharged without specific instructions to follow-up with an outpatient provider for further treatment . CONCLUSIONS Approximately 144,000 pediatric patients present to emergency departments each year with a concussion . Most of these patients undergo computed tomography of the head , and nearly one-third are discharged without specific instructions to follow-up with an outpatient provider for further treatment OBJECTIVES The aim was to examine functional outcomes following traumatic brain injury ( TBI ) during early childhood , to investigate impairments up to 5 years postinjury and identify predictors of outcome . METHODS The study compared three groups of children ( mild = 11 , moderate = 22 , severe = 15 ) , aged 2.0 - 6.11 years at injury , to a healthy control group ( n = 17 ) . Using a prospect i ve , longitudinal design , adaptive abilities , behavior , and family functioning were investigated acutely , 6 , 30 months and 5 years postinjury , with educational progress investigated at 30 months and 5 years postinjury . RESULTS A strong association was suggested between injury severity and outcomes across all domains . Further , 5-year outcomes in adaptive and behavioral domains were best predicted by preinjury levels of child function , and educational performance by injury severity . CONCLUSION Children who sustain a severe TBI in early childhood are at greatest risk of long-term impairment in day-to-day skills in the long-term postinjury Primary objective : To investigate the occurrence of post-concussive symptoms ( PCS ) and symptoms of post-traumatic stress disorder ( PTSD ) in children following mild traumatic brain injuries ( TBI ) . Research design : Longitudinal study comparing the outcomes of mild TBI and orthopaedic injuries ( OI ) in children aged 8–15 . Methods and procedures : One hundred and eighty-six children with mild TBI and 99 with OI were recruited prospect ively . Parents rated children 's PCS and symptoms of PTSD at 2 weeks , 3 months and 12 months post-injury . One hundred and sixty-seven with mild TBI and 84 with OI completed all assessment s. Main outcomes and results : Controlling for symptoms of PTSD , the mild TBI group demonstrated more PCS than the OI group , although the magnitude of group differences diminished with time . Controlling for PCS , the OI group displayed more symptoms of PTSD than the mild TBI group at baseline , but not thereafter . Symptoms of PTSD and PCS were correlated significantly , but more highly in the OI group than the mild TBI group . Conclusions : Although PCS and symptoms of PTSD are correlated , children with mild TBI are more distinguishable from children with OI based on PCS than on symptoms of PTSD . The latter symptoms , moreover , do not account for increased PCS following mild TBI in children The objective was to examine the effects of traumatic brain injury ( TBI ) , as compared with orthopedic injury ( OI ) , relative to the risk for psychiatric disorder . There has only been one previous prospect i ve study of this nature . Participants were age 7 - 17 years at the time of hospitalization for either TBI ( complicated mild-to-severe ) or OI . The study used a prospect i ve , longitudinal , controlled design , with st and ardized psychiatric assessment s conducted at baseline ( reflecting pre-injury functioning ) and 3 months post-injury . Assessment s of pre-injury psychiatric , adaptive functioning , family adversity , and family psychiatric history status were conducted . Severity of injury was assessed by st and ard clinical scales . The outcome measure was the presence of a psychiatric disorder not present before the injury ( " novel " ) , during the first 3 months after TBI . Enrolled participants ( N=141 ) included children with TBI ( N=75 ) and with OI ( N=66 ) . The analyses focused on 118 children ( 84 % ) ( TBI : N=65 ; OI : N=53 ) who returned for follow-up assessment at 3 months . Novel psychiatric disorder ( NPD ) occurred significantly more frequently in the TBI ( 32/65 ; 49 % ) than the OI ( 7/53 ; 13 % ) group . This difference was not accounted for by pre-injury lifetime psychiatric status ; pre-injury adaptive functioning ; pre-injury family adversity , family psychiatric history , socioeconomic status , injury severity , or age at injury . Furthermore , none of these variables significantly discriminated between children with TBI who developed , versus those who did not develop , NPD . These findings suggest that children with complicated mild-to-severe TBI are at significantly higher risk than OI-controls for the development of NPD in the first 3 months after injury |
13,409 | 18,606,047 | There is evidence , however , that transitory developmental expression of psychosis ( psychosis proneness ) may become abnormally persistent ( persistence ) and subsequently clinical ly relevant ( impairment ) , depending on the degree of environmental risk the person is additionally exposed to .
The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development , poor prognosis of which , in terms of persistence and clinical need , is predicted by environmental exposure interacting with genetic risk | null | null |
13,410 | 24,075,633 | AUDs are highly prevalent in BD .
Our study revealed a substantial heterogeneity across studies . | AIMS To assess the comorbidity rates of alcohol use disorders ( AUDs ) in bipolar disorder ( BD ) and to explore possible sources of heterogeneity . | BACKGROUND Substance abuse frequently complicates the course of bipolar illness , promotes mixed states , and contributes to poor outcome in mania . Preliminary open trials suggest that anticonvulsant mood stabilizers may enhance remission rates and outcome for bipolar patients with substance abuse . This study compared remission patterns for mixed or pure manic episodes among bipolar in patients with or without substance abuse histories . METHOD Hospital records were retrospectively review ed for 204 DSM-III-R bipolar I in patients . Clinical features were compared for those with or without substance abuse/dependence histories predating the index manic episode . Time until remission was analyzed by Kaplan-Meier survival analysis . Naturalistic treatment outcome with lithium or anticonvulsant mood stabilizers was compared for those with or without past substance abuse . RESULTS Past substance abuse was evident in 34 % of the bipolar sample and comprised most often alcoholism ( 82 % ) , followed by cocaine ( 30 % ) , marijuana ( 29 % ) , sedative-hypnotic or amphetamine ( 21 % ) , and opiate ( 13 % ) abuse . Substance abuse was more common among men ( p < .05 ) and those with mixed rather than pure mania ( p < .05 ) . Remission during hospitalization was less likely among patients with prior substance abuse ( p < .05 ) , especially alcohol or marijuana abuse , and among mixed manic patients with past substance abuse ( p < .05 ) . Bipolar patients with substance abuse histories who received divalproex or carbamazepine remitted during hospitalization more often than did those who received lithium as the sole mood stabilizer ( p < .05 ) . CONCLUSION These findings support previous reports suggesting that bipolar patients with past substance abuse have poorer naturalistic treatment outcomes , but may show a better response to anticonvulsant mood stabilizers than lithium CONTEXT Although an association between mood disorders and substance use disorders has been well established , there is a lack of long-term prospect i ve data on the order of onset and subtypes of mood disorders associated with specific substances and their progression . OBJECTIVE To estimate the respective risks posed by subtypes of mood disorders or bipolar spectrum conditions for the subsequent development of substance use disorders . DESIGN Six waves of direct diagnostic interviews were administered to a sample of young adults during a 20-year period . Mood disorders and syndromes assessed at each interview were used to predict the cumulative incidences of substance use disorders at subsequent interview waves . PARTICIPANTS We followed up 591 individuals ( 292 men and 299 women ) who were selected at study enrollment from a representative sample of young adults in Zurich , Switzerl and . MAIN OUTCOME MEASURES Structured Diagnostic Interview for Psychopathologic and Somatic Syndromes , a semistructured clinical interview that collected data on the spectrum of expression of mood disorders and substance use and disorders for DSM-III-R and DSM-IV criteria . RESULTS Individuals having manic symptoms were at significantly greater risk for the later onset of alcohol abuse/dependence , cannabis use and abuse/dependence , and benzodiazepine use and abuse/dependence . Bipolar II disorder predicted both alcohol abuse/dependence and benzodiazepine use and abuse/dependence . In contrast , major depression was predictive only of later benzodiazepine abuse/dependence . CONCLUSIONS In comparison with major depression , bipolar II disorder was associated with the development of alcohol and benzodiazepine use and disorders . There was less specificity of manic symptoms that tended to predict all levels of the substances investigated herein . The different patterns of association between mood disorders and substance use trajectories have important implication s for prevention and provide lacking information about underlying mechanisms BACKGROUND The association between early childhood abuse and the course of illness , including psychiatric comorbidities , in adults with bipolar disorder has not been examined in a predominantly male or veteran population . METHODS As part of the VA Cooperative Study 430 , " Reducing the Efficacy-Effectiveness Gap in Bipolar Disorder , " 330 veterans ( 91 % male ) with bipolar I or II disorder who were enrolled in a 3-year prospect i ve study were examined for baseline data obtained at study entry . Diagnoses were determined by the use of the SCID . A semistructured interview design ed to elicit data about exposure to childhood physical , sexual , or combined abuse was conducted as part of baseline demographic and clinical information . Other reports from this data set have not addressed the issues of childhood adversity . RESULTS Childhood abuse was reported by 48.3 % of the subjects ( 47.3 % of men ) . Any abuse ( AA ) was reported by 48.3 % ; sexual abuse without physical abuse ( SA ) was reported by 8 % , physical abuse without sexual abuse ( PA ) by 20.7 % , and both types of abuse ( combined abuse , CA ) by 18.7 % of the male subjects . Female veterans reported more SA ( 27 % ) and less PA ( 6.7 % ) . AA subjects were more likely to have current PTSD and lifetime diagnoses of panic disorder and alcohol use disorders . CA was associated with lower SF-36 Mental scores , higher likelihood of current PTSD and lifetime diagnoses of alcohol use disorders , as well as more lifetime episodes of major depression and higher likelihood of at least one suicide attempt . Younger age at study entry was associated with AA and PA . LIMITATIONS Potential limitations include generalizability beyond the male , veteran population of patients with bipolar disorder and the methodology used to elicit abuse histories . CONCLUSIONS Similar to studies of predominantly female nonveteran sample s , this study extends the finding that a history of childhood abuse acts as a disease course modifier in male veterans with bipolar disorder . Clinicians should routinely seek information regarding abuse and be aware that these patients may be more difficult to treat than bipolar patients who have no abuse histories OBJECTIVE To evaluate the prevalence of substance abuse dependence and /or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry . METHOD One hundred r and omly selected registrants in a voluntary case registry for bipolar disorder were interviewed , using the Structured Clinical Interview for DSM-IV Axis I Disorders , to vali date the diagnosis of this registry . Corroborative information was obtained from medical records , family members and the treating psychiatrist . Eighty-nine adults ( 18 - 65 years ) met criteria for bipolar disorder ( bipolar I = 71 , bipolar II = 18 ) and were included in this analysis . RESULTS Forty-one ( 57.8 % ) subjects with bipolar I disorder abused , or were dependent on one or more substances or alcohol , 28.2 % abused , or were dependent on , two substances or alcohol , and 11.3 % abused or were dependent on three or more substances or alcohol . Nearly 39 % of bipolar II subjects abused or were dependent on one or more substances , nearly 17 % were dependent on two or more substances or alcohol , and 11 % were dependent on three or more substances or alcohol . Alcohol was the most commonly abused drug among either bipolar I or II subjects . CONCLUSIONS Consistent with other epidemiologic and hospital population studies , this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and /or substance abuse dependence . Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects ; however , as the number of bipolar II subjects was rather small , this suggestion needs confirmation OBJECTIVE The prevalence of lifetime alcohol abuse and /or dependence ( alcoholism ) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses . This study examined gender-specific relationships between alcoholism and bipolar illness , which have previously received little systematic study . METHOD The prevalence of lifetime alcoholism in 267 out patients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV . Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered question naires . RESULTS As in the general population , more men ( 49 % , 57 of 116 ) than women with bipolar disorder ( 29 % , 44 of 151 ) met the criteria for lifetime alcoholism . However , the risk of having alcoholism was greater for women with bipolar disorder ( odds ratio=7.35 ) than for men with bipolar disorder ( odds ratio=2.77 ) , compared with the general population . Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder . CONCLUSIONS This study suggests that there are gender differences in the prevalence , risk , and clinical correlates of alcoholism in bipolar illness . Although this study is limited by the retrospective assessment of illness variables , the magnitude of these gender-specific differences is substantial and warrants further prospect i ve study OBJECTIVE Previous work has shown that manic-depressive illness and alcohol abuse are linked . This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method . METHOD Diagnosis was accomplished according to Research Diagnostic Criteria ( RDC ) : controls = 469 ; bipolars = 277 ; unipolar depressives = 678 . Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism . Both patients and comparison subjects were then followed prospect ively for 10 years . First degree family members were interviewed using the RDC family history method . RESULTS The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined . However , primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group . In contrast , primary bipolar patients had higher rates of alcoholism , stimulant abuse , and ever having abused a drug than the primary unipolar group and the control group . In an evaluation of the bipolar patients , drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder . There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients . LIMITATION As in all adult sample s of patients with affective illness , the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively . CONCLUSIONS ( 1 ) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients . ( 2 ) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs . ( 3 ) In a bipolar patient , familial diathesis for mania is significantly associated with the abuse of alcohol and drugs . ( 4 ) More provocatively , these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I , alcohol and stimulant abuse . CLINICAL IMPLICATION S The present analyses , coupled with two previous ones from the CDS , suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania . Furthermore , in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history , mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems , and should be studied in systematic controlled trials In light of the established influence of substance use on the onset , course , and outcome of bipolar disorder , we performed a retrospective chart review of patients with bipolar I disorder participating in a r and omized controlled trial to further investigate the relationship between alcohol and substance use and first onset of mania . A total of 59.4 % ( N=101 ) of the 170 participants were determined to have a history of substance and /or alcohol use . Among the 101 participants with SU , use was coded in 10 ( 9.9 % ) as immediately preceding , in 50 ( 49.5 % ) as preceding mania , in 7 ( 6.9 % ) as following mania , and in 34 ( 33.7 % ) as indeterminable . Of the 10 participants with immediately preceding use , 5 experienced their first manic episode immediately after discontinuing a substance . Our findings support earlier reports detailing the high prevalence of substance use among patients with bipolar disorder . Treatments targeting alcohol and substance use among individuals with bipolar disorder are clearly needed , as are prophylactic treatments targeting adolescents and young adults who are at risk for either bipolar disorder or alcohol and substance related disorders BACKGROUND There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms , especially the course of comorbid alcohol/substance abuse . METHOD A naturalistic sample of bipolar I patients ( n=120 ) was followed prospect ively for up to 10years . At baseline , number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes , respectively . 25 patients were excluded from the analyses . Outcomes including episodes , hospitalisations and suicide attempts were recorded at bimonthly visits . Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients . RESULTS Of the 95 patients analyzed , 44 ( 46.3 % ) had predominantly manic episodes and 51 ( 53.7 % ) had predominantly depressive episodes . At baseline , the predominantly depressive group had more history of suicide attempts ( 45.1 % vs. 20.5 % ; p=0.021 ) and more family history of affective disorders ( 64.7 % vs. 38.6 % ; p=0.020 ) , but they had fewer previous hospitalisations than the manic group ( mean 0.38 vs. 0.50 ; p=0.025 ) . During the 10-year follow-up , the predominantly depressive group was associated with more episodes ( p=0.001 ) , more hospitalisations ( p=0.004 ) and more suicide attempts ( p=0.002 ) . At baseline , there were no differences between the manic and depressive groups in the frequency of alcohol abuse ( 43.2 % and 35.3 % , p=0.565 ) or other substance abuse ( 13.6 % and 9.8 % , p=0.794 ) . During the 10-year follow-up , the frequency of alcohol and other substance abuse decreased significantly in the manic group only , after controlling by age at onset and civil ( marital ) status . CONCLUSION Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients , with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse . These differences should be considered when design ing treatment approaches for bipolar patients with comorbid alcohol/substance abuse OBJECTIVE To study patterns of co-occurrence of lifetime DSM-III-R alcohol disorders in a household sample . METHODS Data came from the National Comorbidity Survey ( NCS ) , a nationally representative household survey . Diagnoses were based on a modified version of the Composite International Diagnostic Interview . RESULTS Respondents with lifetime NCS/DSM-III-R alcohol abuse or dependence had a high probability of carrying at least 1 other lifetime NCS/DSM-III-R diagnosis . Retrospective reports have suggested that most lifetime co-occurring alcohol disorders begin at a later age than at least 1 other NCS/DSM-III-R disorder . Earlier disorders are generally stronger predictors of alcohol dependence than alcohol abuse and stronger among women than men . Lifetime co-occurrence is positively , but weakly , associated with the persistence of alcohol abuse among men and of alcohol dependence among both men and women . CONCLUSIONS Caution is needed in interpreting the results due to the fact that diagnoses were made by nonclinicians and results are based on retrospective reports of the age at onset . Within the context of these limitations , though , these results show that alcohol abuse and dependence are often associated with other lifetime DSM-III-R disorders and suggest that , at least in recent cohorts , the alcohol use disorders are usually temporally secondary . Prospect i ve data and data based on clinical ly confirmed diagnoses are needed to verify these findings OBJECTIVE Bipolar disorder is highly comorbid with substance use disorders , and this comorbidity may be associated with a more severe course of illness , but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined . The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder . METHOD Subjects ( N=3,750 ) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) were followed prospect ively for up to 2 years . Prospect ively observed depressive episodes were identified for this analysis . Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic , hypomanic , or mixed episode . RESULTS During follow up , 2,154 subjects developed a new-onset major depressive episode ; of these , 457 subjects switched to a manic , hypomanic , or mixed episode prior to recovery . Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity . However , those with current or past substance use disorder were more likely to experience switch from depression directly to a manic , hypomanic , or mixed state . CONCLUSIONS Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic , mixed , or hypomanic states . The mechanism conferring this increased risk merits further study OBJECTIVES Data from the Australian National Study of Low Prevalence ( Psychotic ) Disorders were used to describe the clinical and sociodemographic profile of individuals with bipolar disorder , their levels of impairment and disability , and use of medication and treatment services . METHODS A 1-month census of contacts with mental health services , private psychiatric and general practice s , as well as contact points in marginalized setting s , was conducted in a national catchment of 1.1 million adults . The census yielded 3,800 individuals who screened positive for psychosis , of whom a r and om sample of 980 were administered a comprehensive semi-structured interview schedule . Results are presented on 112 persons with an ICD-10 diagnosis of bipolar disorder . RESULTS Overall , 69.6 % of the 112 persons who met the ICD-10 criteria for bipolar disorder reported a recurrent episodic illness , 25.0 % had a chronic course without clear remissions , and 5.4 % had a single episode of mania . Assessed on a lifetime basis , suicidal ideation was common ( 78.6 % ) and levels of drug and alcohol abuse/dependence were high ( 32.1 % ) . The majority ( 84.8 % ) had had at least one contact with inpatient , outpatient or emergency services in the previous year . Those with serious impairment had levels of service utilization similar to the rest of the sample , but were more likely to report a poorer quality of life and unmet service needs . While the percentage experiencing social and occupational dysfunction was substantial and similar for both sexes , women appeared to be better integrated socially than men . Comparisons with schizophrenia patients within the same survey sample highlighted less chronic impairment but equal or greater utilization of services by bipolar patients . CONCLUSIONS Despite low levels of chronicity , the burden of social disablement associated with bipolar disorder is high . The data suggest a number of important gaps in the provision of services for this predominantly treated population |
13,411 | 23,516,098 | Compared with single-agent erlotinib , doublets ( erlotinib plus another targeted agent ) significantly improve ORR and DCR , but not OS , and induce no significance of more frequent and serious AEs .
The benefit-to-risk ratio of doublets in advanced NSCLC may be more favorable than that of single-agent .
The results of this systematic review suggest that patients with advanced NSCLC might benefit from doublet-targeted therapy based on erlotinib compared to erlotinib alone . | In patients with advanced non-small cell lung cancer ( NSCLC ) , the benefit-to-risk ratio of doublet-targeted agents versus single agent is not clear .
A systematic review and quantitative meta- analysis were , therefore , undertaken to evaluate the available evidence from r and omized trials .
This study aims to evaluate the efficacy and safety of erlotinib versus doublets ( erlotinib plus another targeted agent ) in advanced NSCLC and , if adequate data are available , to investigate whether or not predefined patient groups benefit more or less from doublet-targeted therapy based on erlotinib . | MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers and causes resistance to EGFR kinase inhibitors . We demonstrate that MET activation by its lig and , HGF , also induces drug resistance , but through GAB1 signaling . Using high-throughput FISH analyses in both cell lines and in patients with lung cancer , we identify sub population s of cells with MET amplification prior to drug exposure . Surprisingly , HGF accelerates the development of MET amplification both in vitro and in vivo . EGFR kinase inhibitor resistance , due to either MET amplification or autocrine HGF production , was cured in vivo by combined EGFR and MET inhibition . These findings highlight the potential to prospect ively identify treatment naive , patients with EGFR-mutant lung cancer who will benefit from initial combination therapy PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC BACKGROUND Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles . On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer ( NSCLC ) , we aim ed to assess efficacy and safety of this combination in a phase 3 trial . METHODS In our double-blind , placebo-controlled , r and omised phase 3 trial ( BeTa ) , we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment . Patients were r and omly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab ( bevacizumab group ) or erlotinib plus placebo ( control group ) according to a computer-generated r and omisation sequence by use of an interactive voice response system . The primary endpoint was overall survival in all enrolled patients . Patients , study staff , and investigators were masked to treatment assignment . We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses . This trial is registered with Clinical Trials.gov , number NCT00130728 . FINDINGS Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group ( hazard ratio [ HR ] 0·97 , 95 % CI 0·80 - 1·18 , p=0·7583 ) . Median overall survival was 9·3 months ( IQR 4·1 - 21·6 ) for patients in the bevacizumab group compared with 9·2 months ( 3·8 - 20·2 ) for controls . Progression-free survival seemed to be longer in the bevacizumab group ( 3·4 months [ 1·4 - 8·4 ] ) than in the control group ( 1·7 months [ 1·3 - 4·1 ] ; HR 0·62 , 95 % CI 0·52 - 0·75 ) and objective response rate suggested some clinical activity of bevacizumab and erlotinib . However , these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done , to control type I error rate . In the bevacizumab group , 130 ( 42 % ) of 313 patients with safety data had a serious adverse event , compared with 114 ( 36 % ) controls . There were 20 ( 6 % ) grade 5 adverse events , including two arterial thromboembolic events , in the bevacizumab group , and 14 ( 4 % ) in the control group . INTERPRETATION Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC . FUNDING Genentech PURPOSE Bevacizumab , a humanized anti-vascular endothelial growth factor monoclonal antibody , and erlotinib , a reversible , orally available epidermal growth factor receptor tyrosine kinase inhibitor , have demonstrated evidence of a survival benefit in the treatment of non-small-cell lung cancer ( NSCLC ) . A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy , with a favorable safety profile . PATIENTS AND METHODS A multicenter , r and omized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy ( docetaxel or pemetrexed ) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone , as measured by progression-free survival ( PFS ) . All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen . RESULTS One hundred twenty patients were r and omly assigned and treated . No unexpected adverse events were noted . Fewer patients ( 13 % ) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone ( 24 % ) or bevacizumab-chemotherapy ( 28 % ) arms . The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1 % . Although not statistically significant , relative to chemotherapy alone , the risk of disease progression or death was 0.66 ( 95 % CI , 0.38 to 1.16 ) among patients treated with bevacizumab-chemotherapy and 0.72 ( 95 % CI , 0.42 to 1.23 ) among patients treated with bevacizumab-erlotinib . One-year survival rate was 57.4 % for bevacizumab-erlotinib and 53.8 % for bevacizumab-chemotherapy compared with 33.1 % for chemotherapy alone . CONCLUSION Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting . No unexpected safety signals were noted . The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials . The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . Background : Sunitinib malate ( SUTENT ) has promising single-agent activity given on Schedule 4/2 ( 4 weeks on treatment followed by 2 weeks off treatment ) in advanced non-small cell lung cancer ( NSCLC ) . Methods : We examined the activity of sunitinib on a continuous daily dosing ( CDD ) schedule in an open-label , multicentre phase II study in patients with previously treated , advanced NSCLC . Patients ⩾18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy , received sunitinib 37.5 mg per day . The primary end point was objective response rate ( ORR ) . Secondary end points included progression-free survival ( PFS ) , overall survival ( OS ) , 1-year survival rate , and safety . Results : Of 47 patients receiving sunitinib , one patient achieved a confirmed partial response ( ORR 2.1 % ( 95 % confidence interval ( CI ) 0.1 , 11.3 ) ) and 11 ( 23.4 % ) had stable disease ( SD ) ⩾8 weeks . Five patients had SD>6 months . Median PFS was 11.9 weeks ( 95 % CI 8.6 , 14.1 ) and median OS was 37.1 weeks ( 95 % CI 31.1 , 69.7 ) . The 1-year survival probability was 38.4 % ( 95 % CI 24.2 , 52.5 ) . Treatment was generally well tolerated . Conclusions : The safety profile and time-to-event analyses , albeit relatively low response rate of 2 % , suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced , refractory NSCLC 3549 Background : ARQ197 ( A ) is a selective , non-ATP competitive inhibitor of c-Met , a receptor tyrosine kinase implicated in tumor cell migration , invasion , and proliferation . Phase I data for ARQ 197 monotherapy is previously reported . Recent evidence suggests c-Met promotes resistance to EGFR-inhibition by driving ERBB3 (HER3)-dependent PI3 K activation . Dual EGFR-Met inhibition is now proposed as a strategy for overcoming resistance to EGFR-inhibition . METHODS Patients ( pts ) were enrolled in a sequential-cohort dose-escalation trial seeking to define safety , tolerability , pharmacokinetics ( PK ) , and preliminary anti-tumor activity of A in combination with 150 mg daily oral erlotinib ( E ) . Oral A was administered at escalating doses of 120 , 240 , and 360 mg bid . Intra-patient dose escalation was allowed in the absence of dose-limiting toxicity ( DLT ) through 1 cycle of therapy ( 21 days ) . RESULTS 25 pts ( 10 F/15 M ; mean 60.5 yrs ) received EA combination with starting A dose of 120 ( 8 pts ) , 240 ( 4 pts ) , and 360 ( 13 pts ) mg bid . PK data reveal linear kinetics through 360 bid and no evidence of drug-drug interaction . Adverse events ( AEs ) considered related to combination therapy were reported in 13 ( 52 % ) of pts incl.sinus bradycardia ( 5 pts ) , fatigue ( 5 pts ) , rash ( 4 pts ) , itching ( 3 pts ) , and diarrhea ( 3 pts ) . 2 pts experienced related serious AEs incl . neutropenia ( 360 bid ) and sinus bradycardia ( 240 bid ) . 1 death occurring on- study was considered unrelated to study drug . 9/10 evaluable pts demonstrated disease stabilization ( SD ) as their best RECIST response ( 5.9 - 27.1 + wks ) . Tumor regressions ( 2.3%-19.4 % ) were observed in 4/10 evaluable pts . Of note , 3/3 evaluable pts with NSCLC achieved SD for duration s ( 14 - 32 wks ) exceeding median PFS in BR.21 ( 9.7 wks ) . CONCLUSIONS Continuous therapy with EA combination appears well tolerated and without drug-drug interaction . While no formal MTD was identified , a phase 2 combination dose ( R2PD ) of 360 mg bid A + 150 mg daily E is recommended . This RP2D is currently being investigated in an ongoing r and omized trial comparing EA to E monotherapy in 2nd/3rd line NSCLC . [ Table : see text ] Introduction : This phase 2 study was conducted to determine the efficacy and safety of erlotinib alone and with bortezomib in patients with non-small cell lung cancer ( NSCLC ) . Methods : Patients with histologically or cytologically confirmed relapsed or refractory stage IIIb/IV NSCLC were r and omized ( 1:1 ; stratified by baseline histology , smoking history , sex ) to receive erlotinib 150 mg/d alone ( arm A ; n = 25 ) or in combination with bortezomib 1.6 mg/m2 , days 1 and 8 ( arm B ; n = 25 ) in 21-day cycles . Responses were assessed using Response Evaluation Criteria in Solid Tumors . Tumor sample s were evaluated for mutations predicting response . Six additional patients received the combination in a prior dose deescalation stage and were included in safety analyses . Results : Response rates were 16 % in arm A and 9 % in arm B ; disease control rates were 52 and 45 % , respectively . The study was halted at the planned interim analysis due to insufficient clinical activity in arm B. Median progression-free survival and overall survival were 2.7 and 7.3 months in arm A , and 1.3 and 8.5 months in arm B. Six-month survival rates were 56.0 % in both arms ; 12-month rates were 40 and 30 % in arms A and B , respectively . Response rate to erlotinib±bortezomib was significantly higher in patients with epidermal growth factor receptor mutations ( 50 versus 9 % for wild type ) . The most common treatment-related grade ≥3 adverse event was skin rash ( three patients in each treatment group ) . Conclusion : Insufficient activity was seen with erlotinib plus bortezomib in patients with relapsed/refractory advanced NSCLC to warrant a phase 3 study of the combination PURPOSE R1507 is a selective , fully human , recombinant monoclonal antibody ( immunoglobulin G1 subclass ) against insulin-like growth factor-1 receptor ( IGF-1R ) . The strong pre clinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor ( EGFR ) as anticancer therapy prompted this study . PATIENTS AND METHODS Patients with advanced-stage non-small-cell lung cancer ( NSCLC ) with progression following one or two prior regimens , Eastern Cooperative Oncology Group ( ECOG ) performance status 0 to 2 , and measurable disease were eligible . Patients were r and omly assigned to receive erlotinib ( 150 mg orally once a day ) in combination with either placebo , R1507 9 mg/kg weekly , or R1507 16 mg/kg intravenously once every 3 weeks . Treatment cycles were repeated every 3 weeks . The primary end point was comparison of the 12-week progression-free survival ( PFS ) rate . RESULTS In all , 172 patients were enrolled : median age , 61 years ; female , 33 % ; never-smokers , 12 % ; and performance status 0 or 1 , 88 % . The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm . Grade s 3 to 4 adverse events occurred in 37 % , 44 % , and 48 % of patients with placebo , R1507 weekly , and R1507 every 3 weeks , respectively . The 12-week PFS rates were 39 % , 37 % , and 44 % , and the median overall survival was 8.1 , 8.1 , and 12.1 months for the three groups , respectively , with statistically nonsignificant hazard ratios . The 12-week PFS rate in patients with KRAS mutation was 36 % with R1507 compared with 0 % with placebo . CONCLUSION The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC . Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR Although some cancers are initially sensitive to EGFR tyrosine kinase inhibitors ( TKIs ) , resistance invariably develops . We investigated mechanisms of acquired resistance to the EGFR TKI gefitinib by generating gefitinib-resistant ( GR ) A431 squamous cancer cells . In GR cells , gefitinib reduced phosphorylation of EGFR , ErbB-3 , and Erk but not Akt . These cells also showed hyperphosphorylation of the IGFI receptor ( IGFIR ) and constitutive association of IRS-1 with PI3 K . Inhibition of IGFIR signaling disrupted the association of IRS-1 with PI3 K and restored the ability of gefitinib to downregulate PI3K/Akt signaling and to inhibit GR cell growth . Gene expression analyses revealed that GR cells exhibited markedly reduced IGF-binding protein 3 ( IGFBP-3 ) and IGFBP-4 RNA . Addition of recombinant IGFBP-3 restored the ability of gefitinib to downregulate PI3K/Akt signaling and to inhibit cell growth . Finally , gefitinib treatment of mice with A431 xenografts in combination with an IGFIR-specific monoclonal antibody prevented tumor recurrence , whereas each drug given alone was unable to do so . These data suggest that loss of expression of IGFBPs in tumor cells treated with EGFR TKIs derepresses IGFIR signaling , which in turn mediates resistance to EGFR antagonists . Moreover , combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospect i ve clinical investigation BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) BACKGROUND V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) , epidermal growth factor receptor ( EGFR ) , and rearranged during transfection ( RET ) tyrosine kinases . In a r and omised phase 2 study in patients with previously treated non-small-cell lung cancer ( NSCLC ) , adding v and etanib 100 mg to docetaxel significantly improved progression-free survival ( PFS ) compared with docetaxel alone , including a longer PFS in women . These results supported investigation of the combination in this larger , definitive phase 3 trial ( ZODIAC ) . METHODS Between May , 2006 , and April , 2008 , patients with locally advanced or metastatic ( stage IIIB-IV ) NSCLC after progression following first-line chemotherapy were r and omly assigned 1:1 through a third-party interactive voice system to receive v and etanib ( 100 mg/day ) plus docetaxel ( 75 mg/m(2 ) intravenously every 21 days ; maximum six cycles ) or placebo plus docetaxel . The primary objective was comparison of PFS between the two groups in the intention-to-treat population . Women were a co primary analysis population . This study has been completed and is registered with Clinical Trials.gov , number NCT00312377 . FINDINGS 1391 patients received v and etanib plus docetaxel ( n=694 [ 197 women ] ) or placebo plus docetaxel ( n=697 [ 224 women ] ) . V and etanib plus docetaxel led to a significant improvement in PFS versus placebo plus docetaxel ( hazard ratio [ HR ] 0.79 , 97.58 % CI 0.70 - 0.90 ; p<0.0001 ) ; median PFS was 4.0 months in the v and etanib group versus 3.2 months in placebo group . A similar improvement in PFS with v and etanib plus docetaxel versus placebo plus docetaxel was seen in women ( HR 0.79 , 0.62 - 1.00 , p=0.024 ) ; median PFS was 4.6 months in the v and etanib group versus 4.2 months in the placebo group . Among grade 3 or higher adverse events , rash ( 63/689 [ 9 % ] vs 7/690 [ 1 % ] ) , neutropenia ( 199/689 [ 29 % ] vs 164/690 [ 24 % ] ) , leukopenia ( 99/689 [ 14 % ] vs 77/690 [ 11 % ] ) , and febrile neutropenia ( 61/689 [ 9 % ] vs 48/690 [ 7 % ] ) were more common with v and etanib plus docetaxel than with placebo plus docetaxel . The most common serious adverse event was febrile neutropenia ( 46/689 [ 7 % ] in the v and etanib group vs 38/690 [ 6 % ] in the placebo group ) . INTERPRETATION The addition of v and etanib to docetaxel provides a significant improvement in PFS in patients with advanced NSCLC after progression following first-line therapy PURPOSE Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer ( NSCLC ) , based on the importance of the signaling pathways involved in tumor growth , angiogenesis , and metastasis . This phase III trial investigated overall survival ( OS ) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC . PATIENTS AND METHODS Patients previously treated with one to two chemotherapy regimens ( including one platinum-based regimen ) for recurrent NSCLC , and for whom erlotinib was indicated , were r and omly assigned ( 1:1 ) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d , stratified by prior bevacizumab use , smoking history , and epidermal growth factor receptor expression . The primary end point was OS . Key secondary end points included progression-free survival ( PFS ) , objective response rate ( ORR ) , and safety . RESULTS In all , 960 patients were r and omly assigned , and baseline characteristics were balanced . Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone ( hazard ratio [ HR ] , 0.922 ; 95 % CI , 0.797 to 1.067 ; one-sided stratified log-rank P = .1388 ) . Median PFS was 3.6 months versus 2.0 months ( HR , 0.807 ; 95 % CI , 0.695 to 0.937 ; one-sided stratified log-rank P = .0023 ) , and ORR was 10.6 % versus 6.9 % ( two-sided stratified log-rank P = .0471 ) , respectively . Treatment-related toxicities of grade 3 or higher , including rash/dermatitis , diarrhea , and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm . CONCLUSION In patients with refractory NSCLC , sunitinib plus erlotinib did not improve OS compared with erlotinib alone , but the combination was associated with a statistically significantly longer PFS and greater ORR . The incidence of grade 3 or higher toxicities was greater with combination therapy PURPOSE c-MET ( MET ) receptor activation is associated with poor prognosis and epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ( TKI ) resistance in non-small-cell lung cancer ( NSCLC ) . This global , r and omized phase II trial examined erlotinib plus tivantinib ( ARQ 197 ; ArQule , Woburn , MA ) , a novel MET inhibitor . METHODS Previously treated patients with EGFR TKI-naive advanced NSCLC were r and omly assigned to receive oral erlotinib ( 150 mg daily ) plus oral tivantinib ( 360 mg twice daily ) or erlotinib plus placebo ( EP ) . The primary end point was progression-free survival ( PFS ) . At the time of progression , cross-over from EP to erlotinib plus tivantinib ( ET ) was permitted . Archival tumor tissue specimens were required . RESULTS One hundred sixty-seven patients were r and omly assigned to ET ( n = 84 ) and to EP ( n = 83 ) . Median PFS was 3.8 months for ET and 2.3 months for EP ( hazard ratio [ HR ] , 0.81 ; 95 % CI , 0.57 to 1.16 ; P = .24 ) . Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 ( 95 % CI , 0.05 to 0.70 ; interaction P = .006 ) . Objective responses were seen in 10 % of patients on ET , 7 % of patients on EP , and in two patients who crossed over from EP to ET , including one with EGFR mutation and MET gene copy number greater than 5 . There were no significant differences in adverse events between study arms . CONCLUSION The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated . Although the study did not meet its primary end point , evidence of activity was demonstrated , especially among patients with KRAS mutations . Additional study of tivantinib and erlotinib in patients with NSCLC is planned PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type Purpose : Sorafenib and erlotinib are potent , orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities . Given their inhibitory target profile and efficacy as single agents , the combination of these drugs is of considerable interest in solid malignancies . This study aim ed to determine the recommended phase II dose of this targeted combination , their toxicity profile , pharmacokinetic interaction , and preliminary clinical activities . Experimental Design : Sorafenib was administered alone for a 1-week run-in period , and then both drugs were given together continuously , with every 28 days considered as a cycle . Three dose levels were assessed . Results : Seventeen patients with advanced solid tumors received 75 cycles of treatment . The most frequent adverse events of all grade s were constitutional and gastrointestinal in nature followed by electrolytes and dermatologic toxicities . Fatigue was the most common adverse event ( 17 patients ; 100 % ) followed by diarrhea ( 15 patients ; 88 % ) , hypophosphatemia ( 13 patients ; 76 % ) , and acneiform rash ( 12 patients ; 71 % ) . These adverse events were predominantly mild to moderate . The recommended phase II dose of this combination was determined as 400 mg twice daily sorafenib and 150 mg daily erlotinib . Pharmacokinetic analysis revealed no significant effect of erlotinib on the pharmacokinetic profile of sorafenib . Among 15 evaluable patients , 3 ( 20 % ) achieved a confirmed partial response and 9 ( 60 % ) had stable disease as best response . Conclusions : Sorafenib and erlotinib are well tolerated and seem to have no pharmacokinetic interactions when administered in combination at their full single-agent recommended doses . This well tolerated combination result ed in promising activity that needs further validation in phase II studies BACKGROUND First-line chemotherapy for advanced non-small-cell lung cancer ( NSCLC ) is usually limited to four to six cycles . Maintenance therapy can delay progression and prolong survival . The oral epidermal growth factor receptor ( EGFR ) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC . We design ed the phase 3 , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy . METHODS Between December , 2005 , and May , 2008 , 1949 patients were included in the run-in phase ( four cycles of platinum-based chemotherapy ) . At the end of the run-in phase , 889 patients who did not have progressive disease were entered into the main study , and were r and omly allocated using a 1:1 adaptive r and omisation method through a third-party interactive voice response system to receive erlotinib ( 150 mg/day ; n=438 ) or placebo ( n=451 ) until progression or unacceptable toxicity . Patients were stratified by EGFR immunohistochemistry status , stage , Eastern Cooperative Oncology Group performance status , chemotherapy regimen , smoking history , and region . Co- primary endpoints were progression-free survival ( PFS ) in all analysable patients irrespective of EGFR status , and PFS in patients whose tumours had EGFR protein overexpression , as determined by immunohistochemistry . This study is registered with www . Clinical Trials.gov , number NCT00556712 . FINDINGS 884 patients were analysable for PFS ; 437 in the erlotinib group and 447 in the placebo group . After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group , median PFS was significantly longer with erlotinib than with placebo : 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group ( HR 0.71 , 95 % CI 0.62 - 0.82 ; p<0.0001 ) . PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib ( n=307 ) compared with EGFR-positive patients given placebo ( n=311 ; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group ; HR 0.69 , 0.58 - 0.82 ; p<0.0001 ) . The most common grade 3 or higher adverse events were rash ( 37 [ 9 % ] of 443 patients in the erlotinib group vs none of 445 in the placebo group ) and diarrhoea ( seven [ 2 % ] of 443 patients vs none of 445 ) . Serious adverse events were reported in 47 patients ( 11 % ) on erlotinib compared with 34 patients ( 8 % ) on placebo . The most common serious adverse event was pneumonia ( seven cases [ 2 % ] with erlotinib and four [ < 1 % ] with placebo ) . INTERPRETATION Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo . First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy . FUNDING F Hoffmann-La Roche PURPOSE Aberrant vascular endothelial growth factor ( VEGF ) and platelet-derived growth factor ( PDGF ) signaling have been shown to play a role in non-small-cell lung cancer ( NSCLC ) pathogenesis and are associated with decreased survival . We evaluated the clinical activity and tolerability of sunitinib malate ( SU11248 ) , an oral , multitargeted tyrosine kinase inhibitor that blocks the activity of receptors for VEGF and PDGF , as well as related tyrosine kinases in patients with previously treated , advanced NSCLC . PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC for whom platinum-based chemotherapy had failed received 50 mg/d of sunitinib for 4 weeks followed by 2 weeks of no treatment in 6-week treatment cycles . The primary end point was objective response rate ( ORR ) ; secondary end points included progression-free survival , overall survival , and safety . RESULTS Of the 63 patients treated with sunitinib , seven patients had confirmed partial responses , yielding an ORR of 11.1 % ( 95 % CI , 4.6 % to 21.6 % ) . An additional 18 patients ( 28.6 % ) experienced stable disease of at least 8 weeks in duration . Median progression-free survival was 12.0 weeks ( 95 % CI , 10.0 to 16.1 weeks ) , and median overall survival was 23.4 weeks ( 95 % CI , 17.0 to 28.3 weeks ) . Therapy was generally well tolerated . CONCLUSION Sunitinib has promising single-agent activity in patients with recurrent NSCLC , with an ORR similar to that of currently approved agents and an acceptable safety profile . Further evaluation in combination with other targeted agents and chemotherapy in patients with NSCLC is warranted PURPOSE Sorafenib is an oral multikinase inhibitor that targets the Ras/Raf/MEK/ERK mitogenic signaling pathway and the angiogenic receptor tyrosine kinases , vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor beta . We evaluated the antitumor response and tolerability of sorafenib in patients with relapsed or refractory , advanced non-small-cell lung cancer ( NSCLC ) , most of whom had received prior platinum-based chemotherapy . PATIENTS AND METHODS This was a phase II , single-arm , multicenter study . Patients with relapsed or refractory advanced NSCLC received sorafenib 400 mg orally twice daily until tumor progression or an unacceptable drug-related toxicity occurred . The primary objective was to measure response rate . RESULTS Of 54 patients enrolled , 52 received sorafenib . The predominant histologies were adenocarcinoma ( 54 % ) and squamous cell carcinoma ( 31 % ) . No complete or partial responses were observed . Stable disease ( SD ) was achieved in 30 ( 59 % ) of the 51 patients who were evaluable for efficacy . Four patients with SD developed tumor cavitation . Median progression-free survival ( PFS ) was 2.7 months , and median overall survival was 6.7 months . Patients with SD had a median PFS of 5.5 months . Major grade s 3 to 4 , treatment-related toxicities included h and -foot skin reaction ( 10 % ) , hypertension ( 4 % ) , fatigue ( 2 % ) , and diarrhea ( 2 % ) . Nine patients died within a 30-day period after discontinuing sorafenib , and one patient experienced pulmonary hemorrhage that was considered drug related . CONCLUSION Continuous treatment with sorafenib 400 mg twice daily was associated with disease stabilization in patients with advanced NSCLC . The broad activity of sorafenib and its acceptable toxicity profile suggest that additional investigation of sorafenib as therapy for patients with NSCLC is warranted |
13,412 | 11,686,985 | REVIEW ER 'S CONCLUSIONS This review provides some evidence for the effectiveness of the modification of training schedules , but there is insufficient evidence to determine the effectiveness of stretching exercises for major lower limb muscle groups in reducing lower limb soft-tissue running injuries . | BACKGROUND Overuse musculoskeletal injuries occur frequently in runners .
Suggestions for prevention have focused on stretching exercises , modifying training schedules and the use of protective devices such as braces and insoles .
To date , no systematic analysis of the literature on the effectiveness of these strategies in the prevention of overuse injuries has been published .
OBJECTIVES The objective of the review was to evaluate the evidence from r and omised controlled trials on the prevention of lower limb soft-tissue running injuries .
The effectiveness of stretching exercises ( 5 trials , 1944 participants in the intervention groups , 3159 controls ) , and of insoles and footwear modification ( 5 trials , 903 participants in the intervention groups , 3006 controls ) in the prevention of lower extremity soft tissue injuries associated with running is unknown . | Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group Soccer referees participating in large soccer tournaments may develop overuse injuries . In this study the effect of shock absorbing heel inserts in the incidence of soreness was investigated . Forty-eight referees were r and omly selected to wear shock absorbing heel inserts ( SAH ) in the 5 day-tournament , while 43 referees were the control group . A daily question naire inquiring about complaints from the locomotive system was completed for each referee and in case of any soreness they were examined by doctors to document and classify the anatomical site . Calf , thigh , back , achilles tendon and knee were the most common localizations of overuse symptoms . The incidence of soreness in achilles tendon , calf and back were significantly reduced by the use of ( SAH ) inserts Three hundred fifty male recruits were r and omly allocated to either the st and ard recruit training program ( N = 180 ) or substituted a weighted march activity for all running periods in the physical training program ( N = 170 ) . There were no other differences in the formal training program . The incidence of injury was 37.6 and 46.6 % in the walk and run groups , respectively . The rate of injury was 52.9/100 recruits in the walk group and 61.7/100 in the run group . The exposure incidence was 12.8/1,000 hours of physical training in the walk group and 14.9/1,000 hours in the run group . There was no statistically significantly difference in the total number of injured recruits in the two groups ( 64 vs. 85 , chi(2 ) = 2.90 , p = 0.09 , relative risk [ RR ] = 1.24 ) . There were , however , significantly more lower-limb ( 43 vs. 75 , chi(2 ) = 9.77 , p = 0.0018 , RR = 1.65 ) and knee injuries ( 15 vs. 35 , chi(2 ) = 6.54 , p = 0.011 , RR = 2.14 ) in the Run group . Lower-limb injuries constituted 79.8 % of all Run injuries and 61.1 % of all Walk injuries . Injuries in the Run group produced more morbidity , with nearly double the number of days of restriction , hospitalization , and not fit for duty . St and ardized morbidity rates showed an average of 5.4 days of restriction per injury in the Run group and 3.96 days of restriction per injury in the Walk group . Reduction of running distance in the physical training program result ed in significant reductions in both the incidence of lower-limb injury and the overall severity of injury Plantar fasciitis is a common problem in running sports . This study was undertaken to determine whether iontophoresis of dexamethasone in conjunction with other traditional modalities provides more immediate pain relief than traditional modalities alone . Forty affected feet were r and omly assigned to one of two groups . Group I feet were treated with traditional modalities and placebo iontophoresis . Group II feet received the traditional modalities plus iontophoresis of dexamethasone . Both groups were treated six times over 2 weeks . The subjects ' clinical course was assessed using the Maryl and Foot Score . At the conclusion of treatment , Group II patients had significantly greater improvement than Group I patients ( increase on Maryl and Foot Score of 6.8 + /- 5.6 for Group II and 3.1 + /- 4.1 for Group I ) . However , at followup 1 month after completion of treatment there was no significant difference between groups ( increase of 5.6 + /- 8.0 for Group I and 7.4 + /- 6.3 for Group II ) . These results suggest that although traditional modalities alone are ultimately effective , iontophoresis in conjunction with traditional modalities provides immediate reduction in symptoms . Based on these results , iontophoresis of dexamethasone for plantar fasciitis should be considered when more immediate results are needed ( i.e. , performance athletes and active patients The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees . Two different companies going through basic training at the same time were used . Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course . The control company ( N 148 ) proceeded through normal basic training . The intervention company ( N 150 ) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program . All subsequent lower extremity overuse injuries were recorded through the troop medical clinic . Hamstring flexibility increased significantly in the intervention group compared with the control group . The number of injuries was also significantly lower in the intervention group . Forty-three injuries occurred in the control group for an incidence rate of 29.1 % , compared with 25 injuries in the intervention group for an incidence rate of 16.7 % . Thus , in this study , the number of lower extremity overuse injuries was significantly lower in infantry basic trainees with increased hamstring flexibility Our prospect i ve study evaluates the use of a knee brace with a silicon patellar support ring as a method of preventing anterior knee pain from developing in young persons undergoing strenuous physical exercise . We studied 60 young athletes , who qualified for a strenu ous physical training course and who had not suffered from anterior knee pain previously . Twenty-seven sub jects were in the brace group and 33 were in the nonbrace control group . The incidence of anterior knee pain syndrome increased with the intensity of exertion as the study progressed ; i.e. , subjects ran 6 km in the 1 st week , gradually increasing each week up to 42 km/week at the 8th week . Yet , there was a significant reduction in the incidence of the syndrome at the end of the study in male athletes who had applied the braces before exercise sessions and in the brace group as a whole , compared with the control group . Prophylactic use of the brace , as described , did not reduce the ability of the athletes who wore braces to improve their physical fitness parameters in response to exercise . These data indicate that the use of a brace may be an effective way to prevent the development of anterior knee pain syndromes in persons participating in strenuous and intensive physical exercise Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles The purpose of this study was to evaluate the effect of a health education intervention on running injuries . The intervention consisted of information on , and the sub sequent performance of , st and ardized warm-up , cool- down , and stretching exercises . Four hundred twenty- one male recreational runners were matched for age , weekly running distance , and general knowledge of preventing sports injuries . They were r and omly split into an intervention and a control group : 167 control and 159 intervention subjects participated throughout the study . During the 16-week study , both groups kept a daily diary on their running distance and time , and reported all injuries . In addition , the intervention group was asked to note compliance with the st and ardized program . At the end of the study period , knowledge and attitude were again measured . There were 23 injuries in the control group and 26 in the intervention group . Injury incidence for control and intervention sub jects was 4.9 and 5.5 running injuries per 1000 hours , respectively . The intervention was not effective in re ducing the number of running injuries ; it proved signifi cantly effective ( P < 0.05 ) in improving specific knowl edge of warm-up and cool-down techniques in the intervention group . This positive change can perhaps be regarded as a first step on the way to a change of behavior , which may eventually lead to a reduction of running injuries A prospect i ve controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities . The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Isl and , South Carolina . Polymer and st and ard mesh insoles were systematic ally distributed in boots that were issued to members of odd and even numbered platoons . The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training . To control for the confounding effects of running in running shoes , which occurred for about one and one-half hours per week for the first five weeks , we also examined the association of age of shoes and cost of shoes with injury incidence . A slight trend of increasing stress injuries by increasing age of shoes was observed . However , this trend did not account for the similarity of rates in the two insole groups . In addition , we observed a strong trend of decreasing stress injury rate by history of increasing physical activity , as well as a higher stress injury rate in White compared to Black recruits . The results of the trial were not altered after controlling for these factors . This prospect i ve study confirms previous clinical reports of the association of stress fractures with physical activity history . The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits . The findings are relevant to civilian population This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training . Prior to training , ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-r and om procedure . The stretch group stretched calf muscles under supervision prior to all intense exercise . The control group stretched upper limb muscles instead . Forty-eight injuries were recorded . Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury ( p = 0.03 ) . Definitive evidence of an effect of stretching on injury risk was not found ( p = 0.76 ) , but the sample size may have been insufficient to detect such an effect PURPOSE This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury . METHODS 1538 male army recruits were r and omly allocated to stretch or control groups . During the ensuing 12 wk of training , both groups performed active warm-up exercises before physical training sessions . In addition , the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up . The control group did not stretch . RESULTS 333 lower-limb injuries were recorded during the training period , including 214 soft-tissue injuries . There were 158 injuries in the stretch group and 175 in the control group . There was no significant effect of preexercise stretching on all-injuries risk ( hazard ratio [ HR ] = 0.95 , 95 % CI 0.77 - 1.18 ) , soft-tissue injury risk ( HR = 0.83 , 95 % CI 0.63 - 1.09 ) , or bone injury risk ( HR = 1.22 , 95 % CI 0.86 - 1.76 ) . Fitness ( 20-m progressive shuttle run test score ) , age , and enlistment date all significantly predicted injury risk ( P < 0.01 for each ) , but height , weight , and body mass index did not . CONCLUSION A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinical ly meaningful reductions in risk of exercise-related injury in army recruits . Fitness may be an important , modifiable risk factor |
13,413 | 30,483,992 | Conclusion Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients , with no severe adverse effects . | Background Based on the results of r and omized , double-blind , placebo-controlled trials , the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain controversial .
We performed a meta- analysis to evaluate the efficacy and safety of edaravone in the treatment of this disease . | Objectives and methods : Compared to age-matched healthy controls ( n = 55 ) , patients with amyotrophic lateral sclerosis ( ALS ) ( n = 26 ) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 ( % CoQ10 ) in total plasma coenzyme Q10 , a significantly decreased level of plasma uric acid , and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids ( FFA ) . Therefore , the efficacy of edaravone , a radical scavenger , in these ALS patients was examined . Results and discussion : Among 26 ALS patients , 17 received edaravone ( 30 mg/day , one to four times a week ) for at least 3 months , and 13 continued for 6 months . Changes in revised ALS functional rating scale ( ALSFRS-R ) were significantly smaller in these patients than in edaravone-untreated ALS patients ( n = 19 ) . Edaravone administration significantly reduced excursions of more than one st and ard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids , plasma markers of tissue oxidative damage , in the satisfactory progress group ( ΔALSFRS-R ≥ 0 ) as compared to the ingravescent group ( ΔALSFRS-R < −5 ) . Edaravone treatment increased plasma uric acid , suggesting that it is an effective scavenger of peroxynitrite . However , edaravone administration did not decrease % CoQ10 . Therefore , combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients Amyotrophic lateral sclerosis ( ALS ) is a neurodegenerative disease that currently has no cure . At present , the only approved treatment for ALS is Riluzole , a glutamate release blocker that improves life expectancy by 3–6 months . ALS-Endotherapia ( GEMALS ) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment . A total of 31 patients with ALS were assessed in the current study . Deceleration of the disease was observed in 83.87 % ( P<0.0001 ) of patients and mean life expectancy was increased by 38 months . Motor functions , including breathing , walking , salivation , speech , swallowing and writing , were also improved in patients treated with GEMALS . The results of the present study demonstrate that long-term treatment with GEMALS has a curative effect in patients with ALS . Furthermore , the overall effectiveness of GEMALS was assessed using the ALS Assessment Question naire . The score improvement was 76.2 and 100 % for men and women , respectively ( P<0.0001 ) , compared with the worldwide reference score . The present study provides a promising basis for the use of GEMALS as a therapeutic treatment for patients with ALS ; however , these results must be confirmed in a double-blinded and r and omized clinical trial The ALS Functional Rating Scale ( ALSFRS ) is a vali date d rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis ( ALS ) . One weakness of the ALSFRS as originally design ed was that it granted disproportionate weighting to limb and bulbar , as compared to respiratory , dysfunction . We have now vali date d a revised version of the ALSFRS , which incorporates additional assessment s of dyspnea , orthopnea , and the need for ventilatory support . The Revised ALSFRS ( ALSFRS-R ) retains the properties of the original scale and shows strong internal consistency and construct validity . ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile , indicating that the quality of function is a strong determinant of quality of life in ALS Amyotrophic lateral sclerosis ( ALS ) is a rare disease involving selective and progressive degeneration and disappearance of motor neurons . Oxidative stress is believed to contribute to its pathogenesis . We have investigated the efficacy and safety of edaravone , a free radical scavenger previously approved for treatment of acute cerebral infa rct ion , in ALS patients . Within an open trial design , 20 subjects with ALS received either 30 mg ( 5 subjects ) or 60 mg ( 15 subjects ) of edaravone via intravenous drip once per day . Two weeks of administration was followed by a two‐week observation period . This four‐week cycle was repeated six times . The primary endpoint was the change in the revised ALS functional rating scale ( ALSFRS‐R ) score , while the secondary endpoint was 3‐nitrotyrosine ( 3NT ) level in cerebrospinal fluid ( CSF ) . Efficacy was evaluated in the 60 mg group . During the six‐month treatment period , the decline in the ALSFRS‐R score ( 2.3±3.6 points ) was significantly less than that in the six months prior to edaravone administration ( 4.7±2.1 points ) ; the difference between the two was 2.4±3.5 points ( Wilcoxon signed rank test , p = 0.039 ) . In almost all patients , CSF 3NT , a marker for oxidative stress , was markedly reduced to almost undetectable levels at the end of the six‐month treatment period . Data from the present study suggest that edaravone is safe and may delay the progression of functional motor disturbances by reducing oxidative stress in ALS patients Edaravone is a free-radical scavenger , an agent being widely used for cerebral ischemia in Japan . To evaluate its efficacy for possible treatment of amyotrophic lateral sclerosis ( ALS ) , we performed a r and omized blind trial in ALS model mice . After identification of the clinical onset in each female G93A mutant SOD1 transgenic mouse , we intraperitoneally administered multiple doses of edaravone to the mice and observed their motor symptoms . We also counted the number of lumbar motoneurons , determined the 3-nitrotyrosine/tyrosine ratio , and evaluated the abnormal SOD1 aggregation in the spinal cord at the 10th day after the edaravone injection . Edaravone significantly slowed the motor decline of the transgenic mice . The remaining motoneurons were significantly preserved in the higher-dose edaravone-administered group , and the 3-nitrotyrosine/tyrosine ratios were reduced dose-dependently . Intriguingly , the area of abnormal SOD1 deposition in the spinal cord was significantly decreased in the higher-dose edaravone-administered group . Our results indicate that edaravone was effective to slow symptom progression and motor neuron degeneration in the ALS model mice . These favorable actions might be attributable to the yet unidentified mechanism responsible for reducing the deposition of mutant SOD1 OBJECTIVES To test the utility of a new , easy to administer instrument for assessing activities of daily living in patients with amyotrophic lateral sclerosis ( ALS ) , to vali date its accuracy , and to assess its ability to record disease progression in patients with ALS against other functional scales , quantitative isometric muscle testing , and global assessment scales . DESIGN Serial assessment s of patients who presented to four ALS treatment centers in two multicenter studies . PATIENTS Study 1 ( cross-sectional ) evaluated 75 consecutive patients who presented to four ALS treatment centers during a 2-month period . Study 2 ( longitudinal ) evaluated the progression of 53 patients who were enrolled in a multicenter , phase I-II clinical trial of recombinant human ciliary neurotrophic factor for treatment of ALS . OUTCOME MEASURES The ALS Functional Rating Scale ( ALSFRS ) was compared with quantitative myometry and with other measures of daily function in patients with ALS both cross-sectionally and longitudinally . RESULTS The first study of 75 patients evaluated the internal consistency , the test-retest reliability , and the construct validity of the ALSFRS . Internal consistency and test-retest reliability were high . Patient self-rating of upper- and lower-extremity-dependent tasks were highly correlated with measures of upper- and lower-extremity strength , respectively . Thus , the ALSFRS has good construct validity . In the second study , ALSFRS scores declined in t and em with deterioration in motor and pulmonary function , indicating its sensitivity to change . CONCLUSIONS The ALSFRS is a useful instrument for evaluation of functional status and functional change in patients with ALS . Its results are in close agreement with objective measures of muscle strength and pulmonary function . The ALSFRS may be used as a screening measure for entry into clinical trials , as a surrogate measure of function in situations in which muscle strength can not be measured directly , or as an adjunct to myometry Objective : To replicate the beneficial effect of brain-derived neurotrophic factor ( BDNF ) in 1,135 ALS patients in a multicenter trial . Background : In a phase I through II study , BDNF appeared to increase survival and retard loss of pulmonary function in ALS patients . Methods : Patients were r and omized to placebo , or 25 or 100 μg/kg BDNF for 9 months . Results : The study failed to show benefit of BDNF treatment for the primary end points . Survival in patients treated with 25 μg/kg BDNF was identical to placebo , but there was a trend toward increased survival in the 100-μg/kg group . As a whole , survival was better than anticipated when planning the study . The 9-month probability of survival was approximately 85 % across all groups . This diminished the power of the study . Among the 60 % of patients with baseline forced vital capacity of ≤91 % , survival was significantly greater for 100 μg/kg BDNF versus placebo . For the 20 % of patients treated with 100 μg/kg BDNF reporting altered bowel function as an adverse effect of BDNF in the first 2 weeks of dosing , defined as BDNF “ responders , ” 9-month survival was significantly better than for placebo ( 97.5 % versus 85 % ) . Conclusions : Although the primary end point analysis failed to demonstrate a statistically significant survival effect of BDNF in ALS , post hoc analyses showed that those ALS patients with early respiratory impairment and those developing altered bowel function showed statistically significant benefit . Further clinical trials of BDNF using either intrathecal delivery or high-dose subcutaneous administration are in progress Abstract Our objective was to explore the efficacy and safety of edaravone in amyotrophic lateral sclerosis ( ALS ) patients with a Japan ALS severity classification of Grade 3 . In a 24-week , double-blind , r and omized study , 25 patients who met all of the following criteria were enrolled : Japan ALS severity classification Grade 3 ; definite , probable , or probable-laboratory supported ALS ( El Escorial/revised Airlie House ) ; forced vital capacity ( % FVC ) ≥60 % ; duration of disease ≤3 years at consent ; and change in the revised ALS functional rating scale ( ALSFRS-R ) score of –1 to –4 points during the 12-week pre-observation period . Patients received edaravone ( n = 13 ) or placebo ( n = 12 ) for six cycles . The efficacy outcome was change in the ALSFRS-R score . The least-squares mean change in the ALSFRS-R score ± st and ard error during the 24-week treatment was –6.52 ± 1.78 in the edaravone group and –6.00 ± 1.83 in the placebo group ; the difference of –0.52 ± 2.46 was not statistically significant ( p = 0.835 ) . Incidence of adverse events was 92.3 % ( 12/13 ) in the edaravone group and 100.0 % ( 12/12 ) in the placebo group . There was no intergroup difference in the changes in the ALSFRS-R score . The incidences of adverse events were similar in the two groups |
13,414 | 28,620,456 | We found a contrast between st and ardised review methods and accuracy of the measurements used . | Background : Exercise may activate a brown adipose-like phenotype in white adipose tissue .
The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha ( PGC-1a ) and fibronectin type III domain-containing protein 5 ( FNDC5 ) in muscle , circulating Irisin and uncoupling protein one ( UCP1 ) of white adipocytes in humans . | To eluci date the effects of endurance training on circulating irisin levels in young and middle-aged/older adults , and to determine the association between endurance training-induced alteration of irisin and reduction in body fat . Twenty-five healthy young ( age 21 ± 1 years ; 16 men , 9 women ) and 28 healthy middle-aged/older adults ( age 67 ± 8 years ; 12 men , 16 women ) participated in the study . Each age cohort was divided into two groups : the endurance-training group ( 14 young , 14 middle-aged/older ) and the control group . Subjects in the training groups completed an 8-week endurance-training program ( cycling at 60 - 70 % peak oxygen uptake [ V˙O2peak ] for 45 min , 3 days/week ) . Before and after the intervention , we evaluated serum irisin level , V˙O2peak , and body composition . The increase in V˙O2peak in the young and middle-aged/older training groups after the intervention period was significantly greater than those in the young and middle-aged/older control groups ( P < 0.05 ) . Serum irisin level was significantly increased in the middle-aged/older training group after the intervention period ( P < 0.01 ) , but not in the young training group . Furthermore , in the middle-aged/older training group , the endurance training-induced reduction in visceral adipose tissue area was negatively correlated with the change in serum irisin level ( r = −0.54 , P < 0.05 ) . These results suggest a possible role for secreted irisin in the exercise-induced alteration of abdominal visceral fat in middle-aged and older adults Aim /hypothesis Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles . Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species ( ROS ) release in skeletal muscle of obese participants with and without type 2 diabetes . Methods Type 2 diabetic men ( n = 13 ) and control ( n = 14 ) participants matched for age , BMI and physical activity completed 10 weeks of aerobic training . Pre- and post-training muscle biopsies were obtained before a euglycaemic – hyperinsulinaemic clamp and used for measurement of respiratory function and ROS release in isolated mitochondria . Results Training significantly increased insulin sensitivity , maximal oxygen consumption and muscle mitochondrial respiration with no difference between groups . When expressed in relation to a marker of mitochondrial density ( intrinsic mitochondrial respiration ) , training result ed in increased mitochondrial ADP-stimulated respiration ( with NADH-generating substrates ) and decreased respiration without ADP . Intrinsic mitochondrial respiration was not different between groups despite lower insulin sensitivity in type 2 diabetic participants . Mitochondrial ROS release tended to be higher in participants with type 2 diabetes . Conclusions /interpretationAerobic training improves muscle respiration and intrinsic mitochondrial respiration in untrained obese participants with and without type 2 diabetes . These adaptations demonstrate an increased metabolic fitness , but do not seem to be directly related to training-induced changes in insulin sensitivity OBJECTIVE Exercise twice every other day has been shown to lead to increasing peroxisome proliferator receptor γ coactivator-1α ( PGC-1α ) expression ( up-stream factor of irisin ) via lowered muscle glycogen level during second of exercise compared with exercise once daily . This study determined the influence of 4weeks of sprint training ( training once daily vs. twice every other day ) on the serum irisin concentration . MATERIAL S AND METHODS Twenty healthy males ( 20.9±1.3years ) were assigned r and omly to either the SINGLE or REPEATED group ( n=10 per group ) . The subjects in the SINGLE group participated in a sprint training session once daily ( 5days per week ) , whereas those in the REPEATED group performed two consecutive training sessions on the same day with a 1-h rest between sessions ( 2 - 3days per week ) . Both groups completed 20 training sessions over 4weeks . Each training session consisted of three consecutive 30-s maximal pedaling exercises with a 10-min rest between sets . Blood sample s were collected before and after training period ( 48h after completing the last training session ) . RESULTS The serum irisin concentration decreased significantly after training in each group ( SINGLE , 338.5±77.8 to 207.6±64.6ng/mL ; REPEATED , 329.5±83.9 to 234.2±72.8ng/mL , p<0.05 ) . The plasma interleukin-6 ( IL-6 ) concentration tended to be lower after training in both groups ( main effect for period , p=0.054 ) . However , there was no significant difference in the serum irisin or plasma IL-6 concentration between groups after training . The serum high-molecular-weight adiponectin concentration did not change significantly after training in either group . CONCLUSION Sprint training for 4weeks significantly decreased the resting serum irisin concentration , despite different training programs ( training once daily vs. twice every other day ) CONTEXT The myokine irisin may increase energy expenditure and affect metabolism . OBJECTIVE The objective of the study was to eluci date predictors of irisin and study whether circulating irisin may have day-night rhythm in humans . DESIGN This was an observational , cross-sectional study with an additional 24-hour prospect i ve observational arm ( day-night rhythm sub study ) and two prospect i ve interventional arms ( mixed meal sub study and exercise sub study ) . SETTING The study was conducted at the Hellenic Military School of Medicine ( Thessaloniki , Greece ) . PATIENTS AND INTERVENTIONS One hundred twenty-two healthy , young individuals were subjected to anthropometric and body composition measurements , and their eating and exercise behavior profiles were assessed with vali date d question naires . Subgroups were subjected to day-night rhythm , st and ardized meal ingestion , and 30-minute aerobic exercise studies . MAIN OUTCOME MEASURES Circulating irisin levels were measured . RESULTS Ιrisin levels were lower in males than females ( P = .02 ) after adjustment for lean body mass , which was its major determinant . Irisin levels followed a day-night rhythm ( P < .001 ) with peak at 9:00 pm . Irisin levels were increased at the end of exercise ( 84.1 ± 10.0 vs 105.8 ± 14.3 ng/mL ; P < .001 ) . Irisin levels were not affected by intake of a st and ardized meal and were not associated with caloric intake or diet quality . CONCLUSIONS In healthy , young individuals , circulating irisin displays a day-night rhythm , is correlated with lean body mass , and increases acutely after exercise RATIONALE The newly discovered myokine irisin has been proposed to affect obesity and metabolism by promoting browning of white adipose tissue . However , clinical and functional studies on the association of irisin with obesity , muscle mass , and metabolic status remain controversial . Here we assessed the effect of 4 distinct exercise regimens on serum irisin levels in children and young adults and systematic ally evaluated the influence of diurnal rhythm , anthropometric and metabolic parameters , and exercise on irisin . RESULTS Serum irisin levels did not show diurnal variations , nor were they affected by meal intake or defined glucose load during oral glucose tolerance testing . Irisin levels decreased with age . In adults , irisin levels were higher in men than in women , and obese subjects had significantly higher levels than lean control subjects . Irisin levels were closely correlated with muscle-associated bioimpedance parameters such as fat-free mass and body cell mass . Of the 4 exercise regimens that differed in duration and intensity , we identified a clear and immediate increase in serum irisin levels after acute strenuous exercise ( cycling ergometry ) and a 30-minute bout of intensive exercise in children and young adults , whereas longer ( 6 weeks ) or chronic ( 1 year ) increases in physical activity did not affect irisin levels . SUMMARY We show that irisin levels are affected by age , sex , obesity , and particularly muscle mass , whereas diurnal rhythm and meals do not contribute to the variation in irisin levels . Short bouts of intensive exercise but not long-term elevations in physical activity , acutely and transiently increase serum irisin levels in children and adults |
13,415 | 30,580,468 | Substantial improvements in muscular hypertrophy and maximal force production were reported regardless of training intensity .
High-intensity ( ≥70 % ) contractions are required for improving tendon structure and function .
Additionally , long muscle length training results in greater transference to dynamic performance .
Despite relatively few studies meeting the inclusion criteria , this review provides practitioners with insight into which isometric training variables ( eg , joint angle , intensity , intent ) to manipulate to achieve desired morphological and neuromuscular adaptations | Isometric training is used in the rehabilitation and physical preparation of athletes , special population s , and the general public .
However , little consensus exists regarding training guidelines for a variety of desired outcomes .
Underst and ing the adaptive response to specific loading parameters would be of benefit to practitioners .
The objective of this systematic review , therefore , was to detail the medium- to long-term adaptations of different types of isometric training on morphological , neurological , and performance variables . | PURPOSE The aim of this study was to compare the effects of isometric training performed with progressive versus rapid rate of contraction on the knee extensor neuromuscular properties over a 7-wk period . METHODS Sixteen healthy male subjects trained quadriceps femoris muscle in a leg extension machine three times a week during 7 wk . The training sessions consisted of six sets of six maximal isometric contractions . A first group trained by performing progressive contractions lasting 4 s , whereas a second group performed contractions with a rapid rate of contraction ( i.e. , ballistic contractions ) lasting about 1 s. RESULTS Both groups significantly increased the isometric and isokinetic voluntary torque , and the respective absolute or relative gains were comparable . Isometric training performed with progressive rate of contraction affected the evoked action potential ( M wave ) of the vastus lateralis muscle and not the related twitch properties . On the other h and , the isometric training completed with ballistic contractions significantly modified the twitch contractile properties of the knee extensors and not the associated M waves of both vastus medialis and vastus lateralis . CONCLUSION Knee extensors adapted specifically their neuromuscular properties to the type of rate of contraction performed during 7-wk isometric resistance training . Progressive isometric contractions produced modifications of the nervous system at peripheral level ( i.e. , muscle membrane electrical activity ) , whereas ballistic isometric contractions affected the knee extensor contractile muscle properties ( i.e. , excitation-contraction coupling ) INTRODUCTION We used transcranial magnetic stimulation ( TMS ) to investigate 3 weeks of unilateral leg strength training on ipsilateral motor cortex ( iM1 ) excitability , and short-latency intracortical inhibition ( SICI ) . METHODS Right leg dominant participants ( n = 14 ) were r and omly divided into either a strength training ( ST ) or control group . The ST group completed 9 training sessions ( 4 sets of 6 to 8 repetitions of single right leg squats ) . RESULTS We observed a 41 % increase in right leg strength , and a 35 % increase in strength of the untrained left leg ( P < 0.01 ) . There was a significant increase in motor evoked potential ( MEP ) amplitude recruitment curve for the untrained left leg ( P < 0.01 ) . SICI of the iM1 decreased by 21 % for the untrained left leg ( P < 0.01 ) . CONCLUSIONS The findings provide evidence for corticomotor adaptation for unilateral leg strength training within the iM1 that is modulated by changes in interhemispheric inhibition Abstract The present study investigated the effects of different intensities of resistance training ( RT ) on elbow flexion and leg press one-repetition maximum ( 1RM ) and muscle cross-sectional area ( CSA ) . Thirty men volunteered to participate in an RT programme , performed twice a week for 12 weeks . The study employed a within-subject design , in which one leg and arm trained at 20 % 1RM ( G20 ) and the contralateral limb was r and omly assigned to one of the three conditions : 40 % ( G40 ) ; 60 % ( G60 ) , and 80 % 1RM ( G80 ) . The G20 started RT session with three sets to failure . After G20 training , the number of sets was adjusted for the other contralateral limb conditions with volume-matched . CSA and 1RM were assessed at pre , post-6 weeks , and post-12 weeks . There was time effect for CSA for the vastus lateralis ( VL ) ( 8.9 % , 20.5 % , 20.4 % , and 19.5 % ) and elbow flexors ( EF ) ( 11.4 % , 25.3 % , 25.1 % , and 25 % ) in G20 , G40 , G60 , and G80 , respectively ( p > .05 ) . G80 showed higher CSA than G20 for VL ( 19.5 % vs. 8.9 % ) and EF ( 25 % vs. 11.4 % ) at post-12 weeks ( p < .05 ) . There was time effect for elbow flexion and unilateral leg press strength for all groups post-12 weeks ( p < .05 ) . However , the magnitude of increase was higher in G60 and G80 . In conclusion , when low to high intensities of RT are performed with volume-matched , all intensities were effective for increasing muscle strength and size ; however , 20 % 1RM was suboptimal in this regard , and only the heavier RT intensity ( 80 % 1RM ) was shown superior for increasing strength and CSA compared to low intensities Objective To assess whether three-dimensional imaging of the Achilles tendon by ultrasonographic tissue characterisation ( UTC ) can differentiate between symptomatic and asymptomatic tendons . Design Case-control study . Setting Sports Medical Department of the Hague Medical Centre . Patients Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included . The “ matched ” control group consisted of 26 asymptomatic tendons . Interventions Symptomatic and asymptomatic tendons were scanned using the UTC procedure . One research er performed the ultrasonographic data collection . These blinded data were r and omised , and outcome measures were determined by two independent observers . Main outcome measurements The raw ultrasonographic images were analysed with a custom design ed algorithm that quantifies the three-dimensional stability of echo patterns , qua intensity and distribution over contiguous transverse images . This threedimensional stability was related to tendon structure in previous studies . UTC categorises four different echotypes that represent ( I ) highly stable ; ( II ) medium stable ; ( III ) highly variable and ( IV ) constantly low intensity and variable distribution . The percentages of echo-types were calculated , and the maximum tendon thickness was measured . Finally , the inter-observer reliability of UTC was determined . Results Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons ( 51.5 % vs 76.6 % , p<0.001 ) , thus less three-dimensional stability of the echo pattern . The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group ( p<0.001 ) . The Intraclass Correlation Coefficient ( ICC ) for the interobserver reliability of determining the echo-types I+II was 0.95 . The ICC for tendon thickness was 0.84 . Conclusion UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons . As such , UTC might be useful to monitor treatment protocol Objective : This study aim ed to compare the immediate analgesic effects of 2 resistance programs in in-season athletes with patellar tendinopathy ( PT ) . Resistance training is noninvasive , a principle stimulus for corticospinal and neuromuscular adaptation , and may be analgesic . Design : Within-season r and omized clinical trial . Data analysis was conducted blinded to group . Setting : Subelite volleyball and basketball competitions . Participants : Twenty jumping athletes aged more than 16 years , participating in games/trainings 3 times per week with clinical ly diagnosed PT . Interventions : Two quadriceps resistance protocol s were compared ; ( 1 ) isometric leg extension holds at 60 degrees knee flexion ( 80 % of their maximal voluntary isometric contraction ) or ( 2 ) isotonic leg extension ( at 80 % of their 8 repetition maximum ) 4 times per week for 4 weeks . Time under load and rest between sets was matched between groups . Main Outcome Measures : ( 1 ) Pain ( 0 - 10 numerical rating score ) during single leg decline squat ( SLDS ) , measured preintervention and postintervention sessions . ( 2 ) VISA-P , a question naire about tendon pain and function , completed at baseline and after 4 weeks . Results : Twenty athletes with PT ( 18 men , mean 22.5 ± 4.7 years ) participated ( isotonic n = 10 , isometric n = 10 ) . Baseline median SLDS pain was 5/10 for both groups ( isotonic range 1 - 8 , isometric range 2 - 8 ) . Isometric contractions produced significantly greater immediate analgesia ( P < 0.002 ) . Week one analgesic response positively correlated with improvements in VISA-P at 4 weeks ( r2 = 0.64 ) . Conclusions : Both protocol s appear efficacious for in-season athletes to reduce pain , however , isometric contractions demonstrated significantly greater immediate analgesia throughout the 4-week trial . Greater analgesia may increase the ability to load or perform Abstract The eccentric contraction mode was proposed to be the primary stimulus for optimum angle ( angle at which peak torque occurs ) shift . However , the training range of motion ( or muscle excursion range ) could be a stimulus as important . The aim of this study was to assess the influence of the training range of motion stimulus on the hamstring optimum length . It was hypothesised that performing a single set of concentric contractions beyond optimal length ( seated at 80 ° of hip flexion ) would lead to an immediate shift of the optimum angle to longer muscle length while performing it below ( supine at 0 ° of hip flexion ) would not provide any shift . Eleven male participants were assessed on an isokinetic dynamometer . In both positions , the test consisted of 30 consecutive knee flexions at 4.19 rad · s−1 . The optimum angle was significantly shifted by ∼15 ° in the direction of longer muscle length after the contractions at 80 ° of hip flexion , while a non-significant shift of 3 ° was found at 0 ° . The hamstring fatigability was not influenced by the hip position . It was concluded that the training range of motion seems to be a relevant stimulus for shifting the optimum angle to longer muscle length . Moreover , fatigue appears as a mechanism partly responsible for the observed shift BACKGROUND AND PURPOSE The purpose of this study was to examine the effect of isometric training of the quadriceps femoris muscles , at different joint angles , on torque production and electromyographic ( EMG ) activity . SUBJECTS One hundred seven women were r and omly assigned to one of four groups . Three groups trained with isometric contractions three times per week at a knee flexion angle of 30 , 60 , or 90 degrees . The fourth group , which served as a control , did not exercise . METHODS Isometric torque was measured using a dynamometer , and EMG activity was measured using a multichannel EMG system . Measurements were obtained during maximal isometric contraction of the quadriceps femoris muscles at 15-degree increments from 15 to 105 degrees of knee flexion . Measurements were taken before and after 8 weeks of training . RESULTS Following isometric exercise , increased torque and EMG activity occurred not only at the angle at which subjects exercised , but also at angles in the range of motion at which exercise did occur . Further analyses indicated that exercising in the lengthened position for the quadriceps femoris muscles ( 90 degrees of knee flexion ) produced increased torque across all angles measured and appeared to be the more effective position for transferring strength and EMG activity to adjacent angles following isometric training as compared with the shorter positions of the muscle ( 30 degrees and 60 degrees of knee flexion ) . CONCLUSION AND DISCUSSION These findings suggest that an efficient method for increasing isometric knee extension torque and EMG activity throughout the entire range of motion is to exercise with the quadriceps femoris muscles in the lengthened position Background Few interventions reduce patellar tendinopathy ( PT ) pain in the short term . Eccentric exercises are painful and have limited effectiveness during the competitive season . Isometric and isotonic muscle contractions may have an immediate effect on PT pain . Methods This single-blinded , r and omised cross-over study compared immediate and 45 min effects following a bout of isometric and isotonic muscle contractions . Outcome measures were PT pain during the single-leg decline squat ( SLDS , 0–10 ) , quadriceps strength on maximal voluntary isometric contraction ( MVIC ) , and measures of corticospinal excitability and inhibition . Data were analysed using a split-plot in time-repeated measures analysis of variance ( ANOVA ) . Results 6 volleyball players with PT participated . Condition effects were detected with greater pain relief immediately from isometric contractions : isometric contractions reduced SLDS ( mean±SD ) from 7.0±2.04 to 0.17±0.41 , and isotonic contractions reduced SLDS ( mean±SD ) from 6.33±2.80 to 3.75±3.28 ( p<0.001 ) . Isometric contractions released cortical inhibition ( ratio mean±SD ) from 27.53%±8.30 to 54.95%±5.47 , but isotonic contractions had no significant effect on inhibition ( pre 30.26±3.89 , post 31.92±4.67 ; p=0.004 ) . Condition by time analysis showed pain reduction was sustained at 45 min postisometric but not isotonic condition ( p<0.001 ) . The mean reduction in pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic . MVIC increased significantly following the isometric condition by 18.7±7.8 % , and was significantly higher than baseline ( p<0.001 ) and isotonic condition ( p<0.001 ) , and at 45 min ( p<0.001 ) . Conclusions A single resistance training bout of isometric contractions reduced tendon pain immediately for at least 45 min postintervention and increased MVIC . The reduction in pain was paralleled by a reduction in cortical inhibition , providing insight into potential mechanisms . Isometric contractions can be completed without pain for people with PT . The clinical implication s are that isometric muscle contractions may be used to reduce pain in people with PT without a reduction in muscle strength Intervention programs are often sought to strengthen the Achilles tendon ( AT ) due to its high injury rate . Long rest periods between loading cycles have been found to increase collagen synthesis by tenocytes , suggesting rest duration may be important for tendon adaptation in vivo ; however , exercise programs comparing long and short rest duration have not been directly compared . Fourteen adults completed a 12-week progressive training intervention ; training sessions consisted of 5 × 10 isometric plantarflexion contractions each of 3-s duration performed at 90 % of MVC three times weekly . Each leg was r and omly allocated to long ( LRT , 10-s rest ) or short rest training ( SRT , 3-s rest ) . We hypothesized that the leg allocated to LRT would demonstrate superior AT collagen organization compared to the leg receiving SRT , which would be related to improved biomechanical function . AT collagen organization and morphology were measured using ultrasound tissue characterization . AT properties were assessed before and after the intervention using a combination of dynamometry , ultrasound imaging , EMG , and motion capture . Contrary to our hypothesis , collagen organization did not improve following either training protocol ; conversely , an unexpected decrease in echotype I proportion was seen after SRT ( P<.001 ) but not LRT ( P=.58 ) , indicating an apparent protective effect of rest on collagen organization during isometric training . In contrast , AT adaptation was not appreciably enhanced by increasing intercycle rest duration ; both protocol s were equally effective at inducing significant strength gains and AT mechanical and material adaptation ( P≤.001 ) . Further research is necessary to identify optimal loading characteristics for injury prevention and rehabilitation Silva , HR , Couto , BP , and Szmuchrowski , LA . Effects of mechanical vibration applied in the opposite direction of muscle shortening on maximal isometric strength . J Strength Cond Res 22 : 1031 - 1036 , 2008-Most studies about human responses to mechanical vibrations involve whole-body vibration and vibration applied perpendicularly to the tendon or muscle . The aim of the present study was to verify the effects of mechanical vibration applied in the opposite direction of muscle shortening on maximal isometric strength of the flexor muscles of the elbow due to neural factors . Conventional isometric training with maximal isometric contractions ( MVCs ) and isometric training with vibrations were compared . Nineteen untrained males , ages 24 ± 3.28 years , were divided into 2 training groups . Group 1 performed conventional isometric training and group 2 isometric training with mechanical vibrations ( frequency of 8 Hz and amplitude of 6 mm ) . Both groups executed 12 MVCs with a duration of 6 seconds and 2-minute intervals between the repetitions . The subjects trained 3 times per week for 4 weeks . The strength of the group subjected to vibrations increased significantly by 26 ± 11 % ( p < 0.05 ) , whereas the strength of the group with conventional isometric training increased only 10 ± 5 % ( p < 0.05 ) . These data suggest that training with vibrations applied in the opposite direction of muscle shortening enhances the mechanism of involuntary control of muscle activity and may improve strength in untrained males . Since these findings were in untrained males , further studies with athletes are necessary in order to generalize the results to athletes ' training , although it seems that it would be possible The aim of this study was to explore and compare the magnitude and time-course of the shift in the angle-force curves obtained from maximal voluntary contractions of the elbow flexors , both before and 4 consecutive days after eccentric and isometric exercise . The maximal isometric force of the elbow flexors of fourteen young male volunteers was measured at five different elbow angles between 50 ° and 160 ° . Subjects were then divided into two groups : the eccentric group ( ECC , n=7 ) and the isometric group ( ISO , n=7 ) . Subjects in the ECC group performed 50 maximal voluntary eccentric contractions of the elbow flexors on an isokinetic dynamometer ( 30 ° .s−1 ) , while subjects in the ISO group performed 50 maximal voluntary isometric muscle contractions with the elbow flexors at a lengthened position . Following the ECC and ISO exercise protocol s , maximal isometric force at the five angles , muscle soreness , and the relaxed ( RANG ) and flexed ( FANG ) elbow angles were measured at 24 h intervals for 4 days . All results were presented as the mean and st and ard error , and a quadratic curve was used to model the maximal isometric force data obtained at the five elbow angles . This approach not only allowed us to mathematically describe the angle-force curves and estimate the peak force and optimum angle for peak force generation , but also enabled us to statistically compare the shift of the angle-force curves between and within groups . A large and persistent shift of the angle-force curve towards longer muscle lengths was observed 1 day after eccentric exercise ( P<0.01 ) . This result ed in a ~16 ° shift of the optimum angle for force generation , which remained unchanged for the whole observation period . A smaller but also persistent shift of the angle-force curve was seen after isometric exercise at long muscle length ( P<0.05 ; shift in optimum angle ~5 ° ) . ECC exercise caused more muscle damage than ISO exercise , as indicated by the greater changes in RANG and ratings of muscle soreness ( P<0.05 ) . It was suggested that the shift in the angle-force curve was proportional to the degree of muscle damage and may be explained by the presence of overstretched sarcomeres that increased in series compliance of the muscle PURPOSE This study was aim ed at exploring the transferability of short range of motion ( RoM ) isokinetic conditioning on quadriceps performance inside and outside the trained range . METHODS Fifty-five women were r and omly assigned to one of four groups : G1 ( N = 14 ) and G2 ( N = 14 ) trained concentrically at 30 and 90degrees x s(-1 ) , respectively , whereas G3 ( N = 13 ) and G4 ( N = 14 ) trained similarly but using the eccentric mode . All four groups trained within 30 - 60degrees of knee flexion . The training paradigm consisted of 4 sets of 10 maximal repetitions , 3x wk(-1 ) for a total period of 6 wk . Before the training period and 2 d after its termination , the isokinetic work output ( Wisk ) was assessed within three angular RoM : 85 - 60degrees ( R1 ) , 60 - 30degrees ( R2 ) , and 30 - 5degrees ( R3 ) . Isometric peak extension moment ( PM ) and rate of force development ( RFD ) were evaluated at 10degrees , 45degrees and 80degrees . RESULTS Significant increases were observed in the isometric output ( at all three angles ) , Wisk ( in R1 and R2 ) , and the RFD ( 45degrees ) . The PM increased significantly more in G3 and G4 compared with G1 and G2 , evidencing specificity of contraction mode . CONCLUSION These findings point out to the potential benefits of short RoM conditioning , particularly in those cases where , during specific phases of rehabilitation , a wider RoM may be contraindicative Research considering combined vibration and strength training is extensive yet results are equivocal . However , to date there appears no research which has considered the combination of both direct vibration and whole --- body vibration when used in an isometric deadlift position . The aims of this study were to compare groups performing isometric training with and without direct and whole --- body vibration . Twenty four participants ( 19 - --24 years ) were r and omly divided into : isometric training with vibration ( ST+VT : n=8 ) , isometric training without vibration ( ST : n=8 ) , and control ( CON : n=8 ) . Within the training groups participants trained twice per week , for 6 weeks , performing 6 - --sets of maximal isometric deadlift contractions , increasing in duration from 30 seconds to 40 seconds ( weeks 1 - --6 ) . Hip and knee angle was maintained at 60 ° and 110 ° , respectively for both testing and training . Training sessions for ST+VT were identical to ST with the addition of a direct vibratory stimulus through h and ---held straps and whole --- body vibration via st and ing on vibration a platform . The amplitude remained constant ( 2 mm ) throughout the intervention whilst the frequency increased from 35Hz to 50Hz . Pre--- and post --- test isometric strength was measured using an isometric deadlift dynamometer . Results revealed significant increases in isometric strength for both ST+VT ( p < 0.001 , 23.8 % ) and ST ( p < 0.001 , 32.5 % ) compared to CON , with no significant differences between ST+VT and ST training groups . The present study provides evidence to suggest that there are no greater gains to be incurred by the addition of a vibratory stimulus to traditional strength training & NA ; Massey , C.D. , J. Vincent , M. Maneval , M. Moore , and J.T. Johnson . An analysis of full range of motion vs. partial range of motion training in the development of strength in untrained men . J. Strength Cond . Res . 18(3):518–521 . 2004.—The purpose of this investigation was to compare partial range of motion versus full range of motion training in the development of maximal strength . The bench press was used as the criterion measurement . The study was conducted over a 10‐week period with training sessions occurring twice per week . Subjects were divided into 3 groups . Group 1 ( N = 11 ) trained with 3 full range of motion sets on the bench press . Group 2 ( N = 15 ) trained with 3 partial range of motion sets . A partial repetition was defined as one that is beyond the sticking point 2 to 5 inches from full extension of the elbows . Group 3 ( N = 30 ) trained with a combination of partial and full range of motion sets . All subjects were pre‐ and posttested on the bench press through a full range of motion using a 1 repetition maximum . Each of the 3 groups demonstrated statistically significant increases in strength from pre‐ to posttest . No differences were found between groups . These findings appear to suggest that partial range of motion training can positively influence the development of maximal strength . Therefore , those involved in the strength and conditioning profession can confidently including this method as an adjunct to their normal training protocol s when working with individuals similar to those found in this investigation . It is suggested that additional research be conducted to further establish the effectiveness of partial range of motion training in developing maximal strength The present study aim ed to investigate the effect of isometric squat training on human tendon stiffness and jump performances . Eight subjects completed 12 weeks ( 4 days/week ) of isometric squat training , which consisted of bilateral leg extension at 70 % of maximum voluntary contraction ( MVC ) for 15 s per set ( 10 sets/day ) . Before and after training , the elongations of the tendon – aponeurosis complex in the vastus lateralis muscle and patella tendon were directly measured using ultrasonography while the subjects performed ramp isometric knee extension up to MVC . The relationship between the estimated muscle force and tendon elongation was fitted to a linear regression , the slope of which was defined as stiffness . In addition , performances in two kinds of maximal vertical jumps , i.e. squatting ( SJ ) and counter-movement jumps ( CMJ ) , were measured . The training significantly increased the volume ( P<0.01 ) and MVC torque ( P<0.01 ) of the quadriceps femoris muscle . The stiffness of the tendon – aponeurosis complex increased significantly from 51±22 ( mean ± SD ) to 59±24 N/mm ( P=0.04 ) , although that of the patella tendon did not change ( P=0.48 ) . The SJ height increased significantly after training ( P=0.03 ) , although the CMJ height did not ( P=0.45 ) . In addition , the relative difference in jump height between SJ and CMJ decreased significantly after training ( P=0.02 ) . These results suggest that isometric squat training changes the stiffness of human tendon – aponeurosis complex in knee extensors to act negatively on the effects of pre-stretch during stretch-shortening cycle exercises Aim : To examine if cross‐sectional area ( CSA ) differs along the length of the human patellar tendon ( PT ) , and if there is PT hypertrophy in response to resistance training Abstract Schoenfeld , BJ , Peterson , MD , Ogborn , D , Contreras , B , and Sonmez , GT . Effects of low- vs. high-load resistance training on muscle strength and hypertrophy in well-trained men . J Strength Cond Res 29(10 ) : 2954–2963 , 2015—The purpose of this study was to compare the effect of low- versus high-load resistance training ( RT ) on muscular adaptations in well-trained subjects . Eighteen young men experienced in RT were matched according to baseline strength and then r and omly assigned to 1 of 2 experimental groups : a low-load RT routine ( LL ) where 25–35 repetitions were performed per set per exercise ( n = 9 ) or a high-load RT routine ( HL ) where 8–12 repetitions were performed per set per exercise ( n = 9 ) . During each session , subjects in both groups performed 3 sets of 7 different exercises representing all major muscles . Training was performed 3 times per week on nonconsecutive days , for a total of 8 weeks . Both HL and LL conditions produced significant increases in thickness of the elbow flexors ( 5.3 vs. 8.6 % , respectively ) , elbow extensors ( 6.0 vs. 5.2 % , respectively ) , and quadriceps femoris ( 9.3 vs. 9.5 % , respectively ) , with no significant differences noted between groups . Improvements in back squat strength were significantly greater for HL compared with LL ( 19.6 vs. 8.8 % , respectively ) , and there was a trend for greater increases in 1 repetition maximum ( 1RM ) bench press ( 6.5 vs. 2.0 % , respectively ) . Upper body muscle endurance ( assessed by the bench press at 50 % 1RM to failure ) improved to a greater extent in LL compared with HL ( 16.6 vs. −1.2 % , respectively ) . These findings indicate that both HL and LL training to failure can elicit significant increases in muscle hypertrophy among well-trained young men ; however , HL training is superior for maximizing strength adaptations The effect of strength training for 14 weeks on patella tendon viscoelastic properties was investigated in a group of elderly individuals . Participants were assigned to training ( age [ mean + /- SD ] 73.6 + /- 3.4 years ; n = 7 ) or control ( age 66.4 + /- 1.7 years ; n = 7 ) groups . Training was performed three times per week and consisted of two series of 10 repetitions of leg-extension and leg-press exercises at 80 % of the 5-repetition maximum . Tendon elongation during an isometric knee-extension contraction-relaxation was measured using ultrasonography . Tendon stiffness was calculated from the gradient of the estimated force-elongation relationship and mechanical hysteresis was calculated as the area between loading-unloading curves . Knee-flexor coactivation , estimated from biceps femoris muscle electromyographic activity , was unaltered ( P > 0.05 ) after the training and control periods . No changes ( P > 0.05 ) were observed in stiffness or hysteresis after the control period . In contrast , tendon stiffness increased from 1376 + /- 811 to 2256 + /- 1476 N x mm(-1 ) ( P < 0.01 ) and hysteresis decreased from 33 + /- 5 to 24 + /- 4 % ( P < 0.05 ) , after training . These training-induced adaptations have implication s for maximal muscle force , rate of force development , and metabolic cost of locomotion We examined the neuromuscular adaptations following 3 and 6 weeks of 80 vs. 30 % one repetition maximum ( 1RM ) resistance training to failure in the leg extensors . Twenty-six men ( age = 23.1 ± 4.7 years ) were r and omly assigned to a high- ( 80 % 1RM ; n = 13 ) or low-load ( 30 % 1RM ; n = 13 ) resistance training group and completed leg extension resistance training to failure 3 times per week for 6 weeks . Testing was completed at baseline , 3 , and 6 weeks of training . During each testing session , ultrasound muscle thickness and echo intensity , 1RM strength , maximal voluntary isometric contraction ( MVIC ) strength , and contractile properties of the quadriceps femoris were measured . Percent voluntary activation ( VA ) and electromyographic ( EMG ) amplitude were measured during MVIC , and during r and omly ordered isometric step muscle actions at 10–100 % of baseline MVIC . There were similar increases in muscle thickness from Baseline to Week 3 and 6 in the 80 and 30 % 1RM groups . However , both 1RM and MVIC strength increased from Baseline to Week 3 and 6 to a greater degree in the 80 % than 30 % 1RM group . VA during MVIC was also greater in the 80 vs. 30 % 1RM group at Week 6 , and only training at 80 % 1RM elicited a significant increase in EMG amplitude during MVIC . The peak twitch torque to MVIC ratio was also significantly reduced in the 80 % , but not 30 % 1RM group , at Week 3 and 6 . Finally , VA and EMG amplitude were reduced during submaximal torque production as a result of training at 80 % 1RM , but not 30 % 1RM . Despite eliciting similar hypertrophy , 80 % 1RM improved muscle strength more than 30 % 1RM , and was accompanied by increases in VA and EMG amplitude during maximal force production . Furthermore , training at 80 % 1RM result ed in a decreased neural cost to produce the same relative submaximal torques after training , whereas training at 30 % 1RM did not . Therefore , our data suggest that high-load training results in greater neural adaptations that may explain the disparate increases in muscle strength despite similar hypertrophy following high- and low-load training programs Nine participants performed two bouts of a step exercise , during which the quadriceps muscle of one leg acted eccentrically . Before and after the exercise , isokinetic torque was measured over a range of knee angles to determine the optimum angle for torque . Immediately after the first bout of exercise , the quadriceps showed a significant ( P < 0.05 ) shift of 15.6 + /- 1.4 degrees ( mean + /-sx ) of its optimum angle in the direction of longer lengths , suggesting the presence of damage . A drop in peak torque , together with delayed soreness and swelling , confirmed that damage to muscle fibres had occurred . After the second bout of exercise , 8 days later , the shift in optimum angle was 10.4 + /- 1.0 degrees , which was significantly less than after the first bout ( P < 0.05 ) . Other indicators of damage were also reduced . In addition , the muscle exhibited a sustained shift in optimum angle ( 3.4 + /- 0.9 degrees ) , suggesting that some adaptation had taken place after the first bout of exercise . We conclude that muscles like the quadriceps can show evidence of damage after a specific programme of eccentric exercise , followed by an adaptation response . This is despite the fact that the quadriceps routinely undergoes eccentric contractions in everyday activities Abstract Tsoukos , A , Bogdanis , GC , Terzis , G , and Veligekas , P. Acute improvement of vertical jump performance after isometric squats depends on knee angle and vertical jumping ability . J Strength Cond Res 30(8 ) : 2250–2257 , 2016—This study examined the acute effects of maximum isometric squats at 2 different knee angles ( 90 or 140 ° ) on countermovement jump ( CMJ ) performance in power athletes . Fourteen national-level male track and field power athletes completed 3 main trials ( 2 experimental and 1 control ) in a r and omized and counterbalanced order 1 week apart . Countermovement jump performance was evaluated using a force-plate before and 15 seconds , 3 , 6 , 9 , and 12 minutes after 3 sets of 3 seconds maximum isometric contractions with 1-minute rest in between , from a squat position with knee angle set at 90 or 140 ° . Countermovement jump performance was improved compared with baseline only in the 140 ° condition by 3.8 ± 1.2 % on the 12th minute of recovery ( p = 0.027 ) , whereas there was no change in CMJ height in the 90 ° condition . In the control condition , there was a decrease in CMJ performance over time , reaching −3.6 ± 1.2 % ( p = 0.049 ) after 12 minutes of recovery . To determine the possible effects of baseline jump performance on subsequent CMJ performance , subjects were divided into 2 groups ( “ high jumpers ” and “ low jumpers ” ) . The baseline CMJ values of “ high jumpers ” and “ low jumpers ” differed significantly ( CMJ : 45.1 ± 2.2 vs. 37.1 ± 3.9 cm , respectively , p = 0.001 ) . Countermovement jump was increased only in the “ high jumpers ” group by 5.4 ± 1.4 % ( p = 0.001 ) and 7.4 ± 1.2 % ( p = 0.001 ) at the knee angles of 90 and 140 ° , respectively . This improvement was larger at the 140 ° angle ( p = 0.049 ) . Knee angle during isometric squats and vertical jumping ability are important determinants of the acute CMJ performance increase observed after a conditioning activity Abstract Oranchuk , DJ , Robinson , TL , Switaj , ZJ , and Drinkwater , EJ . Comparison of the hang high pull and loaded jump squat for the development of vertical jump and isometric force-time characteristics . J Strength Cond Res 33(1 ) : 17–24 , 2019—Weightlifting movements have high skill dem and s and require expert coaching . Loaded jumps have a comparably lower skill dem and but may be similarly effective for improving explosive performance . The purpose of this study was to compare vertical jump performance , isometric force , and rate of force development ( RFD ) after a 10-week intervention using the hang high pull ( hang-pull ) or trap-bar jump squat ( jump-squat ) . Eighteen National Collegiate Athletic Association Division II swimmers ( 8 males , 10 females ) with at least 1 year of resistance training experience volunteered to participate . Testing included the squat jump ( SJ ) , countermovement jump , and the isometric midthigh pull ( IMTP ) . Vertical ground reaction forces were analyzed to obtain jump height and relative peak power . Relative peak force , peak RFD , and relative force at 5 time b and s were obtained from the IMTP . Subjects were r and omly assigned to either a hang pull ( n = 9 ) or jump-squat ( n = 9 ) training group and completed a 10-week , volume-equated , periodized training program . Although there was a significant main effect of training for both groups , no statistically significant between-group differences were found ( p ≥ 0.17 ) for any of the dependent variables . However , medium effect sizes in favor of the jump-squat training group were seen in SJ height ( d = 0.56 ) and SJ peak power ( d = 0.69 ) . Loaded jumps seem equally effective as weightlifting derivatives for improving lower-body power in experienced athletes . Because loaded jumps require less skill and less coaching expertise than weightlifting , loaded jumps should be considered where coaching complex movements is difficult Morton , SK , Whitehead , JR , Brinkert , RH , and Caine , DJ . Resistance training vs. static stretching : Effects on flexibility and strength . J Strength Cond Res 25(12 ) : 3391–3398 , 2011—The purpose of this study was to determine how full-range resistance training ( RT ) affected flexibility and strength compared to static stretching ( SS ) of the same muscle – joint complexes in untrained adults . Volunteers ( n = 25 ) were r and omized to an RT or SS training group . A group of inactive volunteers ( n = 12 ) served as a convenience control group ( CON ) . After pretesting hamstring extension , hip flexion and extension , shoulder extension flexibility , and peak torque of quadriceps and hamstring muscles , subjects completed 5-week SS or RT treatments in which the aim was to stretch or to strength train the same muscle – joint complexes over similar movements and ranges . Posttests of flexibility and strength were then conducted . There was no difference in hamstring flexibility , hip flexion , and hip extension improvement between RT and SS , but both were superior to CON values . There were no differences between groups on shoulder extension flexibility . The RT group was superior to the CON in knee extension peak torque , but there were no differences between groups on knee flexion peak torque . The results of this preliminary study suggest that carefully constructed full-range RT regimens can improve flexibility as well as the typical SS regimens employed in conditioning programs . Because of the potential practical significance of these results to strength and conditioning programs , further studies using true experimental design s , larger sample sizes , and longer training duration s should be conducted with the aim of confirming or disproving these results The aim of this study was to determine the optimal intensity for isometric strength training . Isometric elbow flexor strength of 51 subjects was measured before and after a six-week training period . Subjects were r and omly assigned to target training intensities between 0 and 100 per cent of a maximal voluntary contraction , and undertook supervised isometric elbow flexor training at the allocated target intensity three times each week for six weeks . Strength increases at the trained angle of the trained limb were linearly or near linearly related to training intensity , with the greatest increases in strength occurring at maximal or near-maximal intensities . These findings suggest that the optimal intensity for isometric strength training is maximal or near maximal The effect of different training intensities on maximum voluntary isometric contraction ( MVIC ) strength was examined in a three week voluntary isometric exercise programme . Eighteen healthy university students were r and omly assigned to one of three training groups : Low Intensity ( LI ) , High Intensity ( HI ) and Maximal Effort ( ME ) groups . The LI and HI groups trained by producing voluntary isometric knee extension torques equivalent to 25 % and 50 % of MVIC strength , respectively . The ME group produced maximal effort contractions during training . Only the HI and ME groups demonstrated significant ( p < .05 ) isometric strength gains . The HI group produced the greatest strength gain ( 45.8 % of MVIC ) , followed by the ME group ( 31.3 % ) and the LI group ( 22.3 % ) . No significant strength retention , cross transfer or isokinetic strength improvement were seen in any group . The strength improvements were of the same magnitude as those previously obtained using electro-motor stimulation at equivalent training intensities Abstract . Isometric unilateral elbow extension training was conducted for 10 weeks ( 3 times per week ) on 12 young adult men to investigate the effects of equivolume exercise programs with different combinations of intensity and duration on the morphological and functional aspects of the triceps brachii muscle . One group of 6 subjects trained by developing maximal voluntary contraction ( MVC ) for 6 s per set with 12 sets per session ( 100%G ) , while the other group of 6 subjects trained at 60 % of MVC for 30 s per set with 4 sets per session ( 60%G ) . Training significantly increased the muscle volume ( Vm ) , fascicle pennation angle of the triceps brachii , and torque output during concentric and eccentric elbow extensions at three constant velocities of 0.52 , 1.57 , and 3.14 rad·s–1 as well as under the training condition , with no significant differences in the relative gains between the two programs . However , 100%G showed significantly greater Vm than 60%G after training , when Vm before training was normalized . Thus , only 60%G significantly increased the ratio of torque to Vm developed in the eccentric actions at the three velocities and concentric action at 1.57 rad·s–1 . The present results indicate that isometric training programs of medium resistance/long duration and high resistance/short duration produce different effects on Vm and dynamic strength relative to Vm , even if the training volume is equalized between the two protocol This study examined the strength of motor unit synchronisation based on time- and frequency-domain measures during postural , shortening and lengthening contractions of a h and muscle in young adults . Single motor unit activity was recorded with intramuscular electrodes in the left first dorsal interosseus muscle as the subject held the index finger at a constant position while supporting a light load for 2 - 5 min . The subject then performed slow ( 1.7 deg s(-1 ) ) shortening and lengthening contractions to lift and lower the load . The movement required subjects to perform 10 - 25 constant-velocity contractions with the index finger over a 10 deg range of motion by using 6 s shortening and lengthening contractions . Individual discharge times were obtained from 23 pairs of motor units in 14 subjects to assess the strength of motor unit synchronisation and coherence during the three tasks . The strength of motor unit synchronisation was approximately 50 % greater during the lengthening contractions compared with the postural and shortening contractions , and the width of the central synchronous peak in the cross-correlation histogram was approximately 4 ms narrower during shortening contractions . These findings reveal that there is an increase in common input to motoneurones during lengthening contractions and a greater relative contribution of direct common inputs to motoneurones during shortening contractions compared with postural tasks . Furthermore , the amount of motor unit coherence in the low-frequency b and ( 2 - 12 Hz ) was reduced during shortening contractions compared with postural and lengthening contractions . These data indicate that the timing of inputs received by the motoneurones innervating the first dorsal interosseus of young adults differs during postural , shortening and lengthening contractions against a light load Fatigue resistance of knee extensor muscles is higher during voluntary isometric contractions at short compared with longer muscle lengths . In the present study we hypothesized that this would be due to lower energy consumption at short muscle lengths . Ten healthy male subjects performed isometric contractions with the knee extensor muscles at a 30 , 60 , and 90 degrees knee angle ( full extension = 0 degrees ) . At each angle , muscle oxygen consumption ( m . VO2 ) of the rectus femoris , vastus lateralis , and vastus medialis muscle was obtained with near-infrared spectroscopy . m . VO2 was measured during maximal isometric contractions and during contractions at 10 , 30 , and 50 % of maximal torque capacity . During all contractions , blood flow to the muscle was occluded with a pressure cuff ( 450 mmHg ) . m . VO2 significantly ( P < 0.05 ) increased with torque and at all torque levels , and for each of the three muscles . m . VO2 was significantly lower at 30 degrees compared with 60 degrees and 90 degrees and m . VO2 was similar ( P > 0.05 ) at 60 degrees and 90 degrees . Across all torque levels , average ( + /- SD ) m . VO2 at the 30 degrees angle for vastus medialis , rectus femoris , and vastus lateralis , respectively , was 70.0 + /- 10.4 , 72.2 + /- 12.7 , and 75.9 + /- 8.0 % of the average m . VO2 obtained for each torque at 60 and 90 degrees . In conclusion , oxygen consumption of the knee extensors was significantly lower during isometric contractions at the 30 degrees than at the 60 degrees and 90 degrees knee angle , which probably contributes to the previously reported longer duration of sustained isometric contractions at relatively short muscle lengths BACKGROUND Loading leads to tendon adaptation but the influence of load-intensity and contraction type is unclear . Clinicians need to be aware of the type and intensity of loading required for tendon adaptation when prescribing exercise . The aim of this study was to investigate the influence of contraction type and load-intensity on patellar tendon mechanical properties . METHOD Load intensity was determined using the 1 repetition maximum ( RM ) on a resistance exercise device at baseline and fortnightly intervals in four r and omly allocated groups of healthy , young males : ( 1 ) control ( no training ) ; ( 2 ) concentric ( 80 % of concentric-eccentric 1RM , 4 × 7 - 8 ) ; ( 3 ) st and ard load eccentric only ( 80 % of concentric-eccentric 1RM , 4 × 12 - 15 repetitions ) and ( 4 ) high load eccentric ( 80 % of eccentric 1RM , 4 × 7 - 8 repetitions ) . Participants exercised three times a week for 12 weeks on a leg extension machine . Knee extension maximum torque , patellar tendon CSA and length were measured with dynamometry and ultrasound imaging . Patellar tendon force , stress and strain were calculated at 25 % , 50 % , 75 % and 100 % of maximum torque during isometric knee extension contractions , and stiffness and modulus at torque intervals of 50 - 75 % and 75 - 100 % . Within group and between group differences in CSA , force , elongation , stress , strain , stiffness and modulus were investigated . The same day reliability of patellar tendon measures was established with a subset of eight participants . RESULTS Patellar tendon modulus increased in all exercise groups compared with the control group ( p<0.05 ) at 50 - 75 % of maximal voluntary isometric contraction ( MVIC ) , but only in the high eccentric group compared with the control group at 75 - 100 % of MVIC ( p<0.05 ) . The only other group difference in tendon properties was a significantly greater increase in maximum force in the high eccentric compared with the control group ( p<0.05 ) . Five repetition maximum increased in all groups but the increase was significantly greater in the high load eccentric compared with the other exercise groups ( p<0.05 ) . CONCLUSION Load at different intensity levels and contraction types increased patellar tendon modulus whereas muscle strength seems to respond more to load-intensity . High load eccentric was , however , the only group to have significantly greater increase in force , stiffness and modulus ( at the highest torque levels ) compared with the control group . The effects and clinical applicability of high load interventions needs to be investigated further Winchester , JB , McBride , JM , Maher , MA , Mikat , RP , Allen , BK , Kline , DE , and McGuigan , MR . Eight weeks of ballistic exercise improves power independently of changes in strength and muscle fiber type expression . J Strength Cond Res 22(6 ) : 1728 - 1734 , 2008-This study investigated the effects of ballistic resistance training and strength training on muscle fiber composition , peak force ( PF ) , maximal strength , and peak power ( PP ) . Fourteen males ( age = 21.3 ± 2.9 , body mass = 77.8 ± 10.1 kg ) with 3 months of resistance training experience completed the study . Subjects were tested pre and post for their squat one-repetition maximum ( 1RM ) and PP in the jump squat ( JS ) . Peak force and rate of force development ( RFD ) were tested during an isometric midthigh pull . Muscle biopsies were obtained from the vastus lateralis for analysis of muscle fiber type expression . Subjects were matched for strength and then r and omly selected into either training ( T ) or control ( C ) groups . Group T performed 8 weeks of JS training using a periodized program with loading between 26 and 48 % of 1RM , 3 days per week . Group T showed significant improvement in PP from 4088.9 ± 520.6 to 5737.6 ± 651.8 W. Rate of force development improved significantly in group T from 12687.5 ± 4644.0 to 25343.8 ± 12614.4 N·s−1 . PV improved significantly from 1.59 ± 0.41 to 2.11 ± 0.75 m·s−1 . No changes occurred in PF , 1RM , or muscle fiber type expression for group T. No changes occurred in any variables in group C. The results of this study indicate that using ballistic resistance exercise is an effective method for increasing PP and RFD independently of changes in maximum strength ( 1RM , PF ) , and those increases are a result of factors other than changes in muscle fiber type expression |
13,416 | 30,690,773 | The overall quality of life ( QoL ) of ETPKU adults was good or comparable to control population s , and there was no evidence for a significant incidence of psychiatric disease or social difficulties .
Neuroimaging revealed that brain abnormalities are present in ETPKU adults , but their clinical significance remains unclear .
Generally , intelligence quotient ( IQ ) appears normal but specific deficits in neuropsychological and social functioning were reported in early-treated adults compared with healthy individuals . | Newborn screening for phenylketonuria ( PKU ) and early introduction of dietary therapy has been remarkably successful in preventing the severe neurological features of PKU , including mental retardation and epilepsy .
However , concerns remain that long-term outcome is still suboptimal , particularly in adult patients who are no longer on strict phenylalanine-restricted diets .
With our systematic literature review we aim ed to describe the neurological phenotype of adults with early-treated phenylketonuria ( ETPKU ) . | Some people with phenylketonuria who were born before screening began were never treated and are still alive . Here we report that far fewer people with untreated phenylketonuria were detected than are thought to exist ( about 2000 ) . The majority of those traced had high support needs , challenging behaviour and other symptoms of phenylketonuria . No significant differences were found between those who had or had not tried the phenylalanine-restricted diet . A r and omised controlled trial is required to examine the effect of trying the low-phenylalanine diet for people with untreated phenylketonuria Concerns about the psychosocial risk of adults with early-treated phenylketonuria ( ETPKU ) are predicated on four sources of scientific data : ( 1 ) consistent documentation of increased behavioural risk in children with ETPKU ; ( 2 ) recent evidence of neurocognitive impairment in adults with ETPKU ; ( 3 ) reports of neuroimaging abnormalities in adults with ETPKU ; and ( 4 ) preliminary evidence of increased rates of psychiatric disturbance in this population . We studied the psychosocial adjustment of 25 patients , aged 18 years and older , with ETPKU . On most pscyhosocial outcome measures , patients were indistinguishable from 15 sibling controls . However , on a self-report inventory of psychiatric symptoms , 20 % of the patients demonstrated significant morbidity . Psychosocial outcome of these patients was unrelated to concurrent or historical biological dietary disease factors , unlike neurocognitive outcome . A strong relationship was demonstrated , however , between neurocognitive measures and psychosocial morbidity . These findings indicate that a significant minority of patients with ETPKU develop psychosocial difficulties with multiple clinical elevations on a psychiatric inventory . However , most adults with ETPKU cope with the challenges of young adulthood with the same degree of success as their unaffected siblings . Neuropsychological surveillance during childhood and adolescence is important in identifying patients at risk for both neurocognitive and psychosocial morbidity Recent studies indicate that individual blood – brain transport characteristics of phenylalanine may lead to different clinical outcomes in phenylketonuria ( PKU ) patients in spite of comparable dietary control . To check these preliminary data , we investigated four pairs of siblings with classical PKU ( and identical genotype ) using in vivo nuclear magnetic resonance spectroscopy in the course of an oral phenylalanine load ( 100 mg/kg body weight ) . Patients ' brain phenylalanine concentrations were different in spite of similar blood levels . Interindividual variations of the apparent transport Michaelis constant , Kt , app , ranged from 0.10 to 0.84 mmol/L. The ratio of the maximal transport velocity , Tmax , over the intracerebral consumption rate , Vmet , varied between 2.61 and 14.0 . Siblings with lower values for Kt , app , higher values for Tmax/Vmet , and higher concurrent brain phenylalanine levels showed a lower IQ and a higher degree of cerebral white matter abnormalities . The results indicate that blood – brain barrier transport characteristics and the result ant brain phenylalanine levels are causative factors for the individual clinical outcome in PKU Background The strict and dem and ing dietary treatment and mild cognitive abnormalities seen in PKU treated from a young age can be expected to affect the health-related quality of life ( HRQoL ) of patients and their families . Our aim was to describe the HRQoL of patients with PKU from a large international study , using generic HRQoL measures and an innovative PKU-specific HRQoL question naire ( PKU-QOL ) . Analyses were exploratory , performed post-hoc on data collected primarily to vali date the PKU-QOL . Methods A multicentre , prospect i ve , non-interventional , observational study conducted in France , Germany , Italy , The Netherl and s , Spain , Turkey and the UK . Patients diagnosed with PKU aged ≥9 years old and treated with a Phe-restricted diet and /or Phe-free amino acid protein supplements and /or pharmacological therapy were included in the study ; parents of at least one patient with PKU aged < 18 years were also included . HRQoL was assessed by generic measures ( Pediatric Quality -of-Life Inventory ; Medical Outcome Survey 36 item Short Form ; Child Health Question naire 28 item Parent Form ) and the newly developed PKU-QOL . Mean generic domain scores were interpreted using published reference values from the general population . PKU-QOL domain scores were described overall and in different subgroups of patients defined according to severity of PKU , overall assessment of patient ’s health status by the investigator and treatment with tetrahydrobiopterin ( BH4 ) . Results Data from 559 subjects were analysed : 306 patients ( 92 children , 110 adolescents , 104 adults ) and 253 parents . Mean domain scores of generic measures in the study were comparable to the general population . The highest PKU-QOL impact scores ( indicating greater impact ) were for emotional impact of PKU , anxiety about blood Phe levels , guilt regarding poor adherence to dietary restrictions or Phe-free amino acid supplement intake and anxiety regarding blood Phe levels during pregnancy . Patients with mild/moderate PKU and those receiving BH4 reported lower practical and emotional impacts of the diet and Phe-free amino acid supplement intake . Conclusion Patients with PKU showed good HRQoL in the study , both with the generic and PKU-specific measures . Negative impacts of PKU on a patient ’s life , including the emotional impact of PKU and its management , was delineated by the PKU-QOLs across all age groups Background : Although early diagnosis and treatment in phenylketonuria ( PKU ) leads to excellent outcomes , a population of adults born before the introduction of newborn screening exists . They can have severe intellectual disabilities and behavioural problems , and are often dependent on full-time carers . Anecdotal evidence suggests that a diet that lowers blood phenylalanine concentration can have significant benefits upon behaviour . Methods : A prospect i ve double-blind r and omised placebo-controlled crossover trial of phenylalanine-restricted diet was performed in a group of 34 adults ( aged 21–61 years , median 49 ) with late diagnosed PKU with severe challenging behaviour . Results : Only 17 completed the 60 week study : seven withdrew before the end of the baseline period ; five withdrew during the first diet period ; five withdrew during the second diet period ( after moving into placebo phase ) . The mean ( SD ) blood phenylalanine was 1570 ( 222 ) μmol/l during baseline , 553(158 ) μmol/l during the active phase and 1444 ( 255 ) μmol/l during the placebo phase . In the 22 participants exposed to both active and placebo phases , no differences were demonstrated in behaviour assessed by the Aberrant Behavior Checklist and Vinel and Adaptive Behavior Scales , behaviour diaries or on video analysis of direct observations . However , 76 % of carers ’ comments were scored as positive during the active phase , compared with 54 % during the placebo phase ( χ2 = 38.06 , p<0.001 ) . Conclusions : There are significant challenges in study ing people with intellectual disabilities and considerable difficulties in instituting phenylalanine-restricted diet in this population . However , if attempted , there are potential benefits to quality of life for the individuals with PKU and their carers The main debate in the treatment of Phenylketonuria ( PKU ) is whether adult patients need the strict phenylalanine (Phe)-restricted diet . Physicians and patients lack evidence -based guidelines to help them make well-informed choices . We have carried out the first r and omised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU . Nine continuously treated adults with PKU underwent two 4-week supplementation periods : one with Phe , mimicking normal dietary intake , and one with placebo in r and omly allocated order via a r and omisation coding list in a double-blind cross-over design . A set of neuropsychological tests ( Amsterdam Neuropsychological Tasks ) was administered at the end of each study period . In addition , patients and for each patient a friend or relative , completed weekly Profile of Mood States ( POMS ) question naires , evaluating the patients ’ mood . Phe levels were measured twice weekly . Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo ( p = 0.008 ) . Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation ( p = 0.029 ) . Both patients and their friend or relative reported lower scores on the POMS question naires during Phe supplementation ( p = 0.017 and p = 0.040 , respectively ) . High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU . A Phe-restricted “ diet for life ” might be an advisable option for many Background The aim of our study was to develop and vali date the first set of PKU-specific Health-related Quality of Life ( HRQoL ) question naires that : 1 ) were developed for patients with PKU and their parents , 2 ) cover the physical , emotional , and social impacts of PKU and its treatment on patients ’ lives , 3 ) are age specific ( Child PKU-QOL , Adolescent PKU-QOL , Adult PKU-QOL ) , 4 ) enable the evaluation of the HRQoL of children by their parents ( Parent PKU-QOL ) , and 5 ) have been cross-culturally adapted for use in seven countries ( i.e. France , Germany , Italy , The Netherl and s , Spain , Turkey and the UK ) . Methods The PKU-QOL question naires were developed according to reference methods including patients ’ , parents ’ and healthcare professionals ’ interviews ; testing in a pilot study ( qualitative step in six countries ) , and linguistic validation of the finalised pilot versions in Turkish . For finalisation and psychometric validation , the pilot versions were included in a multicentre , prospect i ve , non-interventional , observational study conducted in 34 sites in France , Germany , Italy , The Netherl and s , Spain , Turkey and the UK . Iterative multi-trait analyses were conducted . Psychometric properties were assessed ( concurrent and clinical validity , internal consistency reliability and test-retest reliability ) . Results Data from 559 subjects ( 306 patients , 253 parents ) were analysed . After finalisation , the PKU-QOL question naires included 40 items ( Child PKU-QOL ) , 58 items ( Adolescent PKU-QOL ) , 65 items ( Adult PKU-QOL ) and 54 items ( Parent PKU-QOL ) , distributed in four modules : PKU symptoms , PKU in general , administration of Phe-free protein supplements and dietary protein restriction . The measurement properties of the Adolescent , Adult and Parent PKU-QOL question naires were overall fairly satisfactory , but weaker for the Child question naire . Conclusions The four PKU-QOL question naires developed for different ages ( Child PKU-QOL , Adolescent PKU-QOL , Adult PKU-QOL ) , and for parents of children with PKU ( Parent PKU-QOL ) are valid and reliable instruments for assessing the multifaceted impact of PKU on patients of different age groups ( children , adolescents and adults ) and their parents , and are available for use in seven countries . They are very promising tools to explore how patients ’ perceptions evolve with age , to increase knowledge of the impact of PKU on patients and parents in different countries , and to help monitor the effect of therapeutic strategies During 1967–1983 , the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria ( PKU ) . Subsequently , financial support was provided by the National Institute of Child Health and Human Development ( NICHD ) . The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then r and omized either to continue the diet or to discontinue dietary treatment altogether . One hundred and twenty-five of the 211 children were then followed until 10 years of age . In 1998 , NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical , nutritional , psychological , and socioeconomic status . Fourteen of the original clinics ( 1967–1983 ) participated in the Follow-up Study effort . Each clinic director was provided with a list of PKU subjects who had completed the original study ( 1967–1983 ) , and was asked to evaluate as many as possible using a uniform protocol and data collection forms . In a subset of cases , magnetic resonance imaging and spectroscopy ( MRI/MRS ) were performed to study brain Phe concentrations . The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers , who had an increased rate of eczema , asthma , mental disorders , headache , hyperactivity and hypoactivity . Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations . Abnormal MRI results were associated with higher brain Phe concentrations . Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability , but also in achievement test scores and increased rates of medical and behavioural problems OBJECTIVE To determine psychiatric disorders in patients with phenylketonuria ( PKU ) and to test whether biochemical control , intellectual functioning , white matter abnormalities visible on magnetic resonance imaging ( MRI ) , and /or style of parenting influence psychopathology . DESIGN AND SUBJECTS This cross-sectional study consisted of 35 PKU patients 17 to 33 years of age ( mean : 22.2 ) . From a total of 67 patients , 3 patients were selected because of other causes of possible brain damage . Then 35 patients were r and omly drawn with comparison with a control sample ( n = 181 ) from an epidemiologic study . METHODS We used a st and ardized , highly structured , face-to-face interview ; intelligence quotient ( IQ ) test ; cranial MRI ( n = 26 ) ; and monitoring of plasma phenylalanine . RESULTS The overall rate of psychiatric disorders was 25.7 % in PKU patients and 16.1 % in controls . This difference was not statistically significant . The pattern of psychiatric disturbances was different for PKU patients and controls ( Fisher 's exact test ) : in PKU patients , externalizing disorders were reduced ( PKU : not present , controls : 7.8 % ) , whereas internalizing disorders ( PKU : 25.7 % , controls : 8.3 % ) were increased . International Classification of Diseases , version 10 , diagnoses were predominantly those of the depressive category and more frequent in women ( 8 of 18 females and 1 of 17 males ) . A correlation between IQ and both biochemical control up to 12 years of age and school education of parents was confirmed . No correlation was found between the severity or pattern of psychiatric disturbances and school education of parents , biochemical control , IQ , or the extension of MRI-visible , white matter abnormalities . It was found that a restrictive controlling style of parenting is a risk factor for the development of psychiatric symptoms . CONCLUSIONS Our results support a psychological perspective for the development of psychiatric symptoms in PKU . Thus , optimizing medical treatment necessary to prevent brain damage should be accompanied by psychiatric monitoring and psychological support for the families The effects of short-term and long-term phenylalanine ( Phe ) levels on sustained attention have been investigated in phenylketonuria ( PKU ) patients . Two studies , one cross-sectional with 103 patients aged 8.5–9.0 years , the other with 15 adult patients following an interventional design with experimentally manipulated concurrent Phe levels are reported . The effects of concurrent Phe levels separated from long-term Phe control on sustained attention and calculation speed in simple addition tasks were investigated . Children with low concurrent Phe levels performed significantly better than children with high concurrent Phe levels when long-term dietary control was good but not when long-term control was poor . Adult PKU patients with high concurrent Phe levels showed significantly longer reaction times and lower speed in calculation than a healthy control group . Deficits were partly reversible by lowering the concurrent Phe level over a period of 4–5 weeks . The results demonstrated the impact of concurrent Phe level on neuropsychological functioning in childhood as well as in adulthood Blood-brain ratios ( BBR ) of phenylalanine ( Phe ) were determined by quantitative in vivo 1H magnetic resonance spectroscopy ( 1H-MRS ) in 17 adult patients with early-treated phenylketonuria who were r and omly selected from a sample of 75 adults . Measurements were performed in all patients during steady-state conditions . The BBR showed a unimodal distribution with a mean of 4.0 ( range 3.3 to 4.5 ) . Blood-brain ratios were comparable for subgroups of patients with genotypes classified as severe , moderate , or mild and for patients on different types of diets . Brain Phe concentrations showed a strong linear correlation with blood Phe values ( r = 0.93 , P < 0.001 ) . There were no saturation effects for blood Phe values up to 1.8 mmol/L , and a local regression analysis did not confirm increasing BBR for increasing blood Phe values . The intellectual outcome ( Wechsler Adult Intelligence Scale ) was correlated with long-term dietary control ( r = −0.65 , P < 0.05 ) , fluctuation of blood Phe values during treatment ( r = −0.60 , P < 0.05 ) , and concurrent blood and brain Phe concentration . The severity of white matter changes visible on magnetic resonance images ( MRI ) was increased with high blood and brain Phe concentrations but failed to reach statistical significance . No correlation was found between BBR values , intelligence quotient , and MRI grade . Based on the assumption that BBR show intraindividual stability , the current data do not support the hypothesis that blood-brain barrier transport of Phe is a key explanatory factor for outcome variability in the vast majority of “ typical ” patients with phenylketonuria BACKGROUND Previous qualitative research among adults and parents of children with phenylketonuria ( PKU ) has identified inattention as an important psychiatric aspect of this condition . The parent-reported ADHD Rating Scale-IV ( ADHD RS-IV ) and the Adult ADHD Self-Report Scale ( ASRS ) have been vali date d for measuring inattention symptoms in persons with attention-deficit/hyperactivity disorder ( ADHD ) ; however , their psychometric attributes for measuring PKU-related inattention have not been established . OBJECTIVE The primary objective of this investigation was to demonstrate the reliability , validity , and responsiveness of the ADHD RS-IV and ASRS inattention symptoms subscales in a r and omized controlled trial of patients with PKU aged 8 years or older . METHODS A post hoc analysis investigated the psychometric properties ( Rasch model fit , reliability , construct validity , and responsiveness ) of the ADHD RS-IV and ASRS inattention subscales using data from a phase 3b , double-blind , placebo-controlled clinical trial in those with PKU aged 8 years or older . RESULTS The Rasch results revealed good model fit , and reliability analyses revealed strong internal consistency reliability ( α ≥ 0.87 ) and reproducibility ( intraclass correlation coefficient ≥ 0.87 ) for both measures . Both inattention measures demonstrated the ability to discriminate between known groups ( P < 0.001 ) created by the Clinical Global Impression-Severity scale . Correlations between the ADHD RS-IV and the ASRS with the Clinical Global Impression-Severity scale and the age-appropriate Behavior Rating Inventory of Executive Function Working Memory subscale were consistently moderate to strong ( r ≥ 0.56 ) . Similarly , results of the change score correlations were of moderate magnitude ( r ≥ 0.43 ) for both measures when compared with changes over time in Behavior Rating Inventory of Executive Function Working Memory subscales . CONCLUSIONS These findings of reliability , validity , and responsiveness of both the ADHD RS-IV and the ASRS inattention scales , in addition to content validation results , support their use for the assessment of inattention symptoms among persons with PKU aged 8 years or older in both clinical and research setting The effect of concurrent phenylalanine levels ( Phe-level ) on sustained attention was tested in a group of 19 early treated adult PKU patients . Mean age was 20.5 years ; WAIS IQs were in the normal range ( M = 109.3 ) . Phe-levels were manipulated in a high-low-high design by re introduction of a strict phenylalanine-reduced diet for 4 to 5 weeks between test time 1 and 2 and returning to usual diet between test time 2 and 3 . A control group of 20 healthy subjects , mean age 20.7 years was tested twice . Results of a sustained attention task are presented . In adult PKU patients with high concurrent Phe-levels , sustained attention is significantly impaired and reaction times are prolonged . In the low Phe-level condition , performance improved significantly . Nevertheless , the PKU group did not reach the level of performance of the control group . Results are not influenced by IQ and suggest a sustained attention deficit in adult PKU patients that varies according to the concurrent Phe-level . The partial reversibility of the deficits provides support for the hypothesis that biochemical mechanisms rather than structural changes of the brain underlie the relationship between concurrent Phe-level and sustained attention BACKGROUND Phenylketonuria ( PKU ) is a rare inborn error of metabolism caused by phenylalanine hydroxylase enzyme ( PAH ) deficiency . Treatment constitutes a strict Phe restricted diet with unpalatable amino acid supplements . Residual PAH activity enhancement with its cofactor tetrahydrobiopterin ( BH4 ) is a novel treatment which increases dietary tolerance in some patients and permits dietary relaxation . Relaxation of diet may improve health related quality of life ( HRQoL ) . This prospect i ve cohort study aims to evaluate HRQoL of patients with PKU and effects of BH4 treatment on HRQoL. METHODS Patients aged 4years and older , diagnosed through newborn screening and early and continuously treated , were recruited from eight metabolic centers . Patients and mothers completed vali date d generic and chronic health-conditions HRQoL question naires ( PedsQL , TAAQOL , and DISABKIDS ) twice : before and after testing BH4 responsivity . Baseline results were compared to the general population . Data collected after BH4 testing was used to find differences in HRQoL between BH4 unresponsive patients and BH4 responsive patients after one year of treatment with BH4 . Also a within patient comparison was performed to find differences in HRQoL before and after treatment with BH4 . RESULTS 69/81 ( 85 % ) patients completed the question naires before BH4 responsivity testing , and 45/69 ( 65 % ) participated again after testing . Overall PKU patients demonstrated normal HRQoL. However , some significant differences were found when compared to the general population . A significantly higher ( thus better ) score on the PedsQL was reported by children 8 - 12 years on physical functioning and by children 13 - 17 years on total and psychosocial functioning . Furthermore , adult patients reported significantly lower ( thus worse ) scores in the TAAQOL cognitive domain . 10 patients proved to be responsive to BH4 treatment ; however improvement in their HRQoL after relaxation of diet could not be demonstrated Background Classic phenylketonuria ( PKU ) is due to an inborn error of metabolism result ing in an inability to metabolize the amino acid phenylalanine . To avoid mental retardation , affected individuals observe a phenylalanine-restricted diet . When dietary control is poor , deficits in prefrontally mediated cognitive functions have been observed . It has been suggested that these deficits are due to disruptions in the mesocortical dopamine system that projects to the prefrontal cortex . Methods In this study , dopamine system reactivity was examined in individuals with PKU , relative to age-matched controls , using the non-specific DA antagonist haloperidol , in a repeated measures placebo-controlled design . Outcome variables included neuroendocrine , physiological , and cognitive measures . Results Regardless of drug condition , PKU participants differed from control participants in their blood phenylalanine and tyrosine levels , and in their times to complete measures of attention and working memory . Also , relative to placebo , haloperidol influenced several variables irrespective of group status , including serum prolactin secretion , times to complete attention and working memory tasks , and accuracy of working memory performance . An interaction between group and drug condition was observed for the digit span task , where PKU participants exhibited greater relative impairments on haloperidol . When composite indices of impairment were derived , PKU participants demonstrated selective disruption in executive function on haloperidol relative to control subjects . Conclusions Findings are consistent with the presence of frontostriatal dysfunction in PKU but are less consistent with the notion that PFC dopamine function is specifically affected The metabolic disorder phenylketonuria ( PKU ) is treated early by a low-phenylalanine diet . While this prevents global cognitive impairment , some patients still experience cognitive and neurophysiological abnormalities . Neuropsychological testing of early treated , currently off-diet , PKU patients attending an adult PKU clinic showed a reduction in the Perceptual Organization Index ( POI ) , Processing Speed Index ( PSI ) from the Wechsler Adult Intelligence Scale Third Edition ( WAIS-III ) , and Part A of the Trail Making Test for the PKU group relative to controls . Taken together , these results supported a profile of reduced information-processing speed To investigate the extent of neurological disease in adults with phenylketonuria and also their requirement for specialist medical services , we assessed 27 such patients in Northern Irel and . Most had been diagnosed early and with one exception had dietary relaxation by early adolescence . Abnormal neurological features were elicited in 21/27 cases with significant delay of visual evoked potentials and somatosensory evoked potentials occurring in 63.6 and 13.6 % of cases respectively . Periventricular white matter abnormalities were observed in 5/12 patients undergoing magnetic resonance imaging , whilst phenylalanine levels were high ( mean 1,226 µmol/l ) . These data accord with the observation that even early treated patients with phenylketonuria can have significant neurological morbidity in adulthood , although the correlation with current or recent dietary control is unclear and requires further study |
13,417 | 19,821,407 | The expected equivalent efficacy with a half dose of dexketoprofen compared to ketoprofen was not demonstrated .
Adverse events were uncommon with both drugs , and not significantly different from placebo .
Both drugs were well tolerated in single doses | BACKGROUND Ketoprofen is a non-selective non-steroidal anti-inflammatory drug ( NSAID ) used to treat acute and chronic painful conditions .
Dexketoprofen is the (S)-enantiomer , which is believed to confer analgesia .
Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose , with a consequent reduction in gastrointestinal adverse events .
OBJECTIVES To assess efficacy , duration of action , and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size & 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 Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale |
13,418 | 28,211,056 | Neither found significant differences between the groups ( low quality evidence ) .
Evidence on behavioural changes , and knowledge and attitudes typically found some effects in favour of receiving personalised content or no significant differences between groups ( very low quality evidence ) .
The available evidence is inadequate for underst and ing whether mass media interventions targeted toward ethnic minority population s are more effective in changing health behaviours than mass media interventions intended for the population at large .
When compared to no intervention , a targeted mass media intervention may increase the number of calls to smoking quit line , but the effect on health behaviours is unclear .
These studies could not distinguish the impact of different components , for instance the effect of hearing a message regarding behavioural change , the cultural adaptation to the ethnic minority group , or increase reach to the target group through more appropriate mass media channels . | BACKGROUND Physical activity , a balanced diet , avoidance of tobacco exposure , and limited alcohol consumption may reduce morbidity and mortality from non-communicable diseases ( NCDs ) .
Mass media interventions are commonly used to encourage healthier behaviours in population groups .
It is unclear whether targeted mass media interventions for ethnic minority groups are more or less effective in changing behaviours than those developed for the general population .
OBJECTIVES To determine the effects of mass media interventions targeting adult ethnic minorities with messages about physical activity , dietary patterns , tobacco use or alcohol consumption to reduce the risk of NCDs . | Background Adequate fruit and vegetable ( F&V ) intake is important for disease prevention . Yet , most Americans , especially low-income and racial/ethnic minorities , do not eat adequate amounts . These disparities are partly attributable to food environments in low-income neighborhoods where residents often have limited access to affordable , healthful food and easy access to inexpensive , unhealthful foods . Increasing access to affordable healthful food in underserved neighborhoods through mobile markets is a promising , year-round strategy for improving dietary behaviors and reducing F&V intake disparities . However , to date , there have been no r and omized controlled trials study ing their effectiveness . The objective of the ‘ Live Well , Viva Bien ’ ( LWVB ) cluster r and omized controlled trial is to evaluate the efficacy of a multicomponent mobile market intervention at increasing F&V intake among residents of subsidized housing complexes . Methods / Design One housing complex served as a pilot site for the intervention group and the remaining 14 demographically-matched sites were r and omized into either the intervention or control group . The intervention group received bimonthly , discount , mobile , fresh F&V markets in conjunction with a nutrition education intervention ( two F&V campaigns , newsletters , DVDs and cooking demonstrations ) for 12 months . The control group received physical activity and stress reduction interventions . Outcome measures include F&V intake ( measured by two vali date d F&V screeners at baseline , six-month and twelve-months ) along with potential psychosocial mediating variables . Extensive quantitative and qualitative process evaluation was also conducted throughout the study . Discussion Modifying neighborhood food environments in ways that increase access to affordable , healthful food is a promising strategy for improving dietary behaviors among low-income , racial and ethnic minority groups at increased risk for obesity and other food-related chronic diseases . Discount , mobile F&V markets address all the major barriers to eating more F&V ( high cost , poor quality , limited access and limited time to shop and cook ) and provide a year-round solution to limited access to healthful food in low-income neighborhoods . LWVB is the first r and omized controlled trial evaluating the effectiveness of mobile markets at increasing F&V intake . If proven efficacious at increasing F&V consumption , LWVB could be disseminated widely to neighborhoods that have low access to fresh F&V.Trials registration Clinicatrials.gov registration number : NCT02669472 First Received : January 19 , 2016 Purpose . To assess the effectiveness of a large-scale , national smoking cessation media campaign , the EX campaign , across racial/ethnic and educational subgroups . Design . A longitudinal r and om-digit-dial panel study conducted prior to and 6 months following the national launch of the campaign . Setting . The sample was drawn from eight design ated media markets in the United States . Subjects . The baseline survey was conducted on 5616 current smokers , aged 18 to 49 years , and 4067 ( 73 % follow-up response rate ) were resurveyed at the 6-month follow-up . Measures . The primary independent variable is confirmed awareness of the campaign advertising , and the outcome variables are follow-up cessation-related cognitions index score and quit attempts . Analysis . Multivariable logistic and linear regression analyses were conducted within racial/ethnic and educational strata to assess the strength of association between confirmed awareness of campaign advertising and cessation-related outcomes . Results . Confirmed awareness of campaign advertising increased favorable cessation-related cognitions among Hispanics and quit attempts among non-Hispanic blacks , and increased favorable cessation-related cognitions and quit attempts among smokers with less than a high school education . Conclusions . These results suggest that the EX campaign may be effective in promoting cessation-related cognitions and behaviors among minority and disadvantaged smokers who experience a disproportionate burden of tobacco-related illness and mortality . ( Am J Health Promot 2011;25[5 Supplement]:S38–S50 . Background Indigenous Australians suffer a disproportionate burden of preventable chronic disease compared to their non-Indigenous counterparts – much of it diet-related . Increasing fruit and vegetable intakes and reducing sugar-sweetened soft-drink consumption can reduce the risk of preventable chronic disease . There is evidence from some general population studies that subsidising healthier foods can modify dietary behaviour . There is little such evidence relating specifically to socio-economically disadvantaged population s , even though dietary behaviour in such population s is arguably more likely to be susceptible to such interventions .This study aims to assess the impact and cost-effectiveness of a price discount intervention with or without an in-store nutrition education intervention on purchases of fruit , vegetables , water and diet soft-drinks among remote Indigenous communities . Methods / Design We will utilise a r and omised multiple baseline ( stepped wedge ) design involving 20 communities in remote Indigenous Australia . The study will be conducted in partnership with two store associations and twenty Indigenous store boards . Communities will be r and omised to either i ) a 20 % price discount on fruit , vegetables , water and diet soft-drinks ; or ii ) a combined price discount and in-store nutrition education strategy . These interventions will be initiated , at one of five possible time-points , spaced two-months apart . Weekly point-of-sale data will be collected from each community store before , during , and for six months after the six-month intervention period to measure impact on purchasing of discounted food and drinks . Data on physical , social and economic factors influencing weekly store sales will be collected in order to identify important covariates . Intervention fidelity and mediators of behaviour change will also be assessed . Discussion This study will provide original evidence on the effectiveness and cost-effectiveness of price discounts with or without an in-store nutrition education intervention on food and drink purchasing among a socio-economically disadvantaged population in a real-life setting .Trial registration Australian New Zeal and Clinical Trials Registry : A self-administered mood management intervention program for smoking cessation provided through the mail to Spanish-speaking Latinos result ed in a 23 % abstinence rate at 3 months compared to an 11 % abstinence rate for a smoking cessation guide alone . Participants ( N = 136 ) were r and omly assigned to receive either the cessation guide ( the Guía ) , or the Guía plus a mood management intervention ( Tom and o Control de su Vida ) presented in writing and in audiotape format . At 3 months after r and om assignment , 16 out of 71 of those assigned to the Guía-plus-mood management condition reported being abstinent ( not smoking for at least 7 days ) compared to 7 out of 65 in the Guía-only condition ( z = 1.8 ; p = .04 , one-tailed ) . Moreover , those with a history of major depressive episodes , but not currently depressed , reported an even higher abstinence rate in the Guía-plus-mood management condition , compared to the Guía-only condition ( 31 vs. 11 % , z = 1.8 , p = .04 , one-tailed ) . We conclude that the mood management mail intervention substantially increases abstinence rates , especially for those with a history of major depressive episodes During the postpartum period , ethnic minority women have higher rates of inactivity/under-activity than white women . The Nā Mikimiki ( “ the active ones ” ) Project is design ed to increase moderate-to-vigorous physical activity over 18 months among multiethnic women with infants 2–12 months old . The study was design ed to test , via a r and omized controlled trial , the effectiveness of a tailored telephone counseling of moderate-to-vigorous physical activity intervention compared to a print/website material s-only condition . Healthy , underactive women ( mean age = 32 ± 5.6 years ) with a baby ( mean age = 5.7 ± 2.8 months ) were enrolled from 2008–2009 ( N = 278 ) . Of the total sample , 84 % were ethnic minority women , predominantly Asian – American and Native Hawaiian . Mean self-reported baseline level of moderate-to-vigorous physical activity was 40 minutes/week with no significant differences by study condition , ethnicity , infant 's age , maternal body mass index , or maternal employment . Women had high scores on perceived benefits , self-efficacy , and environmental support for exercise but low scores on social support for exercise . This multiethnic sample 's demographic and psychosocial characteristics and their perceived barriers to exercise were comparable to previous physical activity studies conducted largely with white postpartum women . The Nā Mikimiki Project 's innovative tailored technology-based intervention and unique population are significant contributions to the literature on moderate-to-vigorous physical activity in postpartum women Purpose . To examine the efficacy of a stage-targeted physical activity intervention among low-income African-Americans . Methods . 207 participants were r and omly assigned to groups and administered baseline measures . Intervention participants were mailed stage-targeted physical activity information , whereas control participants received low-sodium diet brochures . Measures were readministered by phone 1 and 6 months later , with response rates of 69 % and 46 % , respectively . Results . 69 % of participants were African-American and 64 % had a monthly household income of < $ 1000 . A doubly-multivariate analysis of variance indicated that intervention participants reported more physical activity than control participants at 1 month ( F(1 , 204 ) = 4.03 , p < .05 ) . Unlike control participants , intervention participants reported significant stage progression at 1 month , according to a McNemar χ2 test . Gains attenuated by 6 months . Conclusions . The current study supports the use of this intervention among low-income African-Americans . Limitations include use of self-report measures and small sample size Background Tailored health communications to date have been based on a rather narrow set of theoretical constructs . Purpose This study was design ed to test whether tailoring a print-based fruit and vegetable ( F & V ) intervention on relatively novel constructs from self-determination theory ( SDT ) and motivational interviewing ( MI ) increases intervention impact , perceived relevance , and program satisfaction . The study also aim ed to explore possible user characteristics that may moderate intervention response . Methods African American adults were recruited from two integrated health care delivery systems , one based in the Detroit Metro area and the other in the Atlanta Metro area , and then r and omized to receive three tailored newsletters over 3 months . One set of newsletters was tailored only on demographic and social cognitive variables ( control condition ) , whereas the other ( experimental condition ) was tailored on SDT and MI principles and strategies . The primary focus of the newsletters and the primary outcome for the study was fruit and vegetable intake assessed with two brief self-report measures . Preference for autonomy support was assessed at baseline with a single item : “ In general , when it comes to my health I would rather an expert just tell me what I should do ” . Most between-group differences were examined using change scores . Results A total of 512 ( 31 % ) eligible participants , of 1,650 invited , were enrolled , of which 423 provided complete 3-month follow-up data . Considering the entire sample , there were no significant between-group differences in daily F & V intake at 3 month follow-up . Both groups showed similar increases of around one serving per day of F & V on the short form and half a serving per day on the long form . There were , however , significant interactions of intervention group with preference for autonomy-supportive communication as well as with age . Specifically , individuals in the experimental intervention who , at baseline , preferred an autonomy-supportive style of communication increased their F & V intake by 1.07 servings compared to 0.43 servings among controls . Among younger controls , there was a larger change in F & V intake , 0.59 servings , than their experimental group counterparts , 0.29 servings . Conversely , older experimental group participants showed a larger change in F & V , 1.09 servings , than older controls , 0.48 . Conclusion Our study confirms the importance of assessing individual differences as potential moderators of tailored health interventions . For those who prefer an autonomy-supportive style of communication , tailoring on values and other motivational constructs can enhance message impact and perceived relevance Background Hypertension is more prevalent and clinical ly severe among African – Americans than whites . Several health behaviors influence blood pressure ( BP ) control , but effective , accessible , culturally sensitive interventions that target multiple behaviors are lacking . Purpose We evaluated a culturally adapted , automated telephone system to help hypertensive , urban African – American adults improve their adherence to their antihypertensive medication regimen and to evidence -based guidelines for dietary behavior and physical activity . Methods We r and omized 337 hypertensive primary care patients to an 8-month automated , multi-behavior intervention or to an education-only control . Medication adherence , diet , physical activity , and BP were assessed at baseline and every 4 months for 1 year . Data were analyzed using longitudinal modeling . Results The intervention was associated with improvements in a measure of overall diet quality ( + 3.5 points , p < 0.03 ) and in energy expenditure ( + 80 kcal/day , p < 0.03 ) . A decrease in systolic BP between groups was not statistically significant ( −2.3 mmHg , p = 0.25 ) . Conclusions Given their convenience , scalability , and ability to deliver tailored messages , automated telecommunications systems can promote self-management of diet and energy balance in urban African – Americans 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 Mexican Americans along the US-Mexico border have been found to be disproportionately affected by chronic diseases particularly related to lack of physical activity and healthful food choices . A community-wide campaign ( CWC ) is an evidence -based strategy to address these behaviors but with few examples of implementation in Mexican descent population s facing profound health disparities . We examined exposure to a CWC , titled Tu Salud ¡ Sí Cuenta ! , and its association with meeting the recommended minutes of moderate and vigorous physical activity weekly and consuming more portions of fruits and vegetables daily . A cross-sectional sample of 1438 Mexican descent participants was drawn from a city-wide , r and omly-selected cohort interviewed between the years 2008 and 2012 . Multivariable comparisons of participants exposed and not exposed to the CWC and meeting physical activity guidelines or their fruit and vegetable consumptions using mixed effects models were conducted . The community-wide campaign components included different forms of mass media and individually-focused components such as community health worker ( CHW ) home visits . After adjusting for gender , age , marital status , educational attainment , language preference , health insurance , and diabetes diagnosis , the strongest association was found between meeting physical activity guidelines and exposure to both CHW discussion s and radio messages ( adjusted OR = 3.83 ; 95 % CI = [ 1.28 , 6.21 ] ; p = 0.0099 ) . Participants who reported exposure to both radio and TV messages consumed more portions of fruits and vegetables than those who reported no exposure ( adjusted RR = 1.30 ; 95 % CI = [ 1.02 , 1.66 ] ; p = 0.0338 ) . This study provides insights into the implementation and behavioral outcomes associated with exposure to a community-wide campaign , a potential model for addressing lifestyle modifications in population s affected by health disparities In a cluster r and omized controlled trial , Anthony Shakeshaft and colleagues measure the effectiveness of a multi-component community-based intervention for reducing alcohol-related harm Background African American women report insufficient physical activity and are disproportionally burdened by associated disease conditions ; indicating the need for innovative approaches to promote physical activity in this underserved population . Social media platforms ( i.e. Facebook ) and text messaging represent potential mediums to promote physical activity . This paper reports the results of a r and omized pilot trial evaluating a theory-based ( Social Cognitive Theory ) multi-component intervention using Facebook and text-messages to promote physical activity among African American women . Methods Participants ( N = 29 ) were r and omly assigned to receive one of two multi-component physical activity interventions over 8 weeks : a culturally-relevant , Social Cognitive Theory-based , intervention delivered by Facebook and text message ( FI ) ( n = 14 ) , or a non-culturally tailored print-based intervention ( PI ) ( n = 15 ) consisting of promotion brochures mailed to their home . The primary outcome of physical activity was assessed by ActiGraph GT3X+ accelerometers . Secondary outcomes included self-reported physical activity , physical activity-related psychosocial variables , and participant satisfaction . Results All r and omized participants ( N = 29 ) completed the study . Accelerometer measured physical activity showed that FI participants decreased sedentary time ( FI = −74 minutes/week vs. PI = + 118 minute/week ) and increased light intensity ( FI = + 95 minutes/week vs. PI = + 59 minutes/week ) and moderate-lifestyle intensity physical activity ( FI = + 27 minutes/week vs. PI = −34 minutes/week ) in comparison to PI participants ( all P ’s < .05 ) . No between group differences for accelerometer measured moderate-to-vigorous intensity physical activity were observed ( P > .05 ) . Results of secondary outcomes showed that in comparison to the PI , FI participants self-reported greater increases in moderate-to-vigorous physical activity ( FI = + 62 minutes/week vs. PI = + 6 minutes/week ; P = .015 ) and had greater enhancements in self-regulation for physical activity ( P < .001 ) and social support from family for physical activity ( P = .044 ) . Satisfaction with the FI was also high : 100 % reported physical activity-related knowledge gains and 100 % would recommend the program to a friend . Conclusions A culturally-relevant Facebook and text message delivered physical activity program was associated with several positive outcomes , including decreased sedentary behavior , increased light- and moderate-lifestyle intensity physical activity , enhanced psychosocial outcomes , and high participant satisfaction . Future studies with larger sample s are warranted to further explore the efficacy of technology-based approaches to promote physical activity among African American women . Trial Registration Clinical Trials.gov NCT02372565 . Registered 25 February 2015 Background Systematic review s have identified a range of brief interventions which increase physical activity in previously sedentary people . There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity . This study assesses whether it is worth providing motivational interviews , three months after giving initial advice , to those who have become more active . Methods / Design Study c and i date s ( n = 1500 ) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD . Only those that have increased their physical activity after three months ( n = 600 ) will be r and omised into the study . These participants will receive either a " mini booster " ( n = 200 ) , " full booster " ( n = 200 ) or no booster ( n = 200 ) . The " mini booster " consists of two telephone calls one month apart to discuss physical activity and maintenance strategies . The " full booster " consists of a face-to-face meeting with the facilitator at the same intervals . The purpose of these booster sessions is to help the individual maintain their increase in physical activity . Differences in physical activity , quality of life and costs associated with the booster interventions , will be measured three and nine months from r and omisation . The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield , which have large , ethnically diverse population s , high levels of economic deprivation , low levels of physical activity , poorer health and shorter life expectancy . Participants will be recruited through general practice s and community groups , as well as by postal invitation , to ensure the participation of minority ethnic groups and those with lower levels of literacy . Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities . A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10 % sample . Discussion The choice of study population , study interventions , brief intervention preceding the study , and outcome measure are discussed . Trial Registration Current Controlled Trials : IS RCT N56495859 ; Clinical Trials.gov : NCT00836459 Although the prevalence of smoking is lower among Hispanics than among the general population , smoking still levies a heavy public health burden on this underserved group . The current study , Adiós al Fumar ( Goodbye to Smoking ) , was design ed to increase the reach of the Spanish‐ language smoking cessation counseling service provided by the National Cancer Institute 's Cancer Information Service ( CIS ) and to evaluate the efficacy of a culturally sensitive , proactive , behavioral treatment program among Spanish‐speaking smokers . Adiós was a 2‐group r and omized clinical trial evaluating a telephone‐based smoking cessation intervention . Spanish‐speaking smokers ( N = 297 ) were r and omized to receive either st and ard counseling or enhanced counseling ( EC ) . Paid media was used to increase the reach of the Spanish‐ language smoking cessation services offered by the CIS . The Adiós sample was of very low socioeconomic status ( SES ) , and more than 90 % were immigrants . Calls to the CIS requesting smoking cessation help in Spanish increased from 0.39 calls to 17.8 calls per month . The unadjusted effect of EC only approached significance ( OR = 2.4 , P = .077 ) , but became significant after controlling for demographic and tobacco‐related variables ( OR = 3.8 , P = .048 ) . Adiós al Fumar demonstrated that it is possible to reach , retain , and deliver an adequate dose of treatment to a very low SES population that has traditionally been viewed as difficult to reach and hard to follow . Moreover , the findings suggest that a proactive , telephone‐counseling program , based on the Treating Tobacco Use and Dependence Clinical Practice Guideline and adapted to be culturally appropriate for Hispanics , is effective . Cancer 2007 . © 2006 American Cancer Society Background : This paper presents the study design and baseline data from Healthy Directions-Health Centers ( HCs ) , a study design ed to address social context ual factors in cancer prevention interventions for working class , multi-ethnic population s. This study is part of the Harvard Cancer Prevention Program Project . Methods : Ten community HCs were paired and r and omly assigned to intervention or control . Patients who resided in low income , multi-ethnic neighborhoods were identified and approached for participation . This study targeted fruit and vegetable consumption , red meat consumption , multi-vitamin intake , and physical activity . The intervention components consisted of : ( 1 ) a brief in-person study endorsement from the participant 's clinician at a scheduled routine care visit ; ( 2 ) an initial in-person counseling session with a health advisor ; ( 3 ) four follow-up telephone counseling sessions ; ( 4 ) multiple mailings of tailored material s ; and ( 5 ) linkages to relevant activities in the local community . Results : Fifteen percent of the sample smoked , 86 % reported eating fewer than five servings of fruits and vegetables per day , 50 % reported eating more than the recommended amounts of red meat , 40 % did not meet recommended physical activity levels , and 63 % did not take a multi-vitamin on a daily basis . Although overall social support was high , participants reported low levels of social norms for the target prevention behaviors . Other social context ual mediators and modifying factors are reported . Conclusions : By examining the relationships between social context ual factors and health behaviors , it may be possible to enhance the effectiveness of interventions aim ed at reducing social inequalities in risk behaviors Background Obesity among Black women continues to exceed that of other women . Most weight loss programs created without reference to specific cultural context s are less effective for Black than White women . Weight control approaches accessible to Black women and adapted to relevant cultural context s are important for addressing this problem . This paper reports the final results of SisterTalk , the r and omized controlled trial of a cable TV weight control program oriented toward Black women . Methods A five group design included a comparison group and a 2 × 2 factorial comparison of a ) interactive vs. passive programming and b ) telephone social support vs no telephone support , with 12 weekly initial cable TV programs followed by 4 monthly booster videos . At baseline , 3 , 8 , and 12 months post r and omization , telephone and in person surveys were administered on diet , physical activity , and physical measurements of height and weight were taken to calculate body mass index ( BMI ) . Analysis of variance ( ANOVA ) was used to examine differences over time , and between treatment and comparison groups . Dose variables reflecting use of the TV/video and written material s were also assessed . Results At 3 months , BMI , weight , and dietary fat were significantly lower and physical activity significantly higher among women exposed to the Cable TV intervention compared to the wait-list comparison group . Significant dietary fat differences were still observed at 8 and 12 month evaluations , but not BMI or physical activity differences . Main effects were not observed for interactive programming or enhanced social support at any time point . Within the intervention group , higher watching of the TV series and higher reading of educational material s were both ( separately ) associated with significantly lower dietary fat . Conclusions Cable TV was an effective delivery channel to assist Black women with weight control , increasing physical activity and decreasing dietary fat during an initial intervention period , but only dietary changes persisted Enhanced social support and the ability to interact with others during the show were not effective complementary intervention components as conducted in this trial . Future research to strengthen the ability of this approach to achieve long term effects may offer even more promising outcomes An interactive multimedia program to encourage individuals to decrease their dietary fat consumption and to increase consumption of fruits and vegetables was developed and evaluated at two worksites . The program presented content tailored to the user by gender , content interests , race , and age group . It was tested using a r and omized treatment and wait list control design ( n = 517 ) . Repeated- measures ANOVAs indicated significant intervention effects after 30 days for self-reported consumption of fat and of fruits and vegetables , for stage of change to adopt a low-fat diet , for intention and self-efficacy to reduce dietary fat , and for attitude toward the importance of diet . In addition , 60-day follow-up of the treatment subjects found that program effects were maintained on all measures . Within- subject analyses showed that program effects were replicated with the wait list group at 30 days . These results demonstrate the potential for short-exposure interactive programs to positively impact eating habits of employee population Physical inactivity , poor dietary habits , and obesity are vexing problems among minorities . SAving Lives , Staying Active ( SALSA ) was an 8-week r and omized controlled crossover design , pilot study to promote regular physical activity ( PA ) and fruit and vegetable ( FV ) consumption as a means to preventing weight gain among women of color . Participants completed measures of demographics , PA , and dietary habits . Women ( N = 50 ; M = 42 years ) who participated were overweight ( M BMI = 29.7 kg/m2 ; Mbody fat = 38.5 % ) and reported low levels of leisure time PA ( M = 10.7 MET-min/wk ) and FV consumption ( M = 4.2 servings/day ) . All were r and omized to a four-week ( 1 ) semiweekly Latin dance group or ( 2 ) internet-based dietary education group . All participants reported a significant increase in weekly leisure time PA from baseline ( M = 10.7 MET-min/wk ) to follow up ( M = 34.0 MET-min/wk , P < .001 ) , and FV consumption increased over time by group ( P = .02 ) . Data suggest that Latin dance interventions to improve PA and web-based interventions to improve dietary habits show promise for improving health among women of color BACKGROUND Ethnic minorities and lower-income adults have among the highest rates of obesity and lowest levels of regular physical activity ( PA ) . The Positive Action for Today 's Health ( PATH ) trial compares three communities that are r and omly assigned to different levels of an environmental intervention to improve safety and access for walking in low income communities . DESIGN AND SETTING Three communities matched on census tract information ( crime , PA , ethnic minorities , and income ) were r and omized to receive either : an intervention that combines a police-patrolled-walking program with social marketing strategies to promote PA , a police-patrolled-walking only intervention , or no-walking intervention ( general health education only ) . Measures include PA ( 7-day accelerometer estimates ) , body composition , blood pressure , psychosocial measures , and perceptions of safety and access for PA at baseline , 6 , 12 , 18 , and 24 months . INTERVENTION The police-patrolled walking plus social marketing intervention targets increasing safety ( training community leaders as walking captains , hiring off-duty police officers to patrol the walking trail , and containing stray dogs ) , increasing access for PA ( marking a walking route ) , and utilizes a social marketing campaign that targets psychosocial and environmental mediators for increasing PA . MAIN HYPOTHESES/ OUTCOMES : It is hypothesized that the police-patrolled walking plus social marketing intervention will result in greater increases in moderate-to-vigorous PA as compared to the police-patrolled-walking only or the general health intervention after 12 months and that this effect will be maintained at 18 and 24 months . CONCLUSIONS Implication s of this community-based trial are discussed Background Daily self-monitoring of diet and physical activity behaviors is a strong predictor of weight loss success . Text messaging holds promise as a viable self-monitoring modality , particularly among racial/ethnic minority population s. Objective This pilot study evaluated the feasibility of a text messaging intervention for weight loss among predominantly black women . Methods Fifty obese women were r and omized to either a 6-month intervention using a fully automated system that included daily text messages for self-monitoring tailored behavioral goals ( eg , 10,000 steps per day , no sugary drinks ) along with brief feedback and tips ( n=26 ) or to an education control arm ( n=24 ) . Weight was objective ly measured at baseline and at 6 months . Adherence was defined as the proportion of text messages received in response to self-monitoring prompts . Results The average daily text messaging adherence rate was 49 % ( SD 27.9 ) with 85 % ( 22/26 ) texting self-monitored behavioral goals 2 or more days per week . Approximately 70 % ( 16/23 ) strongly agreed that daily texting was easy and helpful and 76 % ( 16/21 ) felt the frequency of texting was appropriate . At 6 months , the intervention arm lost a mean of 1.27 kg ( SD 6.51 ) , and the control arm gained a mean of 1.14 kg ( SD 2.53 ; mean difference –2.41 kg , 95 % CI –5.22 to 0.39 ; P=.09 ) . There was a trend toward greater text messaging adherence being associated with greater percent weight loss ( r=–.36 ; P=.08 ) , but this did not reach statistical significance . There was no significant association between goal attainment and text messaging adherence and no significant predictors of adherence . Conclusions Given the increasing penetration of mobile devices , text messaging may be a useful self-monitoring tool for weight control , particularly among population s most in need of intervention . Trial Registration Clinical trials.gov : NCT00939081 ; http:// clinical trials.gov/show/NCT00939081 ( Archived by WebCite at http://www.webcitation.org/6KiIIcnk1 ) 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 This study tested the effects of two theory-based interventions to increase fruit and vegetable intake . Hypothesized intervention mediators included self-efficacy ( SE ) , social support ( SS ) , autonomous motivation ( AM ) , and controlled motivation ( CM ) . At baseline , 1,021 African American adults were recruited from 16 churches r and omized to one comparison and two intervention groups : Group 1 ( st and ard educational material s ) , Group 2 ( culturally targeted material s ) , and Group 3 ( culturally targeted material s and telephone-based motivational interviewing ) . A well-fitted model based on structural equation modeling — χ2(df = 541 , N = 353 , 325 ) = 864.28 , p < .001 , normed fit index = .96 , nonnormed fit index = .98 , comparative fit index = .98 , root mean square error of approximation = .042—demonstrated that AM was both a significant mediator and moderator . In the subgroup with low baseline AM , AM mediated 17 % of the effect of the Group 3 intervention on fruit and vegetable intake . Conversely , SS , SE , and CM were not significant mediators . Implication s related to theory and intervention development are discussed OBJECTIVE This paper describes the design and findings of a pilot Mothers In Motion ( P-MIM ) program . DESIGN A r and omized controlled trial that collected data via telephone interviews and finger stick at 3 time points : baseline and 2 and 8 months post-intervention . SETTING Three Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) sites in southern Michigan . PARTICIPANTS One hundred and twenty nine overweight and obese African-American and white mothers , 18 - 34 years old . INTERVENTION The 10-week , theory-based , culturally sensitive intervention messages were delivered via a series of 5 chapters on a DVD and complemented by 5 peer support group teleconferences . MAIN OUTCOME MEASURES Dietary fat , fruit , and vegetable intake ; physical activity ; stress ; feelings ; body weight ; and blood glucose . ANALYSIS General linear mixed model was applied to assess treatment effects across 2 and 8 months post-intervention . RESULTS No significant effect sizes were found in primary and secondary outcome variables at 2 and 8 months post-intervention . However , changes in body weight and blood glucose showed apparent trends consistent with the study 's hypotheses . CONCLUSIONS AND IMPLICATION S The P-MIM showed promise for preventing weight gain in low-income overweight and obese women . However , a larger experimental trial is warranted to determine the effectiveness of this intervention Objective To evaluate the acceptability and feasibility of a scalable obesity treatment program integrated with pediatric primary care and delivered using interactive voice technology ( IVR ) to families from underserved population s. Design and Methods Fifty parent-child dyads ( child 9–12 yrs , BMI > 95th percentile ) were recruited from a pediatric primary care clinic and r and omized to either an IVR or a wait-list control ( WLC ) group . The majority were lower-income , African-American ( 72 % ) families . Dyads received IVR calls for 12 weeks . Call content was informed by two evidence d-based interventions . Anthropometric and behavioral variables were assessed at baseline and 3 mo follow-up . Results Forty-three dyads completed the study . IVR parents ate 1 cup more fruit than WLC ( p < .05 ) . No other groups differences were found . Children classified as high users of the IVR decreased weight , BMI and BMI z-score compared to low users ( p<.05 ) . Mean number of calls for parents and children were 9.1 ( 5.2 SD ) and 9.0 ( 5.7 SD ) , respectively . Of those who made calls , > 75 % agreed that the calls were useful , made for people like them , credible , and helped them eat healthy foods . Conclusion An obesity treatment program delivered via IVR may be an acceptable and feasible re source for families from underserved population OBJECTIVE Computer-tailored and Internet-based interventions to promote physical activity behavior have shown some promise , but only few have been tested among African Americans . We examined the feasibility and efficacy of three 1-year , multiple contact physical activity interventions ( Tailored Internet , Tailored Print , St and ard Internet ) in a sub sample of African American participants ( n = 38 ) enrolled in a r and omized controlled trial . MATERIAL S AND METHODS Participants r and omly assigned to Tailored Internet and Print programs received individually tailored computer expert system feedback delivered via Internet or print . Participants in the St and ard Internet program received access to six currently available physical activity Web sites . Self-reported physical activity was assessed at baseline and 6 and 12 months with the 7-Day Physical Activity Recall . RESULTS Across all participants , physical activity changed from 17.24 min/week ( st and ard deviation [ SD ] = 20.72 ) at baseline to 139.44 min/week ( SD = 99.20 ) at 6 months , to 104.26 min/week ( SD = 129.14 ) at 12 months . According to available consumer satisfaction data ( n = 30 ) , 70 % reported reading most or all of the physical activity information received by Internet or mail . Most participants described the Internet- and print-based physical activity programs as " somewhat " or " very " helpful ( 80 % ) and enjoyable ( 87 % ) . CONCLUSIONS These findings suggest that computer-tailored and Internet-based interventions are able to produce long-term increases in physical activity and associated process variables among African American participants . Future studies with larger numbers of African American participants are needed to determine which of the programs ( Tailored Print , Tailored Internet , St and ard Internet ) are more effective and what program modifications might be helpful in assisting this population in becoming more active 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 To pilot the design and methodology for a large r and omised controlled trial ( RCT ) of two interventions to promote healthier food purchasing : culturally appropriate nutrition education and price discounts . DESIGN A 12-week , single-blind , pilot RCT . Effects on food purchases were measured using individualised electronic shopping data ( ' Shop ' N Go ' system ) . Partial data were also collected on food expenditure at other ( non-supermarket ) retail outlets . SETTING A supermarket in Wellington , New Zeal and . PARTICIPANTS Eligible customers were those who were the main household shoppers , shopped mainly at the participating store , and were registered to use the Shop ' N Go system . Ninety-seven supermarket customers ( 72 % women ; age 40 + /- 9.6 years , mean + /- st and ard deviation ) were r and omised to one of four intervention groups : price discounts , nutrition education , a combination of price discounts and nutrition education , or control ( no intervention ) . RESULTS There was a 98 % follow-up rate of participants , with 85 % of all reported supermarket purchases being captured via the electronic data collection system . The pilot did , however , demonstrate difficulty recruiting Maori , Pacific and low-income shoppers using the electronic register and mail-out . CONCLUSIONS This pilot study showed that electronic sales data capture is a viable way to measure effects of study interventions on food purchases in supermarkets , and points to the feasibility of conducting a large-scale RCT to evaluate the effectiveness of price discounts and nutrition education . Recruitment strategies will , however , need to be modified for the main trial in order to ensure inclusion of all ethnic and socio-economic groups INTRODUCTION Research indicates that low fruit and vegetable intake is a risk factor for many chronic diseases . Despite large-scale education campaigns , the great majority of Americans do not consume recommended levels . We tested the ability of a single brief interactive experience of the Little by Little CD-ROM to increase fruit and vegetable intake in low-income women . METHODS A r and omized placebo-controlled , parallel-group trial included 481 low-income , female participants : mean age 50.1 years , 48.4 % African American , 51.6 % non-Hispanic white , and 92.5 % below 185 % of the federally design ated poverty level . Participants received one of three conditions : 1 ) a one-time experience with the Little by Little CD-ROM , 2 ) the Little by Little CD-ROM plus two reminder telephone calls , or 3 ) a stress management CD-ROM ( control condition ) . We assessed baseline and follow-up dietary intake with a modified 24-hour recall . RESULTS Two months after the one-time experience with the CD-ROMs , both intervention groups reported significantly higher intakes of fruits and vegetables than the control group . The Little by Little group with reminder calls increased daily intake by 1.32 fruits/vegetables , an 86 % greater increase than the control group ( P = .016 ) . The Little by Little group without reminder calls increased daily intake by 1.20 fruits/vegetables , a 69 % greater increase than the control group ( P = .052 ) . Significantly greater movement in Stage of Readiness for Change also occurred in the Little by Little groups compared with the control group . CONCLUSION The Little by Little CD-ROM may be useful in public health and clinical situations to increase fruit and vegetable intake Background The beneficial effect of physical activity for the prevention of a range of chronic diseases is widely acknowledged . These conditions are most prevalent in low-income groups where physical activity levels are consistently lower . Social marketing is the government ’s recommended approach to promoting physical activity but evidence of its effectiveness is limited . The purpose of this study was to examine the effect of a social marketing campaign on the monthly recruitment , attendance and retention levels at a community-based physical activity programme in a low income area . Methods A six-month social marketing campaign was design ed and delivered in a highly-deprived suburban neighbourhood . Analysis of variance was used to assess effects on recruitment and attendance . χ2 tests of independence were used to compare dropouts and adherers and effectiveness of recruitment mechanisms . Percentages were used to compare adherence rates at intervention , pre-existing sessions in the intervention area and control area sessions . Results Attendance data were collected weekly and presented and analysed monthly to provide a view of changing participation over the six month intervention period , as compared to attendance at pre-existing sessions in the intervention area and in a control area . Recruitment into intervention sessions was significantly greater than into pre-existing and control area sessions in Month 1 ( 18.13v1.04 p = .007 , 18.13v.30 p=.005 ) , Month 5 ( 3.45v.84 p=.007 , 3.45v.30 p<.001 ) and Month 6 ( 5.60v.65 p<.001 , 5.60v.25 p<.001 ) . Attendance at intervention sessions was significantly greater in all six months than at pre-existing and control area sessions ; Month 1 ( 38.83v7.17 p<.001 , 38.83v4.67 , p<.001 ) , Month 2 ( 21.45v6.20 p<.001 , 21.45v4.00 , p<.001 ) , Month 3 ( 9.57v6.15 p<.001 , 9.57v3.77 , p<.001 ) , Month 4 ( 17.35v7.31 p<.001 , 17.35v4.75 , p<.001 ) , Month 5 ( 20.33v8.81 p=.007 , 20.33v4.54 p<.001 ) and Month 6 ( 28.72v8.28 p<.001 , 28.72v.4.00 p<.001 ) . Drop-out rates in the intervention area were similar to the control area ( 66.2%v69.9 % ) , and considerably lower than in pre-existing sessions ( 83 % ) . In months one and two , traditional marketing techniques ( posters/outdoor banners/flyers ) had the greatest influence on recruitment compared to word of mouth communication ( 84.5%v15.5 % ) . In months five and six word of mouth influenced 57.5 % of new recruits . Conclusions Direct comparisons with other programmes were difficult due to a lack of st and ard definitions of recruitment and adherence and limited reporting of findings . However when compared to pre-existing sessions and sessions delivered in a control area , monthly attendance patterns indicated that a reasonably well funded social marketing campaign increased recruitment into exercise sessions , maintained good levels of attendance and reasonable levels of adherence . Good attendance levels support on-going campaign success by offering evidence of peer and social support for the activity and increasing opportunities for social interaction . They also increase the capacity and reach of the word of mouth communication channels , the most effective form of promotion . Further study into methods of improving exercise adherence is required Background Over 45 % of American women 20–39 years old are at risk for type 2 diabetes , cardiovascular disease , and other health conditions because they are overweight or obese . The prevalence of overweight and obesity is disproportionately high among low-income women . This paper describes the study design and rationale of a community based intervention ( Mothers In Motion , MIM ) aim ed to prevent weight gain among low-income overweight and obese mothers18 - 39 years old by promoting stress management , healthy eating , and physical activity . Methods / Design Peer recruiters approach participants from 5 Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) in Michigan . The MIM delivers theory-based , culturally-sensitive intervention messages via a combination of DVDs and peer support group teleconferences ( PSGTs ) . The DVD features African American and white overweight and obese WIC mothers who participated in a healthy lifestyle intervention patterned after MIM . The PSGTs are led by paraprofessionals from Michigan State University Extension and WIC providers in Michigan who are trained in motivational interviewing and group facilitation skills . Participants are r and omly assigned to an intervention ( n = 350 ) or comparison group ( n = 175 ) . The intervention group receives a 16-week intervention on a weekly or bi-weekly basis . Participants are asked to watch 10 MIM DVD chapters at home and join 10 PSGT sessions by phone . The comparison group receives printed educational material s. The primary outcome is body weight . Secondary outcomes include dietary fat , fruit , and vegetable intake ; physical activity ; stress , and affect . Mediators are self-efficacy , emotional coping response , social support , and autonomous motivation . Telephone interviews and in-person data collection at WIC offices occur at 3 time points : baseline , immediately , and 3 months after the 16-week intervention . Discussion If MIM shows effectiveness , it could have a favorable impact on public health and community programs . The DVDs and PSGTs will be disseminated in WIC , Extension , clinical practice that promote healthy lifestyles for similar target audiences to make a broad contribution to the prevention of weight gain in low-income mothers . Also , our methodology can be adapted by research ers and community stakeholders to help other low-income population s prevent weight gain . Trial registration Clinical Trials Number : NCT01839708 Background Mothers of an infant are much less likely to exercise regularly compared to other women . This study tested the efficacy of a brief tailored intervention to increase physical activity ( PA ) in women 3–12 months after childbirth . The study used a pretest-posttest design . Sedentary women ( n = 20 ) were recruited from a parenting organization . Half the participants were ethnic minorities , mean age was 33 ± 3.8 , infants ' mean age was 6.9 ± 2.4 months , 50 % were primiparas , and mean body mass index was 23.6 ± 4.2 . Methods The two-month intervention included telephone counseling , pedometers , referral to community PA re sources , social support , email advice on PA/pedometer goals , and newsletters . The primary outcome of the study was minutes per week of moderate and vigorous leisure-time physical activity measured by the Godin physical activity instrument . Results All women ( 100 % ) returned for post-test measures ; thus , paired t-tests were used for pre-post increase in minutes of moderate and vigorous leisure-time physical activity and comparisons of moderate and vigorous leisure-time physical activity increases among ethnic groups . At baseline participants ' reported a mean of 3 ± 13.4 minutes per week moderate and vigorous leisure-time physical activity . At post-test this significantly increased to 85.5 ± 76.4 minutes per week of moderate and vigorous leisure-time physical activity ( p < .001 , Cohen 's d = 2.2 ; effect size r = 0.7 ) . There were no differences in pre to post increases in minutes of moderate and vigorous leisure-time physical activity among races . Conclusion A telephone/email intervention tailored to meet the needs of postpartum women was effective in increasing physical activity levels . However , r and omized trials comparing tailored telephone and email interventions to st and ard care and including long-term follow-up to determine maintenance of physical activity are warranted Background The prevention of type 2 diabetes is a globally recognised health care priority , but there is a lack of rigorous research investigating optimal methods of translating diabetes prevention programmes , based on the promotion of a healthy lifestyle , into routine primary care . The aim of the study is to establish whether a pragmatic structured education programme targeting lifestyle and behaviour change in conjunction with motivational maintenance via the telephone can reduce the incidence of type 2 diabetes in people with impaired glucose regulation ( a composite of impaired glucose tolerance and /or impaired fasting glucose ) identified through a vali date d risk score screening programme in primary care . Design Cluster r and omised controlled trial undertaken at the level of primary care practice s. Follow-up will be conducted at 12 , 24 and 36 months . The primary outcome is the incidence of type 2 diabetes . Secondary outcomes include changes in HbA1c , blood glucose levels , cardiovascular risk , the presence of the Metabolic Syndrome and the cost-effectiveness of the intervention . Methods The study consists of screening and intervention phases within 44 general practice s coordinated from a single academic research centre . Those at high risk of impaired glucose regulation or type 2 diabetes are identified using a risk score and invited for screening using a 75 g-oral glucose tolerance test . Those with screen detected impaired glucose regulation will be invited to take part in the trial . Practice s will be r and omised to st and ard care or the intensive arm . Participants from intensive arm practice s will receive a structured education programme with motivational maintenance via the telephone and annual refresher sessions . The study will run from 2009–2014 . Discussion This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme conducted within routine primary care in the United Kingdom . Trial registration Clinical trials.gov Background Despite the significant health benefits of regular physical activity , approximately half of American adults , particularly women and minorities , do not meet the current physical activity recommendations . Mobile phone technologies are readily available , easily accessible and may provide a potentially powerful tool for delivering physical activity interventions . However , we need to underst and how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women . The purpose of this paper is to describe the study design and protocol of the mPED ( mobile phone based physical activity education ) r and omized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions . Methods A r and omized controlled trial ( RCT ) with three arms ; 1 ) PLUS ( 3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention ) , 2 ) REGULAR ( 3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention ) , and 3 ) CONTROL ( pedometer only , but no intervention will be conducted ) . A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be r and omized into one of the three groups . The mobile phone serves as a means of delivering the physical activity intervention , setting individualized weekly physical activity goals , and providing self-monitoring ( activity diary ) , immediate feedback and social support . The mobile phone also functions as a tool for communication and real-time data capture . The primary outcome is objective ly measured physical activity . Discussion If efficacy of the intervention with a mobile phone is demonstrated , the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth . Trial Registration Clinical Tested a 7-month , media-based , community intervention among Hispanics in San Francisco design ed to change levels of information on the damaging effects of cigarette smoking and on the availability of culturally appropriate cessation services . Three community-wide surveys of Hispanics were conducted with independent r and om sample s , two as baselines ( n = 1,660 and 2,053 ) and one postintervention ( n = 1,965 ) . Results showed that changes in the level of awareness of cessation services had taken place after implementation of the intervention . Furthermore , those changes took place primarily among the less acculturated Spanish-speaking Hispanics who were the target of the intervention . The changes in information reported here demonstrate that a culturally appropriate information dissemination campaign that utilizes multiple channels can produce changes in a community 's level of information even when the campaign is implemented for a relatively short period BACKGROUND Stroke is a disease with tremendous individual , family , and societal impact across all race/ethnic groups . Mexican Americans , the largest subgroup of Hispanic Americans , are at even higher risk of stroke than European Americans . AIM To test the effectiveness of a culturally sensitive , church-based , multi-component , motivational enhancement intervention for Mexican Americans and European Americans in reducing stroke risk factors . METHODS Participants enroll in family or friendship pairs , from the same Catholic church in the Corpus Christi Texas area , and are encouraged to change diet and physical activity behaviors and provide support for behavior change to their partners . Churches are r and omized to either the intervention or control group . Goal enrollment for each of the 10 participating churches is 40 participant pairs . The intervention consists of self-help material s ( including a motivational short film , cookbook/healthy eating guide , physical activity guide with pedometer , and photonovella ) , five motivational interviewing calls , two tailored newsletters , parish health promotion activities and environmental changes , and a peer support workshop where participants learn to provide autonomy supportive counseling to their partner . SHARE 's three primary outcomes are self-reported sodium intake , fruit and vegetable intake , and level of physical activity . Participants complete question naires and have measurements at baseline , six months , and twelve months . Persistence testing is performed at 18 months in the intervention group . The trial is registered with clinical trials.gov ( NCT01378780 ) 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 The prevalence of obesity is significantly higher among American Indians ( AIs ) and is associated with increased rates of diabetes , hypertension , and cardiovascular disease . We implemented a 14-mo intervention trial ( Navajo Healthy Stores ) on the Navajo Nation that sought to increase availability of healthier foods in local food stores and to promote these foods at the point of purchase and through community media . We divided the Navajo Nation into 10 store regions , half of which were r and omized to intervention and half to comparison . We evaluated the program by using a pre-post sample of systematic ally sample d adult Navajo consumers ( baseline , n = 276 ; postintervention , n = 145 ) . Intervention impact was examined by analyzing pre-post differences by intervention group and by intervention exposure level . When intervention and comparison groups were compared , only body mass index ( BMI ) showed a trend toward impact of the intervention ( P = 0.06 ) . However , greater exposure to the intervention was associated with significantly reduced BMI ( P ≤ 0.05 ) and improved healthy food intentions ( P ≤ 0.01 ) , healthy cooking methods ( P ≤ 0.05 ) , and healthy food getting ( P ≤ 0.01 ) . With increasing exposure , the odds of improving overweight or obese status was 5.02 ( 95 % CI : 1.48 , 16.99 ; P ≤ 0.01 ) times the odds of maintaining or worsening overweight or obese status . In summary , a food store intervention was associated with reduced overweight/obesity and improved obesity-related psychosocial and behavioral factors among those persons most exposed to the intervention on an AI reservation BACKGROUND Text messaging programs on mobile phones have shown some promise in helping people quit smoking . Text2Quit is an automated , personalized , interactive mobile health program that sends text messages to offer advice , support , and reminders about quitting smoking . PURPOSE To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. METHODS Participants ( n=503 ) were recruited on the Internet and r and omized to receive Text2Quit or self-help material . Between 2011 and 2013 , participants were surveyed at baseline and at 1 , 3 , and 6 months post-enrollment to assess smoking status . Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up . An intent to treat analysis was used , and those lost to follow-up were categorized as smokers . All analyses were completed in 2013 . RESULTS Biochemically confirmed repeated point prevalence abstinence favored the intervention group , with 11.1 % abstinent compared to 5.0 % of the control group ( relative risk=2.22 , 95 % CI=1.16 , 4.26 , p<0.05 ) . Similarly , self-reported repeated point prevalence abstinence was higher in the intervention group ( 19.9 % ) than in the control group ( 10.0 % ) ( p<0.01 ) . Effects were found to be uniform across the analyzed demographic subgroups , although suggestive of a larger effect for non-whites than whites . CONCLUSIONS These results provide initial support for the relative efficacy of the Text2Quit program 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 This r and omized controlled trial tested a tailored , telephone-based physical activity coaching intervention for a predominantly African American group of women with severe obesity and mobility disability . METHODS We recruited 92 clinic patients from the University of Illinois at Chicago Medical Center referred by their physicians during 2004 - 2007 and r and omized participants to one of three groups -- awareness(informational brochure , no coaching ) , lower support ( phone coaching only ) and higher support ( phone coaching plus monthly exercise support group)--to determine the efficacy of a tailored coaching intervention on key health outcomes , which included body weight and body mass index , blood pressure , cholesterol , physical activity ( barriers and self-reported activity ) , movement and mobility , general health , and social support . RESULTS The higher support group had the greatest reduction in Body Mass Index ( BMI ) ( 7.4 % ) compared with a 0.2 % and 1.6 % increase in BMI for the lower support and awareness groups , respectively ( pb.01 ) . Both the higher and lower support groups had a greater increase in physical activity scores ( 39 % and 30 % , respectively)compared with a decline of 13 % in the awareness group ( pb.05 ) . CONCLUSION Providing phone-based coaching and monthly in-person exercise support group sessions appear to be an effective approach for reducing body weight and increasing physical activity among severely obese , disabled adults residing in difficult social environments BACKGROUND The greater presence of supermarkets in low-income , high-minority neighborhoods has the potential to positively affect diet quality among those at greatest risk of obesity . In-store marketing strategies that draw attention to healthier products may be effective , sustainable , and scalable for improving diet quality and health . Few controlled studies of in-store marketing strategies to promote sales of healthier items in low-income , high-minority neighborhoods have been conducted . OBJECTIVE The objective of this study was to evaluate the effects of in-store marketing strategies to promote the purchase of specific healthier items in 5 product categories : milk , ready-to-eat cereal , frozen meals , in-aisle beverages , and checkout cooler beverages . DESIGN The design was a cluster-r and omized controlled trial conducted from 2011 to 2012 . Eight urban supermarkets in low-income , high-minority neighborhoods were the unit of r and omization , intervention , and analysis . Stores were matched on the percentage of sales from government food-assistance programs and store size and r and omly assigned to an intervention or control group . The 4 intervention stores received a 6-mo , in-store marketing intervention that promoted the sales of healthier products through placement , signage , and product availability strategies . The 4 control stores received no intervention and were assessment -only controls . The main outcome measure was weekly sales of the targeted products , which was assessed on the basis of the stores ' sales data . RESULTS Intervention stores showed significantly greater sales of skim and 1 % milk , water ( in aisle and at checkout ) , and 2 of 3 types of frozen meals compared with control store sales during the same time period . No differences were found between the stores in sales of cereal , whole or 2 % milk , beverages , or diet beverages . CONCLUSIONS These data indicate that straightforward placement strategies can significantly enhance the sales of healthier items in several food and beverage categories . Such strategies show promise for significant public health effects in communities with the greatest risk of obesity AIMS To determine whether a smoking cessation service using mobile phone text messaging is as effective for Maori as non-Maori . METHODS A single-blind r and omised controlled trial was undertaken with recruitment targeted to maximise the participation of young Maori . The intervention included regular , personalised text messages providing smoking cessation advice , support , and distraction . Maori text messages related to Maori language , support messages ( in Maori and English ) and information on Maori traditions . Text messaging was free for 1 month . After 6 weeks , the number of messages reduced from 5 per day to 3 per week until the 26-week follow-up . RESULTS Participants included 355 Maori and 1350 non-Maori . Maori in the intervention group were more likely to report quitting ( no smoking in the past week ) at 6 weeks ( 26.1 % ) than those in the control group ( 11.2 % ) RR 2.34 , 95 % CI : 1.44 - 3.79 . There was no significant difference between the RR for Maori and that for non-Maori ( RR : 2.16 , 95%CI : 1.72 - 2.71 ) . CONCLUSIONS A mobile phone-based cessation programme was successful in recruiting young Maori , and was shown to be as effective for Maori as non-Maori at increasing short-term self-reported quit rates . This shows clear potential as a new public health initiative BACKGROUND Fruit and vegetable ( FV ) intake in black men are far below national recommendations . METHODS Urban , primarily immigrant , black men ( n=490 ) from the New York City metropolitan area participating in the Cancer Awareness and Prevention ( CAP ) Trial ( 2005 - 2007 ) were r and omly assigned to one of two intervention groups : 1 ) FV Education ( FVE ) or 2 ) Prostate Education ( PE ) . Both interventions entailed a mailed brochure plus two tailored telephone education ( TTE ) calls . Outcomes , measured at baseline and at eight months , included knowledge of FV recommendations , perceived benefits , stage of readiness to adopt recommendations and self-reported FV consumption . RESULTS At follow-up , the FVE group consumed an average of 1.2 more FV servings per day than the PE group ( P<0.001 ; adjusted for baseline ) . The FVE group also demonstrated increases in knowledge about recommended FV amounts ( P<0.01 ) and appropriate serving sizes ( P<0.05 ) , and in the percent of participants moving from a lower to a higher stage of readiness to adopt FV recommendations ( P<0.05 ) . The FVE group did not demonstrate increases in knowledge related to the importance of eating a colorful variety or in the ability to name potential health benefits . CONCLUSIONS TTE can be a practical and moderately effective intervention for raising awareness of FV recommendations and for promoting FV consumption in urban and primarily immigrant black men 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 BACKGROUND Among Alaska Native women residing in the Yukon-Kuskokwim ( Y-K ) Delta region of Western Alaska , about 79 % smoke cigarettes or use smokeless tobacco during pregnancy . Treatment methods developed and evaluated among Alaska Native pregnant tobacco users do not exist . This pilot study used a r and omized two-group design to assess the feasibility and acceptability of a targeted cessation intervention for Alaska Native pregnant women . METHODS Recruitment occurred over an 8-month period . Enrolled participants were r and omly assigned to the control group ( n = 18 ; brief face-to-face counseling at the first visit and written material s ) or to the intervention group ( n = 17 ) consisting of face-to-face counseling at the first visit , four telephone calls , a video highlighting personal stories , and a cessation guide . Interview-based assessment s were conducted at baseline and follow-up during pregnancy ( > or=60 days postr and omization ) . Feasibility was determined by the recruitment and retention rates . RESULTS The participation rate was very low with only 12 % of eligible women ( 35/293 ) enrolled . Among enrolled participants , the study retention rates were high in both the intervention ( 71 % ) and control ( 94 % ) groups . The biochemically confirmed abstinence rates at follow-up were 0 % and 6 % for the intervention and control groups , respectively . DISCUSSION The low enrollment rate suggests that the program was not feasible or acceptable . Alternative approaches are needed to improve the reach and efficacy of cessation interventions for Alaska Native women The Internet is a new technology for health communication in communities . The 5 a Day , the Rio Gr and e Way website intended to increase fruits and vegetables ( FV ) consumption was evaluated in a rural region enrolling 755 adults ( 65 % Hispanic , 9 % Native American , 88 % female ) in a r and omized pretest – posttest controlled trial in 2002–2004 . A total of 473 ( 63 % ) adults completed a 4-month follow-up . The change in daily intake on a food frequency question naire ( control : mean = − 0.26 servings ; intervention : mean = 0.38 ; estimated difference = 0.64 , SD = 0.52 , t(df = 416 ) = 1.22 , p = 0.223 ) and single item ( 13.9 % eating 5 + servings at pretest , 19.8 % posttest for intervention ; 17.4 % , 13.8 % for controls ; odds ratio ( OR ) = 1.84 , 95 % CI = 1.07 , 3.17 ) was in the expected direction but significant only for the single item . Website use was low and variable ( logins : M = 3.3 , range = 1 to 39.0 ; total time : M = 22.2 minutes , range = 0 to 322.7 ) , but it was associated positively with fruit and vegetable intake ( total time : Spearman r = 0.14 , p = 0.004 for food frequency ; Spearman r = 0.135 , p = 0.004 for single item ) . A nutrition website may improve FV intake . The comparison on the food frequency measure may have been undermined by its high variability . Websites may be successful in community setting s only when they are used enough by adults to influence them 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 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 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 Summary We evaluated the effect of home telehealth on weight maintenance after a group-based weight loss programme . The home telehealth intervention comprised telephone counselling and home Internet-enabled digital video recorders ( DVRs ) with three channels of video programmes . The video content provided reinforcement and support to promote problem solving , prevent relapse and sustain motivation . Eighty-eight obese or overweight African-American women were r and omized to receive monthly telephone counselling ( control ) or the home telehealth intervention . The weight change during maintenance was not significant in either group ( 0.6 kg in the intervention group , 0.0 kg in the control group ) , and there was no significant difference between them . Changes in diet , physical activity , social support and self-efficacy during the maintenance period did not differ significantly between groups . DVR use was low : during the intervention , the number of valid DVR viewings ranged from zero to 42 per person . DVR use was positively associated with previous attendance at the weight loss classes . Home video-based telehealth is a new method of delivering a weight loss maintenance intervention to African-American women . It had no effect on weight maintenance in the present study 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 Telephone quitlines are utilized by diverse individuals and represent an effective tobacco-cessation modality . Quitlines allow tobacco users to seek support for multiple quit attempts . Little is known about how frequently tobacco users take advantage of this opportunity . No studies have been conducted to determine how communication strategies affect quitline re-enrollments . This study aim ed to determine the rates of quitline re-enrollment and to compare the responses of people of varying racial/ethnic identities to invitations utilizing different communication strategies . DESIGN Four-cell RCT . SETTING / PARTICIPANTS R and om sample of 2400 tobacco users who enrolled into services during 2006 , with oversampling of ethnic population s. INTERVENTION Between November 2006 and January 2007 , participants received either no invitation to re-enroll or were invited to re-enroll into services via a letter , a letter with ethnic-specific content , or a letter and a telephone call . MAIN OUTCOME MEASURES Re-enrollment into quitline services . RESULTS Analysis of the 252 days prior to the intervention result ed in a spontaneous re-enrollment rate of 0.54 % per 30 days . Recruitment using mailers did not significantly change this rate ; the addition of telephone calls increased re-enrollment to 6.93 % per 30 days . No significant differences were found among the sub population s studied . Invalid addresses ( 16 % ) ; invalid telephone numbers ( 29.1 % ) ; and the inability to reach subjects after five call attempts ( 37.9 % ) were barriers to recruitment . CONCLUSIONS For those who have previously called quitlines for help , proactive re-enrollment can be one way to initiate a new quit attempt after relapse . This study has shown that it is feasible to re-enroll former quitline participants , making the test of effectiveness the next logical step OBJECTIVE To evaluate the feasibility and efficacy of an individually tailored , Internet-plus-email physical activity intervention design ed for adult women . METHOD Healthy and ethnically-diverse adult females ( N=156 ) ( mean age=42.8 years , 65 % Caucasian ) from California were r and omly assigned to an intervention ( access to a tailored website and weekly emails ) or wait-list control group . Participants completed web-based assessment s of physical activity , stage of behavior change , and psychosocial variables at baseline , one month , two months , and three months . Data were collected during 2006 - 2007 . Multilevel r and om coefficient modeling examined group differences in rates of change . RESULTS As compared to the control condition , the intervention group increased walking ( + 69 versus + 32 min per week ) and total moderate-to-vigorous physical activity ( + 23 versus -25 min per week ) after three months . The intervention did not impact stage of behavior change or any of the other psychosocial variables . CONCLUSION A tailored , Internet-based intervention for adult women had a positive effect on walking and moderate-to-vigorous physical activity in an ethnically-diverse sample . However , given the lack of comparable research contact in the control group , these findings should be taken cautiously 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 We report on the results of a low-intensity behavioral intervention to reduce second h and smoke ( SHS ) exposure of children with asthma from low income minority households in Los Angeles , California . In this study , 242 child/adult dyads were r and omized to a behavioral intervention ( video , workbook , minimal counseling ) or control condition ( brochure ) . Main outcome measures included child ’s urine cotinine and parental reports of child ’s hours of SHS exposure and number of household cigarettes smoked . Implementation of household bans was also considered . No differences in outcomes were detected between intervention and control groups at follow-up . Limitations included high attrition and low rates of collection of objective measures ( few children with urine cotinine sample s ) . There continues to be a need for effective culturally and linguistically appropriate strategies that support reduction of household SHS exposure among children with asthma in low income , minority households BACKGROUND This article describes the process and results of a smoking cessation intervention r and omized clinical trial ( RCT ) that was conducted as a community-based participatory research project . This RCT tested whether outcomes are improved by adding social justice and tobacco industry targeting messages to a smoking cessation program conducted among African American adults within a low-income community in San Francisco , California . This study provides lessons for future similar research projects that focus on urban low-income population s. METHODS Participants were r and omly allocated to receive a smoking-cessation program ( control group [ CG ] ) or CG care plus tobacco industry and media ( IAM ) messages . Primary interventions were behavioral . At intake , participants reporting severe withdrawal or smoking > or = 25 cigarettes daily were offered free nicotine replacement therapy . Baseline data were from an in-person interview . Outcome measures included self-reported smoking status ; validation of quitting was by salivary cotinine assays . RESULTS Of 87 participants providing baseline data , 31 % ( 27 ) did not join the RCT . Proportions quitting in the CG and IAM group were 11.5 % and 13.6 % at 6 months and 5.3 % and 15.8 % at 12 months , respectively . CONCLUSION African Americans in underserved inner-city neighborhoods can be recruited into RCTs with community participatory approaches . Differences between the CG and IAM in proportions who quit were 2.1 % and 10.5 % at 6 and 12 months , respectively . More than 3 years with adequate funding , high staffing ratios , and intense outreach and follow-up schedules are needed to achieve recruitment and study goals Participants ( N=357 ) were r and omly assigned to 1 of 3 conditions : lay health advisor ( promotora ) plus tailored print material s , tailored print material s only ( tailored ) , or off-the-shelf print material s ( control ) . The primary outcomes were calories from fat and daily grams of fiber . Secondary outcomes included total energy intake , total and saturated fat intake , and total carbohydrates . Adjusted for baseline values , calories from fat were 29 % , 30 % , and 30 % for the promotora , tailored , and control conditions , respectively , and grams of fiber consumed were 16 g , 17 g , and 16 g. Significant Condition X Time interactions were not observed between baseline and 12-weeks postintervention . The LHA condition achieved significantly lower levels of energy intake , total fat and saturated fat , and total carbohydrates . The relative superiority of the promotora condition may derive from the personal touch achieved in the face-to-face interactions or from the women 's use of print material s under the promotora 's guidance Objective : To carry out a community-based research approach to determine the most effective educational interventions to reduce smoking among African-American smokers . The intervention included preparation of the community , planning and developing a model of change , and developing a community-based intervention . The study population consisted of 2,544 r and omly selected adult African-American smokers residing in four sites in the northeastern and southeastern parts of the United States . The research design provided a comparison of active intervention sites with passive control sites as well as low income and moderate income areas . Major Outcome Measures : Point prevalence of non-smoking at the time of interview ; Period prevalence of non-smoking at the time of interview ; Period prevalence of quit attempts in the prior six months ; Number of smoke-free days in the prior six months ; Number of cigarettes smoked daily at the time of interview . Results : Based upon a survey eighteen months after baseline data was collected , all four measures of cigarette smoking behavior showed a strong statistically significant reduction of personal smoking behavior among those receiving active interventions versus the passive group . On the basis of process variable analysis , direct contact with the project staff in the prior six months was significantly higher in the active intervention areas . There was only a small non-significant increase in personal smoking behavior in moderate income groups as opposed to low income groups . Conclusion : An analysis of process variables strongly suggests that , within this African-American Community , “ h and s on ” or “ face to face ” approaches along with mass media , mailings , and other less personal approaches were more effective in reducing personal smoking behavior than media , mailings , and other impersonal approaches alone addressed to large audiences Abstract Objective : To determine the impact of My Student Body (MSB)–Nutrition , an Internet-based obesity prevention program for college students . Participants : Three hundred and twenty ethnically diverse undergraduate students were r and omly assigned to 1 of 3 conditions : MSB-Nutrition program , an on-campus weight management course , and a comparison group . Methods : Students completed baseline and follow-up surveys regarding their nutrition and physical activity behaviors , self-efficacy , stress , attitudes , and body weight . Results : Compared with the on-campus course and a comparison group , the MSB-Nutrition program increased fruit and vegetable consumption , reduced stress , and increased fruit and vegetable self-efficacy but had no significant effect on students ’ exercise self-efficacy , exercise behavior , or weight loss . Conclusions : The MSB-Nutrition program was effective in changing students ’ nutrition behaviors but had no effect on physical activity behaviors or weight loss . Suggestions for improving Internet-based interventions aim ed at decreasing obesity rates among college students are offered BACKGROUND Although telephone counseling services ( quitlines ) have become a popular behavioral intervention for smoking cessation in the United States , such services are scarce for Asian immigrants with limited English proficiency . In this study , we tested the effects of telephone counseling for smoking cessation in Chinese- , Korean- , and Vietnamese-speaking smokers . METHODS A culturally tailored counseling protocol was developed in English and translated into Chinese , Korean , and Vietnamese . We conducted a single r and omized trial embedded in the California quitline service . Smokers who called the quitline 's Chinese , Korean , and Vietnamese telephone lines between August 2 , 2004 , and April 4 , 2008 , were recruited to the trial . Subjects ( N = 2277 ) were stratified by language and r and omly assigned to telephone counseling ( self-help material s and up to six counseling sessions ; n = 1124 subjects ) or self-help ( self-help material s only ; n = 1153 subjects ) groups : 729 Chinese subjects ( counseling = 359 , self-help = 370 ) , 848 Korean subjects ( counseling = 422 , self-help = 426 ) , and 700 Vietnamese subjects ( counseling = 343 , self-help = 357 ) . The primary outcome was 6-month prolonged abstinence . Intention-to-treat analysis was used to estimate prolonged abstinence rates for all subjects and for each language group . All statistical tests were two-sided . RESULTS In the intention-to-treat analysis , counseling increased the 6-month prolonged abstinence rate among all smokers compared with self-help ( counseling vs self-help , 16.4 % vs 8.0 % , difference = 8.4 % , 95 % confidence interval [ CI ] = 5.7 % to 11.1 % , P < .001 ) . Counseling also increased the 6-month prolonged abstinence rate for each language group compared with self-help ( counseling vs self-help , Chinese , 14.8 % vs 6.0 % , difference = 8.8 % , 95 % CI = 4.4 % to 13.2 % , P < .001 ; Korean , 14.9 % vs 5.2 % , difference = 9.7 % , 95 % CI = 5.8 % to 13.8 % , P < .001 ; Vietnamese , 19.8 % vs 13.5 % , difference = 6.3 % , 95 % CI = 0.9 % to 11.9 % , P = .023 ) . CONCLUSIONS Telephone counseling was effective for Chinese- , Korean- , and Vietnamese-speaking smokers . This protocol should be incorporated into existing quitlines , with possible extension to other Asian language INTRODUCTION Smoking is prevalent among Korean American men . Quitting is Winning , an Internet-based , cognitive-behavioral smoking cessation program , was developed using community-based participatory research principles . METHODS A r and omized controlled trial was used to evaluate whether participants were more likely to complete the program and quit smoking at 6-months of follow-up with additional reinforcement . The main outcomes were the proportion of participants who completed the online program and the proportion who quit smoking for at least 30days , 26weeks after enrollment , among those r and omized into the high-reinforcement ( HR ) condition compared with those in the low-reinforcement ( LR ) condition . RESULTS The study achieved a final enrollment of 403 participants including 56 women . Program completion was greater for the HR as compared to the LR condition ( 17 % vs. 10 % , p=.035 ) . There was no significant difference in 30-day smoking cessation ( intent-to-treat [ ITT ] ) between the HR and LR conditions ( 9 % vs. 8 % , ns ) . Smoking cessation was greater among program completers as compared to those who did not complete the program ( 28 % vs. 5 % , p<.001 ) . CONCLUSIONS The addition of interim surveys and financial incentives for interim survey completion and program completion significantly increased the likelihood of program completion . Moreover , program completers were significantly more likely to quit smoking . Although smoking cessation rates did not significantly differ between the HR and LR conditions , the results suggest that future studies should explore the efficacy of larger financial incentives for program completion ( Clinical Trial # NCT02584127 ) OBJECTIVE To examine whether tailored cancer communication for African American women can be enhanced by tailoring on 4 sociocultural constructs : religiosity , collectivism , racial pride , and time orientation . METHODS In a r and omized trial , participants ( n=1,227 ) received a women 's health magazine tailored using behavioral construct tailoring ( BCT ) , culturally relevant tailoring ( CRT ) , or both ( COMBINED ) . Two follow-up interviews assessed responses to the magazines . RESULTS Responses to all magazines were positive . The health focus of the magazines was initially obscured in the CRT condition , but this disappeared over time , and CRT magazines were better liked . CONCLUSIONS Implication s for developing and underst and ing effects of tailored cancer communication are discussed This study examined the impact of a tailored nutrition intervention at 3 and 6 months postintervention . In all , 357 Latinas were r and omly assigned to one of three conditions : ( 1 ) a control condition comprised of previously developed Spanish language targeted material s , ( 2 ) tailored print material s , or ( 3 ) tailored print material s accompanied by personalized dietary counseling via lay heath advisors ( promotoras ) . At 6 months postintervention , significant group by time interactions were observed on the dietary behavioral strategies scales . The promotora condition result ed in significant behavior change initially ; however , receipt of tailored and control material s was instrumental in continued behavior change after intervention activities had ceased . Group main effects suggested that the promotora condition was superior at reducing barriers and improving family interactions supporting healthy behaviors . The promotora model is an effective method for changing important dietary behaviors and psychosocial determinants , but longer term behavior change is achievable with less expensive intervention methods 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 Objectives : To assess the effect of community tobacco interventions in Aboriginal communities 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 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 Previous research has highlighted the importance of cultural relevance in health risk communications , including tobacco interventions . However , few studies have examined the active components of smoking cessation messages targeting low-income African American smokers . This study tested the influence of message content and culturally specific framing in a sample of adult smokers . In a 2 x 2 factorial experiment , 243 African American smokers ( M = 19 cigarettes/day ) recruited from the community ( 55 % women ; mean age = 43 years ) were r and omly assigned to 1 of 4 conditions : culturally specific smoking messages , st and ard smoking messages , culturally specific exercise/weight messages , or st and ard exercise/weight messages . The primary outcome measures were theoretical antecedents to behavior change , including risk perceptions ( general , personal , and culturally specific ) , readiness to quit smoking , and smoking-related knowledge . The results showed that the smoking messages produced greater culturally specific risk perceptions , readiness to quit smoking , and smoking-related knowledge . The culturally specific messages produced greater personal risk perceptions and intentions to quit . Culturally specific risk perceptions were most affected by culturally specific smoking messages . Findings support the roles of message content and culturally specific framing in the efficacy of brief written interventions for smoking cessation in this population . Future research is needed to examine the influence of these constructs on behavior change This pilot study sought to dismantle the efficacy of culturally specific print material s for smoking cessation . Two-hundred sixty-one African American smokers were r and omized into 1 of 2 conditions : st and ard booklet or culturally specific booklet . The content and length of the interventions were identical yet varied in their degree of cultural specificity . Three-month follow-up assessment s were completed by 70 % ( N = 183 ) of participants . Dependent variables included content evaluation , readiness to quit smoking , and actual behavior change . Evidence suggested that the culturally specific material was more effective at capturing attention , providing encouragement and gaining interest compared to st and ard material s ; however , greater credibility was found for st and ard material s. In addition , greater readiness to quit and more 24-hour quit attempts were found in the st and ard condition . No differences were found in abstinence rates . In conclusion , culturally specific interventions may be preferred over st and ard approaches among African American smokers . Culturally specific approaches , however , may not result in greater behavior change . Implication s for written interventions and cultural specificity are discussed 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 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 Abstract Objectives : To evaluate the feasibility and acceptability of an e-mail – delivered program to promote nutrition and physical activity in African American college students . Participants : Forty-seven students ( 76 % female , aged 18–20 years ) . Methods : Students participated in a 24-week r and omized controlled trial , receiving either general health information or the intervention focused on diet and physical activity . Results : At baseline , 80.9 % and 76.0 % of participants reported interest in improving diet and physical activity , respectively . Participants evidence d poor nutrition behaviors and 46 % were overweight or obese . At 24 weeks , most participants ( 70 % control , 84 % intervention ) were “ somewhat ” or “ very ” satisfied with the program . The program was feasible to administrate , with the exception of measurement of physical activity using accelerometers . Conclusions : An innovative e-mail – delivered program promoting positive health behaviors appears to be feasible and acceptable in African American college students . Further research is needed to evaluate program efficacy in this population , including prevention of excess weight gain OBJECTIVES To evaluate the efficacy of an in- language intervention of 2 lectures plus printed material s versus printed material s alone on knowledge and adherence to nutrition and physical activity guidelines among older Chinese Americans in San Francisco , California . METHODS From August 2010 to September 2013 , we r and omized 756 Chinese Americans aged 50 to 75 years to either lectures plus print ( n = 361 ) or print ( n = 357 ) . Clusters were the participants recruited by each lay health worker . Intervention outcomes were changes in knowledge of recommended vegetable intake , fruit intake , and physical activity level and adherence to those recommendations from pre- to 6 months postintervention . RESULTS The retention rate was 99 % . At baseline , knowledge and adherence to recommendations were low . Print yielded increases in knowledge of recommended vegetable intake and physical activity level and adherence to fruit intake and physical activity recommendations . Lectures plus print had significant increases in all 6 outcomes . In multivariable models , lectures plus print was superior to print for knowledge of vegetable ( adjusted odds ratio [ AOR ] = 12.61 ; 95 % confidence interval [ CI ] = 6.50 , 24.45 ) and fruit ( AOR = 16.16 ; 95 % CI = 5.61 , 46.51 ) intake recommendations and adherence to vegetable intake recommendations ( AOR = 5.53 ; 95 % CI = 1.96 , 15.58 ) . CONCLUSIONS In- language print material s , alone and combined with lectures , increased nutrition and physical activity knowledge and behaviors among older Chinese Americans BACKGROUND Traditional methods to improve population diets have largely relied on individual responsibility , but there is growing interest in structural interventions such as pricing policies . OBJECTIVE The aim was to evaluate the effect of price discounts and tailored nutrition education on supermarket food and nutrient purchases . DESIGN A 2 x 2 factorial r and omized controlled trial was conducted in 8 New Zeal and supermarkets . A total of 1104 shoppers were r and omly assigned to 1 of the following 4 interventions that were delivered over 6 mo : price discounts ( 12.5 % ) on healthier foods , tailored nutrition education , discounts plus education , or control ( no intervention ) . The primary outcome was change in saturated fat purchased at 6 mo . Secondary outcomes were changes in other nutrients and foods purchased at 6 and 12 mo . Outcomes were assessed by using electronic scanner sales data . RESULTS At 6 mo , the difference in saturated fat purchased for price discounts on healthier foods compared with that purchased for no discount on healthier foods was -0.02 % ( 95 % CI : -0.40 % , 0.36 % ; P = 0.91 ) . The corresponding difference for tailored nutrition education compared with that for no education was -0.09 % ( 95 % CI : -0.47 % , 0.30 % ; P = 0.66 ) . However , those subjects who were r and omly assigned to receive price discounts bought significantly more predefined healthier foods at 6 mo ( 11 % more ; mean difference : 0.79 kg/wk ; 95 % CI : 0.43 , 1.16 ; P < 0.001 ) and 12 mo ( 5 % more ; mean difference : 0.38 kg/wk ; 95 % CI : 0.01 , 0.76 ; P = 0.045 ) . Education had no effect on food purchases . CONCLUSIONS Neither price discounts nor tailored nutrition education had a significant effect on nutrients purchased . However , the significant and sustained effect of discounts on food purchases suggests that pricing strategies hold promise as a means to improve population diets |
13,419 | 32,385,757 | However , this difference was not statistically significant .
Treatment with anti-sclerostin antibodies can be a proper therapeutic option in patients with osteoporosis and low bone mineral density .
Based on the results of this meta- analysis , it seems that Romosozumab , with its dual function , has a positive role in the treatment of osteoporosis and low bone mineral density | Osteoporosis is a chronic skeletal disease with an increasing prevalence .
Romosozumab , as a monoclonal anti-sclerostin antibody with a dual function , has been produced .
In this meta- analysis , we aim ed to examine the efficacy of Romosozumab in patients with low bone mineral density . | BACKGROUND Sclerostin is an osteocyte-derived inhibitor of osteoblast activity . The monoclonal antibody romosozumab binds to sclerostin and increases bone formation . METHODS In a phase 2 , multicenter , international , r and omized , placebo-controlled , parallel-group , eight-group study , we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women , 55 to 85 years of age , who had low bone mineral density ( a T score of -2.0 or less at the lumbar spine , total hip , or femoral neck and -3.5 or more at each of the three sites ) . Participants were r and omly assigned to receive subcutaneous romosozumab monthly ( at a dose of 70 mg , 140 mg , or 210 mg ) or every 3 months ( 140 mg or 210 mg ) , subcutaneous placebo , or an open-label active comparator -- oral alendronate ( 70 mg weekly ) or subcutaneous teriparatide ( 20 μg daily ) . The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months . Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover . RESULTS All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine , including an increase of 11.3 % with the 210-mg monthly dose , as compared with a decrease of 0.1 % with placebo and increases of 4.1 % with alendronate and 7.1 % with teriparatide . Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck , as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker . Except for mild , generally nonrecurring injection-site reactions with romosozumab , adverse events were similar among groups . CONCLUSIONS In postmenopausal women with low bone mass , romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption . ( Funded by Amgen and UCB Pharma ; Clinical Trials.gov number , NCT00896532 . ) Summary The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis . Treatment for up to 8 years was associated with persistent reduction of bone turnover , continued increases in bone mineral density , low fracture incidence , and a favorable benefit/risk profile . Introduction This study aims to report the results through year 5 of the FREEDOM Extension study , representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis . Methods Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab , since placebo assignment was discontinued for ethical reasons . A total of 4550 women enrolled in the Extension ( 2343 long-term ; 2207 cross-over ) . In this analysis , women in the long-term and cross-over groups received denosumab for up to 8 and 5 years , respectively . Results Throughout the Extension , sustained reduction of bone turnover markers ( BTMs ) was observed in both groups . In the long-term group , mean bone mineral density ( BMD ) continued to increase significantly at each time point measured , for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip , respectively . In the cross-over group , mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip , respectively . The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups . The incidence of adverse and serious adverse events did not increase over time . Through Extension year 5 , eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed . Conclusions Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs , continued BMD gains , low fracture incidence , and a consistent safety profile Background A restriction in functional capacity occurs in all hip fractures and a variety of factors have been shown to influence patient functional outcome . This study sought to provide new and comprehensive insights into the role of factors influencing functional recovery six months after an accidental hip fracture . Methods A prospect i ve cohort study was conducted of patients aged 65 years or more who attended the Emergency Room ( ER ) for a hip fracture due to a fall . The following were studied as independent factors : socio-demographic data ( age , sex , instruction level , living condition , received help ) , comorbidities , characteristics of the fracture , treatment performed , destination at discharge , health-related quality of life ( 12-Item Short Form Health Survey ) and hip function ( Short Western Ontario and McMaster Universities Osteoarthritis Index ) . As main outcome functional status was measured ( Barthel Index and Lawton Instrumental Activities of Daily Living Scale ) . Data were collected during the first week after fracture occurrence and after 6 months of follow-up . Patients were considered to have deteriorated if there was worsening in their functional status as measured by Barthel Index and Lawton IADL scores . Factors associated with the outcome were studied via logistic regression analysis . Results Six months after the fall , deterioration in function was notable , with mean reductions of 23.7 ( 25.2 ) and 1.6 ( 2.2 ) in the Barthel Index and Lawton IADL Scale scores respectively . Patients whose status deteriorated were older , had a higher degree of comorbidity and were less educated than those who remained stable or improved . The multivariate model assessing the simultaneous impact of various factors on the functional prognosis showed that older patients , living with a relative or receiving some kind of social support and those with limited hip function before the fall had the highest odds of having losses in function . Conclusion In our setting , the functional prognosis of patients is determined by clinical and social factors , already present before the occurrence of the fracture . This could make it necessary to perform comprehensive assessment s for patients with hip fractures in order to identify those with a poor functional prognosis to tackle their specific needs and improve their recovery Biochemical markers of bone turnover may be useful aids for managing patients with osteoporosis . A 12-month , phase 3 , multicenter trial of Japanese patients at high risk of fracture was conducted to assess the effects of teriparatide 20 μg/day on BMD , serum markers of bone turnover , and safety . Two-hundred and seven subjects ( 93 % female ; median age 70 years ) were r and omized in double-blind fashion 2:1 to teriparatide versus placebo . Bone turnover markers including procollagen type I N-terminal propeptide ( PINP ) , bone-specific alkaline phosphatase ( bone ALP ) and type I collagen cross-linked C-telopeptide ( CTX ) were collected at baseline , 1 , 3 , 6 , and 12 months . Lumbar spine , femoral neck , and total hip BMD were measured at baseline , 3 , 6 , and 12 months . Increases in PINP at 1 month correlated best with increases in lumbar spine BMD at 12 months ( r=0.76 ; P<0.01 ) . The proportions of patients with an increase from baseline in PINP > 10 μg/L at 1 , 3 , and 6 months were 3 % , 0 % , and 2 % in the placebo , and 93 % , 87 % , and 83 % in the teriparatide group . The proportions of patients with an increase in PINP > 10 μg/L at either 1 or 3 months were 3 % in the placebo and 95 % in the teriparatide group ( P<0.001 ) . The proportions of patients with a significant increase in lumbar spine BMD ( increase from baseline ≥3 % ) at 12 months were 20 % in the placebo and 94 % in the teriparatide group . The proportions of patients with an increase in PINP > 10 μg/L at 1 or 3 months and an increase in lumbar spine BMD ≥3 % at 12 months was 0 % of placebo group patients and 92 % of teriparatide group patients ( P<0.001 ) . These data confirm a strong relationship between early change in PINP and later change in lumbar spine BMD during teriparatide therapy . Also , these results suggest that monitoring with PINP and lumbar spine BMD successfully identifies positive responses in most patients taking teriparatide and negative responses in most patients not taking teriparatide . PINP monitoring may be a useful aid in the management of patients with osteoporosis during teriparatide treatment BACKGROUND Romosozumab is a monoclonal antibody that inhibits sclerostin and rapidly increases bone mineral density ( BMD ) through a dual effect on bone by increasing bone formation and decreasing bone resorption , as shown in a global phase 2 study in postmenopausal women with low bone mass . Here , we report the key results of a phase 2 , double-blind , placebo-controlled , dose-ranging study to assess the efficacy and safety of romosozumab in postmenopausal Japanese women with osteoporosis . METHODS Participants were postmenopausal Japanese women with osteoporosis aged 55 - 85years with a lumbar spine , total hip , or femoral neck dual-energy X-ray absorptiometry T-score≤-2.5 . Women were r and omized to receive placebo or romosozumab ( 70 , 140 , or 210 mg ) subcutaneously once monthly ( QM ) for 12months . The primary efficacy endpoint was the percentage change from baseline in lumbar spine BMD at month 12 . Secondary efficacy endpoints included the percentage change from baseline in lumbar spine BMD at month 6 , total hip and femoral neck BMD at months 6 and 12 , and serum bone turnover markers procollagen type 1N-terminal propeptide ( P1NP ) and C-terminal telopeptide of type 1 collagen ( CTX ) at multiple visits . RESULTS This study enrolled 252 women who had a mean age of 67.7years and mean T-scores of -2.7 , -1.9 , and -2.3 at the lumbar spine , total hip , and femoral neck , respectively . All romosozumab doses significantly increased BMD at month 12 compared with placebo ( p<0.01 ) , with the largest mean gains from baseline observed with romosozumab 210 mg QM ( lumbar spine=16.9 % , total hip=4.7 % , and femoral neck=3.8 % ) . All doses of romosozumab significantly increased the levels of bone-formation marker P1NP and reduced the levels of bone-resorption marker CTX by week 1 ( p<0.001 vs placebo ) . In the 210 mg QM group , P1NP levels peaked at month 1 and fell below placebo levels by month 12 ; CTX levels were lowest at week 1 and remained below placebo through month 12 . The patient incidences of adverse events and serious adverse events were generally comparable between treatment groups . CONCLUSIONS In postmenopausal Japanese women with osteoporosis , romosozumab treatment result ed in large and significant gains in BMD from baseline and compared with placebo . Romosozumab 210 mg QM showed the largest gains in BMD and was generally well tolerated . The efficacy and safety of romosozumab 210 mg QM in this phase 2 study of postmenopausal women with osteoporosis were similar to those in an international phase 2 study PURPOSE To compare the power of FRAX ® without bone mineral density ( BMD ) and simpler screening tools ( OST , ORAI , OSIRIS , SCORE and age alone ) in predicting fractures . METHODS This study was a prospect i ve , population -based study performed in Denmark comprising 3614 women aged 40 - 90 years , who returned a question naire concerning items on risk factors for osteoporosis . Fracture risk was calculated using the different screening tools ( FRAX ® , OST , ORAI , OSIRIS and SCORE ) for each woman . The women were followed using the Danish National Register registering new major osteoporotic fractures during 3 years , counting only the first fracture per person . Area under the receiver operating characteristic curve ( ROC ) and statistics and Harrell 's index were calculated . Agreement between the tools was calculated by kappa statistics . RESULTS A total of 4 % of the women experienced a new major osteoporotic fracture during the follow-up period . There were no differences in the area under the curve ( AUC ) values between FRAX ® and the simpler tools ; AUC values between 0.703 and 0.722 ( p = 0.86 ) . Also , Harrell 's C values were very similar between the tools . Agreement between the tools was modest . CONCLUSION During 3 years follow-up FRAX ® did not perform better in the fracture risk prediction compared with simpler tools such as OST , ORAI , OSIRIS , SCORE or age alone in a screening scenario where BMD was not measured . These findings suggest that simpler models based on fewer risk factors , which would be easier to use in clinical practice by the GP or the patient herself , could just as well as FRAX ® be used to identify women with increased risk of fracture . SUMMARY Comparison of FRAX ® and simpler screening tools ( OST , ORAI , OSIRIS , SCORE ) in predicting fractures indicate that FRAX ® did not perform better in fracture risk prediction compared with the simpler tools or even age alone in a screening scenario without bone mineral density assessment Romosozumab , a monoclonal antibody that binds sclerostin , has a dual effect on bone by increasing bone formation and reducing bone resorption , and thus has favorable effects in both aspects of bone volume regulation . In a phase 2 study , romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo , alendronate , and teriparatide in postmenopausal women with low bone mass . In additional analyses from this international , r and omized study , we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD ( vBMD ) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo , s.c . teriparatide ( 20 µg once daily ) , and s.c . romosozumab ( 210 mg once monthly ) . QCT measurements were performed at the lumbar spine ( mean of L1 and L2 entire vertebral bodies , excluding posterior processes ) and hip . One year of treatment with romosozumab significantly increased integral vBMD and BMC at the lumbar spine and total hip from baseline , and compared with placebo and teriparatide ( all p < 0.05 ) . Trabecular vertebral vBMD improved significantly and similarly from baseline ( p < 0.05 ) with both romosozumab ( 18.3 % ) and teriparatide ( 20.1 % ) , whereas cortical vertebral vBMD gains were larger with romosozumab compared with teriparatide ( 13.7 % versus 5.7 % , p < 0.0001 ) . Trabecular hip vBMD gains were significantly larger with romosozumab than with teriparatide ( 10.8 % versus 4.2 % , p = 0.01 ) , but were similar for cortical vBMD ( 1.1 % versus -0.9 % , p = 0.12 ) . Cortical BMC gains were larger with romosozumab compared with teriparatide at both the spine ( 23.3 % versus 10.9 % , p < 0.0001 ) and hip ( 3.4 % versus 0.0 % , p = 0.03 ) . These improvements are expected to result in strength gains and support the continued clinical investigation of romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing phase 3 studies . © 2016 American Society for Bone and Mineral Research Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months . In a phase II , r and omized , placebo-controlled clinical trial of treatment-naïve postmenopausal women with low bone mass , romosozumab increased bone mineral density ( BMD ) at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption . In a sub study of that trial , which included placebo and teriparatide arms , here we investigated whether those observed increases in BMD also result ed in improvements in estimated strength , as assessed by finite element analysis . Participants received blinded romosozumab s.c . ( 210 mg monthly ) or placebo , or open-label teriparatide ( 20 μg daily ) for 12 months . CT scans , obtained at the lumbar spine ( n = 82 ) and proximal femur ( n = 46 ) at baseline and month 12 , were analyzed with finite element software ( VirtuOst , O.N. Diagnostics ) to estimate strength for a simulated compression overload for the spine ( L1 vertebral body ) and a sideways fall for the proximal femur , all blinded to treatment assignment . We found that , at month 12 , vertebral strength increased more for romosozumab compared with both teriparatide ( 27.3 % versus 18.5 % ; p = 0.005 ) and placebo ( 27.3 % versus -3.9 % ; p < 0.0001 ) ; changes in femoral strength for romosozumab showed similar but smaller changes , increasing more with romosozumab versus teriparatide ( 3.6 % versus -0.7 % ; p = 0.027 ) , and trending higher versus placebo ( 3.6 % versus -0.1 % ; p = 0.059 ) . Compartmental analysis revealed that the bone-strengthening effects for romosozumab were associated with positive contributions from both the cortical and trabecular bone compartments at both the lumbar spine and hip . Taken together , these findings suggest that romosozumab may offer patients with osteoporosis a new bone-forming therapeutic option that increases both vertebral and femoral strength within 12 months . © 2017 American Society for Bone and Mineral Research BACKGROUND Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide . We compared the effects of 12 months of romosozumab ( AMG 785 ) , a sclerostin monoclonal antibody , versus teriparatide on bone mineral density ( BMD ) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy . METHODS This r and omised , phase 3 , open-label , active-controlled study was done at 46 sites in North America , Latin America , and Europe . We enrolled women ( aged ≥55 to ≤90 years ) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening ; an areal BMD T score of -2·5 or lower at the total hip , femoral neck , or lumbar spine ; and a history of fracture . Patients were r and omly assigned ( 1:1 ) via an interactive voice response system to receive subcutaneous romosozumab ( 210 mg once monthly ) or subcutaneous teriparatide ( 20 μg once daily ) . The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 ( mean of months 6 and 12 ) , which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12 . All r and omised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis . This trial is registered with Clinical Trials.gov , number NCT01796301 . FINDINGS Between Jan 31 , 2013 , and April 29 , 2014 , 436 patients were r and omly assigned to romosozumab ( n=218 ) or teriparatide ( n=218 ) . 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis . Through 12 months , the mean percentage change from baseline in total hip areal BMD was 2·6 % ( 95 % CI 2·2 to 3·0 ) in the romosozumab group and -0·6 % ( -1·0 to -0·2 ) in the teriparatide group ; difference 3·2 % ( 95 % CI 2·7 to 3·8 ; p<0·0001 ) . The frequency of adverse events was generally balanced between treatment groups . The most frequently reported adverse events were nasopharyngitis ( 28 [ 13 % ] of 218 in the romosozumab group vs 22 [ 10 % ] of 214 in the teriparatide group ) , hypercalcaemia ( two [ < 1 % ] vs 22 [ 10 % ] ) , and arthralgia ( 22 [ 10 % ] vs 13 [ 6 % ] ) . Serious adverse events were reported in 17 ( 8 % ) patients on romosozumab and in 23 ( 11 % ) on teriparatide ; none were judged treatment related . There were six ( 3 % ) patients in the romosozumab group compared with 12 ( 6 % ) in the teriparatide group with adverse events leading to investigational product withdrawal . INTERPRETATION Transition to a bone-forming agent is common practice in patients treated with bisphosphonates , such as those who fracture while on therapy . In such patients , romosozumab led to gains in hip BMD that were not observed with teriparatide . These data could inform clinical decisions for patients at high risk of fracture . FUNDING Amgen , Astellas , and UCB Pharma BACKGROUND Romosozumab , a monoclonal antibody that binds sclerostin , increases bone formation and decreases bone resorption . METHODS We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck . Patients were r and omly assigned to receive subcutaneous injections of romosozumab ( at a dose of 210 mg ) or placebo monthly for 12 months ; thereafter , patients in each group received denosumab for 12 months , at a dose of 60 mg , administered subcutaneously every 6 months . The co primary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months . Secondary end points included clinical ( a composite of nonvertebral and symptomatic vertebral ) and nonvertebral fractures . RESULTS At 12 months , new vertebral fractures had occurred in 16 of 3321 patients ( 0.5 % ) in the romosozumab group , as compared with 59 of 3322 ( 1.8 % ) in the placebo group ( representing a 73 % lower risk with romosozumab ; P<0.001 ) . Clinical fractures had occurred in 58 of 3589 patients ( 1.6 % ) in the romosozumab group , as compared with 90 of 3591 ( 2.5 % ) in the placebo group ( a 36 % lower risk with romosozumab ; P=0.008 ) . Nonvertebral fractures had occurred in 56 of 3589 patients ( 1.6 % ) in the romosozumab group and in 75 of 3591 ( 2.1 % ) in the placebo group ( P=0.10 ) . At 24 months , the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab ( 0.6 % [ 21 of 3325 patients ] in the romosozumab group vs. 2.5 % [ 84 of 3327 ] in the placebo group , a 75 % lower risk with romosozumab ; P<0.001 ) . Adverse events , including instances of hyperostosis , cardiovascular events , osteoarthritis , and cancer , appeared to be balanced between the groups . One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group . CONCLUSIONS In postmenopausal women with osteoporosis , romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and , after the transition to denosumab , at 24 months . The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year . ( Funded by Amgen and UCB Pharma ; FRAME Clinical Trials.gov number , NCT01575834 . ) Romosozumab ( formerly AMG 785/CDP7851 ) is a monoclonal antibody that blocks sclerostin from inhibiting osteoblast maturation and function . This double-blind , placebo-controlled , r and omized , ascending multiple-dose study enrolled 32 postmenopausal women and 16 healthy men with low bone mass . Women received six doses of 1 or 2 mg/kg once every 2 weeks ( Q2W ) or three doses of 2 or 3 mg/kg once every 4 weeks ( Q4W ) or placebo ; and men received 1 mg/kg Q2W or 3 mg/kg Q4W or placebo . Mean serum romosozumab exposures increased approximately dose-proportionally . Romosozumab increased serum type 1 aminoterminal propeptide ( PINP ) by 66 - 147 % , decreased serum C-telopeptide ( sCTX ) by 15 - 50 % , and increased lumbar spine bone mineral density by 4 - 7 % . Two subjects developed neutralizing antibodies without discernable effects on pharmacokinetics , pharmacodynamics , or safety . Adverse event rates were balanced between groups without any significant safety findings . These data support continued investigation of sclerostin inhibition in disorders that could benefit from increased bone formation Making a diagnosis is the bread and butter of clinical practice , but in light of the number of tests now available to clinician , diagnosing illness has become a complicated process . Guidelines for making an evidence -based diagnosis abound , but those making recommendations about diagnostic tests or test strategies must realize that clinicians require support to make diagnostic decisions that they can easily implement in daily practice . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group has developed a rigorous , transparent , and increasingly adopted approach for grading the quality of research evidence and strength of recommendations to guide clinical practice . This editorial summarizes GRADE 's process for developing recommendations for tests ( 1 ) . Clinicians are trained to use tests for screening and diagnosis ; identifying physiologic derangements ; establishing a prognosis ; and monitoring illness and treatment response by assessing signs and symptoms , imaging , biochemistry , pathology , and psychological testing techniques ( 2 ) . Sensitivity , specificity , positive predictive value , likelihood ratios , and diagnostic odds ratios are among the challenging terms that diagnostic studies typically deliver to clinicians , and all have to do with diagnostic accuracy . Not only do clinicians have difficulties remembering the definitions and calculations for these terms , application of the concepts to individual patients is often complicated . Many clinicians order a test despite uncertainty about how to interpret the result , and they also contribute to testing errors by incorrectly ordering tests ( 3 , 4 ) . GRADE 's framework for developing recommendations for diagnostic management studies is based on what is needed for practical clinical applicationthat is , how to weigh the benefits and harms of ordering and using a diagnostic test in caring for patients ( 1 ) . The approach begins with specifying the PICO : the relevant population ( P ) , diagnostic intervention or test ( I ) ( including its purpose , such as triage , replacement , or an add-on test ) , comparison test ( C ) , and patient-important outcomes ( O ) related to the use of a test for a focused clinical question . If a test fails to improve patient-important outcomes , there is no reason to use it , whatever its accuracy . For example , the results of genetic testing for Huntington chorea , an untreatable condition , may provide either welcome reassurance that a patient will not have the condition or the ability to plan for his future knowing that he will sadly fall victim ( 1 ) . Here , the ability to plan is analogous to an effective treatment , and the benefits of planning need to be balanced against the downsides of receiving an early diagnosis ( 5 - 7 ) . The best evidence of test performance comes from large r and omized trials of diagnostic strategies that directly measure patient-important outcomes ( 1 ) . However , these trials are few and far between : An informal review of the Cochrane data base of r and omized trials revealed < 100 such studies . Therefore , most recommendations about diagnostic testing are based on an implicit 2-step process of how the accuracy of a test indirectly changes patient-important outcomes . In the first step , a diagnostic-test accuracy study ( Figure ) , patients may receive both a new test and a reference test ( i.e. , the best available method for detecting the target condition ) . Investigators can then calculate the accuracy of the test compared with the reference test ( first step ) . In the second step , judgments about the patient importance of test accuracy are based on the consequences of being correctly or incorrectly classified as having or not having the disease . These include the benefits and harms of receiving treatment or follow-up tests for those correctly classified as having the disease , reassurance or receipt of other follow-up tests for those correctly classified as not having the disease , receipt of unnecessary treatment or additional tests for those incorrectly classified as having the disease , delayed or no treatment for those incorrectly classified as not having the disease , and any adverse effects of the diagnostic test ( e.g. , from invasive tests ) . Those making recommendations about diagnostic tests must then compare patient-important outcomes ( and costs ) in all patients receiving the new test with all patients receiving the old , or comparator , test . For the first step ( i.e. , assessing test accuracy ) , there are well-described method ological criteria for assessing risk for bias in an estimate of test accuracy , ideally based on a systematic review of relevant studies . For instance , studies of diagnostic test accuracy with a low risk for bias enroll consecutive patients for whom there is legitimate diagnostic uncertaintythat is , the type of patients to whom clinicians would apply the test in the course of regular clinical practice . If studies fail this criterion ( e.g. , only enroll patients with severe disease and healthy controls ) , the apparent accuracy of a test is likely to be misleadingly high ( 8 , 9 ) . The second step shown in the Figure is , in most situations , based on judgments of test accuracy as a surrogate for patient-important outcomes . The key issue about these judgments is that they should be made transparent to those using the recommendations . For example , in the diagnosis of suspected acute urolithiasis , well- design ed studies demonstrate fewer false-negative results with noncontrast helical computed tomography ( CT ) than with intravenous pyelography ( IVP ) ( 10 ) . However , those ureteric stones that CT detects but IVP misses are smaller and therefore are more likely to spontaneously pass . Before r and omized trials evaluating outcomes in patients treated for smaller stones , evidence from observational studies was of lower quality . Thus , it remained uncertain how patients were affected by missed cases and follow-up of incidental findings unrelated to renal calculi with CT . Recommendations about using one test ( IVP ) over the other ( helical CT ) were based on judgments of how the cases that were detected or missed would fare with or without treatment ( 11 ) . These judgments were likely to be based on indirect evidence and would be less certain than judgments based on direct evidence from a r and omized trial comparing the 2 tests . The GRADE approach requires making these judgments about the relation between accuracy and patient-important outcomes transparent . The example of IVP versus helical CT for patients with suspected acute shows exemplifies how the quality of evidence for an accurate test would be down grade d because of the lack of direct evidence on patient-important outcomes . Uncertainty about patient-important consequences and associated uncertainty about benefits and harms would probably have result ed in weak GRADE recommendations about the use of IVP compared with helical CT . Those making recommendations using the GRADE approach should also explicitly consider judgments and evidence about the values and preferences that patients attach to important consequences , as described more fully elsewhere ( 1 ) . Acknowledgments : This work was partially funded by a The human factor , mobility and Marie Curie Actions Scientist Reintegration European Commission Grant ( IGR 42192 ) GRADE to Dr. Schnemann Context Globally , one in five men aged > 50 years is predicted to experience an osteoporotic fracture . Because of the treatment gap in osteoporosis and the paucity of bone-forming agents for men , new osteoporosis treatments are needed . Objective To evaluate the safety and efficacy of romosozumab in men with osteoporosis . Design Phase III r and omized BRIDGE study ( placebo-controlled double-blind study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis ; Clinical Trials.gov identifier , NCT02186171 ) for 12 months . Setting Thirty-one centers in Europe , Latin America , Japan , and North America . Patients Men aged 55 to 90 years with a baseline bone mineral density ( BMD ) T-score at the lumbar spine ( LS ) , total hip ( TH ) , or femoral neck of ≤-2.5 or ≤-1.5 with a history of a fragility nonvertebral or vertebral fracture . Interventions The subjects were r and omized 2:1 to receive romosozumab 210 mg subcutaneously monthly or placebo for 12 months . Main Outcome Measures The primary efficacy endpoint was percentage change from baseline in LS BMD at month 12 . Results In 245 subjects ( 163 romosozumab , 82 placebo ) , at month 12 , the mean percentage change from baseline in the LS and TH BMD was significantly greater for the romosozumab group than for the placebo group ( LS , 12.1 % vs 1.2 % ; TH , 2.5 % vs -0.5 % ; P < 0.001 ) . Adverse events and serious adverse events were balanced between the two groups , with a numerical imbalance in the positively adjudicated cardiovascular serious adverse events [ romosozumab , 8 ( 4.9 % ) vs placebo , 2 ( 2.5 % ) ] . Conclusions Treatment with romosozumab for 12 months increased the spine and hip BMD compared with placebo and was well tolerated in men with osteoporosis BACKGROUND Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin , increases bone formation , and decreases bone resorption . METHODS We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and r and omly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab ( 210 mg ) or weekly oral alendronate ( 70 mg ) in a blinded fashion for 12 months , followed by open‐label alendronate in both groups . The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture ( nonvertebral and symptomatic vertebral fracture ) at the time of the primary analysis ( after clinical fractures had been confirmed in ≥330 patients ) . Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis . Serious cardiovascular adverse events , osteonecrosis of the jaw , and atypical femoral fractures were adjudicated . RESULTS Over a period of 24 months , a 48 % lower risk of new vertebral fractures was observed in the romosozumab‐to‐alendronate group ( 6.2 % [ 127 of 2046 patients ] ) than in the alendronate‐to‐alendronate group ( 11.9 % [ 243 of 2047 patients ] ) ( P<0.001 ) . Clinical fractures occurred in 198 of 2046 patients ( 9.7 % ) in the romosozumab‐to‐alendronate group versus 266 of 2047 patients ( 13.0 % ) in the alendronate‐to‐alendronate group , representing a 27 % lower risk with romosozumab ( P<0.001 ) . The risk of nonvertebral fractures was lower by 19 % in the romosozumab‐to‐alendronate group than in the alendronate‐to‐alendronate group ( 178 of 2046 patients [ 8.7 % ] vs. 217 of 2047 patients [ 10.6 % ] ; P=0.04 ) , and the risk of hip fracture was lower by 38 % ( 41 of 2046 patients [ 2.0 % ] vs. 66 of 2047 patients [ 3.2 % ] ; P=0.02 ) . Overall adverse events and serious adverse events were balanced between the two groups . During year 1 , positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate ( 50 of 2040 patients [ 2.5 % ] vs. 38 of 2014 patients [ 1.9 % ] ) . During the open‐label alendronate period , adjudicated events of osteonecrosis of the jaw ( 1 event each in the romosozumab‐to‐alendronate and alendronate‐to‐alendronate groups ) and atypical femoral fracture ( 2 events and 4 events , respectively ) were observed . CONCLUSIONS In postmenopausal women with osteoporosis who were at high risk for fracture , romosozumab treatment for 12 months followed by alendronate result ed in a significantly lower risk of fracture than alendronate alone . ( Funded by Amgen and others ; ARCH Clinical Trials.gov number , NCT01631214 . BACKGROUND The impact of hip fracture because of a fall on health-related quality of life ( HRQoL ) and activities of daily living ( ADL ) have not been well established . AIM To evaluate changes in HRQoL and the ability to conduct ADL among patients with hip fracture because of a fall and to compare these changes with patients who did not fall and break a hip , adjusting by gender and age . METHODS Adults aged 65 or more who attended the emergency departments of seven public hospitals were recruited in a prospect i ve double-cohort study ( fracture cohort , n = 776 ; non-fracture cohort , n = 115 ) . ADL and HRQoL were assessed at baseline ( during the postfall hospitalisation or by telephone afterwards ) and 6 months later using the Barthel Index and the Lawton Brody Index for ADL , and the Short Form Health Survey ( SF-12 ) and Western Ontario and McMaster Universities Osteoarthritis Index short form ( WOMAC-SF ) for HRQoL. RESULTS Adjusting by gender , age and baseline status , a hip fracture was a strong predictor of decline in all outcomes measured except for mental quality of life among men ( measured by SF-12 ) . Hip fracture patients younger than 74 years reported significantly more pain ( measured by WOMAC-SF ) than the comparison group ( p = 0.02 ) , but this difference was not observed among older patients ( p = 0.19 for 75 - 84 years ; p = 0.39 for ≥ 85 years ) . DISCUSSION Hip fractures have profound effects on HRQoL and ADL in both men and women , regardless of age . This indicates the need for special follow-up care of elderly hip fracture patients in the immediate and late postfracture periods |
13,420 | 25,973,282 | Overall , hydration with sodium bicarbonate could significantly reduce CIN and the length of hospital stay compared to sodium chloride .
In addition NAC added as a supplement to sodium bicarbonate could increase prophylactic effects against nephropathy | This systematic review with meta- analysis sought to determine comparison of efficacy and safety of hydration with sodium bicarbonate versus sodium chloride on contrast induced nephropathy and clinical outcomes . | We sought to clarify whether a single-bolus intravenous administration of sodium bicarbonate in addition to hydration with sodium chloride prevents contrast-induced nephropathy ( CIN ) . One hundred forty-four patients with mild renal insufficiency ( serum creatinine > 1.1 to < 2.0 mg/dl ) undergoing an elective coronary procedure were r and omly assigned to the following 2 groups : st and ard hydration with sodium chloride plus single-bolus intravenous administration of sodium bicarbonate ( 20 mEq ) immediately before contrast exposure ( group A , n = 72 ) and st and ard hydration alone ( group B , n = 72 ) . The primary end point was development of CIN , defined as an increase > 25 % or > 0.5 mg/dl in serum creatinine within 3 days after the procedure . Incidence of the primary end point was lower in group A than in group B ( 1.4 % vs 12.5 % , p = 0.017 ) . Incidence of adverse clinical events ( acute pulmonary edema , acute renal failure requiring dialysis , and death within 7 days of procedure ) did not differ between the 2 groups ( 0 % vs 1.4 % ) . In conclusion , single-bolus intravenous administration of sodium bicarbonate in addition to st and ard hydration can more effectively prevent CIN than st and ard hydration alone in patients with mild renal insufficiency undergoing an elective coronary procedure CONTEXT Contrast-induced nephropathy remains a common complication of radiographic procedures . Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure . Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury . However , no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy . OBJECTIVE To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast . DESIGN , SETTING , AND PATIENTS A prospect i ve , single-center , r and omized trial conducted from September 16 , 2002 , to June 17 , 2003 , of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL ( > or = 97.2 micromol/L ) who were r and omized to receive a 154-mEq/L infusion of either sodium chloride ( n = 59 ) or sodium bicarbonate ( n = 60 ) before and after iopamidol administration ( 370 mg iodine/mL ) . Serum creatinine levels were measured at baseline and 1 and 2 days after contrast . INTERVENTIONS Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate , as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast , followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure . MAIN OUTCOME MEASURE Contrast-induced nephropathy , defined as an increase of 25 % or more in serum creatinine within 2 days of contrast . RESULTS There were no significant group differences in age , sex , incidence of diabetes mellitus , ethnicity , or contrast volume . Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment ( mean [ SD ] , 1.71 [ 0.42 ] mg/dL [ 151.2 [ 37.1 ] micromol/L ] for sodium chloride and 1.89 [ 0.69 ] mg/dL [ 167.1 [ 61.0 ] micromol/L ] for sodium bicarbonate ; P = .09 ) . The primary end point of contrast-induced nephropathy occurred in 8 patients ( 13.6 % ) infused with sodium chloride but in only 1 ( 1.7 % ) of those receiving sodium bicarbonate ( mean difference , 11.9 % ; 95 % confidence interval [ CI ] , 2.6%-21.2 % ; P = .02 ) . A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study result ed in 3 cases of contrast-induced nephropathy ( 1.6 % ; 95 % CI , 0%-3.4 % ) . CONCLUSION Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure BACKGROUND Several protective therapies have been developed to prevent contrast-induced nephropathy ( CIN ) . We aim ed to investigate the efficacy of sodium bicarbonate by comparing 2 other regimens , including combination of N-acetylcysteine ( NAC ) plus sodium chloride and sodium chloride alone , to prevent CIN in patients undergoing cardiovascular procedures . METHODS We prospect ively enrolled 264 patients who were scheduled for cardiovascular procedures and had a baseline creatinine level > 1.2 mg/dL. The patients were assigned 1 of 3 prophylactic regimens : infusion of sodium bicarbonate , sodium chloride , sodium chloride plus oral NAC ( 600 mg bid ) . Contrast-induced nephropathy was defined as an increase in serum creatinine level > 25 % or 0.5 mg/dL after 48 hours . RESULTS There were no significant differences among groups regarding baseline demographic properties and nephropathy risk factors . The change in creatinine clearance was significantly better in the sodium bicarbonate group than other 2 groups ( P = .007 ) . The incidence of CIN was significantly lower in the sodium bicarbonate group ( 4.5 % ) compared with sodium chloride alone ( 13.6 % , P = .036 ) and tended to be lower than in the combination group ( 12.5 % , P = .059 ) . After adjusting the Mehran nephropathy risk score , the risk of CIN significantly reduced with sodium bicarbonate compared with sodium chloride alone ( adjusted risk ratio 0.29 , P = .043 ) . CONCLUSIONS Hydration with sodium bicarbonate provides better protection against CIN than the sodium chloride infusion does alone . Combination therapy of NAC plus sodium chloride did not offer additional benefit over hydration with sodium chloride alone BACKGROUND Contrast-induced nephropathy ( CIN ) continues to be a common cause of acute renal failure in high-risk patients undergoing radiocontrast studies . However , there is still a lack of consensus regarding the most effective measures to prevent CIN . METHODS ONE HUNDRED EIGHTEEN PATIENTS WITH DIABETES MELLITUS AND /OR RENAL INSUFFICIENCY , SCHEDULED FOR CORONARY ANGIOGRAPHY OR INTERVENTION , WERE R AND OMLY ASSIGNED TO ONE OF FOUR TREATMENT GROUPS : intravenous ( IV ) 0.9 % NaCl alone , IV 0.9 % NaCl plus N-acetylcysteine ( NAC ) , IV 0.9 % sodium bicarbonate ( NaHCO(3 ) ) alone or IV 0.9 % NaHCO(3 ) plus NAC . All patients received IV hydration as a preprocedure bolus and as maintenance . Iso-osmolar contrast was used in all patients . CIN was defined as an increase of greater than 25 % in the serum creatinine concentration from baseline to 72 h. RESULTS The overall incidence of CIN was 6 % . There was no statistically significant difference in the incidence of CIN among the groups . There was a CIN incidence of 7 % in the NaCl only group , 5 % in the NaCl/NAC group , 11 % in the NaHCO(3 ) only group and 4 % in the NaHCO(3)/NAC group ( P=0.86 ) . The maximum increase in serum creatinine was 14.14±12.38 μmol/L in the NaHCO(3 ) group , 10.60±29.14 μmol/L in the NaCl only group , 9.72±13.26 μmol/L in the NaCl/NAC group and 0.177±15.91 μmol/L for the NaHCO(3)/NAC group ( P=0.0792 ) . CONCLUSION CIN in high-risk patients may be effectively minimized solely through the use of an aggressive hydration protocol and an iso-osmolar contrast agent . The addition of NaHCO(3 ) and /or NAC did not have an effect on the incidence of CIN Despite myriad improvements in the care of hospitalized patients , a decline in renal function remains a common event . Renal function in 4,622 consecutive patients admitted to the medical and surgical services of an urban tertiary care hospital was followed up prospect ively from the time of admission . Some degree of renal insufficiency developed in 7.2 % of patients . Decreased renal perfusion , medications , surgery , and radiographic contrast media were the most common causes of hospital-acquired renal insufficiency ( HARI ) . The overall mortality rate was 19.4 % and was similar among patients for all causes of renal insufficiency , except sepsis . For patients with a greater than 3.0-mg/dL increase in serum creatinine level , the mortality rate was 37.8 % . As shown by previous investigators , age and preexisting renal insufficiency were risk factors for HARI . Women and blacks had less hospital-acquired renal failure . The increasing acuity of hospital admissions has been accompanied by a greater incidence of acute renal insufficiency in patients admitted to hospitals . There is a trend toward better survival in patients with a severe deterioration in renal function AIMS The most effective regimen for the prevention of contrast-induced nephropathy ( CIN ) remains uncertain . Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9 % infusion in the prevention of CIN . METHODS AND RESULTS We performed a prospect i ve , r and omized trial between March 2005 and December 2009 , including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures . Patients were r and omized to receive intravenous volume supplementation with either ( A ) sodium chloride 0.9 % 1 mL/kg/h for at least 12h prior and after the procedure or ( B ) sodium bicarbonate ( 166 mEq/L ) 3 mL/kg for 1 h before and 1 mL/kg/h for 6 h after the procedure or ( C ) sodium bicarbonate ( 166 mEq/L ) 3 mL/kg over 20 min before the procedure plus sodium bicarbonate orally ( 500 mg per 10 kg ) . The primary endpoint was the change in estimated glomerular filtration rate ( eGFR ) within 48 h after contrast . Secondary endpoints included the development of CIN . The maximum change in eGFR was significantly greater in Group B compared with Group A { mean difference -3.9 [ 95 % confidence interval ( CI ) , -6.8 to -1 ] mL/min/1.73 m2 , P = 0.009 } and similar between groups C and B [ mean difference 1.3 ( 95 % CI , -1.7 - 4.3 ) mL/min/1.73 m(2 ) , P = 0.39 ] . The incidence of CIN was significantly lower in Group A ( 1 % ) vs. Group B ( 9 % , P = 0.02 ) and similar between Groups B and C ( 10 % , P = 0.9 ) . CONCLUSION Volume supplementation with 24 h sodium chloride 0.9 % is superior to sodium bicarbonate for the prevention of CIN . A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen . Clinical Trials.gov Identifier : NCT00130598 OBJECTIVES This study was design ed to determine the effectiveness of a protocol for rapid intravenous hydration to prevent contrast-induced nephropathy ( CIN ) in patients undergoing emergency percutaneous coronary intervention ( PCI ) . BACKGROUND Contrast-induced nephropathy frequently complicates PCI , result ing in prolonged hospitalization and increased in-hospital and long-term morbidity and mortality . Little is known regarding prevention of CIN in patients undergoing urgent PCI . METHODS We conducted a prospect i ve , controlled , r and omized , single-center trial in 111 consecutive patients with acute coronary syndrome undergoing emergency PCI . As part of the hydration therapy , 56 patients ( group A ) received an infusion of sodium bicarbonate plus N-acetylcysteine ( N-AC ) started just before contrast injection and continued for 12 h after PCI . The remaining 55 patients ( group B ) received the st and ard hydration protocol consisting of intravenous isotonic saline for 12 h after PCI . In both groups , 2 doses of oral N-AC were administered the next day . RESULTS The 2 groups were similar with respect to age , gender , diabetes mellitus , and baseline serum creatinine . A serum creatinine concentration > 0.5 mg/dl from baseline after emergency PCI was observed in 1 patient in group A ( 1.8 % ) and in 12 patients in group B ( 21.8 % ; p < 0.001 ) . Acute anuric renal failure was observed in 1 patient ( 1.8 % ) in group A and in 7 patients ( 12.7 % ) in group B ( p = 0.032 ) . CONCLUSIONS Rapid intravenous hydration with sodium bicarbonate plus N-AC before contrast injection is effective and safe in the prevention of CIN in patients undergoing emergency PCI OBJECTIVES The purpose of this study was to compare the efficacy of sodium bicarbonate versus isotonic saline in addition to N-acetylcysteine ( NAC ) to prevent contrast-induced nephropathy ( CIN ) in a larger population of patients with renal dysfunction undergoing coronary angiography or intervention . BACKGROUND Contrast-induced nephropathy accounts for more than 10 % of hospital-acquired renal failure . Recent studies suggest that hydration with sodium bicarbonate is more protective than isotonic saline in the prevention of CIN . METHODS The prospect i ve , single center study included 502 patients with estimated creatinine clearance < 60 ml/min , r and omized to receive infusion of either saline or sodium bicarbonate before and after iso-osmolar contrast medium administration . All patients received oral NAC 600 mg twice a day . Contrast-induced nephropathy was defined as an absolute increase of serum creatinine > or = 0.5 mg/dl measured within 5 days . RESULTS Contrast-induced nephropathy occurred in 54 patients ( 10.8 % ) ; 25 ( 10 % ) were treated with sodium bicarbonate and 29 ( 11.5 % ) with saline ( p = 0.60 ) . In patients with CIN , the mean increase in creatinine was not significantly different in the 2 study groups ( 0.9 + /- 0.6 mg/dl vs. 0.7 + /- 0.2 mg/dl , respectively ; p = 0.15 ) . Only 2 patients needed temporary hemofiltration . CONCLUSIONS Hydration with sodium bicarbonate plus NAC before contrast medium exposure is not more effective than hydration with isotonic saline plus NAC for prophylaxis of CIN in patients with moderate-to-severe renal dysfunction . ( Sodium Bicarbonate Versus Saline for the Prevention of Contrast-Induced Nephropathy ; NCT00606827 ) Few studies have compared the ability of sodium bicarbonate plus N-acetylcysteine ( NAC ) and sodium chloride plus NAC to prevent contrast-induced nephropathy ( CIN ) in diabetic patients with impaired renal function undergoing coronary or endovascular angiography or intervention . Diabetic patients ( n = 382 ) with renal disease ( serum creatinine ≥1.1 mg/dl and estimated glomerular filtration rate < 60 ml/min/1.73 m(2 ) ) were r and omly assigned to receive prophylactic sodium chloride ( saline group , n = 189 ) or sodium bicarbonate ( bicarbonate group , n = 193 ) before elective coronary or endovascular angiography or intervention . All patients received oral NAC 1,200 mg 2 times/day for 2 days . The primary end point was CIN , defined as an increase in serum creatinine > 25 % or an absolute increase in serum creatinine ≥0.5 mg/dl within 48 hours after contrast exposure . There were no significant between-group differences in baseline characteristics . The primary end point was met in 10 patients ( 5.3 % ) in the saline group and 17 ( 9.0 % ) in the bicarbonate group ( p = 0.17 ) , with 2 ( 1.1 % ) and 4 ( 2.1 % ) , respectively , requiring hemodialysis ( p = 0.69 ) . Rates of death , myocardial infa rct ion , and stroke did not differ significantly at 1 month and 6 months after contrast exposure . In conclusion , hydration with sodium bicarbonate is not superior to hydration with sodium chloride in preventing CIN in patients with diabetic nephropathy undergoing coronary or endovascular angiography or intervention BACKGROUND Volume supplementation by saline infusion combined with N-acetylcysteine ( NAC ) represents an effective strategy to prevent contrast agent-induced nephrotoxicity ( CIN ) . Preliminary data support the concept that sodium bicarbonate and ascorbic acid also may be effective in preventing CIN . METHODS AND RESULTS Three hundred twenty-six consecutive patients with chronic kidney disease , referred to our institutions for coronary and /or peripheral procedures , were r and omly assigned to prophylactic administration of 0.9 % saline infusion plus NAC ( n=111 ) , sodium bicarbonate infusion plus NAC ( n=108 ) , and 0.9 % saline plus ascorbic acid plus NAC ( n=107 ) . All enrolled patients had serum creatinine > or = 2.0 mg/dL and /or estimated glomerular filtration rate < 40 mL x min(-1 ) x 1.73 m(-2 ) . Contrast nephropathy risk score was calculated in each patient . In all cases , iodixanol ( an iso-osmolar , nonionic contrast agent ) was administered . The primary end point was an increase of > or = 25 % in the creatinine concentration 48 hours after the procedure ( CIN ) . The amount of contrast media administered ( 179+/-102 , 169+/-92 , and 169+/-94 mL , respectively ; P=0.69 ) and risk scores ( 9.1+/-3.4 , 9.5+/-3.6 , and 9.3+/-3.6 ; P=0.21 ) were similar in the 3 groups . CIN occurred in 11 of 111 patients ( 9.9 % ) in the saline plus NAC group , in 2 of 108 ( 1.9 % ) in the bicarbonate plus NAC group ( P=0.019 by Fisher exact test versus saline plus NAC group ) , and in 11 of 107 ( 10.3 % ) in the saline plus ascorbic acid plus NAC group ( P=1.00 versus saline plus NAC group ) . CONCLUSIONS The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk We conducted a prospect i ve study to determine whether a bolus injection of sodium bicarbonate before emergent coronary procedures in patients with chronic kidney disease ( CKD ) might prevent contrast-induced nephropathy ( CIN ) . We enrolled 59 patients with CKD , defined by a serum creatinine concentration of > 1.1 mg/dl or an estimated glomerular filtration rate of < 60 ml/min , who were scheduled at admission to undergo an emergent coronary procedure . The patients were r and omized to receive a bolus intravenous injection of 154 mEq/L of sodium bicarbonate ( n = 30 ) or sodium chloride ( n = 29 ) at the dose of 0.5 ml/kg , before contrast administration , followed by infusion of 154 mEq/L sodium bicarbonate at 1 ml/kg/hour for 6 hours in both groups . The primary end point was the occurrence of CIN , defined as an increase by > 25 % or > 0.5 mg/dl of the serum creatinine level within 2 days after the procedure . In the sodium bicarbonate group , the serum creatinine concentration remained unchanged within 2 days of contrast administration ( from 1.32 ± 0.46 to 1.38 ± 0.60 mg/dl , p = 0.33 ) . In contrast , it had increased in the sodium chloride group ( 1.51 ± 0.59 to 1.91 ± 1.19 mg/dl , p = 0.006 ) . The incidence of CIN was significantly lower in the sodium bicarbonate group than in the sodium chloride group ( 3.3 % vs 27.6 % , p = 0.01 ) . In conclusion , rapid alkalization by bolus injection of sodium bicarbonate was effective for the prevention of CIN in patients with CKD undergoing emergent procedures BACKGROUND There is controversy about the prophylactic measures proposed for the prevention of contrast-induced nephropathy ( CIN ) . We aim to compare the efficacy of the combination of sodium bicarbonate and isotonic saline and that of isotonic saline alone in preventing CIN . STUDY DESIGN R and omized double-blind controlled trial . SETTING & PARTICIPANTS 265 consecutive patients 18 years or older with a serum creatinine level of 1.5 mg/dL or greater undergoing elective coronary angiography from August 2007 to June 2008 in Tehran Heart Center , Tehran , Iran . INTERVENTION Study participants were r and omly assigned to receive either 75 mL of 8.4 % sodium bicarbonate added to 1 L of isotonic saline ( n = 135 ) or isotonic saline alone ( n = 130 ) as a bolus of 3 mL/kg for 1 hour before contrast injection , followed by an infusion of 1 mL/kg/h for 6 hours after the procedure . OUTCOMES & MEASUREMENTS The primary end point was an absolute ( > or=0.5 mg/dL ) or relative ( > or=25 % ) increase in serum creatinine level 48 hours after the procedure ( CIN ) . RESULTS There were no significant differences between the bicarbonate and saline groups regarding baseline demographic and biochemical characteristics , including baseline serum creatinine level ( 1.63 + /- 0.32 [ SD ] versus 1.66 + /- 0.50 mg/dL ) , baseline glomerular filtration rate ( 46.4 + /- 12 versus 45.4 + /- 12 mL/min/1.73 m(2 ) ) , and baseline urine pH ( 5.42 + /- 0.6 versus 5.46 + /- 0.8 ) . Nine patients ( 7.4 % ) receiving sodium bicarbonate developed CIN as opposed to 7 patients ( 5.9 % ) in the saline group , which was not statistically different ( odds ratio , 1.26 ; 95 % confidence interval , 0.45 to 3.50 ; P = 0.6 ) . LIMITATIONS The trial did not follow up participants to assess need for dialysis and mortality rate . CONCLUSION The combination therapy of sodium bicarbonate plus saline does not offer additional benefits over hydration with saline alone in the prevention of CIN BACKGROUND The contrast-induced nephropathy ( CIN ) is the third most common cause of acute renal failure ( ARF ) and the worsening in a pre-existing chronic renal failure ( CRF ) , with a foreseeable increase of morbidity , mortality , length of the stay in hospital and , as a consequence , of the health costs . We studied the effectiveness of N-acetylcysteine ( NAC ) associated with sodium bicarbonate ( Na2HCO3 ) infusion in order to prevent CIN in patients undergoing coronary angiography with administration of contrast medium . MATERIAL S AND METHODS 296 patients with indication to perform coronary angiography were included in a r and omized , observational study . All patients were r and omly assigned to receive pre- and post-contrast hydration with 1500 ml of 0.9 % saline solution infusion ( Group A ) or NAC ( 1200 mg × 2 days ) + Na2HCO3 ( Group B ) . The primary end-point was to examine CIN appearance , defined as a raise in serum values of Cr ( Creatinine ) ≥ 0.5 mg/dl or ≥ 25 % within 24 - 72 hours after the exposure to the contrast medium . RESULTS It has been observed a frequency of CIN of 9.4 % in Gr . A compared to 7.2 % in Gr . B. Nevertheless , when we put these results through a more accurate screening according to gender , degree of raise in creatinine levels and the extent of change in GFR ( glomerular filtration rate ) , we observed a very different behaviour . In patients with normal Cr and CrCl ( Clearance of Creatinine ) the frequency of CIN was similar in both group A and B ( approximately 5 % ) . In patients with normal Cr but reduced ClCr the use of NAC was more effective than hydration in preventing CIN ( 0 % vs 18 % in prevalence respectively in B and A group ) . In patients with moderately reduced Cr and CrCl , hydration with saline solution was more effective than NAC + Na2HCO3 ( 8.6 % vs 17.6 % ) while in patients with severe CRF the combined use of NAC + Na2HCO3 showed off to be very successful in preventing CIN compared to the merely hydration ( 0 % vs 50 % ) . CONCLUSIONS In patients affected by severe CRF who are undergoing investigations with contrast medium administration , such as coronary angiography , the combined use of NAC + Na2HCO3 infusion significantly reduces the risk of developing CIN . In other circumstances the final result is related to the degree of previous GFR or creatinine values alteration or to gender . In such situations the combined use of both substances is more question able and sometimes ineffective BACKGROUND Sodium bicarbonate has been recently proposed as a prophylactic measure for the prevention of contrast-induced nephropathy ( CIN ) . We aim ed to compare the efficacy of the combination of sodium bicarbonate with half saline , and half saline alone in preventing CIN in patients having uncontrolled hypertension , compensated severe heart failure or a history of pulmonary edema . METHODS Seventy-two patients undergoing elective coronary angiography with a serum creatinine level > or = 1.5 mg/dL who had uncontrolled hypertension , compensated severe heart failure or a history of pulmonary edema were prospect ively enrolled in a single-center , double-blind , r and omized , controlled trial from August 2007 to July 2008 and were assigned to either an infusion of sodium bicarbonate plus half saline ( n=36 ) or half saline alone ( n=36 ) . The primary end point was an absolute ( > or = 0.5 mg/dL ) or relative ( > or = 25 % ) increase in serum creatinine 48 hours after the procedure ( CIN ) . RESULTS There were no significant differences between the groups regarding their baseline demographic and biochemical characteristics , as well as the underlying disease . A total of 6.1 % of the patients receiving sodium bicarbonate plus half saline developed CIN as opposed to 6.3 % of the patients in the half saline group , which was not statistically different ( odds ratio = 0.97 ; 95 % confidence interval , 0.13 - 7.3 ; p=1.0 ) . CONCLUSION The combination therapy of sodium bicarbonate plus half saline does not offer additional benefits over hydration with half saline alone in the prevention of CIN Background This study aim ed to observe the preventive potential of different hydration solutions on contrast-induced nephropathy ( CIN ) after percutaneous coronary intervention . Methods We initially screened 627 patients who were admitted to the Division of Cardiology , Beijing Anzhen Hospital between October 2010 and October 2011 . The research subjects were r and omly divided into four groups and were given : normal physiological saline ( PS ) , sodium bicarbonate ( SB ) , oral administration of PS + N-acetylcysteine ( NAC ) ( PS + NAC ) , or oral administration of SB + NAC ( SB + NAC ) . These patients were administered a hypotonic nonionic contrast agent , and the incidence of CIN in each group was observed . Results The total incidence rate of CIN was 4.47 % , while the CIN incidence rates in the PS group , the SB group , the PS + NAC group and the SB + NAC group were 3.11 , 5.03 , 4.46 and 5.33 % , respectively . The differences between these groups were not statistically significant ( P = 0.238 ) , and for patients with diabetes and /or renal dysfunction , the incidence rates of CIN among the four groups did not show statistically significant differences ( P = 0.238 , 0.156 , 0.287 ) . Conclusion Use of PS , SB , and NAC caused no significant reduction in the incidence of CIN , but in high-risk patients with diabetes and /or renal dysfunction , SB + NAC might be superior to the application of isotonic crystalloid solution AIMS Chronic renal failure ( CRF ) is a major risk factor for contrast-induced nephropathy ( CIN ) and could be prevented by bicarbonate hydration . The effect of N-acetylcysteine ( NAC ) in preventing CIN in patients treated by bicarbonate hydration has never been investigated . METHODS Patients admitted for cardiac angiography from January 2002 to November 2004 , with stable CRF ( glomerular filtration rate ( GFR ) < 56 ml/min , Cockcroft-Gault formula ) were included in a prospect i ve , r and omized , double-blind study comparing the efficacy of oral NAC + bicarbonate hydration vs oral placebo + bicarbonate hydration to prevent CIN . NAC 1,200 mg twice daily or placebo was given on Day -1 and Day 0 ( Day 0 = cardiac angiography ) . A 1.4 % bicarbonate solution ( 1 ml/ kg/h ) was administered 12 hours before and after cardiac angiography . The overall CIN incidence on Day 2 was defined by one or more of the following criteria : increase in serum creatinine > 44.2 micromol/l , increase in serum creatinine > 25 % or decrease in GFR > 5 ml/ min . RESULTS Between NAC group ( n = 28 ) and placebo group ( n = 32 ) there was no difference in baseline demographics ( age , sex ratio , weight , arterial hypertension , diabetes ) , in Day 0 characteristics ( serum creatinine , GFR , hematocrit , protidemia ) and in Day 0 cardiac angiography procedure ( diagnostic or interventional , number of stents , type and volume of contrast media infused ) . The overall incidence of CIN in the NAC and placebo groups was 7.1 vs 9.3 % ( p = 1 ) , respectively , and the rates of the observed criteria a , b , and c were 0 vs 6.3 % ( p = 0.49 ) , 3.5 vs 6.3 % ( p = 1 ) , and 7.1 vs 9.3 % ( p = 1 ) . CONCLUSION In CRF patients undergoing cardiac angiography , the use of bicarbonate hydration is associated with a very low incidence of CIN . In these conditions , on the basis of our results , we can not draw any meaningful conclusion on the effect of NAC on the prevention of CIN Objective : We compared use of intravenous ( IV ) normal saline ( NS ) to sodium bicarbonate ( NaHCO3 ) with or without oral N‐acetylcysteine ( NAC ) for prevention of contrast‐induced acute kidney injury ( CI‐AKI ) . Background : CI‐AKI is associated with significant adverse clinical events . Use of NAC has produced variable results . Recently , intravenous hydration with NaHCO3 for CI‐AKI prophylaxis has been adopted as st and ard treatment for patients with stable chronic renal disease undergoing catheterization procedures . Methods : We prospect ively enrolled 320 patients with baseline renal insufficiency scheduled to undergo catheterization . Patients were r and omly assigned to receive either IV NS ± NAC ( n = 161 ) or IV dextrose 5 % in water containing 154 mEq/l of NaHCO3 ± NAC ( n = 159 ) . IV NS was administered at 1 ml/kg body weight for 12 hr preprocedure and 12 more hr postprocedure . IV NaHCO3 was administered at 3 ml/kg body weight for 1 hr preprocedure followed by 1 ml/kg body weight postprocedure . A 1,200 mg oral dose of NAC was given 2–12 hr preprocedure and 6–12 hr postprocedure in 50 % of patients in each study arm . CI‐AKI was defined as an increase of > 0.5 mg/dl or > 25 % above baseline creatinine . Results : Overall incidence of CI‐AKI was 10.3 % . There was no significant difference in incidence among the two groups ( NS ± NAC 11.8 % vs. NaHCO3 ± NAC 8.8 % , p = ns ) . Incidence of CI‐AKI increased with increasing age ( p = 0.001 ) , contrast agent use > 3 ml/kg body weight ( p = 0.038 ) and diuretic use ( p = 0.005 ) . Conclusion : Incidence of CI‐AKI was no different in the NaHCO3 group compared to NS group , and NAC did not reduce CI‐AKI in the two study arms . © 2011 Wiley Periodicals , INTRODUCTION Contrast-induced acute kidney injury ( CI-AKI ) is one of the leading causes of hospital-acquired acute kidney injury . Multiple clinical studies have proposed several preventive strategies . AIMS To examine the efficacy of sodium bicarbonate compared with sodium chloride and oral N-acetylcysteine ( NAC ) for preventive hydration after cardiac catheterization . METHODS We conducted a prospect i ve , single-center trial . Patients with chronic kidney disease ( CKD ) stage III-IV undergoing cardiac catheterization were allocated to receive either an infusion of 0.9 % sodium chloride and oral NAC or 154 mEq/L sodium bicarbonate . MAIN : Outcome measure CI-AKI , defined as an increase of 25 % or 0.3 mg/dL or more in plasma creatinine within 2 days of contrast administration . RESULTS Ninety-three patients were allocated to one of the two groups : 42 patients in the saline plus NAC group and 51 patients in the bicarbonate group . There were no statistically significant differences between the groups in the most important clinical and procedural characteristics . Baseline plasma creatinine levels , estimated glomerular filtration rate , incidence of diabetes mellitus , hypertension , congestive heart failure , and contrast medium volume were similar . Mean plasma creatinine concentration was 1.76 + /- 0.54 mg/dL in the saline and NAC group and 1.9 + /- 1 mg/dL in the bicarbonate group ( P = 0.23 ) . The rate of CI-AKI was 9.8 % in the bicarbonate group and 8.4 % in the saline plus NAC group . No patient required renal replacement therapy . CONCLUSION Hydration with sodium bicarbonate is not more effective than hydration with sodium chloride and oral NAC for prophylaxis of CI-AKI in patients with CKD stage III-IV undergoing cardiac catheterization AIMS Diabetes mellitus and decreased renal function are important risk factors for contrast-induced nephropathy ( CIN ) in which oxidative stress damage may play a role . Alkalinization with sodium bicarbonate ( NaHCO₃ ) has been proposed as a means of reducing free-radical mediated renal injury ; however , the effectiveness of NaHCO₃ treatment to prevent CIN in high-risk patients remains uncertain . METHODS We performed a prospect i ve , r and omized , double blind , sodium chloride ( NaCl ) hydration-controlled study of NaHCO₃ in 120 diabetic patients with impaired renal function ( serum creatinine ≥100 μmol/L ) undergoing an elective procedure with use of low-osmolar contrast media . The primary endpoint was the incidence of CIN defined as creatinine increase of ≥25 % and /or ≥44 μmol/L within 2 days after contrast . Secondary end-points were maximal changes in serum creatinine and estimated glomerular filtration rate . Urine F₂-isoprostane levels were also assessed as measure of oxidative stress . RESULTS There were no significant group differences in baseline characteristics except for the marginally lower age of the NaHCO₃ treated patients ( 63 ± 11 vs. 67 ± 10 years ; p=0.05 ) . CIN occurred in 7 ( 11.5 % ) and 5 ( 8.5 % ) patients of the NaHCO₃ and NaCl groups , respectively ( p=0.76 ; incidence rate ratio 1.35 ; 95 % CI 0.37 - 5.41 ) . No significant differences were seen in secondary outcome measures and changes in the parameter of oxidative stress . CONCLUSIONS In diabetic patients with renal function impairment sodium bicarbonate does not confer protection against contrast-induced nephropathy greater than sodium chloride-based hydration . Its specific role in mitigating oxidative stress damage in CIN is also not supported by our data Contrast-induced nephropathy ( CIN ) is associated with increased morbidity and mortality rates . Although a previous study reported that pretreatment with sodium bicarbonate is more effective than sodium chloride for prophylaxis of CIN , this has not been a universal finding . We performed a prospect i ve r and omized trial to investigate whether CIN can be avoided using sodium bicarbonate . In total 155 patients with a glomerular filtration rate ( GFR ) < 60 ml/min/1.73 m(2 ) who were undergoing coronary angiography were enrolled . We assigned patients to sodium chloride plus sodium bicarbonate ( bicarbonate group , n = 78 ) or sodium chloride alone ( chloride group , n = 77 ) . Infusion of sodium bicarbonate at 1 ml/kg/hour continued from 3 hours before to 6 hours after coronary angiography . CIN was defined as a 25 % increase in serum creatinine from baseline value or an absolute increase of ≥0.5 mg/dl , which appeared within 2 days of contrast . Baseline GFR was not significantly different between the 2 groups . Patients in the bicarbonate group had a higher GFR than those in the chloride group on day 2 ( 45.8 ± 13.4 vs 40.9 ± 14.6 ml/min/1.73 m(2 ) , p = 0.031 ) and at 1 month ( 49.5 ± 14.7 vs 43.7 ± 15.5 ml/min/1.73 m(2 ) , p = 0.019 ) . CIN occurred in 10 patients ( 13 % ) in the chloride group but in only 2 patients ( 2.6 % ) in the bicarbonate group ( p = 0.012 ) . Sodium chloride plus sodium bicarbonate is more effective than sodium chloride alone for prophylaxis of CIN and can lead to retention of better long-term renal function Introduction For the prevention of contrast-induced nephropathy ( CIN ) after coronary angiography , hydration by 0.9 % sodium chloride solution and N-acetylcysteine is currently recommended . However , it is unclear whether volume supplementation with sodium bicarbonate is better than with sodium chloride when used in conjunction with nonionic , low-osmolar iopamidol . The aim of this study was to analyze and compare the effects of sodium bicarbonate and sodium chloride on renal function in 145 patients exposed to nonionic iso-osmolar contrast medium iodixanol in a r and omized study . Patients and methods Renal Insufficiency Following Radiocontrast Exposure is a prospect i ve , r and omized , single-center , double-blinded trial of 145 patients ( age 72.6±6.7 years ) with elevated baseline serum creatinine levels ( mean 132.6±29.3 μmol/l ) . Eligible patients were r and omized to either a 154 mEq/l infusion of sodium bicarbonate ( n=71 , group I ) or sodium chloride 0.9 % solution ( n=74 , group II ) . The primary endpoint was serum creatinine elevation beyond 25 % or 44 μmol/l on the first or second day following exposure to the contrast medium . Serum creatinine , serum cystatin C , plasma viscosity , urinary enzymes alanine aminopeptidase and N-acetyl-&bgr;-D-glucosaminidase , and & agr;1-microglobulin were measured at baseline and on days 1 and 2 after contrast medium administration . Results An overall proportion of five CIN ( 3.4 % ) was observed with equal distribution among the groups ( 4.2 % in sodium bicarbonate group vs. 2.7 % in sodium chloride group ; P=0.614 ) . Parameters of renal function demonstrated no differences between the two hydration regimens on day 1 after angiography ; even on day 2 most parameters were similar in groups I and II . Conclusion Renal Insufficiency Following Radiocontrast Exposure demonstrates a homogeneously low rate of CIN after exposure to nonionic , iso-osmolar iodixanol regardless of the use of either bicarbonate sodium or sodium chloride solution for volume supplementation . Low-toxicity contrast media and any hydration may offset potential antioxidant effects of sodium bicarbonate Background Contrast-induced nephropathy ( CIN ) is commonly encountered . Because the therapy of choice for prevention of CIN is controversial , in this study we compared the preventive efficacy of bicarbonate ( Bi ) infusion in dextrose water versus normal saline ( NLS ) infusion alone or in combination with oral acetazolamide ( AZ ) . Methods In a double-blind and r and omized clinical trial , all patients undergoing coronary angiography or percutaneous coronary intervention received NLS ( NLS group ) , its combination with AZ ( AZ group ) or infusion of Bi ( Bi group ) before the procedures . RIFLE ( risk of renal failure , injury to the kidney , failure of kidney function , loss of kidney function , and end-stage renal disease ) criteria were used to define CIN-associated acute kidney injury ( AKI ) . Results The risk of AKI in CIN was significantly lower in the Bi and AZ groups than in the NLS group ( P ≤ 0.04 ) . Comparing pre-treatment and post-treatment values in each group the following results were obtained : serum creatinine ( Scr ) increased and eGFR decreased significantly in the NLS group ( P = 0.04 ) and in all patients ( P = 0.001 , P = 0.02 , respectively ) . In addition , serum potassium decreased significantly in the Bi and NLS groups ( P ≤ 0.02 ) . Also , serum Bi increased significantly in the Bi group ( P = 0.001 ) whereas it decreased significantly in the AZ group ( P = 0.001 ) . Urinary pH also increased in all groups ( P ≤ 0.04 ) except the NLS group ( P > 0.05 ) . Conclusions It seems that both Bi and AZ reduce the risk of CIN-related AKI , and close monitoring of serum potassium is needed during bicarbonate infusion In the case of an emergency coronary procedure where the risk of contrast-induced nephropathy is especially high , there are few reliable methods to attenuate renal injury . We examined the efficacy of sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure . We enrolled 59 patients who were scheduled to undergo an emergency coronary angiography or intervention . These patients were r and omized to receive a 154-mEq/L infusion of sodium bicarbonate ( n = 30 ) or sodium chloride ( n = 29 ) , as a bolus of 3 ml/kg/hour for 1 hour before the administration of contrast , followed by an infusion of 1 ml/kg/hour for 6 hours during and after the procedure . In the sodium bicarbonate group , serum creatinine concentration remained unchanged within 2 days of contrast administration ( 1.31 + /- 0.52 to 1.31 + /- 0.59 mg/dl ) , whereas it increased in the sodium chloride group ( 1.32 + /- 0.65 to 1.52 + /- 0.92 mg/dl , p = 0.01 ) . The incidence of contrast-induced nephropathy ( an increase > 0.5 mg/dl or > 25 % in serum creatinine concentration within 2 days of contrast ) was significantly lower in the sodium bicarbonate group than in the sodium chloride group ( 7 % vs 35 % , p = 0.01 , risk ratio 0.19 , 95 % confidence interval 0.046 to 0.80 ) . In conclusion , hydration with sodium bicarbonate is more effective than with sodium chloride for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure BACKGROUND IV hydration before and after cardiac catheterization is effective in preventing contrast-associated renal dysfunction for patients with mild-to-moderate renal insufficiency , but necessitates overnight hospital admission . We tested an outpatient oral precatheterization hydration strategy in comparison with overnight IV hydration . METHODS We r and omized 36 patients with renal dysfunction ( serum creatinine > or = 1.4 mg/dL ) undergoing elective cardiac catheterization to receive either overnight IV hydration ( 0.45 normal saline solution at 75 mL/h for both 12 h precatheterization and postcatheterization ; n = 18 ) or an outpatient hydration protocol including precatheterization oral hydration ( 1,000 mL clear liquid over 10 h ) followed by 6 h of IV hydration ( 0.45 normal saline solution at 300 mL/h ) beginning just before contrast exposure . The predefined primary end point was the maximal change in creatinine up to 48 h after cardiac catheterization . RESULTS The inpatient and outpatient groups were well matched for baseline characteristics and contrast volume . By protocol design , the outpatient group received a greater volume of hydration , although the net volume changes were comparable in the two groups . The maximal changes in serum creatinine in the inpatient ( 0.21+/-0.38 mg/dL ; 95 % confidence interval [ CI ] , 0.02 to 0.39 mg/dL ) and outpatient groups ( 0.12+/-0.23 mg/dL ; 95 % CI , 0.01 to 0.24 mg/dL ) were comparable ( p = not significant ) . There were no instances of protocol intolerance . CONCLUSIONS A hydration strategy compatible with outpatient cardiac catheterization is comparable to precatheterization and postcatheterization IV hydration in preventing contrast-associated changes in serum creatinine . Hospital admission for IV hydration is unnecessary before elective cardiac catheterization in the setting of mild-to-moderate renal dysfunction BACKGROUND Radiographic contrast media exposition can cause acute renal function impairment . There is limited and conflicting evidence that hydration with sodium bicarbonate prevents contrast-induced nephropathy ( CIN ) in patients undergoing cardiac catheterization . OBJECTIVE The present study was aim ed at determining whether sodium bicarbonate is superior to hydration with saline to prevent nephropathy in patients at risk undergoing cardiac catheterization . METHODS Three hundred and one patients undergoing coronary angiography or percutaneous coronary intervention with serum creatinine > 1.2mg/dL or glomerular filtration rate ( GFR ) < 50 ml/min were r and omized to receive hydration with sodium bicarbonate starting 1 hour before the procedure and 6 hours after the procedure , or hydration with 0.9 % saline . CIN was defined as an increase of 0.5mg/dL in creatinine in 48 h RESULTS Eighteen patients ( 5.9 % ) developed contrast induced nephropathy : 9 patients in the bicarbonate group ( 6.1 % ) and 9 patients in the saline group ( 6.0 % ) , p = 0.97 . The change in serum creatinine was similar in both groups , 0.01 ± 0.26 mg/dL in the bicarbonate group and 0.01 ± 0.35 mg/dL in the saline group , p = 0.9 . No statistical difference was observed between the change in glomerular filtration rate ( 0.89 ± 9 ml/min vs. 2.29 ± 10 ml/min , p = 0.2 bicarbonate group and saline group , respectively ) . CONCLUSION Hydration with sodium bicarbonate was not superior to saline to prevent contrast media induced nephropathy in patients at risk undergoing cardiac catheterization BACKGROUND The administration of radiographic contrast agents remains an important cause of acute renal failure . The optimal infusion for hydration has not been evaluated . OBJECTIVE To compare the incidence of contrast media-associated nephrotoxicity with isotonic or half-isotonic hydration . DESIGN Prospect i ve , r and omized , controlled , open-label study . METHODS Patients scheduled for elective or emergency coronary angioplasty were r and omly assigned to receive isotonic ( 0.9 % saline ) or half-isotonic ( 0.45 % sodium chloride plus 5 % glucose ) hydration beginning the morning of the procedure for elective interventions and immediately before emergency interventions . An increase in serum creatinine of at least 0.5 mg/dL ( 44 micromol/L ) within 48 hours was defined as contrast media-associated nephrotoxicity . Secondary end points were cardiac and peripheral vascular complications . RESULTS A total of 1620 patients were assigned to receive isotonic ( n = 809 ) or half-isotonic ( n = 811 ) hydration . Primary end point analysis was possible in 1383 patients . Baseline characteristics were well matched . Contrast media-associated nephropathy was significantly reduced with isotonic ( 0.7 % , 95 % confidence interval , 0.1%-1.4 % ) vs half-isotonic ( 2.0 % , 95 % confidence interval , 1.0%-3.1 % ) hydration ( P = .04 ) . Three predefined subgroups benefited in particular from isotonic hydration : women , persons with diabetes , and patients receiving 250 mL or more of contrast . The incidence of cardiac ( isotonic , 5.3 % vs half-isotonic , 6.4 % ; P = .59 ) and peripheral vascular ( isotonic , 1.6 % vs half-isotonic , 1.5 % , P = .93 ) complications was similar between the 2 hydration groups . CONCLUSION Isotonic hydration is superior to half-isotonic hydration in the prevention of contrast media-associated nephropathy Introduction Contrast-induced nephropathy ( CIN ) is a leading cause of acute renal failure and affects mortality and morbidity . Although the incidence of CIN is quite low in the general population , CIN incidence is significantly increased in patients with diabetes mellitus ( DM ) . Objectives We compared the efficacy of prophylactic use consisting of a saline infusion or a sodium bicarbonate infusion for the prevention of CIN in patients with DM . Material s and Methods A total of 195 DM patients who had unselected renal function were r and omized into 2 groups : 101 patients were assigned to saline infusion , and 94 patients were assigned to bicarbonate infusion . The primary end point was the maximum increase in the serum creatinine ( SCr ) level , whereas the secondary end point was the development of CIN after the procedure . Results The maximum increase in SCr levels was significantly lower in the saline group than in the bicarbonate group : −0.03 mg/dL ( IQR , −0.09 to 0.10 mg/dL ) versus 0.02 mg/dL ( IQR , −0.09 to 0.13 mg/dL ) ( P = 0.014 ) . The rate of CIN was significantly lower in the saline group than in the bicarbonate group ( 5.9 % vs 16 % , P = 0.024 ) . In the subset of study participants with a baseline creatinine clearance of less than 60 mL/min , the maximum increase in SCr levels was significantly lower , −0.08 mg/dL ( IQR , −0.13 to −0.04 mg/dL ) , in the saline group than in the bicarbonate group , 0.03 mg/dL ( IQR , −0.13 to 0.12 mg/dL ) ( P = 0.004 ) . Conclusions The use of prophylactic hydration with isotonic saline before coronary procedures may decrease SCr levels and reduce the incidence of CIN in patients with DM with unselected renal functions to a greater extent than sodium bicarbonate can Background : Contrast-induced acute kidney injury [ contrast-induced nephropathy ( CIN ) ] is one of the major causes of hospital-acquired acute renal failure . Volume supplementation is the most effective strategy to prevent acute renal failure caused by contrast ; but the effects of sodium bicarbonate regimens are unknown in CIN prevention . The aim of this survey is to compare the efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of the CIN in patients undergoing coronary angiography . Material s and Methods : In a clinical trial , 350 patients undergoing coronary interventions were r and omized into two groups : One group received normal saline and another group received sodium bicarbonate before and after infusion of the contrast . Patients in both the groups had received N-acetylcysteine . CIN was defined as relative increase in serum creatinine equal to or more than 25 % of baseline or increase to 0.5 mg/dl in 48 h after the injection of the contrast . Results : CIN was seen in 46 patients ( 13.1 % ) after coronary interventions . Incidence of CIN in patients receiving normal saline ( 19.4 % ) was more than in patients receiving sodium bicarbonate ( 6.9 % ) ( P = 0.001 ) . Hemodialysis was needed only in one patient who received saline normal . Relative risk to induce CIN in both groups was as 2.8 and was in the range of 1.50 - 5.25 with confidence interval of 95 % and P = 0.001 . Thus , the probability of CIN was significantly more in the usage of normal saline . Conclusion : This survey showed that hydration with sodium bicarbonate is superior to hydration with normal saline and has better protection effects |
13,421 | 20,587,790 | We also can not conclude that reminder-only intervention strategies are more effective than alternate strategies . | BACKGROUND Various interventions to promote repeat use of mammography have been evaluated , but the efficacy of such interventions is not well understood . | Background : Interventions to improve adherence to regular mammography screening have had conflicting results . Many studies have depended on women ’s self-report rather than clinical evidence of a mammography encounter . Methods : We tested the impact of two interventions on a population -based sample of NH women who were not receiving routine mammography to determine if adherence to screening could be improved . The interventions included a mailing of women ’s health information and a telephone counseling intervention based on the Transtheoretical Model . Participant eligibility and outcome measures were based on clinical events obtained from a population -based mammography registry . Results : Two hundred and fifty eight women completed all aspects of the intervention study . The women were r and omly assigned to one of two study groups : 51 % received the mail intervention and 49 % received the telephone intervention . Among women who received the telephone counseling intervention , 67 % percent reported being in either an action or maintenance stage at Call 1 , which increased to 84 % at Call 2 ( p<0.001 ) . Seventy-six percent of women identified barriers to screening mammography at Call 1 , which decreased to 44 % at Call 2 ( p<0.01 ) . The most frequently identified barrier was confusion over the guidelines for screening mammography . At the first assessment time interval , greater than 60 % of women were up-to- date for screening mammography in the group that received telephone counseling versus 48 % in the group that received health information by mail ( p = 0.04 ) . However , women ’s status as up-to- date fell for both groups between the first and second assessment time intervals . Conclusions : Tailored telephone counseling based on the Transtheoretical Model can improve adherence to screening mammography , though the duration of this effect is in question The effect on women ’s breast cancer screening utilization of a barrier-specific telephone counseling ( BSTC ) intervention , with and without a concurrent continuing medical education ( CME ) activity for their physicians , was evaluated . All participants ( 50 - 80 years of age ) were not regular mammography users at baseline . A 4-arm quasi-experimental design was employed . Women were r and omized to the BSTC or no BSTC group and assigned ( with their physicians ) to the CME or no CME group based on place of residence . Pre- and postintervention data were obtained for 1,601 women using telephone interviews conducted during 1995 and 1998 , respectively . Among women who had ever used mammography at baseline , those who received BSTC were more likely than the control group to become regular mammography users at follow-up ( OR = 1.4 , p = .033 ) . Greater reductions in perceived barriers to mammography , from baseline to follow-up , were significantly associated with receiving BSTC compared with the control group ( p = .001 ) , among women with previous mammography experience . Findings suggest that CME may have potential for initiating mammography use among women who never had a previous mammogram . However , because of the small sample available for analyses of the CME intervention and differential attrition among women who never had a previous mammogram , further study is needed to confirm this hypothesis BACKGROUND Few health promotion trials have evaluated strategies to increase regular mammography screening . We conducted a r and omized controlled trial of two theory-based interventions in a population -based , nationally representative sample of women veterans . METHODS Study c and i date s 52 years and older were r and omly sample d from the National Registry of Women Veterans and r and omly assigned to three groups . Groups 1 and 2 received interventions that varied in the extent of personalization ( tailored and targeted vs targeted-only , respectively ) ; group 3 was a survey-only control group . Postintervention follow-up surveys were mailed to all women after 1 and 2 years . Outcome measures were self-reported mammography coverage ( completion of one postintervention mammogram ) and compliance ( completion of two postintervention mammograms ) . In decreasingly conservative analyses ( intention-to-treat [ ITT ] , modified intention-to-treat [ MITT ] , and per- protocol [ PP ] ) , we examined crude coverage and compliance estimates and adjusted for covariates and variable follow-up time across study groups using Cox proportional hazards regression . For the PP analyses , we also used logistic regression . RESULTS None of the among-group differences in the crude incidence estimates for mammography coverage was statistically significant in ITT , MITT , or PP analyses . Crude estimates of compliance differed at statistically significant levels in the PP analyses and at levels approaching statistical significance in the ITT and MITT analyses . Absolute differences favoring the intervention over the control groups were 1%-3 % for ITT analysis , 1%-5 % for MITT analysis , and 2%-6 % for the PP analysis . Results from Cox modeling showed no statistically significant effect of the interventions on coverage or compliance in the ITT , MITT , or PP analyses , although hazard rate ratios ( HRRs ) for coverage were consistently slightly higher in the intervention groups than the control group ( range for HRRs = 1.05 - 1.09 ) . A PP analysis using logistic regression produced odds ratios ( ORs ) that were consistently higher than the corresponding hazard rate ratios for both coverage and compliance ( range for ORs = 1.15 - 1.29 ) . CONCLUSIONS In none of our primary analyses did the tailored and targeted intervention result in higher mammography rates than the targeted-only intervention , and there was limited support for either intervention being more effective than the baseline survey alone . We found that adjustment for variable follow-up time produced more conservative ( less favorable ) intervention effect estimates Community clinics provide inadequate breast cancer screening services to low-income , racially- and ethnically-diverse communities . This study develops and evaluates the effectiveness of multifaceted organizational system interventions —operational assessment s , tracking systems , reminder calls , tailored education , physician prompts and a tailored counseling call — on mammography rescreening rates within three community clinics . We used the Chronic Care Model and Put Prevention Into Practice framework to re design breast screening delivery services within the California Cancer Detection Programs : Every Woman Counts(CDP : EWC ) , community clinic setting s. We used a quasi-experimental design with a r and om selection of 400 patients at pre-intervention . To establish a post-intervention clinic ’s rescreening rate a new comparable cross-sectional r and om sample of 347 women was drawn . Measures A chart abstract ion instrument was used to establish clinics ’ rescreening rates . Subjects Participants at pre and post-intervention were low-income women 50 years of age and older who had received normal mammography results and had not been diagnosed with breast cancer in the last five years . General linear mixed model analysis revealed significant improvements for the organizational system re design condition [ pre-intervention rescreening rate : 32.1 percent v. post-intervention rescreening rate 50.2 percent , ( p < .001 ) ] . For the organizational system re design plus tailored counseling call condition , there was maintenance in the rescreening rate following the intervention [ pre-intervention : 44.4 percent v. post-intervention : 45.1 percent , ( p > 0.05 ) ] . Multilevel interventions directed at re design ing community clinics primary care breast cancer screening services , can improve mammography rescreening rates OBJECTIVES This study assessed the effectiveness of telephone counseling in a church-based mammography promotion intervention trial . METHODS Thirty churches were r and omized to telephone counseling and control conditions ; telephone interview data were used in assessing intervention effects on mammography adherence . Separate analyses were conducted for baseline-adherent participants ( maintaining adherence ) and baseline-nonadherent participants ( conversion to adherence ) . RESULTS Year 1 follow-up data indicated that the telephone counseling intervention maintained mammography adherence among baseline-adherent participants and reduced the nonadherence rate from 23 % to 16 % . CONCLUSIONS Partnerships between the public health and faith communities are potentially effective conduits to promote maintenance of widely endorsed health behaviors such as regular cancer screening Mammography screening continues to be under-utilized , especially among women from lower socioeconomic groups . In order to determine whether having direct access to health care services has an effect on mammography use among low income women , we conducted a r and omized trial of two alternative letter reminders among 1,717 women who were enrolled at two locations of a multi-site inner city health department in Detroit . All participants were 39 1/2 years of age and older and were due for a screening mammogram at r and omization . A physician-directed reminder form was placed in each of the participant ’s medical records at the beginning of the study . In addition participants were r and omized to receive either a letter directing them to visit their primary care physician , a letter directing them to contact the clinic directly to schedule a mammogram , or no letter . Study participants were predominantly African – American , two-thirds of whom were over age 50 , and who had minimal health insurance coverage . During the intervention year , mammograms were completed by 179 out of 967 study women at site one ( 18.5 % ) , and 90 out of 750 study women at site two ( 12 % ) . A multivariate model controlling for the simultaneous effect of age , insurance type , visit history and past mammography use , showed no significant independent effect of either type of letter reminder on mammography completion during the study year . In conclusion , letters targeted at women due for screening mammograms did not have a beneficial effect on mammography utilization above and beyond that of a physician medical record reminder Participation in breast cancer screening programmes often declines in the course of the programme . The purpose of the present study was to examine whether health education could diminish the amount of drop-outs between two screening rounds . The health education was tailored to women who previously underwent mammography . Based on the Elaboration Likelihood Model two versions of the tailored leaflet were made : a simple version and a version with additional peripheral cues . In an experimental study among 2961 women the effects of the tailored leaflets on reparticipation were tested against a st and ard leaflet . Re-participation rates were high ( > 90 % ) and did not differ between the 3 groups . No significant differences regarding beliefs about re-participating were found between the 3 groups . Results indicate that the tailored information leaflets did not enhance re-participation . Therefore , the required additional efforts and costs do not seem to be justified . The results of the study provide indications that less painful mammograms and friendly staff might improve re-participation BACKGROUND Despite widespread promotion of mammography screening , a distinct minority of women have remained underusers of this effective preventive measure . We sought to measure the effects of barrier-specific telephone counseling ( BSTC ) and a physician-based educational intervention ( MD-ED ) on mammography utilization among underusers of mammography screening . DESIGN This was a r and omized controlled trial . Women meeting criteria for mammography underuse at baseline ( grouped by practice affiliation ) were r and omized to a reminder control condition ( RC group received annual mailed reminders ) , BSTC or MD-ED interventions and followed for 3 years . Underuse was defined by failure to get two annual or biannual mammograms over a 2- to 4-year period prior to a baseline survey . PARTICIPANTS AND SETTING The study included 1655 female underusers of mammography aged 50 - 80 years who were members of two health maintenance organizations ( HMO ) in central Massachusetts . INTERVENTIONS BSTC consisted of periodic brief , scripted calls from trained counselors to women who had not had a mammogram in the preceding 15 months . Women could receive up to three annual calls during the study . MD-ED consisted of physician and office staff trainings aim ed at improving counseling skills and office reminder systems . MAIN OUTCOME MEASURE Self-report of mammography use during the study period was the main outcome measure . Regular use was defined as > or = 1 mammogram every 24 months . RESULTS Forty-four percent in each intervention group became regular users compared to 42 % in the RC group . Among subjects who had prior but not recent mammograms at baseline , BSTC was effective ( OR=1.48 ; 95 % CI=1.04 ; 2 . 10 ) , and MD-ED marginally effective ( OR=1.28 ; 95 % CI=0.88 , 1.85 ) . Most recent users at baseline and few never users became regular users ( 61 % and 17 % , respectively ) regardless of intervention status . CONCLUSIONS Among mammography underusers BSTC modestly increases utilization for former users at a reasonable cost ( $ 726 per additional regular user ) OBJECTIVE To assess added value of a booster dose of a tailored mammography intervention . METHODS Participants , non-adherent at baseline , were r and omly assigned to usual care or one of three tailored interventions . Intervention group members ( n=657 ) were further r and omly assigned to receive/not receive a booster intervention dose . Electronic record mammography data were collected following initial intervention and at 6 and 15 months post-booster . RESULTS Booster had no effect among women not screened after first intervention dose ( n=337 ) . Among women screened after initial dose ( n=320 ) , booster predicted re-screening at 6 but not 15 months . A boosterxrace interaction showed a booster effect at 6 months for African Americans ( OR=4.66 , p=.0005 ) but not Caucasians ( OR=0.74 , p=.44 ) . CONCLUSIONS Findings suggest if a first-dose intervention does not facilitate screening , neither will a booster dose . However , among women for whom a first dose is effective , boosters can facilitate timely repeat adherence , especially among African Americans . At 6 months booster recipients were less likely to be off-schedule but , by 15 months , the groups were similar . PRACTICE IMPLICATION S Boosters may effect when , but not whether , women continue screening BACKGROUND Our objective was to determine whether a tailored , stage-matched educational intervention , guided by the transtheoretical model ( TTM ) , would increase rates of repeat-screening mammography . DESIGN SETTING / PARTICIPANTS : A total of 1324 women ( N=1026 after attrition ) aged 50 to 74 years were recruited from a staff-model health maintenance organization . Some of the women were not due for mammograms at the time of recruitment . INTERVENTION Women were r and omly assigned to one of three intervention conditions : Group 1 , no educational material s ( usual care ) ; Group 2 , st and ard material s ; and Group 3 , stage-matched/tailored material s. Women in Groups 2 and 3 received a mailed education packet after both a baseline and a follow-up telephone interview . All women in Group 2 received the same material s regardless of differences in baseline mammography-related attitudes and behaviors . Each woman in Group 3 received material s based on her stage of adoption for mammography and TTM constructs . MAIN OUTCOME Using clinical records , repeat screening was defined as receipt of a second mammogram within 14 months after obtaining an initial postbaseline mammogram . RESULTS Women in Group 3 were more likely to obtain repeat-screening mammograms than women in Group 1 ( 44.2 % vs 35.8 % ; adjusted rate ratio = 1.29 , 95 % confidence interval [CI]=1.11 - 1.46 ; adjusted rate difference = 0.06 , 95 % CI=-0.01 - 0.13 ) . The screening percentage in Group 2 was intermediate ( 39.3 % ) , and did not differ from either Group 3 or Group 1 . CONCLUSIONS The effect of the stage-matched/tailored intervention was sustained for repeat screening , although no educational material s were delivered to coincide with the timing for a second mammogram . However , the stage-matched/tailored intervention was not sufficient to have a substantial impact on screening beyond the effect of st and ard educational material s. Future interventions may need to administer " booster " sessions to increase repeat screenings BACKGROUND AND OBJECTIVES Mammography is an important screening tool for the early detection of breast cancer . However , mammogram screening rates are low , despite interventions to improve them . We investigated two methods to improve mammogram screening and compared mammogram rates among women who received these interventions to mammogram screening rates in a control group . We also investigated the costs involved in these interventions . METHODS We studied mammogram screening rates of three r and omized groups of women ages 50 and older from the Deighton Family Practice Center in Southfield , Mich. All women had had a mammogram 1 year previously and were due for another mammogram . Our control group ( n = 110 ) received no intervention . The second group of women ( n = 102 ) received a reminder letter from the radiology department . The third group ( n = 86 ) received a reminder letter followed by a phone call from the physician 's office staff if no mammogram had been obtained within 8 weeks after the due date for the mammogram . All three groups were monitored for 14 weeks after the due date to determine mammogram screening rates in each group . RESULTS A mammogram was obtained by 33 % of women in group 1 , 37 % of women in group 2 , and 57 % of women in group 3 . The mammogram screening rate of the third group was significantly greater than in the first two groups . In the third group , the additional cost added by the phone call intervention was $ 9 per mammogram obtained . CONCLUSION Mammogram screening rates are increased when patients are contacted by both a reminder letter and a phone call BACKGROUND Cancer screening in primary care offices is reaching only a modest percentage of adults 50 years and older . The objectives of this study were to determine if screening rates for breast , cervical , and colorectal cancer could be significantly increased by two simple office interventions in community-based primary care offices and then maintained over 3 years . METHODS Twenty-two community-based primary care practice s were divided r and omly into four arms : control , practice -based intervention , patient-based intervention , and both interventions combined . At baseline and annually for 3 years , medical records from approximately 100 male and 100 female patients 50 years and older were r and omly selected . The outcome measures were screening rates for mammogram , Pap smear , fecal occult blood test , and flexible sigmoidoscopy or other colonic imaging . RESULTS Generally each study arm evidence d a significant 1-year increase in screening rates , followed by an overall decline to approximate baseline levels . The first year increases in screening were not related to either invention , alone or in combination . CONCLUSIONS These interventions do not have a significant impact on cancer screening rates in adults over several years . A variety of possible variables may have affected the long-term outcomes Objective : To inform female Hodgkin disease ( HD ) survivors , younger than 35 at diagnosis , of their increased risk for breast cancer and encourage them to seek breast cancer screening . Methods : An evidence -based intervention , telephone counseling , was used in a pre-post test design , r and omized trial with the control group being offered the intervention following the post-test . Women treated at Stanford University who received thoracic irradiation before age 35 , alive and HD-free at last contact , were referred to the project ( n = 471 ) . Of 261 eligible women who could be located , 157 completed the pretest and were r and omized ( 60 % response rate ) and 133 completed the post-test ( 85 % retention rate ) . Results : There was a positive intervention effect on mammography maintenance : the odds of being in maintenance at post-test compared with pretest were greater in the intervention group than in the control group [ odds ratio ( OR ) = 3.6 ] . Women were more likely to be in mammography maintenance at pre- or post-test if at pretest they were married ( OR = 5.7 ) , employed ( OR = 2.3 ) , more worried about breast cancer ( OR = 1.4 per unit of scale ) , or received an annual physical examination ( OR = 2.2 ) . Women under age 40 were much less likely to be in maintenance than were those age 45 and over ( age 35–39 , OR = 0.2 ; under age 35 , OR = 0.07 ) . Conclusions : The findings indicate that providing risk information encourages cancer survivors to take health preventive actions . Telephone counseling is a method that can provide risk information and is easily transferable to setting s where people seek health information , such as telephone information lines Abstract OBJECTIVE : To determine if women would have higher breast and cervical cancer screening rates if lay health advisers recommended screening and offered a convenient screening opportunity . DESIGN : Controlled trial . SETTING : Urban county teaching hospital . PARTICIPANTS : Women aged 40 years and over attending appointements in several non- primary -care outpatient clinics . INTERVENTIONS : Lay health advisers assessed the participants ’ breast and cervical cancer screening status and offered women in the intervention group who were due for screening an appointment with a female nurse practitioner . MEASUREMENTS AND MAIN RESULTS : Screening rates at base-line and at follow-up 1 year after the intervention were determined . At follow-up , the mammography rate was 69 % in the intervention group versus 63 % in the usual care group ( p=.009 ) , and the Pap smear rate was 70 % in the intervention group versus 63 % in the usual care group ( p=.02 ) . In women who were due for screening at baseline , the mammography rate was 60 % in the intervention group versus 50 % in the usual care group ( p=.006 ) , and the Pap smear rate was 63 % in the intervention group versus 50 % in the usual care group ( p=.002 ) . The intervention was effective across age and insurance payer strata , and was particularly effective in Native American women . CONCLUSIONS : Breast and cervical cancer screening rates were improved in women attending non- primary -care outpatient clinics by using lay health advisers and a nurse practitioner to perform screening . The effect was strongest in women in greatest need of screening INTRODUCTION The Community Trial of Mammography Promotion assessed the effectiveness of mammography promotion by community volunteer groups in rural areas . Three interventions were tested . One used an individual counseling strategy , one used a community activities strategy , and a third combined the two strategies . METHODS The effects of the interventions were tested by r and omizing 40 communities either to the study interventions or to a control group . A cohort of 352 women from each community was r and omly selected and used to evaluate the interventions ' effectiveness . Of these , 6592 women were eligible for screening mammography at baseline and follow-up and were successfully interviewed prior to and after study intervention activities . RESULTS Although the interventions did not significantly increase women 's overall use of mammography , the community activities intervention increased use at follow-up by regular users over baseline by 2.9 % ( p = 0.01 ) . Intervention appears to have increased the use of mammography among certain groups of women who were not regular users at baseline , including those in communities without female physicians ( 10 % to 16 % ; p < 0.05 ) , and among women with no health insurance ( 10 % to 23 % ; p < /= 0.05 ) . CONCLUSION Volunteers can effectively promote mammography in rural communities Background . Screening for breast cancer using mammography has been shown to be effective in reducing mortality from breast cancer . The authors attempted to determine if use of a wallet‐size plastic screening “ credit ” card would increase participants ' compliance for subsequent mammograms when compared with traditional methods of increasing compliance BACKGROUND The main benefits of mammography come from regular on-schedule screening . However , few studies have examined interventions to achieve repeat screening . SETTING AND PARTICIPANTS Participants were women aged 50 to 74 , recruited through one setting in Rhode Isl and and another in North Carolina . Participants had a mammogram already scheduled at recruitment , and had to keep that appointment in order to be eligible for the repeat mammography intervention . A total of 1614 women were in the intervention sample . DESIGN A four-group r and omized design was used : Group 1 , a simple reminder letter ; Group 2 , a 2-month , tailored , stepped intervention delivered 2 months after the completed mammogram ; Group 3 , a 10-month , tailored , stepped intervention delivered 2 months before the repeat mammogram was due ; and Group 4 , self-choice of one of the above three strategies . INTERVENTION The intervention took place between June 1996 and May 1997 . The reminder letter and two levels of the stepped intervention were delivered by mail . The third level of the stepped strategy was a counselor telephone call . Groups 2 and 3 were identical , except for timing . OUTCOME MEASURE Obtaining the next due mammogram within 15 months , based on clinic records . RESULTS There were no statistically significant differences among the four groups , both in the total sample and at the two sites separately . CONCLUSIONS On average , a simple reminder may be as effective as more complex strategies for women with a prior on-schedule exam . However , attention is still needed to identify women at risk of lapsing from screening . Some women may require more-intensive interventions BACKGROUND Most health promotion trials in cancer screening offer limited evidence of external validity . We assessed internal and external validity in a nationwide , population -based trial of an intervention to promote regular mammography screening . METHODS Beginning in September 2000 , study c and i date s age 52 years and older ( n = 23,000 ) were r and omly selected from the National Registry of Women Veterans and sent an eligibility survey . Consistent with intention-to-treat principles for effectiveness trials , we r and omly assigned eligible respondents and nonrespondents to one of five groups . We mailed baseline surveys to groups 1 - 3 followed by intervention material s of varying personalization to groups 1 and 2 . We delayed mailing baseline surveys to two additional control groups to coincide with the mailing of postintervention follow-up surveys to groups 1 - 3 at year 1 ( group 4 ) and year 2 ( group 5 ) . Mammography rates were determined from self-report and Veterans Health Administration records . To assess internal validity , we compared groups on participation and factors associated with mammography screening at each stage . To assess external validity , we compared groups 3 , 4 , and 5 on mammography rates at the most recent follow-up to detect any cueing effects of prior surveys and at the respective baselines to uncover any secular trends . We also compared non participants with participants on factors associated with mammography screening at the trial 's end . RESULTS We established study eligibility for 21,340 ( 92.8 % ) of the study c and i date s. Groups 1 - 3 were similar throughout the trial in participation and correlates of mammography screening . No statistically significant survey cueing effects or differences between non participants and participants across groups were observed . Mammography screening rates over the 30 months preceding the respective baselines were lower in group 5 ( 82.3 % by self-report ) than in groups 1 - 4 ( 85.1 % , P = .024 , group 5 vs groups 1 - 4 combined ) , suggesting a decline over time similar to that reported for US women in general . CONCLUSION This systematic assessment provides evidence of the trial 's internal and external validity and illustrates an approach to evaluating validity that is readily adaptable to future trials of behavioral interventions Abstract Although the rising incidence of breast cancer has prompted a surge of intervention strategies aim ed at increasing women 's use of mammography screening , the majority of patient-directed interventions have not been driven by relevant theoretical work on persuasive health communication . The authors evaluated an intervention derived from prospect theory that was design ed to increase women 's adherence to recommendations for annual mammography screening . They sent 1 of 3 reminder letters ( positive frame , negative frame , or st and ard hospital prompt ) to 929 r and omly selected women who were due for mammography screening and had been identified as having either a positive or negative family history of breast cancer . The primary hypothesis that women with a positive history would be more responsive to negatively framed messages , whereas women with a negative history would be more responsive to positively framed letters , was not confirmed . The lack of support for predictions derived from prospect theory raises important questions about the generalizability of laboratory research to natural setting BACKGROUND Treating multiple health behavior risks on a population basis is one of the most promising approaches to enhancing health and reducing health care costs . Previous research demonstrated the efficacy of expert system interventions for three behaviors in a population of parents . The interventions provide individualized feedback that guides participants through the stages of change for each of their risk behaviors . This study extended that research to a more representative population of patients from primary care practice and to targeting of four rather than three behaviors . METHODS Stage-based expert systems were applied to reduce smoking , improve diet , decrease sun exposure , and prevent relapse from regular mammography . A r and omized clinical controlled trial recruited 69.2 % of primary care patients ( N = 5407 ) at home via telephone . Three intervention contacts were delivered for each risk factor at 0 , 6 , and 12 months . The primary outcome measures were the percentages of at-risk patients at baseline who progressed to the action or maintenance stages at 24-month follow-up for each of the risk behaviors . RESULTS Significant treatment effects were found for each of the four behaviors , with 25.4 % of intervention patients in action or maintenance for smoking , 28.8 % for diet , and 23.4 % for sun exposure . The treatment group had less relapse from regular mammography than the control group ( 6 % vs. 10 % ) . CONCLUSION Proactive , home-based , and stage-matched expert systems can produce relatively high population impacts on multiple behavior risks for cancer and other chronic diseases OBJECTIVE To test the effectiveness of interventions intended to increase rates of regular breast cancer screening , according to recommended guidelines . STUDY DESIGN A r and omized controlled trial of 2 outreach interventions ( a mail reminder and a telephone reminder plus appointment scheduling ) compared with a routine publicity campaign to encourage continued participation in mammography screening . PARTICIPANTS AND METHODS Participants were 1908 women aged 50 to 75 years continuously enrolled in a large group-model HMO during the study who underwent a bilateral mammogram during the first quarter of 1994 and no subsequent mammogram during the next 18 to 21 months . Data were obtained from health plan administrative data files supplemented by medical chart review . Women were r and omly assigned to receive ( 1 ) a mail reminder , ( 2 ) a telephone reminder , or ( 3 ) routine publicity on mammography for all women . The outcome measure was a mammogram received after the intervention period and within 2 years of the initial mammogram date . RESULTS Bivariate and multivariate statistical analyses showed that participation was significantly higher for women contacted by telephone than through routine publicity . Mail reminders were no more effective than a routine publicity campaign . Primary care physician and gynecologist visits increased the likelihood of a subsequent mammogram for women in all intervention groups . CONCLUSIONS Telephone contact by regular health plan staff was more successful than publicity in encouraging continued participation in mammography screening in women enrolled in a group-model managed health care plan . Because mailings did not influence participation in mammography screening , health plans should be cautious about investing in member mailings without first evaluating their effectiveness in the context of existing outreach efforts BACKGROUND In response to identified low mammography use among older women in three geographic areas in Connecticut , a physician office-based mammography intervention was initiated under the Health Care Financing Administration 's Health Care Quality Improvement Program . OBJECTIVE To evaluate the intervention 's impact on older women 's mammography use . DESIGN A quasi-experimental design comparing mammography rates for women in the intervention program with a r and omly selected control sample . SETTING Community-based physician offices . PATIENTS Female Medicare beneficiaries aged 65 to 74 years seen by participating and control physicians for at least one primary care visit in 1995 ( baseline ) and 1996 ( follow-up ) . In the baseline period , 1720 women in the intervention sample and 2761 women in the control sample were included in the study . INTERVENTION The recruitment strategies included the use of physician opinion leaders and modified academic detailing . The multifaceted intervention incorporated patient education , physician reminders , and audit-with-feedback MEASUREMENTS Biennial mammography rates . Patient adherence to physician mammography referral was evaluated in a restricted cohort of women selected from the intervention sample . RESULTS The mammography rate for the intervention sample increased from 62.7 % ( baseline ) to 73.1 % ( follow-up ) , ( P<.001 ) , whereas the control sample 's rate remained essentially unchanged ( 68.3 to 69.5 % ) , ( P = .34 ) . The intervention patients were 48 % more likely than controls to experience an increase in biennial mammography use ( OR = 1.48 ; 95 % CI , 1.22 - 1.79 ) after adjustment for patient race and income and physician gender , specialty , and age . The proportion of women who adhered to their physicians ' mammography referral was 70.6 % . CONCLUSIONS These data demonstrate the effectiveness of a multifaceted intervention program administered in the setting of community physician practice s. The relatively low rate of patients ' acceptance of their physicians ' mammography recommendations has identified the need to address more effectively older women 's concerns about mammography screening BACKGROUND As overall mammography rates approach national goals , mammography promotion efforts must increasingly focus on repeat adherence . This r and omized controlled trial examined the effect of two interventions on repeat mammography utilization using various adherence definitions . METHODS 1,558 women aged 40 - 63 receiving a mammogram through a federally funded screening program were r and omized to three groups : mailed reminder ( minimum group ) ; mailed thank you card , newsletters , and reminder ( maximum group ) ; no mailings ( control ) . The primary outcome ( repeat mammogram ) was assessed 13 , 15 , 18 , and 24 months after the qualifying mammogram using administrative data . RESULTS The proportions receiving a repeat mammogram within 13 months were 0.28 , 0.30 , and 0.32 for control , minimum , and maximum groups , respectively . The corresponding proportions were 0.38 , 0.43 , and 0.45 at 15 months ; 0.43 , 0.49 , and 0.51 at 18 months ; and 0.47 , 0.52 , and 0.54 at 24 months . There were no significant differences across study groups at 13 months . The differences between control and maximum subjects at 15 , 18 , and 24 months were statistically significant . The differences between control and minimum subjects were significant only at 18 months . CONCLUSIONS The two low-cost mailed interventions evaluated modestly increased repeat mammography utilization . However , effects were not visible until at least 15 months after the qualifying mammogram BACKGROUND This study evaluated the impact of a telephone outcall intervention ( based on the Transtheoretical Model ) on screening mammography behavior among lower income , older women . METHODS A geodemographic data base , INFORUM , was used to identify low-income and minority neighborhoods throughout the state of Colorado . Residences were assigned r and omly to three study groups : ( 1 ) control , ( 2 ) outcall only , and ( 3 ) advance " invitation " + outcall . Information Specialists of the Cancer Information Service implemented the protocol . Mammography adherence was assessed in telephone interviews conducted 6 months and 2 years after the initial call . RESULTS Neither intervention had a significant effect on the main outcome , receipt of mammography in the 6-month follow-up period . At 6 months , intentions to have a mammogram were significantly stronger in the intervention groups compared with the control group , particularly among those who were precontemplators at baseline . The 2-year follow-up indicated a small increase in mammography adherence attributable to the advance invitation + outcall , but this effect was restricted to those adherent at baseline . Mammography behavior during the 6-month follow-up period was predicted strongly by decisional balance , intentions , receipt of a physical and clinical breast exam , and previous mammography behavior . CONCLUSIONS The intervention promoted minimal movement in the stages of change for mammography . Outcall interventions may have promise for encouraging repeat mammography behavior , but more intensive interventions are likely to be necessary to promote behavior change among nonadherent women BACKGROUND Telephone counseling and tailored print communications have emerged as promising methods for promoting mammography screening . However , there has been little research testing , within the same r and omized field trial , of the efficacy of these two methods compared to a high- quality usual care system for enhancing screening . This study addressed the question : Compared to usual care , is tailored telephone counseling more effective than tailored print material s for promoting mammography screening ? DESIGN Three-year r and omized field trial . PARTICIPANTS One thous and ninety-nine women aged 50 and older recruited from a health maintenance organization in North Carolina . INTERVENTION Women were r and omized to 1 of 3 groups : ( 1 ) usual care , ( 2 ) tailored print communications , and ( 3 ) tailored telephone counseling . MAIN OUTCOME Adherence to mammography screening based on self-reports obtained during 1995 , 1996 , and 1997 . RESULTS Compared to usual care alone , telephone counseling promoted a significantly higher proportion of women having mammograms on schedule ( 71 % vs 61 % ) than did tailored print ( 67 % vs 61 % ) but only after the first year of intervention ( during 1996 ) . Furthermore , compared to usual care , telephone counseling was more effective than tailored print material s at promoting being on schedule with screening during 1996 and 1997 among women who were off-schedule during the previous year . CONCLUSIONS The effects of the intervention were most pronounced after the first intervention . Compared to usual care , telephone counseling seemed particularly effective at promoting change among nonadherent women , the group for whom the intervention was developed . These results suggest that telephone counseling , rather than tailored print , might be the preferred first-line intervention for getting nonadherent women on schedule for mammography screening . Many questions would have to be answered about why the tailored print intervention was not more powerful . Nevertheless , it is clear that additional interventions will be needed to maintain women 's adherence to mammography . Medical Subject Headings ( MeSH ) : mammography screening , telephone counseling , tailored print communications , barriers Introduction . Mammography can reduce breast cancer mortality through routine screening . We tested an intervention to increase re-screening in a county program . Methods . The program requires enrollment before screening . We r and omized women who had previously been screened by the program to a telephone call reminder for re-enrollment or usual care ( postcard reminder ) . We followed re-enrollment and re-screening rates for both groups . Results . Compared with the control group ( n=610 ) , women in the intervention group ( n=599 ) had higher rates of initial re-enrollment at one month ( 10 % vs. 24 % , p<.001 ) and re-screening at two months ( 11 % vs. 19 % , p<.001 ) . These effects persisted over time ( five-month re-enrollment : 24 % vs. 35 % , p<.001 ; six-month re-screening : 23 % vs. 31 % , p=.004 ) . The intervention did not alter the odds of a woman 's being re-screened once re-enrolled . Conclusion . The increase in our re-screening rate after this simple intervention was as great or greater than the rates reported in other studies . A telephone reminder for women previously enrolled in a county breast screening program can increase re-enrollment and subsequent re-screening rates BACKGROUND Factors associated with attending screening for colorectal cancer with faecal occult blood testing was studied . METHODS Sixty-eight per cent of 34,144 subjects participated in the primary screening and /or rescreening in a r and omized screening study . The mortality and causes of death in the two groups were studied . A sample of the subjects received a question naire , in which they were asked about their reaction to the invitation . A statistical sample was called for a telephone interview . RESULTS The mortality among the non-attenders was higher than among the attenders ( p < 0.001 ) , which might reflect a higher morbidity among the non-attenders . The mortality was equal in the test and control groups . There was no difference among the attenders and non-attenders who had a full or 50 % pension . Among immigrants the attitude to screening was less positive among those born in 1918 but was the same as that of the whole group among those born in 1929 . Significantly fewer persons among the non-attenders than among the attenders could be reached for a telephone interview ( p < 0.001 ) . CONCLUSION There is a possibility that the compliance can be increased . The non-attenders ' attitude to screening was more negative than that of the attenders PURPOSE We describe a controlled trial of a community outreach intervention to promote recognition , receipt , and screening-interval maintenance of clinical breast examinations ( CBE ) , mammograms , and Pap smears among Vietnamese-American women . METHODS Over a 3-year period , indigenous lay health workers conducted small-group sessions of Vietnamese women in a low-income district of San Francisco , California . Women in Sacramento , California , served as controls . Lay workers conducted 56 sessions on general prevention , 86 on cervical cancer , and 90 on breast cancer . Surveys of 306 to 373 women were conducted in the study communities in 1992 and 1996 . RESULTS In the intervention community , recognition of screening tests increased significantly between pre- and postintervention surveys : CBE , 50 to 85 % ; mammography , 59 to 79 % ; and Pap smear , 22 to 78 % ( P = 0.001 for all ) . Receipt of screening tests also increased significantly : CBE , 44 to 70 % ( P = 0.001 ) ; mammography , 54 to 69 % ( P = 0.006 ) ; and Pap smear , 46 to 66 % ( P = 0.001 ) . Best-fitting logistic regression models , adjusting for preintervention rates and significant covariates , also showed statistically significant odds ratios for the intervention effect ( P < 0.0001 ) . CONCLUSIONS Trained Vietnamese lay health workers significantly increased Vietnamese women 's recognition , receipt , and maintenance of breast and cervical cancer screening tests OBJECTIVES The authors conducted a r and omized controlled trial to evaluate the sustained effectiveness of a computerized reminder system in promoting mammography during a second year of continuing intervention at three primary care practice s of a Health Department and a health maintenance organization in Detroit , Michigan . METHODS Out-of-pocket mammography cost was eliminated for all participants ( limited intervention ) . Computer-generated reminders promoting physician referral for mammography were placed in the medical records of women due for mammography 1 month in advance of their due date ( full intervention ) . RESULTS Among 1,225 year 2 visitors , mammography rates were 44 % for full intervention versus 28 % for limited intervention at the health department ( adjusted odds ratio [ OR ] for effect of full intervention 1.84 ; 95 % confidence interval [ CI ] : 1.40 - 2.40 ) and 45 % for full versus 46 % for limited at the health maintenance organization ( adjusted OR 1.06 ; 95 % CI 0.80 - 1.42 ) . These second year results contrasted with those observed for year 1 , during which a significant effect of full intervention was demonstrated for both organizations . After controlling for patient characteristics and site , the effect sizes of full intervention were reduced significantly in the second year compared with the first year ( P = 0.05 ) . CONCLUSIONS The effect of computerized mammography reminders can be sustained in a second year of continued intervention , but individual practice sites and organizations vary in their responsiveness to the intervention . Strategies to promote periodic and repetitive procedure use must identify and address time-varying barriers to their effectiveness Background : In a previous study we found immediate effectiveness of a nurse-initiated intervention on improving mammography recommendation rates in a family practice residency program . To determine the long-term effectiveness of this ongoing intervention , we performed a chart audit study on two different groups of charts 5 years after the institution of the intervention . Methods : Chart audits for mammogram recommendation and completion rates were conducted on an original cohort group of women aged 40 years and older ( n = 91 ) and a new 5-year postintervention group of women aged 53 years and older ( n = 189 ) . Preintervention , postintervention , and 5-year postintervention rates were compared within the cohort group . Rates of the new 5-year postintervention group were compared with rates of women 50 years and older from the original pre intervention group and postintervention group . Results : For the original cohort group the improvement in “ mammograms done at least once in the past 3 years ” was maintained 5 years later , and there was a statistically significant increased rate from the postintervention to 5 years later ( 73.9 percent versus 86.8 percent , P<0.02 ) for “ mammograms done or recommended at least once in the past 3 years . ” This improvement was also noted for the new 5-year postintervention group when their rates were compared with the pre intervention and postintervention group rates . For “ mammograms done at least once in the past 3 years , ” the rates were 34.2 percent , 45.5 percent , and 64 percent , respectively . For “ mammograms done or recommended at least once in the past 3 years , ” the rates were 42.6 percent , 72.7 percent , and 90.0 percent , respectively . In a separate analysis , annual mammogram rates in the new 5-year postintervention group for the 3 years preceding this study were 44.8 percent ( 1990 ) , 36.5 percent ( 1991 ) , and 36.5 percent ( 1992 ) . Eleven percent of women had a mammogram done in each of the 3 consecutive years . Conclusion : An ongoing nurse-initiated intervention is a feasible method of improving and maintaining mammogram recommendation and completion rates . Further studies of interventions to improve the rate at which eligible women get consecutive annual mammograms are needed BACKGROUND AND OBJECTIVE This study demonstrates the impact of survey nonresponse bias on conclusions from a mammography trial targeting a disadvantaged population . METHODS The trial r and omized 1558 women to three interventions design ed to promote repeat mammography : mailed reminder ( minimum group ) ; mailed thank-you card , patient newsletters , and reminder ( maximum group ) ; and no mailings ( control group ) . The primary outcome , repeat mammogram within 15 months , was assessed from administrative and phone survey data . RESULTS Administrative estimates revealed a statistically significant difference of 7 % between the maximum and control groups on the primary outcome . Survey estimates ( response rate 80 % ) revealed no significant differences . The differences by data source were traced to a survey nonresponse bias . There was a statistically significant difference of 16 % between the maximum and control groups among survey nonrespondents for the primary outcome , but there were no differences among survey respondents . CONCLUSION The findings reiterate that even a low survey nonresponse rate can bias study conclusions and suggest studies targeting disadvantaged population s should avoid relying solely on survey data for outcome analyses BACKGROUND This study assessed the effects of a reminder letter from a physician ( relative to a mammography facility letter or no letter ) on appointment compliance among women 50 - 74 years of age due for an annual screening mammogram . METHODS A total of 1,562 women were r and omly as signed to the groups . Each Group 1 subject received a reminder letter from her physician , each Group 2 subject received a reminder letter from her mammography facility , and Group 3 served as a control group . RESULTS The return rates for Groups 1 , 2 , and 3 were 47.7 , 46.6 , and 28.3 % , respectively ; the overall difference was significant using a chi(2 ) analysis ( P < 0.001 ) . Bonferroni pairwise comparisons indicated no difference between Groups 1 and 2 but significant differences ( P < 0.001 ) between Group 3 and the other two groups . Logistic regression indicated that relative to Group 3 , the adjusted odds of returning for Groups 1 and 2 were 2.37 and 2.24 , respectively . CONCLUSIONS Mammography providers and their patients likely will benefit from in-reach reminder systems . Physicians who do not use reminder systems should refer their patients to facilities that use these systems BACKGROUND This study compares the efficacy of three types of reminders in promoting annual repeat mammography screening . DESIGN RCT . SETTING AND PARTICIPANTS Study recruitment occurred in 2004 - 2005 . Participants were recruited through the North Carolina State Health Plan for Teachers and State Employees . All were aged 40 - 75 years and had a screening mammogram prior to study enrollment . A total of 3547 women completed baseline telephone interviews . INTERVENTION Prior to study recruitment , women were assigned r and omly to one of three reminder groups : ( 1 ) printed enhanced usual care reminders ( EUCRs ) ; ( 2 ) automated telephone reminders ( ATRs ) identical in content to EUCRs ; or ( 3 ) enhanced letter reminders that included additional information guided by behavioral theory . Interventions were delivered 2 - 3 months prior to women 's mammography due date s. MAIN OUTCOME MEASURES Repeat mammography adherence , defined as having a mammogram no sooner than 10 months and no later than 14 months after the enrollment mammogram . RESULTS Each intervention produced adherence proportions that ranged from 72 % to 76 % . Post-intervention adherence rates increased by an absolute 17.8 % from baseline . Women assigned to ATRs were significantly more likely to have had mammograms than women assigned to EUCRs ( p=0.014 ) . Comparisons of reminder efficacy did not vary across key subgroups . CONCLUSIONS Although all reminders were effective in promoting repeat mammography adherence , ATRs were the most effective and lowest in cost . Health organizations should consider using ATRs to maximize proportions of members who receive mammograms at annual intervals |
13,422 | 26,209,739 | Conclusions The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence .
These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies , which will enhance comparability of study results | Background Many publications report the prevalence of chronic kidney disease ( CKD ) in the general population .
Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods . | INTRODUCTION Chronic kidney disease ( CKD ) is an independent cardiovascular risk factor . The knowledge of prevalence in general population may help to early detection of CKD and prevent or delay its progression . METHODS Sociodemographic , baseline characteristics , and CKD prevalence ( measured by central ized serum creatinine and MDRD equation ) were evaluated in a r and omly selected sample of general population aged 20 years or older , collected in all Spanish regions and stratified by habitat , age and sex according to 2001 census ( n=2746 ) . Univariate and multivariate logistic regression analyses were used to evaluate associations with CKD risk factors . RESULTS Mean age was 49.5 years . The overall prevalence of Kidney Disease Outcomes Quality Initiative grade s 3 - 5 CKD was 6.8 % , with a 95 % confidence interval ( CI ) of 5.4 to 8.2 ( 3.3 % for age 40 - 64 years and 21.4 % for age > 64 years ) . The prevalence estimates of CKD stages were : 0.99 % for stage 1 ( glomerular filtration rate [ GFR ] > or=90 ml/min per 1.73 m2 with proteinuria ) ; 1.3 % for stage 2 ( GFR 60 - 89 ) ; 5.4 % for stage 3a ( GFR 45 - 59 ) ; 1.1 % for stage 3b ( GFR 30 - 44 ) ; 0.27 % for stage 4 ( GFR 15 - 29 ) ; and 0.03 % for stage 5 ( GFR < 15 ) . An important prevalence of classical cardiovascular risk factors was observed : dyslipemia ( 29.3 % ) , obesity ( 26.1 % ) , hypertension ( 24.1 % ) , diabetes ( 9.2 % ) and current smoking ( 25.5 % ) . The independent predictor factors for CKD were age , obesity and previously diagnosed hypertension . CONCLUSION The prevalence of CKD at any stage in general population from Spain is relatively high , especially in the elderly , and similar to countries of the same geographical area . Independently of age , two modifiable risks factors , hypertension and obesity , are associated with an increased prevalence of CKD Background . The prognostic value of reduced glomerular filtration rate ( GFR ) was examined in a community-based cohort of British women . Methods . Serum creatinine measurements were available for 90 % ( n = 3851 ) of a representative r and om sample of 4286 women aged 60 - 79 years . GFR was estimated using the Modification of Diet in Renal Disease equation . Hazard ratios ( HR ) were calculated using Cox regression with outcomes of all-cause and cardiovascular disease ( CVD ) mortality . Results . Eight hundred and thirty-two women ( 21.6 % ) had a GFR < 60 ml/min/1.73 m(2 ) . Over a median follow-up of 5.6 years , there were 318 deaths ( 100 CVD deaths ) . Women with GFR < 60 ml/min/1.73 m(2 ) compared to all others showed only a borderline increased risk of all-cause mortality [ HR 1.35 ( 95 % confidence intervals : 0.99 , 1.85 ) ] and CVD mortality [ 1.34 ( 0.97 , 1.85 ) ] . Adjustment for conventional CVD risk factors had little impact . The association with CVD mortality was attenuated in women with pre-existing CVD [ adjusted HR : 0.51 ( 0.24 , 1.04 ) ] . Only the subset of women without CVD at baseline were at risk for later CVD death [ adjusted HR : 1.80 ( 1.13 , 2.88 ) ] . Conclusions . A substantial proportion of older British women have GFR < 60 ml/min/1.73 m(2 ) without strong evidence for statistical association with all-cause mortality . The effect on CVD mortality is partly explained by existing CVD and its risk factors . GFR measurement appears only to play a useful role in the subset of older women without pre-existing CVD who are at higher risk of premature CVD death BACKGROUND In older adults , current equations to estimate glomerular filtration rate ( GFR ) are not vali date d and may misclassify elderly persons in terms of their stage of chronic kidney disease . OBJECTIVE To derive the Berlin Initiative Study ( BIS ) equation , a novel estimator of GFR in elderly participants . DESIGN Cross-sectional . Data were split for analysis into 2 sets for equation development and internal validation . SETTING R and om community-based population of a large insurance company . PARTICIPANTS 610 participants aged 70 years or older ( mean age , 78.5 years ) . INTERVENTION Iohexol plasma clearance measurement as gold st and ard . MEASUREMENTS GFR , measured as the plasma clearance of the endogenous marker iohexol , to compare performance of existing equations of estimated GFR with measured GFR of the gold st and ard ; estimation of measured GFR from st and ardized creatinine and cystatin C levels , sex , and age in the learning sample ; and comparison of the BIS equations ( BIS1 : creatinine-based ; BIS2 : creatinine- and cystatin C-based ) with other estimating equations and determination of bias , precision , and accuracy in the validation sample . RESULTS The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and Cockcroft-Gault equations . All other equations considerably overestimated GFR . The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m2 ( BIS1 , 50.4 % ; BIS2 , 47.4 % ; measured GFR , 47.9 % ) . The total misclassification rate for this criterion was smallest for the BIS2 equation ( 11.6 % ) , followed by the cystatin C equation 2 ( 15.1 % ) proposed by the Chronic Kidney Disease Epidemiology Collaboration . Among the creatinine-based equations , BIS1 had the smallest misclassification rate ( 17.2 % ) , followed by the Chronic Kidney Disease Epidemiology Collaboration equation ( 20.4 % ) . LIMITATION There was no validation by an external data set . CONCLUSION The BIS2 equation should be used to estimate GFR in persons aged 70 years or older with normal or mild to moderately reduced kidney function . If cystatin C is not available , the BIS1 equation is an acceptable alternative . PRIMARY FUNDING SOURCE Kuratorium für Dialyse und Nierentransplatation ( KfH ) Foundation of Preventive Medicine Background The prevalence of chronic kidney disease ( CKD ) using available estimating equations with the Republic of Irel and is unknown . Methods A r and omly selected population based cross-sectional study of 1,098 adults aged 45 years and older was conducted using data from the 2007 Survey of Lifestyle , Attitudes and Nutrition ( SLÁN ) . Estimated Glomerular Filtration Rate ( eGFR ) was calculated from a single IDMS aligned serum creatinine using the CKD-EPI and the MDRD equations , and albumin to creatinine ratio was based on a single r and om urine sample . Results The sample clinical characteristics and demography was similar to middle and older age adults in the general Irish population , though with an underrepresentation of subjects > 75 years and of males . All results are based on subjects with available blood and urine sample s. Applying weighting to obtain survey based population estimates , using Irish population census data , the estimated weighted prevalence of CKD-EPI eGFR<60 mL/min/1.73m2 was 11.6 % , ( 95 % confidence interval ; 9.0 , 14.2 % ) , 12.0 % ( 9.0 , 14.2 % ) of men and 11.2 % ( 7.3 , 15.2 % ) of women . Unweighted prevalence estimates were similar at 11.8 % ( 9.9 , 13.8 % ) . Albuminuria increased with lower CKD-EPI eGFR category . 10.1 % of all subjects had albuminuria and an eGFR≥60 mL/min/1.73 m2 giving an overall weighted estimated prevalence of National Kidney Foundation ( NKF ) defined CKD 21.3 % ( 18.0 , 24.6 % ) , with the unadjusted estimate of 21.9 % ( 19.5 , 24.4 % ) . MDRD related estimates for eGFR < 60 mL/min/1.73 m2 , and NFK defined CKD were higher than CKD-EPI and differences were greater in younger and female subjects . Conclusions CKD is highly prevalent in middle and older aged adults within the Republic of Irel and . In this population , there is poor agreement between CKD-EPI and MDRD equations especially at higher GFRs . CKD is associated with lower educational status and poor self rated health BACKGROUND We investigate whether the urinary proteome refines the diagnosis of renal dysfunction , which affects over 10 % of the adult population . METHODS We measured serum creatinine , estimated glomerular filtration rate ( eGFR ) and 24-h albuminuria in 797 people r and omly recruited from a population . We applied capillary electrophoresis coupled with mass spectrometry to measure multi-dimensional urinary proteomic classifiers developed for renal dysfunction ( CKD273 ) or left ventricular dysfunction ( HF1 and HF2 ) . Renal function was followed up in 621 participants and the incidence of cardiovascular events in the whole study population . RESULTS In multivariable-adjusted cross-sectional analyses , higher biomarker levels analysed separately or combined by principal component analysis into a single factor ( SF ) , correlated ( P ≤ 0.010 ) with worse renal function . Over 4.8 years , higher HF1 and SF predicted ( P ≤ 0.014 ) lowering of eGFR ; higher HF2 predicted ( P ≤ 0.049 ) increase in serum creatinine and decrease eGFR . HF1 , HF2 and SF predicted progression from CKD Stages 2 or ≤2 to Stage ≥3 , with risk estimates for a 1-SD increment in the urinary biomarkers ranging from 38 to 71 % ( P ≤ 0.039 ) . HF1 , HF2 and SF yielded a net reclassification improvement of 31 - 51 % ( P ≤ 0.029 ) . Over 6.1 years , 47 cardiovascular events occurred . HF2 and SF , independent of baseline eGFR , 24-h albuminuria and other covariables were significant predictors of cardiovascular complications with risk estimates for 1-SD increases ranging from 32 to 41 % ( P ≤ 0.047 ) . CONCLUSIONS The urinary proteome refines the diagnosis of existing or progressing renal dysfunction and predicts cardiovascular complications Background Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events , even below the threshold for diabetes . We aim ed to assess the association between HbA1c and chronic kidney disease ( CKD ) and cardiovascular disease ( CVD ) . Methods A cross-sectional study involving a r and om representative sample of 2270 adults from southern Spain ( Malaga ) was undertaken . We measured HbA1c , serum creatinine and albuminuria in fasting blood and urine sample s. Results Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes . Overall , a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors . The patients with known diabetes had a 2-fold higher odds of CKD or CVD . However , when both parameters were introduced in the same model , the HbA1c concentration was only significantly associated with clinical endpoints ( OR : 1.4 , 95 % CI , 1.1 - 1.6 , P = 0.002 ) . An increase in HbA1c of one percentage point was associated with a 30 % to 40 % increase in the rate of CKD or CVD . This relationship was apparent in persons with and without known diabetes . ROC curves illustrated that a HbA1c of 37 mmol/mol ( 5.5 % ) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population . Conclusion HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally , regardless of diabetes status . These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population BACKGROUND national policy is focused on early identification , referral and management of chronic kidney disease ( CKD ) to prevent both progression to endstage renal failure and cardiovascular disease . However , the significance of identifying CKD in older people is unclear . OBJECTIVE to determine the frequency of CKD in older people using estimated glomerular filtration rate ( eGFR ) , and its associations with morbidity and functional measures . DESIGN observational cross-sectional analysis of baseline data from a large cluster r and omised trial of health and social assessment of older people in the community . SETTING included 53 general practice s in Great Britain . SUBJECTS subjects were people aged 75 and over , living in the community participating in the trial arm where systematic blood testing was undertaken . METHODS the response rate for participation at baseline assessment of those eligible was 73 % ( 15,536/20,934 ) , of whom 13,109 ( 86 % ) participants had a serum creatinine measured , and an eGFR derivable using the Modification of Diet in Renal Disease formula ( MDRD ) in ml/min/1.73 m(2 ) . Key outcomes were the prevalence of CKD stages and their associations with morbidity and functional status . RESULTS prevalence of CKD was 56.1 % ( 95 % CI 55.3 - 57.0 ) for eGFR < 60 , 17.7 % for eGFR < 45 ( 95 % CI 17.1 - 18.4 ) , and 2.7 % ( 95 % CI 2.4 - 2.9 ) for eGFR < 30 . It was higher in older ages , females , and those with cardiovascular comorbidity and doctor-diagnosed hypertension but not with diabetes . The strength of the association with measures of morbidity and functional impairment increased as eGFR fell , especially once the eGFR was < 45 . For example , the odds ratios in males for anaemia for an eGFR < 30 , 30 - 44 and 45 - 59 versus reference GFR > 60 were 8.3 ( 5.1 - 13.7 ) , 3.0 ( 2.1 - 4.2 ) and 1.2(0.8 - 1.7 ) respectively ; similar figures for partial dependence on activities of daily living were 2.2 ( 1.4 - 3.3 ) , 1.6 ( 1.2 - 2.1 ) and 1.0 ( 0.9 - 1.3 ) and for lack of physical activity 2.20 ( 1.39 - 3.48 ) , 1.78 ( 1.37 - 2.32 ) and 1.10 ( 0.92 - 1.32 ) . CONCLUSIONS an eGFR < 60 is very common in older people . An eGFR < 45 identifies a smaller sub-group of older people with significant comorbidity , impaired functional state and a high risk of potentially reversible consequences such as anaemia . The benefits of identifying older people with an eGFR > 45 need to be determined Chronic kidney disease ( CKD ) has a high prevalence in the elderly . It has been recognized as an independent cardiovascular risk factor and detecting CKD is also important to ensure the appropriate dose of medication and to prevent further damage by limiting the use of potential harmful drugs . The aim of the research was to study the prevalence of CKD in elderly ( > or = 65 years ) in a St. Petersburg district and to study the impact of using different methods to estimate the GFR on the prevalence of different stages of CKD . The cross-sectional analysis of prospect i ve population based study in the district of Kolpino was conducted . All creatinine measurements were performed in the same laboratory . Renal function was assessed calculating the eGFR using different creatinine based formulas . 611 elderly ( 65 - 91 years ) were examined . Using the MDRD formula a prevalence of CKD stage III-V for males of 11 % was found in stratum 1 and of 15 % in stratum 2 and for females prevalence was 14 and 29 % , respectively . A considerable mismatch in classification of stages of CKD was found when comparing the MDRD based estimations with the CG-based ones . Compared to what has been reported internationally in other studies a considerable lower prevalence of CKD stage IV-V was found in both age groups . Thus , the prevalence of an impaired renal function in elderly in the St. Petersburg district is relatively low , especially in the subgroup of males aged 75 years and over compared to what been reported in other studies . The CG and MDRD formula generate significantly different results when they are used to classify the population of elderly according to the stages of CKD BACKGROUND AND OBJECTIVES Sufficiently powered studies to investigate the CKD prevalence are few and do not cover southern Europe . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS For the INCIPE study , 6200 Caucasian patients ≥40 years old were r and omly selected in northeastern Italy in 2006 . Laboratory determinations were central ized . The albumin to creatinine ratio in urine and estimated GFR from calibrated creatinine ( SCr ) were determined . A comparison with 2001 through 2006 NHANES surveys was performed . RESULTS Prevalence of CKD was 13.2 % in northeastern ( NE ) Italy ( age and gender st and ardized to the U.S. 2007 Caucasian population ) . Prevalence of CKD in U.S. Caucasians is higher ( 20.3 % ) , the major difference being in CKD 3 . Risk factors for CKD are more prevalent in the United States than in Italy . With use of CKD 3a and 3b stages , CKD prevalence decreased in NE Italy ( 8.5 % ) and in the United States ( 12.8 % ) . CONCLUSIONS The prevalence of CKD is high in NE Italy , but lower than that in the United States . A large part of the difference in CKD prevalence in NE Italy versus that in the United States is due to the different prevalence of CKD 3 . The higher prevalence of a number of renal risk factors in persons from the United States explains in part the different dimensions of the CKD problem in the two population The aim of this study was to assess the kidney function of an older community-dwelling population at baseline and appraise its evolution after 3 years of follow-up in terms of chronic kidney disease ( CKD ) stage progression , magnitude of glomerular filtration rate ( GFR ) changes , and value of serum creatinine . This was a prospect i ve population -based study of 676 Italian participants , aged 65 years and older . GFR was estimated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease Study equation . Using the Cockcroft-Gault equation . A total of 33 % of participants had criteria of CKD ( GFR < 60 mL/min ) at baseline ; among them , the majority remained stable , 10 % improved , and 7 % progressed to more severe CKD stages at follow-up . Loss of GFR in participants with GFR < 60 mL/min was significantly lower ( 1.4 mL/min per year ) than in participants with GFR ≥ 60 mL/min ( 3.3 mL/min per year ) at baseline . Most participants classified with CKD stage 2 ( GFR 60 - 89 mL/min ) or stage 3 ( GFR 30 - 59 mL/min ) at baseline did not change stage , whereas 55 % of people with CKD stage 1 ( GFR > 90 mL/min ) at baseline worsened to stage 2 and 10 % worsened to stage 3 . An abnormal high level of serum creatinine at baseline did not help to predict who might worsen at follow-up . Older people with CKD displayed a low progression of renal disease and therefore are at higher risk for co-morbidities related to CKD than for progression to end-stage renal disease OBJECTIVES HERMEX is a population -based study which tries to evaluate the relative weight of cardiovascular risk factors in inhabitants of Extremadura , Spain . This report presents the data about chronic kidney disease ( CKD ) in a Spanish population sample . METHODS For an observational cross-sectional population -based study , 3,402 subjects were r and omly selected from health care system records . The final sample included 2,813 participants ( mean age 51.2 years , 53.5 % women ) . Renal function was estimated from serum creatinine using the 4-variable Modification of Diet in Renal Disease ( MDRD-4 ) Study and Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) equations . Individual renal risk was calculated using the Kidney Disease Improving Global Outcomes ( KDIGO ) table . RESULTS Using the CKD-EPI formula , 3.6 % of participants had a glomerular filtration rate ( GFR ) < 60 ml/min . MDRD-4 gave a result of 4.0 % . Prevalence of albuminuria was 5.5 % . Taken together , in patients with albuminuria and /or reduced GFR , the prevalence of renal disease was 8.1 % . The KDIGO renal risk table suggested that 0.05 % of patients were at high or very high risk of CKD progression and 1.6 % at medium risk . CKD was more common in those who were obese , hypertensive , dyslipidemic or had diabetes . Multivariate analysis showed an independent negative association of CKD as dependent variable with systolic blood pressure and body mass index , but a positive correlation with diastolic blood pressure and male sex . CONCLUSIONS A low frequency of abnormal GFR was detected in a r and omly selected sample of the Spanish general population . This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors BACKGROUND Rapidly progressing ageing of worldwide population s is likely to increase the occurrence of chronic kidney disease ( CKD ) in the next decades . However , until now little is known about the prevalence of CKD in the Polish elderly population . The aim of this study was to assess the prevalence of CKD and its relation to socioeconomic conditions in the Polish elderly population . METHODS A glomerular filtration rate estimated ( eGFR ) according to the CKD-EPI formula and urine albumin/creatinine ratio were determined in 3797 out of 4979 r and omly selected elderly subjects from the national survey study PolSenior . Additionally , some socioeconomic factors related to the prevalence of CKD were also analysed . RESULTS The prevalence of CKD in the Polish elderly population was 29.4 % . Only 3.2 % of elderly subjects with CKD were aware of the disease . CKD was more frequent among urban dwellers , non-smokers , alcohol abstinents and those with low physical activity . Decreased eGFR was more frequent among less educated women , better educated men , blue collar female workers and white collar male workers . Increased albuminuria was associated with low physical activity . CONCLUSIONS ( i ) CKD affects almost one-third of the elderly Polish population . ( ii ) In Pol and elderly subjects with CKD are usually unaware of their kidney disease . ( iii ) In Polish elderly population , CKD is more frequently present among urban residents , non-smokers , abstainers and less physically active people . ( iv ) Only in women is higher educational status related to the lower risk of CKD BACKGROUND Impaired renal function is evolving as an independent marker of the risk of cardiovascular morbidity and mortality . Little is known about the prevalence of impaired renal function and its relationship to cardiovascular risk factors in the Swiss general population . METHODS SAPALDIA comprises a r and om sample of the Swiss population established in 1991 , originally to investigate the health effects of long-term exposure to air pollution . Participants were reassessed in 2002/3 and blood measurements were obtained ( n = 6317 ) . Renal function was estimated using the Cockcroft-Gault equation and the modified MDRD ( four-component ) equation incorporating age , race , gender and serum creatinine level . RESULTS The estimated prevalence of impaired renal function [ estimated glomerular filtration rate < 60 ml/min/1.73 m(2 ) ] differed substantially between men and women , particularly at higher ages , and amounted to 13 % [ 95 % confidence interval ( CI ) 10 - 16 % ] and 36 % ( 95 % CI 32 - 40 % ) in men and women , respectively , of 65 years or older . Smoking , obesity , blood lipid levels , high systolic blood pressure and hyperuricaemia were all more common in men when compared with women . These cardiovascular risk factors were also associated independently with creatinine in both women and men . Women were less likely to receive cardiovascular drugs , in particular angiotensin-converting enzyme inhibitors and beta-blockers , when compared with men of the same age . CONCLUSION Moderate renal impairment seems to be prevalent in the general population , with an apparent excess in females which is not explained by conventional cardiovascular risk factors . The unexpected finding questions the validity of the prediction equations , in particular in females |
13,423 | 27,182,424 | There was no significant difference between tertiles in mean change in VO2max ( tertile 1:+0.29±0.15 l/min , ES ( effect size ) = 0.77 ; 2:+0.26±0.10 l/min , ES=0.68 ; 3:+0.35±0.17 l/min , ES=0.80 ) , despite significant ( p<0.05 ) reductions in session dose and total training volume as training intensity increased .
These data suggest that exercise training intensity has no effect on the magnitude of training-induced increases in maximal oxygen uptake in young healthy human participants , but similar adaptations can be achieved in low training doses at higher exercise intensities than higher training doses of lower intensity ( endurance training ) | Exercise training at a variety of intensities increases maximal oxygen uptake ( VO2max ) , the strongest predictor of cardiovascular and all-cause mortality .
The purpose of the present study was to perform a systematic review , meta-regression and meta- analysis of available literature to determine if a dose-response relationship exists between exercise intensity and training-induced increases in VO2max in young healthy adults . | The distinction between positive and negative training adaptation is an important prerequisite in the identification of any marker for monitoring training in athletes . To investigate the glutamine responses to progressive endurance training , twenty healthy males were r and omly assigned to a training group or a non-exercising control group . The training group performed a progressive ( 3 to 6 x 90 minute sessions per week at 70 % V.O ( 2max ) ) six-week endurance training programme on a cycle ergometer , while the control group did not participate in any exercise during this period . Performance assessment s ( V.O ( 2max ) and time to exhaustion ) and resting blood sample s ( for haemoglobin concentration , haematocrit , cortisol , ferritin , creatine kinase , glutamine , uric acid and urea analysis ) were obtained prior to the commencement of training ( Pre ) and at the end of week 2 , week 4 and week 6 . The training group showed significant improvements in time to exhaustion ( p < 0.01 ) , and V.O ( 2max ) ( p < 0.05 ) at all time points ( except week 2 for V.O ( 2max ) ) , while the control group performance measures did not change . In the training group , haemoglobin concentration and haematocrit were significantly lower ( p < 0.01 ) than pretraining values at week 2 and 4 , as percentage changes in plasma volume indicated a significant ( p < 0.01 ) haemodilution ( + 6 - 9 % ) was present at week 2 , 4 and 6 . No changes were seen in the control group . In the training group , plasma glutamine ( week 2 , 4 and 6 ) , creatine kinase ( week 2 and 4 ) , uric acid ( week 2 and 4 ) and urea ( week 2 and 4 ) all increased significantly from pretraining levels . No changes in cortisol or ferritin were found in the training group and no changes in any blood variables were present in the control group . Plasma glutamine was the only blood variable to remain significantly above pretraining ( 966 + /- 32 micromol . 1 ( -1 ) ) levels at week 6 ( 1176 + /- 24 micromol . 1 ( -1 ) ; p < 0.05 ) The elevation seen here in glutamine levels , after 6 weeks of progressive endurance training , is in contrast to previous reports of decreased glutamine concentrations in overtrained athletes . In conclusion , 6 weeks of progressive endurance training steadily increased plasma glutamine levels , which may prove useful in the monitoring of training responses Eleven men sprint trained two to three times per week for 6 wk to investigate possible exercise-induced slow-to-fast fiber type conversions . Six individuals served as controls . Both groups were tested at the beginning and end of the study to determine anaerobic performance and maximal oxygen consumption . In addition , pre- and postbiopsies were extracted from the vastus lateralis muscle and were analyzed for fiber type composition , cross-sectional area , and myosin heavy chain ( MHC ) content . No significant changes were found in anaerobic or aerobic performance variables for either group . Although a trend was found for a decrease in the percentage of type IIb fibers , high-intensity sprint cycle training caused no significant changes in the fiber type distribution or cross-sectional area . However , the training protocol did result in a significant decrease in MHC IIb with a concomitant increase in MHC IIa for the training men . These data appear to support previous investigations that have suggested exercise-induced adaptations within the fast fiber population ( IIb-->IIa ) after various types of training ( endurance and strength ) BACKGROUND Recently , there has been an increase in popularity and participation in the sport of snowshoeing . While the sport has gained considerable recognition , to date there is little or no scientific research regarding training responses to snowshoeing as a form of exercise . Therefore , the purpose of this study was to determine whether snowshoe training could improve fitness measures . A further purpose was to compare responses from a snowshoe training program to a similarly design ed run training program . METHODS This prospect i ve , comparative study was conducted with healthy males and females between the ages of 19 and 24 . These subjects were recruited from the University of Vermont population and surrounding community . Following baseline measurements in VO2max , running time to exhaustion ( RTE ) , and anthropometry , 17 subjects ( 10 snowshoers and 7 runners ) participated in a six week conditioning program . Both groups exercised for 30 min at 75 - 85 % age predicted maximum heart rate , 3 - 4 times per week , for a total of 18 sessions . RESULTS VO2max improved significantly in both running and snowshoeing groups , 6.3 and 8.5 % , respectively . Run time to exhaustion also improved significantly in both groups , 23.3 and 33.5 % , respectively . There were no changes in anthropometry for either group . With the exception of RTE , there were no statistically significant differences between groups in any other measurements at baseline . CONCLUSIONS These results support the acceptability of snowshoeing as a valid means to improve or maintain cardiovascular endurance UNLABELLED Repeated maximal-intensity short- duration exercise ( sprint interval training , SIT ) can produce muscle adaptations similar to endurance training ( ET ) despite a much reduced training volume . However , most SIT data use cycling , and little is known about its effects on body composition or maximal cardiac output ( Qmax ) . PURPOSE The purpose of this study was to assess body composition , 2000-m run time trial , VO(2max ) , and Q(max ) effects of run SIT versus ET . METHODS Men and women ( n = 10 per group ; mean ± SD : age = 24 ± 3 yr ) trained three times per week for 6 wk with SIT , 30-s all-out run sprints ( manually driven treadmill ) , four to six bouts per session , 4-min recovery per bout , versus ET , 65 % VO(2max ) for 30 to 60 min·d(-1 ) . RESULTS Training improved ( P < 0.05 ) body composition , 2000-m run time trial performance , and VO(2max ) in both groups . Fat mass decreased 12.4 % with SIT ( mean ± SEM ; 13.7 ± 1.6 to 12.0 ± 1.6 kg ) and 5.8 % with ET ( 13.9 ± 1.7 to 13.1 ± 1.6 kg ) . Lean mass increased 1 % in both groups . Time trial performance improved 4.6 % with SIT ( -25.6 ± 8.1 s ) and 5.9 % with ET ( -31.9 ± 6.3 s ) . VO(2max ) increased 11.5 % with SIT ( 46.8 ± 1.6 to 52.2 ± 2.0 mL·kg·(-1)·min(-1 ) ) and 12.5 % with ET ( 44.0 ± 2.0 to 49.5 ± 2.6 mL·kg·(-1)·min(-1 ) ) . None of these improvements differed between groups . In contrast , Q(max ) increased by 9.5 % with ET only ( 22.2 ± 2.0 to 24.3 ± 1.6 L·min(-1 ) ) . CONCLUSIONS Despite a fraction of the time commitment , run SIT induces similar body composition , VO(2max ) , and performance adaptations as ET , but with no effect on Q(max ) . These data suggest that adaptations with ET are of central origin primarily , whereas those with SIT are more PURPOSE To determine whether various intensities of aerobic training differentially affect aerobic capacity as well as resting HR and resting blood pressure ( BP ) . METHODS Sixty-one health young adult subjects were matched for sex and VO2max and were r and omly assigned to a moderate- ( 50 % VO2 reserve ( VO2R ) , vigorous ( 75 % VO2R ) , near-maximal-intensity ( 95 % VO2R ) , or a nonexercising control group . Intensity during exercise was controlled by having the subjects maintain target HR based on HR reserve . Exercise volume ( and thus energy expenditure ) was controlled across the three training groups by varying duration and frequency . Fifty-five subjects completed a 6-wk training protocol on a stationary bicycle ergometer and pre- and posttesting . During the final 4 wk , the moderate-intensity group exercised for 60 min , 4 d.wk the vigorous-intensity group exercised for 40 min , 4 d.wk and the near-maximal-intensity group exercised 3 d.wk performing 5 min at 75 % VO2R followed by five intervals of 5 min at 95 % VO2R and 5 min at 50 % VO2R . RESULTS VO2max significantly increased in all exercising groups by 7.2 , 4.8 , and 3.4 mL.min.kg in the near-maximal- , the vigorous- , and the moderate-intensity groups , respectively . Percent increases in the near-maximal- ( 20.6 % ) , the vigorous- ( 14.3 % ) , and the moderate-intensity ( 10.0 % ) groups were all significantly different from each other ( P < 0.05 ) . There were no significant changes in resting HR and BP in any group . CONCLUSION When volume of exercise is controlled , higher intensities of exercise are more effective for improving VO2max than lower intensities of exercise in healthy , young adults To determine whether high-intensity interval training ( HIT ) would increase respiratory muscle strength and expiratory flow rates more than endurance training ( ET ) , 15 physically active , healthy subjects ( untrained ) were r and omly assigned to an ET group ( n = 7 ) or a HIT group ( n = 8) . All subjects performed an incremental test to exhaustion ( VO2max ) on a cycle ergometer before and after training . St and ard pulmonary function tests , maximum inspiratory pressure ( PImax ) , maximum expiratory pressure ( PEmax ) , and maximal flow volume loops were performed pre training and after each week of training . HIT subjects performed a 4-week training program , 3 days a week , on a cycle ergometer at 90 % of their VO2max final workload , while the ET subjects performed exercise at 60–70 % VO2max . The HIT group performed five 1-min bouts with 3-min recovery periods and the ET group cycled for 45 min continuously . A five-mile time trial ( TT ) was performed prior to , after 2 weeks , and after completion of training . Both groups showed improvements ( P < 0.05 ) in VO2max ( ~8–10 % ) and TT ( HIT 6.5 ± 1.3 % , ET 4.4 ± 1.8 % ) following training with no difference ( P > 0.05 ) between groups . Both groups increased ( P < 0.05 ) PImax post training ( ET ~ 25 % , HIT ~ 43 % ) with values significantly higher for HIT than ET . There was no change ( P > 0.05 ) in expiratory flow rates with training in either group . These data suggest that both whole-body exercise training and HIT are effective in increasing inspiratory muscle strength with HIT offering a time-efficient alternative to ET in improving aerobic capacity and performance PURPOSE The present study compared the effects of aerobic endurance training at different intensities and with different methods matched for total work and frequency . Responses in maximal oxygen uptake ( VO2max ) , stroke volume of the heart ( SV ) , blood volume , lactate threshold ( LT ) , and running economy ( CR ) were examined . METHODS Forty healthy , nonsmoking , moderately trained male subjects were r and omly assigned to one of four groups:1 ) long slow distance ( 70 % maximal heart rate ; HRmax ) ; 2)lactate threshold ( 85 % HRmax ) ; 3 ) 15/15 interval running ( 15 s of running at 90 - 95 % HRmax followed by 15 s of active resting at 70 % HRmax ) ; and 4 ) 4 x 4 min of interval running ( 4 min of running at 90 - 95 % HRmax followed by 3 min of active resting at 70%HRmax ) . All four training protocol s result ed in similar total oxygen consumption and were performed 3 d.wk for 8 wk . RESULTS High-intensity aerobic interval training result ed in significantly increased VO2max compared with long slow distance and lactate-threshold training intensities ( P<0.01 ) . The percentage increases for the 15/15 and 4 x 4 min groups were 5.5 and 7.2 % , respectively , reflecting increases in V O2max from 60.5 to 64.4 mL x kg(-1 ) x min(-1 ) and 55.5 to 60.4 mL x kg(-1 ) x min(-1 ) . SV increased significantly by approximately 10 % after interval training ( P<0.05 ) . CONCLUSIONS : High-aerobic intensity endurance interval training is significantly more effective than performing the same total work at either lactate threshold or at 70 % HRmax , in improving VO2max . The changes in VO2max correspond with changes in SV , indicating a close link between the two The aim of this longitudinal study was to compare two recovery modes ( active vs. passive ) during a seven-week high-intensity interval training program ( SWHITP ) aim ed to improve maximal oxygen uptake ( $ $ \dot{V}{\text{O } } _ { { 2 { \text{max } } } } $ $ ) , maximal aerobic velocity ( MAV ) , time to exhaustion ( tlim ) and time spent at a high percentage of $ $ \dot{V}{\text{O } } _ { { 2 { \text{max } } } } $ $ , i.e. , above 90 % ( t90 $ $ \dot{V}{\text{O } } _ { { 2 { \text{max } } } } $ $ ) and 95 % ( t95 $ $ \dot{V}{\text{O } } _ { { 2 { \text{max } } } } $ $ ) of $ $ \dot{V}{\text{O } } _ { { 2 { \text{max } } } } $ $ . Twenty-four adults were r and omly assigned to a control group that did not train ( CG , n = 6 ) and two training groups : intermittent exercise ( 30 s exercise/30 s recovery ) with active ( IEA , n = 9 ) or passive recovery ( IEP , n = 9 ) . Before and after seven weeks with ( IEA and IEP ) or without ( CG ) high-intensity interval training ( HIT ) program , all subjects performed a maximal grade d test to determine their $ $ \dot{V}{\text{O } } _ { { 2 { \text{max } } } } $ $ and MAV . Subsequently only the subjects of IEA and IEP groups carried out an intermittent exercise test consisting of repeating as long as possible 30 s intensive runs at 105 % of MAV alternating with 30 s active recovery at 50 % of MAV ( IEA ) or 30 s passive recovery ( IEP ) . Within IEA and IEP , mean tlim and MAV significantly increased between the onset and the end of the SWHITP and no significant difference was found in t90 VO2max and t95 VO2max . Furthermore , before and after the SWHITP , passive recovery allowed a longer tlim for a similar time spent at a high percentage of VO2max . Finally , within IEA , but not in IEP , mean VO2max increased significantly between the onset and the end of the SWHITP both in absolute ( p < 0.01 ) and relative values ( p < 0.05 ) . In conclusion , our results showed a significant increase in VO2max after a SWHITP with active recovery in spite of the fact that tlim was significantly longer ( more than twice longer ) with respect to passive recovery Regular exercise training improves maximal oxygen uptake ( VO2max ) , but the optimal intensity and volume necessary to obtain maximal benefit remains to be defined . A growing body of evidence suggests that exercise training with low-volume but high-intensity may be a time-efficient means to achieve health benefits . In the present study , we measured changes in VO2max and traditional cardiovascular risk factors after a 10 wk . training protocol that involved three weekly high-intensity interval sessions . One group followed a protocol which consisted of 4 × 4 min at 90 % of maximal heart rate ( HRmax ) interspersed with 3 min active recovery at 70 % HRmax ( 4-AIT ) , the other group performed a single bout protocol that consisted of 1 × 4 min at 90 % HRmax ( 1-AIT ) . Twenty-six inactive but otherwise healthy overweight men ( BMI : 25–30 , age : 35–45 y ) were r and omized to either 1-AIT ( n = 11 ) or 4-AIT ( n = 13 ) . After training , VO2max increased by 10 % ( ∼5.0 mL⋅kg−1⋅min−1 ) and 13 % ( ∼6.5 mL⋅kg−1⋅min−1 ) after 1-AIT and 4-AIT , respectively ( group difference , p = 0.08 ) . Oxygen cost during running at a sub-maximal workload was reduced by 14 % and 13 % after 1-AIT and 4-AIT , respectively . Systolic blood pressure decreased by 7.1 and 2.6 mmHg after 1-AIT and 4-AIT respectively , while diastolic pressure decreased by 7.7 and 6.1 mmHg ( group difference , p = 0.84 ) . Both groups had a similar ∼5 % decrease in fasting glucose . Body fat , total cholesterol , LDL-cholesterol , and ox-LDL cholesterol only were significantly reduced after 4-AIT . Our data suggest that a single bout of AIT performed three times per week may be a time-efficient strategy to improve VO2max and reduce blood pressure and fasting glucose in previously inactive but otherwise healthy middle-aged individuals . The 1-AIT type of exercise training may be readily implemented as part of activities of daily living and could easily be translated into programs design ed to improve public health . Trial Registration Clinical Trials.gov PURPOSE The aim of the present study was to study the effects of aerobic training on performance during soccer match and soccer specific tests . METHODS Nineteen male elite junior soccer players , age 18.1 + /- 0.8 yr , r and omly assigned to the training group ( N = 9 ) and the control group ( N = 10 ) participated in the study . The specific aerobic training consisted of interval training , four times 4 min at 90 - 95 % of maximal heart rate , with a 3-min jog in between , twice per week for 8 wk . Players were monitored by video during two matches , one before and one after training . RESULTS In the training group : a ) maximal oxygen uptake ( VO2max ) increased from 58.1 + /- 4.5 mL x kg(-1 ) x min(-1 ) to 64.3 + /- 3.9 mL x kg(-1 ) x min(-1 ) ( P < 0.01 ) ; b ) lactate threshold improved from 47.8 + /- 5.3 mL x kg(-1 ) x min(-1 ) to 55.4 + /- 4.1 mL x kg(-1 ) x min(-1 ) ( P < 0.01 ) ; c ) running economy was also improved by 6.7 % ( P < 0.05 ) ; d ) distance covered during a match increased by 20 % in the training group ( P < 0.01 ) ; e ) number of sprints increased by 100 % ( P < 0.01 ) ; f ) number of involvements with the ball increased by 24 % ( P < 0.05 ) ; g ) the average work intensity during a soccer match , measured as percent of maximal heart rate , was enhanced from 82.7 + /- 3.4 % to 85.6 + /- 3.1 % ( P < 0.05 ) ; and h ) no changes were found in maximal vertical jumping height , strength , speed , kicking velocity , kicking precision , or quality of passes after the training period . The control group showed no changes in any of the tested parameters . CONCLUSION Enhanced aerobic endurance in soccer players improved soccer performance by increasing the distance covered , enhancing work intensity , and increasing the number of sprints and involvements with the ball during a match Swart , J , Lamberts , RP , Derman , W , and Lambert , MI . Effects of high-intensity training by heart rate or power in well-trained cyclists . J Strength Cond Res 23(2 ) : 619 - 625 , 2009-The aim of this study was to determine whether the performance of cyclists after 4 weeks of high-intensity training improved similarly using either heart rate or power to prescribe training . Twenty-one well-trained men cyclists ( age , 32 ± 6 years ; peak power output , 371 ± 46 W ) were r and omly assigned to a power-based ( GPOWER ) or heart rate-based ( GHEART ) high-intensity training ( HIT ) group or a control group ( GCONTROL ) . Training consisted of 8 repetitions of 4 minutes at either 80 % of peak power output ( GPOWER ) or at the heart rate coinciding with 80 % of peak power output ( GHEART ) , with rest periods of 90 seconds . A 40-km time trial and & OV0312;o2max test were performed before and after 8 training sessions . There were significant improvements ( p < 0.05 ) in peak power output ( GPOWER = 3.5 % ; GHEART = 5.0 % ) and 40-km time trial performance ( GPOWER = 2.3 % ; GHEART = 2.1 % ) for both of the high-intensity groups . Although there were no significant differences between groups for these variables , when the data were analyzed using magnitude-based effects , the GHEART group showed greater probability of a “ beneficial ” effect for peak power output . The current general perception that prescribing training based only on power is more effective than prescribing training based on heart rate was not supported by the data from this study . Coaches who are unable to monitor progress frequently should prescribe training based on heart rate , when intervals are performed under stable conditions , because this may provide an additional advantage over prescribing training using power The goal of the study was to determine the effects of continuous ( CT ) vs. intermittent ( IT ) training yielding identical mechanical work and training duration on skeletal muscle and cardiorespiratory adaptations in sedentary subjects . Eleven subjects ( 6 men and 5 women , 45 + /- 3 years ) were r and omly assigned to either of the two 8-wk training programs in a cross-over design , separated by 12 wk of detraining . Maximal oxygen uptake ( Vo2max ) increased after both trainings ( 9 % with CT vs. 15 % with IT ) , whereas only IT was associated with faster Vo2 kinetics ( tau : 68.0 + /- 1.6 vs. 54.9 + /- 0.7 s , P < 0.05 ) measured during a test to exhaustion ( TTE ) and with improvements in maximal cardiac output ( Qmax , from 18.1 + /- 1.1 to 20.1 + /- 1.2 l/min ; P < 0.01 ) . Skeletal muscle mitochondrial oxidative capacities ( Vmax ) were only increased after IT ( 3.3 + /- 0.4 before and 4.5 + /- 0.6 micromol O2 x min(-1 ) x g dw(-1 ) after training ; P < 0.05 ) , whereas capillary density increased after both trainings , with a two-fold higher enhancement after CT ( + 21 + /- 1 % for IT and + 40 + /- 3 % after CT , P < 0.05 ) . The gain of Vmax was correlated with the gain of TTE and the gain of Vo2max with IT . The gain of Qmax was also correlated with the gain of VO2max . These results suggest that fluctuations of workload and oxygen uptake during training sessions , rather than exercise duration or global energy expenditure , are key factors in improving muscle oxidative capacities . In an integrative view , IT seems optimal in maximizing both peripheral muscle and central cardiorespiratory adaptations , permitting significant functional improvement . These data support the symmorphosis concept in sedentary subjects Very high-intensity , low-volume , sprint interval training ( SIT ) increases muscle oxidative capacity and may increase maximal oxygen uptake ( $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ ) , but whether circulatory function is improved , and whether SIT is feasible in overweight/obese women is unknown . To examine the effects of SIT on $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ and circulatory function in sedentary , overweight/obese women . Twenty-eight women with BMI > 25 were r and omly assigned to SIT or control ( CON ) groups . One week before pre-testing , subjects were familarized to $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ testing and the workload that elicited 50 % $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ was calculated . Pre- and post-intervention , circulatory function was measured at 50 % of the pre-intervention $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ , and a GXT was performed to determine $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ . During the intervention , SIT training was given for 3 days/week for 4 weeks . Training consisted of 4–7 , 30-s sprints on a stationary cycle ( 5 % body mass as resistance ) with 4 min active recovery between sprints . CON maintained baseline physical activity . Post-intervention , heart rate ( HR ) was significantly lower and stroke volume ( SV ) significantly higher in SIT ( −8.1 and 11.4 % , respectively ; P < 0.05 ) during cycling at 50 % $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ ; changes in CON were not significant ( 3 and −4 % , respectively ) . Changes in cardiac output ( $ $ { \dot{\text{Q } } } $ $ ) and arteriovenous oxygen content difference [ ( a − v)O2 diff ] were not significantly different for SIT or CON . The increase in $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ by SIT was significantly greater than by CON ( 12 vs. −1 % ) . Changes by SIT and CON in HRmax ( −1 vs. −1 % ) were not significantly different . Four weeks of SIT improve circulatory function during submaximal exercise and increases $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ in sedentary , overweight/obese women Abstract We hypothesised that habitual physical activity ( PA ) together with progressive endurance training contributes to the differences in training response ( Δ[Vdot]O2max ) in healthy and physically active male participants . Twenty volunteers ( age 30±3 years and [Vdot]O2max 54±7 ml·kg−1·min−1 ) participated in an eight-week training program which included four to six heart rate-guided exercise sessions weekly . PA data over the whole period were collected by an accelerometer-equipped wristwatch . Individual relative intensities of endurance training and PA were separately determined by adjusting to [Vdot]O2max reserve and calculated as mean daily duration ( min ) of training and PA at light , moderate , high and very high intensity levels . [Vdot]O2max increased 6.4±4.1 % ( p < 0.0001 ) during the training period . Δ[Vdot]O2max correlated with the amount of habitual PA that was mainly of light intensity ( r = 0.53 , p = 0.016 ) , but not with the duration of moderate , high or very high intensity PA ( p = ns for all ) . Age , body mass index , and daily amount of training at any intensity level of exercise were not related to Δ[Vdot]O2max ( p = ns for all ) . In conclusion , a high amount of habitual PA together with prescribed endurance training was associated with good training response in physically active males This study examined the effect of high-intensity interval training on the VO2 response during severe , constant-load exercise . Prior to , and following training , 10 females ( V O2 peak 37.4+/-6.0 mL kg-1 min-1 ) performed a grade d exercise test to determine VO2 peak and lactate threshold ( LT ) and a 6 min cycle test ( CT ) at the pre-training VO2 peak intensity . Training involved high-intensity intervals ( 2 min work , 1 min rest ) performed 3x week for 8 weeks . Breath-by-breath data from 0 to 6 min during the CT were smoothed using 5s averages and fit to a bi-exponential model starting from 20s . Training result ed in significant improvements in VO2 max ( 2.34+/-0.37 - 2.78+/-0.30 L min-1 ) , power at VO2 max ( 170+/-26 - 204+/-25 W ) and power at LT ( 113+/-17 - 136+/-20 W ) ( p<0.05 ) . Following training , the VO2 response showed a significant increase in the amplitude of the primary phase ( A1 ) ( 1396+/-103 - 1695+/-100 mL min-1 ; p<0.05 ) and end-exercise VO2 ( VO2 EE ) , with no difference ( p>0.05 ) in the time constants of either phase or the amplitude of the slow component ( 318+/-67 - 380+/-48 mL ; p=0.15 ) . In conjunction , accumulated oxygen deficit ( AOD ) ( 43.7+/-9.8 - 17.2+/-2.8 mL O2 eq kg-1 ) and anaerobic contribution to the CT ( 19.4+/-4.4 - 7.2+/-1.2 % ) were significantly reduced . In contrast to previous moderate-intensity research , a high-intensity interval training program increased A1 and VO2 EE for the same absolute exercise intensity , decreasing the AOD during a severe-intensity CT Ziemann , E , Grzywacz , T , Łuszczyk , M , Laskowski , R , Olek , RA , and Gibson , AL . Aerobic and anaerobic changes with high-intensity interval training in active college-aged men . J Strength Cond Res 25(4 ) : 1104 - 1112 , 2011-We investigated the aerobic and anaerobic benefits of high-intensity interval training performed at a work-to-rest ratio of 1:2 because little performance enhancement data exist based on this ratio . Recreationally active male volunteers ( 21 years , 184 cm , 81.5 kg ) were r and omly assigned to a training ( interval training [ IT ] n = 10 ) or control group ( n = 11 ) . Baseline assessment s were repeated after the last training session . Each participant underwent basic anthropometric assessment and performed a & OV0312;o2max test on an electronically braked cycle ergometer and a 30-second Wingate test . Venous sample s were acquired at the antecubital vein and subsequently processed for lactate ( LA ) ; sample s were obtained at rest , and 5 and 15-minute post-Wingate test . The interval training used a cycling power output equivalent to 80 % of & OV0312;o2max ( 80 % p & OV0312;o2max ) applied for 6 90-second bouts ( each followed by 180-second rest ) per session , 3 sessions per week , for 6 weeks . The control group maintained their normal routine for the 6-week period . Group × time repeated- measures analyses of variance revealed that IT improved & OV0312;o2max ( 5.5 ml·kg−1·min−1 ) , anaerobic threshold ( 3.8 ml·kg−1·min−1 ) , work output ( 12.5 J·kg−1 ) , glycolytic work ( 11.5 J·kg−1 ) , mean power ( 0.3 W·kg−1 ) , peak power ( 0.4 W·kg−1 ) , and max power ( 0.4 W·kg−1 ) ; p < 0.05 . Posttesting LA was lower on average for IT at the 5-minute mark but significantly so at the 15-minute mark . Twenty-seven minutes of cycling at 80 % p & OV0312;o2max applied with a work-to-rest ratio of 1:2 and spread over 3 sessions per week for 6 weeks provided sufficient stimulus to significantly improve markers of anaerobic and aerobic performance in recreationally active college-aged men . Inclusion of such a protocol into a training program may rapidly restore or improve a client 's or athlete 's maximal functional capacity Clark , JE . The use of an 8-week mixed-intensity interval endurance-training program improves the aerobic fitness of female soccer players . J Strength Cond Res 24(7 ) : 1773 - 1781 , 2010-The purpose of this study is to examine improvements in cardiorespiratory fitness ( & OV0312;o2 ) after the use of a mixed-intensity interval endurance-training ( MI-ET ) program in female soccer players , to vali date the MI-ET program as an appropriate training regimen to improve cardiorespiratory fitness ( & OV0312;o2 ) in soccer players . 32 female soccer players ( average 18.66 ± 0.31 years ) were recruited from a group of currently conditioning local U-19 and college soccer teams and r and omly assigned to participate in an 8-week periodized training program that involved either the MI-ET program or the continuation of a current endurance-training ( ET ) program . Analysis of variance indicates no differences in & OV0312;o2 values within the group of athletes before participating in the exercise program . After the 8 weeks of training , the MI-ET group of athletes had significantly greater average & OV0312;o2 values ( 62.13 ± 0.96 ml O2·kg−1·min−1 vs. 57.27 ± 1.59 ml O2·kg−1·min−1 ) , p = 0.015 , along with a greater group average of change in & OV0312;o2 ( 12.44 ± 0.92 ml O2·kg−1·min−1 vs. 7.72 ± 0.99 ml O2·kg−1·min−1 ) , p < 0.001 . The MI-ET program is shown to be a valid means to improve aerobic fitness as indicated by the MI-ET group exhibiting significantly greater & OV0312;o2 measures after training Improvement of exercise capacity by continuous ( CT ) versus interval training ( IT ) remains debated . We tested the hypothesis that CT and IT might improve peripheral and /or central adaptations , respectively , by r and omly assigning 10 healthy subjects to two periods of 24 trainings sessions over 8 weeks in a cross-over design , separated by 12 weeks of detraining . Maximal oxygen uptake ( VO2max ) , cardiac output ( Qmax ) and maximal arteriovenous oxygen difference ( Da-vO2max ) were obtained during an exhaustive incremental test before and after each training period . VO2max and Qmax increased only after IT ( from 26.3 + /- 1.6 to 35.2 + /- 3.8 ml min(-1 ) kg(-1 ) and from 17.5 + /- 1.3 to 19.5 + /- 1.8 l min(-1 ) , respectively ; P < 0.01 ) . Da-vO2max increased after both protocol s ( from 11.0 + /- 0.8 to 12.7 + /- 1.0 ; P < 0.01 and from 11.0 + /- 0.8 to 12.1 + /- 1.0 ml 100 ml(-1 ) , P < 0.05 in CT and IT , respectively ) . At submaximal intensity a significant rightward shift of the Q/Da-vO2 relationship appeared only after CT . These results suggest that in isoenergetic training , central and peripheral adaptations in oxygen transport and utilization are training-modality dependant . IT improves both central and peripheral components of Da-vO2max whereas CT is mainly associated with greater oxygen extraction Sprint interval training ( SIT ) has been proposed as a time efficient alternative to endurance training ( ET ) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions . In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT . Sixteen young sedentary males ( age 21 ± SEM 0.7 years , BMI 23.8 ± SEM 0.7 kg m(-2 ) ) were r and omly assigned to 6 weeks of ET ( 40 - 60 min cycling at ∼65 % , 5 times per week ) or SIT ( 4 - 6 Wingate tests , 3 times per week ) . Muscle biopsies were taken from the m. vastus lateralis before and following 60 min cycling at 65 % to measure muscle microvascular endothelial eNOS content , eNOS serine(1177 ) phosphorylation , NOX2 content and capillarisation using quantitative immunofluorescence microscopy . Whole body insulin sensitivity , arterial stiffness and blood pressure were also assessed . ET and SIT increased skeletal muscle microvascular eNOS content ( ET 14 % ; P < 0.05 , SIT 36 % ; P < 0.05 ) , with a significantly greater increase observed following SIT ( P < 0.05 ) . Sixty minutes of moderate intensity exercise increased eNOS ser(1177 ) phosphorylation in all instances ( P < 0.05 ) , but basal and post-exercise eNOS ser(1177 ) phosphorylation was lower following both training modes . All microscopy measures of skeletal muscle capillarisation ( P < 0.05 ) were increased with SIT or ET , while neither endothelial nor sarcolemmal NOX2 was changed . Both training modes reduced aortic stiffness and increased whole body insulin sensitivity ( P < 0.05 ) . In conclusion , in sedentary males SIT and ET are effective in improving muscle microvascular density and eNOS protein content |
13,424 | 12,804,439 | All studies reported small and inconstant improvements in fatigue , whereas the clinical relevance of these findings and the impact on patient 's functioning and health related quality of life remains undetermined . | BACKGROUND Fatigue is one of the most common and disabling symptoms of people with Multiple Sclerosis ( MS ) .
The effective management of fatigue has an important impact on the patient 's functioning , abilities , and quality of life .
Although a number of strategies have been devised for reducing fatigue , treatment recommendations are based on a limited amount of scientific evidence .
Many textbooks report amantadine as a first-choice drug for MS-related fatigue because of published r and omised controlled trials ( RCTs ) showing some benefit .
We performed a systematic review in order to gather existing evidence , and contribute to the topic .
OBJECTIVES To determine the effectiveness and safety of amantadine in reducing fatigue in people with MS . | Fifty-eight patients with severe , progressive multiple sclerosis were prospect ively r and omized to one of three treatments : 20 received intravenous ACTH , 20 received high-dose intravenous cyclophosphamide plus ACTH , and 18 were placed on a regimen consisting of plasma exchange , low-dose oral cyclophosphamide , and ACTH . The three groups were similar in age , sex , duration and type of disease , and degree of disability . Before treatment and six months and one year after treatment , a disability-status score , ambulation index , and functional-status score were determined , and a quantitative neurologic examination was performed . In the ACTH group , the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year ; in the cyclophosphamide-ACTH group , 18 of 20 at six months and 16 of 20 at one year ; and in the plasma exchange group , 11 of 18 at six months and 9 of 18 at one year . High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at both 6 and 12 months ( at 12 months , cyclophosphamide-ACTH vs. ACTH , P = 0.0004 ; cyclophosphamide-ACTH vs. plasma exchange , P = 0.087 ) . Thus , progressive multiple sclerosis may be stabilized by short-term , intensive immunosuppression with cyclophosphamide plus ACTH A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Treatment with acetyl L-carnitine ( ALCAR ) has been shown to improve fatigue in patients with chronic fatigue syndrome , but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis ( MS ) . To compare the efficacy of ALCAR with that of amantadine , one of the drugs most widely used to treat MS-related fatigue , 36 MS patients presenting fatigue were enrolled in a r and omised , double-blind , crossover study . Patients were treated for 3 months with either amantadine ( 100 mg twice daily ) or ALCAR ( 1 g twice daily ) . After a 3-month washout period , they crossed over to the alternative treatment for 3 months . Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale ( FSS ) , the primary endpoint of the study . Secondary outcome variables were : Fatigue Impact Scale ( FIS ) , Beck Depression Inventory ( BDI ) and Social Experience Checklist ( SEC ) . Six patients withdrew from the study because of adverse reactions ( five on amantadine and one on ALCAR ) . Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale ( p = 0.039 ) . There were no significant effects for any of the secondary outcome variables . The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue Fatigue is a complex phenomenon that , for those not affected , is hard to underst and . To achieve better assessment s , caregivers need reliable and valid tools . The aim of this study was to investigate the reliability and validity of the Swedish version of the Fatigue Impact Scale ( FIS ) among working-aged individuals diagnosed with multiple sclerosis ( MS ) , as well as in a comparative group r and omly selected from the general population in the same geographical area . Both individuals with MS ( n=161 ) and individuals recruited from the general population ( n=194 ) participated in the study . A question naire was used for the data collection . The data were analysed using non-parametric statistical methods . Reliability of FIS was addressed by item-to-item and item-to-total correlations . Concurrent validity was tested for by analysing correlations between the FIS and general questions , and construct validity by investigation of differences in the FIS scores between known groups . The FIS was found to be homogenous , with item-to-total correlation coefficients of 0.42 ≤ rs≤0.86 ( p<0.001 ) , reflecting the instrument 's reliability . The correlations between the FIS and the general questions confirm its concurrent validity , 0.27 ≤ rs≤0.84 ( p<0.001 ) . The differences in FIS scores between known groups demonstrate its construct validity . Furthermore , the FIS showed the ability to discriminate between groups of individuals with differences in perceived impact of fatigue Fatigue is a common symptom of multiple sclerosis ( MS ) that is without an effective treatment . A double-blind , controlled study of fatigue treatment was conducted to evaluate the efficacy of amantadine hydrochloride in treating MS-associated fatigue . Since fatigue can not be characterized by a single symptom or behavior , a variety of neuropsychological , behavioral , and self-report measures were used to monitor changes across different systems . According to patients ' daily diary ratings , amantadine produced small but statistically significant improvements in fatigue across four of seven dimensions ( overall energy level , concentration , problem solving , and sense of well-being ) . In addition , patients with MS who were taking amantadine performed slightly better on the Stroop Interference Test , an attentional measure of freedom from distracting information . Although retrospective reports by patients with MS did not confirm the degree of improvement recorded on a daily basis , the study 's results suggested that amantadine may offer modest benefits in alleviating the day-to-day subjective experience of fatigue As part of a larger study on the quality of life of cancer patients under treatment , the positive and negative experiences in social interaction have been examined as compared to those of a control group ( non patients , n = 201 ) . Two patient groups were included : 109 patients who had recently undergone surgery and 108 patients receiving chemotherapy . The respondents returned a mailed question naire . Contrary to the assumptions based on a review from the literature , cancer patients appear to have more positive and fewer negative social experiences than a r and om sample from the ' normal ' population . Even under more severe medical circumstances ( a poor prognosis or heavy chemotherapy , a large number of chemotherapy cycles , poor progress after surgery ) the poorer the patients , medically speaking , the more help and support they perceive . The results of this study do not support the idea of stigmatization . The personality characteristics , neuroticism and self-esteem are especially important for the having of positive and negative experiences in social interaction . Positive social experiences show a relationship with self-esteem and negative social experiences show a relationship with neuroticism In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis , we found amantadine hydrochloride therapy to be effective in improving fatigability in six . Administration of the drug was associated with significantly higher levels of beta-endorphin-beta-lipotropin and responders had significantly higher levels than nonresponders . Lactate levels were significantly higher and pyruvate levels lower in nonresponders . Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation Objective To determine the relative efficacy of amantadine , pemoline , and placebo in treatment of multiple sclerosis (MS)-related fatigue . Background Fatigue is a complication of MS . Both pemoline and amantadine have been used to treat MS fatigue , but their relative efficacy is not known . Methods Amantadine , pemoline , and placebo were compared in a r and omized , double-blind , placebo-controlled study using a parallel-group design . Ninety-three ambulatory MS patients completed the study . Primary outcome measures were the fatigue seventy scale ( FSS ) ; the MS-specific fatigue scale ( MS-FS ) ; and subjective response determined by verbal self-report . Secondary outcome measures consisted of assessment s of sleep , depression , and vitality . Repeated- measures analysis of variance with planned post-hoc contrasts and Fisher 's exact test were used to compare treatment response . Results Amantadine-treated patients showed a significantly greater reduction in fatigue , as measured by the MS-FS , than did patients treated with placebo ( p = 0.04 ) . By verbal report at the end of the study , 79 % of patients treated with amantadine versus 52 % treated with placebo and 32 % treated with pemoline preferred drug therapy compared with no treatment ( p = 0.03 ) . No significant differences in any primary outcome measures were noted between pemoline and placebo . Neither amantadine nor pemoline affected sleep or depression relative to placebo . Conclusion Amantadine was significantly better than placebo in treating fatigue in MS patients , whereas pemoline was not . The benefit of amantadine was not due to changes in sleep , depression , or neurologic disability We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis ( MS ) and fatigue with objective electrophysiological measures . Behavioral methods ( Reaction Time , RT ) and two different Event Related Potential ( ERP ) components measuring i ) stimulus selection ( Selection Negativity , SN ) and ii ) response selection ( Lateralized Readiness Potential , LRP ) were employed . Twenty-four patients with clinical definite MS ( 10 relapsing remitting and 14 secondary progressive ) and confirmed fatigue in the past three months ( Fatigue Severity Scale ( FSS ) > 4 ) were included . Patients were r and omized in a double-blind , placebo-controlled cross-over design . We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms . This negativity had a higher amplitude during amantadine treatment regardless of treatment order . The RT did not differ significantly between the treated and untreated groups . Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position ( practice effect ) , but no treatment effect , while patients with a longer MS duration showed no practice effect , but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine . The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS , but appears to be limited to subjects with a longer duration of the disease BACKGROUND Amantadine hydrochloride and pemoline , both frequently used to treat the fatigue of multiple sclerosis ( MS ) , may also improve attention and other cognitive functions in MS . To our knowledge , these agents have never been compared in a placebo-controlled trial of patients with MS . OBJECTIVE To evaluate the effects of amantadine and pemoline on cognitive functioning in MS . METHODS A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine , pemoline , or placebo using a parallel group design . They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning . Primary outcome measures were tests of attention ( Digit Span , Trail Making Test , and Symbol Digit Modalities Test ) , verbal memory ( Selective Reminding Test ) , nonverbal memory ( Benton Visual Retention Test ) , and motor speed ( Finger Tapping Test ) . RESULTS Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment . All three treatment groups improved on tests of attention ( P < .003 ) , verbal memory ( P < .001 ) , and motor speed ( P < .002 ) . There were no significant differences between amantadine , pemoline , and placebo . CONCLUSIONS Cognitive functioning in MS is independent of fatigue . Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis , comparing amantadine hydrochloride 100 mg twice a day and placebo . On amantadine 31 % had marked improvement ; 15.6 % moderate improvement ; 15.6 % mild improvement ; and 36.5 % unchanged . On placebo , none noted marked improvement ; one cl aim ed moderate improvement on either amantadine or placebo . 18.7 % reported mild improvement on placebo ; and most of them had similar or more response to amantadine . No patient selected placebo over amantadine at the end of the trial . Overall improvement was seen in 62.5 % of patients on amantadine and 21.8 % on placebo . Additional experience up to two years suggests continued benefit but common and important side-effects During a study of efficacy of amantadine prophylaxis of influenza A virus infection in young adults , gross and subtle side effects were monitored . Eighty-eight students were r and omly selected to receive either amantadine or placebo for four weeks or both in a sequential crossover design of two weeks each . Side effects ( i.e. , dizziness , nervousness , and insomnia ) occurred in 33 % of those receiving amantadine and in 10 % of those receiving placebo ( P less than 0.005 ) . Although side effects were well tolerated by most subjects , six volunteers discontinued amantadine because of marked complaints . Cessation of side effects occurred in more than half of those continuing amantadine . Sixteen students receiving amantadine had decreased performance on sustained attention tasks as compared with ones receiving placebo ( P less than 0.05 ) . Gross and subtle side effects of amantadine observed in this study on currently recommended dosage are higher than previously reported , which may be an important factor in consideration of mass prophylaxis Fifty-three patients with multiple sclerosis were assessed in a double-blind multicentre study for the effect of amantadine . The patients were observed in general practice s for up to four years . Relapses occurred in 5 of the 24 patients treated with amantadine and in 14 of the 29 placebo-treated patients . Neurological deterioration was not significantly different in the two groups We studied 30 patients with clinical ly definite MS according to the Mc Alpine et al. clinical criteria ( 20 patients received isoprinosine and 10 amantadine for a period of 12 months ) . In each patient pattern reversal stimulation was presented to each eye successively and potentials were recorded over both occipital lobes . For each condition the average evoked response to 200 pattern reversals was computed on DISA 2000 . During the 24 month-lasting observation high clinical improvement and simultaneous shortening of the latency to peak of the first major positive component of the response in visual evoked potentials was observed in 12 cases with relapsing form treated 12 months with isoprinosine . In 3 cases , despite of the treatment with isoprinosine , new relapses were observed ; in these patients delayed response in VEP was observed . In cases treated with amantadine no shortening of the latency to the major positive peak of the potential was observed , also no diminish of relapses frequency was observed Background Although levodopa is the most common drug prescribed to relieve the symptoms of Parkinson 's disease it is associated with motor and psychiatric side-effects . Consequently , interest has turned to alternative drugs with improved side-effect profiles to replace or augment levodopa . Amantadine , originally used as an antiviral drug , has been shown to improve the symptoms of Parkinson 's disease . Objectives To compare the efficacy and safety of amantadine therapy ( monotherapy or adjuvant therapy ) versus placebo in treating people with Parkinson 's disease . Search methods Electronic search es of The Cochrane Controlled Trials Register ( The Cochrane Library Issue 3 , 2001 ) , MEDLINE ( 1966 - 2001 ) , EMBASE ( 1974 - 2001 ) , SCI SEARCH ( 1974 - 2001 ) , BIOSIS ( 1993 - 2001 ) , GEROLIT ( 1979 - 2001 ) , OLD MEDLINE ( 1957 - 1965 ) , LILACS ( 1982 - 2001 ) , MedCarib ( 17th Century - 2001 ) , PASCAL ( 1973 - 2001 ) , JICST-EPLUS ( 1985 - 2001 ) , RUSSMED ( 1973 - 2001 ) , DISSERTATION ABSTRACT S ( 2000 - 2001 ) , SIGLE ( 1980 - 2001 ) , ISI-ISTP ( 1990 - 2001 ) , Aslib Index to Theses ( 2001 ) , Clinical trials.gov ( 2001 ) , metaRegister of Controlled Trials ( 2001 ) , NIDRR ( 2001 ) and NRR ( 2001 ) were conducted . Grey literature was h and search ed and the reference lists of identified studies and review s examined . The manufacturers of amantadine were contacted . Selection criteria R and omised controlled trials comparing amantadine with placebo in the treatment of patients with a clinical diagnosis of idiopathic Parkinson 's disease . Data collection and analysis Data was abstract ed independently by NC and KD onto st and ardised forms and disagreements were resolved by discussion . Main results Six r and omised controlled trials were found comparing amantadine monotherapy or adjuvant therapy with placebo in the treatment of idiopathic Parkinson 's disease . Five examined amantadine as adjuvant therapy with optimal levels of levodopa or anticholinergics and one examined amantadine as an adjuvant therapy with minimum tolerated levels of anticholinergics or as a monotherapy . Five were double-blind cross-over studies and one was a double-blind parallel group study . In total they examined 215 patients . The parallel group study allowed the r and omisation codes to be broken and allowed patients in the placebo group to then receive amantadine . This could have led to bias . One study did not present the results of the placebo arm of the trial , hence we could not determine the difference between the two treatment groups . Two cross-over studies presented the results of the combined data from both treatment and placebo arms . The risk of carry-over effect into the second arm meant that these results could not be analysed . The final two studies presented at least some of their data from the end of the first arm of the trials . However only means were given , without st and ard deviations , so we could not determine the statistical significance of any difference between the amantadine and placebo groups . Although the authors did report on the side-effects from amantadine ( such as livido recticularis , dry mouth and blurred vision ) , they state that none of them were severe . Authors ' conclusions A considerable amount of evidence on the effectiveness of amantadine has accrued from non-controlled trials , often in patients with Parkinsonian conditions other than idiopathic Parkinson 's disease . However , rigorous analysis of the six r and omised controlled trials of amantadine reveals insufficient evidence of its efficacy and safety in the treatment of idiopathic Parkinson 's disease Four hundred fifty volunteers participated in a placebo-controlled , double-blind , r and omized trial of the prophylactic effects of rimantadine and amantadine during an outbreak of influenza A. The subjects received drugs orally at a dose of 100 mg twice a day for six weeks . Influenza-like illness occurred in 41 per cent of the subjects receiving placebo but in only 14 per cent of those receiving rimantadine and 9 per cent of these receiving amantadine ( P less than 0.001 for either drug vs. placebo ) . Laboratory-documented influenza occurred in 21 per cent of placebo recipients , 3 per cent of rimantadine recipients , and 2 per cent of amantadine recipients ( P less than 0.001 ) . These findings represent efficacy rates of 85 per cent for rimantadine and 91 per cent for amantadine , as compared with placebo . More recipients of amantadine ( 13 per cent ) than recipients of rimantadine ( 6 per cent ; P less than 0.05 ) or placebo ( 4 per cent ; P less than 0.01 ) withdrew from the study because of central -nervous-system side effects . On the basis of this study , rimantadine appears to be the drug of choice for the prophylaxis of influenza |
13,425 | 26,670,324 | None of the investigated SNPs consistently affected the risk reduction for cardiovascular events .
However , as effect sizes are modest , there is no evidence for the value of genetic testing in clinical practice | AIM We evaluated the evidence of pharmacogenetic associations with statins in a systematic review . | Objective —Although statins are efficacious for lowering low-density lipoprotein cholesterol , there is wide interindividual variation in response . We tested the extent to which combined effects of common alleles of LDLR and HMGCR can contribute to this variability . Methods and Results —Haplotypes in the LDLR 3′-untranslated region ( 3-UTR ) were tested for association with lipid-lowering response to simvastatin treatment in the Cholesterol and Pharmacogenetics trial ( 335 blacks and 609 whites ) . LDLR haplotype 5 ( LDLR L5 ) was associated with smaller simvastatin-induced reductions in low-density lipoprotein cholesterol , total cholesterol , non-high-density lipoprotein cholesterol , and apolipoprotein B ( P=0.0002 to 0.03 ) in blacks but not whites . The combined presence of LDLR L5 and previously described HMGCR haplotypes in blacks was associated with significantly attenuated apolipoprotein B reduction ( −22.4±1.5 % , N=89 ) compared with both noncarriers ( −30.6±1.5 % , N=78 , P=0.0001 ) and carriers of either individual haplotype ( −28.2±1.1 % , N=158 , P=0.001 ) . We observed similar differences when measuring simvastatin-mediated induction of low-density lipoprotein receptor surface expression using lymphoblast cell lines ( P=0.03 ) . Conclusion —We have identified a common LDLR 3-UTR haplotype that is associated with attenuated lipid-lowering response to simvastatin treatment . Response was further reduced in individuals with both LDLR and previously described HMGCR haplotypes . Previously identified racial differences in statin efficacy were partially explained by the greater prevalence of these combined haplotypes in blacks In vitro data indicate that biotransformation of the synthetic 3‐hydroxy‐3‐methylglutaryl – coenzyme A reductase inhibitor fluvastatin is catalyzed by the cytochrome P450 ( CYP ) enzyme 2C9 . The consequences of CYP2C9 genetic polymorphisms on fluvastatin pharmacokinetics and on its efficacy have not been investigated in humans thus far Background — Hypothesis-generating data raise the possibility that carriers of the kinesin-like protein 6 ( KIF6 ) 719 arginine ( Arg ) allele preferentially benefit from statin therapy , and , on this basis , a commercial assay for KIF6 has been developed . Methods and Results — In the recently completed JUPITER trial , men and women without prior cardiovascular disease or diabetes who had baseline low-density lipoprotein cholesterol < 130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L were r and omly allocated to rosuvastatin 20 mg daily or to placebo and followed for first major vascular events ( nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for unstable angina , arterial revascularization , or vascular death ) and for all-cause mortality . We evaluated the effect of polymorphism at rs20455 encoding the KIF6 719Arg allele on outcomes in this primary prevention trial , both among Caucasian participants and in the trial as a whole . Among 8781 Caucasian trial participants , we observed no increase in vascular event rates among carriers of the KIF6 719Arg allele as compared with noncarriers ( hazard ratio , 0.91 ; 95 % confidence interval , 0.66 to 1.26 ) nor any difference in percent low-density lipoprotein cholesterol reduction with rosuvastatin according to genotype ( −52 versus −52 mg/dL , P=0.11 ) . Rosuvastatin allocation was associated with an almost identical reduction in the trial primary end point among carriers ( hazard ratio , 0.61 ; 95 % confidence interval , 0.43 to 0.87 ) as among noncarriers ( hazard ratio , 0.59 ; 95 % confidence interval , 0.39 to 0.88 ) ( P-interaction=0.90 ) . Genotype had no impact on rosuvastatin efficacy in further analyses that included all-cause mortality , in analyses conducted in the total trial cohort that adjusted for race , or in analyses using generalized models of inheritance rather than recessive models . Conclusions — In the large primary prevention JUPITER trial , rosuvastatin was equally effective at reducing cardiovascular event rates among carriers and noncarriers of the KIF6 719Arg allele . Thus , at least for rosuvastatin , there appears to be no clinical utility to screening for KIF6 genotype as a method to determine vascular risk or to predict statin efficacy . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00239681 OBJECTIVE To investigate whether ScrF I polymorphism in the 2nd intron of the HMG-COA reductase gene ( HMGCR ) influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor , simvastatin . METHODS One hundred sixty-eight patients with type 2 diabetes mellitus ( T2DM ) prospect ively received simvastatin as a single-agent therapy ( 20 mg day-1 p.o . ) for 12 weeks . Serum lipid levels were determined before and after simvastatin treatment . Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) . RESULTS Subjects with the AA homozygotes had significantly higher serum very low-density lipoprotein cholesterol ( VLDL-C ) levels than those with the aa homozygotes . In addition , in 168 patients with T2DM who took 20 mg simvastatin , the VLDL-C lowering effect by simvastatin in subjects with the aa homozygotes was significantly lower than in those with the Aa heterozygotes and AA homozygotes . CONCLUSIONS Simvastatin treatment significantly decreased plasma lipids in all patients ( P<0.01 ) . Importantly , we demonstrate that ScrF I polymorphism of the HMGCR gene in patients with T2DM groups is associated with significant elevation of serum VLDL-C levels . Subjects with the AA homozygotes had significantly higher serum high VLDL-C levels than those with the Aa heterozygotes and aa homozygotes ( AA : 2.18+/-0.51 ; Aa : 2.04+/-0.59 , aa : 1.86+/-0.43 , P<0.05 for comparison among three genotypes and P<0.01 for difference between AA and aa ) . Furthermore , this polymorphism tends to show an enhanced response to an HMG-CoA reductase inhibitor in terms of the cholesterol-lowering effect . In 168 patients with T2DM who took 20 mg simvastatin , the VLDL-C lowering effect by simvastatin in subjects with the AA homozygotes was significantly lower than in those with the Aa heterozygotes and aa homozygotes ( the reduction in serum VLDL-C levels ; 37.03+/-5.67 versus 28.97+/-4.96 , P<0.01 ; 34.62+/-5.87 versus 28.97+/-4.96 , P<0.05 ) . These results suggest that the HMGCR gene may serve as a modifier gene for hypercholesterolemia in Chinese diabetic patients We carried out a genome-wide association study ( GWAS ) of LDL-c response to statin using data from participants in the Collaborative Atorvastatin Diabetes Study ( CARDS ; n = 1,156 ) , the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT ; n = 895 ) , and the observational phase of ASCOT ( n = 651 ) , all of whom were prescribed atorvastatin 10 mg . Following genome-wide imputation , we combined data from the three studies in a meta- analysis . We found associations of LDL-c response to atorvastatin that reached genome-wide significance at rs10455872 ( P = 6.13 × 10−9 ) within the LPA gene and at two single nucleotide polymorphisms ( SNP ) within the APOE region ( rs445925 ; P = 2.22 × 10−16 and rs4420638 ; P = 1.01 × 10−11 ) that are proxies for the ε2 and ε4 variants , respectively , in APOE . The novel association with the LPA SNP was replicated in the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) trial ( P = 0.009 ) . Using CARDS data , we further showed that atorvastatin therapy did not alter lipoprotein(a ) [ Lp(a ) ] and that Lp(a ) levels accounted for all of the associations of SNPs in the LPA gene and the apparent LDL-c response levels . However , statin therapy had a similar effect in reducing cardiovascular disease ( CVD ) in patients in the top quartile for serum Lp(a ) levels ( HR = 0.60 ) compared with those in the lower three quartiles ( HR = 0.66 ; P = 0.8 for interaction ) . The data emphasize that high Lp(a ) levels affect the measurement of LDL-c and the clinical estimation of LDL-c response . Therefore , an apparently lower LDL-c response to statin therapy may indicate a need for measurement of Lp(a ) . However , statin therapy seems beneficial even in those with high Lp(a ) BACKGROUND Although statin therapy is known to increase concentrations of PCSK9 , whether this effect is related to the magnitude of LDL reduction is uncertain . This study was undertaken to underst and the extent of this effect and examine the relationship between PCSK9 and LDL cholesterol ( LDL-C ) reduction . METHODS We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 500 men and 500 women participating in the Justification for Use of Statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) trial that r and omly allocated participants to rosuvastatin 20 mg daily or placebo . We also evaluated rs11591147 , a single nucleotide polymorphism known to have an impact on plasma PCSK9 concentrations . RESULTS At baseline , median ( interquartile range ) PCSK9 concentrations were higher in women [ 73 ( 62 - 90 ) ] ng/mL than in men [ 69 ( 57 - 81 ) ng/mL ] ( P<0.005 ) . During 1 year , there was no change in PCSK9 concentrations in the placebo arm , suggesting stability in time . In contrast , the rosuvastatin increased PCSK9 by 35 % in women [ 101 ( 82 - 117 ) ng/mL ] and 28 % in men [ 89 ( 71 - 109 ) ng/mL ] ( P<0.0001 ) . Among those allocated to rosuvastatin , greater reductions in LDL-C were associated with greater increases in PCSK9 on both absolute and relative scales ( r=-0.15 , P<0.0005 ) . Furthermore PCSK9 ( rs11591147 ) did not alter the magnitude of LDL-C reduction associated with rosuvastatin use . CONCLUSIONS In this r and omized trial , rosuvastatin increased plasma concentration of PCSK9 in proportion to the magnitude of LDL-C reduction ; the LDL-C response to statin could not be inferred by PCSK9 concentrations Background Statins effectively lower total and plasma LDL-cholesterol , but the magnitude of decrease varies among individuals . To identify single nucleotide polymorphisms ( SNPs ) contributing to this variation , we performed a combined analysis of genome-wide association ( GWA ) results from three trials of statin efficacy . Methods and Principal Findings Bayesian and st and ard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol , total cholesterol , HDL-cholesterol , and triglyceride on a total of 3932 subjects using data from three studies : Cholesterol and Pharmacogenetics ( 40 mg/day simvastatin , 6 weeks ) , Pravastatin/Inflammation CRP Evaluation ( 40 mg/day pravastatin , 24 weeks ) , and Treating to New Targets ( 10 mg/day atorvastatin , 8 weeks ) . Genotype imputation was used to maximize genomic coverage and to combine information across studies . Phenotypes were normalized within each study to account for systematic differences among studies , and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies . Two SNP associations were assessed as having posterior probability greater than 50 % , indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response . SNP rs8014194 , located within the CLMN gene on chromosome 14 , was strongly associated with statin-mediated change in total cholesterol with an 84 % probability by Bayesian analysis , and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis ( P = 1.8 × 10−8 ) . This SNP was less significantly associated with change in LDL-cholesterol ( posterior probability = 0.16 , P = 4.0 × 10−6 ) . Bayesian analysis also assigned a 51 % probability that rs4420638 , located in APOC1 and near APOE , was associated with change in LDL-cholesterol . Conclusions and Significance Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin , pravastatin , or atorvastatin , we have identified SNPs that may be associated with variation in the magnitude of statin-mediated reduction in total and LDL-cholesterol , including one in the CLMN gene for which statistical evidence for association exceeds conventional levels of genome-wide significance . Trial Registration PRINCE and TNT are not registered . CAP is registered at Clinical trials.gov 1 In the present study , we investigated the effects of the R219 K polymorphism of the ATP‐binding cassette transporter A1 ( ABCA1 ) gene on serum lipid levels and the response to statin therapy in Chinese patients with coronary heart disease ( CHD ) . 2 The study population consisted of 365 patients with CHD and 246 control subjects without signs or symptoms of CHD . Patients with CHD were treated with 20 mg/day pravastatin . Fasting serum lipids were determined before and after 12 weeks of treatment . Genotyping was performed by polymerase chain reaction – restriction fragment length polymorphism ( PCR‐RFLP ) . 3 The R219 K polymorphism of the ABCA1 gene was not significantly associated with CHD ( P > 0.05 ) . Compared with controls , patients with the RR genotype had significantly higher serum triglyceride levels and lower high‐density lipoprotein – cholesterol ( HDL‐C ) levels than those with the KK genotype ( P < 0.05 ) . In addition , the effects of pravastatin in increasing HDL‐C levels were significantly greater in patients with the KK genotype compared with those with the RR genotype ( P < 0.05 ) . 4 In conclusion , the R219 K polymorphism of ABCA1 was associated with altered lipoprotein levels and the R219 K variant significantly modulated the HDL‐C response to pravastatin in Chinese patients with CHD Statin therapy reduces the risk of coronary heart disease ( CHD ) , however , the person-to-person variability in response to statin therapy is not well understood . We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin . First , we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events ( CARE ) trial and 383 CHD cases from the West of Scotl and Coronary Prevention Study ( WOSCOPS ) , two r and omized , placebo-controlled studies of pravastatin . In a combined case-only analysis , 79 single nucleotide polymorphisms ( SNPs ) were associated with differential CHD event reduction by pravastatin according to genotype ( P<0.0001 ) , and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspect i ve Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease ( PROSPER/PHASE ) , a r and omized placebo controlled study of pravastatin in the elderly . We found that one of these SNPs ( rs13279522 ) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies : P = 0.002 in CARE , P = 0.01 in WOSCOPS , P = 0.002 in PROSPER/PHASE . In a combined analysis of CARE , WOSCOPS , and PROSPER/PHASE , the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 ( 95 % CI : 0.52 to 0.75 ) for each extra copy of the minor allele ( P = 4.8 × 10−7 ) . This SNP is located in DnaJ homolog subfamily C member 5B ( DNAJC5B ) and merits investigation in additional r and omized studies of pravastatin and other statins Abstract Aim : To investigate the SLCO1B1 388A > G and 521T > C polymorphisms in hyperlipidemia patients and evaluate the effect of the two polymorphisms on the lipid-lowering efficacy of pitavastatin . Methods : The functional polymorphisms of SLCO1B1 ( 388A > G and 521T > C ) were genotyped in 140 Chinese patients with essential hyperlipidemia using polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) and one-step tetra-primers ARMS-PCR . Eighty-five patients were enrolled in the clinical trial and given 2 mg of pitavastatin daily for 8 weeks . Total cholesterol ( TC ) , triglyceride ( TG ) , high-density lipoprotein ( HDL ) , and low-density lipoprotein ( LDL ) serum levels were measured at baseline , after 4 weeks and after 8 weeks of treatment . Results : The allele frequencies of SLCO1B1 388A > G and 521T > C in essential hyperlipidemia patients were 71.1 % and 11.1 % , respectively . The 4- and 8-week treatment with pitavastatin significantly reduced TC , TG , and LDL levels , but there was no statistical difference among patients with wild type , SLCO1B1 388A > G or SLCO1B1 521T > C in the lipid-lowering efficacy of pitavastatin . Conclusion : The present study found that the allele frequencies of SLCO1B1 388A > G and 521T > C in Chinese patients with essential hyperlipidemia are comparable to those in healthy Chinese population . SLCO1B1 388A > G and 521T > C do not affect the lipid-lowering efficacy of pitavastatin OBJECTIVE The cholesteryl ester transfer protein ( CETP ) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles . Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes . RESEARCH DESIGN AND METHODS We performed a 30-week r and omized double-blind placebo-controlled trial with atorvastatin 10 mg ( A10 ) and 80 mg ( A80 ) in 217 unrelated patients with diabetes . RESULTS CETP TaqIB and A-629C polymorphisms were tightly concordant ( P < 0.001 ) . At baseline , B1B1 carriers had lower plasma HDL cholesterol ( 0.99 + /- 0.2 vs. 1.11 + /- 0.2 mmol/l , P < 0.05 ) , higher CETP mass ( 2.62 + /- 0.8 vs. 2.05 + /- 0.4 mg/l , P < 0.001 ) , and slightly increased , though not significant , plasma TGs ( 2.7 + /- 1.05 vs. 2.47 + /- 0.86 , P = 0.34 ) compared with B2B2 carriers . Atorvastatin treatment significantly reduced CETP mass dose-dependently by 18 % ( A10 ) and 29 % ( A80 ; both vs. placebo P < 0.001 , A10-A80 P < 0.001 ) . CETP mass and activity were strongly correlated ( r = 0.854 , P < 0.0001 ) . CETP TaqIB polymorphism appeared to modify the effect of atorvastatin on HDL cholesterol elevation ( B1B1 7.2 % , B1B2 6.1 % , B2B2 0.5 % ; P < 0.05 ) , TG reduction ( B1B1 39.7 % , B1B2 38.4 % , B2B2 18.4 % ; P = 0.08 ) , and CETP mass reduction ( B1B1 32.1 % , B1B2 29.6 % , B2B2 21.9 % ; P = 0.27 , NS ) . Similar results were obtained for the A-629C polymorphism . CONCLUSIONS In conclusion , the B1B1/CC carriers of the CETP polymorphisms have a more atherogenic lipid profile , including low HDL , and they respond better to statin therapy . These results favor the hypothesis that CETP polymorphisms modify the effect of statin treatment and may help to identify patients who will benefit most from statin therapy Background Combined hyperlipidemia ( CHL ) is one of the dyslipidemias more frequently found in clinical practice , and lipid‐lowering drugs are often necessary in its management . Some genetic loci have been associated with CHL expression , and some studies have shown modulation of drugs efficiency in the treatment of dyslipidemias by genetic polymorphisms . We have investigated whether common polymorphisms and mutations in the apolipoprotein ( apo ) E , lipoprotein lipase ( LPL ) , and apo CIII genes influence atorvastatin or bezafibrate responses in patients with CHL Objective —The purpose of this study was to test the association between polymorphisms in genes involved in either LDL cholesterol ( LDL-C ) metabolism or statin pharmacokinetics and LDL-C reduction with statins . Methods and Results —49 tagging and c and i date polymorphisms in 9 genes were genotyped in 1507 post-ACS subjects r and omized to atorvastatin or pravastatin . Two polymorphisms ( rs7412 , rs429358 ) that define the ϵ2 , ϵ3 , and ϵ4 isoforms of apolipoprotein E were significantly associated with percent reduction in LDL-C with atorvastatin ( ϵ2 carriers 53.8 % , ϵ3/ϵ3 48.1 % , and ϵ4 carriers 46.4 % , respectively , P=0.00039 ) and replicated in the pravastatin arm ( ϵ2 carriers 22.1 % , ϵ3/ϵ3 21.8 % , and ϵ4 carriers 16.6 % , respectively , P=0.00038 ) . The proportion of subjects achieving an LDL-C ≤70 mg/dL at day 30 was higher for ϵ2 than ϵ4 carriers ( P=1.3 × 10−5 ) . In the pravastatin group , the triallelic rs2032582 variant ( G2677T/A ) in ABCB1 was associated with the percent reduction in LDL-C ( GG 23.3 % , non-G heterozygote 20.3 % , and non-G homozygote 17.4 % , P=0.042 ) . Conclusion —Carriers of APOE ϵ2 versus ϵ4 had significantly greater LDL-C reduction with atorvastatin and with pravastatin , and more frequently achieved a guideline -recommended LDL-C ≤70 mg/dL. Polymorphisms in triallelic G2677T/A variant in ABCB1 were associated with the degree of LDL-C lowering with pravastatin AIMS Controversy exists with regard to the influence of APOE polymorphisms on coronary heart disease development and on the efficacy of statin treatment . we investigated the relationship between apoe , mortality and the response to treatment in Mediterranean myocardial infa rct ion ( mi ) survivors . METHODS AND RESULTS We analysed 3304 Italian patients with MI r and omized to pravastatin or no treatment in the GISSI-Prevenzione study , with a mean follow-up time of 23.0 + /- 6.7 months ( median 24.3 months ) . Mortality curves were calculated using Kaplan-Meier method , and differences in survival were tested using the log-rank test . There were 109 deaths during follow-up . Patients treated with pravastatin showed a significant decrease in mortality compared with non-treated patients ( HR 0.67 , 95 % confidence interval 0.45 - 0.97 , P = 0.038 ) . Among the 3304 patients , 554 ( 16.8 % ) were epsilon4 carriers and 2750 ( 83.2 % ) were non-epsilon4 carriers . No significant difference in terms of mortality was observed between the epsilon4 and the non-epsilon4 carriers ( 3.61 % vs. 3.24 % , P = 0.67 ) . However , although in non-epsilon4 carriers no significant difference in mortality was observed between patients treated with pravastatin and non-treated ( 2.81 % vs. 3.67 % , P = 0.21 ) , among the epsilon4 carriers a significant reduction in mortality was observed in patients treated compared with non-treated ( 1.85 % vs. 5.28 % , P = 0.023 ) . CONCLUSION We found that epsilon4 allele is a determinant of pravastatin response in terms of survival . Though in the entire population investigated , we found a beneficial effect of pravastatin in terms of survival , only the epsilon4 carriers seemed to have gained a significant benefit from this treatment . We suggest that the effect of statins is of particular interest in this fraction of the population . Genetic markers can help in identifying patients that benefit more from statin treatment Objective Niemann – Pick C1‐like 1 protein ( NPC1L1 ) plays a key role in lipoprotein metabolism . We examined the association of common genetic polymorphisms in NPC1L1 on apolipoprotein ( apo ) B‐100 metabolism and the response to statin treatment in 37 men with central obesity Toll-like receptor-4 ( TLR-4 ) gene polymorphisms have been associated with a lower risk of atherosclerosis . High levels of soluble P-selectin ( sP-selectin ) and von Willebr and factor predict an increased risk for cardiovascular events and correlate to atherosclerotic risk factors . The relationship between these markers and TLR-4 gene polymorphisms was evaluated in a cohort of consecutive hypercholesterolemic out patients . TLR-4 gene polymorphisms were detected in 48 out of 330 ( 14 % ) patients with hypercholesterolemia . Lipid and inflammatory markers , sP-selectin and von Willebr and were evaluated in carriers and in 96 ( ratio 2:1 to cases ) age- and sex-matched TLR-4 wild-type patients r and omly selected from the same population . A cohort of normocholesterolemic out patients ( n = 262 ) served as the control group . sP-selectin was sensibly lower in carriers of TLR-4 variants as compared to wild-types and controls ( 89 ng/ml vs. 162 ng/ml and 163 ng/dl , respectively , p = 0.0001 ) . Similarly , carriers showed lower von Willebr and factor values ( 683 mU/ml ) than wild-types ( 910 mU/ml ; p = 0.001 ) . In multivariate analysis , TLR-4 gene polymorphisms were positively associated with sP-selectin , whereas the relationship with von Willebr and factor was no longer significant . HMG-CoA reductase inhibitors reduced sP-selectin and von Willebr and factor levels independently of TLR-4 gene variants . Plasma concentrations of these markers , however , remained lower in carriers of TLR-4 gene polymorphisms even after cholesterol lowering . In conclusion , carriership of Asp299 and Thr399Ile TLR-4 gene polymorphisms is associated with lower levels of sP-selectin and von Willebr and factor among hypercholesterolemic patients . While the underlying mechanisms remain to be investigated , such an association may indicate a protective effect of TLR-4 variants for atherosclerosis OBJECTIVES The aim of this study was to test the effects of the KIF6 Trp719Arg polymorphism ( rs20455 ) on vascular risk and response to statin therapy in 18,348 participants from the Heart Protection Study . BACKGROUND There have been cl aims that noncarriers of the KIF6 719Arg variant receive little benefit from statin therapy . Screening for this genetic variant is now being used to influence statin use . METHODS Participants received 40 mg simvastatin daily for 4 to 6 weeks before being r and omly allocated 40 mg simvastatin daily or placebo for 5 years . Major coronary event was pre-defined as coronary death or nonfatal myocardial infa rct ion , and major vascular event was pre-defined as major coronary event plus revascularization or stroke . RESULTS The KIF6 genotype was not significantly associated , among placebo-allocated participants , with the risks of incident major vascular events , major coronary events , revascularizations , or strokes . Overall , 40 mg simvastatin daily produced a 42 % reduction in low-density lipoprotein cholesterol , which did not differ significantly by KIF6 719Arg carrier status ( p = 0.51 ) . Proportional reductions in the risk of major vascular events with statin therapy were similar ( interaction p = 0.70 ) and highly significant across KIF6 genotypes : 23 % ( 95 % confidence interval : 16 % to 29 % ; p = 5.3 × 10⁻¹⁰ ) in carriers ( Arg/Arg or Trp/Arg ) , and 24 % ( 95 % confidence interval : 17 % to 31 % ; p = 4.6 × 10⁻⁹ ) in noncarriers ( Trp/Trp ) . A similar lack of interaction was observed for major coronary events , revascularizations , and strokes considered separately . CONCLUSIONS Statin therapy significantly reduces the incidence of coronary and other major vascular events to a similar extent , irrespective of KIF6 genotype . Consequently , the use of KIF6 genotyping to guide statin therapy is not warranted . ( Heart Protection Study ; IS RCT N48489393 ) Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) locus have been reported to have 15 % lower low-density lipoprotein ( LDL ) cholesterol ( C ) levels and 47 % lower coronary heart disease ( CHD ) risk . Our objective was to examine two PCSK9 single nucleotide polymorphisms ( SNPs ) , R46L and E670 G , in 5783 elderly participants in Prospect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , of whom 43 % had a history of vascular disease at baseline , and who were r and omized to pravastatin or placebo with followup . In this population 3.5 % were carriers of the T allele at R46L , and these subjects had significantly ( p<0.001 ) lower levels of LDL C ( mean , -10 % ) , no difference in LDL C lowering response to pravastatin , and a non-significant 19 % unadjusted and 9 % adjusted decreased risk of vascular disease at baseline , with no on trial effect . Moreover , 6.0 % were carriers of the G allele at E670 G with no significant relationships with baseline LDL C , response to pravastatin , or vascular disease risk being observed . Our data support the concept that the rare allele of the R46L SNP at the PCSK9 locus significantly lowers LDL C , but does not greatly reduce CHD risk in an elderly population with a high prevalence of cardiovascular disease Objectives To determine the frequencies of CYP3A4 alleles ( CYP3A4 * 4,*5 and * 6 ) in Chinese hyperlipidemic patients and to observe the impact of CYP3A4 * 4 ( Ile118Val ) genetic polymorphism on the lipid-lowering effects of simvastatin and on the activity of CYP3A4 . Methods From hospitalized and non-hospitalized patients , 211 unrelated hyperlipidemic patients were recruited for genotyping . CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis . Of the non-hospitalized hyperlipidemic patients , 8 with CYP3A4 * 1/*1 and 8 with CYP3A4 * 1/*4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks . Serum triglycerides ( TG ) , cholesterol ( CHO ) and low-density lipoprotein ( LDL ) levels were determined using an automated analyzer ( Hitachi 747 , Boehringer Mannheim , Mannheim , Germany ) . CYP3A4 activity was determined by the ratio of 6-hydroxycortisol to free cortisol ( 6-OHC/FC ) in the morning spot urine with a high-throughput liquid chromatography – t and em mass spectrometry method . Results Of 211 subjects , 14 ( allele frequency 3.32 % ) were heterozygous for CYP3A4 * 4 ( Ile118Val ) . Nevertheless , no subjects with a CYP3A4 * 5 or CYP3A4 * 6 allele or homozygous for CYP3A4 * 4 were identified . The ratio of 6β-OHC/FC was 9.9±13.7 and 56.6±35.7 in subjects with the Ile118Val variant ( n=8 ) and in CYP3A4 wild-type subjects ( n=8 ) , respectively ( P=0.0039 ) . After oral intake of simvastatin 20 mg daily for 4 weeks , the change of serum lipids in CYP3A4 * 1/*1 and CYP3A4 * 1/*4 groups showed a significant difference , with a mean decrease in triglycerides and total cholesterol of 38.1±7.6 % versus 25.1±8.3 % ( P=0.034 ) and of 35.8±9.6 % versus 22.0±20.4 % ( P=0.0015 ) ( means ± SD ) , respectively . We found no statistically significant difference in the reductions of LDL between subjects carrying the * 1 and * 4 genotypes ( 29.0±7.4 % versus 36.8±8.8 % , P=0.0721 ) . Conclusions The allele frequency of CYP3A4 * 4 was 3.32 % among the hyperlipidemic patients from the Chinese mainl and . CYP3A4 * 4 was an allelic variant related to a functional decrease of CYP3A4 activity , and * 4 expression seemed to increase the lipid-lowering effects of simvastatin Background —Atherosclerosis is increasingly considered to be a chronic inflammatory process . We examined whether genetic variants of the toll-like receptor 4 ( TLR4 ) , which are correlated with impaired innate immunity and with progression of carotid atherosclerosis , are also associated with coronary atherosclerosis and predict the risk of cardiovascular events . Methods and Results —Two polymorphisms of the TLR4 gene ( Asp299Gly and Thr399Ile ) were determined in 655 men with angiographically documented coronary atherosclerosis . All patients participated in a prospect i ve cholesterol-lowering trial evaluating the effect on coronary artery disease and were r and omly assigned to either pravastatin or placebo for 2 years . There were no significant differences between genetically defined subgroups with respect to baseline risk factors , treatment , or in-trial changes of lipid , lipoprotein , or angiographic measurements . Genotype was not associated with progression of atherosclerosis . In the pravastatin group , 299Gly carriers had a lower risk of cardiovascular events during follow-up than noncarriers ( 2.0 % versus 11.5 % , P = 0.045 ) . Among noncarriers , pravastatin reduced the risk of cardiovascular events from 18.1 % to 11.5 % ( P = 0.03 ) , whereas among 299Gly carriers this risk was strikingly reduced from 29.6 % to 2.0 % ( P = 0.0002 , P = 0.025 for interaction ) . Conclusions —Among symptomatic men with documented coronary artery disease , the TLR4 Asp299Gly polymorphism was associated with the risk of cardiovascular events . This variant also modified the efficacy of pravastatin in preventing cardiovascular events , such that carriers of the variant allele had significantly more benefit from pravastatin treatment Response to statin therapy for cardiovascular disease is variable among different individuals . The authors aim ed to investigate the effect of the CYP3AP1 * 3 polymorphism on the lipid-lowering efficacy of statins . They recruited 379 unrelated hyperlipidemic patients : 202 ( 103 men ) treated with simvastatin and 177 ( 87 men ) with atorvastatin as single-agent therapy ( 20 mg day(-1 ) orally ) for 4 weeks . CYP3AP1 * 3(-44G > A ) was genotyped using the PCR restriction fragment-length polymorphism method . Serum levels of total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides ( TGs ) were determined before and after treatment . The frequency of the CYP3AP1 * 3 variant allele in Chinese hyperlipidemic patients was 70.6 % . In the simvastatin treatment group , the percentage reduction of LDL-C level was greater in the CYP3AP1 * 3/*3 carriers than in the CYP3AP1 * 1 carriers . This difference was statistically significant for women but not for men . In contrast , the authors found no significant association between the lipid-lowering efficacy of atorvastatin and the CYP3AP1 * 3 polymorphism in all participants . However , in women , the percentage change of the TC level was significantly lower in the CYP3AP1 * 3/*3 carriers than in the CYP3AP1 * 1 carriers . These findings suggest that the CYP3AP1 * 3 allele may be a biomarker for the lipid-lowering efficacy of simvastatin and atorvastatin in Chinese women with hyperlipidemia Summary Background CYP2C9 * 3 allele has been reported to correlate with increased plasma concentration of fluvastatin active form in healthy volunteers . We analyzed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients . Material / Methods The study was prospect i ve , without any interventions to st and ard procedures of hypolipidemic treatment . CYP2C9 genotype was determined by PCR – RFLP assay in 87 patients on concomitant fluvastatin therapy , in 48 patients on monotherapy , and in a control group of 254 healthy volunteers of Czech nationality . Biochemical and clinical data were collected before the initiation of fluvastatin treatment and 12 weeks later . Results The frequency of CYP2C9 alleles did not differ significantly among groups of patients and volunteers . The most frequently observed allele was CYP2C9 * 2 . Treatment with 80 mg of fluvastatin daily of 48 patients on monotherapy for 12 weeks result ed in mean low-density lipoprotein cholesterol ( LDL-C ) reduction by 25 % , mean serum total cholesterol ( TC ) reduction by 21 % , and mean triglyceride ( TG ) reduction by 28 % . The CYP2C9 * 1/*3 genotype was associated with a decrease in LDL-C levels ( by 40.0 % for CYP2C9 * 1/*3 , but only by 22.4 % for CYP2C9 * 1/*1 ) , and with the reduction of TC ( by 28.6 % in CYP2C9 * 1/*3 versus 20.2 % in CYP2C9 * 1/*1 ) . Conclusions In hypercholesterolemic patients , LDL-C serum concentration was decreased more significantly in fluvastatin-treated subjects bearing the CYP2C9 * 1/*3 genotype compared to CYP2C9 * 1/*1 genotype . However , due to rare occurrence of some CYP genotypes , it was impossible to report a definitive positive genotype-fluvastatin effect association BACKGROUND The high-density lipoprotein ( HDL ) cholesterol concentration is inversely related to the risk of coronary artery disease . The cholesteryl ester transfer protein ( CETP ) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis . METHODS The DNA of 807 men with angiographically documented coronary atherosclerosis was analyzed for the presence of a polymorphism in the gene coding for CETP . The presence of this DNA variation was referred to as B1 , and its absence as B2 . All patients participated in a cholesterol-lowering trial design ed to induce the regression of coronary atherosclerosis and were r and omly assigned to treatment with either pravastatin or placebo for two years . RESULTS The B1 variant of the CETP gene was associated with both higher plasma CETP concentrations ( mean [ + /-SD ] , 2.29+/-0.62 microg per milliliter for the B1B1 genotype vs. 1.76+/-0.51 microg per milliliter for the B2B2 genotype ) and lower HDL cholesterol concentrations ( 34+/-8 vs. 39+/-10 mg per deciliter ) . In addition , we observed a significant dose-dependent association between this marker and the progression of coronary atherosclerosis in the placebo group ( decrease in mean luminal diameter : 0.14+/-0.21 mm for the B1B1 genotype , 0.10+/-0.20 mm for the B1B2 genotype , and 0.05+/-0.22 mm for the B2B2 genotype ) . This association was abolished by pravastatin . Pravastatin therapy slowed the progression of coronary atherosclerosis in B1B1 carriers but not in B2B2 carriers ( representing 16 percent of the patients taking pravastatin ) . CONCLUSIONS There is a significant relation between variation at the CETP gene locus and the progression of coronary atherosclerosis that is independent of plasma HDL cholesterol levels and the activities of lipolytic plasma enzymes . This common DNA variant appears to predict whether men with coronary artery disease will benefit from treatment with pravastatin to delay the progression of coronary atherosclerosis Abstract The influence of genetic polymorphism of the apolipoprotein B on lipid metabolism and coronary heart disease ( CHD ) risk has been demonstrated in different population s , but few studies have shown the contribution of this risk factor in individuals from Brazil . The Ins/del , XbaI and EcoRI polymorphisms of apo B were evaluated in 93 controls and in 104 Caucasian individuals presenting with a high risk lipid profile ( HR1 ) for CHD ; 54 of these subjects ( HR2 ) were treated with fluvastatin during 16 weeks . DNA polymorphisms of the apo B gene were analyzed by polymerase chain reaction – restriction fragment length polymorphism . The X(−)X(− ) genotype for XbaI polymorphism was associated with higher serum concentrations of total cholesterol ( TC ) and low density lipoprotein cholesterol ( LDL-C ) ( p<0.01 ) in women of the HR1 group . The Ins/del and EcoRI polymorphisms were not associated with variation of lipid profile . After treatment with fluvastatin , TC and LDL-C levels of HR2 individuals were reduced by 23 % and 30 % , respectively . Individuals with II genotype had significantly greater reduction ( 34 % ) of LDL-C than those with ID/DD genotypes ( 27 % ) . These results indicate that the XbaI polymorphism is associated with variation of serum TC and LDL-C levels in Brazilian women with lipid profile of risk for CHD and the Ins/del polymorphism is associated with the therapeutic response to fluvastatin Background —There is interindividual variation in low-density lipoprotein cholesterol ( LDLc ) lowering by statins and limited study into the genetic associations of the dose dependant LDLc lowering by statins . Methods and Results —Five hundred nine patients with hyperlipidemia were r and omly assigned atorvastatin 10 mg , simvastatin 20 mg , or pravastatin 10 mg ( low-dose phase ) followed by 80 mg , 80 mg , and 40 mg ( high-dose phase ) , respectively . Thirty-one genes in statin , cholesterol , and lipoprotein metabolism were sequenced and 489 single nucleotide polymorphisms with minor allele frequencies > 2 % were tested for associations with percentage LDLc lowering at low doses using multivariable adjusted general linear regression . Significant associations from the analysis at low dose were then repeated at high-dose statins . At low doses , only 1 single nucleotide polymorphism met our experiment-wide significance level , ABCA1 rs12003906 . Twenty-six subjects carried the minor allele of rs12003906 , which was associated with an attenuated LDLc reduction ( LDLc reduction in carriers versus noncarriers −24.1±2.6 % versus −32.2±1.5 % ; P=0.0001 ) . In addition , we replicated the association with the APOE ϵ3 allele and a reduced LDLc reduction . At high doses , carriers of the minor allele of ABCA1 rs12003906 and the APOE ϵ3 allele improved their LDLc reduction but continued to have a diminished LDLc reduction compared with noncarriers ( −30.5±4.0 % versus −42.0±2.4 % ; P=0.005 ) and ( −38.5±1.9 % versus −45.3±2.8 % ; P=0.009 ) , respectively . Conclusions —An intronic single nucleotide polymorphism in ABCA1 and the APOE ϵ3 allele are associated with reduced LDLc lowering by statins and identify individuals who may be resistant to maximal LDLc lowering by statins Single nucleotide polymorphisms ( SNPs ) at the KIF6 ( kinesin like protein 6 , rs20455 or 719Arg ) , LPA ( lipoprotein(a ) , rs3798220 ) , TAS2R50 ( taste receptor type 2 , member 50 , rs1376251 ) and VAMP8 ( vesicle-associated membrane protein 8 , rs1010 ) have previously been associated with low density lipoprotein cholesterol ( LDL-C ) lowering response to statins , coronary heart disease ( CHD ) at baseline , or CHD events on trial . We examined SNPs at the KIF6 ( rs20455 or 719Arg ) , LPA ( rs3798220 ) , TAS2R50 ( rs1376251 ) and VAMP8 ( rs1010 ) in 5,411 participants in PROSPER ( PROspect i ve Study of Pravastatin in the Elderly at Risk ) ( mean age 75.3 years ) , who had been r and omized to pravastatin 40 mg/day or placebo and were followed for a mean of 3.2 years . No SNP was related to vascular disease at baseline . Only the KIF6 SNP was related to LDL-C lowering with homozygous Arg 719 subjects being significantly less responsive than other groups ( p=0.025 , -34.2 vs. -36.1 % ) . With regard to the primary CHD endpoint on trial ( fatal or non-fatal myocardial infa rct ion or stroke ) , we observed a significant relationship for KIF6 719Arg homozygotes ( p=0.03 , hazards ratio 0.47 , 12.8 % of the population ) in women on pravastatin only , and for TAS2R50 for the AA genotype ( p=0.03 , hazards ratio 1.76 , 8.9 % of the population ) , also only in women on pravastatin . Our data indicate that the assessment of KIF6 rs20455 and TAS2R50 rs1376251 genotypes are not useful for predicting statin induced cardiovascular risk reduction in men , but do predict CHD risk reduction in women in this elderly population . However , these differences are no longer significant after correction for multiple comparisons , and we do not recommend the assessment of any of these SNPs in clinical practice Background Statin therapy has been found to substantially and significantly reduce coronary events in carriers of the KIF6 719Arg variant ( rs20455 ) but not in noncarriers . We investigated whether , among the elderly , statin therapy also significantly reduced coronary events in carriers but not in noncarriers . Design and methods Among 5752 patients of the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) study , we assessed the effect of pravastatin , compared with placebo , on coronary events according to 719Arg carrier status using proportional hazards models . Results Since benefit from statin therapy in elderly patients has been primarily shown among those with prior vascular disease , we performed analyses in PROSPER patients with prior disease and found that pravastatin therapy significantly reduced events in 719Arg carriers [ hazards ratio ( HR ) : 0.66 , 95 % confidence interval ( CI ) : 0.52–0.86 ] but not in noncarriers ( HR : 0.94 , 95 % CI : 0.69–1.28 ) , P= 0.09 for interaction between treatment and carrier status . Among those without prior disease , no significant benefit was observed in either carriers or noncarriers . Among those with prior vascular disease in the placebo arm , Trp719Arg heterozygotes were at significantly greater risk , compared with noncarriers ( HR : 1.36 , 95 % CI : 1.03–1.81 , P = 0.03 ) ; the HR of 719Arg carriers , compared with noncarriers , was 1.28 ( 95 % CI : 0.98–1.69 , P = 0.07 ) . Conclusion Elderly carriers of the KIF6 719Arg variant with prior vascular disease received significant benefit from pravastatin therapy ; no benefit was observed in noncarriers with prior disease or in those without prior disease ( carriers or noncarriers ) A single nucleotide polymorphism ( SNP ) in KIF6 , a member of the KIF9 family of kinesins , is associated with differential coronary event reduction from statin therapy in four r and omized controlled trials ; this SNP ( rs20455 ) is also associated with the risk for coronary heart disease ( CHD ) in multiple prospect i ve studies . We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy . Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial ( CARE ) , 28 were associated with differential event reduction from statin therapy ( Pinteraction < 0.1 in Caucasians , adjusted for age and sex ) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infa rct ion 22 ( PROVE IT-TIMI22 ) and West of Scotl and Coronary Prevention Study ( WOSCOPS ) . These analyses revealed that two SNPs ( rs9462535 and rs9471077 ) , in addition to rs20455 , were associated with event reduction from statin therapy ( Pinteraction < 0.1 in each of the three studies ) . The relative risk reduction ranged from 37 to 50 % ( P < 0.01 ) in carriers of the minor alleles of these SNPs and from −4 to 13 % ( P > 0.4 ) in non-carriers . These three SNPs are in high linkage disequilibrium with one another ( r2 > 0.84 ) . Functional studies of these variants may help to underst and the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy Warfarin dosing is correlated with polymorphisms in vitamin K epoxide reductase complex 1 ( VKORC1 ) and the cytochrome P450 2C9 ( CYP2C9 ) genes . Recently , the FDA revised warfarin labeling to raise physician awareness about these genetic effects . R and omized clinical trials are underway to test genetically based dosing algorithms . It is thus important to determine whether common single nucleotide polymorphisms ( SNPs ) in other gene(s ) have a large effect on warfarin dosing . A retrospective genome-wide association study was design ed to identify polymorphisms that could explain a large fraction of the dose variance . White patients from an index warfarin population ( n = 181 ) and 2 independent replication patient population s ( n = 374 ) were studied . From the approximately 550 000 polymorphisms tested , the most significant independent effect was associated with VKORC1 polymorphisms ( P = 6.2 x 10(-13 ) ) in the index patients . CYP2C9 ( rs1057910 CYP2C9 * 3 ) and rs4917639 ) was associated with dose at moderate significance levels ( P approximately 10(-4 ) ) . Replication polymorphisms ( 355 SNPs ) from the index study did not show any significant effects in the replication patient sets . We conclude that common SNPs with large effects on warfarin dose are unlikely to be discovered outside of the CYP2C9 and VKORC1 genes . R and omized clinical trials that account for these 2 genes should therefore produce results that are definitive and broadly applicable Background — Carriers of the KIF6 719Arg variant may be at increased risk for CVD and may benefit more from statin therapy , in terms of CVD risk reduction , than noncarriers . Our objective was to investigate whether carriers of the KIF6 719Arg genetic variant ( rs20455 ) are at increased cardiovascular risk and obtain more benefit from high-dose statin therapy than do noncarriers . Methods and Results — We used an adjusted Cox proportional hazard model to assess the hazard ratio ( HR ) for the reduction of major cardiovascular events by 80 mg/d atorvastatin over 10 mg/d atorvastatin in 4599 patients of the Treating to New Targets ( TNT ) study and by 80 mg/d atorvastatin over 20–40 mg/d simvastatin in 6541 patients of the Incremental Decrease in End Points Through Aggressive Lipid-Lowering ( IDEAL ) study . A total of 381 and 648 patients had a cardiovascular event during follow-up in TNT and IDEAL , respectively . Heterozygotes and homozygotes for the minor allele were not at increased risk compared with noncarriers . In TNT , for noncarriers of the 719Arg allele , the HR for high- versus low-dose atorvastatin was 0.81 ( 95 % confidence interval , 0.59–1.11 ) . In carriers of 1 or 2 minor alleles , the HR was 0.85 ( 0.66–1.11 ) and carriers of 2 copies of the minor allele obtained a significant risk reduction ( HR : 0.44 , 95 % confidence interval , 0.23–0.84 ) . In IDEAL , the respective HRs were 0.85 ( 0.67–1.10 ) , 0.88 ( 0.62–1.07 ) and 0.91 ( 0.58–1.43 ) . The interaction term for carrier status by treatment was also nonsignificant ( P=0.810 in TNT and P=0.909 in IDEAL ) . Conclusions — In these 2 large , r and omized clinical trials , carriers of the KIF6 719Arg allele were not at increased cardiovascular risk and did not obtain consistent cardiovascular benefit from high-dose statin therapy compared with noncarriers . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00327691 Although the efficacy of fluvastatin ( HMG-CoA reductase inhibitor ) in the treatment of primary hypercholesterolemia is well documented , a wide interindividual variation treatment response has been observed . We have studied the possible role of the AvaII ( exon 13 ) , HincII ( exon 12 ) , and PvuII ( intron 15 ) polymorphisms at the low-density lipoprotein receptor ( LDLR ) gene on lipid-lowering response in 55 patients ( 36 to 70 years old ) with primary hypercholesterolemia treated with fluvastatin for 16 weeks . LDLR genotypes were determined by PCR-RFLP . The results indicate that the AvaII and PvuII polymorphisms influence the cholesterol-lowering response of the HMG-CoA reductase inhibitor Fluvastatin . Patients carrying A+A+ ( AvaII ) or P1P1 ( PvuII ) homozygous genotypes presented lower reduction in total cholesterol , LDL-C and apolipoprotein B levels after 16 weeks of treatment with fluvastatin , when compared to other genotypes ( P<0.05 ) . Our data also support the previous assumption that the AvaII , HincII , and PvuII polymorphisms of the LDLR gene are associated with variation of serum cholesterol levels . Therefore , the identification of the LDLR genetic profile may provide better prediction of a patient 's clinical response to fluvastatin BACKGROUND The aim of this study was to determine whether the angiotensin-converting enzyme ( ACE ) insertion-deletion ( ID ) polymorphism interacts with pravastatin to modify the risk of coronary heart disease ( CHD ) and other cardiovascular end points in a large clinical trial . METHODS GenHAT is an ancillary study of the ALLHAT . The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants r and omly assigned to pravastatin ( n = 4741 ) or to usual care ( n = 4726 ) . The efficacy of pravastatin in reducing the risk of primary outcome ( all-cause mortality ) and secondary outcomes ( fatal CHD and nonfatal myocardial infa rct ion , cardiovascular disease [ CVD ] mortality , CHD , stroke , other CVD , non-CVD mortality , stroke , and heart failure ) was compared between the genotype strata ( dominant model ID + II vs DD , additive model II vs ID vs DD ) , by examining an interaction term in a Cox proportional hazards model . RESULTS The relative risk of fatal CHD and nonfatal myocardial infa rct ion among subjects r and omized to pravastatin compared with subjects r and omized to usual care was similar in subjects with the II genotype ( hazard ratio [ HR ] 0.84 , 95 % CI 0.59 - 1.18 ) , the ID genotype ( HR 0.84 , 95 % CI 0.68 - 1.03 ) , and the DD genotype ( HR 0.99 , 95 % CI 0.77 - 1.27 ) . CONCLUSIONS We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events A number of studies have evaluated the effect of the -514C/T polymorphism of the hepatic lipase ( HL ) gene on concentration and composition of the plasma lipoproteins . However , the effect of this polymorphism on the response to hypolipaemic treatment has not been addressed . We evaluated the effect of this polymorphism on baseline lipids and lipoproteins and their response to treatment comprising 20mg/day pravastatin for 3 months . The study was multi-centred , prospect i ve and interventional in 236 hypercholesterolaemic subjects ( mean age 57.3 years ; 45 % males ) from 21 Primary Health-care Centres . The lipid and genotype measurements were conducted central ly . The genotype distribution was 60.2 % homozygous for the C allele and 36.0 % heterozygous . No significant differences in baseline lipid concentrations between the genotypes were observed , except that carriers of the T allele had higher concentrations of triglycerides ( p=0.021 ) . Post-pravastatin , concentrations of HDL-C increased by 6.9 % ( 95 % CI : 2.9 - 10.8 % ) in those carrying the T allele with almost no change ( 0.8 % ) in the CC genotypes ( 95 % CI : -2.3 - 4.0 % ) ( p=0.019 ) . The significance remained ( p=0.014 ) following adjustment for other confounding factors ( age , basal HDL-cholesterol , LDL-cholesterol and triglycerides ) . We conclude that the -514C/T polymorphism modulates significantly the HDL-C response to pravastatin , irrespective of the baseline lipoprotein concentrations We aim ed to assess whether the effectiveness of statins in the prevention of myocardial infa rct ion , stroke and total mortality is influenced by apolipoprotein E ( apoE ) genotype in an elderly population . We used data from the Rotterdam Study , a prospect i ve population -based cohort study in the Netherl and s which started in 1990 and included 7983 subjects aged 55 years and older . Subjects who were treated with cholesterol lowering drugs at baseline or with a serum total cholesterol > or = 6.5 mmol/l at baseline were included . We compared the incidence of myocardial infa rct ion , stroke and total mortality in subjects who received > or = 2 years of statin treatment with that in subjects who had been treated for less than 2 years , and in untreated subjects , using a Cox proportional hazard model with cumulative statin use defined as time-dependent covariates . The adjusted relative risk of all-cause mortality was 0.79 [ 95 % confidence interval ( CI ) 0.51 - 1.22 ] and of myocardial infa rct ion and stroke 0.50 ( 95 % CI 0.28 - 0.91 ) for subjects treated with statins for > or = 2 years compared to untreated subjects . The adjusted relative risks for subjects with the epsilon4 allele were 0.91 ( 95 % CI 0.45 - 1.84 ) for all-cause mortality and 0.63 ( 95 % CI 0.23 - 1.78 ) for myocardial infa rct ion and stroke . In subjects without the epsilon4 allele , adjusted relative risks were 0.71 ( 95 % CI 0.41 - 1.24 ) for all-cause mortality and 0.46 ( 95 % CI 0.22 - 0.95 ) for myocardial infa rct ion and stroke . We found a protective effect of statins on the risk of myocardial infa rct ion and stroke that was independent of apoE genotype . The protective effect of statins on total mortality was not statistically significant , but did not seem to differ between subjects with different apoE genotypes Background — In statin trials , each 20 mg/dL reduction in cholesterol results in a 10–15 % reduction of annual incidence rates for vascular events . However , interindividual variation in low-density lipoprotein cholesterol ( LDL-C ) response to statins is wide and may partially be determined on a genetic basis . Methods and Results — A genome-wide association study of LDL-C response was performed among a total of 6989 men and women of European ancestry who were r and omly allocated to either rosuvastatin 20 mg daily or placebo . Single nucleotide polymorphisms ( SNPs ) for genome-wide association ( P<5 × 10−8 ) with LDL-C reduction on rosuvastatin were identified at ABCG2 , LPA , and APOE , and a further association at PCSK9 was genome-wide significant for baseline LDL-C and locus-wide significant for LDL-C reduction . Median LDL-C reductions on rosuvastatin were 40 , 48 , 51 , 55 , 60 , and 64 mg/dL , respectively , among those inheriting increasing numbers of LDL-lowering alleles for SNPs at these 4 loci ( P trend=6.2 × 10−20 ) , such that each allele approximately doubled the odds of percent LDL-C reduction greater than the trial median ( odds ratio , 1.9 ; 95 % confidence interval , 1.8–2.1 ; P=5.0 × 10−41 ) . An intriguing additional association with sub – genome-wide significance ( P<1 × 10 - 6 ) was identified for statin related LDL-C reduction at IDOL , which mediates posttranscriptional regulation of the LDL receptor in response to intracellular cholesterol levels . In c and i date analysis , SNPs in SLCO1B1 and LDLR were confirmed as associated with LDL-C lowering , and a significant interaction was observed between SNPs in PCSK9 and LDLR . Conclusions — Inherited polymorphisms that predominantly relate to statin pharmacokinetics and endocytosis of LDL particles by the LDL receptor are common in the general population and influence individual patient response to statin therapy AIM Recently , minor alleles of two strongly linked polymorphisms in the PPARA gene , rs4253728 G > A and rs4823613 A > G , were related to decreased CYP3A4 expression and activity . We studied whether they were associated with the cholesterol-lowering effect of simvastatin . MATERIAL S & METHODS We identified 123 incident users with cholesterol measurements before and after starting statin therapy in a prospect i ve population -based cohort study . Associations between PPARA polymorphisms and change in total and low-density lipoprotein (LDL)-cholesterol levels were analyzed using linear regression . RESULTS The minor G allele of the rs4823613 A > G polymorphism was associated with a 0.258 mmol/l ( 95 % CI : -0.470 to -0.046 ) and a 0.294 mmol/l ( 95 % CI : -0.495 to -0.093 ) larger reduction in total and LDL-cholesterol , respectively , after starting simvastatin therapy . Results were similar for the rs4253728 G > A polymorphism . CONCLUSION The minor alleles of the PPARA rs4253728 and rs4823613 polymorphisms are associated with a better total and LDL-cholesterol-lowering response to simvastatin , possibly through influence on CYP3A4 Background High homocysteine blood concentrations predispose to coronary artery disease and statins influence homocysteine levels . Aim To study whether genes that regulate homocysteine metabolism interact with statins to modify the risk of coronary heart disease ( CHD ) and other cardiovascular outcomes . Methods The Genetics of Hypertension Associated Treatment is an ancillary study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) . The genotyped population in the Lipid-Lowering Trial of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial included 9624 participants r and omly assigned to pravastatin or to usual care . The efficacy of pravastatin in reducing risk of all-cause mortality and CHD was compared among genotype strata ( MTHFR 677 CC , CT , and TT , MTHFR 1298 AA , AC , and CC , CBSins DD and I+ ) by examining an interaction term in a proportional hazards model . Results No evidence existed of a pharmacogenetic effect on statins with the MTHFR 1298 A > C genotype for CHD risk . However , in persons with the CC variant for the MTHFR 677 C > T genotype , a significantly protective effect against CHD [ 0.71 ( 95 % CI 0.58–0.87 ) ] was shown , although in the CT [ 1.25 ( 95 % CI 0.97–1.61 ) ] and TT groups [ 0.80 ( 95 % CI 0.50–1.28 ) ] there were no such effects ( interaction hazard ratio P=0.004 ) . The CBSins , I+ variant was associated with a significantly reduced risk for CHD among those on statin treatment [ 0.58 ( 95 % CI 0.44–0.78 ) ] whereas the DD genotype showed no effect of statin therapy [ 1.01 ( 95 % CI 0.84–1.20 ; P=0.002 for interaction ] . For the endpoint all-cause mortality , no significant differences in efficacy were noted . Conclusion Polymorphisms in genes in the homocysteine pathway ( MTHFR 677 C > T and CBSins ) appear to modify the efficacy of pravastatin in reducing risk of cardiovascular events Bile-acid bio synthesis is a key determinant of intracellular cholesterol and , in turn , cholesterol synthesis rate in hepatocytes . This suggests that variation in the cholesterol 7alpha-hydroxylase gene ( CYP7A1 ) , a key enzyme in bile-acid bio synthesis , may influence the statin response . To test this hypothesis , a promoter polymorphism ( A-204C ) in CYP7A1 was examined in 324 hypercholesterolemic patients treated with atorvastatin 10 mg . The variant C allele was significantly and independently associated with poor LDL cholesterol reductions ; -39 % in wild type allele homozygotes , -37 % in variant allele heterozygotes , and -34 % in variant allele homozygotes ( p<0.0001 for trend ) . Differences were more striking in men , and were enhanced by the coexistence of common variants of apolipoprotein E gene ( APOE ) , epsilon2 or epsilon4 . In subjects having wild type alleles at both loci , the mean reduction in LDL cholesterol was -40 % , while the value in subjects having two CYP7A1 variant alleles and at least one variant APOE allele was -31 % ( p<0.0001 ) . Combination analysis of these two loci more accurately predicted the achievement of goal LDL cholesterol , than did both single locus analysis . We concluded that the CYP7A1 A-204C promoter variant was associated with poor response to atorvastatin , which were additively enhanced by common variants in another locus , APOE Human serum paraoxonase ( PON1 ) is a high-density lipoprotein (HDL)-associated enzyme that is responsible for the protective effect of HDL against oxidation of low-density lipoprotein ( LDL ) . PON1 has a Glu to Arg polymorphism at codon 192 ( CGA-->CAA ) which is design ated R/Q192 . The R/Q192 polymorphism has been associated with coronary artery disease ( CAD ) in several , but not all , case-control studies . We prospect ively studied the association of the Q/R192 genotypes with the severity , progression and regression of CAD , plasma lipid levels , clinical events and response to treatment with fluvastatin in a well-characterized cohort . Genotypes were determined by polymerase chain reaction ( PCR ) and restriction mapping with AlwI enzyme in 356 subjects in the Lipoprotein and Coronary Atherosclerosis Study ( LCAS ) . Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following r and omization to fluvastatin or placebo . A total of 177 ( 50 % ) , 142 ( 40 % ) and 37 ( 10 % ) subjects had Q/Q , Q/R and R/R genotypes , respectively . Baseline and final plasma levels of HDL , LDL , triglyceride and other lipoproteins , lesion-specific minimum lumen diameters ( MLD ) , mean MLD , number of coronary lesions and total occlusions at baseline and follow-up and clinical event rates were not significantly different among the genotypes . There was no genotype-treatment interaction with respect to plasma lipid levels and angiographic indices of CAD . The Q/R192 variants of PON1 are not associated with severity , progression or regression of coronary atherosclerosis , plasma lipid levels , clinical events , or response to treatment with fluvastatin . Thus , the Q/R192 polymorphism is not a major risk factor in susceptibility to CAD in the LCAS population The efficacy of the inhibitors of HMG CoA reductase shows considerable interindividual variation and intense research has focused in the recent years to identify the genetic loci and environmental factors responsible for this variability . A r and omized , double-blind , placebo-controlled clinical trial with simvastatin , an HMG CoA reductase inhibitor , was conducted in 63 adolescents ( 47 treated versus 17 controls ) with heterozygous FH . The patients were grouped according to known low-density lipoprotein ( LDL ) receptor gene mutation class . After 6 weeks of treatment with 20 mg/d of simvastatin , the mean reduction in plasma LDL-cholesterol in patients with a receptor-negative mutation ( n=33 ) was 39 % whereas , in the receptor-defective mutation group ( n=14 ) , it was 31 % ( P=0.01 ) . Multiple regression analyses showed that there was a significant association between the apo E polymorphism and LDL-cholesterol response to simvastatin only among heterozygotes for a receptor-negative mutation . In subjects carrying a receptor-defective mutation , however , we observed that 51 % of the variability in LDL-cholesterol response was explained by variations in the dosage of simvastatin expressed in mg/kg/day ( P=0.0028 ) . There was no significant association between LDL-cholesterol response and the dosage of simvastatin among heterozygotes for a receptor-negative mutation . The results of the present study have shown that the contribution of apo E polymorphism and the dosage of simvastatin to the LDL-cholesterol responsiveness is influenced by the nature of the LDL receptor gene mutation Our purpose was to evaluate associations of single nucleotide polymorphisms ( SNPs ) at the low density lipoprotein ( LDL ) receptor ( LDLR C44857 T , minor allele frequency ( MAF ) 0.26 , and A44964 G , MAF 0.25 , both in the untranslated region ) and HMG-CoA reductase ( HMGCR i18 T > G , MAF 0.019 ) gene loci with baseline lipid values , statin-induced LDL-cholesterol ( C ) lowering response , and incident coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) on trial . Our population consisted of 5804 elderly men and women with vascular disease or one or more vascular disease risk factors , who were r and omly allocated to pravastatin or placebo . Other risk factors and apolipoprotein ( apo ) E phenotype were controlled for in the analysis . Despite a prior report , no relationships with the HMGCR SNP were noted . For the LDLR SNPs C44857 T and A44964 G we noted significant associations of the rare alleles with baseline LDL-C and triglyceride levels , a modest association of the C44857 T with LDL-C lowering to pravastatin in men , and significant associations with incident CHD and CVD of both SNPs , especially in men on pravastatin . Our data indicate that genetic variation at the LDLR locus can affect baseline lipids , response to pravastatin , and CVD risk in subjects placed on statin treatment Elevated mean levels of lipoprotein[a ] ( Lp[a ] ) have been associated with symptomatic cardiovascular diseases such as clinical ly manifest myocardial infa rct ion ( MI ) , coronary artery disease , restenosis of coronary artery vein grafts after bypass , and a family history of MI . Associations of Lp[a ] with arterial wall thickening in asymptomatic individuals previously have not been addressed and are evaluated in this report among participants of the Atherosclerosis Risk in Communities ( ARIC ) Study . Intima-media wall thickening in the extracranial carotid arteries was assessed noninvasively with B-mode ultrasonography ; Lp[a ] was measured as its total protein component . Individuals with wall thickening > or = 90th percentile of the population maximum far-wall thickness were pair matched to participants < 75th percentile of wall thickness by race , gender , center , 10-year age group , and time of examination . These selection criteria yielded 492 matched pairs , with 395 white pairs and 97 black pairs . The mean Lp[a ] protein level for all black participants was 174.6 micrograms/mL compared with 77.8 micrograms/mL for whites . Conditional logistic regression analysis for the association of Lp[a ] with case-control status yielded a statistically significant prevalence odds ratio ( OR ) estimate of 1.49 , based on a 1-SD difference in Lp[a ] protein , after adjusting for age , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , fibrinogen , hypertension , and cigarette smoking . None of these risk factors significantly altered the OR , in agreement with reports that Lp[a ] is unaffected by environmental influences . In addition , no differential effect of Lp[a ] protein on case-control status ( effect modification ) was observed by race , gender , low-density lipoprotein cholesterol , or fibrinogen in this population . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Combined hyperlipidemia ( CHL ) is a very frequent dyslipidemia , being lipid-lowering drugs often necessary in its management . Some genetic loci have been associated with CHL , and modulation of lipid-lowering treatment by genetic polymorphisms has been reported . We have investigated whether common polymorphisms in the hepatic lipase gene ( LIPC ) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL . METHODS Two genetic polymorphisms in LIPC ( -514C-->T and + 651A-->G ) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX ( Atorvastatin in Mixed dyslipidemia ) study who were r and omized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls . RESULTS The -514 T allele frequency was higher in the ATOMIX group ( 0.297 ) than in the control group ( 0.193 ) ( P = .01 ) . The -514 T allele carriers in the control group showed higher high-density lipoprotein cholesterol ( HDL-C ) concentrations than the -514C homozygotes , 50.8 + /- 1.86 versus 45.9 + /- 1.40 mg/dL ( P = .02 ) . The + 651 G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the + 651A homozygotes , 274 + /- 3.72 and 181 + /- 3.50 mg/dL versus 289 + /- 4.0 and 194 + /- 3.76 mg/dL , respectively ( P < .01 ) . Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514 T allele carriers after 12 months of bezafibrate treatment , -39.4 % and + 35.8 % versus -25.5 % and + 20.4 % , respectively ( P = .080 and P = .007 , respectively ) . CONCLUSIONS A higher frequency of the -514 T allele of LIPC suggests a role of this locus in the pathogenesis of CHL . The -514 T allele is associated with higher HDL-C concentration in normolipidemic population . The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate , with a better effect in homozygous CC subjects We investigated the effect of single-nucleotide polymorphisms in sterol regulatory element-binding factors-1a and -2 ( SREBF-1a and SREBF-2 ) and SREBF cleavage-activating protein ( SCAP ) genes on lipid-lowering response to simvastatin . In all , 146 hypercholesterolemic patients of European descent were prospect ively treated with simvastatin 20 mg/day for over 6 months . Of these 99 subjects completed the 6-month follow-up . Plasma lipids and lipoproteins were measured before and throughout the study . The mean percentage decrease in plasma total cholesterol ( TC ) was greater in subject carriers of SCAP 2386 G allele compared with those homozygous for 2386A allele ( −29.6±13.4 vs −22.1±13.8 % , P=0.007 ) . About 61 % of the 2386 G carriers were above-average responders for TC levels ( ΔTC −27.8 % ) , whereas only 29 % of 2386A homozygous reached this reduction ( P=0.009 ) . Our data suggest that the SCAP 2386A > G gene polymorphism was a significant predictor of TC and triglyceride responses to simvastatin treatment Statins can modestly raise the levels of HDL cholesterol and apolipoprotein A-I ( APOA1 ) . Recently , associations between polymorphisms in the estrogen receptor alpha ( ESR1 ) and the HDL cholesterol response to hormone replacement therapy were reported . To test the hypothesis that common polymorphisms in ESR1 and APOA1 genes are associated with the response to statin therapy , two ESR1 ( PvuII and XbaI ) and two APOA1 ( G-75A and + 83 ) polymorphisms were examined in 338 hypercholesterolemic patients treated with atorvastatin 10 mg . The ESR1 PvuII-XbaI+ haplotype was significantly , and independently , associated with a greater response of HDL raising in women ( + 13 % versus + 7 % , p=0.010 ) but not in men ( + 9 % versus + 7 % , p=0.248 ) . Effects of the APOA1 + 83 variant allele on HDL cholesterol response also differed significantly by gender ( p=0.012 ) . The APOA1 + 83 variant allele was associated with higher basal LDL cholesterol levels in men as well , but not in women . Finally , significant interactions were observed between the ESR1 PvuII-XbaI+ haplotype and the APOA1 + 83 variant allele regarding both HDL ( p=0.042 ) and LDL ( p=0.031 ) cholesterol responses . In conclusion , the ESR1 haplotype was associated with a greater HDL-raising to atorvastatin in a gender-specific manner , and the interactions between ESR1 and APOA1 genotypes regarding HDL and LDL cholesterol response were also gender specific The polymorphism of SLCO1B1 ( solute carrier organic anion transporter family , member 1B1 ) , encoding the hepatic uptake transporter organic anion transporting polypeptide 1B1 , has been associated with increased pravastatin concentrations in single‐dose studies . We have investigated whether this polymorphism influences the pharmacokinetics and lipid‐lowering efficacy of multiple‐dose pravastatin Atherosclerosis is at least in part an inflammatory disease . CD14 is an endotoxin receptor that after binding of lipopolysaccharides evokes endothelial activation and secretion of several cytokines . A polymorphism of CD14 has been associated with myocardial infa rct ion . We evaluated the role of the -159 T/C polymorphism in the promoter region of the CD14 gene in relation to severity and progression of coronary atherosclerosis and response to the HMG CoA reductase inhibitor pravastatin . We recruited patients from the multi-center double-blind r and omized placebo controlled REGRESS trial and genotyped the -159T/C CD14 polymorphism . DNA and angiographic follow-up were available from 759 patients with objectivated coronary artery disease . We measured changes in mean segment diameter ( MSD ) and minimum obstruction diameter ( MOD ) with quantitative coronary angiography and noted the occurrence of major adverse cardiac events . The genotype distribution was 28 % TT , 49 % CT , 23 % CC . We did not find any association between genotype and MSD and MOD at baseline , frequency of previous myocardial infa rct ion , changes in MSD and MOD or major clinical events . Treatment with the HMG CoA reductase inhibitor pravastatin reduced progression of coronary atherosclerosis and adverse events equally for all genotypes . We conclude , that the -159T/C polymorphism in the CD14 monocyte receptor gene was not associated with progression of coronary atherosclerosis in this population nor did it influence the efficacy of pravastatin in the treatment of atherosclerosis OBJECTIVES We sought to evaluate the association between cholesteryl ester transfer protein ( CETP ) genotypes and the risk of future cardiovascular mortality in patients with coronary artery disease ( CAD ) . BACKGROUND Polymorphisms of the CETP gene influence CETP activity and high-density lipoprotein ( HDL ) cholesterol concentration and might affect the long-term prognosis and response to statin therapy in patients with CAD . METHODS We used serum sample s and deoxyribonucleic acid collected at baseline from a prospect i ve cohort of 1,211 patients with CAD prospect ively followed up ( median follow-up of 4.1 years ) , 82 of whom experienced a fatal cardiovascular event . The CETP/C-629A and I405V polymorphisms , CETP activity , and HDL cholesterol were determined . RESULTS Patients carrying the -629A allele had significantly lower CETP activity and higher HDL cholesterol levels . There was a significant association between this polymorphism and the risk of future cardiovascular death . Mortality decreased from 10.8 % in CC homozygotes to 4.6 % in CA heterozygotes and 4.0 % in AA homozygotes ( p < 0.0001 ) . This association was independent of potential confounders , particularly HDL cholesterol and CETP activity levels . The clinical benefit of statin therapy was restricted to CC homozygotes , in whom cardiovascular mortality was divided by half ( p = 0.01 for treatment x genotype interaction ) . Similar trends were observed with the CETP/I405V polymorphism , but these effects seemed to be mainly the consequence of linkage disequilibrium with the CETP/C-629A polymorphism . CONCLUSIONS In patients with CAD , the CETP/-629A allele had a strong protective effect on future mortality from cardiovascular causes , independent of its role on HDL cholesterol and CETP activity levels . Additionally , this common polymorphism appeared to predict which patients with CAD will experience a survival benefit from statin therapy Purpose Our aim was to observe the impact of CYP3A4 * 1 G genetic polymorphism on lipid-lowering efficacy of statins . Methods We studied 217 unrelated hyperlipidemic patients who prospect ively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy ( 20 mg day-1 p.o . ) for 4 weeks . Genotyping of CYP3A4 * 1 G was conducted by a polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) analysis . Serum triglyceride ( TG ) , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , and high-density lipoprotein cholesterol ( HDL-C ) levels were determined before and after treatment by enzymatic assays . Results The frequency of CYP3A4 * 1 G in Chinese hyperlipidemic patients was 0.276 . After atorvastatin treatment , the mean percentage reduction in serum TC was 16.8 ± 3.3 % ( * 1/*1 ) , 17.8 ± 3.8 % ( * 1/*1 G ) , and 20.9 ± 5.0 % ( * 1G/*1 G ) , respectively . The CYP3A4 * 1 G polymorphism had a gene-dose-dependent effect on percentage reduction in serum TC ( P < 0.01 ) . Conversely , there was no significant association between lipid-lowering efficacy of simvastatin and CYP3A4 * 1 G polymorphism . Conclusions Carrying CYP3A4 * 1 G increase the lipid-lowering efficacy of atorvastatin and may have no significant effect on simvastatin treatment The investigators quantified the relationship between the genetic polymorphism of HMGCR ( 3-hydroxy-3-methylglutaryl coenzyme A reductase ) and the low-density lipoprotein cholesterol (LDL-C)-lowering effects of atorvastatin in a prospect i ve clinical study . Twenty-four healthy participants were grouped into HMGCR rs3846662 GG ( n = 13 ) and AA ( n = 11 ) genotypes and given atorvastatin ( 20 mg/d ) for 14 days . Serum levels of LDL-C , high-density lipoprotein cholesterol , total cholesterol , triglycerides , and creatinine kinase ( CK ) were measured before ( day 1 ) and 7 , 13 , 14 , 15 , 16 , 21 , and 28 days after dosing initiation . Blood sample s for pharmacokinetics were taken on days 14 through 16 . The levels of LDL-C in the GG group were significantly higher than in the AA group at all observation times , with mean differences of 18 % to 33 % ( P < .05 ) . The area under the LDL-C-time curve and the minimum value of LDL-C in the GG group were 24 % and 23 % higher than in the AA group , respectively ( P < .01 ) . There was no significant difference in other lipids , CK , and pharmacokinetic parameters . The HMGCR rs3846662 GG genotype was quantitatively documented to be a significant determinant for higher LDL-C level in basal state and possibly in response to atorvastatin BACKGROUND Statin therapy is widely used in the prevention and treatment of cardiovascular events and is associated with significant risk reductions . However , there is considerable variation in response to statin therapy both in terms of LDL cholesterol reduction and clinical outcomes . It has been hypothesized that genetic variation contributes importantly to this individual drug response . METHODS AND RESULTS We investigated the interaction between genetic variants and pravastatin or placebo therapy on the incidence of cardiovascular events by performing a genome-wide association study in the participants of the PROspect i ve Study of Pravastatin in the Elderly at Risk for vascular disease -- PHArmacogenetic study of Statins in the Elderly at risk ( PROSPER/PHASE ) study ( n = 5244 ) . We did not observe genome-wide significant associations with a clinical ly meaningful differential cardiovascular event reduction by pravastatin therapy . In addition , SNPs with p-values lower than 1 × 10(-4 ) were assessed for replication in a case-only analysis within two r and omized placebo controlled pravastatin trials , CARE ( n = 711 ) and WOSCOPS ( n = 522 ) . rs7102569 , on chromosome 11 near the ODZ4 gene , was replicated in the CARE study ( p = 0.008 ) , however the direction of effect was opposite . This SNP was not associated in WOSCOPS . In addition , none of the SNPs replicated significantly after correcting for multiple testing . CONCLUSIONS We could not identify genetic variation that was significantly associated at genome-wide level with a clinical ly meaningful differential event reduction by pravastatin treatment in a large prospect i ve study . We therefore assume that in daily practice the use of genetic characteristics to personalize pravastatin treatment to improve prevention of cardiovascular disease will be limited Background Pharmacogenetic research has shown that genetic variation may influence statin responsiveness . Statins exert a variety of beneficial effects beyond lipid lowering , including antithrombotic effects , which contribute to the risk reduction of cardiovascular disease . Statins have been shown to influence the expression of coagulation factors II , V , VII , XII and XIII . Aim Data from a large r and omized clinical trial of pravastatin , design ed to show efficacy relative to usual care , were used to investigate whether a pharmacogenetic effect of polymorphisms in genes coding for coagulation factors II , V , VII , XII and XIII is associated with reduced fatal coronary heart disease ( CHD ) and nonfatal myocardial infa rct ion , combined CHD and all-cause mortality . Methods The Genetics of Hypertension Associated Treatment is an ancillary study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial . The genotyped population in the lipid-lowering trial of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial included 9624 participants r and omly assigned to pravastatin or to usual care . The efficacy of pravastatin in reducing risk of all-cause mortality , CHD and nonfatal myocardial infa rct ion and combined CHD , was compared among genotype strata by examining an interaction term in a proportional hazards model . Results None of the polymorphisms were associated with the clinical outcomes . For the F7 ( –323 ) ins/del polymorphism there was no interaction with pravastatin for either outcome . For both the F5 Arg506Gln G > A ( rs6025 ) polymorphism and F7 Arg353Gln G > A ( rs6046 ) polymorphism there were no interactions with pravastatin in relation to all-cause mortality , but there were significant interactions with combined CHD [ interaction hazard ratio = 1.33 , 95 % confidence interval ( 1.01–1.76 ) and interaction hazard ratio = 1.92 , 95 % confidence interval ( 1.00–3.65 ) , respectively ] . There were no interactions between the polymorphisms in the other coagulation genes and pravastatin in relation to any outcome . Conclusion Polymorphisms in anticoagulation genes ( F5 and F7 ) seem to modify the efficacy of pravastatin in reducing risk of cardiovascular events Objective To investigate whether leptin receptor ( LEPR ) 223A > G polymorphism influences serum lipid levels and whether this polymorphism affects the effectiveness of simvastatin in Chinese patients with coronary heart disease ( CHD ) . Methods A total of 312 patients with CHD were treated with simvastatin 20 mg/day . Fasting serum lipids were determined before and after 12 weeks of treatment . Results Patients with AA genotype had significantly higher total cholesterol ( TC ) levels and lower high-density lipoprotein cholesterol ( HDL-C ) levels than those with GG genotype ( P < 0.05 ) before simvastatin treatment . In addition , the ability of simvastatin to increase HDL-C levels was significantly lower in patients with AA genotype than those with GG genotype ( P < 0.05 ) . Conclusions The 223A > G polymorphism of LEPR significantly modulates the HDL-C response to simvastatin in Chinese patients with CHD Chromosome 17q21 - 23 harbors genes for platelet glycoprotein IIIa and angiotensin-converting enzyme ( ACE ) , which are polymorphic for alleles Pl(A2 ) and ACE " D. " These alleles have been independently and often associated with ischemic coronary artery disease ( CAD ) . We sought to determine if the Pl(A2 ) and ACE D polymorphisms were risk factors for recurrent coronary events . In the Cholesterol And Recurrent Events ( CARE ) trial , 4,159 men and women with documented myocardial infa rct ion ( MI ) were r and omized to receive either placebo or pravastatin , and were followed prospect ively for 5 years . Pl(A ) and ACE genotypes were determined in 767 patients : 385 cases who had experienced a recurrent primary event ( death due to coronary disease or nonfatal MI ) , and 382 age- and gender-matched controls . In patients receiving placebo , the Pl(A1,A2 ) genotype conferred a relative risk ( RR ) of 1.38 ( confidence intervals [ CI ] 1.04 to 1.83 ; p = 0.028 ; adjusted RR = 1.32 , CI = 0.99 to 1.76 ; p = 0.058 ] ) for the primary end point . Compared with the placebo group , pravastatin reduced the excess RR of coronary disease death and recurrent MI in the Pl(A1,A2 ) patient population by 31 % ( p = 0.06 ) . The ACE D allele appeared to have modestly additive effects on the Pl(A1,A2 ) risk . Among the Pl(A1,A2 ) patients , pravastatin had little effect on the risk of recurrent events with the ACE II genotype , but reduced the adjusted RR from 1.42 ( placebo ) to 0.58 for ACE ID patients , and from 1.56 ( placebo ) to 0.83 for ACE DD . The Pl(A1,A2 ) genotype was associated with an excess of recurrent coronary events in patients after MI who did not receive pravastatin , and the ACE D allele added to this risk . These data suggest that it would be important to perform a larger study to address the potential role of these genotypes in therapeutic decision making BACKGROUND In recent years , one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment . Polymorphisms in apolipoprotein E ( APOE ) , cholesteryl ester transfer protein ( CETP ) and hepatic lipase ( LIPC ) , proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response . METHODS One hundred forty-six hypercholesterolemic patients of European descent were prospect ively enrolled and treated with simvastatin 20 mg per day for over 6 months . Ninety-nine subjects completed the 6-month follow-up . Plasma lipids and lipoproteins were measured before and throughout the study . APOE ( E*2 , E*3 and E*4 ) , LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping . RESULTS After a 6-month follow-up , no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed . After adjustment for covariates , CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects ( 14.1 % vs. 1.7 % and 1.3 % , P < 0.05 , respectively ) . CONCLUSION Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated , in part , by the CETP gene locus , with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele AIMS Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor , which is widely used both in primary and secondary prevention of coronary heart disease ( CHD ) . Pravastatin is not subject to metabolism by cytochrome P450s , but it is actively transported from blood into target tissues ( e.g. hepatocytes in the liver ) by the organic anion transporting polypeptide 1B1 ( OATP1B1 ) , encoded by SLCO1B1 . The aim of the present study was to evaluate the impact of SLCO1B1 521T-->C ( Val174Ala ) functional genetic polymorphism on the lipid-lowering efficacy of multiple-dose pravastatin in Chinese patients with CHD . METHODS Forty-five hospitalized patients with CHD prospect ively received pravastatin as a single-agent therapy ( 20 mg day(-1 ) p.o . ) for 30 days . Serum triglycerides , total cholesterol , low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol concentrations were determined before and after pravastatin treatment . RESULTS Pravastatin treatment significantly decreased plasma lipids in all patients ( P < 0.001 ) . Importantly , we showed an attenuated pravastatin pharmacodynamic effect on total cholesterol in patients with 521TC heterozygote genotype ( from 5.52 + /- 0.51 mmol l(-1 ) to 4.70 + /- 0.35 mmol l(-1 ) , % change -14.5 + /- 6.6 % , N = 9 ) compared with 521TT homozygote genotype ( from 5.47 + /- 1.15 mmol l(-1 ) to 4.21 + /- 0.89 mmol l(-1 ) , % change -22.4 + /- 10.3 % , N = 36 ) ( mean + /- SD , P = 0.03 , two-tailed test with alpha set at 5 % ) . SLCO1B1 521T-->C functional polymorphism did not significantly influence pravastatin pharmacodynamics on other plasma lipids ( P > 0.05 ) . CONCLUSIONS The 521T-->C polymorphism of SLCO1B1 appears to modulate significantly the total cholesterol-lowering efficacy of pravastatin in Chinese patients with CHD . Further studies are warranted to determine the extent to which SLCO1B1 genetic variation may contribute to resistance to pravastatin in Asian patients treated with st and ard doses of pravastatin 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been used clinical ly for lowering total and low-density lipoprotein cholesterol . Interindividual pharmacological differences observed with this treatment have been attributed to genetic differences . The aim of this study was to assess the association in the low-density lipoprotein cholesterol reduction by atorvastatin and (TTA)n polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene in patients with coronary artery disease . Changes in total cholesterol levels , triglycerides , high-sensitivity C-reactive protein and free F(2)-isoprostanes were also evaluated . In an open study , patients received 40 mg atorvastatin daily for 8 weeks . Genotyping was done through polymerase chain reaction . The genotype distribution of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (TTA)n polymorphism was : > 10/>10 in 22 out of 64 patients ( 34 % ) , > 10/10 in 14 out of 64 patients ( 22 % ) and 10/10 in 28 out of 64 patients ( 44 % ) . The reduction of low-density lipoprotein cholesterol levels by atorvastatin was not different between allelic variants (TTA)n repeat polymorphism . Reductions in high-sensitivity C-reactive protein were observed in atorvastatin-treated patients with alleles > 10/>10 and 10/10 . Free F(2)-isoprostanes and total cholesterol were also significantly lower after treatment for all alleles , irrespective of type of polymorphism . In conclusion , the changes induced by atorvastatin treatment on low-density lipoprotein cholesterol , total cholesterol , triglycerides , high-sensitivity C-reactive protein and free F(2)-isoprostane concentrations were not related to the presence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase polymorphism (TTA)n The objective of this study was to investigate whether common variation in genes involved in lipid metabolism modify the effect of statins on serum total cholesterol concentration . Statin users were identified in the Rotterdam Study , a prospect i ve population -based cohort study of subjects > 55 years of age . We studied the association between single nucleotide polymorphisms ( SNPs ) in genes involved in lipid metabolism and total cholesterol response to statin therapy , using linear regression analysis and adjusting for potential confounders . Replication was performed in an independent extended cohort of the Rotterdam Study . Genotype data and total cholesterol concentrations after start of statin therapy were available for 554 newly started statin users . Two SNPs were associated with a significantly higher cholesterol concentration under statin therapy : SNP rs1532624 in the CETP gene ( β : 0.141 mmol l−1 , P=0.004 per additional allele ) and SNP rs533556 in the APOA1 gene ( β : 0.138 mmol l−1 , P=0.005 per additional allele ) . In the replication sample , only the CETP rs1532624 SNP again showed a significant association . The SNPs were not related to baseline total cholesterol in non-statin users . In conclusion , we found that the CETP rs1532624 polymorphism is associated with cholesterol response to statin therapy in a cohort of elderly subjects in the general population AIMS We investigated whether KIF6 Trp719Arg genotypes affect cardiovascular outcomes and efficacy of statin therapy in patients with type 2 diabetes mellitus undergoing hemodialysis . METHODS AND RESULTS We conducted a post hoc analysis of the 4D- study , a r and omized trial including 1255 patients . Patients were r and omly assigned to double-blind treatment with either 20 mg of atorvastatin ( n = 619 ) or placebo ( n = 636 ) once daily and followed for 4 years ( median ) . DNA was available for 1232 patients and we assessed KIF6 Trp719Arg genotypes by PCR and subsequent restriction digest . Carriers of the Arg719 allele showed no increased prevalence of cardiovascular disease . The incidence of cardiac death , MI , and stroke did not differ across KIF6 genotypes , irrespective of whether the patients were treated with atorvastatin or not . CONCLUSION In patients with type 2 diabetes mellitus on hemodialysis , KIF6 Trp719Arg genotypes were not associated with adverse cardiovascular outcomes during follow-up or with the efficacy of atorvastatin therapy |
13,426 | 30,422,677 | Nuts did not affect sense of fullness and weight in the overall estimate .
Subgroup analysis based on participants ’ BMI revealed that energy intake of overweight/obese individuals was increased following nut consumption while such effect was not observed in normal weight participants .
In conclusion , pooled estimates of available clinical trials showed increased energy intake following nut consumption in overweight/obese individuals but not in persons with normal weight .
Nut consumption was associated with decreased hunger but no effect was observed on fullness and weight | Abstract Despite high energy content , nut consumption has not been associated with weight gain in epidemiological and clinical investigations .
Since a satiety effect a decreased sense of hunger in the following meals has been proposed as the mechanism of nuts against obesity , the present meta- analysis was performed to examine how nut consumption affects “ energy intake ” , “ hunger ” , and “ fullness ” . | OBJECTIVE Evaluate the effect of high-oleic and conventional peanuts within a hypocaloric-diet on energy metabolism and body composition . METHODS This 4-week r and omized clinical trial included males with BMI of 29.7 ± 2.4 kg m(-2 ) and aged between 18 and 50 years . Participants were assigned to the groups : control ( CT , n = 22 ) that followed a hypocaloric-diet ; conventional peanuts ( CVP , n = 22 ) or high-oleic peanuts ( HOP , n = 21 ) that received the hypocaloric-diet including ( not adding ) 56 g day(-1 ) of peanuts . Glucose , fat oxidation , and body fatness and lean mass were the main outcomes . RESULTS Body weight and composition did not differ between groups . However , within group total body fat ( kg ) reduced with CVP and HOP , with a significant decrease in body fat percentage in HOP . While total lean mass ( kg ) decreased in CT , total lean mass ( % ) increased in HOP . Truncal lean mass decreased in the CT . At baseline , HOP had greater postpr and ial fat oxidation than the CVP . After 4-weeks , fasting fat oxidation increased in CVP and HOP . Fat oxidation increased in CT and HOP during the 200 min after meal intake compared to the fasting condition . CONCLUSION Regular peanut consumption , especially the high-oleic type , within a hypocaloric-diet increased fat oxidation and reduced body fatness in overweigh and obese men BACKGROUND Data concerning the long-term association between nut consumption and weight change in a free-living population are sparse . OBJECTIVE The objective was to determine the relation between nut consumption and long-term weight change . DESIGN The participants were 51,188 women in the Nurses ' Health Study II aged 20 - 45 y , who had no cardiovascular disease , diabetes , or cancer . We prospect ively evaluated the dietary intake of nuts and subsequent weight changes from 1991 to 1999 . RESULTS Women who reported eating nuts > or = 2 times/wk had slightly less mean ( + /- SE ) weight gain ( 5.04 + /- 0.12 kg ) than did women who rarely ate nuts ( 5.55 + /- 0.04 kg ) ( P for trend < 0.001 ) . For the same comparison , when total nut consumption was subdivided into peanuts and tree nuts , the results were similar ( ie , less weight gain in women eating either peanuts or tree nuts > or = 2 times/wk ) . The results were similar in normal-weight , overweight , and obese participants . In multivariate analyses in which lifestyle and other dietary factors were controlled for , we found that greater nut consumption ( > or = 2 times/wk compared with never/almost never ) was associated with a slightly lower risk of obesity ( hazard ratio : 0.77 ; 95 % CI : 0.57 , 1.02 ; P for trend = 0.003 ) . CONCLUSIONS Higher nut consumption was not associated with greater body weight gain during 8 y of follow-up in healthy middle-aged women . Instead , it was associated with a slightly lower risk of weight gain and obesity . The results of this study suggest that incorporating nuts into diets does not lead to greater weight gain and may help weight control Regular nut consumption is associated with lower adiposity and reduced weight gain in adulthood . Walnut feeding studies have observed minimal effect on body weight despite potential additional energy intake . Several mechanisms may explain why consuming nuts promotes weight control , including increased early phase satiety , possibly reflected in postpr and ial response of gastrointestinal and pancreatic peptides hypothesized to affect appetite . The purpose of this study was to compare postpr and ial insulin , glucagon and gastrointestinal peptide response and satiety following a meal with ~54 % of energy from walnuts or cream cheese , using a within-subject crossover study design in overweight/obese adults ( N = 28 ) . Sixty minutes after the walnut-containing meal , glucagon-like peptide-1 was lower than after the reference meal ( p=0.0433 ) , and peptide YY , cholecystokinin and ghrelin did not differ after the two meals . Sixty and 120 min after the walnut-containing meal , pancreatic polypeptide ( p = 0.0014 and p = 0.0002 ) and glucose-dependent insulinotropic peptide ( p < 0.0001 and p = 0.0079 ) were lower than after the reference meal , and 120 min after the walnut-containing meal , glucagon was higher ( p=0.0069 ) . Insulin and C-peptide increased at 60 min in response to both meals but were lower at 120 min after the walnut-containing meal ( p=0.0349 and 0.0237 , respectively ) . Satiety measures were similar after both meals . These findings fail to support the hypothesis that acute postpr and ial gastrointestinal peptide response to a walnut-containing meal contributes to increased satiety . However , inclusion of walnuts attenuated the postpr and ial insulin response , which may contribute to the more favorable lipid profile observed in association with regular walnut consumption Nut consumption is associated with a reduced risk of type 2 diabetes mellitus ( T2DM ) . The aim of the present study was to assess the effects of adding peanuts ( whole or peanut butter ) on first ( 0 - 240 min)- and second ( 240 - 490 min)-meal glucose metabolism and selected gut satiety hormone responses , appetite ratings and food intake in obese women with high T2DM risk . A group of fifteen women participated in a r and omised cross-over clinical trial in which 42·5 g of whole peanuts without skins ( WP ) , peanut butter ( PB ) or no peanuts ( control ) were added to a 75 g available carbohydrate-matched breakfast meal . Postpr and ial concentrations ( 0 - 490 min ) of glucose , insulin , NEFA , glucagon-like peptide-1 ( GLP-1 ) , peptide YY ( PYY ) , cholecystokinin ( CCK ) , appetitive sensations and food intake were assessed after breakfast treatments and a st and ard lunch . Postpr and ial NEFA incremental AUC ( IAUC ) ( 0 - 240 min ) and glucose IAUC ( 240 - 490 min ) responses were lower for the PB breakfast compared with the control breakfast . Insulin concentrations were higher at 120 and 370 min after the PB consumption than after the control consumption . Desire-to-eat ratings were lower , while PYY , GLP-1 and CCK concentrations were higher after the PB intake compared with the control intake . WP led to similar but non-significant effects . The addition of PB to breakfast moderated postpr and ial glucose and NEFA concentrations , enhanced gut satiety hormone secretion and reduced the desire to eat . The greater bioaccessibility of the lipid component in PB is probably responsible for the observed incremental post-ingestive responses between the nut forms . Inclusion of PB , and probably WP , to breakfast may help to moderate glucose concentrations and appetite in obese women Nuts have high energy and fat contents , but nut intake does not promote weight gain or obesity , which may be partially explained by their proposed high satiety value . The primary aim of this study was to assess the effects of consuming almonds versus a baked food on postpr and ial appetite and neural responses to visual food stimuli . Twenty-two adults ( 19 women and 3 men ) with a BMI between 25 and 40 kg/m2 completed the current study during a 12-week behavioral weight loss intervention . Participants consumed either 28 g of whole , lightly salted roasted almonds or a serving of a baked food with equivalent energy and macronutrient contents in r and om order on two testing days prior to and at the end of the intervention . Pre- and postpr and ial appetite ratings and functional magnetic resonance imaging scans were completed on all four testing days . Postpr and ial hunger , desire to eat , fullness , and neural responses to visual food stimuli were not different following consumption of almonds and the baked food , nor were they influenced by weight loss . These results support energy and macronutrient contents as principal determinants of postpr and ial appetite and do not support a unique satiety effect of almonds independent of these variables Purpose Almonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic population s but this relationship has never been tested in Koreans . Thus , we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors . Methods We conducted a r and omized , crossover trial in a free-living setting with a 2-week run-in period , two 4-week intervention phases , and a 2-week washout period between interventions . Eighty four overweight/obese participants ( 11 M/73 F ; 52.4 ± 0.6 year ; 25.4 ± 0.22 kg/m2 ) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks . Results Mean % daily energy intake at baseline was 64.8 , 21.3 , and 14.9 % from carbohydrate , fat , and protein , respectively . The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0 % , increased fat to 32.0 % , and maintained protein at 14.7 % . Consuming the almonds increased intake of MUFA by 192.3 % , PUFA by 84.5 % , vitamin E by 102.7 % , and dietary fiber by 11.8 % and decreased % energy from carbohydrate by 14.1 % . Total caloric intake was increased by the almonds , but body weight , waist circumference , and body composition were not affected . Almonds in overweight and obese Korean adults decreased TC , LDL-C , and non-HDL-C by 5.5 , 4.6 , and 6.4 % , respectively , compared to the cookie control ( P ≤ 0.05 ) . Almonds increased plasma α-tocopherol by 8.5 % ( P ≤ 0.05 ) from the baseline and tended to increase its value as compared to cookies ( P = 0.055 ) . Neither the almonds nor cookies altered plasma protein carbonyls , MDA or oxLDL . Of serum inflammatory markers , IL-10 was decreased by almond intake ( P ≤ 0.05 ) , and ICAM-1 , IL-1β , and IL-6 tended to be lower with almonds , compared to the cookies . Conclusions Almonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA , PUFA , vitamin E , and dietary fiber intake and decreasing % energy intake from carbohydrate . Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans . Thus , including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD Nut consumption has been associated with reduced coronary heart disease ( CHD ) risk . In addition to cholesterol-lowering properties , almonds have been shown to lower oxidized LDL concentrations . However , little is known regarding their effects on other markers of oxidative stress . The dose-response effects of whole almonds , taken as snacks , were compared with low-saturated fat ( < 5 % energy ) whole-wheat muffins ( control ) in the therapeutic diets of hyperlipidemic subjects . In a r and omized crossover study , 27 hyperlipidemic men and women consumed 3 isoenergetic ( mean 423 kcal/d or 1770 kJ/d ) supplements each for 1 mo . Supplements consisted of full-dose almonds ( 73 + /- 3 g/d ) , half-dose almonds plus half-dose muffins ( half-dose almonds ) , and full-dose muffins ( control ) . Subjects were assessed at wk 0 , 2 and 4 . Mean body weights differed < or = 300 g between treatments , although the weight loss on the half-dose almond treatment was greater than on the control ( P < 0.01 ) . At 4 wk , the full-dose almonds reduced serum concentrations of malondialdehyde ( MDA ) ( P = 0.040 ) and creatinine-adjusted urinary isoprostane output ( P = 0.026 ) compared with the control . Serum concentrations of alpha- or gamma-tocopherol , adjusted or unadjusted for total cholesterol , were not affected by the treatments . Almond antioxidant activity was demonstrated by their effect on 2 biomarkers of lipid peroxidation , serum MDA and urinary isoprostanes , and supports the previous finding that almonds reduced oxidation of LDL-C. Antioxidant activity provides an additional possible mechanism , in addition to lowering cholesterol , that may account for the reduction in CHD risk with nut consumption The aim of the study was to evaluate the effect of preloads differing in fatty acid composition , content , and delivery form on acute behavioral , subjective , and biological outcomes of satiety . Four energy- and volume-matched preloads were tested in normal weight men and women ( n = 12 and 13 , respectively ) , using a r and om , crossover design . Preloads were semisolid shakes differing in fat source [ walnut or safflower ( SAFF ) ] , delivery [ ground walnuts ( WNT ) or walnut oil ( WOL ) ] or content [ 39 % fat energy ( SAFF , WNT , WOL ) or 4 % low-fat control ( LFC ) ] . Blood was collected and subjective satiety assessed at 0 ( fasting ) , 15 , 30 , and 45 min after preload consumption . Lunch ( test meal ) was provided thereafter . Energy intake at lunch was not affected by preload ; however , subjects selected more carbohydrate , fiber-rich foods at the test meal lunch after walnut preloads than after LFC or SAFF preloads . Compared with the LFC preload , appetite satisfaction was significantly greater after SAFF and WNT , but not after WOL . Women were hungrier after SAFF than after WOL , whereas men were less hungry after SAFF and LFC than after WOL or WNT . Plasma cholecystokinin ( CCK ) concentrations reflected preload fat content and availability , particularly among men ; CCK was higher after WOL and SAFF preloads than after LFC or WNT preloads . Plasma insulin was higher after LFC and SAFF preloads , corresponding to hunger suppression in men . Dietary restraint was associated with a blunted CCK response to preloads , whereas insulin was not affected by restraint . The results indicate that test meal energy intake after preloads containing approximately 40 % walnut or safflower fat or 4 % fat did not differ ; however , walnut consumption may promote food patterns consistent with consuming diets higher in fiber Abstract Favorable health benefits of almond have been shown in several previous studies . However , repeated measures , r and omized , controlled trials to investigate the changes due to almond intake based on the time effects have not yet been reported . The current study was conducted to evaluate the effects of daily almond intake on changes in body composition and lipid profiles for 20 weeks with four measurements among healthy adults . Participants in the almond group showed favorable changes on blood lipid profiles , including levels of triglycerides ( TG ) , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , and non-high-density lipoprotein ( non-HDL-C ) after consuming 56 g of almond per day for 20 weeks compared with those at baseline . At week 20 , subjects in the almond group showed significantly decreased TC , LDL-C , non-HDL-C , TG , body fat mass , and waist – hip ratio compared with those of the control group who consumed isocaloric control food . The mixed model also confirmed that there were significant time effects in several bioimpedance indicators ( i.e. , total body protein , fat-free mass , etc . ) and all of the lipid profile parameters in the almond group . These results confirm the effects of lipid-lowering and modifying body composition of almond consumption . In addition , our results suggest that the measuring time points would be critical to capture the effects of dietary intervention ABSTRACT Background : Being more specific about individual food choices may be advantageous for weight loss . Including a healthy food ( e.g. walnuts ) may help to expose effects . Objective : To examine the impact of including walnuts in diets for weight loss . Design : Secondary analysis of the HealthTrack lifestyle intervention trial . Overweight and obese participants were r and omized to : usual care ( C ) , interdisciplinary intervention including individualized dietary advice ( I ) , or interdisciplinary intervention including 30 g walnuts/day ( IW ) . Changes in body weight , energy intake , intake of key foods , physical activity , and mental health over three and 12 months were explored . Results : A total of 293 participants completed the intensive three-month study period , and 175 had data available at 12 months . The IW group achieved the greatest weight loss at three months . IW reported significant improvements in healthy food choices , and decreased intakes of discretionary foods/beverages , compared to C. Weight loss remained greatest in IW at 12 months . Discussion : Significant effects were seen after three months , with the IW group achieving greater weight loss and more favorable changes in food choices . Conclusions : Including 30 grams walnuts/day in an individualized diet produced weight loss and positive changes in food choice OBJECTIVE To evaluate the effects of acute and daily consumption of high-oleic peanuts ( HOP ) on inflammation and glucose homeostasis in overweight/obese men . METHODS In a 4-week r and omized clinical trial , males with body mass index of 29.8 ± 2.3 kg/m(2 ) and aged 18 - 50 years were assigned to the groups : control ( CT , n = 22 ) ; conventional peanuts ( CVP , n = 22 ) ; or HOP ( n = 21 ) . They followed a hypocaloric-diet with or without 56 g/day of CVP or HOP . Main outcomes were changes in fasting blood biomarkers and postpr and ial insulin , glucose , tumor necrosis factor-alfa ( TNF-α ) , and interleukin-10 ( IL-10 ) responses after acute peanut intake . RESULTS At baseline , HOP showed significantly lower postpr and ial responses of glucose , insulin , and TNF-α than CVP and CT . Changes in fasting blood biomarkers did not differ between groups after the 4-week intervention . However , within groups , total cholesterol decreased in CT , and all groups reduced High-density lipoprotein ( HDL-c ) . Triglycerides were reduced in HOP and CVP . IL-10 increased significantly in all groups while only the CT and CVP showed increased TNF-α after intervention . CONCLUSION Acute high-oleic peanut consumption leads to stronger moderation of postpr and ial glucose , insulin , and TNF-α concentrations than CVP and control meal intake . Whether daily intake of high-oleic peanuts has additional benefits to CVP remains uncertain Appetite suppressants may be one strategy in the fight against obesity . This study evaluated whether Korean pine nut free fatty acids ( FFA ) and triglycerides ( TG ) work as an appetite suppressant . Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin ( CCK-8 ) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids , oleic acid , linoleic acid , alpha-linolenic acid , and capric acid used as a control . At 50 μM concentration , Korean pine nut FFA produced the greatest amount of CCK-8 release ( 493 pg/ml ) relative to the other fatty acids and control ( 46 pg/ml ) . A r and omized , placebo-controlled , double-blind cross-over trial including 18 overweight post-menopausal women was performed . Subjects received capsules with 3 g Korean pine ( Pinus koraiensis ) nut FFA , 3 g pine nut TG or 3 g placebo ( olive oil ) in combination with a light breakfast . At 0 , 30 , 60 , 90 , 120 , 180 and 240 minutes the gut hormones cholecystokinin ( CCK-8 ) , glucagon like peptide-1 ( GLP-1 ) , peptide YY ( PYY ) and ghrelin , and appetite sensations were measured . A wash-out period of one week separated each intervention day . CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo ( p < 0.01 ) . GLP-1 was higher 60 min after pine nut FFA compared to placebo ( p < 0.01 ) . Over a period of 4 hours the total amount of plasma CCK-8 was 60 % higher after pine nut FFA and 22 % higher after pine nut TG than after placebo ( p < 0.01 ) . For GLP-1 this difference was 25 % after pine nut FFA ( P < 0.05 ) . Ghrelin and PYY levels were not different between groups . The appetite sensation " prospect i ve food intake " was 36 % lower after pine nut FFA relative to placebo ( P < 0.05).This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospect i ve food intake Background / Objectives : Snacks contribute toward a significant proportion of human total daily energy intake . This study investigated the effects of almonds , a satiating and nutrient-rich , common snack , on postpr and ial glycemia , appetite , short-term body weight and fasting blood parameters when consumed with meals or alone as a snack . Methods : This was a 4-week r and omized , parallel-arm study that entailed consuming almonds ( 43 g/day ) with breakfast ( BF ) or lunch ( LN ) , alone as a morning ( MS ) or afternoon ( AS ) snack or no almonds ( CL ) . Participants ( N=137 ) with increased risk for type 2 diabetes completed an oral glucose tolerance test ( OGTT ) and acute-feeding session at baseline , followed by almond consumption for 4 weeks before repeating the OGTT and acute-feeding trials . Anthropometric , biochemical and appetite responses were assessed . Results : Almonds lowered serum glucose responses postpr and ially . Effects were most prominent in the snack groups . Almonds , consumed as snacks , also reduced hunger and desire to eat during the acute-feeding session . After 4 weeks , anthropometric measurements and fasting blood biochemistries did not differ from the control group or across intervention groups . Without specific guidance , daily energy intake was reduced to compensate for energy from the provided almonds . Dietary monounsaturated fat and α-tocopherol intakes were significantly increased in all almond groups . Conclusion : Almonds provide post-ingestive metabolic and appetitive benefits and did not increase the risk for weight gain . This suggests that almonds may be a healthful snack option Background Peanut consumption favorably influences satiety . This study examined the acute effect of peanut versus grain bar preloads on postmeal satiety and glycemia in healthy adults and the long-term effect of these meal preloads on body mass in healthy overweight adults . Methods In the acute crossover trial ( n = 15 ; 28.4 ± 2.9 y ; 23.1 ± 0.9 kg/m2 ) , the preload ( isoenergetic peanut or grain bar with water , or water alone ) was followed after 60 min with ingestion of a st and ardized glycemic test meal . Satiety and blood glucose were assessed immediately prior to the preload and to the test meal , and for two hours postmeal at 30-min intervals . In the parallel-arm , r and omized trial ( n = 44 ; 40.5 ± 1.6 y , 31.8 ± 0.9 kg/m2 ) , the peanut or grain bar preload was consumed one hour prior to the evening meal for eight weeks . Body mass was measured at 2-week intervals , and secondary endpoints included blood hemoglobin A1c and energy intake as assessed by 3-d diet records collected at pre-trial and trial weeks 1 and 8 . Results Satiety was elevated in the postpr and ial period following grain bar ingestion in comparison to peanut or water ingestion ( p = 0.001 , repeated- measures ANOVA ) . Blood glucose was elevated one hour after ingestion of the grain bar as compared to the peanut or water treatments ; yet , total glycemia did not vary between treatments in the two hour postpr and ial period . In the 8-week trial , body mass was reduced for the grain bar versus peanut groups after eight weeks ( −1.3 ± 0.4 kg versus −0.2 ± 0.3 kg , p = 0.033 , analysis of covariance ) . Energy intake was reduced by 458 kcal/d in the first week of the trial for the grain bar group as compared to the peanut group ( p = 0.118 ) . Hemoglobin A1c changed significantly between groups during the trial ( −0.25 ± 0.07 % and −0.18 ± 0.12 % for the grain bar and peanut groups respectively , p = 0.001 ) . Conclusions Compared to an isoenergetic peanut preload , consumption of a grain bar preload one hour prior to a st and ardized meal significantly raised postmeal satiety . Moreover , consumption of the grain bar prior to the evening meal was associated with significant weight loss over time suggesting that glycemic carbohydrate ingestion prior to meals may be a weight management strategy Objective Almonds reduce cardiovascular disease risk via cholesterol reduction , anti-inflammation , glucoregulation , and antioxidation . The objective of this r and omized , controlled , cross-over trial was to determine whether the addition of 85 g almonds daily to a National Cholesterol Education Program ( NCEP ) Step 1 diet ( ALM ) for 6 weeks would improve vascular function and inflammation in patients with coronary artery disease ( CAD ) . Research design and methods A r and omized , controlled , crossover trial was conducted in Boston , MA to test whether as compared to a control NCEP Step 1 diet absent nuts ( CON ) , incorporation of almonds ( 85 g/day ) into the CON diet ( ALM ) would improve vascular function and inflammation . The study duration was 22 weeks including a 6-weeks run-in period , two 6-weeks intervention phases , and a 4-weeks washout period between the intervention phases . A total of 45 CAD patients ( 27 F/18 M , 45–77 y , BMI = 20 - 41 kg/m2 ) completed the study . Drug therapies used by patients were stable throughout the duration of the trial . Results The addition of almonds to the CON diet increased plasma α-tocopherol status by a mean of 5.8 % , reflecting patient compliance ( P ≤0.05 ) . However , the ALM diet did not alter vascular function assessed by measures of flow-mediated dilation , peripheral arterial tonometry , and pulse wave velocity . Further , the ALM diet did not significantly modify the serum lipid profile , blood pressure , C-reactive protein , tumor necrosis factor-α or E-selectin . The ALM diet tended to decrease vascular cell adhesion molecule-1 by 5.3 % ( P = 0.064 ) and increase urinary nitric oxide by 17.5 % ( P = 0.112 ) . The ALM intervention improved the overall quality of the diet by increasing calcium , magnesium , choline , and fiber intakes above the Estimated Average Requirement ( EAR ) or Recommended Dietary Allowance ( RDA ) . Conclusions Thus , the addition of almonds to a NECP Step 1 diet did not significantly impact vascular function , lipid profile or systematic inflammation in CAD patients receiving good medical care and polypharmacy therapies but did improve diet quality without any untoward effect . Trial registration The trial was registered with the Clinical Trials . Gov with the identifier : NCT00782015 IMPORTANCE A better underst and ing of the cause of obesity is a clinical priority . Obesity is highly heritable , and specific genes are being identified . Discovering the mechanisms through which obesity-related genes influence weight would help pinpoint novel targets for intervention . One potential mechanism is satiety responsiveness . Lack of satiety characterizes many monogenic obesity disorders , and lower satiety responsiveness is linked with weight gain in population sample s. OBJECTIVE To test the hypothesis that satiety responsiveness is an intermediate behavioral phenotype associated with genetic predisposition to obesity in children . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional observational study of a population -based cohort of twins born January 1 , 1994 , to December 31 , 1996 ( Twins Early Development Study ) . Participants included 2258 unrelated children ( 53.3 % female ; mean [ SD ] age , 9.9 [ 0.8 ] years ) , one r and omly selected from each twin pair . EXPOSURE Genetic predisposition to obesity . We created a polygenic risk score ( PRS ) comprising 28 common obesity-related single-nucleotide polymorphisms identified in a meta- analysis of obesity-related genome-wide association studies . MAIN OUTCOMES AND MEASURES Satiety responsiveness was indexed with a st and ard psychometric scale ( Child Eating Behavior Question naire ) . Using 1990 United Kingdom reference data , body mass index SD scores and waist SD scores were calculated from parent-reported anthropometric data for each child . Information on satiety responsiveness , anthropometrics , and genotype was available for 2258 children . We examined associations among the PRS , adiposity , and satiety responsiveness . RESULTS The PRS was negatively related to satiety responsiveness ( β coefficient , -0.060 ; 95 % CI , -0.019 to -0.101 ) and positively related to adiposity ( β coefficient , 0.177 ; 95 % CI , 0.136 - 0.218 for body mass index SD scores and β coefficient , 0.167 ; 95 % CI , 0.126 - 0.208 for waist SD scores ) . More children in the top 25 % of the PRS were overweight than in the lowest 25 % ( 18.5 % vs 7.2 % ; odds ratio , 2.90 ; 95 % CI , 1.98 - 4.25 ) . Associations between the PRS and adiposity were significantly mediated by satiety responsiveness ( P = .006 for body mass index SD scores and P = .005 for waist SD scores ) . CONCLUSIONS AND RELEVANCE These results support the hypothesis that low satiety responsiveness is one of the mechanisms through which genetic predisposition leads to weight gain in an environment rich with food . Strategies to enhance satiety responsiveness could help prevent weight gain in genetically at-risk children INTRODUCTION Few studies have evaluated the effect of nuts processing on the glycemic response and satiety . OBJECTIVE To evaluate the effect of peanut processing on glycemic response , and energy and nutrients intake . METHOD Thirteen healthy subjects ( 4 men and 9 women ) , with a mean age of 28.5 ± 10 years , BMI 22.7 ± 2.5 kg/m² , and body fat 23.7 ± 5.7 % participated in this r and omized crossover clinical trial . After 10 - 12 h of fasting , one of the following types of test meals were consumed : raw peanuts with skin ( RPS ) , roasted peanuts without skin , ground-roasted peanuts without skin ( GRPWS ) or control meal . The test meals had the same nutrient composition , and were consumed with 200 ml of water in 15 minutes . Glycemic response was evaluated 2 hours after each meal . Energy and nutrients intake were assessed through diet records reflecting the habitual food intake and food consumption 24 hours after the ingestion of test meal . RESULT The area under the glycemic response curve after GRPWS was lower ( p = 0.02 ) the one obtained for RPS . There was no treatment effect on energy intake , macronutrients and fiber consumption after the test meal . CONCLUSION The consumption of ground-roasted peanuts may favor the control and prevention of diabetes due to its reduction on postpr and ial glucose response . However , more prospect i ve studies are needed to confirm this hypothesis OBJECTIVE To compare serum lipid profiles and dietary intakes of people with normal lipid levels who consumed pecans and those who did not consume nuts . DESIGN Eight-week , r and omized , controlled study of pecan treatment group vs control group . SUBJECT Nineteen people with normal lipid levels completed the study ; 10 had been r and omly assigned to the pecan treatment group ( 7 women , 3 men , mean age = 45 + /- 10 years ) and 9 to the control group ( 8 women , 1 man , mean age = 37 + /- 12 years ) . INTERVENTION The pecan treatment group consumed 68 g pecans per day for 8 weeks plus self-selected diets . The pecans contributed 459 kcal and 44 g fat daily . The control group avoided nuts and consumed self-selected diets . MAIN OUTCOME MEASURES Total serum cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , and total triglyceride levels were measured at the time of entrance to the study ( baseline ) , week 4 , and week 8 . Computer analyses were done on five 3-day food records . STATISTICAL ANALYSIS Comparisons were made using analysis of variance or paired t test . RESULTS LDL-C was lowered in the pecan treatment group from 2.61 + /- 0.49 mmol/L at baseline to 2.35 + /- 0.49 at week 4 ( P < .05 ) and to 2.46 + /- 0.59 at week 8 ( P < .05 ) . At week 8 , total cholesterol and HDL-C in the pecan treatment group were significantly lower ( P < .05 ) than in the control group ( total cholesterol : 4.22 + /- 0.83 vs 5.02 + /- 0.54 mmol/L ; HDL-C : 1.37 + /- 0.23 vs 1.47 + /- 0.34 mmol/L ) . Dietary fat , monounsaturated fat , polyunsaturated fat , insoluble fiber , magnesium , and energy were significantly higher in the pecan treatment group than in the control group . Body mass indexes and body weights were unchanged in both groups . APPLICATIONS Pecans can be included in a healthful diet when energy intake and potential weight gain are addressed OBJECTIVE : To explore the relative importance of a food 's macronutrient composition , energy value , energy density , fiber content , weight , volume , sensory properties and rheology on hunger and food intake . DESIGN : Preloads of peanuts , peanut butter ( rheology control ) , almonds ( tree nut ) , chestnuts ( macronutrient control ) , chocolate ( sensory control ) , rice cakes ( volume control ) , pickles ( weight control ) and no load ( time control ) were consumed by subjects in r and om order at weekly intervals and hunger was assessed over the subsequent 180 min . Free-feeding energy and macronutrient intake were monitored 24 h before and following preload ingestion . SUBJECTS : Twelve male and 12 female healthy , normal weight ( 12–28 % body fat ) , adults ( mean ( s.d . ) age 22±2.5 y ) with low dietary restraint . RESULTS : Hunger ratings following consumption of the 2092 kJ ( 500 kcal ) preloads of peanuts , peanut butter , almonds , chestnuts and chocolate were significantly lower than the low energy preloads or no preload condition , but with the exception of peanut butter , did not vary from each other . The rate of hunger recovery was consistent across all preloads so the overall impact of each food on hunger was determined by the initial drop it evoked . Total energy , but not macronutrient , compensation was observed with all preloads . Consequently , the fatty acid profile of the total diet reflected the composition of the preloads . CONCLUSIONS : Energy content may be the primary determinant of a food 's impact on hunger . Because macronutrient compensation is weak , a dietary supplement or substitute may influence the daily dietary nutrient profile Regular nut consumption may improve markers of inflammation and endothelial dysfunction . The quantity of nuts required to achieve these health benefits without compromising body weight and acceptance is unknown . This study compared the effects of incorporating hazelnuts at 2 different doses with a diet without nuts on inflammatory markers , cell adhesion molecules , and body composition in 107 overweight and obese individuals . This was a r and omized , controlled , parallel 12-wk intervention including 3 treatment arms : no nuts ( control group ) , 30 g/d of hazelnuts , or 60 g/d of hazelnuts . Blood pressure , body composition , plasma high-sensitivity C-reactive protein ( hs-CRP ) , interleukin 6 ( IL-6 ) , intercellular adhesion molecule 1 ( ICAM-1 ) , vascular cell adhesion molecule 1 ( VCAM-1 ) , lipid , and apolipoprotein ( apo ) profiles were assessed at baseline and at 6 and 12 wk . " Desire " and " liking " for nuts were assessed during the intervention . Results showed no significant differences in follow-up clinical outcomes between groups after adjusting for baseline values , age , sex , and BMI ( all P ≥ 0.10 ) , except for a tendency toward improvement in VCAM-1 concentration in the 60-g/d nut group ( P = 0.07 ) . Hazelnut consumption significantly improved diet quality in a dose-response manner . Desire and liking for nuts remained stable in the 30-g/d group , whereas these ratings decreased significantly over time in the 60-g/d group ( both P < 0.001 ) . In conclusion , 12 wk of hazelnut consumption appears to have minimal effect on inflammatory markers and cell adhesion molecules in this group of healthy , normocholesterolemic overweight and obese individuals . Nut consumption improves diet quality without adversely affecting body composition . Consuming 30 g/d of nuts regularly is achievable , whereas 60 g/d appears to compromise desire and liking BACKGROUND With the increasing prevalence of being overweight and obesity , dietary strategies to curb hunger levels and increase satiety at lower energy intakes are sought . The frequency of eating and type of snack may influence total energy intake . The present study aim ed to assess the impact of providing either a conventional snack ( cereal bar ) or a nonconventional snack ( almonds ) on eating frequency , hunger rating , dietary intake , body weight and blood lipids . METHODS Forty-five healthy men ( aged 25 - 50 years , body mass index = 25 - 35 kg m(-2 ) ) were recruited and allocated to a control , cereal bar or almond snack group . Two packets of cereal bars and almonds were introduced for 12 weeks to the cereal bar group and the almond snack group , respectively . Dietary intakes and eating frequency were assessed by 4-day unweighed diet diaries ; visual analogue scales were used to assess hunger ratings ; and fasting blood parameters ( i.e. glucose , insulin , total cholesterol , triglycerides , low-density lipoprotein cholesterol and high-density lipoprotein cholesterol ) were measured at baseline , 6 and 12 weeks . In addition , anthropometric measures ( height , weight , skinfold thickness , waist and hip circumference ) were measured at baseline , 6 and 12 weeks . RESULTS The present study found no significant change in the eating frequency within groups at 12 weeks . However , the almond snack group had a significantly higher eating frequency than the control group ( P < or = 0.05 ) and cereal bar group ( P < or = 0.01 ) . This did not result in higher energy intake , body weight or percentage body fat in the almond snack group . CONCLUSION The present study demonstrated that snacking on almonds , in comparison to cereal bars , promoted a higher eating frequency , but not a higher energy intake . Advice to snack on either almonds or cereal bars did not result in weight gain , suggesting that energy compensation took place BACKGROUND The inclusion of almonds in an energy-restricted diet has been reported both to enhance or to have no effect on weight loss . Their effects specifically on visceral body fat stores during energy restriction have not been widely examined . In addition , almond consumption has been associated with reduced blood pressure ( BP ) , but whether this is linked to or independent of changes in body composition has to our knowledge not been examined . OBJECTIVE We evaluated the effects of consuming almonds as part of an energy-restricted diet on body composition , specifically visceral adipose tissue ( VAT ) and BP , compared to a nut-free energy-restricted diet . METHODS A r and omized controlled 12-wk clinical trial of 86 healthy adults [ body mass index ( in kg/m2 ) : 25 - 40 ] was conducted . Participants were r and omly assigned to 1 of 2 energy-restricted ( 500-kcal deficit/d ) diets : an almond-enriched diet ( AED ) ( 15 % energy from almonds ) or a nut-free diet ( NFD ) . A linear mixed-model analysis on primary outcomes such as body weight , body fat , VAT , and BP was performed on all participants [ intention-to-treat ( ITT ) analysis ] and compliant participants ( complier analysis ) . RESULTS Body weight , truncal and total fat percentage , VAT , and systolic BP decreased after 12 wk of energy restriction in both the ITT and complier analyses ( P < 0.05 ) . The complier analysis ( but not the ITT analysis ) indicated a greater mean ± SEM reduction in truncal fat ( AED : -1.21 % ± 0.26 % ; NFD : -0.48 % ± 0.24 % ; P = 0.025 ) , total fat ( AED : -1.79 % ± 0.36 % ; NFD : -0.74 % ± 0.33 % ; P = 0.035 ) , and diastolic BP ( AED : -2.71 ± 1.2 mm Hg ; NFD : 0.815 ± 1.1 mm Hg ; P = 0.029 ) , and a greater tendency for VAT loss ( AED : -8.19 ± 1.8 cm2 ; NFD : -3.99 ± 1.7 cm2 ; P = 0.09 ) over time in the AED group than the NFD group . CONCLUSIONS Moderate almond consumption by compliant overweight and obese individuals during energy restriction results in greater proportional reductions of truncal and total body fat as well as diastolic BP and hence may help to reduce metabolic disease risk in obesity . This trial was registered at clinical trials.gov as NCT02360787 BACKGROUND & AIMS To compare the acute effects of three fatty meals with different fat quality on postpr and ial thermogenesis , substrate oxidation and satiety . METHODS Twenty-nine healthy men aged between 18 and 30 years participated in a r and omised crossover trial comparing the thermogenic effects of three isocaloric meals : high in polyunsaturated fatty acids from walnuts , high in monounsaturated fatty acids from olive oil , and high in saturated fatty acids from fat-rich dairy products . Indirect calorimetry was used to determine resting metabolic rate , respiratory quotient , 5-h postpr and ial energy expenditure and substrate oxidation . Satiety was estimated by using visual analogue scales and measuring caloric intake in a subsequent ad libitum meal . RESULTS Five-h postpr and ial thermogenesis was higher by 28 % after the high-polyunsaturated meal ( p=0.039 ) and by 23 % higher after the high-monounsaturated meal ( p=0.035 ) compared with the high-saturated meal . Fat oxidation rates increased nonsignificantly after the two meals rich in unsaturated fatty acids and decreased nonsignificantly after the high-saturated fatty acid meal . Postpr and ial respiratory quotient , protein and carbohydrate oxidation , and satiety measures were similar among meals . CONCLUSIONS Fat quality determined the thermogenic response to a fatty meal but had no clear effects on substrate oxidation or satiety UNLABELLED The composition of fats within a high-fat ( HF ) meal may differentially affect hunger and satiety . PURPOSE Compare HF meals rich in either monounsaturated fatty acids ( MUFAs ) , polyunsaturated fatty acids ( PUFAs ) , or saturated fatty acids ( SFAs ) on the satiety hormone , peptide YY ( PYY ) , and subjective feelings of hunger and fullness . METHODS Fifteen normal weight women ( 18 - 45 year ) were r and omized in a crossover design to complete three study visits . The three treatments ( three visits ) were HF meals ( 70 % of energy from fat ) rich in MUFAs ( 42 % of total energy ) , PUFAs ( 42 % of total energy ) , or SFAs ( 45 % of total energy ) . At each visit , subjects consumed a HF meal and eight blood draws were collected over a 5 h period . A visual analog scale ( VAS ) was completed at the same time as each blood draw for subjective feelings of hunger and fullness . RESULTS The postpr and ial PYY response ( area under the curve ) was significantly lower ( p<0.05 ) for the MUFA-rich meal ( MUFA : 534.5±27.2 pg/mL/5 h ) vs. the SFA-rich or PUFA-rich meals ( SFA : 607.3±51.6 pg/mL/5h , PUFA : 633.1±35.8 pg/mL/5 h ) . The SFA-rich meal elicited greater subjective feelings of fullness compared to MUFA- and PUFA-rich meals ( 288.1±9.6 vs. 236.8±7.9 and 220.9±7.4 mm/5 h ; p=0.04 , for 5h AUC for SFA , MUFA , and PUFA , respectively ) . The only significant correlations between PYY levels and VAS measures were found with the SFA-rich meal . CONCLUSION Our data shows that liquid meals rich in MUFAs may elicit a weaker satiety response based on PYY levels compared to liquid meals rich in PUFAs or SFAs in normal weight women Improved vascular function after the incorporation of walnuts into controlled or high-fat diets has been reported ; however , the mechanism(s ) underlying this effect of walnuts is(are ) poorly defined . The objective of the current study was to evaluate the acute and short-term effects of walnut intake on changes in microvascular function and the relationship of these effects to plasma epoxides , the cytochrome-P450-derived metabolites of fatty acids . Thirty-eight hypercholesterolemic postmenopausal women were r and omized to 4 weeks of 5 g or 40 g of daily walnut intake . All outcomes were measured after an overnight fast and 4 h after walnut intake . Microvascular function , assessed as the reactive hyperemia index ( RHI ) , was the primary outcome measure , with serum lipids and plasma epoxides as secondary measures . Compared to 5 g of daily walnut intake , consuming 40 g/d of walnuts for 4 weeks increased the RHI and Framingham RHI . Total cholesterol and low- and high-density cholesterol did not significantly change after walnut intake . The change in RHI after 4 weeks of walnut intake was associated with the change in the sum of plasma epoxides ( r=0.65 , P=.002 ) but not with the change in the sum of plasma hydroxyeicosatetraenoic acids . Of the individual plasma epoxides , arachidonic-acid-derived 14(15)-epoxyeicosatrienoic acid was most strongly associated with the change in microvascular function ( r=0.72 , P<.001 ) . These data support the concept that the intake of walnut-derived fatty acids can favorably affect plasma epoxide production , result ing in improved microvascular function Objective : To compare postpr and ial whole-body fat oxidation rates in humans , following high-fat ( 43 % of total energy ) mixed breakfast meals , of fixed energy and macronutrient composition , rich in either monounsaturated fat ( MUFA ) from extra virgin olive oil or saturated fat ( SFA ) from cream . Design : Paired comparison of resting metabolic rate ( RMR ) , thermic effect of a meal and substrate oxidation rates following consumption of isocaloric breakfast meals , differing only in the type of fat , administered in r and om order 1–2 weeks apart . Subjects : Fourteen male volunteers , body mass index ( BMI ) in the range 20–32 kg/m2 , aged 24–49 y and resident in Melbourne , Australia , were recruited by advertisement in the local media or by personal contact . Measurements : Body size and composition was determined by anthropometry and dual energy X-ray absorptiometry ( DEXA ) . Indirect calorimetry was used to measure RMR , thermic effect of a meal , post-meal total energy expenditure and substrate oxidation rate . Blood pressure and pulse rates were measured with an automated oscillometric system . Fasting and 2 h postpr and ial glucose and insulin concentrations and the fasting lipid profile were also determined . Results : In the 5 h following the MUFA breakfast , there was a significantly greater postpr and ial fat oxidation rate ( 3.08±4.58 g/5 h , P=0.017 ) , and lower postpr and ial carbohydrate oxidation rate ( P=0.025 ) , than after the SFA breakfast . Thermic effect of a meal was significantly higher ( 55 kJ/5 h , P=0.034 ) after the MUFA breakfast , in subjects with a high waist circumference ( HWC≥99 cm ) than those with a low waist circumference ( LWC<99 cm ) . This difference was not detected following the SFA breakfast ( P=0.910 ) . Conclusion : If postpr and ial fat oxidation rates are higher after high MUFA , rather than SFA meals , then a simple change to the type of dietary fat consumed might have beneficial effects in curbing weight gain in men consuming a relatively high-fat diet . This may be particularly evident in men with a large waist circumference OBJECTIVE : To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin . DESIGN : R and omised , double-blind , placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/min . SUBJECTS : In all , 12 healthy lean subjects ( mean body mass index ( BMI ) 20.5±0.17 kg/m2 ) and 12 healthy overweight and obese subjects ( mean BMI 31.9±1.02 kg/m2 ) . MEASUREMENTS : Food intake , appetite and palatability of food , ghrelin and other obesity-related hormones , growth hormone . RESULTS : Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only ( mean increase 36.6±9.4 % , P<0.01 . ) High-dose ghrelin infusion increased energy intake in both groups ( mean increase 20.1±10.6 % in the lean and 70.1±15.5 % in the obese , P<0.01 in both cases . ) Ghrelin infusion increased palatability of food in the obese group . CONCLUSION : Ghrelin increases food intake in obese as well as lean subjects . Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity BACKGROUND Ileal delivery of fat reduces hunger and food intake through activation of the ileal brake . Physicochemical properties of fat have been shown to affect satiety and food intake . OBJECTIVE The objective of this study was to assess the effect of ileal fat emulsions with differing degrees of fatty acid saturation on satiety , food intake , and gut peptides ( cholecystokinin and peptide YY ) . We hypothesized that long-chain triacylglycerols with diunsaturated fatty acids would increase satiety and reduce energy intake compared with long-chain triacylglycerols with monounsaturated or saturated fatty acids . DESIGN We performed a double-blind , r and omized , crossover study in which 15 healthy subjects [ mean age : 24 y ; mean body mass index ( in kg/m(2 ) ) : 22 ] were intubated with a naso-ileal catheter and participated in 4 experiments performed in r and om order on 4 consecutive days . After consumption of a liquid meal , subjects received a fat or control infusion in the ileum . Fat emulsions consisted of 6 g of 18:0 ( shea oil ; mainly 18:0 ) , 18:1 ( canola oil ; mainly 18:1 ) , or 18:2 ( safflower oil ; mainly 18:2 ) oils . Food intake was measured during an ad libitum lunch . Satiety question naires ( visual analog scale ) and blood sample s were collected at regular intervals . RESULTS Compared with the control , only 18:2 and 18:1 significantly increased fullness and reduced hunger . No effect on food intake was observed . 18:1 and 18:2 increased cholecystokinin secretion significantly compared with the control . Fatty acid saturation did not affect peptide YY secretion . CONCLUSIONS When infused into the ileum , triacylglycerols with unsaturated fatty acids increase satiety , whereas triacylglycerols with saturated fatty acids does not . This trial was registered with the Dutch Trial Register as : IS RCT N51742545 The aim of this study was to investigate the prevention of diet-induced obesity by a high safflower oil diet and adipocytic gene expression in mice . Forty 3-week-old C57BL/6 mice were r and omly divided into three groups : control group ( CON , 5 % lard + 5 % safflower oil ) , high lard group ( LAR , 45 % lard + 5 % safflower oil ) , and high safflower oil group ( SAF , 45 % safflower oil + 5 % lard ) . After 10 weeks , 10 mice of the LAR group were switched to high safflower oil diet ( LAR-SAF ) . Ten weeks later , glucose tolerance tests were performed by intraperitoneal injection of glucose . Circulating levels of lipid and insulin were measured and white adipose tissues were taken for gene chip and reverse transcriptase-polymerase chain reaction analysis . The LAR group showed higher body weight , adiposity index , insulin , and lipids than the CON group ( P<0.05 ) . The body weight in the LAR-SAF group decreased after dietary reversal . The plasma biochemical profiles decreased in the LAR-SAF and SAF groups ( P<0.05 ) compared with those of the LAR group . The blood glucose level of the LAR-SAF group was reduced during intraperitoneal glucose tolerance test compared with that of the LAR group . The LAR-SAF group had lower levels of Orexin and Ghrelin gene expression , whereas the level of PPARalpha gene expression was significantly enhanced compared with that of the LAR group . So , the SAF diet can alter adipocytic adiposity-related gene expression and result in effective amelioration of diet-induced obesity OBJECTIVE Determine subjective and physiological appetite responses and ad libitum intake to high-fat ( HF ) meals rich in either monounsaturated ( MUFAs ) , polyunsaturated ( PUFAs ) , or saturated fatty acids ( SFAs ) in women with obesity . METHODS In this single-blind crossover study , three HF meals ( 70 % of energy ) rich in MUFAs , PUFAs , or SFAs in 16 women with obesity were tested . At each visit , anthropometrics and a fasting blood sample were collected . Participants then consumed one of the HF meals , and postpr and ial blood draws and visual analog scale ( VAS ) measures were collected over 5 h. An ad libitum buffet lunch was provided 5 h after the HF meal . RESULTS Decrease in ghrelin was significantly greater for PUFA ( P < 0.05 ) and MUFA ( P < 0.01 ) vs. SFA while the increase in peptide YY was significantly greater for PUFA vs. both SFA and MUFA ( P < 0.05 ) . Change in glucagon-like peptide-1 , VAS measurements , or total energy consumed at the buffet showed no differences between HF meals ( ns ) . CONCLUSIONS Fatty acid composition differentially affected physiological markers of hunger and satiety . However , it was unable to show changes in subjective appetite ratings or changes in energy intake when alterations were made to fatty acid composition from an acute HF meal Objective : The authors tested the hypothesis that in adults with prediabetes , an almond-enriched American Diabetes Association ( ADA ) diet improves measures of insulin sensitivity and other cardiovascular risk factors compared with an ADA nut-free diet . Methods : Design : R and omized parallel-group trial . Setting : Outpatient dietary counseling and blood analysis . Subjects : Sixty-five adult participants with prediabetes . Intervention : Sixteen weeks of dietary modification featuring an ADA diet containing 20 % of energy from almonds ( approximately 2 oz per day ) . Measures of Outcome : Outcomes included fasting glucose , insulin , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides , TC : HDL-C , and HbA1c , which were measured at weeks 0 , 8 , and 16 . Body weight , body mass index ( BMI ) , waist circumference , blood pressure , and nutrient intake were measured at weeks 0 , 4 , 8 , 12 , and 16 . Results : The almond-enriched intervention group exhibited greater reductions in insulin ( −1.78 µU/ml vs. + 1.47 µU/ml , p = 0.002 ) , homeostasis model analysis for insulin resistance ( −0.48 vs. + 0.30 , p = 0.007 ) , and homeostasis model analysis for beta-cell function ( −13.2 vs. + 22.3 , p = 0.001 ) compared with the nut-free control group . Clinical ly significant declines in LDL-C were found in the almond-enriched intervention group ( −12.4 mg/dl vs. −0.4 mg/dl ) as compared with the nut-free control group . No changes were observed in BMI ( −0.4 vs. −0.7 kg/m2 , p = 0.191 ) , systolic blood pressure ( −4.4 mm Hg vs. −3.5 mm Hg , p = 0.773 ) , or for the other measured cardiovascular risk factors . Conclusions : An ADA diet consisting of 20 % of calories as almonds over a 16-week period is effective in improving markers of insulin sensitivity and yields clinical ly significant improvements in LDL-C in adults with prediabetes Abstract Objective : To study the effects of snacking based on fast acting carbohydrates ( c and y ) or fat and protein ( peanuts ) in a prospect i ve r and omized , parallel intervention study . Methods : Basal metabolic rate ( BMR ) and cardiovascular risk factors were measured before and after hyper-alimentation by addition of 20kcal/kg ( 84kJ/kg ) body weight of either c and y or roasted peanuts , to the regular caloric intake , for two weeks in healthy subjects . Eleven men and 14 women completed the r and omized study . Results : Energy-intake increased similarly in the groups ( c and y : + 46.1±35 % , peanuts : + 46.8±28 % p=0.96 ) . Body-weight ( c and y : from 67.3±7.6 kg to 68.1±7.3 kg , p=0.01 , nuts : from 68.7±6.1 kg to 69.0±5.7 kg p=0.3 ) and waist circumference increased significantly only in the c and y group . At the end of the study LDL cholesterol ( c and y : 2.6±0.4mmol/l peanuts : 2.1±0.4mmol/l , p=0.005 ) and ApoB/ApoA-1-ratio ( c and y : 0.68±0.16 peanuts 0.53±0.11 , p=0.01 ) were higher in the c and y group than in the peanut group . On the other h and , BMR increased only in the peanut group ( c and y : from 6.657±1.1MJ/24h to 6.762±1.1MJ/24h , p=0.3 nuts : from 6.896±0.98MJ/24h to 7.256±1.1MJ/24h , p=0.02 ) . Conclusion : Two weeks of snacking based on peanuts does not cause the same negative metabolic effects as an isocaloric diet in which the snacking is based on short acting carbohydrates in the form of c and y in non-obese healthy subjects We assessed evidence for changes in efficacy of food-based interventions aim ed at reducing appetite or energy intake ( EI ) , and whether this could be used to provide guidance on trial design . A systematic search identified r and omized controlled trials testing sustained efficacy of diets , foods , supplements or food ingredients on appetite and /or EI . Trials had to include sufficient exposure duration ( ≥3 days ) with appetite and /or EI measured after both acute and repeated exposures . Twenty-six trials met the inclusion criteria and reported data allowing for assessment of the acute and chronic effects of interventions . Most ( 21/26 ) measured appetite outcomes and over half ( 14/26 ) had objective measures of EI . A significant acute effect of the intervention was retained in 10 of 12 trials for appetite outcomes , and six of nine studies for EI . Initial effects were most likely retained where these were more robust and studies adequately powered . Where the initial , acute effect was not statistically significant , a significant effect was later observed in only two of nine studies for appetite and none of five studies for EI . Maintenance of intervention effects on appetite or EI needs to be confirmed but seems likely where acute effects are robust and replicable in adequately powered studies Purpose Regular nut consumption reduces cardiovascular disease risk , partly from improvements to dietary quality . Examining how individuals make dietary changes when consuming nuts may reveal key behavioural eating patterns beneficial for the development of dietary interventions . We examined the effects of nuts in comparison with other energy-dense snacks on energy compensation , nutrient displacement , and food group patterns . Methods This was a 12-week r and omised , controlled , parallel study with four arms : ~1100 kJ/day for each of hazelnuts ( 42 g ) , chocolate ( 50 g ) , potato crisps ( 50 g ) , or no added snack food . Diet records , body composition , and physical activity were measured at baseline and week 12 , in 102 non-obese participants . Results Significant improvements in diet quality were observed in the hazelnut group , particularly when consumed as snacks . Intakes of monounsaturated fat ( MUFA ) and vitamin E were significantly higher ( all P < 0.05 ) , whereas saturated fat and carbohydrate were significantly lower ( both P ≤ 0.022 ) in the hazelnut group compared to the other groups . Partial energy compensation did not differ significantly between groups , but nutrient displacement values for MUFA and fibre differed significantly . Within the hazelnut group , there was nearly complete displacement for fibre , partial displacement for energy , protein , total fat , MUFA , PUFA , potassium , folate , and vitamin E , and overcompensation for carbohydrate and sugar . Conclusions Our results demonstrate that energy compensation occurs for all three intervention snacks in this non-obese population . Regular nut consumption significantly improves nutrient profiles compared to other snacks with changes occurring at the snack level |
13,427 | 31,515,657 | DED is estimated to be present in more than a quarter of persons with type 2 diabetes and half of persons with type 1 diabetes underlining the importance of regular monitoring . | null | null |
13,428 | 31,603,999 | The global scale-up of HIV treatment for PLHIV using a tenofovir-based ART regimen provides an opportunity to simultaneously treat those with HBsAg co-infection and reduce mother-to-child transmission of HBV alongside HIV | Globally , 35 million people are living with HIV ( PLHIV ) and 257 million have chronic HBV infection ( HBsAg positive ) .
The extent of HIV-HBsAg co-infection is unknown .
We undertook a systematic review to estimate the global burden of HBsAg co-infection in PLHIV . | Objectives To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations . Methods This was a prospect i ve , multicentre cohort study with 532 HIV-infected patients receiving nevirapine as a part of their initial antiretroviral therapy . Plasma sample s were collected at trough or peak time at the end of week 2 ( lead-in period ) and week 4 , 12 , 24 , 36 , and 48 ( steady-state period ) , and nevirapine concentrations were determined using a vali date d HPLC method . Potential influencing factors associated with nevirapine concentrations were evaluated using univariate and multivariate logistic regression . Results A total of 2348 nevirapine plasma concentrations were collected , including 1510 trough and 838 peak values . The median nevirapine trough and peak concentration during the lead-in period were 4.26 µg/mL ( IQR 3.05–5.61 ) and 5.07 µg/mL ( IQR 3.92–6.44 ) respectively , which both exceeded the recommended thresholds of nevirapine plasma concentrations . Baseline hepatic function had a moderate effect on median nevirapine trough concentrations at week 2 ( 4.25 µg/mL v.s. 4.86 µg/mL , for ALT < 1.5 × ULN and ≥1.5 × ULN , respectively , P = 0.045 ) . No significant difference was observed in median nevirapine trough concentration between lead-in and steady-state periods in patients with baseline ALT and AST level ≥1.5 × ULN ( P = 0.171 , P = 0.769 ) , which was different from the patients with ALT/AST level < 1.5ULN . The median trough concentrations were significantly higher in HIV/HCV co-infected patients than those without HCV at week 48 ( 8.16 µg/mL v.s. 6.15 µg/mL , P = 0.004 ) . Conclusions The 200 mg once-daily regimen of nevirapine might be comparable to twice-daily in plasma pharmacokinetics in Chinese population . Hepatic function prior to nevirapine treatment and HIV/HCV coinfection were significantly associated with nevirapine concentrations . Registration Clinical trial.gov ID : Purpose Sexually transmitted infections ( STIs ) occur frequently in risk population s. Hereby , the role of screening-programmes remains controversial . Our study aim ed to determine the prevalence of STI infections in HIV-positive men-who-have-sex-with-men ( MSM ) . Methods We enrolled asymptomatic , HIV-MSM in a prospect i ve cross-sectional study from February to August 2016 at seven German HIV-centres . All subjects were screened for Treponema-pallidum ( TP ) and hepatitis-B/C-infection . HIV RNA and screening for oral , rectal and urethral colonisation by Chlamydia-trachomatis ( CT ) and /or Neisseria-gonorrhoeae ( NG ) was performed . All subjects were asked to complete a sexual-risk-behaviour- question naire . Results In total , 296 subjects with a median age of 43.2 ( 36.2–49.5 ) years were enrolled ; 99.3 % were on ART for 5.5 ( 2.3–11.2 ) years . HIV RNA was < 50 copies/mL in 93.6 % . Active syphilis infection was found in 5.0 % of all patients , whereas 55.4 % had history of infection . HCV seropositivity was found in 33 patients ( 13.2 % ) and positive HCV RNA was available in 39.4 % . 66/294 ( 22.5 % ) showed negative anti-HBs-antibodies , indicating lack of immunity . Overall , 40/296 ( 13.5 % ) had positive CT/NG swabs ( CT in 8.8 % ; 7.3 % anorectal , 1.7 % oropharyngeal , 1.0 % urethral and NG in 6.8 % ; 4.5 % anal , 2.0 % oropharyngeal , 1.4 % urethral ) . Time since HIV infection < 7 years ( OR 2.6 ( 1.2–5.5 ) ; p = 0.012 ) , the use of inhalative nitrites ( “ poppers ” ) ( OR 2.8 ( 1.3–5.9 ; p = 0.008 ) and reporting unprotected intercourse with > 20 partners within the last 6 months [ OR 3.0 ( 1.2–7.8 ) ; p = 0.003 ] were significantly associated in multivariate analysis . Conclusion We found high numbers of asymptomatic syphilis , hepatitis-C and CT/NG infections in HIV-MSM , remarkably in patients with shorter duration of HIV-infection with more sexual partners within last 6 months OBJECTIVES This study was design ed to assess the prevalence of HBV and HCV infection in HIV patients and evaluate the risk of infection compared with HIV negative control subjects . METHOD This is a prospect i ve case control study in which 240 HIV/AIDS patients and age and sex matched controls were evaluated . The diagnosis of HIV infection was based on a positive HIV screening test using Capillus test kits ( Trinity Biotech PLC , Irel and ) and confirmed using Western blot assay . HBsAg and anti-HCV were assayed by commercially available chromatographic immunoassay ( SD BIOLINE ) . RESULTS Eleven ( 9.2 % ) of the 120 HIV/AIDS patients and 8 ( 7 % ) of the 120 control subjects were positive for the HBsAg ( OR=1 , p=0.27 ) . HBeAg was detected in 3 of the 11 ( 27.3 % ) subjects with HIV/HBV co infections . HIV positive patients were 7 times more likely to have HCV infection than control patients ( 5.8 % compared with 0.8 % , OR=7.3 , p= 0.03 ) . CONCLUSION The lack of a strong association between HBV and HIV infection may be related to different exposure routes in this population where HBV infection is highly endemic and childhood infection almost universal . In this African population , HIV infection may be a super-infection of HBV infections contracted in childhood . This high HCV/HIV co-infection rate is consistent with the shared parenteral and sexual routes of transmission The purpose of this study is to determine the rate of human immunodeficiency virus ( HIV ) and hepatitis B surface antigen ( HBsAg ) among commercial blood donors in the University of Benin Teaching Hospital . Five thous and seven hundred and thirty-seven prospect i ve commercial blood donors were screened for both HIV and HBsAg . Three hundred and eighty-three ( 7 % ) donors were positive for HIV while 609 donors ( 11 % ) were positive for HBsAg . Thirty-seven donors were positive for both HIV and HBsAg . The need to make the screening of blood donors for HIV and HBsAg compulsory in all hospitals is crucial so that the spread of HIV and HBsAg can be prevented BACKGROUND An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy ( cART ) are due to complications of liver diseases . METHODS We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study , which prospect ively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons . Multivariable Poisson regression analyses identified factors associated with liver-related , AIDS-related , and other causes of death . RESULTS There were 1246 deaths ( 5.3 % ; 1.6 per 100 person-years ) ; 14.5 % were from liver-related causes . Of these , 16.9 % had active hepatitis B virus ( HBV ) , 66.1 % had hepatitis C virus ( HCV ) , and 7.1 % had dual viral hepatitis co-infections . Predictors of liver-related deaths were latest CD4 cell count ( adjusted relative rate [ RR ] , 16.1 ; 95 % confidence interval [ CI ] , 8.1 - 31.7 for < 50 vs > or = 500/microL ) , age ( RR , 1.3 ; 95 % CI , 1.2 - 1.4 per 5 years older ) , intravenous drug use ( RR , 2.0 ; 95 % CI , 1.2 - 3.4 ) , HCV infection ( RR , 6.7 ; 95 % CI , 4.0 - 11.2 ) , and active HBV infection ( RR , 3.7 ; 95 % CI , 2.4 - 5.9 ) . Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death ( RR , 1.00 ; 95 % CI , 0.93 - 1.07 ) . Adjustment for the most recent CD4 cell count and patient characteristics result ed in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART ( RR , 1.09 ; 95 % CI , 1.02 - 1.16 ; P = .008 ) and per year of cART ( RR , 1.11 ; 95 % CI , 1.02 - 1.21 ; P = .02 ) . CONCLUSIONS Liver-related death was the most frequent cause of non-AIDS-related death . We found a strong association between immunodeficiency and risk of liver-related death . Longer follow-up is required to investigate whether clinical ly significant treatment-associated liver-related mortality will develop ABSTRACT Outbreaks of sexually transmitted hepatitis C virus ( HCV ) infections have been recently reported in HIV-infected men who have sex with men ( MSM ) in Europe , Australia , and North America . Little is known concerning whether this also occurs in other Asia-Pacific countries . Between 1994 and 2010 , a prospect i ve observational cohort study was performed to assess the incidence of recent HCV seroconversion in 892 HIV-infected patients ( 731 MSM and 161 heterosexuals ) who were not injecting drug users . A nested case-control study was conducted to identify associated factors with recent HCV seroconversion , and phylogenetic analysis was performed using NS5B sequences amplified from seroconverters . During a total followup duration of 4,270 person-years ( PY ) , 30 patients ( 3.36 % ) had HCV seroconversion , with an overall incidence rate of 7.03 per 1,000 PY . The rate increased from 0 in 1994 to 2000 and 2.29 in 2001 to 2005 to 10.13 per 1,000 PY in 2006 to 2010 ( P < 0.05 ) . After adjustment for age and HIV transmission route , recent syphilis remained an independent factor associated with HCV seroconversion ( odds ratio , 7.731 ; 95 % confidence interval , 3.131 to 19.086 ; P < 0.01 ) . In a nested case-control study , seroconverters had higher aminotranferase levels and were more likely to have CD4 ≥ 200 cells/μl and recent syphilis than nonseroconverters ( P < 0.05 ) . Among the 21 patients with HCV viremia , phylogenetic analysis revealed 7 HCV transmission clusters or pairs ( 4 within genotype 1b , 2 within genotype 2a , and 1 within genotype 3a ) . The incidence of HCV seroconversion that is associated with recent syphilis is increasing among HIV-infected patients in Taiwan Objectives Men who have sex with men ( MSM ) are at higher risk for coinfection with hepatitis B virus ( HBV ) , hepatitis C virus ( HCV ) , and syphilis than the general population . HIV infection and these coinfections accelerate disease progression reciprocally . This study evaluated the prevalence and incidence of these coinfections in HIV1-positive MSM in Germany . Material s and Methods As part of a nationwide , multicenter , prospect i ve cohort study of HIV-infected MSM , plasma sample s collected yearly were screened for HBsAg and antibodies to HBc , HBs , HCV , and syphilis . Sample s with indications of active HBV or HCV infection were confirmed by polymerase chain reaction . Prevalence and incidence of each infection and incidence rates per study participant were calculated , and incidences over 4-year time intervals compared . Results This study screened 5,445 sample s from 1,843 MSM . Median age at HIV seroconversion was 33 years . Prevalences of active , cleared , and occult HBV , and of active/cleared HCV were 1.7 % , 27.1 % , 0.2 % , and 8.2 % , respectively , and 47.5 % had been effectively vaccinated against HBV . Prevalence of antibodies to Treponema pallidum and of triple or quadruple sexually transmitted infections ( STIs ) were 39.6 % and 18.9 % , respectively . Prevalence of STI , cleared HBV , HBV vaccination , and history of syphilis differed significantly among age groups . Incidences of HBV , HCV , and syphilis were 2.51 , 1.54 , and 4.06 per 100 person-years , respectively . Incidences of HCV and syphilis increased over time . HCV incidence was significantly higher in MSM coinfected with syphilis and living in Berlin , and syphilis incidence was significantly higher for MSM living in Berlin . Discussion Despite extensive HBV vaccination campaigns , fewer than 50 % of screened MSM were effectively vaccinated , with a high proportion of HIV-positive MSM coinfected with HBV . High rates of STI coinfections in HIV-positive MSM and increasing incidences emphasize the need for better tailored campaigns for HBV vaccination and STI prevention BACKGROUND Although coinfection with HIV-1 and hepatitis B virus ( HBV ) is common , few long-term studies on liver-disease mortality in coinfected people have been undertaken . Our aim was to examine liver-related mortality among people at risk for HIV-1 and HBV infections . METHODS We used data from a multicentre , prospect i ve cohort study to classify 5293 men who had sex with men , according to their HIV-1 antibody status , ascertained semiannually , and their hepatitis-B surface antigen status ( HBsAg ) , which we ascertained at baseline . Mortality rates were estimated in terms of person-years and Poisson regression methods were used to test for significance of relative risks . FINDINGS 326 ( 6 % ) men were HBsAg positive , of whom 213 ( 65 % ) were HIV-1 positive . Of the 4967 HBsAg negative men , 2346 ( 47 % ) were infected with HIV-1 . The liver-related mortality rate was 1.1/1000 person years , and was higher in men with HIV-1 and HBsAg ( 14.2/1000 ) than in those with only HIV-1 infection ( 1.7/1000 , p<0.001 ) or only HBsAg ( 0.8/1000 , p<0.001 ) . In coinfected individuals , the liver-related mortality rate was highest with lower nadir CD4 + cell counts and was twice as high after 1996 , when highly active antiretroviral therapy ( HAART ) was introduced . INTERPRETATION Individuals coinfected with HIV-1 and HBV , especially those with low CD4 + nadir counts , are at increased risk for liver-related mortality , underscoring the importance of prevention , identification , and comprehensive management of hepatitis B in people infected with HIV-1 Background : Differences in adverse events by gender and race/ethnicity have not been described extensively in r and omized clinical trials of HIV antiretroviral therapy ( ART ) . Methods : Antiretroviral-naive HIV-infected participants enrolled in a long-term r and omized clinical trial of 3 different initial ART strategies-protease inhibitor ( PI ) , nonnucleoside reverse transcriptase inhibitor ( NNRTI ) , or PI plus NNRTI-based combinations-with a median follow-up of 5 years , were compared by gender and race for 14 categories of grade 4 adverse events , discontinuation of initial antiretroviral regimen , and all-cause mortality . Multivariate analysis was used to identify predictors of events and death . Results : Among 1301 participants with complete data , there were 701 blacks , 225 Latinos , and 263 women . Several baseline characteristics differed by gender and race , including age , HIV transmission risk , hepatitis B or C coinfection , viral load , diagnosis of AIDS , body mass index , and baseline hypertension . Grade 4 events occurred in 409 participants ( rate : 8.9/100 person-years ) . There were 176 deaths ( rate : 3.0/100 person-years ) and 523 discontinuations of regimen for any toxicity ( rate : 13/100 person-years ) . In the fully adjusted regressions , blacks had greater risk for cardiovascular ( hazard ratio [ HR ] = 2.64 , 95 % confidence interval [ CI ] : 1.04 to 6.67 ) and renal ( HR = 3.83 , 95 % CI : 1.28 to 11.5 ) events . Black men had more psychiatric events ( HR = 2.45 , 95 % CI : 1.13 to 5.30 ) . Women had a higher risk for anemia ( HR = 2.34 , 95 % CI : 1.09 to 4.99 ) . Conclusion : Among HIV-infected participants initiating ART , there were significant risk-adjusted differences for specific adverse events by gender and race but not in the overall adverse event rates , all-cause mortality , or rates of toxicity-related treatment discontinuations Human herpesvirus 8 ( HHV-8 ) is etiologically linked to Kaposi 's sarcoma , a common cancer in Ug and a. The authors assessed HHV-8 seroprevalence , risk factors for infection , and HHV-8 assays in a cross-sectional study of Ug and an blood donors . Of 3,736 specimens , the authors selected 203 reactive for HIV , hepatitis B surface antigen ( HBsAg ) , or syphilis , and , r and omly , 203 nonreactive specimens . For HHV-8 testing , the authors used two peptide-based enzyme-linked immunosorbent assays ( EIAs ) , ORFK8.1 and ORF65 , and an immunofluorescence assay ( IFA ) . Specimens reactive in at least two assays or on IFA alone were considered HHV-8-seropositive . Prevalence estimates were weighted to account for the sampling scheme . Overall HHV-8 seroprevalence was 40 % . HHV-8 seroprevalence was higher among HBsAg-positive donors ( 53 % ) than HBsAg-negative donors ( 39 % ; p = .02 ) and higher among HIV-positive donors ( 63 % ) than HIV-negative donors ( 39 % ; p < .001 ) . HHV-8 seroreactivity showed no trend with age . Kappa values for assay concordances were 0.68 ( ORFK8.1 EIA and IFA ) , 0.37 ( ORF65 EIA and K8.1 EIA ) , and 0.29 ( ORF65 EIA and IFA ) . The association between HHV-8 and HBsAg positivity and the lack of association between HHV-8 and age point to primarily nonsexual HHV-8 transmission during childhood . The association with HIV indicates sexual transmission may also occur . The role of ORF65 EIA in testing specimens from Africa warrants further evaluation Objectives : Hepatitis B virus ( HBV ) and HIV infections share risk factors ; therefore , coinfection is common . Interactions have been reported but controlled studies have been limited . Our objective was to study the effect of HIV infection on the natural history of chronic HBV infection and the reverse effect of the HBV carrier state on HIV infection . Design : Prospect i ve observational cohort study . Setting : Open-access outpatient HIV/genitourinary medicine clinic at a Central London hospital . Patients : Total of 152 untreated homosexual male HBV carriers and 212 HBV surface antigen-negative controls ( 41.4 and 70.3 % HIV-seropositive , respectively ) . Outcome measures : The rate of loss of serum HBV e antigen ( HBeAg ) and its reappearance in HIV-infected and HIV-uninfected HBV carriers ; serum HBV DNA levels ( measured by dot-blot hybridization assay ) , HBV DNA polymerase activity and liver transaminase activities ; the progression of HIV infection to symptomatic disease or AIDS in HIV-infected compared with HBV-HIV coinfected patients . Results : In HIV-infected HBV carriers , serum HBV DNA polymerase activity was higher , alanine aminotransferase was lower and loss of serum HBeAg ( mean follow-up , 2.8 years ) occurred at a lower rate when compared with HIV-uninfected HBV carriers ( estimated relative hazard , 0.39 ; 95 % confidence interval , 0.161–0.942 ) . Concomitant chronic HBV infection had no detectable effect on the rate of progression of HIV disease after correction for lead-time bias . Conclusion : This study strengthens the evidence for a significant effect of HIV infection on the natural history of chronic HBV infection , which by prolonging the period of infectivity could have an important impact on the epidemiology of HBV infection in regions , or patient groups , with high HIV seroprevalence . There was no evidence of an important effect of HBV carriage on HIV disease progression Most HIV positive people have not been tested for viral hepatitis and their treatments have not been optimized for possible co-infections . The aim of this study was to investigate the serological pattern of hepatitis B virus ( HBV ) and hepatitis C virus ( HCV ) infections among antiretroviral (ARV)-naive and -experienced HIV co-infected adults in Addis Ababa , Ethiopia . A total of 500 frozen HIV positive serum and plasma sample s collected from ARV-naive ( n = 250 ) and -experienced ( n = 250 ) adults were r and omly selected and screened for HBsAg , anti-HBs , HBeAg and anti-HCV using rapid two-site s and wich immunochromatographic assay . The test was performed at Aklilu Lemma Institute of Pathobiology , Addis Ababa University . Positive specimens for HBsAg and anti-HCV markers were further confirmed using third generation ELISA . Of the 500 specimens tested , 15 ( 3 % ) , 58 ( 11.6 % ) , 3 ( 0.6 % ) , 18 ( 3.6 % ) , 3 ( 0.6 % ) and 1 ( 0.2 % ) were positive for HBsAg , anti-HBs , HBeAg , anti-HCV , HBsAg and HBeAg , and HBsAg and anti-HBs markers , respectively . No specimen tested positive for both HBeAg and anti-HBs , and 442 ( 88.4 % ) individuals were non-immune to HBV . Of the 250 ARV-naive individuals , 8 ( 3.2 % ) , 33 ( 13.2 % ) , 2 ( 0.8 % ) , 10 ( 4 % ) , 2 ( 0.8 % ) , and 1 ( 0.4 % ) were positive for HBsAg , anti-HBs , HBeAg , anti-HCV , HBsAg and HBeAg , and HBsAg and anti-HBs markers , respectively . Of the 250 ARV-experienced individuals , 7 ( 2.8 % ) , 25 ( 10 % ) , 1 ( 0.4 % ) , 8 ( 3.2 % ) , 1 ( 0.4 % ) , and 0 ( 0 % ) were positive for HBsAg , Anti-HBs , HBeAg , anti-HCV , HBsAg and HBeAg , and HBsAg and anti-HBs markers , respectively . In summary , seroprevalence of HIV/HBV and HIV/HCV co-infections was lower in Addis Ababa , Ethiopia , than in Sub-Saharan Africa and globally . HBV and HCV infections were not significantly different between HIV positive subjects who were or who were not on ARV . This suggests that the two groups have equal chance of being infected with these two viruses ; despite this , disease progression could be different Introduction Globally , hepatitis B virus ( HBV ) infection is the leading cause of liver-related mortality . Newborn vaccination , maternal antiviral therapy and administering hepatitis B immune globulin shortly after birth can greatly reduce the risk of perinatal and infant infection . However , evidence -based policy regarding these interventions in Africa is hampered by gaps in knowledge of HBV epidemiology . We describe maternal chronic hepatitis B ( CHB ) prevalence and infant infection during the first year of life within a cohort of women living with HIV . Methods We recruited and prospect ively followed pregnant women living with HIV and their infants from prenatal clinics in an urban area of South Africa . Hepatitis B surface antigen , anti-hepatitis B surface antibodies and HBV DNA were assessed in all women . Hepatitis B testing was also performed at 6 and 52 weeks for all infants born to mothers with either positive surface antigen or detectable HBV DNA . Results We enrolled 189 women with a median age of 29 years and median CD4 count of 348 cells/mm3 . Fourteen had a positive surface antigen ( 7.4 % ) , of which six were positive for “ e ” antigen . An additional three had detectable HBV DNA without positive surface antigen . One infant developed CHB and three others had evidence of transmission based on positive HBV DNA assays . HBV vaccinations were delivered at six weeks of life to all infants . Conclusions Our findings highlight the risk of peripartum HBV transmission in this setting . Approaches to reducing this transmission should be considered BACKGROUND It is not known whether antiretroviral therapy ( ART ) including lopinavir/r has a different effect on the lipid metabolism in HIV patients co-infected with HCV . This study investigated changes in lipid levels , comparing patients with HIV infection alone and those with HCV too , in the lopinavir/r cohort of the SCOLTA project . METHODS We analyzed the data for the lopinavir/r nationwide cohort from 25 Italian infectious disease departments , which comprises 743 HIV-infected patients followed prospect ively , comparing subjects with HIV-HCV co-infection and those with single-infection . RESULTS At enrolment , co-infected patients had significantly lower mean cholesterol than HCV negative cases ( 162+/-43mg/dL vs. 185+/-52mg/dL , p=0.0009 ) . Total and non-HDL cholesterol and triglycerides rose significantly from baseline in HIV single-infection patients , but not in those with co-infection . The patients with dual HIV-HCV infection , treated with an ART regimen including lopinavir/r , have only limited increases in total and non-HDL cholesterol and triglycerides . CONCLUSIONS Changes in serum lipids in co-infected patients differed significantly from those in patients without HCV . It remains to be seen whether this is associated with a lower risk of progression of atherosclerotic disease We undertook this study to assess the association between the various potential causes of liver disease in HIV-seropositive patients and mortality due to liver failure . Three hundred and eight in-hospital deaths were observed from 1987 to December 1995 in a prospect ively followed cohort of 1894 HIV-seropositive patients . For each study subject , clinical data were evaluated to assess whether liver failure had substantially contributed to mortality . A case control study nested in the cohort was then performed , which compared demographic and clinical variables observed at enrollment and during follow-up between patients who died for liver disease as the main or concurrent cause of death ( cases ) and those who died as a result of illness related to AIDS or other causes ( controls ) . Among 308 in-hospital deaths , liver failure was found the cause of death in 35 patients ( 12 % ) ; in 16 cases , it was the primary cause and in 19 cases it was concurrent . Multivariate analysis showed that in-hospital liver-disease-related mortality was independently associated with hepatitis B surface antigen reactivity ( odds ratio [ OR ] , 9 ; 95 % confidence interval [ CI ] , 3.8 - 21.7 ) and history of alcohol abuse ( OR , 2.3 ; 95 % CI , 1 - 5.2 ) . Prevention and treatment of hepatitis B virus infection and alcohol intake are management priorities in HIV-seropositive patients Introduction Highly active antiretroviral therapy ( HAART ) has improved survival of human immunodeficiency virus ( HIV ) patients . Concurrent morbidities from liver diseases among these patients have also been observed due to co-infection with hepatitis B and C viruses ( HBV and HCV ) . HAART reduces liver-associated morbidities and mortalities in such patients . Unfortunately free testing of HBV and HCV are not provided alongside free HIV testing and treatment in Nigeria . We assessed the seroprevalence of HBV and HCV among HIV patients presenting for treatment in our center . Methods This prospect i ve study of adult patients with HIV/AIDS assessed the seroprevalence of HBV and HCV co-infection using a 19-item question naire and collection of 2ml venous blood for hepatitis B surface antigens ( HBsAg ) and anti-HCV antibodies . All previously diagnosed HIV patients of the unit were excluded from the study . Results Of the 404 patients , 69.2 % were females while 30.8 % were males . Married participants were 59.6 % , 25.3 % were single and 15 % were previously married . A large proportion ( 69 % ) of patients were farmers , artisans and traders . Most had some formal education ; secondary ( 55.3 % ) , primary 27.3 % , tertiary 13.8 % . HBsAg positive participants were 9 ( 2.2 % ) while 3 ( 0.7 % ) were positive for HCV . No participant had triple infection of HIV/HBV/HCV . Conclusion Seroprevalence of HBV and HCV is low among HIV patients in Orlu . However there is a need for HBV and HCV testing of all HIV positive patients to reduce morbidities and mortalities from liver diseases Maternal-fetal transmission of hepatitis B virus ( HBV ) is a global public health problem leading to the implementation of strengthened prevention measures . Viral replication in HIV-positive mother , assessed based on HBeAg positivity and the rate of viral load , determines the contamination risk which is very important during perinatal period . Mothers with chronic HBV are a real reservoir of vertical transmission of this infection . This is a prospect i ve investigation of 1120 pregnant Moroccan women aim ing to study the seroprevalence of HBsAg which was 2.35 % , in order to supply the national evidence on this topic . Among these HIV-positive women who were HBsAg positive , 79.1 % were HBeAg negative and underwent molecular research that was positive in 89.4 % of cases . Immunization of women of childbearing age is one of the major pillars of prevention of HBV vertical transmission . Only 2.4 % of our patients were vaccinated . This highlights the role of screening during pregnancy , which should focus on raising awareness about the importance of immunization in HIV-negative women and of monitoring using molecular biology tools in HIV-positive mothers in order to establish an appropriate prophylactic treatment The aim of this study was to determine hepatitis co-infection in a cohort of HIV infected patients at their inclusion in the Senegalese Initiative of ART Access . B , C , and D Hepatitis viruses serological markers were checked retrospectively on 363 stored plasma . For HBV , the Abbott laboratories equipment IMx was used to detect HBs Ag and anti Core Ab on negative HBs Ag sample s. For HDV , anti Delta Ab was performed using the Abbott Murex Kit on all HBs Ag positive sample s. For HCV , anti HCV Ab was detected by IMx as double screening test and confirmed by INNO-LIA(TM ) HCV Core of Innogenetics laboratories . The statistical analysis was done with STATA V8 . The study population was composed of 164 men and 199 women aged between 16 and 66 years . The immune and virological markers averages at their enrollment were 154 cell/mm(3 ) for TLCD4 + ( n = 355 patients ) and 4.9 log for viral load ( n = 277 patients ) . HBs Ag was found in 61 patients or 16.8 % and the prevalence of anti-HBc Ab was 83.2 % ( 252/295 ) . 2 patients or 3 % on HBs Ag positive sample presents HBV/HDV co-infection Ab anti HCV was detects in 6 patients or 1.6 % after confirmation and 2 patients had triple infection with HBV . These results showed that the prevalence of HBV and HCV in the population of persons living with HIV/AIDS in Senegal is similar to that found in the general population . Our data indicated that hepatitis pathology in the PLwHIV was essentially due to HBV . Further studies are needed to diagnose occult hepatitis in order to set up therapeutic strategies taking into account co-infections by hepatitis viruses in the ART programmes AIM For several years Nonnucleoside reverse transciptase inhibitors ( NNRTIs ) in antiretroviral therapy have been associated with hepatic side effects . Particularly the hepatotoxic potential of Nevirapine is well analysed today . We performed a prospect i ve , multicenter study to compare the hepatotoxicity of Efavirenz ( EFV ) with that of Nevirapine ( NVP ) and to investigate further risk factors . MATERIAL AND METHODS The study included HIV-1-infected patients from five clinics and private medical practice s in southwestern Germany who initiated an antiretroviral therapy with NVP or EFV between July 1998 and December 2001 . Among 296 patients in total , 151 received EFV and 145 received NVP . Laboratory tests during the course of treatment included liver enzymes , HIV-RNA and CD4 cell-count . Additionally , signs of clinical hepatitis were recorded . Hepatotoxicity was grade d in the manner of Sulkowsky et al. ( 2000 ) , who used a scale modified from that of the AIDS Clinical Trials Group . RESULTS Hepatitis C virus and hepatitis B virus were detected in 10.1 % and 4.1 % of patients , respectively . The overall rate of severe hepatotoxicity ( grade 3 to 4 elevations in aspartate aminotransferase and /or alanine aminotransferase ) was 2 of 151 ( 1.3 % ) in patients prescribed EFV and 3 of 145 ( 2.1 % ) in patients prescribed NVP . Mild-to-moderate hepatotoxicity ( grade 2 elevation ) was observed in 6.0 % ( EFV ) and 3.4 % ( NVP ) of patients . Incidence of mild-to-moderate and severe hepatotoxicity did not differ significantly between the study groups . 3 of 14 patients ( 2.1 % ) with grade 2 elevation of liver enzymes ( LEE ) and 4 of 5 patients ( 80 % ) with grade 3 to 4 LEE were symptomatic . Only risk factor for the development of mild-to-moderate hepatotoxicity was hepatitis C coinfection . CONCLUSION Increases of liver enzymes during therapy with NVP or EFV are not unusual , but are mostly mild-to-moderate and asymptomatic . LEE occurs just as frequent in patients prescribed EFV as in patients prescribed NVP Background This study was aim ed at evaluating the seroprevalence and trend of blood-borne pathogens ( HIV , HCV , HBV , and Syphilis ) among asymptomatic adults at Akwatia during a four-year period ( 2013–2016 ) . Material s and Methods The study was a retrospective analysis of secondary data of blood donors who visited the hospital from January 2013 to December 2016 . Archival data from 11,436 prospect i ve donors was extracted . Data included age , sex , and place of residence as well as results of infectious markers ( HIV , HBV , HCV , and Syphilis ) . Results The prevalence of blood-borne pathogens in the donor population was 4.06 % , 7.23 % , 5.81 % , and 10.42 % for HIV , HBV , HCV , and Syphilis infections , respectively . A significant decline in HBV and HCV infections was observed in the general donor population and across genders . HIV infection rate remained steady while Syphilis infections recorded a significantly increasing trend , peaking in the year 2015 ( 14.20 % ) . Age stratification in HBV infection was significant , peaking among age group 40–49 years ( 8.82 % ) . Conclusion Asymptomatic blood-borne pathogen burden was high among the adult population in Akwatia . Gender variations in HBV , HCV , and Syphilis infections in the cumulative four-year burden were observed . Awareness needs to be created , especially in the older generation BACKGROUND Sexually transmitted infections ( STIs ) are major health problems in developing countries where access to adequate diagnostic and treatment facilities are very limited . Ethiopia is amongst the countries where STIs are highly prevalent . However , information on seroprevalence of STIs among antenatal care ( ANC ) attendees is very scarce in the country . OBJECTIVE To determine the seroprevalence of HIV , HBV , HCV and syphilitic infections . METHODS A prospect i ve cross-sectional study was performed involving pregnant women attending antenatal clinic at Gondar Health Center from August 01 to December 30 , 2006 . Data on socio-demographic characteristics and sexual behaviors were collected using structured question naire . Blood was collected and serum was tested for the presence of HBsAg , antibodies to HIV , HCV and Treponema pallidum . RESULTS Among the 480 ANC attendees , the seroprevalences of HIV , HBV ( HBVsAg ) , HCV and syphilis were 11.9 % , 7.3 % , 1.3 % and 2.3 % , respectively . Higher seroprevalence of HIV was observed in age groups of 20 - 29 ( 13 % ) and 30 - 39 ( 12.1 % ) years . ANC attendees from Gondar town had higher seropositivity rate ( 12.6 % ) than those who came from outside Gondar ( 9.4 % ) . Serostatus of HIV was significantly correlated with knowledge of the ANC attendees on curability of HIV infection by treatment ( OR , 95 % CI : 0.40 , 0.19 - 0.82 , P = 0.012 ) and transmission of HIV by blood and blood products ( OR , 95 % CI : 2.10 , 1.21 - 3.68 , P = 0.009 ) . Co-infection of HBV , HCV and Treponema pallidum with HIV was observed but no statistical association was noted . CONCLUSION The results indicate relatively declined prevalence of multiple STIs in Gondar , and call for the need to strengthen the exiting health education program & screening of all pregnant women for HIV , HBV , HCV infections and syphilis to prevent transmission of the infections in women , their children and the population at large Around the world , there has been an increase in epidemiological surveillance of bloodborne infections . This is due to the fact that blood transfusion has served as a prominent route for transmission of such infections ; however , prevalence varies from one region to another . In order to prevent the transmission of these infections through blood transfusion , plans , policies and procedures have been put in place to screen prospect i ve blood donors in Nigeria . Although a variety of agents are transmissible through blood , hepatitis B ( HBV ) , hepatitis C ( HCV ) and human immunodeficiency virus ( HIV ) rank high on the list of frequently screened infectious agents because of their pathological course . Routine screening of blood donors for HBV and HIV is now carried out by most blood banks in Nigeria , but only a few centres routinely screen for HCV . In West Africa , prevalence of HCV among blood donors is 1.1–6.7 % , but there is no national policy for screening donors for HCV in Nigeria . The aim of this study is to estimate the seroprevalence and possible co-infections of HBV , HCV and HIV among prospect i ve blood donors attending the authors ’ institution . A total of 2496 asymptomatic prospect i ve blood donors ( voluntary and replacement ) attending the blood bank at Ladoke Akintola University Teaching Hospital between July 2004 and December 2005 were recruited to the study . Informed consent was obtained from each participant . A 5 mL clotted sample of venous blood was obtained from each donor , and the serum was stored at –20 ̊C until tested . Hepatitis A surface antigen ( HBsAg ) was detected by a s and wich immunoassay test strip ( Clinotech Diagnostics , Canada ) in which monoclonal and polyclonal antibodies are employed . The strip was dipped into the serum for 2–3 sec and read for visibility of one test line and one procedural control line after 10–20 min . The limit of sensitivity provided by the manufacturer was 5 ng/mL. Antibody to HCV was detected using a recombinant double antigen s and wich immunoassay ( Clinotech Diagnostics , Canada ) , following a procedure similar to that adopted for HBsAg . Antibodies to HIV-1 , HIV-2 and HIV-1 O subtypes were detected using the HIV1/2/O Tri-line HIV rapid test device , which is a qualitative immunochromatographic assay employing a membrane strip precoated with recombinant HIV antigens in the test lines , T1 ( HIV-1 and subtype O ) and T2 ( HIV-2 ) regions , and a procedural control line C ( relative sensitivity : 99.9 % , relative specificity : 99.6 % , relative accuracy : 99.7 % , correlation with HIV enzyme-linked immunosorbent assay [ ELISA ] : 99.7 % ) . All 2496 prospect i ve donors , comprising 1988 ( 79.6 % ) males and 508 ( 20.4 % ) females ( male : female ratio 3.9:1 ) in the study were screened . Age ranged from 18 to 65 years , and the majority ( 68.3 % ) were in the 21 - 40 age group ( Table 1 ) . Table 2 shows the prevalence of HBV , HCV and HIV infection among the group of blood donors studied , and Table 3 shows the age/gender distribution . No gender differences were seen in the distribution of single HBV , HCV and HIV infections ( odds ratio [ OR ] 0.7986 , 1.219 and 1.023 , respectively ) . Apparently healthy blood donors have been a constant source of transfusion-related infection , especially in the developing world where facilities for screening blood before transfusion are inadequate . In the present study , the prevalence of 19.9 % for HBsAg , a marker of chronic HBV infection is high when compared to values reported from other regions of Nigeria and from other countries around the world . However , the level reported here is less than the 21.3 % reported in Ibadan , which is in the same geographical zone . This indicates that there is a high prevalence of HBV infection in south-west Nigeria , which may be due to the socio-cultural practice s reported by Otegbayo et al. Hepatitis C virus is now the most common bloodborne infection in the USA and is a leading cause of chronic hepatitis , cirrhosis and hepatocellular carcinoma . However , few blood banks in Nigeria screen routinely for HCV , and there are no national records of HCV seroprevalence , although a prevalence rate of 1.28 % among blood donors has been reported . In West Africa , HCV seroprevalence of 1.1–6.7 % has been reported , and the 6.4 % reported in the present study is consistent with that reported in other tropical African countries , but is higher than rates reported in the Middle East , Asia , Europe and the USA . Factors responsible for the transmission of HBV also aid transmission of HCV , hence dual infection is not uncommon , especially in frequently transfused patients and in injected drug users . However , a dual infection rate of 1.6 % reported in the present study is lower than rates reported among injected drug users or haemodialysis patients . Currently , injected drug abuse is not a problem in Nigeria and therefore is not a major factor involved in the transmission of HBV or HCV in this environment . The HIV seroprevalence rate of 3.2 % among donors Objectives : Nitrite inhalants ( poppers ) are commonly used recreational drugs among MSM and were previously associated with elevated rates of high-risk sexual behavior , HIV and human herpesvirus type 8 ( HHV-8 ) seroconversion , and transient immunosuppressive effects in experimental models . Whether long-term popper use is associated with cancer risk among MSM in the HAART era is unclear . Design : Prospect i ve cohort study of cancer risk in 3223 HIV-infected and uninfected MSM in the Multicenter AIDS Cohort Study from 1996–2010 . Methods : Poisson regression models were used to examine the association between heavy popper use ( defined as daily or weekly use for at least 1 year ) and risk of individual cancers or composite category of virus-associated cancers . Results : Among all participants , heavy popper use was not associated with increased risk of any individual cancers . Among HIV-uninfected men aged 50–70 , heavy popper use was associated with increased risk of virus-associated cancer with causes linked to human papillomavirus , HHV-8 , and Epstein – Barr virus in models adjusted for demographics , number of sexual partners , immunological parameters ( CD4 + cell counts or CD4+/CD8 + ratios ) , and hepatitis B and C viruses [ incidence rate ratio ( IRR ) , 95 % confidence interval ( CI ) 3.24 , 1.05–9.96 ] , or sexually transmitted infections ( IRR 3.03 , 95 % CI , 1.01–9.09 ) , as was cumulative use over a 5-year period ( IRR 1.012 , 95 % CI 1.003–1.021 ; P = 0.007 ) . There was no significant association between heavy popper use and virus-associated cancer in HIV-infected men . Conclusions : Long-term heavy popper use is associated with elevated risk of some virus-associated cancers with causes related to human papillomavirus , HHV-8 , and Epstein – Barr virus infections in older HIV-uninfected MSM independent of sexual behavior and immunological parameters RATIONALE Little is known about the incidence of isoniazid-associated hepatitis in HIV-infected Africans who receive both isoniazid preventive therapy ( IPT ) and antiretroviral therapy ( ART ) . OBJECTIVES To assess the rate of and risk factors for isoniazid (INH)-associated hepatitis in persons living with HIV ( PLWH ) during IPT . METHODS PLWH recruited for a clinical trial received 6 months of open-label , daily , self-administered INH at public health clinics . At screening PLWH were excluded if they had any cough , weight loss , night sweats , or other illness . Alcohol abuse was defined as meeting any CAGE criterion . INH-associated hepatitis ( INH-hepatitis ) was defined as having either alanine or aspartate aminotransferase greater than 5.0 times the upper limit of normal regardless of symptoms when INH was not excluded as the cause . MEASUREMENTS AND MAIN RESULTS Of 1,995 PLWH enrolled between 2004 and 2006 , 1,762 adhered to at least 4 months of IPT and were analyzed . Nineteen ( 1.1 % ) developed hepatitis probably or possibly associated with INH including one death at month 6 ; 14 of 19 ( 74 % ) occurred in months 1 - 3 . Antiretroviral therapy ( ART ) was received by 480 participants but was not statistically associated with INH-hepatitis ( relative risk [ RR ] , 1.56 ; 95 % confidence intervals [ CI ] , 0.62 - 3.9 ) ; those receiving nevirapine had a higher rate ( 2.0 % ) than those receiving efavirenz ( 0.9 % ; P = 0.34 ) . Although alcohol use did not reach significance ( RR , 1.42 ; 95 % CI , 0.57 - 3.51 ) , meeting at least one CAGE criterion approached statistical significance ( RR , 2.37 ; 95 % CI , 0.96 - 5.84 ) . Neither age greater than 35 years nor the presence of hepatitis B virus core antibody was associated with INH-hepatitis . CONCLUSIONS The observed rates of INH-hepatitis were similar to published data . Six months of IPT , which is recommended by the World Health Organization , was relatively safe in this , the largest cohort of African PLWH . Clinical trial registered with www . clinical trials.gov ( NCT 00164281 ) |
13,429 | 21,154,370 | There was no significant differences in the patient survival , graft rejection , re-transplantation , or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes .
Life-threatening adverse events were not reported in either group in any of the comparisons .
There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or re-transplantation . | BACKGROUND It is not clear whether prophylactic antiviral therapy is indicated in patients undergoing liver transplantation for chronic decompensated hepatitis C virus ( HCV ) infection .
OBJECTIVES To compare the benefits and harms of different prophylactic anti-viral therapies for patients undergoing liver transplantation for chronic HCV infection . | Hepatitis C is the most common indication for liver transplantation ( LT ) in the United States . Recurrence of hepatitis C virus ( HCV ) infection post-LT remains a problem for which there is no completely satisfactory treatment . The aim of the present study is to evaluate mycophenolate mofetil ( MMF ) , which has both immunosuppressive and antiviral properties , to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival . Between August 1995 and May 1998 , a total of 106 patients who were HCV positive before LT were r and omized to tacrolimus ( TAC ) and prednisone versus TAC , prednisone , and MMF therapy . The rate of recurrence of HCV , patient and graft survival , incidences of rejection , and histological findings were examined . Fifty six patients were r and omized to TAC and steroid therapy ( double [ D ] drug ; group D ) , and 50 patients were r and omized to TAC , steroid , and MMF therapy ( triple [ T ] drug ; group T ) . Liver biopsies were performed when liver function was abnormal ; protocol liver biopsies were not performed . Mean follow-up was 4.3 + /- 0.8 years . Actuarial patient survivals at 4 years were 72.6 % in group D and 73.8 % in group T ( P = not significant ) . Actuarial graft survivals at 4 years were 65.6 % in group D and 65.4 % in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV . One patient in each group died of recurrent HCV without re-LT . Twenty-six patients in group D ( 46.4 % ) and 23 patients in group T ( 46.0 % ) showed signs of recurrent HCV . Mean hepatitis activity index ( HAI ) scores were 7.4 + /- 2.7 in group D and 7.0 + /- 3.4 in group T , and mean fibrosis scores were 2.9 + /- 1.7 in group D and 2.6 + /- 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period . None of these values reached statistical significance . Rates of HCV recurrence , graft loss or death from recurrent HCV , and 4-year actuarial patient and graft survival were not different between the groups . In liver transplant recipients with HCV , MMF has no impact on patient survival , graft survival , rejection , or rate of HCV recurrence based on biochemical changes and histological findings . In addition , there was no difference in HAI or fibrosis score between the two groups . Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting C IRRHOSIS caused by hepatitis C virus ( HCV ) accounts for at least 30 % of all liver transplants ( OLT ) currently performed in adults . ’ Good survival of patients with such an indication has been described , even though the reappearance of viral genome ( HCV-RNA ) occurs in more than 90 % of patients during the first year after transplantation . ‘ . ’ The course of recurrent HCV graft infection is generally benign . Nevertheless , some concerns about the long-term outcome of the disease have arisen since at least 50 % of HCV-RNA positive patients develop chronic hepatitis within two years’,2 and 35 % of livers are seriuosly injured ( chronic active hepatitis and cirrhosis ) 5 years after transplantation.4 In the present study , a therapeutic attempt to prevent recurrent HCV infection was undertaken in a group of HCV-RNA positive transplant recipients , using a combination of interferon and ribavirin early after OLT . The preliminary results of this pilot experience , the first of its kind , are reported herein OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials The aim of the study was to observe the frequency of neutropenia during Pegylated Interferon/Ribavirin therapy in patient with chronic hepatitis C ; to compare the efficacy of two strategies of management of neutropenia -- with Interferon dose modification and with Neupogen administration ; to compare the effectiveness rate of sustained viral response ( SVR ) in patients with Pegylated Interferon dose modification and in patients treated by using granulocyte colony-stimulating factor G-CSF-filgrastim . ( Neupogen ) . Study enrolled 47 patients with chronic active hepatitis C , aged 23 - 64 . ( 38 male and 9 female ) . All patients had HCV genotype 1b . Significant neurtopenia ( ANC<750 mm3 ) and severe neurtopenia ( ANC<500 mm3 ) developed in 41 of 47 patients ( 87 % ) . 41 patients with neurtopenia were r and omized into two groups . The first group--22 patients who received granulocyte colony-stimulating factor ( G-CSF , or filgrastim ) 300 mcg s/c weekly for correction of neutropenia and the second group--19 patients treated either with Interferon dose reduction or temporarily inhibit of Interferon treatment . In all 22 patients of the first group neutropenia was normalized without reduction and /or inhibit of Pegylated interferon . Neupogen was well tolerated and in all 22 patients the improvement of quality of life ( QOL ) was observed . It was concluded that dose reduction or temporary inhibit of Pegylated Interferon in the second group negatively acts on antiviral treatment response in patients with HCV genotype 1 . In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose ( without reduction ) . Neupogen has the potential to improve adherence rates , which may in turn improve SVR Ischemic preconditioning ( IPC ) has the potential to decrease graft injury and morbidity after liver transplantation . We prospect ively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers r and omized 1:1 to st and ard ( STD ) recovery ( N = 28 ) or IPC ( N = 34 ) . Safety was assessed by measurement of heart rate , blood pressure , and visual inspection of abdominal organs during recovery , and efficacy by recipient aminotransferases ( aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] , both measured in U/L ) , total bilirubin , and international normalized ratio of prothrombin time ( INR ) after transplantation . IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion . Recipient median AST , median ALT , and mean INR , in STD vs. IPC were as follows : day 1 AST 696 vs. 841 U/L ; day 3 AST 183 vs. 183 U/L ; day 1 ALT 444 vs. 764 U/L ; day 3 ALT 421 vs. 463 U/L ; day 1 INR 1.7 + /- .4 vs. 2.0 + /- .8 ; and day 3 INR 1.3 + /- .2 vs. 1.4 + /- .3 ; all P > .05 . No instances of nonfunction occurred . The 6-month graft and patient survival STD vs. IPC were 82 vs. 91 % and median hospital stay was 10 vs. 8 days ; both P > .05 . In conclusion , deceased donor livers tolerated 5 minutes of hilar clamping well , but IPC did not decrease graft injury . Further trials with longer periods of preconditioning such as 10 minutes are needed A r and omized , double-blind , dose-escalation study evaluated the safety and efficacy of hepatitis C virus (HCV)-Ab(XTL)68 , a neutralizing , high-affinity , fully human , anti-E2 monoclonal antibody , in 24 HCV-positive patients undergoing liver transplantation . HCV-Ab(XTL)68 or placebo was administered at doses from 20 - 240 mg as 2 - 4 infusions during the first 24 hours after transplantation , followed by daily infusions for 6 days , weekly infusions for 3 weeks , and either 2 or 4 weekly infusions for 8 weeks . Serum concentrations of total anti-E2 obtained during daily infusions of 120 - 240 mg HCV-Ab(XTL)68 were 50 - 200 microg/mL above concentrations in the placebo group . Median serum concentration of HCV RNA dropped below baseline in all groups immediately after transplantation . On day 2 , median change from baseline in HCV RNA was -1.8 and -2.4 log in the 120-mg and 240-mg groups , respectively , compared with -1.5 log with placebo . The difference was lost after day 7 when the dosing frequency was reduced . The coincidence of increases in anti-E2 with decreases in HCV RNA concentration indicate that the dose-related changes in HCV RNA concentration were a result of HCV-Ab(XTL)68 administration in the 120- and 240-mg groups . The overall incidence of nonfatal serious adverse events was higher with placebo ( 60 % ) vs. all active treatments combined ( 42 % ) . In conclusion , HCV-Ab(XTL)68 may decrease serum concentrations of HCV RNA in patients after liver transplantation . Studies evaluating more frequent daily dosing at doses > 120 mg are necessary to investigate sustained viral suppression in this population The effect of ischemic preconditioning ( IPC ) in orthotopic liver transplantation ( OLT ) has not yet been clarified . We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors r and omly assigned to receive ( IPC+ group , n = 23 ) or not ( IPC- group , n = 24 ) IPC ( 10-min ischemia + 15-min reperfusion ) . In 10 cases in the IPC+ group and in 12 in the IPC- group , the expression of inducible nitric oxide synthase ( iNOS ) , neutrophil infiltration , and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies . Median aspartate aminotransferase ( AST ) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 ( 398 vs. 1,234 U/L , P = 0.002 ; and 283 vs. 685 U/L , P = 0.009 ) . Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1 , 2 , and 3 ( 333 vs. 934 U/L , P = 0.016 ; 492 vs. 1,040 U/L , P = 0.008 ; and 386 vs. 735 U/L , P = 0.022 ) . Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks , incidence of graft nonfunction and graft and patient survival rates were similar between groups . Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups . iNOS was higher postreperfusion vs. prereperfusion in the IPC- group ( P = 0.008 ) . Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups ( IPC+ , P = 0.007 ; IPC- , P = 0.003 ) . Prereperfusion and postreperfusion apoptosis was minimal in both groups . In conclusion , IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis , but it showed no clinical benefits 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 . The aim of the 18 months follow up study was to assess the frequency of anemia during IFN/RBV therapy in patients with chronic hepatitis C ; to manage anemia either with recombinant human erythropoietin (rHuEPO)--epoetin alpha or with RBV dose reduction and to compare the rate of SVR in patients with RBV dose reduction and with administration of epoetin alpha . Study enrolled 61 patients with chronic active hepatitis C aged 33 - 61 years . All patients had HCV genotype 1b . Out of them 41 were male and 20 female . Anemia ( Hb < 10 or > 2 g/dL Hgb drop from baseline ) developed in 41 patients out of 61 ( 67,21 % ) during the therapy . These 41 patients were r and omized into two groups : 21 patients who received 40 000 IU epoetin alpha weekly ( I group ) and 20 patients in whom for managing anemia we used st and ard of care ( SOC ) or RBV dose reductions from 1000/1200 to 800/600 mg ( II group ) . In all 21 patients of the I group the Hb level normalized without reduction of RBV dose . In this group of patients SVR at 6 months after completion of full course of treatment was achieved in 17 ( 66 % ) patients . Improvement of quality of life ( QOL ) was observed in all 21 patients . Out of 20 patients of II group with st and ard of care ( SOC ) 5 patients developed symptomatic anemia with fatigue and dyspnoea ; RBV was stopped temporarily . In 15 patients RBV dose was reduced from 1200 mg to 600 mg for correction of anemia . In this group of patients SVR at 6 months after treatment completion was achieved in 7 ( 25 % ) patients . Lower RBV doses yield a lower treatment response in patients with HCV genotype 1 . In anemic HCV-infected patients on RBV/PEG-IFN therapy , EPO maintains RBV dose and significantly improves anemia and QOL . EPO has the potential to improve adherence rate , which may in turn improve SVR Preliminary studies suggest preemptive anti‐HCV therapy in liver transplant recipients may enhance the rates of viral clearance , but the applicability and tolerability of preemptive therapy has not been evaluated in a contemporary cohort . In this r and omized study , the safety and tolerability of preemptive st and ard ( IFN ) or pegylated ( peg‐IFN ) interferon alfa‐2b ( 3 MU thrice weekly or 1.5 μg/kg weekly ) , or IFN/peg‐IFN plus ribavirin ( 600 mg increased to 1.0–1.2 g daily ) was initiated 2–6 weeks post‐transplantation and continued for a total of 48 weeks . Only 51 ( 41 % ) of 124 transplant recipients were eligible for preemptive treatment ; eligible patients had lower model for end‐stage liver disease ( MELD ) and Childs‐Pugh scores pre‐transplantation and were more frequently live donor transplant recipients than ineligible patients . Dose reductions and discontinuations were required in 85 % and 37 % of patients , respectively , and 27 % experienced serious adverse events . Growth factor ( GF ) use ( erythropoietin and GCSF ) in the latter half of the study did not significantly affect the frequency of dose reductions . Only 15 % of patients were able to achieve full‐dose treatment during treatment . End‐of‐treatment and sustained virological responses were 13.6 % and 9.1 % , respectively , with most responders in the combination therapy group . We conclude that preemptive antiviral therapy is applicable to only a portion of transplant recipients , with ‘ sicker ’ patients less likely to be managed by this approach . Living donor liver transplant recipients were more frequently eligible for treatment than deceased donor recipients . Virological response rates are low , likely related to the poor tolerability of therapy and the lack of achievement of target drug doses . Future studies should focus on alternative dosing schedules with more aggressive use of adjuvant therapies , including GFs Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection . Steroids also have been held responsible for increased infections , posttransplantation diabetes , and recurrent hepatitis after orthotopic liver transplantation ( OLT ) . The purpose of this ongoing prospect i ve r and omized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin ( RATG ) . This is the first report of a prospect i ve r and omized trial in OLT achieving complete absence of steroids . Seventy-one adult patients were prospect ively r and omized to administration of RATG or steroids . Thirty-six patients were r and omized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously ( IV ) beginning during the anhepatic phase . No steroids were administered . Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1 . Thirty-five patients were r and omized to the administration of methylprednisolone , which had been our st and ard immunosuppressive protocol . These patients were administered methylprednisolone , 1,000 mg IV , initiated during the anhepatic phase and followed by steroid taper . Maintenance immunosuppression consisted of tacrolimus and mycophenolate , with or without prednisone . Three patients died in each group , for an overall survival rate of 91 % in each group . One patient in each group required re-OLT , for a graft survival rate of 89 % in each group . Seven patients administered RATG had biopsy-proven rejection ( 20.5 % ) , all of whom were successfully treated by increasing tacrolimus doses . Eleven patients administered steroid had biopsy-proven rejection ( 32 % ) , 7 ( 64 % ) of whom required additional steroids for treatment , whereas 4 patients ( 36 % ) were successfully treated by increasing tacrolimus doses . The incidence of rejection was not statistically significant ; however , there was a significant difference in the incidence of steroid-requiring rejection ( P = .01 ) . The incidence of recurrent hepatitis C was 50 % in RATG patients and 71 % in steroid patients ( P = not significant ) . The incidence and severity of infectious complications were slightly lower in RATG patients , accounted for by a greater incidence of cytomegalovirus ( CMV ) infection in the steroid patients . RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate , decreased incidence of post-OLT diabetes and recurrent hepatitis C , and decreased CMV infection . This prospect i ve r and omized trial gives encouraging support that steroids can be safely eliminated in OLT Recurrence of hepatitis C virus ( HCV ) following liver transplantation ( LT ) is universal . A subset of these patients develop advanced fibrosis and cirrhosis and it is believed that this leads to increased posttransplantation mortality . The specific aims of this study were to determine the incidence of advanced fibrosis and those factors associated with this process , and to evaluate causes for mortality in patients with recurrent HCV . A total of 227 patients who underwent LT with chronic HCV were monitored prospect ively . The mean age of this group at LT was 49.5 yr ; 76 % were male and 85 % were Caucasian . Fibrosis progression was monitored by protocol liver biopsy , initially performed 6 months after LT and then at 6- to 24-month intervals . Advanced fibrosis , defined as the bridging fibrosis or cirrhosis , developed in 1 % , 11 % , 25 % , and 41 % of patients after 1 , 3 , 5 , and 6 - 10 yr , respectively . Acute cellular rejection hepatic steatosis , a persistent elevation in serum alanine aminotransferase and donor-race were associated with the development of advanced fibrosis . In contrast , the development of advanced fibrosis was not affected by the use of interferon prior to undergoing LT , cytomegalovirus disease , or donor age . A total of 60 patients ( 26 % ) died over 15 yr of follow-up . Although graft failure accounted for 45 % of deaths in patients with advanced fibrosis , this represented only 8 % of all deaths in patients with recurrent HCV . Sepsis was the most common cause of death and this was observed with similar frequency in patients who developed advanced fibrosis ( 45 % ) and in those with less advanced fibrosis ( 47 % ) . In conclusion , approximately 41 % of patients with recurrent HCV developed advanced fibrosis 6 - 10 yr after LT . However , complications associated with sepsis , not recurrent cirrhosis , was the most common cause of death in patients with recurrent HCV and this was similar in patients with or without advanced fibrosis Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis , liver failure , and death . In patients undergoing liver transplantation for hepatitis C , we assessed the efficacy of interferon alfa‐2b ( IFN ) in preventing recurrent hepatitis . We r and omized 86 patients to either an IFN group ( 3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year ) or a control ( no IFN ) group . Recurrence , the primary end point , was diagnosed on biopsy performed at 1 year or for abnormal biochemistries . HCV RNA levels were measured by branched‐chain DNA ( bcDNA ) assay and arbitrarily defined as low , moderate , or high ( < 10 × 105 , 10‐100 × 105 , or > 100 × 105Eq/mL , respectively ) . Data on 30 IFN patients and 41 no‐IFN patients who survived ≥3 months were review ed . Mean follow‐up was 669 ± 228 days for IFN patients and 594 ± 254 days for no‐IFN patients . IFN patients were less likely to develop recurrent hepatitis ( 8 IFN vs. 22 no‐IFN patients , P= .017 , log rank analysis ) . IFN and 1‐month HCV RNA level were independent predictors of recurrence . IFN reduced the risk of recurrence by a factor of 0.4 ( P= .04 , Cox proportional hazards model ) ; HCV RNA level > 100 × 105 Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 ( P = .01 ) . Low , moderate , and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients ( P = .05 at 1 month and P = .003 at 3 months ) but not in untreated patients ( P = .28 at 1 month and P = .25 at 3 months ) . In patients with two or more rejections , the risk of recurrence was increased by a factor of 2.17 ( P = .05 ) . On 47 1‐year biopsies ( 24 IFN ; 23 no IFN ) , piecemeal necrosis was more common in untreated patients ( P < .02 ) . One‐ and 2‐year patient survival , respectively , was 96 % and 96 % with IFN and 91.2 % and 87.2 % without ( P = NS ) . Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant . Although IFN was most effective in patients with low HCV RNA levels , we also noted an effect in patients with moderate levels . IFN did not prevent viremia , suggesting that it may work through alternative mechanisms There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation ( OLT ) . We therefore performed two r and omized , controlled trials -- a prophylaxis trial and a treatment trial -- to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT . The prophylaxis trial enrolled 54 patients within 3 weeks after OLT , and the treatment trial enrolled 67 patients 6 to 60 months after OLT . In each trial , patients were r and omized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter . Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls . However , only 2 treated patients in the prophylaxis trial ( 8 % ) and 3 in the treatment trial ( 12 % ) achieved a sustained virological response . In the prophylaxis trial , 8 patients ( 31 % ) in the peginterferon alfa-2a group and 9 ( 32 % ) in the untreated group were withdrawn prematurely ; whereas in the treatment trial , 10 patients ( 30 % ) in the peginterferon alfa-2a group and 6 ( 19 % ) in the untreated group were withdrawn prematurely . The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis ( 12 % vs. 21 % ; P = .5 ) and treatment ( 12 % vs. 0 % ; P = .1 ) trials . In conclusion , peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting . R and omized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT Chronic hepatitis C is the most common indication for liver transplantation , but viral recurrence is universal and progressive graft injury occurs in most recipients . Our aim was to assess the safety , pharmacokinetics ( PK ) , and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product ( HCIG ) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter , r and omized , open-label , controlled trial conducted at 4 transplant centers in the United States . A total of 18 patients with chronic hepatitis C , who underwent liver transplantation , were r and omized to receive low-dose HCIG ( 75 mg/kg ) or high-dose HCIG ( 200 mg/kg ) , or no treatment . A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients . Hepatitis C virus levels , liver enzymes , and liver biopsies were obtained serially throughout the study period . PK profiles of HCV antibodies were determined on days 4 , 10 , and 98 . HCIG infusions were safe and tolerated . The infusion rate could not be maximized because of symptoms for 18 % to 30 % of the doses . The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged . In the high-dose group , serum alanine aminotransferase ( ALT ) levels normalized in most subjects and no patient developed hepatic fibrosis . However , serum HCV RNA levels were not suppressed at either dose . In conclusion , HCIG , an anti-HCV enriched immune globulin product , appears to be safe in patients with chronic hepatitis C undergoing liver transplantation . Further studies are required to determine whether the drug has beneficial effects in this group of patients BACKGROUND & AIMS Combination therapy with interferon alpha ( IFN-alpha ) and ribavirin ( RBV ) or pegylated IFN-alpha (PEG-IFN-alpha)/RBV for chronic hepatitis C virus ( HCV ) infection often causes anemia , prompting RBV dose reduction/discontinuation . This study assessed whether epoetin alfa could maintain RBV dose , improve quality of life ( QOL ) , and increase hemoglobin ( Hb ) in anemic HCV-infected patients . METHODS HCV-infected patients ( n = 185 ) on combination therapy who developed anemia ( Hb < or = 12 g/dL ) were r and omized into a U. S. multicenter , placebo-controlled , clinical trial of epoetin alfa , 40,000 U subcutaneously , once weekly vs. matching placebo . The study design used an 8-week , double-blind phase ( DBP ) followed by an 8-week , open-label phase ( OLP ) , in which placebo patients were crossed over to epoetin alfa . RESULTS At the end of the DBP , RBV doses were maintained in 88 % of patients receiving epoetin alfa vs. 60 % of patients receiving placebo ( P < 0.001 ) . Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment ( LASA ) and on 7 of the 8 domains of the Short Form-36 , version 2 ( SF-36v2 ) . Mean Hb increased by 2.2 + /- 1.3 g/dL ( epoetin alfa ) and by 0.1 + /- 1.0 g/dL ( placebo ) in the DBP ( P < 0.001 ) . Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP . Epoetin alfa was well tolerated ; the most common adverse effects were headache and nausea . CONCLUSIONS Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy |
13,430 | 30,286,948 | According to multiple r and omized trials , combining and rogen deprivation therapy ( ADT ) with external-beam radiotherapy ( EBRT ) outperforms EBRT alone for both relapse-free and overall survival .
Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone .
GETUG 12 , RTOG 0521 , and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT , although mature metastasis-free survival data are still pending .
Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy .
In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT , its role after prostatectomy remains unclear especially in pN0 patients .
Adding docetaxel to EBRT-ADT improves relapse-free survival , with immature results on overall survival . | CONTEXT Systemic therapies , combined with local treatment for high-risk prostate cancer , are recommended by the international guidelines for specific subgroups of patients ; however , for many of the clinical scenarios , it remains a research field .
OBJECTIVE To perform a systematic review , and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer .
The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated , with lack of data from phase 3 trials in pN0 patients . | Therapeutic strategy remains unclear with no clear consensus for men with high-risk prostate cancer ( PCa ) after radical prostatectomy . We aim ed to evaluate into a prospect i ve r and omized trial the effectiveness and feasibility of adjuvant weekly paclitaxel combined with and rogen deprivation therapy ( ADT ) in these patients . A total of 47 patients with high-risk PCa were r and omized 6 weeks after radical prostatectomy : ADT alone versus combination of ADT and weekly paclitaxel . Toxicity , quality -of-life and functional results were compared between the two arms . All 23 patients completed eight cycles of paclitaxel . Toxicity was predominantly of grade 1–2 severity . There were no differences in EORTC QLQ-C30 scores between the two groups and between baseline and last assessment at 24 months after surgery . Urinary continence was complete at 1 year after surgery for all patients and no significant differences were noted at each assessment between the two groups . The interim analysis of this trial confirms the feasibility of weekly paclitaxel in combination with ADT in men at high-risk PCa with curative intent . This adjuvant combined therapy does not alter quality -of-life and continence recovery after surgery plus ADT . A larger cohort is awaited to determine the oncological outcomes of this strategy Treatment of high‐risk localized prostate cancer remains inadequate . The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy Background The optimal management of high-risk prostate cancer remains uncertain . In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer . Methods This was a prospect i ve phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy , concurrent intensified-dose docetaxel-based chemotherapy and long-term and rogen deprivation therapy . Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0 . Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method . Results Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23 % and 20 % of patients , and grade 3 in 9 % and 3 % of patients , respectively . Acute blood/bone marrow toxicity was grade 2 in 20 % of patients . No acute grade ≥4 toxicity was observed . Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9 % of patients each . No late grade ≥3 toxicity was observed . Median follow-up was 63 months ( interquartile range 31–79 ) . Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55 % ( 95 % confidence interval , 35 - 75 % ) and 70 % ( 95 % confidence interval , 52 - 88 % ) , respectively . Conclusions In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer , toxicity was acceptably low and mid-term oncological outcome was good . This treatment paradigm , thus , may warrant further evaluation in phase III r and omized trials PURPOSE Trial RTOG 9202 was a phase 3 r and omized trial design ed to determine the optimal duration of and rogen deprivation therapy ( ADT ) when combined with definitive radiation therapy ( RT ) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate . Long-term follow-up results of this study now available are relevant to the management of this disease . METHODS AND MATERIAL S Men ( N=1554 ) with adenocarcinoma of the prostate ( cT2c-T4 , N0-Nx ) with a prostate-specific antigen ( PSA ) < 150 ng/mL and no evidence of distant metastasis were r and omized ( June 1992 to April 1995 ) to short-term ADT ( STAD : 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month ) and definitive RT versus long-term ADT ( LTAD : STAD with definitive RT plus an additional 24 months of monthly goserelin ) . RESULTS Among 1520 protocol -eligible and evaluable patients , the median follow-up time for this analysis was 19.6 years . In analysis adjusted for prognostic covariates , LTAD improved disease-free survival ( 29 % relative reduction in failure rate , P<.0001 ) , local progression ( 46 % relative reduction , P=.02 ) , distant metastases ( 36 % relative reduction , P<.0001 ) , disease-specific survival ( 30 % relative reduction , P=.003 ) , and overall survival ( 12 % relative reduction , P=.03 ) . Other-cause mortality ( non-prostate cancer ) did not differ ( 5 % relative reduction , P=.48 ) . CONCLUSIONS LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the st and ard of care Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer : Evaluation of Drug Efficacy is a r and omized controlled trial using a multiarm , multistage , platform design . It recruits men with high-risk , locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy . We report survival data for two celecoxib (Cel)-containing comparisons , which stopped accrual early at interim analysis on the basis of failure-free survival . Patients and Methods St and ard of care ( SOC ) was hormone therapy continuously ( metastatic ) or for ≥ 2 years ( nonmetastatic ) ; prostate ( ± pelvic node ) radiotherapy was encouraged for men without metastases . Cel 400 mg was administered twice a day for 1 year . Zoledronic acid ( ZA ) 4 mg was administered for six 3-weekly cycles , then 4-weekly for 2 years . Stratified r and om assignment allocated patients 2:1:1 to SOC ( control ) , SOC + Cel , or SOC + ZA + Cel . The primary outcome measure was all-cause mortality . Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors . Results A total of 1,245 men were r and omly assigned ( Oct 2005 to April 2011 ) . Groups were balanced : median age , 65 years ; 61 % metastatic , 14 % N+/X M0 , 25 % N0M0 ; 94 % newly diagnosed ; median prostate-specific antigen , 66 ng/mL. Median follow-up was 69 months . Grade 3 to 5 adverse events were seen in 36 % SOC-only , 33 % SOC + Cel , and 32 % SOC + ZA + Cel patients . There were 303 control arm deaths ( 83 % prostate cancer ) , and median survival was 66 months . Compared with SOC , the adjusted hazard ratio was 0.98 ( 95 % CI , 0.80 to 1.20 ; P = .847 ; median survival , 70 months ) for SOC + Cel and 0.86 ( 95 % CI , 0.70 to 1.05 ; P = .130 ; median survival , 76 months ) for SOC + ZA + Cel . Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 ( 95 % CI , 0.62 to 0.98 ; P = .033 ) for SOC + ZA + Cel . Conclusion These data show no overall evidence of improved survival with Cel . Preplanned subgroup analyses provide hypotheses for future studies Study Type – Therapy ( phase 1 BACKGROUND This was a phase I study to find the maximum tolerable dose ( MTD ) of weekly docetaxel combined with high-dose intensity-modulated radiotherapy ( IMRT ) and and rogen deprivation therapy ( ADT ) . PATIENTS AND METHODS Men with localized high-risk prostate cancer ( HRPC ) were treated with weekly docetaxel at 10 to 30 mg/m(2 ) concurrent with IMRT of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles . ADT consisted of a gonadotropin-releasing hormone agonist ( GnRHa ) and bicalutamide beginning 2 months before and during chemoradiation . GnRHa was continued for 24 months . RESULTS Nineteen patients were enrolled . No dose-limiting toxicity ( DLT ) was seen with docetaxel doses up to 25 mg/m(2 ) . At the 30 mg/m(2 ) level , 2 of 4 patients experienced DLTs of both grade 3 fatigue and dyspepsia . At 41 months ' median follow-up , 2 patients had died--1 from metastatic prostate cancer and the other from heart failure . Two other patients experienced biochemical failure . One patient with bladder invasion at diagnosis experienced late grade 2 urinary hesitancy 9 months after completion of radiotherapy , requiring short-term intermittent catheterization . All patients had erectile dysfunction , but no late toxicities worse than grade 2 were identified . CONCLUSION Weekly docetaxel may be combined with high-dose IMRT and long-term ADT up to a MTD of 25 mg/m(2 ) . Acute toxicities and long-term side effects of this regimen were acceptable . Future studies evaluating the efficacy of docetaxel , ADT , and IMRT for localized HRPC should use a weekly dose of 25 mg/m(2 ) when limiting the irradiated volume to the prostate and seminal vesicles BACKGROUND Prostate cancer ( PC ) is the most commonly diagnosed noncutaneous malignancy in American men . PC , which exhibits a slow growth rate and multiple potential target epitopes , is an ideal c and i date for immunotherapy . GVAX for prostate cancer is a cellular immunotherapy , composed of PC-3 cells ( CG1940 ) and LNCaP cells ( CG8711 ) . Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor . Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease , we initiated a phase II trial of neoadjuvant docetaxel and GVAX . For the trial , the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy ( RP ) . METHODS Patients received docetaxel administered at a dose of 75 mg/m(2 ) every 3 weeks for 4 cycles . GVAX was administered 2 - 3 days after chemotherapy preoperatively for four courses of immunotherapy . The first dose of GVAX was a prime immunotherapy of 5 × 10(8 ) cells . The subsequent boost immunotherapies consisted of 3 × 10(8 ) cells . After RP , patients received an additional six courses of immunotherapy . Pathologic complete response , toxicity , and clinical response were assessed . The primary endpoint of the trial was a pathologic state of pT0 , which is defined as no evidence of cancer in the prostate . RESULTS Six patients completed neoadjuvant docetaxel and GVAX therapy . No serious drug-related adverse events were observed . Median change in prostate-specific antigen ( PSA ) following neoadjuvant therapy was 1.47 ng/ml . One patient did not undergo RP due to the discovery of positive lymph nodes during exploration . Of the five patients completing RP , four had a downstaging of their Gleason score . Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP . CONCLUSIONS Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC . No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted . These results justify further study of neoadjuvant immunotherapy To determine long‐term oncological outcomes of radical prostatectomy ( RP ) after neoadjuvant chemohormonal therapy ( CHT ) for clinical ly localised , high‐risk prostate cancer PURPOSE To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy ( 3D-CRT ) in patients with localized high-risk prostate cancer . METHODS AND MATERIAL S Fifty patients received estramustine , 600 mg/m(2 ) daily , and vinorelbine , 25 mg/m(2 ) , on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT ( total dose of 70.2 gray [ Gy ] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions ) . Additionally , patients received luteinizing hormone-releasing hormone analogs for 3 years . RESULTS All patients were evaluated for response and toxicity . Progression-free survival at 5 years was 72 % ( 95 % confidence interval [ CI ] : 52 - 86 ) . All patients who relapsed had only biochemical relapse . The most frequent severe toxicities were cystitis ( 16 % of patients ) , leucopenia ( 10 % of patients ) , diarrhea ( 10 % of patients ) , neutropenia ( 8 % of patients ) , and proctitis ( 8 % of patients ) . Six patients ( 12 % ) did not complete study treatment due to the patient 's decision ( n = 1 ) and to adverse events such as hepatotoxicity , proctitis , paralytic ileus , and acute myocardial infa rct ion . CONCLUSIONS Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer . A r and omized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and and rogen ablation Background : Radical prostatectomy ( RP ) has limited cancer control potential for the patient with high-risk prostate cancer ( Pca ) . We prospect ively examined the efficacy and safety of neoadjuvant therapy with luteinizing hormone-releasing hormone ( LHRH ) agonist + low-dose estramustine phosphate ( EMP ) ( LHRH+EMP ) followed by RP . Methods : High-risk Pca was defined by the D’Amico stratification system . A total of 142 patients with high-risk Pca were enrolled in this trial from September 2005 to March 2011 . The LHRH+EMP therapy included administration of LHRH agonist and 280 mg day–1 EMP for 6 months before RP . Pathological cancer-free ( pT0 ) rate on the surgical specimen was the primary end point . Secondary end points were PSA-free survival and toxicity . Results : The average patient age was 67.4 years ( interquartile range ( IQR ) 72 , 65 ) and the median initial PSA level was 14.80 ng ml–1 ( IQR 26.22 , 7.13 ) . The median Gleason score was 9 ( IQR 9 , 7 ) and 97 patients ( 68.3 % ) had clinical stage T2c or T3 . All patients completed 6 months of LHRH+EMP neoadjuvant therapy with no delays in RP . Seven patients ( 4.9 % ) achieved pT0 . Surgical margins were negative in 125 patients ( 87.0 % ) . At a median follow-up period of 34.9 months , PSA-free survival was 84.3 % . No serious adverse events were reported during the study and there were no toxicity-related deaths . Conclusions : Six months of LHRH+EMP neoadjuvant therapy followed by RP is safe and oncological outcomes are acceptable . Although this study was a single-arm trial with a relatively short follow-up , this treatment may have a potential to improve PSA-free survival in high-risk Pca patients . Further clinical trials are warranted Purpose : Degarelix , a new gonadotropin-releasing hormone ( GnRH ) receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer , possesses some theoretical advantages over luteinizing hormone – releasing hormone ( LHRH ) analogues in terms of avoiding “ testosterone flare ” and lower follicle-stimulating hormone ( FSH ) levels . We set out to determine whether preoperative degarelix influenced surrogates of disease control in a r and omized phase II study . Experimental Design : Thirty-nine patients were r and omly assigned to one of three different neoadjuvant arms : degarelix only , degarelix/bicalutamide , or LHRH agonist/bicalutamide . Treatments were given for 3 months before prostatectomy . Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment . The primary end point was treatment effect on intratumoral dihydrotestosterone levels . Results : Intratumoral DHT levels were higher in the degarelix arm than both the degarelix/bicalutamide and LHRH agonist/bicalutamide arms ( 0.87 ng/g vs. 0.26 ng/g and 0.23 ng/g , P < 0.01 ) . No significant differences existed for other intratumoral and rogens , such as testosterone and dehydroepi and rosterone . Patients in the degarelix-only arm had higher AMACR levels on immunohistochemical analysis ( P = 0.01 ) . Serum FSH levels were lower after 12 weeks of therapy in both degarelix arms than the LHRH agonist/bicalutamide arm ( 0.55 and 0.65 vs. 3.65 , P < 0.01 ) , and inhibin B levels were lower in the degarelix/bicalutamide arm than the LHRH agonist/bicalutamide arm ( 82.14 vs. 126.67 , P = 0.02 ) . Conclusions : Neoadjuvant degarelix alone , compared with use of LHRH agonist and bicalutamide , is associated with higher levels of intratumoral dihydrotestosterone , despite similar testosterone levels . Further studies that evaluate the mechanisms behind these results are needed . Clin Cancer Res ; 23(8 ) ; 1974–80 . © 2016 AACR Background Patients with locally advanced and high-risk prostate cancer ( LAPC ) are prone to experience biochemical recurrence despite radical prostatectomy ( RP ) . We evaluated feasibility , safety and activity of a neoadjuvant chemohormonal therapy ( NCHT ) with 3-weekly full dose docetaxel and complete and rogen blockade ( CAB ) in locally advanced and high-risk prostate cancer patients ( LAPC ) undergoing RP . Methods Patients ( n = 30 ) were selected by Kattans ’ preoperative score and received trimestral buserelin 9,45 mg , bicalutamide 50 mg/day and 3 cycles docetaxel ( 75 mg/m2 ) followed by RP . Primary endpoints were biochemical ( PSA ) and local downstaging . Secondary endpoints included toxicity and operability assessment s , pathological complete response ( pCR ) , time to PSA progression , 5-year biochemical recurrence free survival ( bRFS ) and overall survival ( OS ) . Results Median baseline PSA was 25.8 ng/ml ( 2.1–293 ) , and the predicted probability of 5-year bRFS was 10 % ( 0–55 ) . NCHT induced PSA-reduction was 97.3 % ( 81.3 - 99.9 % ; p < 0.001 ) and post-RP 96.7 % of patients were therapy responders , with undetectable PSA-values . Post- vs. pretreatment MRI indicated a median tumor volume reduction of 46.4 % ( −31.3 - 82.8 ; p < 0.001 ) . A pathological downstaging was observed in 48.3 % . Severe hematologic toxicities ( ≥CTC3 ) were frequent with 53.8 % leucopenia , 90 % neutropenia and 13.3 % febrile neutropenia . RP was performed in all patients . While resectability was hindered in 26.7 % , continence was achieved in 96.7 % . Pathologic analyses revealed no pCR . Lymph node- and extracapsular involvement was observed in 36.7 % and 56.7 % with 33.3 % positive surgical margins . After a median of 48.6 ( 19.9 - 87.8 ) months , 55.2 % of therapy responders experienced PSA-recurrence . The estimated median time to PSA-progression was 38.6 months ( 95%CI 30.9 - 46.4 ) and 85.3 months ( 95%CI 39.3–131.3 ) for OS . The 5-year bRFS was improved to 40 % , but limiting for interpretation adjuvant treatment was individualized . Conclusions NCHT is feasible despite high hematotoxicity , with excellent functional results . Significant downstaging was observed without pCR . NCHT seems to improve the cohort adjusted 5-year bRFS , but clinical value needs further investigation in r and omized trials Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy . We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing long-term hormone therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial . Herein , the clinical trial CU1005 prospect ively evaluated two regimens of maximum and rogen blockage or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer . Overall , 209 consecutive patients were recruited in this study , 107 of whom received 9 months of adjuvant maximum and rogen blockage , whereas 102 received 9 months of adjuvant bicalutamide 150 mg . The median postoperative follow-up time was 27.0 months . The primary endpoint was biochemical recurrence . Of the 209 patients , 59 patients developed biochemical recurrence . There was no difference between the two groups with respect to clinical characteristics , including age , pretreatment prostate-specific antigen , Gleason score , surgical margin status , or pathological stages . The maximum and rogen blockage group experienced longer biochemical recurrence-free survival ( P = 0.004 ) compared with the bicalutamide 150 mg group . Side-effects in the two groups were similar and could be moderately tolerated in all patients . In conclusion , immediate , 9-month maximum and rogen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy 252 Background : Post radical prostatectomy patients ( RP ) with extra prostatic extension or high Gleason grade are considered to have a high risk of treatment failure . Actual role of LH-RH agonists after RP in patients with high risk of recurrence remains unclear , except for the patients with positive lymph nodes . No r and omized prospect i ve study has been published with LH-RH agonists in the PSA era . Recent SWOG 9921 study shows a favorable disease-free and 5-year overall survival of 96 % for high-risk patients treated with 24 months of ADT after surgery . However , this study does not define the optimal protocol of adjuvant ADT , and does not demonstrate the superiority of immediate vs delayed treatment . The Objective of the AFU-GETUG 20 study is to evaluate the benefit of leuprorelin acetate for 24 months after RP in patients with high risk of recurrence . METHODS Academic Phase III r and omised , open-label , multicenter trial starting in late 2011 . INCLUSION CRITERIA R0 , N0-Nx M0 patients after RP in the 3 months preceding inclusion and with postoperative Gleason score > 7 , or ≥ 7 with the presence of 5 grade Gleason patterns or , or pT3b tumor , and with postoperative PSA < 0.1 ng/mL. EXCLUSION CRITERIA previous/current therapy for PCa . Primary endpoint is the evaluation of metastatic progression free survival . Secondary endpoints include overall survival , disease-specific survival , PSA evolution , evaluation of testosterone level , and quality of life . RESULTS A total of 700 patients ( 350 in each arm ) and 250 events are required to have 80 % ability to detect a difference with a bilateral Logrank test with α= 0.05 and β= 0.20 . Decision rules will be determined by the O ' Brien-Fleming sequential boundaries at the time of the analysis . Interim analysis is planned at the 125th event ( 50 % of events ) for 6.5 years after the start of the trial . Final analysis is planned for 12 years after the inclusion of the first patient . CONCLUSIONS The AFU-GETUG 20 study is a pioneering French multicenter trial aim ing to evaluate the actual role and place of ADT after RP for patients with high-risk prostate cancer The current trial evaluated 2 common therapies for patients with advanced prostate cancer , docetaxel and hormonal therapy ( HT ) , in the surgical adjuvant setting No Abstract Editorial Comment : Since r and omized data have supported use of and rogen deprivation therapy ( ADT ) at external beam radiation for men with high risk prostate cancer , the use of ADT has become the st and ard of care for most . There has been considerable controversy regarding duration of use , risk profiles in which benefit could be achieved and timing relative to radiation therapy . Recently demonstration of substantive long-term cardiovascular , metabolic and cognitive toxicity has result ed in more caution in recommending ADT , particularly in elderly patients with preexisting cardiovascular disease . In this study the authors evaluate long-term outcomes among men receiving external beam radiation therapy with or without 6 months of ADT for unfavorable risk prostate cancer . Early analysis of the data indicated that the addition of ADT result ed in improved mortality . However , at the current followup of 16.62 years no reduction in mortality was seen overall for men receiving radiation alone . When segregating men by level of comorbid conditions , improved overall and cancer specific survival was seen with the addition of ADT in men with little to no comorbidity . The opposite effect was seen in men with moderate to high comorbidity . In these men the addition of ADT reduced overall survival , increased cardiac event related mortality and had no effect on cancer specific mortality . The implication s of the findings are broad and suggest , as in many other examples , that individualized application of beneficial therapies likely supersedes level I evidence derived at the population level . One could argue that the duration of ADT may influence effects on cancer specific mortality in the whole group , although the effect of ADT on cardiac mortality in the ADT treated moderate to severe comorbidity group is hard to deflate . In this group 23 of 24 men died , of whom 16 died of cardiac causes and 1 of prostate cancer . In the whole group of men with moderate to severe comorbidity 46 of 49 died , of which only 4 deaths were prostate attributed . The take home message ? Prostate cancer treatment among those with high risk prostate cancer should be approached with caution , and judicious use of ADT in this setting , despite the evidence -based benefit , is warranted PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 OBJECTIVE To up date the results with 10-year data of a phase II prospect i ve trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy for locally advanced prostate cancer ( SWOG 9109 ) . The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer is uncertain . MATERIAL S AND METHODS Sixty-two patients with clinical stage T3 and T4 N0,M0 prostate cancer were enrolled . Cases were classified by stage T3 vs T4 and by volume of disease ( bulky > 4 cm and nonbulky ≤ 4 cm ) . RESULTS Fifty-five of 61 eligible patients completed the trial with radical prostatectomy after neoadjuvant and rogen deprivation therapy ( ADT ) . The median preoperative prostate-specific antigen value was 19.8 ng/mL , and 67 % of patients had a Gleason score of ≥ 7 . Among 41 patients last known to be alive , median follow-up is 10.6 years ( range 5.1 - 12.6 ) . In all , 38 patients have had disease progression ( 30/55 , 55 % ) or died without progression ( 8/55 , 15 % ) for a 10-year progression-free survival ( PFS ) estimate of 40 % ( 95 % CI 27 - 53 ) . Median PFS was 7.5 years , and median survival has not been reached . The 10-year overall survival ( OS ) estimate is 68 % ( 95 % CI 56 - 80 ) . CONCLUSIONS In this small , prospect i ve phase II study , neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy achieves long-term PFS and OS comparable with alternative treatments . This approach is feasible and may be an alternative to a strategy of combined radiation and ADT OBJECTIVE To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced , lymph node-negative prostate cancer . METHODS Men with locally advanced , lymph node-negative prostate cancer were r and omized after radical prostatectomy to receive either flutamide 750 mg daily or no adjuvant treatment . Recurrence-free and overall survival were the study end points . Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence . RESULTS 309 patients ( 157 in the control arm and 152 in the flutamide arm ) were eligible for efficacy analysis . The median follow-up was 6.1 years . Recurrence-free survival was better in the flutamide group ( P=0.0041 ) , there was , however , no detectable difference in overall survival ( p=0.92 ) . Moreover , there was a considerable toxicity reported in the flutamide group . CONCLUSION Although having some effect on disease recurrence , adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced , lymph node-negative prostate cancer Purpose To determine the pharmacodynamic effects of Sonidegib ( LDE-225 ) in prostate tumor tissue from men with high-risk localized prostate cancer , by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy . Methods We conducted a prospect i ve r and omized ( Sonidegib vs. observation ) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy . The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue . Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy , and safety . Results Fourteen men were equally r and omized ( 7 per arm ) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy . Six of seven men ( 86 % ) in the Sonidegib arm ( and none in the control group ) achieved a GLI1 suppression of at least two-fold . In the Sonidegib arm , drug was detectable in plasma and in prostatic tissue ; and median intra-patient GLI1 expression decreased by 63-fold , indicating potent suppression of Hedgehog signaling . Sonidegib was well tolerated , without any Grade 3 - 4 adverse events observed . Disease-free survival was comparable among the two arms ( HR = 1.50 , 95 % CI 0.26–8.69 , P = 0.65 ) . Conclusions Hedgehog pathway activity ( as measured by GLI1 expression ) was detectable at baseline in men with localized high-risk prostate cancer . Sonidegib penetrated into prostatic tissue and induced a > 60-fold suppression of the Hedgehog pathway . The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear BACKGROUND AND PURPOSE We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy ( 3D-CRT ) and and rogen deprivation in high-risk prostate carcinomas . METHODS Fifty men with high-risk localized prostate cancer ( 16 ) , locally advanced ( 28 ) or very high-risk prostate cancer ( 6 ) were included . Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions , concurrently with weekly docetaxel ( 20mg/m(2 ) ) . Three weeks after the completion of 3D-CRT , docetaxel was given for 3 cycles ( 60mg/m(2 ) ) , every 3 weeks . Patients had to receive LHRH agonist during 3 years . RESULTS The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3 - 4 acute toxicity . In the per protocol analysis , 46 patients completed a full-dose chemoradiation regimen representing 413 cycles : five patients experienced a grade 3 toxicity , and 15 patients experienced a grade 2 toxicity . With a median follow-up of 54 months , the 5-year clinical disease-free survival was 66.72 % and the 5-year survival was 92.15 % . CONCLUSIONS 3D-CRT with and rogen deprivation and concurrent weekly docetaxel , followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III r and omized trial BACKGROUND The optimal timing of endocrine therapy in non-metastatic prostate cancer ( PCa ) is still an issue of debate . METHODS A r and omised , double-blind , parallel-group trial comparing bicalutamide 150 mg once daily with placebo in addition to st and ard care in patients with hormone-naïve , non-metastatic PCa . Kaplan-Meier analysis was used to estimate overall survival ( OS ) and multivariate Cox proportional hazard model was performed to analyse time-to-event ( death ) . FINDINGS A total of 1218 patients were included into the Sc and inavian Prostate Cancer Group (SPCG)-6 study of which 607 were r and omised to receive bicalutamide in addition to their st and ard care and 611 to receive placebo . Median follow-up was 14.6years . Overall , 866 ( 71.1 % ) patients died , 428 ( 70.5 % ) in the bicalutamide arm and 438 ( 71.7 % ) in the placebo arm , p=0.87 . Bicalutamide significantly improved OS in patient with locally advanced disease ( hazard ratios (HR)=0.77 ( 95 % confidence interval ( CI ) : 0.63 - 0.94 , p=0.01 ) , regardless of baseline prostate-specific antigen ( PSA ) , with a survival benefit which was apparent throughout the study period . In contrast , survival favoured r and omisation to the placebo arm in patients with localised disease ( HR=1.19 ( 95 % CI : 1.00 - 1.43 ) , p=0.056 ) . However , a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at r and omisation . In multivariate Cox proportional hazard model , only including patients managed on watchful waiting as their st and ard of care ( n=991 ) OS depended on age , World Health Organisation ( WHO ) grade , baseline PSA , clinical stage and r and omised treatment . INTERPRETATION Throughout the 14.6year follow-up period the addition of early bicalutamide to st and ard of care result ed in a significant OS benefit in patients with locally advanced PCa . In contrast , patients with localised PCa and low PSA derived no survival benefit from early bicalutamide . The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free survival ( 3.42 [ 1.96 - 5.98 ] , p<0.0001 ) . Of 49 histopathology slides received ( 19 immediate ADT , 30 observation ) , 16 were down grade d from the original Gleason score ( between groups < or = 6 , 7 , and > or = 8) and five were up grade d. We recorded similar proportions of score changes in each group ( p=0.68 ) , and no difference in score distribution by treatment ( p=0.38 ) . After adjustment for score , associations were still significant between treatment and survival ( overall , p=0.02 ; disease-specific , p=0.002 ; progression-free survival , p<0.0001 ) . INTERPRETATION Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy , compared with those who receive deferred treatment . The beneficial effects of early ADT , rather than an imbalance in risk factors , are likely to explain the differences in outcomes between treatments PURPOSE Long-term ( LT ) and rogen suppression ( AS ) with radiation therapy ( RT ) is a st and ard treatment of high-risk , localized prostate cancer ( PCa ) . Radiation Therapy Oncology Group 9902 was a r and omized trial testing the hypothesis that adjuvant combination chemotherapy ( CT ) with paclitaxel , estramustine , and oral etoposide plus LT AS plus RT would improve overall survival ( OS ) . METHODS AND MATERIAL S Patients with high-risk PCa ( prostate-specific antigen 20 - 100 ng/mL and Gleason score [ GS ] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were r and omized to RT and AS ( AS + RT ) alone or with adjuvant CT ( AS + RT + CT ) . CT was given as four 21-day cycles , delivered beginning 28 days after 70.2 Gy of RT . AS was given as luteinizing hormone-releasing hormone for 24 months , beginning 2 months before RT plus an oral anti and rogen for 4 months before and during RT . The study was design ed based on a 6 % improvement in OS from 79 % to 85 % at 5 years , with 90 % power and a 2-sided alpha of 0.05 . RESULTS A total of 397 patients ( 380 eligible ) were r and omized . The patients had high-risk PCa , 68 % with GS 8 to 10 and 34 % T3 to T4 tumors , and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years . The trial closed early because of excess thromboembolic toxicity in the CT arm . The 10-year results for all r and omized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS ( 65 % vs 63 % ; P=.81 ) , biochemical failure ( 58 % vs 54 % ; P=.82 ) , local progression ( 11 % vs 7 % ; P=.09 ) , distant metastases ( 16 % vs 14 % ; P=.42 ) , or disease-free survival ( 22 % vs 26 % ; P=.61 ) . CONCLUSIONS NRG Oncology RTOG 9902 showed no significant differences in OS , biochemical failure , local progression , distant metastases , or disease-free survival with the addition of adjuvant CT to LT AS + RT . The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implication s for the feasibility of clinical trial accrual and tolerability using CT for PCa PURPOSE To evaluate the feasibility of administering sunitinib in combination with and rogen deprivation therapy and external-beam intensity modulated radiation therapy ( XRT ) in patients with localized high-risk prostate cancer . METHODS AND MATERIAL S Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8 - 10 or prostate-specific antigen > 20 ng/mL received initial and rogen deprivation ( leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily ) for 4 - 8 weeks before oral sunitinib 12.5 , 25 , or 37.5 mg daily for 4 weeks as lead-in , then concurrently with and 4 weeks after XRT ( 75.6 Gy in 42 fractions to prostate and seminal vesicles ) . A 3 + 3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity ( DLT ) and establish a maximal tolerated dose of sunitinib . RESULTS Sunitinib at 12.5- and 25-mg dose levels was well tolerated . The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in , and a drug interaction between sunitinib and bicalutamide was suspected . The protocol was revised and concurrent bicalutamide omitted . Of the next 3 patients enrolled at 37.5 mg , 2 of 3 receiving concurrent therapy experienced DLTs during radiation : grade 3 diarrhea and grade 3 proctitis , respectively . Only 1 of 7 patients completed sunitinib at 37.5 mg daily , whereas 3 of 3 patients ( 25 mg as starting dose ) and 3 of 4 patients ( 25 mg as reduced dose ) completed therapy . CONCLUSIONS The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor ( PDGFR ) inhibitor therapy , and rogen deprivation , and radiation therapy for prostate cancer was established . Using a daily dosing regimen with lead-in , concurrent , and post-XRT therapy , the recommended phase 2 dose of sunitinib is 25 mg daily PURPOSE Weekly paclitaxel , concurrent radiation , and and rogen deprivation ( ADT ) were evaluated in patients with high-risk prostate cancer ( PC ) with or without prior prostatectomy ( RP ) . METHODS AND MATERIAL S Eligible post-RP patients included : pathological T3 disease , or rising prostate-specific antigen ( PSA ) ≥ 0.5 ng/mL post-RP . Eligible locally advanced PC ( LAPC ) patients included : 1 ) cT2b-4N0N+ , M0 ; 2 ) Gleason score ( GS ) 8 - 10 ; 3 ) GS 7 + PSA 10 - 20 ng/mL ; or 4 ) PSA 20 - 150 ng/mL. Treatment included ADT ( 4 or 24 months ) , weekly paclitaxel ( 40 , 50 , or 60 mg/m(2)/wk ) , and pelvic radiation therapy ( total dose : RP = 64.8 Gy ; LAPC = 70.2 Gy ) . RESULTS Fifty-nine patients were enrolled ( LAPC , n = 29 ; RP , n = 30 ; ADT 4 months , n = 29 ; 24 months , n = 30 ; whites n = 29 , African Americans [ AA ] , n = 28 ) . Baseline characteristics ( median [ range ] ) were : age 67 ( 45 - 86 years ) , PSA 5.9 ( 0.1 - 92.1 ng/mL ) , GS 8 ( 6 - 9 ) . At escalating doses of paclitaxel , 99 % , 98 % , and 95 % of doses were given with radiation and ADT , respectively , with dose modifications required primarily in RP patients . No acute Grade 4 toxicities occurred . Grade 3 toxicities were diarrhea 15 % , urinary urgency/incontinence 10 % , tenesmus 5 % , and leukopenia 3 % . Median follow-up was 75.3 months ( 95 % CI : 66.8 - 82.3 ) . Biochemical progression occurred in 24 ( 41 % ) patients and clinical progression in 11 ( 19 % ) patients . The 5- and 7-year OS rates were 83 % and 67 % . There were no differences in OS between RP and LAPC , 4- and 24-month ADT , white and AA patient categories . CONCLUSIONS In addition to LAPC , to our knowledge , this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients . With a median follow-up of 75.3 months , this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer . Concurrent ADT , radiation , and weekly paclitaxel at 40 mg/m(2)/week in RP patients and 60 mg/m(2)/week in LAPC patients is feasible and well-tolerated BACKGROUND Early risk-stratified chemotherapy is a st and ard treatment for breast , colorectal , and lung cancers , but not for high-risk localised prostate cancer . Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer . We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer . METHODS We did this r and omised phase 3 trial at 26 hospitals in France . We enrolled patients with treatment-naive prostate cancer and at least one risk factor ( ie , stage T3-T4 disease , Gleason score of ≥8 , prostate-specific antigen concentration > 20 ng/mL , or pathological node-positive ) . All patients underwent a staging pelvic lymph node dissection . Patients were r and omly assigned ( 1:1 ) to either and rogen deprivation therapy ( ADT ; goserelin 10·8 mg every 3 months for 3 years ) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2 ) and estramustine 10 mg/kg per day on days 1 - 5 , every 3 weeks , or ADT only . The r and omisation was done central ly by computer , stratified by risk factor . Local treatment was administered at 3 months . Neither patients nor investigators were masked to treatment allocation . The primary endpoint was relapse-free survival in the intention-to-treat population . Follow-up for other endpoints is ongoing . This study is registered with Clinical Trials.gov , number NCT00055731 . FINDINGS We r and omly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group . Median follow-up was 8·8 years ( IQR 8·1 - 9·7 ) . 88 ( 43 % ) of 207 patients in the ADT plus docetaxel and estramustine group had an event ( relapse or death ) versus 111 ( 54 % ) of 206 in the ADT only group . 8-year relapse-free survival was 62 % ( 95 % CI 55 - 69 ) in the ADT plus docetaxel and estramustine group versus 50 % ( 44 - 57 ) in the ADT only group ( adjusted hazard ratio [ HR ] 0·71 , 95 % CI 0·54 - 0·94 , p=0·017 ) . Of patients who were treated with radiotherapy and had data available , 31 ( 21 % ) of 151 in the ADT plus docetaxel and estramustine group versus 26 ( 18 % ) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect ( p=0·61 ) . We recorded no excess second cancers ( 26 [ 13 % ] of 207 vs 22 [ 11 % ] of 206 ; p=0·57 ) , and there were no treatment-related deaths . INTERPRETATION Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer . Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival . FUNDING Ligue Contre le Cancer , Sanofi-Aventis , AstraZeneca , Institut National du Cancer PURPOSE Cure rates for localized high-risk prostate cancers ( PCa ) and some intermediate-risk PCa are frequently suboptimal with local therapy . Outcomes are improved by concomitant and rogen-deprivation therapy ( ADT ) with radiation therapy , but not by concomitant ADT with surgery . Luteinizing hormone-releasing hormone agonist ( LHRHa ; leuprolide acetate ) does not reduce serum and rogens as effectively as abiraterone acetate ( AA ) , a prodrug of abiraterone , a CYP17 inhibitor that lowers serum testosterone ( < 1 ng/dL ) and improves survival in metastatic PCa . The possibility that greater and rogen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the re assessment of neoadjuvant ADT with more robust and rogen suppression . PATIENTS AND METHODS A neoadjuvant r and omized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa ( N = 58 ) . For the first 12 weeks , patients were r and omly assigned to LHRHa versus LHRHa plus AA . After a research prostate biopsy , all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy . RESULTS The levels of intraprostatic and rogens from 12-week prostate biopsies , including the primary end point ( dihydrotestosterone/testosterone ) , were significantly lower ( dehydroepi and rosterone , Δ(4)- and rostene-3,17-dione , dihydrotestosterone , all P < .001 ; testosterone , P < .05 ) with LHRHa plus AA compared with LHRHa alone . Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease , with residual T3- or lymph node-positive disease in the majority . CONCLUSION LHRHa plus AA treatment suppresses tissue and rogens more effectively than LHRHa alone . Intensive intratumoral and rogen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden PURPOSE Radiation Therapy Oncology Group ( RTOG ) 8610 was the first phase III r and omized trial to evaluate neoadjuvant and rogen deprivation therapy ( ADT ) in combination with external-beam radiotherapy ( EBRT ) in men with locally advanced prostate cancer . This report summarizes long-term follow-up results . MATERIAL S AND METHODS Between 1987 and 1991 , 456 assessable patients ( median age , 70 years ) were enrolled . Eligible patients had bulky ( 5 x 5 cm ) tumors ( T2 - 4 ) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system . Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT , or they received EBRT alone . Study end points included overall survival ( OS ) , disease-specific mortality ( DSM ) , distant metastasis ( DM ) , disease-free survival ( DFS ) , and biochemical failure ( BF ) . RESULTS Ten-year OS estimates ( 43 % v 34 % ) and median survival times ( 8.7 v 7.3 years ) favored ADT and EBRT , respectively ; however , these differences did not reach statistical significance ( P = .12 ) . There was a statistically significant improvement in 10-year DSM ( 23 % v 36 % ; P = .01 ) , DM ( 35 % v 47 % ; P = .006 ) , DFS ( 11 % v 3 % ; P < .0001 ) , and BF ( 65 % v 80 % ; P < .0001 ) with the addition of ADT , but no differences were observed in the risk of fatal cardiac events . CONCLUSION The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinical ly meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events BACKGROUND The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant and rogen deprivation therapy ( NADT ) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer . Here we report the 10-year results . METHODS Between June , 1996 , and February , 2000 , 818 men with T2b , T2c , T3 , and T4 N0 M0 prostate cancers were r and omly assigned to receive radiotherapy alone , 3 months of NADT plus radiotherapy , or 6 months of NADT plus radiotherapy . The radiotherapy dose for all groups was 66 Gy , delivered to the prostate and seminal vesicles ( excluding pelvic nodes ) in 33 fractions of 2 Gy per day ( excluding weekends ) over 6·5 - 7·0 weeks . NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day . NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group . Primary endpoints were prostate-cancer-specific mortality and all-cause mortality . Treatment allocation was open label and r and omisation was done with a minimisation technique according to age , clinical stage , tumour grade , and initial prostate-specific antigen concentration ( PSA ) . Analysis was by intention-to-treat . The trial has been closed to follow-up and all main endpoint analyses are completed . The trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12607000237482 . FINDINGS 802 men were eligible for analysis ( 270 in the radiotherapy alone group , 265 in the 3-month NADT group , and 267 in the 6-month NADT group ) after a median follow-up of 10·6 years ( IQR 6·9 - 11·6 ) . Compared with radiotherapy alone , 3 months of NADT decreased the cumulative incidence of PSA progression ( adjusted hazard ratio 0·72 , 95 % CI 0·57 - 0·90 ; p=0·003 ) and local progression ( 0·49 , 0·33 - 0·73 ; p=0·0005 ) , and improved event-free survival ( 0·63 , 0·52 - 0·77 ; p<0·0001 ) . 6 months of NADT further reduced PSA progression ( 0·57 , 0·46 - 0·72 ; p<0·0001 ) and local progression ( 0·45 , 0·30 - 0·66 ; p=0·0001 ) , and led to a greater improvement in event-free survival ( 0·51 , 0·42 - 0·61 , p<0·0001 ) , compared with radiotherapy alone . 3-month NADT had no effect on distant progression ( 0·89 , 0·60 - 1·31 ; p=0·550 ) , prostate cancer-specific mortality ( 0·86 , 0·60 - 1·23 ; p=0·398 ) , or all-cause mortality ( 0·84 , 0·65 - 1·08 ; p=0·180 ) , compared with radiotherapy alone . By contrast , 6-month NADT decreased distant progression ( 0·49 , 0·31 - 0·76 ; p=0·001 ) , prostate cancer-specific mortality ( 0·49 , 0·32 - 0·74 ; p=0·0008 ) , and all-cause mortality ( 0·63 , 0·48 - 0·83 ; p=0·0008 ) , compared with radiotherapy alone . Treatment-related morbidity was not increased with NADT within the first 5 years after r and omisation . INTERPRETATION 6 months of neoadjuvant and rogen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer , particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged and rogen deprivation . FUNDING Australian Government National Health and Medical Research Council , Hunter Medical Research Institute , AstraZeneca , and Schering-Plough Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . BACKGROUND The combination of radiotherapy plus long-term medical suppression of and rogens ( > or = 2 years ) improves overall survival in patients with locally advanced prostate cancer . We compared the use of radiotherapy plus short-term and rogen suppression with the use of radiotherapy plus long-term and rogen suppression in the treatment of locally advanced prostate cancer . METHODS We r and omly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of and rogen suppression to two groups , one to receive no further treatment ( short-term suppression ) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist ( long-term suppression ) . An outcome of noninferiority of short-term and rogen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival , with a one-sided alpha level of 0.05 . An interim analysis showed futility , and the results are presented with an adjusted one-sided alpha level of 0.0429 . RESULTS A total of 1113 men were registered , of whom 970 were r and omly assigned , 483 to short-term suppression and 487 to long-term suppression . After a median follow-up of 6.4 years , 132 patients in the short-term group and 98 in the long-term group had died ; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group . The 5-year overall mortality for short-term and long-term suppression was 19.0 % and 15.2 % , respectively ; the observed hazard ratio was 1.42 ( upper 95.71 % confidence limit , 1.79 ; P=0.65 for noninferiority ) . Adverse events in both groups included fatigue , diminished sexual function , and hot flushes . CONCLUSIONS The combination of radiotherapy plus 6 months of and rogen suppression provides inferior survival as compared with radiotherapy plus 3 years of and rogen suppression in the treatment of locally advanced prostate cancer . ( Clinical Trials.gov number , NCT00003026 . CONTEXT Comorbidities may increase the negative effects of specific anticancer treatments such as and rogen suppression therapy ( AST ) . OBJECTIVES To compare 6 months of AST and radiation therapy ( RT ) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality . DESIGN , SETTING , AND PATIENTS At academic and community-based medical centers in Massachusetts , between December 1 , 1995 , and April 15 , 2001 , 206 men with localized but unfavorable-risk prostate cancer were r and omized to receive RT alone or RT and AST combined . All-cause mortality estimates stratified by r and omized treatment group and further stratified in a postr and omization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test . MAIN OUTCOME MEASURE Time to all-cause mortality . RESULTS As of January 15 , 2007 , with a median follow-up of 7.6 ( range , 0.5 - 11.0 ) years , 74 deaths have occurred . A significant increase in the risk of all-cause mortality ( 44 vs 30 deaths ; hazard ratio [ HR ] , 1.8 ; 95 % confidence interval [ CI ] , 1.1 - 2.9 ; P = .01 ) was observed in men r and omized to RT compared with RT and AST . However , the increased risk in all-cause mortality appeared to apply only to men r and omized to RT with no or minimal comorbidity ( 31 vs 11 deaths ; HR , 4.2 ; 95 % CI , 2.1 - 8.5 ; P < .001 ) . Among men with moderate or severe comorbidity , those r and omized to RT alone vs RT and AST did not have an increased risk of all-cause mortality ( 13 vs 19 deaths ; HR , 0.54 ; 95 % CI , 0.27 - 1.10 ; P = .08 ) . CONCLUSIONS The addition of 6 months of AST to RT result ed in increased overall survival in men with localized but unfavorable-risk prostate cancer . This result may pertain only to men without moderate or severe comorbidity , but this requires further assessment in a clinical trial specifically design ed to assess this interaction . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116220 |
13,431 | 32,200,197 | Interventions based on behavior change theory yielded an increase in the initiation of effective contraception as compared with provision of written information material s. The effect was more pronounced when the intervention provided on-site contraceptive counseling and free access to birth control .
Financial incentives also seemed to effectively increase women 's contraception intake .
Case management interventions including pregnant and postpartum women with heavy levels of substance use showed promising results in terms of initiation of contraception , but rates of unintended pregnancy over long-term follow-up were nevertheless elevated .
Finally , some interventions integrated family planning services into specialized centers taking care of pregnant and postpartum women with substance abuse .
All interventions with a primary or secondary focus on the prevention of unintended pregnancy in women using psychoactive substances short-term improvements in contraception intake , but it is unclear if these effects last or have any impact on unintended pregnancy rates in the long-term | This systematic review seeks to evaluate the efficacy of interventions aim ed at preventing unintended pregnancies in women using psychoactive substances . | BACKGROUND Alcohol-exposed pregnancies ( AEPs ) are a preventable cause of birth defects and developmental disabilities for which many women are at risk . The initial 5-session Project CHOICES intervention was found to prevent AEPs . In the ensuing decade , there have been several additional CHOICES-like studies . This study , Project Healthy CHOICES , had 2 objectives : ( i ) to compare outcomes for students versus nonstudents ; and ( ii ) to test a self-administered mail-based version of the Project CHOICES intervention . METHODS A r and omized controlled trial ( RCT ) compared 2 interventions for women of childbearing age ( 18 to 44 ) who were at risk of an AEP : ( i ) motivational feedback based on Project CHOICES and ( ii ) information only . Advertisements recruited 354 women ( 145 college students ; 209 nonstudents ) at risk of an AEP . Intervention and study material s were available in English and Spanish . Of the 354 women , 44 % were minorities ( 25 % identified as Hispanics ) . RESULTS At the 6-month follow-up , the interventions did not differ and there was no Intervention by Student Study interaction . However , over the entire 6-month follow-up , significantly more students ( 68 % ) than nonstudents ( 46 % ) were not at risk of an AEP ( 2.1 odds ratio ; confidence interval = 1.47 to 2.95 ) . For all groups , risk reduction occurred primarily through effective contraception . CONCLUSIONS There was no significant difference between the 2 interventions . However , over the entire 6-month follow-up interval , college students were significantly more likely than nonstudents to not be at risk of an AEP and to use effective contraception . While the student groups had significantly higher reduced risk of AEP outcomes , there was also substantial risk reduction for women in the information only condition . These results suggest that the most effective AEP prevention efforts would be to inform women at risk that they could become pregnant . Because about half of all pregnancies are unplanned , identifying women at risk and preventing the risk of AEPs should be a public health priority BACKGROUND Fetal alcohol spectrum disorders ( FASD ) comprise a continuum of lifelong outcomes in those born prenatally exposed to alcohol . Although studies have shown no differences in rates by race , FASD is of particular concern for American Indian communities . One tribally run prevention program is the Oglala Sioux Tribe ( OST ) CHOICES Program , which is modeled after the evidence -based CHOICES program that was focused on preconceptional prevention of alcohol-exposed pregnancy ( AEP ) by reducing risky drinking in women at risk for pregnancy and /or preventing unintended pregnancy . METHODS The OST CHOICES Program was made culturally appropriate for American Indian women and implemented with 3 communities , 2 on the reservation and 1 off . Data on drinking , sexual activity , and contraception use were collected at baseline and 3 and 6 months postintervention . Data were analyzed using descriptive statistics , 1-way analysis of variance , and a r and om intercept generalized estimating equation model . RESULTS A total of 193 nonpregnant American Indian women enrolled in the OST CHOICES Program , and all were at risk for AEP because of binge drinking and being at risk for an unintended pregnancy . Fifty-one percent of participants completed both 3- and 6-month follow-ups . Models showed a significant decrease in AEP risk from baseline at both 3- and 6-month follow-ups , indicating the significant impact of the OST CHOICES intervention . Women in the OST CHOICES Program were more likely to reduce their risk for AEP by utilizing contraception , rather than decreasing binge drinking . CONCLUSIONS Even with minor changes to make the CHOICES intervention culturally and linguistically appropriate and the potential threats to program validity those changes entail , we found a significant impact in reducing AEP risk . This highlights the capacity for the CHOICES intervention to be implemented in a wide variety of setting s and population ABSTRACT Background : Postpartum contraception is especially important for women who use alcohol and other substances , given the risk of possible rapid repeat pregnancy and prenatal substance exposure . However , little is known about postpartum contraceptive use among women with substance use histories . Objective : To characterize postpartum contraceptive initiation , 24-month continuation , and rapid repeat pregnancy among women who used substances during pregnancy . Methods : This is a secondary analysis of 161 pregnant women who enrolled in a r and omized clinical trial to treat substance use in pregnancy and completed at least one follow-up assessment . Women were eligible if they were less than 28 weeks gestation and reported alcohol or illicit drug use within the past 30 days . Participants were recruited from two hospital-based OB/GYN clinics between 2006 and 2010 , and completed assessment s at delivery and 3- , 12- , and 24-months postpartum . Results : Past 30-day use of any substance ( not including tobacco ) was 52.4 % , 58.3 % , and 59.8 % at 3- , 12- , and 24-month follow-up , respectively . Marijuana was the most commonly reported illicit substance ( as high as 48.1 % ) . Rates of any contraceptive use were 71.3 % , 66.7 % and 65.3 % at 3- , 12- , and 24-month follow-up , respectively ; DepoProvera and condoms were the most common methods . Rapid repeat pregnancy occurred in 28 % of participants by 24-month follow-up . Conclusions / Importance : Postpartum contraceptive use among substance using women was at or near 70 % , which is comparable to other sample s of postpartum women . Innovative efforts are needed to promote effective contraceptive use among postpartum women in general and among those who use substances in particular BACKGROUND The study was conducted to determine whether perceived racial , economic and gender discrimination has an impact on contraception use and choice of method . METHODS We analyzed the first 2,500 women aged 14 - 45 years enrolled in the Contraceptive CHOICE Project , a prospect i ve cohort study aim ed to reduce barriers to obtaining long-acting reversible contraception . Items from the " Experiences of Discrimination " ( EOD ) scale measured experienced race- , gender- and economic-based discrimination . RESULTS Overall , 57 % of women reported a history of discrimination . Thirty-three percent reported gender- or race-based discrimination , and 24 % reported discrimination attributed to socioeconomic status ( SES ) . Prior to study enrollment , women reporting discrimination were more likely to report any contraception use ( 61 % vs. 52 % , p<.001 ) but were more likely to use less effective methods ( e.g. , barrier methods , natural family planning or withdrawal ; 41 % vs. 32 % , p<.001 ) . In adjusted analyses , gender- , race- or SES-based discrimination were associated with increased current use of less effective methods [ adjusted risk ratio ( aRR ) 1.22 , 95 % confidence interval ( CI ) 1.06 - 1.41 ; aRR 1.25 , CI 1.08 - 1.45 ; aRR 1.23 , CI 1.06 - 1.43 , respectively ] . After enrollment , 66 % of women with a history of experience of discrimination chose a long-acting reversible contraceptive method ( intrauterine device or implantable ) and 35 % chose a depo-medroxyprogesterone acetate or contraceptive pill , patch or ring . CONCLUSIONS Discrimination negatively impacts a woman 's use of contraception . However , after financial and structural barriers to contraceptive use were eliminated , women with EOD overwhelmingly selected effective methods of contraception . Future interventions to improve access and utilization of contraception should focus on eliminating barriers and targeting interventions that encompass race- , gender- and economic-based discrimination Objective To document the contraceptive choices and continuation rates for different contraceptives in a group of pregnant women who use opiates . Methods A prospect i ve study set in a large city in the north of Engl and that looked at 40 pregnant women who used opiates in the index pregnancy . The study involved review ing the records from the patients ' general practitioners with information on the continuation rates of the chosen method of contraception and any related problems . Results The women given Depo-Provera ® ( n = 14 ) did not continue the method after the first injection . Those given implants ( n = 20 ) had a 95 % continuation rate at a mean follow-up of over 11 months . Conclusions Implants had a good continuation rate when used for postnatal contraception in women who used opiates in pregnancy . Depo-Provera may not be a suitable choice since all the women who chose this contraceptive method failed to continue with it Home visitation interventions show promise for helping at-risk mothers , yet few programs have been developed and evaluated specifically for alcohol and drug-abusing pregnant women . This study examines outcomes among 216 women enrolled in the Washington State Parent-Child Assistance Program , a three-year intervention program for women who abuse alcohol and drugs during an index pregnancy . Pretest-posttest comparison was made across three sites : the original demonstration ( 1991–1995 ) , and the Seattle and Tacoma replications ( 1996–2003 ) . In the original demonstration , the client group performed significantly better than controls . Compared to the original demonstration , outcomes at replication sites were maintained ( for regular use of contraception and use of reliable method ; and number of subsequent deliveries ) , or improved ( for alcohol/drug treatment completed ; alcohol/drug abstinence ; subsequent delivery unexposed to alcohol/drugs ) . Improved outcomes at replication sites are not attributable to enrolling lower-risk women . Public policies and programs initiated over the study period may have had a positive effect on outcomes . Study findings suggest that this community-based intervention model is effective over time and across venues Many college women are at risk for pregnancy , and binge drinking college women are often at risk for alcohol-exposed pregnancy . Brief interventions with sustainable outcomes are needed , particularly for college women who are binge drinking , at risk for pregnancy , and at increased risk of alcohol-exposed pregnancy . Two-hundred-twenty-eight women at a Mid-Atlantic urban university at risk for alcohol-exposed pregnancy enrolled in the r and omized clinical trial , and 207 completed the 4 month follow-up . The BALANCE intervention used Motivational Interviewing plus feedback to target drinking and contraception behaviors . Main outcome measures included ( 1 ) the rate of risk for alcohol-exposed pregnancy , ( 2 ) the rate of risk drinking , and ( 3 ) the rate of pregnancy risk . At 4-month follow-up , the rate of alcohol-exposed pregnancy risk was significantly lower in the intervention ( 20.2 % ) than the control condition ( 34.9 % ) , ( P < .02 ) . Assignment to the intervention condition halved the odds of women remaining at risk for alcohol-exposed pregnancy , while not receiving the intervention doubled the odds of continued alcohol-exposed pregnancy risk ( OR = 2.18 ; 95 % CI = 1.16–4.09 ) . A baseline history of blackouts , continued high blood alcohol drinking days at 1 month , and continued risk for pregnancy at 1 month independently contributed to a multivariate model of continued alcohol-exposed pregnancy risk at 4 month follow-up . BALANCE reduced alcohol-exposed pregnancy risk , with similar outcomes to longer interventions . Because early response predicted sustained alcohol-exposed pregnancy risk reduction , those who fail to achieve initial change could be identified for further intervention . The BALANCE intervention could be adopted into existing student health or university alcohol programs . The risks of unintended pregnancy and alcohol-exposed pregnancy among binge drinking women in college merit greater prevention efforts A significant number of college women are at risk for alcohol-exposed pregnancy ( AEP ) owing to binge drinking paired with using contraception ineffectively . This article describes a r and omized controlled trial of a one-session motivational interviewing-based intervention to reduce AEP risk among college women and presents 1-month outcomes demonstrating the early impact of this intervention . There were 228 female students from a mid-Atlantic urban university enrolled in the trial . Eligibility criteria were being in the age range of 18 - 24 years and being at risk for AEP . Risk for AEP was defined as having sexual intercourse with a man in the past 90 days while using contraception ineffectively ( no use , incorrect use of an effective method , or use of an ineffective method only ) ; drinking at risky levels was defined as engaging in at least one binge in the past 90 days or consuming an average of eight st and ard drinks per week . One-month outcome data were available for 212 of the 228 enrolled women ( a follow-up rate of 93 % ) , with complete data available for 105 women assigned to the control condition and 94 assigned to the intervention condition . At 1-month follow-up , 15 % of the control subjects and 25 % of the intervention women reported no risk drinking , a significant difference favoring the intervention group . Significantly fewer control subjects ( 48 % ) used effective contraception at 1-month follow-up as compared with intervention women ( 64 % ) , chi(2)(1 ) = 5.1 , p < .03 . Significantly more intervention women ( 74 % ) were no longer at risk for AEP at 1 month as compared with control subjects ( 54 % ) , chi(2)(1 ) = 8.15 , p < .005 . Factors that were associated with continued AEP risk at 1-month follow-up were a higher number of st and ard drinks per day consumed in the month prior to baseline ( odds ratio , 1.1 ) and assignment to the control condition ( odds ratio , 2.9 ) . The risks of unintended pregnancy and AEP among drinking women in college merit greater prevention efforts . The results of this study show the promise of one preventive intervention that warrants additional study Brief , effective interventions are needed to reduce the risk of an alcohol-exposed pregnancy in women who drink and do not use effective contraception . The Healthy Choices study compared telephone and in-person administration of a brief intervention . In addition to indicators of alcohol use and effective contraception , compliance with the intervention was examined . Women between the ages of 18 and 44 who were drinking above recommended levels and not using effective contraception were r and omly assigned to either a telephone ( n=68 ) or in-person ( n=63 ) brief ( two sessions ) intervention . Overall , participants showed small but significant reductions in alcohol use and larger increases in effective use of contraception . Risk of alcohol-exposed pregnancy was thus significantly reduced , largely due to improved contraception with minor reductions in alcohol use . There was no significant difference in success of the intervention between the two conditions ( telephone versus in-person ) . These findings suggest telephone-based brief intervention may be equally successful and cost-effective in reducing the risk of an alcohol-exposed pregnancy and thus fetal alcohol syndrome Background Methamphetamine ( MA ) use during pregnancy is associated with many pregnancy complications , including preterm birth , small for gestational age , preeclampsia , and abruption . Hawaii has lead the nation in MA use for many years , yet prior to 2007 , did not have a comprehensive plan to care for pregnant substance-using women . In 2006 , the Hawaii State Legislature funded a pilot perinatal addiction clinic . The Perinatal Addiction Treatment Clinic of Hawaii was built on a harm-reduction model , encompassing perinatal care , transportation , child-care , social services , family planning , motivational incentives , and addiction medicine . We present the implementation model and results from our first one hundred three infants ( 103 ) seen over 3 years of operation of the program . Methods Referrals came from community health centers , hospitals , addiction treatment facilities , private physician offices , homeless outreach services and self-referral through word-of-mouth and bus ads . Data to describe sample characteristics and outcome was obtained prospect ively and retrospectively from chart abstract ion and delivery data . Drug use data was obtained from the women 's self-report and r and om urine toxicology during the pregnancy , as well as urine toxicology at the time of birth on mothers , and urine and meconium toxicology on the infants . Post-partum depression was measured in mothers with the Edinburgh Post-Partum depression scale . Data from Path clinic patients were compared with a representative cohort of women delivering at Kapiolani Medical Center for Women and Children during the same time frame , who were enrolled in another study of pregnancy outcomes . Ethical approval for this study was obtained through the University of Hawaii Committee for Human Studies . Results Between April 2007 and August 2010 , 213 women with a past or present history of addiction were seen , 132 were pregnant and 97 delivered during that time . 103 live-born infants were delivered . There were 3 first-trimester Spontaneous Abortions , two 28-week intrauterine fetal deaths , and two sets of twins and 4 repeat pregnancies . Over 50 % of the women had lost custody of previous children due to substance use . The majority of women who delivered used methamphetamine ( 86 % ) , either in the year before pregnancy or during pregnancy . Other drugs include marijuana ( 59.8 % ) , cocaine ( 33 % ) , opiates ( 9.6 % ) , and alcohol ( 15.2 % ) . Of the women served , 85 % smoked cigarettes upon enrollment . Of the 97 women delivered during this period , all but 4 ( 96 % ) had negative urine toxicology at the time of delivery . Of the 103 infants , 13 ( 12.6 % ) were born preterm , equal to the state and national average , despite having many risk factors for prematurity , including poverty , poor diet , smoking and polysubstance use . Overwhelmingly , the women are parenting their children , > 90 % retained custody at 8 weeks . Long-term follow-up showed that women who maintained custody chose long-acting contraceptive methods ; while those who lost custody had a very high ( > 50 % ) repeat pregnancy rate at 9 months post delivery . Conclusion Methamphetamine use during pregnancy does n't exist is isolation . It is often combined with a multitude of other adverse circumstances , including poverty , interpersonal violence , psychiatric comorbidity , polysubstance use , nutritional deficiencies , inadequate health care and stressful life experiences . A comprehensive harm reduction model of perinatal care , which aims to ameliorate some of these difficulties for substance-using women without m and ating abstinence , provides exceptional birth outcomes and can be implemented with limited re sources BACKGROUND Alcohol-exposed pregnancy ( AEP ) is a leading cause of birth defects . Effective face-to-face preconception interventions based on motivational interviewing ( MI ) exist and should be translated into remote formats for maximum public health impact . This study investigated the feasibility and promise of a one-session , remote-delivered , preconception , MI-based AEP intervention ( EARLY Remote ) for non-treatment-seeking community women . SUBJECTS AND METHODS This was a single-arm , prospect i ve pilot intervention study . All participants received the intervention via telephone and mail . Feasibility of remote-delivery methods , treatment engagement , treatment credibility , MI treatment integrity , and therapeutic alliance were examined . Outcomes were 3- and 6-month drinks per drinking day ( DDD ) , rate of unreliable contraception , and proportion of women at risk for AEP due to continued risk drinking and no or unreliable contraception use . RESULTS Feasibility of remote delivery was established ; participants were engaged by the intervention and rated it as credible . Integrity to MI and therapeutic alliance were good . Both DDD and rate of unreliable contraception decreased significantly over time . Proportions of women who drank at risk levels , used unreliable or no contraception , and /or were at risk for AEP in the past 90 days decreased significantly from baseline to 6 months . CONCLUSIONS Remote delivery was feasible , and the translated remote intervention may reduce AEP risk . Refinement of EARLY Remote may facilitate its placement within a spectrum of effective MI-based preconception AEP interventions as part of a stepped-care approach . EARLY Remote may have an important role within a stepped-care model for dissemination to geographically disperse women at risk for AEP . This could result in substantial public health impact through reduction of AEP on a larger scale OBJECTIVE An unsettling aspect of the US opioid epidemic is the high rate of in utero exposure , especially since most of these pregnancies are unintended , due in part to low rates of effective contraceptive use among opioid-using women . This study tested an intervention informed by behavioral economic theory and aim ed at promoting effective contraceptive use among opioid-maintained women at risk of unintended pregnancy in the Burlington , VT , area between 2011 and 2013 . METHODS Thirty-one women were assigned ( initial 5 consecutively , subsequent 26 r and omly ) to either usual care or an experimental intervention . Participants in usual care received condoms , a dose of emergency contraception , and referral to local providers . Participants in the experimental condition received usual care plus the World Health Organization 's contraception initiation protocol , including free prescription contraceptives , and financial incentives for attending 13 follow-up visits over 6months to help manage side effects and other issues . RESULTS Significantly more women in the experimental vs. usual care control conditions initiated prescription contraceptive use ( 100 % vs. 29 % ) and reported prescription contraceptive use at 1-month ( 63 % vs. 13 % ) , 3-month ( 88 % vs. 20 % ) , and 6-month ( 94 % vs. 13 % ) assessment s. None of the experimental condition participants became pregnant during the 6-month protocol vs. three women ( 20 % ) in the control condition . CONCLUSIONS These results provide the first experimental evidence supporting the efficacy of an intervention for increasing prescription contraceptive use among opioid-maintained women at risk of unintended pregnancy Abstract We prospect ively compared gender outcome among 470 MMT patients admitted between June 1993 and Dec 2002 . Urine sample s were analyzed for drug abuse after one month and after one year . On admission females 131(27.9 % ) were significantly younger ( 34.5 ± 7.5 years ) than males 339(72.1 % ) ( 37.3 ± 8.3 years ) ( ANOVA;F = 11 , p = 0.001 ) and had significantly higher cocaine abuse ( 20 % vs. 11.3 % ) ( Fisher 's Exact Test , p = 0.02 ) . After one year , groups had : ( a ) similar retention in treatment ( 76.3%-females , 72.6%-males ) , ( b ) stop in opiate abuse ( 65%-females , 65.3%-males ) , ( c ) a net decrease in cocaine abuse ( % positive that became negative minus % negative that became positive ) ( 68.0%-females , 51.6%-males ) . Females who were admitted to treatment while pregnant ( n = 45 ) were significantly younger ( 31.5 ± 5.4 years ) compared to 86 non-pregnant ( 36.1 ± 7.9 , ANOVA F = 12.1 , p = 0.001 ) . We concluded that compared to males , females started MMT younger and had a higher proportion of cocaine abuse even though females ' outcome were similar to males ' The aim of this study was to estimate the prevalence of unintended pregnancy and its three subtypes ( mistimed , unwanted , and ambivalent ) among opioid-abusing women . In the general population , 31%-47 % of pregnancies are unintended ; data on unintended pregnancy in opioid- and other drug-abusing women are lacking . Pregnant opioid-abusing women ( N = 946 ) screened for possible enrollment in a multisite r and omized controlled trial comparing opioid maintenance medications completed a st and ardized interview assessing sociodemographic characteristics , current and past drug use , and pregnancy intention . Almost 9 of every 10 pregnancies were unintended ( 86 % ) , with comparable percentages mistimed ( 34 % ) , unwanted ( 27 % ) , and ambivalent ( 26 % ) . Irrespective of pregnancy intention , more than 90 % of the total sample had a history of drug abuse treatment , averaging more than three treatment episodes . Interventions are sorely needed to address the extremely high rate of unintended pregnancy among opioid-abusing women . Drug treatment programs are likely to be an important setting for such interventions Alcohol exposed pregnancy ( AEP ) is a leading cause of preventable birth defects . While r and omized controlled trials ( RCTs ) have shown that multi-session motivational interviewing-based interventions reduce AEP risk , a one-session intervention could facilitate broader implementation . The purpose s of this study were to : ( 1 ) test a one-session motivational AEP prevention intervention for community women and ( 2 ) compare outcomes to previous RCTs . Participants at risk for AEP ( N=217 ) were r and omized to motivational interviewing+ assessment feedback ( EARLY ) , informational video , or informational brochure conditions . Outcomes were drinks per drinking day ( DDD ) , ineffective contraception rate , and AEP risk at 3 and 6 months . All interventions were associated with decreased DDD , ineffective contraception rate , and AEP risk . Participants who received EARLY had larger absolute risk reductions in ineffective contraception and AEP risk , but not DDD . Effect sizes were compared to previous RCTs . The one-session EARLY intervention had less powerful effects than multi-session AEP prevention interventions among community women , but may provide a new option in a continuum of preventive care AIM To test the effectiveness of motivational interviewing ( MI ) to reduce the risk of an alcohol exposed pregnancy ( AEP ) in a high-risk population . DESIGN R and omized controlled trial . SETTING Rural population in the Western Cape , South Africa . PARTICIPANTS A total of 165 women aged 18 - 44 years at risk of AEP . INTERVENTION Five-session MI intervention . MEASUREMENTS Structured question naires were administered pre-intervention and at 3 and 12 months follow-up . The primary outcome measure was AEP at 12 months . Secondary outcomes were AEP at 3 months , and alcohol use and effective contraception at 3 and 12 months . FINDINGS There was a significant difference in the decline in the proportion of women at risk for an AEP in the MI group at 3 months ( 50 versus 24.59 % ; P = 0.004 ) , maintained at 12 months ( 50.82 versus 28.12 % ; P = 0.009 ) . In an intention-to-treat analysis these differences were also significant ( 32.93 versus 18.07 % ; P = 0.029 ; and 37.80 versus 21.69 % ; P = 0.024 , respectively ) . The odds ratio for no longer being at risk of an AEP ( MI versus control ) at 12 months was 2.64 [ 95 % confidence interval ( CI ) : 1.18 - 5.94 ] . In the intention-to-treat analysis this ratio was 2.19 ( 95 % CI : 1.05 - 4.65 ) . CONCLUSIONS A five-session motivational interviewing intervention was found to be effective with women at risk of an alcohol-exposed pregnancy , and could be implemented as part of routine primary care clinic services in similar population s. The message of ' no alcohol in pregnancy ' should be adapted to include better family planning and early recognition of pregnancy |
13,432 | 28,483,983 | Intervention programs design ed to increase immunosuppressive adherence in patients with kidney transplant improve treatment adherence | Immunosuppressive treatment regimens are complex and require ongoing self-management .
Medication adherence can be difficult to achieve for several reasons .
The current meta- analysis and systematic review investigated whether adherence interventions improved immunosuppressive treatment adherence in kidney transplant recipients . | Noncompliance with medication and follow-up care was evaluated in 538 renal , 50 heart , and 13 liver transplant recipients . In a retrospective review of 260 kidney transplant recipients followed from three months posttransplant , the incidence of medication noncompliance was 18 % . It was 15 % in a prospect i ve study of 196 kidney recipients from 1984 to 1987 . Patients most likely to become noncompliant were young and in a lower socioeconomic group . There was no significant difference in the incidence of noncompliance with respect to cadaveric vs. living-related donor kidney source , or in male vs. female patients . There was a higher incidence of noncompliance in blacks and Hispanics , but that may have been due to a higher incidence of lower socioeconomic status in those groups . Noncompliance can occur many years posttransplant and was seen in heart and liver transplant recipients . In the retrospective study , 91 % of kidney transplant recipients who were noncompliant with medications and follow-up care either lost their grafts or died . Noncompliant behavior was usually not predictable and was often without an identifiable reason . Efforts to increase compliance , such as better patient selection , more education , and simplified medical regimens may have reduced the incidence of noncompliance in recent patients The objective of this r and omized controlled trial was to assess the effects of a 1‐year behavioral contract intervention on immunosuppressant therapy ( IST ) adherence and healthcare utilizations and costs among adult renal transplant recipients ( RTRs ) . The sample included adult RTRs who were at least 1 year posttransplant , taking tacrolimus or cyclosporine and served by a specialty pharmacy . Pharmacy refill records were used to measure adherence and monthly question naires were used to measure healthcare utilizations . Direct medical costs were estimated using the 2009 Medicare Expenditure Panel Survey . Adherence was analyzed using the GLM procedure and the MIXED procedure of SAS . Rate ratios and 95 % confidence intervals were estimated to quantify the rate of utilizing healthcare services relative to treatment assignment . One hundred fifty RTRs were enrolled in the study . Intervention group RTRs ( n = 76 ) had higher adherence than control group RTRs ( n = 74 ) over the study period ( p < 0.01 ) . And 76.1 % of the intervention group compared with 42.7 % of the control group was not hospitalized during the 1‐year study period ( RR = 1.785 ; 95 % CI : 1.314 , 2.425 ) , result ing in cost savings . Thus , evidence supports using behavioral contracts as an effective adherence intervention that may improve healthcare outcomes and lower costs Russell C , Conn V , Ashbaugh C , Madsen R , Wakefield M , Webb A , Coffey D , Peace L. Taking immunosuppressive medications effectively ( TIMELink ) : a pilot r and omized controlled trial in adult kidney transplant recipients . Clin Transplant 2011 : 25 : 864–870 . © 2010 John Wiley & Sons Background Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities ( eg , hypertension , diabetes ) . These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients ’ physiological data . This technology is also relatively inexpensive , has an intuitive interface , and provides the capability for real-time personalized feedback to help motivate patient self-efficacy . Automated summary reports of patients ’ adherence and blood pressure can easily be uploaded to providers ’ networks helping reduce clinical inertia by reducing regimen alteration time . Objective The aim of this study was to assess the feasibility , acceptability , and preliminary outcomes of a prototype mobile health ( mHealth ) medication and blood pressure ( BP ) self-management system for kidney transplant patients with uncontrolled hypertension . Methods A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design . The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback . A 3-month proof-of-concept r and omized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray . Participants r and omized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging . Controls received st and ard of care and their adherence continued to be monitored with the medication tray reminders turned off . Providers received weekly summary reports of patient medication adherence and BP readings . Results Participation and retention rates were 41/55 ( 75 % ) and 31/34 ( 91 % ) , respectively . The prototype system appears to be safe , highly acceptable , and useful to patients and providers . Compared to the st and ard care control group ( SC ) , the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations . Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the st and ard care group ( 7 adjustments in 5 patients versus 3 adjustments in 3 patients ) during the 3-month trial based on the information provided in the weekly reports . Conclusions These data support the acceptability and feasibility of the prototype mHealth system . Further trials with larger sample sizes and additional biomarkers ( eg , whole blood medication levels ) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control after kidney transplantation over longer time periods . Trial Registration Clinical trials.gov NCT01859273 ; http:// clinical trials.gov/ct2/show/NCT01859273 ( Archived by WebCite at http://www.webcitation.org/6IqfCa3A3 ) ONCOMPLIANCE posttransplant is postulated to account for up to one third of graft failures due to chronic graft dysfunction . Due to its covert nature , determining the extent of the problem is not easy , and traditional methods tend to underestimate the true scale . More recently , methods of electronic monitoring have been introduced that tend to give a more accurate picture . One hundred stable renal transplant patients ( transplanted 1 year ) were approached and asked if they would use a “ smart top ” pill bottle ( Aardex , Switzerl and ) for their azathioprine/ prednisolone . The tops contain a microprocessor that records the date and time on each occasion the bottle is opened . This information can then be downloaded onto a computer via a modem at their regular clinic visits . The patients were r and omly assigned to groups ; 75 were given smart top bottles , and the other 25 were given plain tops . This latter group received regular interviews by a nurse practitioner and pill counts to assess their compliance . Of 92 patients whose data was available after 3 months ( 93 days ) , 11 ( 46 % ) of the plain top group and 31 ( 46 % ) of the smart top group missed at least one dose in the 3-month period . Twenty-two ( 33 % ) of the smart top group took extra doses in the 3-month period , none of the plain top group were found to have taken extra doses . Only 13 ( 54 % ) of the plain top group and 25 ( 37 % ) of the smart top group were 100 % compliant in the 3-month period ( not significant , chi-square test ) . Both electronic monitoring and nurse practitioner interviews with pill counting appear to be equally sensitive for detecting missed doses , but electronic monitoring measures timing of dosage and can also pick up when consecutive doses are missed . It also picks up when extra doses are taken . Missed doses and extra doses can cancel each other out when pill counts alone are used , which probably accounts for the higher 100 % compliance rate in the plain top group . METHOD One hundred stable renal transplant patients more than 1 year posttransplant were asked if they would use a smart top bottle for their regular once-daily azathioprine or prednisolone . Smart top bottles are medicine bottles with a microprocessor in the cap that records the date and time on each occasion the bottle is opened and closed . This information can then be downloaded onto a computer data base via a special modem at their regular outpatient visits . The patients were r and omly placed into one of two groups . Twenty-five of the patients were given a pill bottle with an ordinary lid on it . They were asked to bring their pill bottles with them to their regular outpatient clinic appointments , at approximately 3-month intervals , along with any remaining medication . They were then interviewed by a nurse practitioner about their compliance , and their remaining tablets were counted . The other 75 patients were given smart top bottles that they were asked to bring with them to their regular out patient appointments . The information was then downloaded from the lid onto the computer data base Background : Non‐compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post‐transplant care . This r and omized , controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients ’ compliance with immunosuppressive agents . Methods : Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were r and omized in the intervention or control group provided they met study criteria . In addition to routine clinic services at each clinic visit , patients in the intervention group received clinical pharmacy services , which included medication histories and review of patients ’ medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events . The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes . To promote medication compliance by using compliance enhancement strategies , the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications . Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction . Compliance rate ( CR ) was calculated and patient 's compliance status was determined from the CR . The CR , the fraction of patients remaining compliant for each month , and the mean time patients were compliant were compared between groups . Whether there was a difference in the frequency of patients achieving ‘ target ’ immunosuppressive levels in the control and study groups was evaluated . Results : The mean CR for patients who had clinical pharmacist intervention ( n=12 ) was statistically higher than the control group 's ( n=12 ) mean CR ( p<0.001 ) . During the 12‐month post‐transplant study period , patients in the intervention group had a longer duration of compliance than patients in the control group ( p<0.05 ) . Additionally , patients who had clinical pharmacy services had a greater achievement of ‘ target ’ levels than patients who did not receive these services ( p<0.05 ) . Conclusions : Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services . Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post‐transplant patients is beneficial for enhancing medication compliance Purpose Solid-organ transplant recipients present a high rate of non-adherence to drug treatment . Few interventional studies have included approaches aim ed at increasing adherence . The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients . Methods In a r and omized prospect i ve study , incident renal transplant patients ( n = 111 ) were divided into two groups : control group ( received usual transplant patient education ) and treatment group ( usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes ) . Treatment adherence was assessed using ITAS adherence question naire after 3 months . Renal function at 3 , 6 , and 12 months , and the incidence of transplant rejection were evaluated . Results The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups ( p = 0.001 ) , respectively . The relative risk for non-adherence was 2.59 times ( CI 1.38–4.88 ) higher in the control group . Multivariate analysis demonstrated a 5.84 times ( CI 1.8–18.8 , p = 0.003 ) higher risk of non-adherence in the control group . There were no differences in renal function and rejection rates between groups . Conclusions A behavioral and educational strategy addressing the patient ’s perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy BACKGROUND Medication adherence is critical for transplant patients because the consequences of non-adherence can result in allograft loss and may be life threatening . METHODS A prospect i ve study with 74 renal transplant recipients using a sequential control group design was performed to investigate the impact of a pharmaceutical intensified care programme led by a clinical pharmacist on daily drug adherence during the first year after renal transplantation . Thirty-nine patients of the control group received the already established st and ardized drug and transplant training , while 35 patients of the intensified care group ( ICG ) received additional inpatient and outpatient pharmaceutical care and counselling by a dedicated clinical pharmacist . Applied interventions were clustered and classified using the behaviour change technique taxonomy according to Michie . Adherence to immunosuppressive drug therapy was monitored up to 1 year using a medication event monitoring system , pill count ( PC ) , drug holiday ( DH ) occurrence , Morisky question naire and self-report . RESULTS Sixty-seven patients ( 35 of the st and ard care and 32 of the ICG ) were analysed . Implementation of DA was significantly ( P = 0.014 ) improved in patients of the ICG ( 91 % ) compared with SCG ( 75 % ) during the first year after transplantion . Daily adherence measures were already improved within 30 - 40 days after start of intensified patient care and continued throughout the study period . Intensified care patients also showed significantly better results for taking adherence ( P = 0.006 ) , PC ( P = 0.008 ) and DHs ( P = 0.001 ) . CONCLUSIONS The additional , intensified pharmaceutical care improved patients ' medication adherence remarkably , suggesting that the applied additional care programme has the potential to improve outcomes after organ transplantation |
13,433 | 24,156,843 | Grasso S , Stripoli T , De Michele M , et al. ARDSnet ventilatory protocol and alveolar hyperinflation : role of positive endexpiratory pressure . | 8 .
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Meade MO , Cook DJ , Guyatt GH , et al. Ventilation strategy using low tidal volumes , recruitment maneuvers , and high positive end‐expiratory pressure for acute lung injury and acute respiratory distress syndrome : a r and omized controlled trial . | Objective : To determine if ketoconazole , a thromboxane A2 synthetase inhibitor , given within the first 24 hrs after diagnosis and arrival in the intensive care unit ( ICU ) would decrease the frequency of adult respiratory distress syndrome in the septic patient population . Design : Prospect i ve , r and omized , double-blind , placeocontrolled study . Setting : Twelve-bed , surgical ICU in a university-affiliated hospital . Patients : Fifty-four consecutive patients admitted to the surgical ICU with the diagnosis of sepsis composed the study sample . Sepsis was defined as including two or more of the following signs in a patient with a systolic blood pressure of < 80 mm Hg or a systemic vascular resistance of < 800 dyne-sec/cm5 : a ) temperature ≥39 ° C or ≤35 ° C ; b ) white blood cell count of > 12,000 leukocytes , or ≤4000 leukocytes/μL , or ≥20 % immature cells ; c ) positive blood culture ; d ) known or strongly suspected source of infection from which a known pathogen was cultured . Interventions : Patients were r and omized to receive either ketoconazole ( 400 mg ) or placebo in a double-blind fashion as early as possible and in < 24 hrs after surgical ICU admission or after the diagnosis of sepsis was established . Measurements and Main Results : Adult respiratory distress syndrome ( ARDS ) was diagnosed if the following criteria were met : a ) intrapulmonary shunt of > 20 % , or a PaO2/Fio2 ratio of < 150 requiring ventilatory support for > 48 hrs ; b ) pulmonary artery occlusion pressure of < 18 nun Hg and no clinical signs of heart failure ; and c ) diffuse infiltrates on chest radiograph . Treatment result ed in significant ( p = .002 ) reduction in the frequency of ARDS compared with the placebo group , 64 % vs. 15 % in the ketoconazole treated group . The mortality rate was also reduced from 39 % in the placebo group to 15 % in the ketoconazole group ( p = .05 ) . A statistically significant reduction in ventilator and ICU days was not achieved . Conclusions : Ketoconazole ( 400 mg through the gastrointestinal tract ) given early in the septic course may prevent ARDS and decrease the mortality rate in high-risk , septic patients . ( Crit Care Med 1993 ; 21:1635–1642 Objective To determine whether caloric intake is associated with risk of nosocomial bloodstream infection in critically ill medical patients . Design Prospect i ve cohort study . Setting Urban , academic medical intensive care unit . Patients Patients were 138 adult patients who did not take food by mouth for ≥96 hrs after medical intensive care unit admission . Measurements Daily caloric intake was recorded for each patient . Participants subsequently were grouped into one of four categories of caloric intake : < 25 % , 25–49 % , 50–74 % , and ≥75 % of average daily recommended calories based on the American College of Chest Physicians guidelines . Simplified Acute Physiology Score II and serum albumin were measured on medical intensive care unit admission . Serum glucose ( average value and maximum value each day ) and route of feeding ( enteral , parenteral , or both ) were collected daily . Nosocomial bloodstream infections were identified by infection control surveillance methods . Main Results The overall mean ( ±sd ) daily caloric intake for all study participants was 49.4 ± 29.3 % of American College of Chest Physicians guidelines . Nosocomial bloodstream infection occurred in 31 ( 22.4 % ) participants . Bivariate Cox analysis revealed that receiving ≥25 % of recommended calories compared with < 25 % was associated with significantly lower risk of bloodstream infection ( relative hazard , 0.24 ; 95 % confidence interval , 0.10–0.60 ) . Simplified Acute Physiology Score II also was associated with risk of nosocomial bloodstream infection ( relative hazard , 1.27 ; 95 % confidence interval , 1.01–1.60 ) . Average daily serum glucose , admission serum albumin , time to initiating nutritional support , and route of nutrition did not affect risk of bloodstream infection . After adjustment for Simplified Acute Physiology Score II in a multivariable analysis , receiving ≥25 % of recommended calories was associated with a significantly lower risk of bloodstream infection ( relative hazard , 0.27 ; 95 % confidence interval , 0.11–0.68 ) . Conclusions In the context of reducing risk of nosocomial bloodstream infections , failing to provide ≥25 % of the recommended calories may be harmful . Higher caloric goals may be necessary to achieve other clinical ly important outcomes We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus . 55 Sprague-Dawley rats were r and omized to either intravenous saline or lipopolysaccharide ( LPS ) . After 50 min of spontaneous respiration , the lungs were excised and r and omized to 2 h of ventilation with one of four strategies : ( a ) control ( C ) , tidal volume ( Vt ) = 7 cc/kg , positive end expiratory pressure ( PEEP ) = 3 cm H2O ; ( b ) moderate volume , high PEEP ( MVHP ) , Vt = 15 cc/kg ; PEEP = 10 cm H2O ; ( c ) moderate volume , zero PEEP ( MVZP ) , Vt = 15 cc/kg , PEEP = 0 ; or ( d ) high volume , zero PEEP ( HVZP ) , Vt = 40 cc/kg , PEEP = 0 . Ventilation with zero PEEP ( MVZP , HVZP ) result ed in significant reductions in lung compliance . Lung lavage levels of TNFalpha , IL-1beta , IL-6 , IL-10 , MIP-2 , and IFNgamma were measured by ELISA . Zero PEEP in combination with high volume ventilation ( HVZP ) had a synergistic effect on cytokine levels ( e.g. , 56-fold increase of TNFalpha versus controls ) . Identical end inspiratory lung distention with PEEP ( MVHP ) result ed in only a three-fold increase in TNFalpha , whereas MVZP produced a six-fold increase in lavage TNFalpha . Northern blot analysis revealed a similar pattern ( C , MVHP < MVZP < HVZP ) for induction of c-fos mRNA . These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung , and thus may play a role in initiating or propagating a local , and possibly systemic inflammatory response OBJECTIVES Recent studies in animal models of sepsis-induced acute respiratory distress syndrome ( ARDS ) have shown that a low-carbohydrate , high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid ( EPA ; fish oil ) , gamma-linolenic acid ( GLA ; borage oil ) ( EPA+GLA ) , and antioxidants improves lung microvascular permeability , oxygenation , and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation . These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS . DESIGN Prospect i ve , multicentered , double-blind , r and omized controlled trial . SETTING Intensive care units of five academic and teaching hospitals in the United States . PATIENTS We enrolled 146 patients with ARDS ( as defined by the American-European Consensus Conference ) caused by sepsis/pneumonia , trauma , or aspiration injury in the study . INTERVENTIONS Patients meeting entry criteria were r and omized and continuously tube-fed either EPA+GLA or an isonitrogenous , isocaloric st and ard diet at a minimum caloric delivery of 75 % of basal energy expenditure x 1.3 for at least 4 - 7 days . MEASUREMENTS AND MAIN RESULTS Arterial blood gases were measured , and ventilator setting s were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2 , a measure of gas exchange . Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points . Clinical outcomes were recorded . Baseline characteristics of 98 evaluable patients revealed that key demographic , physiologic , and ventilatory variables were similar at entry between both groups . Multiple bronchoalveolar lavages revealed significant decreases ( approximately 2.5-fold ) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet . Significant improvements in oxygenation ( PaO2/FIO2 ) from baseline to study days 4 and 7 with lower ventilation variables ( FIO2 , positive end-expiratory pressure , and minute ventilation ) occurred in patients fed EPA+GLA compared with controls . Patients fed EPA+GLA required significantly fewer days of ventilatory support ( 11 vs. 16.3 days ; p = .011 ) , and had a decreased length of stay in the intensive care unit ( 12.8 vs. 17.5 days ; p = .016 ) compared with controls . Only four of 51 ( 8 % ) patients fed EPA+GLA vs. 13 of 47 ( 28 % ) control patients developed a new organ failure during the study ( p = .015 ) . CONCLUSIONS The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment , gas exchange , requirement for mechanical ventilation , length of intensive care unit stay , and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 ) , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS OBJECTIVE To determine whether the implementation of a nutritional management protocol in the ICU leads to the increased use of enteral nutrition , earlier feeding , and improved clinical outcomes in patients . DESIGN Prospect i ve evaluation of critically ill patients before and after the introduction of an evidence -based guideline for providing nutritional support in the ICU . SETTING The medical-surgical ICUs of two teaching hospitals . PATIENTS Two hundred critically ill adult patients who remained npo > 48 h after their admission to the ICU . One hundred patients were enrolled into the preimplementation group , and 100 patients were enrolled in the postimplementation group . INTERVENTION Implementation of an evidence -based ICU nutritional management protocol . MEASUREMENT AND RESULTS Nutritional outcome measures included the number of patients who received enteral nutrition , the time to initiate nutritional support , and the percent caloric target administered on day 4 of nutritional support . Clinical outcomes included the duration of mechanical ventilation , ICU and in-hospital length of stay ( LOS ) , and in-hospital mortality rates . Patients in the postimplementation group were fed more frequently via the enteral route ( 78 % vs 68 % , respectively ; p = 0.08 ) , and this difference was statistically significant after adjusting for severity of illness , baseline nutritional status , and other factors ( odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.2 to 5.0 ; p = 0.009 ) . The time to feeding and the caloric intake on day 4 of nutritional support were not different between the groups . The mean ( + /- SD ) duration of mechanical ventilation was shorter in the postimplementation group ( 17.9 + /- 31.3 vs 11.2 + /- 19.5 days , respectively ; p = 0.11 ) , and this difference was statistically significant after adjusting for age , gender , severity of illness , type of admission , baseline nutritional status , and type of nutritional support ( p = 0.03 ) . There was no difference in ICU or hospital LOS between the two groups . The risk of death was 56 % lower in patients who received enteral nutrition ( hazard ratio , 0.44 ; 95 % CI , 0.24 to 0.80 ; p = 0.007 ) . CONCLUSION An evidence -based nutritional management protocol increased the likelihood that ICU patients would receive enteral nutrition , and shortened their duration of mechanical ventilation . Enteral nutrition was associated with a reduced risk of death in those patients studied Effective prophylaxis against acute respiratory failure ( ARDS ) has not been established . This study investigated whether or not ketoconazole could prevent ARDS in critically ill surgical patients . Seventy-one Surgical Intensive Care Unit ( SICU ) patients without liver dysfunction received either ketoconazole ( n = 35 ) , 200 mg daily via the gastrointestinal tract , or placebo ( n = 36 ) , for 21 days or until discharge from the SICU , in a prospect i ve , r and omized , double-blind study . Patients were monitored clinical ly for signs of ARDS , defined as all the following : intrapulmonary shunt greater than 15 % , a PaO2/FIO2 ratio less than 150 , normal central venous , pulmonary capillary wedge , or left atrial pressure , no other cause of hypoxemia , and a consistent chest X-ray . Thirteen patients ( 18 % ) developed ARDS with significantly increased mortality versus non-ARDS patients ( 69 % vs. 29 % ) . The incidence of ARDS was decreased among ketoconazole patients compared to placebo ( 6 % vs. 31 % ; p less than 0.01 ) , as was median SICU stay ( 7.0 days vs. 15.5 days ; p less than 0.05 ) , and median SICU cost ( + 5,600 . vs. + 12,400 . ; p less than 0.05 ) . Mortality is increased with ARDS after trauma and surgery . We conclude that ketoconazole prevents ARDS , shortens SICU stay , and lowers hospital costs From November 1 , 1982 through December 31 , 1985 , there were 19 centers and 382 patients that evaluated the effect of methylprednisolone sodium succinate ( MPSS ) on the septic syndrome . Seventeen of these centers enrolled 304 patients in a prospect i ve , r and omized , double-blind , placebo-controlled study to determine if early treatment with MPSS would decrease the incidence of severity of the adult respiratory distress syndrome ( ARDS ) in patients at risk of ARDS from sepsis . To ensure early institution of the MPSS or placebo therapy ( PLA ) , patients with the presumptive diagnosis of sepsis were identified . That diagnosis was based on the presence of fever or hypothermia ( temperature greater than 38.3 degrees C or less than 35.5 degrees C , rectal ) , tachypnea ( greater than 20 bpm ) , tachycardia ( greater than 90 bpm ) and the presence of one of the following indices of organ dysfunction : a change in mental status , hypoxemia , elevated lactate levels or oliguria . The treatment , either MPSS 30 mg/kg or PLA , was given in four 20-minute infusions six hours apart and was initiated within two hours of the presumptive diagnosis of sepsis . The development and reversal of the adult respiratory distress syndrome ( ARDS ) was followed and result ed in data on 304 of the 382 r and omized patients . A trend toward increased incidence of ARDS was seen in the MPSS group 50/152 ( 32 percent ) compared to the placebo group 38/152(25 percent ) p = 0.10 . Significantly fewer MPSS patients reversed their ARDS 15/50 ( 31 percent ) compared to placebo 23/38 ( 61 percent ) p = 0.005 . The 14-day mortality in patients with ARDS treated with MPSS was 26/50 ( 52 percent ) compared to placebo 8/22 ( 22 percent ) p = 0.004 . We conclude that early treatment of septic syndrome with MPSS does not prevent the development of ARDS . Additionally , MPSS treatment impedes the reversal of ARDS and increases the mortality rate in patients with ARDS BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water . Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients . METHODS We r and omly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels , which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen . RESULTS Mean ( + /-SD ) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group ( P<0.001 ) . The rates of death before hospital discharge were 24.9 percent and 27.5 percent , respectively ( P=0.48 ; 95 percent confidence interval for the difference between groups , -10.0 to 4.7 percent ) . From day 1 to day 28 , breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group ( P=0.50 ) . CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water , clinical outcomes are similar whether lower or higher PEEP levels are used We conducted a prospect i ve , r and omized , double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury , including the adult respiratory distress syndrome ( ARDS ) , or improve mortality when administered early in septic shock . All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1 , 1983 and August 29 , 1986 were eligible for admission to the study if they had either ( 1 ) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values ( in already hospitalized patients ) , or ( 2 ) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg ( in newly admitted patients ) . Patients meeting these criteria were excluded if they ( 1 ) had severe immunodeficiency , ( 2 ) were less than 18 or greater than 76 yr of age , ( 3 ) had multilobar roentgenographic infiltrates , or ( 4 ) were already receiving corticosteroids . Eighty-seven patients enrolled in the study received either methylprednisolone , 30 mg/kg per dose , or mannitol placebo for a total of 4 doses every 6 h , following the presumptive diagnosis of septic shock . Of these patients , 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry . Thirteen of the patients who received methylprednisolone developed ARDS , compared to 14 patients who received placebo . Lesser degrees of parenchymal lung injury did not differ between the 2 groups . ( ABSTRACT TRUNCATED AT 250 WORDS STUDY OBJECTIVES To assess the consistency of caloric intake with American College of Chest Physicians ( ACCP ) recommendations for critically ill patients and to evaluate the relationship of caloric intake with clinical outcomes . DESIGN Prospect i ve cohort study . SETTING Adult ICUs at two teaching hospitals . PARTICIPANTS Patients with an ICU length of stay of at least 96 h. MEASUREMENTS AND RESULTS On ICU admission , severity of illness ( ie , simplified acute physiology score II ) and markers of nutritional status ( ie , serum albumin level and body mass index ) were recorded . The route of feeding ( ie , enteral or parenteral ) , actual caloric intake ( ie , percentage of ACCP recommendations : 0 to 32 % [ tertile I ] ; 33 to 65 % [ tertile II ] ; > /== " BORDER="0 " > 66 % [ tertile III ] ) , and evidence of GI intolerance ( ie , gastric aspirate levels , > /== " BORDER="0 " > 100 mL ) were recorded daily . The following outcomes were assessed : status on hospital discharge ( alive vs dead ) ; spontaneous ventilation before ICU discharge ( yes vs no ) ; and ICU discharge without developing nosocomial sepsis ( yes vs no ) . The average caloric intake among 187 participants was 50.6 % of the ACCP targets and was similar in both hospitals . Caloric intake was inversely related to the mean number of gastric aspirates > /== " BORDER="0 " > 100 mL/d ( Spearman rho = -0.04 ; p = 0.06 ) , but not to severity of illness , nutritional status , or route of feeding . After accounting for the number of gastric aspirates > /== " BORDER="0 " > 100 mL , severity of illness , nutritional status , and route of feeding , tertile II of caloric intake ( vs tertile I ) was associated with a significantly greater likelihood of achieving spontaneous ventilation prior to ICU discharge . Tertile III of caloric intake ( vs tertile I ) was associated with a significantly lower likelihood of both hospital discharge alive and spontaneous ventilation prior to ICU discharge . CONCLUSIONS Study participants were underfed relative to ACCP targets . These targets , however , may overestimate needs , since moderate caloric intake ( ie , 33 to 65 % of ACCP targets ; approximately 9 to 18 kcal/kg per day ) was associated with better outcomes than higher levels of caloric intake Objective To determine the association of pulmonary artery catheter ( PAC ) use with in-hospital mortality . Design Prospect i ve , observational study . Setting The medical intensive care units ( MICU ) of two teaching hospitals . Methods The study included 751 adults who were admitted to the MICU , excluding those who stayed for < 24 hrs . Demographics and the worst Acute Physiology and Chronic Health Evaluation ( APACHE ) II score within the first 24 hrs of MICU admission were obtained . Daily logistic organ dysfunction system ( LODS ) scores were calculated . The associations of in-hospital mortality with the admission source , admission disease category , APACHE II scores , the worst LODS scores , mechanical ventilation , and PAC use were determined using chi-square , Mann-Whitney U , and multiple logistic regression analysis tests . p Values < 0.05 were considered significant . Results Mean patient age was 52.6 ± 17.1 yrs ; 425 ( 57 % ) were male ; 464 ( 62 % ) were African-American , 275 ( 37 % ) Caucasian , 6 ( 1 % ) Asian , and 6 ( 1 % ) Hispanic . PAC was used in 119/751 ( 16 % ) . The median APACHE II and worst LODS scores were 19 and 4 , respectively . The in-hospital mortality rate was 159/751 ( 21 % ) . The median APACHE II score for survivors was 17.5 , compared with 28.0 for nonsurvivors ( p < .0001 ) . The worst median LODS score was 4 for survivors , compared with 11 for nonsurvivors ( p < .0001 ) . Sixty-four ( 54 % ) of the 119 patients with PAC died , compared with 95 ( 15 % ) of the 632 without PAC ( p < .0001 ) . Multiple logistic regression analysis showed that higher APACHE II-predicted mortality rate ( p = .0088 ) and worst daily LODS score ( p < .0001 ) were associated with increased mortality . The admission source , admission disease category , PAC use , and mechanical ventilation were not associated with in-hospital mortality . Conclusions This study could not detect an association between PAC use and mortality . The APACHE II-predicted mortality rate and the development of multiple organ dysfunction were the main determinants of poor outcome in critically ill patients admitted to MICU PURPOSE The purpose of this study was to develop , implement , and evaluate a practice guideline using ketoconazole for the prevention of the adult respiratory distress syndrome ( ARDS ) in critically ill patients . MATERIAL S AND METHODS In hospital A ( study hospital ) , we developed a guideline for ketoconazole prophylaxis in patients at high risk of ARDS using evidence from two r and omized trials . We prospect ively implemented the guideline using intensive care unit ( ICU ) teaching sessions , in-services , informational posters , and patient-specific individual audit and feedback . ICU caregivers in hospital B ( concurrent control hospital ) did not participate in the guideline development or implementation and were unaware of the conduct of the study . RESULTS Patients at risk of ARDS were similar in hospitals A and B. Implementation of the guideline was associated with a significantly higher use of ketoconazole use for ARDS prevention ( P < .0001 ) and a significantly lower rate of ARDS ( P < .05 ) in hospital A compared with hospital B. Mortality , duration of ventilation , and ICU stay were similar . CONCLUSION Development and implementation of a prophylactic ketoconazole practice guideline for ICU patients at high risk of ARDS was associated with a higher prescription of ketoconazole and a lower rate of ARDS in the study hospital than in the control hospital BACKGROUND This study sought to compare 2 strategies for the administration of enteral feeding to mechanically ventilated medical patients . METHODS The prospect i ve , controlled , clinical trial was carried out in a medical intensive care unit ( 19 beds ) in a university-affiliated , urban teaching hospital . Between May 1999 and December 2000 , 150 patients were enrolled . Patients were scheduled to receive their estimated total daily enteral nutritional requirements on either day 1 ( early-feeding group ) or day 5 ( late-feeding group ) of mechanical ventilation . Patients in the late-feeding group were also scheduled to receive 20 % of their estimated daily enteral nutritional requirements during the first 4 days of mechanical ventilation . RESULTS Seventy-five ( 50 % ) consecutive eligible patients were entered into the early-feeding group and 75 ( 50 % ) patients were enrolled in the late-feeding group . During the 5 five days of mechanical ventilation , the total intake of calories ( 2370 + /- 2000 kcal versus 629 + /- 575 kcal ; p < .001 ) and protein ( 93.6 + /- 77.2 g versus 26.7 + /- 26.6 g ; p < .001 ) were statistically greater for patients in the early-feeding group . Patients in the early-feeding group had statistically greater incidences of ventilator-associated pneumonia ( 49.3 % versus 30.7 % ; p = .020 ) and diarrhea associated with Clostridium difficile infection ( 13.3 % versus 4.0 % ; p = .042 ) . The early-feeding group also had statistically longer intensive care unit ( 13.6 + /- 14.2 days versus 9.8 + /- 7.4 days ; p = .043 ) and hospital lengths of stay ( 22.9 + /- 19.7 days versus 16.7 + /- 12.5 days ; p = .023 ) compared with patients in the late-feeding group . No statistical difference in hospital mortality was observed between patients in the early-feeding and late-feeding groups ( 20.0 % versus 26.7 % ; p = .334 ) . CONCLUSIONS The administration of more aggressive early enteral nutrition to mechanically ventilated medical patients is associated with greater infectious complications and prolonged lengths of stay in the hospital . Clinicians must balance the potential for complications result ing from early enteral feeding with the expected benefits of such therapy Corticosteroids are widely used as therapy for the adult respiratory distress syndrome ( ARDS ) without proof of efficacy . We conducted a prospect i ve , r and omized , double-blind , placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia , diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization . The causes of ARDS included sepsis ( 27 percent ) , aspiration pneumonia ( 18 percent ) , pancreatitis ( 4 percent ) , shock ( 2 percent ) , fat emboli ( 1 percent ) , and miscellaneous causes or more than one cause ( 42 percent ) . Fifty patients received methylprednisolone ( 30 mg per kilogram of body weight every six hours for 24 hours ) , and 49 received placebo according to the same schedule . Serial measurements were made of pulmonary shunting , the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen , the chest radiograph severity score , total thoracic compliance , and pulmonary-artery pressure . We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry . Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality ( respectively , 30 of 50 [ 60 percent ; 95 percent confidence interval , 46 to 74 ] and 31 of 49 [ 63 percent ; 95 percent confidence interval , 49 to 77 ] ; P = 0.74 ) or in the reversal of ARDS ( 18 of 50 [ 36 percent ] vs. 19 of 49 [ 39 percent ] ; P = 0.77 ) . However , the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment . Infectious complications were similar in the methylprednisolone group ( 8 of 50 [ 16 percent ] ) and the placebo group ( 5 of 49 [ 10 percent ] ; P = 0.60 ) . Our data suggest that in patients with established ARDS due to sepsis , aspiration , or a mixed cause , high-dose methylprednisolone does not affect outcome The ability of the imidazole derivative , ketoconazole , to inhibit thromboxane (Tx)A2 synthesis in response to ischemia was tested in ten volunteers . Two hours after taking placebo or ketoconazole 400 mg by mouth , plasma levels of the stable degradation product of TxA2 , TxB2 , were 300 + /- 129 pg/ml ( mean + /- SEM ) and 297 + /- 80 pg/ml , respectively . Arm ischemia for 10 min induced by inflation of a cuff to 220 mm Hg led to a rise in TxB2 levels to 657 + /- 157 pg/ml after placebo ( p less than 0.05 ) and 337 + /- 81 pg/ml after ketoconazole . One hour after cuff deflation , TxB2 returned to pre-ischemia levels in both groups . Platelet TxB2 concentrations were 27 + /- 6 ng in the placebo and 35 + /- 6 ng/10(9 ) platelets in the ketoconazole group , and were unchanged by cuff inflation . The fact that plasma and platelet TxB2 values were not lower 2 hr after ketoconazole treatment was explored in another group of four nonstressed volunteers who received 400 mg of drug . After 2 hr , TxB2 values had fallen from 170 + /- 30 pg to 120 + /- 10 pg ; at 4 hr , 6 hr , and 8 hr they were 30 + /- 20 pg , 5 + /- 5 pg , and 5 + /- 5 pg/ml , respectively . These results indicate that tourniquet ischemia provokes TxA2 synthesis , and that the source of this prostanoid is likely to be ischemic tissue and not platelets . Finally , ketoconazole can profoundly inhibit both background and stimulated TxA2 synthesis BACKGROUND The objective of this study was to determine whether caloric intake independently influences mortality and morbidity of critically ill patients . METHODS The study was conducted as a nested cohort study within a r and omized controlled trial in a tertiary care intensive care unit ( ICU ) . The main exposure in the study was average caloric intake/target for the first 7 ICU days . The primary outcomes were ICU and hospital mortality . Secondary outcomes included ICU-acquired infections , ventilator-associated pneumonia ( VAP ) , duration of mechanical ventilation days , and ICU and hospital length of stay ( LOS ) . The authors divided patients ( n = 523 ) into 3 tertiles according to the percentage of caloric intake/target : tertile I < 33.4 % , tertile II 33.4%-64.6 % , and tertile III > 64.6 % . To adjust for potentially confounding variables , the authors assessed the association between caloric intake/target and the different outcomes using multivariate logistic regression for categorical outcomes ( tertile I was used as reference ) and multiple linear regression for continuous outcomes . RESULTS Tertile III was associated with higher adjusted hospital mortality , higher risk of ICU-acquired infections , and a trend toward higher VAP rate . Increasing caloric intake was independently associated with a significant increase in duration of mechanical ventilation , ICU LOS , and hospital LOS . CONCLUSIONS The data demonstrate that near-target caloric intake is associated with significantly increased hospital mortality , ICU-acquired infections , mechanical ventilation duration , and ICU and hospital LOS . Further studies are needed to explore whether reducing caloric intake would improve the outcomes in critically ill patients |
13,434 | 29,271,339 | VCE technologies , using HD systems without magnification , could potentially be used for the real-time assessment of diminutive colorectal polyps , if endoscopists have adequate experience and training . | BACKGROUND Current clinical practice is to remove a colorectal polyp detected during colonoscopy and determine whether it is an adenoma or hyperplastic by histopathology .
Identifying adenomas is important because they may eventually become cancerous if untreated , whereas hyperplastic polyps do not usually develop into cancer , and a surveillance interval is set based on the number and size of adenomas found .
Virtual chromoendoscopy ( VCE ) ( an electronic endoscopic imaging technique ) could be used by the endoscopist under strictly controlled conditions for real-time optical diagnosis of diminutive ( ≤ 5 mm ) colorectal polyps to replace histopathological diagnosis .
OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of the VCE technologies narrow-b and imaging ( NBI ) , flexible spectral imaging colour enhancement ( FICE ) and i-scan for the characterisation and management of diminutive ( ≤ 5 mm ) colorectal polyps using high-definition ( HD ) systems without magnification . | BACKGROUND Chromoendoscopy can accurately differentiate neoplastic from nonneoplastic polyps in the colon . Narrow b and imaging ( NBI ) has been described as " electronic chromoendoscopy , " but it is unclear whether pit patterns seen with chromoendoscopy are identical to those with NBI . OBJECTIVE Pilot study to compare features of diminutive polyps assessed with magnification NBI and chromoendoscopy . DESIGN Prospect i ve polyp series . SETTING Single tertiary referral center in the United Kingdom . PATIENTS Twenty patients seen for routine colonoscopy . INTERVENTION Digital images of each polyp recorded with NBI and chromoendoscopy were subsequently assessed as single images in a r and om order and as paired polyp images by experienced European- and Japanese-trained endoscopists . MAIN OUTCOME MEASUREMENTS Pit pattern ( Kudo classification ) ; vascular pattern intensity ( weak , normal , strong ) ; predicted histology ; pit pattern and vessel network clarity ( scale 1 - 3 , 1 poor , 3 excellent ) . RESULTS A total of 33 polyps < or=6 mm were assessed . Chromoendoscopic and NBI pit patterns were different for 12 and 20 of 33 polyps ( Japanese and European , respectively ) , combined kappa 0.23 , P < .001 compared with published intraobsever variation . Sensitivity , specificity , and accuracy for neoplasia were comparable for chromoendoscopic and NBI pit patterns and vascular pattern intensity for both observers . Vessel network clarity was better with NBI , P < .001 ( both ) , as was pit pattern clarity , P = .04 ( European ) . LIMITATIONS Small sample size ; pilot study . CONCLUSIONS Pit patterns were not always identical with NBI and chromoendoscopy . The Kudo classification may need to be modified and revali date d before it can be used with confidence with NBI . Vascular pattern intensity , a simple color change , appears as accurate as pit pattern Objective Cap-assisted colonoscopy ( CAC ) uses a small plastic transparent cap attached to the tip of the colonoscope that can depress and flatten colonic folds and thus improve visualisation of their proximal aspects . The aim of this study was to compare CAC with st and ard colonoscopy ( SC ; high-definition white light ) for adenoma detection rates . Design This is a prospect i ve r and omised controlled trial . Setting The study was performed in a tertiary-care Veterans Affairs Medical Center in the USA . Patients Subjects undergoing screening or surveillance colonoscopy were enrolled . Interventions Subjects were r and omised to undergo either CAC or SC . Main outcome measures The outcome measures were the proportion of subjects with at least one adenoma , the number of adenomas detected per subject , insertion time , caecal intubation rates and complications . Results 420 subjects were enrolled and included in the study ( 210 in each group ) . The proportion of subjects with at least one adenoma was higher with CAC compared to SC ( 69 % vs 56 % , p=0.009 ) . CAC also detected a higher number of adenomas per subject ( 2.3 vs 1.4 , p<0.001 ) . The caecal intubation time was shorter with CAC ( 3.29 min vs 3.98 min , p<0.001 ) . The caecal intubation rates were similar in the two groups ( 99 % vs 98 % , p=0.37 ) . There were no complications associated with CAC or SC . Conclusions CAC detected a 13 % higher number of subjects with at least one adenoma and 59 % higher adenomas per subject . CAC is a safe , effective and practical means to improve adenoma detection rates . Clinical Trial Registration NCT 01211132 Objectives Colonoscopy is central to colorectal cancer ( CRC ) screening . Success of CRC screening is dependent on colonoscopy quality . The NHS Bowel Cancer Screening Programme ( BCSP ) offers biennial faecal occult blood ( FOB ) testing to 60–74 year olds and colonoscopy to those with positive FOB tests . All colonoscopists in the screening programme are required to meet predetermined st and ards before starting screening and are subject to ongoing quality assurance . In this study , the authors examine the quality of colonoscopy in the NHS BCSP and describe new and established measures to assess and maintain quality . Design The NHS BCSP data base collects detailed data on all screening colonoscopies . Prospect ively collected data from the first 3 years of the programme ( August 2006 to August 2009 ) were analysed . Colonoscopy quality indicators ( adenoma detection rate ( ADR ) , polyp detection rate , colonoscopy withdrawal time , caecal intubation rate , rectal retroversion rate , polyp retrieval rate , mean sedation doses , patient comfort scores , bowel preparation quality and adverse event incidence ) were calculated along with measures of total adenoma detection . Results 2 269 983 individuals returned FOB tests leading to 36 460 colonoscopies . Mean unadjusted caecal intubation rate was 95.2 % , and mean withdrawal time for normal procedures was 9.2 min . The mean ADR per colonoscopist was 46.5 % . The mean number of adenomas per procedure ( MAP ) was 0.91 ; the mean number of adenomas per positive procedure ( MAP+ ) was 1.94 . Perforation occurred after 0.09 % of procedures . There were no procedure-related deaths . Conclusions The NHS BCSP provides high- quality colonoscopy , as demonstrated by high caecal intubation rate , ADR and comfort scores , and low adverse event rates . Quality is achieved by ensuring BCSP colonoscopists meet a high st and ard before starting screening and through ongoing quality assurance . Measuring total adenoma detection ( MAP and MAP+ ) as adjuncts to ADR may further enhance quality assurance Background Diminutive ( ≤5 mm ) colorectal polyps are common , and overwhelmingly benign . Routinely , after polypectomy , they are examined pathologically to determine the surveillance intervals . Advances in equipment and techniques , such as narrow-b and imaging ( NBI ) colonoscopy , now permit reliable real-time optical diagnosis . Methods We conducted a r and omised single-masked study involving three institutions to determine whether optical diagnosis of diminutive colorectal polyps meets clinical practice st and ards and reduces the need for histopathology . We r and omly assigned eligible patients undergoing routine high-definition colonoscopy to optical diagnosis using near focus versus st and ard view , using computer-generated block sequence . By vali date d criteria , we rendered an optical diagnosis and a confidence level ( high vs low ) for all polyps , using NBI . Our primary endpoint was the number of accurate high-confidence optical diagnoses compared with central blinded pathology in the two groups . We analysed data using intention to treat . Findings We enrolled 558 subjects , and r and omly assigned 281 to near focus and 277 to st and ard view optical diagnosis . We detected 1309 predominantly diminutive ( 74.5 % ) and neoplastic ( 60.0 % ) polyps . Endoscopists were significantly more likely , OR 2.2 ( 95 % CI 1.6 to 3.0 , p<0.0001 ) , to make a high-confidence optical diagnosis with near focus ( 85.1 % ) than st and ard ( 72.6 % ) view . High-confidence diagnoses had 96.4 % and 92.0 % negative predictive value , respectively . Of all polyps , 75.3 % ( 95 % CI71.3 % to 78.9 % ) had a high-confidence accurate prediction using near focus , compared with 63.1 % ( 95 % CI 58.5 % to 67.6 % ) using st and ard view . Optical versus histopathological diagnosis showed excellent agreement between the surveillance intervals , 93.5 % in near focus and 92.2 % in st and ard view . The median diagnosis time was 14 s. Conclusions Real-time optical diagnosis using NBI colonoscopy may replace the pathology diagnosis for the majority of diminutive colorectal polyps . Using colonoscopy with near focus view increases the confidence level of the optical diagnosis . Optical diagnosis would be a paradigm shift in clinical practice of colonoscopy for colorectal cancer screening . Trial registration number Clinical Trials.gov Identifier : NCT01288833 BACKGROUND The EPKi system ( Pentax , Japan ) enables resolution above HDTV . Aim of the study was to test the efficacy of HD+ alone and with the new post-processing digital filter i-Scan or chromoendoscopy ( Methylene blue 0.1 % ) in screening for colorectal cancer . We focused on lesions less than 5 mm as a surrogate marker for the optical possibilities of the EPKi system . METHODS The last 30 cm of the colon in a screening population were inspected with HD+ alone , in combination with i-Scan ( 2:1 r and omisation ) and subsequently with chromoendoscopy . All lesions were characterized and targeted biopsies were performed . RESULTS i-Scan augmented in 69 patients the identification of lesions from 176 to 335 ( p<0.001 ) and chromoendoscopy to 646 ( p<0.001 ) . The additional lesions were mainly flat ( type IIb , 74 % ) , which were only recognized using i-Scan or chromoendoscopy . The amount of neoplasias was not significantly different ( HD+ : 5 , i-Scan : 11 , Chromoendoscopy : 11 ) , but all could correctly be predicted using i-Scan or chromoendoscopy . CONCLUSIONS HD+ colonoscopy with and without i-Scan unmask a plethora of small lesions but chromoendoscopy can even advance the number . However , i-Scan was able to predict neoplasia as precisely as chromoendoscopy and might shortly replace chromoendoscopy as a more time efficient tool BACKGROUND AND STUDY AIMS Narrow-b and imaging ( NBI ) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps . In patients with small polyps ( < 10 mm ) , the application of NBI within a " resect and discard " strategy , might allow post-polypectomy surveillance intervals to be determined independently from histopathology . The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice . PATIENTS AND METHODS Consecutive colonoscopy out patients with one or more polyps smaller than 10 mm were prospect ively included . Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria , and future post-polypectomy surveillance interval was assigned accordingly . Following histopathology , post-polypectomy surveillance interval was subsequently re-assigned , and the accordance between endoscopy- and histology-directed surveillance strategies was calculated . RESULTS Among 942 colonoscopy patients , 286 ( 30.4 % ) with only small polyps were included . In total , 511 small polyps were evaluated ; 350 ( 68.5 % ) were adenomas and 18 of these ( 5.1 % ) had histologic features of advanced neoplasia . For the in vivo diagnosis of adenoma , NBI sensitivity , specificity , accuracy , and positive and negative likelihood ratios were 94.9 % , 65.8 % , 85.7 % , 2.80 , and 0.08 , respectively . The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients ( 82.9 % ) . In 9.8 % and 7.3 % patients , the endoscopy-directed approach would have result ed in early and delayed surveillance , respectively . CONCLUSIONS The resect and discard strategy seems to be a viable , safe , and cost-effective approach for the management of patients with small polyps . However , caution in the application of the strategy should be advocated for patients with polyps 6 - 9 mm in size and those with right-sided lesions , due to their malignant potential . The study was registered on Clinical trials.gov ( NCT01462123 ) OBJECTIVES : St and ard white light colonoscopy has limited ability to differentiate between polyp types ( adenomatous vs. hyperplastic ) . Narrow b and imaging ( NBI ) highlights the superficial mucosal/vascular patterns on polyps and may facilitate real-time characterization of polyp histology . The aim of this study was to prospect ively evaluate and compare the diagnostic characteristics of high-definition white light colonoscopy ( HDWL ) and NBI without magnification in the real-time prediction of polyp histology ( adenomatous vs. hyperplastic ) by evaluating the surface mucosal and vascular patterns . METHODS : We conducted a prospect i ve comparative study in a tertiary referral center . A total of 100 patients referred for screening or surveillance colonoscopy were prospect ively enrolled and underwent colonoscopy using a high-definition colonoscope with NBI capability . Every polyp detected was initially evaluated with HDWL followed by NBI for the presence of surface mucosal/vascular patterns . Based on these patterns , polyp histology was predicted by both modalities . The main outcome measurements were : ( i ) diagnostic characteristics of HDWL and NBI in predicting polyp histology and ( ii ) impact of polyp size and learning effect ( first half of study vs. second half ) on the ability of NBI to predict adenomas . RESULTS : A total of 236 polyps were detected in 100 patients —143 adenomas , 77 hyperplastic , and 16 others . Surface patterns ( type A : hyperplastic ; type B : adenomatous ) were recognized in all polyps with NBI ( 100 % ) compared to 45 % with HDWL . For predicting adenomas , NBI had a significantly higher sensitivity and greater accuracy ( 96 and 93 % respectively ) compared with HDWL ( 38 and 61 % respectively ) ( all P<0.0001 ) . Although the accuracy of NBI for predicting adenomas improved with increasing polyp size ( ≤5 mm ; 6–9 mm ; ≥10 mm ) and in the second half compared with the first half of the study , these differences were not statistically significant . CONCLUSIONS : Using a simple surface mucosal/vascular pattern classification , NBI without magnification was highly accurate and significantly superior to HDWL for the real-time prediction of adenomas Abstract Background “ Resect and discard ” ( RD ) is a new paradigm for management of diminutive polyps . Aim To compare concordance of surveillance interval recommendations and diagnostic performance between RD and st and ard of care in a hospital outpatient department with both academic and community gastroenterologists . Methods Prospect i ve , observational study conducted at a single outpatient endoscopy center over 12 months . Patients with diminutive polyps on screening or surveillance colonoscopy were included . Histology predictions for all diminutive polyps ( ≤5 mm ) were made based on endoscopic imaging . Concordance of recommended surveillance intervals and diagnostic performance of histology predictions were compared to histopathological review . Results A total of 606 diminutive polyps were found in 315 patients ( mean age 62.4 years , 49 % female ) . Histological prediction was made in 95.7 % of polyps ( 97.4 % of patients ) , with high confidence in 74.3 % . The concordance for surveillance intervals was 82.1 % compared to histopathological review and was similar between community and academic gastroenterologists ( 80.2 vs. 76.3 % , p = 0.38 ) . Overall , sensitivity , specificity , and accuracy of histological predictions made with high confidence were 0.81 , 0.36 , and 77.1 % . Predictions made with narrow-b and imaging ( NBI ) had lower accuracy ( 73.9 % with NBI vs. 82.5 % with high-definition white light ( HWDL ) only , p = 0.017 ) as well as lower prediction confidence ( score of 7.6 with NBI vs. 8.6 with HDWL only , p < 0.001 ) . Conclusions Our surveillance interval concordance was below the 90 % threshold deemed acceptable by the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations statement . Diagnostic performance using optical imaging to predict histology was equal between community and academic endoscopists BACKGROUND Digital chromoendoscopy ( DCE ) has the potential for the in vivo optical diagnosis of colon polyps . However , no comparison of different DCE technologies currently exists . OBJECTIVE To compare the diagnostic efficacies of narrow-b and imaging ( NBI ) with those of I-Scan for the real-time histological prediction of diminutive colonic polyps ( DCPs ) ( ≤5 mm ) by using the simple unified endoscopic classification . DESIGN Prospect i ve cohort study . SETTING Academic hospital . PATIENTS In total , 296 DCPs from 142 patients undergoing screening or surveillance colonoscopy were assessed . INTERVENTIONS All DCPs detected during withdrawal were evaluated for the surface details by using high-definition white-light colonoscopy , and thereafter by using DCE ( NBI or I-Scan ) without optical magnification . The histology of all polyps was predicted in real-time and confirmed through the evaluation of biopsy or polypectomy specimens . MAIN OUTCOME MEASUREMENTS Diagnostic efficacies of NBI and I-Scan . RESULTS NBI and I-Scan displayed a significantly higher sensitivity and improved accuracy compared with high-definition white-light colonoscopy for the prediction of adenomas ( P < .05 ) . No significant differences were evident between the NBI and I-Scan ( sensitivity , 88.8 % vs 94.6 % ; specificity , 86.8 % vs 86.4 % ; accuracy , 87.8 % vs 90.7 % , respectively ; P > .05 ) . Additionally , substantial levels of intra- and interobserver agreement between the NBI and I-Scan were measured ( κ values > 0.7 ) . LIMITATIONS No r and omized or crossover design . CONCLUSIONS NBI and I-Scan displayed a similar efficacy for the real-time histological prediction of DCPs . The simple unified endoscopic classification can be used for the interpretation of DCE , regardless of the type of technology . ( CLINICAL TRIAL REGISTRATION NUMBER NCT1133041 . ) BACKGROUND Experts can accurately characterize the histology of diminutive polyps with narrow-b and imaging ( NBI ) . There are limited data on the performance of non-experts . OBJECTIVE To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts ( in academics and community practice ) by using video clips . DESIGN Prospect i ve , observational study . SETTING Academic and community practice . PARTICIPANTS A total of 15 gastroenterologists participated-5 experts in NBI , 5 non-experts in academic practice , and 5 non-experts in community practice . INTERVENTION Participants review ed a 20-minute , computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps . MAIN OUTCOME MEASUREMENTS Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before ( pretest ) and after ( posttest ) review ing the teaching module . RESULTS Non-experts in academic practice showed a significant improvement in the sensitivity ( 54 % vs 79 % ; P < .001 ) , accuracy ( 64 % vs 81 % ; P < .001 ) , and proportion of high-confidence diagnoses ( 49 % vs 69 % ; P < .001 ) in the posttest . Non-experts in community practice had significantly higher sensitivity ( 58 % vs 75 % ; P = .004 ) , specificity ( 76 % vs 90 % ; P = .04 ) , accuracy ( 64 % vs 81 % ; P < .001 ) , and proportion of high-confidence diagnoses ( 49 % vs 72 % ; P < .001 ) in the posttest . Performance of experts in NBI was significantly better than non-experts in both academic and community practice . LIMITATIONS Selection bias in selecting good quality videos . Performance not assessed during live colonoscopy . CONCLUSION Academic and community gastroenterologists without prior experience in NBI can achieve significant improvements in characterizing diminutive polyp histology after a brief computer-based training . The durability of these results and applicability in everyday practice are uncertain BACKGROUND Missing adenomas and the inability to accurately differentiate between polyp histology remain the main limitations of st and ard-definition white-light ( SD-WL ) colonoscopy . OBJECTIVE To compare the adenoma detection rates of SD-WL with those of high-definition white-light ( HD-WL ) and narrow-b and imaging ( NBI ) as well as the accuracy of predicting polyp histology . DESIGN Multicenter , prospect i ve , r and omized , controlled trial . SETTING Two academic medical centers in the United States . PATIENTS Subjects undergoing screening or surveillance colonoscopy . INTERVENTION Subjects were r and omized to undergo colonoscopy with one of the following : SD-WL , HD-WL , or NBI . MAIN OUTCOME MEASUREMENTS The proportion of subjects detected with adenomas , adenomas detected per subject , and the accuracy of predicting polyp histology real time . RESULTS A total of 630 subjects were included . The proportion of subjects with adenomas was 38.6 % with SD-WL compared with 45.7 % with HD-WL and 46.2 % with NBI ( P = .17 and P = .14 , respectively ) . Adenomas detected per subject were 0.69 with SD-WL compared with 1.12 with HD-WL and 1.13 with NBI ( P = .016 and P = .014 , respectively ) . HD-WL and NBI detected more subjects with flat and right-sided adenomas compared with SD-WL ( all P values < .005 ) . NBI had a superior sensitivity ( 90 % ) and accuracy ( 82 % ) to predict adenomas compared with SD-WL and HD-WL ( all P values < .005 ) . LIMITATIONS Academic medical centers with experienced endoscopists . CONCLUSIONS There was no difference in the proportion of subjects with adenomas detected with SD-WL , HD-WL , and NBI . However , HD-WL and NBI detected significantly more adenomas per subject ( > 60 % ) compared with SD-WL . NBI had the highest accuracy in predicting adenomas in real time during colonoscopy . ( CLINICAL TRIAL REGISTRATION NUMBER NCT 00614770 . ) BACKGROUND This r and omised controlled trial is examining the hypothesis that a single flexible sigmoidoscopy screening offered at around age 60 years can lower the incidence and mortality of colorectal cancer . We report here on acceptability , safety , feasibility , and yield . METHODS Men and women aged 55 - 64 years , in 14 UK centres , who responded to a mailed question naire that they would attend for flexible sigmoidoscopy screening if invited , were r and omly assigned screening or control ( ratio one to two ) . The control group was not contacted . Small polyps were removed during screening , and colonoscopy was undertaken if high-risk polyps ( three or more adenomas , size 1 cm or greater , villous , severely dysplastic , or malignant ) were found . FINDINGS Of 354,262 people asked about their interest in having flexible sigmoidoscopy screening , 194,726 ( 55 % ) responded positively , and 170,432 eligible individuals were r and omised . Attendance among those assigned screening was 71 % ( 40,674 of 57,254 ) . 2131 ( 5 % ) were classified as high-risk and referred for colonoscopy ; 38,525 with no polyps or only low-risk polyps detected were discharged . Distal adenomas were detected in 4931 ( 12.1 % ) and distal cancer in 131 ( 0.3 % ) . Proximal adenomas were detected in 386 ( 18.8 % of those undergoing colonoscopy ) and proximal cancer in nine cases ( 0.4 % ) . 62 % of cancers were Dukes ' stage A or locally excised . There was one perforation after flexible sigmoidoscopy and four after colonoscopy . An average of 48 people were screened , and two or three colonoscopy referrals generated , per centre each week . Interpretation Our flexible sigmoidoscopy screening regimen is acceptable , feasible , and safe . The prevalence of neoplasia is high , and colonoscopy referral rates of 5 % are acceptable BACKGROUND AND AIMS The aim of the study was to identify endoscopist-related and procedural factors that may be associated with the quality of optical diagnosis of diminutive polyps using narrow-b and imaging ( NBI ) . METHODS All subjects who participated in a r and omized trial on cap-assisted colonoscopy were eligible for the current study . Optical polyp diagnosis was an a priori outcome of the initial trial . Ten participating endoscopists used NBI to assess all of the diagnosed polyps as adenomatous or non-adenomatous in real-time and provided a degree of diagnostic certainty . The main outcome measures were quality benchmarks of optical diagnosis ( negative predictive value [ NPV ] for diminutive rectosigmoid adenomas , agreement with pathology-based surveillance interval ) and assessment of endoscopist-related and procedural factors potentially associated with the quality of optical diagnosis . RESULTS A total of 1650 polyps were found in 607 patients , with 1311 polyps ( 79 % ) being diminutive , of which 672 ( 53 % ) were adenomatous . The NPV of optical diagnosis for rectosigmoid adenomas was 95 % . The optical diagnosis-based surveillance interval agreed with the pathology-based recommendation in 93 % of patients . Prior experience with image-enhanced endoscopy had no effect on optical diagnosis . Low and high adenoma detectors were not different in achieving the quality benchmarks . Cap-assisted colonoscopy was not associated with quality of optical diagnosis . Quality metrics of optical diagnosis remained similar during the first and second half of the study period . CONCLUSION High quality optical diagnosis of diminutive polyps can be achieved and sustained by endoscopists previously inexperienced in this practice with minimal training . None of the examined factors appear to affect the quality of optical diagnosis ; particularly , endoscopists ' adenoma detection was not associated with optical diagnosis BACKGROUND In vivo prediction of colorectal polyp histology by narrow-b and imaging ( NBI ) could potentially avoid post-polypectomy histologic examination or resection of diminutive lesions , thereby reducing costs and risk . OBJECTIVE To assess whether NBI is able to predict colonoscopy surveillance intervals and histology of distal diminutive polyps according to American Society for Gastrointestinal Endoscopy ( ASGE ) criteria . DESIGN Prospect i ve , multicenter study . SETTING Five endoscopic centers . PATIENTS Consecutive patients undergoing colonoscopy in 5 centers were included . INTERVENTION Participating endoscopists were required to pass a before- study qualifying examination . Histology of polyps that were < 10 mm was predicted at NBI and assigned a design ation of high or low confidence . MAIN OUTCOME MEASUREMENTS Accuracy of high-confidence NBI prediction for polyps ≤5 mm in predicting surveillance intervals and negative predictive value ( NPV ) for adenomatous histology in the rectosigmoid colon were compared with the ASGE thresholds ( 90 % agreement , 90 % NPV ) . RESULTS A total of 278 patients ( mean age , 63 years ; 58 % male ) were enrolled . At colonoscopy , 574 ( 97.3 % ) polyps < 10 mm ( 429 ≤5 mm , 60 % adenomatous ) were retrieved for histologic analysis . Sensitivity , specificity , positive and negative predictive values , and accuracy of high confidence-NBI predictions for adenomatous histology in lesions ≤5 mm were 90 % , 88 % , 89 % , 89 % , and 89 % , respectively . High-confidence characterization of polyps ≤5 mm predicted the correct surveillance interval in 92 % to 99 % of cases , according to the American and European guidelines . NPV of high-confidence NBI for adenomatous histology for the rectosigmoid colon lesions ≤5 mm was 92 % . LIMITATIONS Only experienced endoscopists were included . CONCLUSION High-confidence prediction of histology for polyps ≤5 mm appears to be sufficiently accurate to avoid post-polypectomy histologic examination of the resected lesions as well as to allow rectosigmoid hyperplastic polyps to be left in place without resection . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01675752 . ) This article is one of a series of statements discussing the use of gastrointestinal endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text . In preparing this guideline , a MEDLINE literature search was performed , and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When little or no data exist from well design ed prospect i ve trials , emphasis is given to results from large series and reports from recognized experts . Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus . Further controlled clinical studies are needed to clarify aspects of this statement , and revision may be necessary as new data appear . Clinical consideration may justify a course of action at variance to these recommendations . This guideline replaces and supplements our previous document on colorectal cancer screening and surveillance BACKGROUND Optical diagnostic involves predicting polyp histopathology from its endoscopic characteristics . It is only recommended for diminutive polyps ( < or = 5 mm ) and for predictions made with high confidence . OBJECTIVES To evaluate the accuracy of optical imaging in clinical practice and to assess if optical diagnosis is useful for predicting future colonoscopy surveillance intervals without waiting for histopathological analysis . METHODS consecutive > 18 years patients were enrolled in this prospect i ve study . Colonoscopies were performed by five expert endoscopists who previously participated in an ex-vivo training . Colonoscopes CF-H180AL and CF-Q180AL were used together with Exera II ( Olympus Medical System , Tokyo , Japan ) processors . Each polyp was characterized in real time using white light and Narrow B and Imaging . Accuracy of optical diagnosis ( S , E , NPV , PPV ) and correlation between surveillance interval based on optical diagnosis and histopathological analysis were calculated . RESULTS 311 colon polyps < 10 mm ( 216 diminutive ) in 195 patients were analyzed . Accuracy of optical diagnostics for predictions made with high confidence : Diminutive polyps(sensitivity 0.59 , specificity 0.92 , NPV 0.48 ) ; polyps < 10 mm ( sensitivity 0.73 , specificity 0.88 , NPV 0.50 ) . An optical diagnosis based surveillance recommendation was given to 90 patients . Concordance with histopathology based recommendation was 92.2 % according to the European guideline and 93.3 % according to the ESGE guideline . CONCLUSIONS Optical diagnostics can be used to predict future surveillance intervals immediately after colonoscopy . However , in this study , based on clinical practice , the accuracy of optical imaging is below the recommended st and ards BACKGROUND Although the risk of bowel perforation is often cited as a major factor in the choice between colonoscopy and sigmoidoscopy for colorectal screening , good estimates of the absolute and relative risks of perforation are lacking . METHODS We used a large population -based cohort that consisted of a r and om sample of 5 % of Medicare beneficiaries living in regions of the United States covered by the Surveillance , Epidemiology , and End Results ( SEER ) Program registries to determine rates of perforation in people aged 65 years and older . We identified individuals who were cancer-free and had undergone colonoscopy or sigmoidoscopy between 1991 and 1998 , calculated both the incidence and risk of perforation within 7 days of the procedure , and explored the impact on incidence and risk of perforation of age , race/ethnicity , sex , comorbidities , and indication for the procedure . We also estimated the risk of death after perforation . Risks were calculated with odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS There were 77 perforations after 39 286 colonoscopies ( incidence = 1.96/1000 procedures ) and 31 perforations after 35 298 sigmoidoscopies ( incidence = 0.88/1000 procedures ) . After adjustment , the OR for perforation from colonoscopy relative to perforation from sigmoidoscopy was 1.8 ( 95 % CI = 1.2 to 2.8 ) . Risk of perforation from either procedure increased in association with increasing age ( P(trend)<.001 for both procedures ) and the presence of two or more comorbidities ( P(trend)<.001 for colonoscopy and P(trend ) = .03 for sigmoidoscopy ) . Compared with those who were endoscopied and did not have a perforation , the risk of death was statistically significantly increased for those who had a perforation after either colonoscopy ( OR = 9.0 , 95 % CI = 3.0 to 27.3 ) or sigmoidoscopy ( OR = 8.8 , 95 % CI = 1.6 to 48.5 ) . The risk of perforation after colonoscopy , especially for screening procedures , declined during the 8-year study period . CONCLUSIONS The risk of perforation after colonoscopy is approximately double that after sigmoidoscopy , but this difference appears to be decreasing . These observations should be useful to clinicians making screening and diagnostic decisions for individual patients and to policy officials setting guidelines for colorectal cancer screening programs Background Distal diminutive colorectal polyps are common and accurate endoscopic prediction of hyperplastic or adenomatous polyp histology could reduce procedural time , costs and potential risks associated with the resection . Within this study we assessed whether digital chromoendoscopy can accurately predict the histology of distal diminutive colorectal polyps according to the ASGE PIVI statement . Methods In this prospect i ve cohort study , 224 consecutive patients undergoing screening or surveillance colonoscopy were included . Real time histology of 121 diminutive distal colorectal polyps was evaluated using high-definition endoscopy with digital chromoendoscopy and the accuracy of predicting histology with digital chromoendoscopy was assessed . Results The overall accuracy of digital chromoendoscopy for prediction of adenomatous polyp histology was 90.1 % . Sensitivity , specificity , positive and negative predictive values were 93.3 , 88.7 , 88.7 , and 93.2 % , respectively . In high-confidence predictions , the accuracy increased to 96.3 % while sensitivity , specificity , positive and negative predictive values were calculated as 98.1 , 94.4 , 94.5 , and 98.1 % , respectively . Surveillance intervals with digital chromoendoscopy were correctly predicted with > 90 % accuracy . Conclusions High-definition endoscopy in combination with digital chromoendoscopy allowed real-time in vivo prediction of distal colorectal polyp histology and is accurate enough to leave distal colorectal polyps in place without resection or to resect and discard them without pathologic assessment . This approach has the potential to reduce costs and risks associated with the redundant removal of diminutive colorectal polyps . Trial registration Clinical Trials NCT02217449 Background and study aims : The real-time optical diagnosis of colorectal polyps with high confidence predictions can achieve high levels of accuracy . Increasing the rates of high confidence optical diagnosis can improve the clinical application of real-time optical diagnosis in routine practice . The primary aim of this prospect i ve study was to evaluate whether high magnifying endoscopy improves the rates of high confidence narrow-b and imaging ( NBI ) – based optical diagnosis for differentiating between neoplastic and non-neoplastic colorectal lesions according to the NBI international colorectal endoscopic ( NICE ) classification . Patients and methods : Consecutive adult patients undergoing colonoscopy with a high magnifying ( maximum , × 80 ) colonoscope between April and August 2012 were recruited . The optical diagnosis for each polyp was evaluated during colonoscopy in two consecutive stages by the same endoscopist , who first used NBI with non-magnifying endoscopy ( NBI-NME ) , then NBI with magnifying endoscopy ( NBI-ME ) . A level of confidence was assigned to each prediction . Results : The analysis included 124 patients ( mean age , 56.4 years ; male-to-female ratio , 72:52 ) with 248 polyps smaller than 10 mm . Of the 248 polyps , 210 were 1 to 5 mm in size and 38 were 6 to 9 mm in size ; 77 polyps were hyperplastic , 4 were sessile serrated adenomas/polyps , 160 were low grade adenomas , 5 were high grade adenomas , and 2 were deep submucosal invasive carcinomas . The rate of high confidence optical diagnosis when NBI-ME was used was significantly higher than the rate when NBI-NME was used for diminutive ( 1 – 5 mm ) polyps ( 92.9 % vs 79.5 % , P < 0.001 ) and for small ( 6 – 9 mm ) polyps ( 94.7 % vs 84.2 % , P = 0.048 ) . Conclusion : High magnifying endoscopy significantly improved the rates of high confidence NBI-based optical diagnosis of diminutive and small colorectal polyps . Study registration : UMIN Background and study aims : Sessile serrated adenoma/polyps ( SSA/Ps ) are considered precursors of colorectal cancers with microsatellite instability . However , it is still difficult to differentiate SSA/Ps from hyperplastic polyps endoscopically ; therefore , the prevalence of SSA/Ps remains uncertain in clinical practice . This study aim ed to clarify the proportion of SSA/Ps in endoscopically diagnosed colorectal polyps with hyperplastic features ( E-HPs ) . Patients and methods : Patients aged ≥ 40 years undergoing colonoscopy for st and ard clinical indications at our center were prospect ively enrolled between June 2013 and May 2014 . During colonoscopy , 0.05 % indigo carmine dye was sprayed throughout the colorectum to highlight lesions . All detected lesions were diagnosed by high definition magnifying narrow-b and imaging and were resected endoscopically or surgically , apart from rectosigmoid E-HPs ≤ 5 mm . The number of rectosigmoid E-HPs ≤ 5 mm was recorded , and some were resected for use as tissue sample s. Results : A total of 343 patients ( male : 42.9 % ; mean age : 61.5 years ) were included . Among 3838 E-HPs ( distal : 96.4 % ) detected in 294 patients , 792 were resected and analyzed . All of 21 SSA/Ps identified in 17 patients were included in E-HPs , and the overall proportion of SSA/Ps in E-HPs was 2.7 % . However , this proportion increased with the size of E-HPs ( ≤ 5 mm : 0.7 % ; 6 – 9 mm : 29.0 % ; ≥ 10 mm : 70 % ) and was higher in the proximal colon than in the distal colorectum ( 10.9 % vs. 0.9 % ) . In addition , no SSA/P was found in the rectum , and no SSA/P had cytological dysplasia . Conclusions : The overall proportion of SSA/Ps in E-HPs was 2.7 % , although this proportion was higher in the proximal colon and increased with the size of E-HPs . SSA/Ps were common in routine colonoscopy , with a prevalence of at least 5.0 % . Study registration : UMIN000010832 Background There are limited data on the performance of narrow b and imaging ( NBI ) and Fujinon intelligent color enhancement ( FICE ) for differentiating polyp histologies . Aims The aim of this study was to compare the diagnostic performances of NBI and FICE in differentiating neoplastic from non-neoplastic colorectal polyps < 10 mm during screening colonoscopy . Methods A total of 955 average-risk adults undergoing screening colonoscopies were r and omly allocated to NBI or FICE groups . Four board-certified staff endoscopists without prior experience using NBI or FICE participated . The main outcomes of this study were overall accuracy , sensitivity , and specificity of FICE and NBI in identifying neoplastic polyps . Results There was no significant difference in the number of subjects with adenoma between the NBI ( 143/475 , 30.1 % ) and FICE groups ( 139/480 , 29.0 % ) ( after excluding adenoma ≥1 cm ) ( P > 0.05 ) . The overall accuracy of NBI was 81.0 % , compared with 81.4 % for FICE ( P = 0.867 ) . The overall sensitivity and specificity of NBI and FICE were 84.6 and 78.0 % ( P = 0.054 ) ; 75.1 and 86.5 % ( P = 0.009 ) , respectively . For polyps measuring ≤5 mm , the accuracy was 79.4 % for NBI and 80.1 % for FICE ( P = 0.835 ; sensitivity 81.9 vs. 74.5 % , P = 0.064 ; specificity 75.7 vs. 88.4 % , P = 0.006 ) . Conclusions The overall accuracy of NBI and FICE was similar for differentiating small polyp histologies during screening colonoscopy . However , better results should be achieved before using NBI or FICE as real-time optical biopsy of colorectal polyps in screening colonoscopy Purpose Aim of the study was the evaluation of high-definition white light ( HDWL ) i-Scan endoscopy for diagnostic prediction of histology , inter- and intraobserver agreement for colorectal polyps . Methods In this prospect i ve single-center cohort study , a skilled endoscopist , with HDWL i-Scan , predicted on real-time the histology of 150 polyps from 78 patients undergoing colonoscopy . Subsequently , four endoscopists , not involved in the collection of cases , predicted the polyps ' histology ( neoplastic vs nonneoplastic ) and repeated the assessment after 6 months . Results Real-time assessment of the lesions predicted a correct histology in 138/150 cases with a sensitivity , specificity , and accuracy of 95 , 82 , and 92 % , respectively . Sensitivity , specificity , and accuracy of post-acquisition evaluation were 87.7 , 61.7 , and 82.2 % , respectively . The κ values of inter- and intraobserver agreement of prediction of histology were 0.462 ( 0.373–0.537 ) and 0.657 ( 0.523–0.917 ) . Among the subset of polyps ( n = 82 ) with good/excellent quality image , sensitivity and accuracy of HDWL i-Scan improved ( 97 % , p = 0.003 and 94 % , p = 0.002 , respectively ) as well as κ value of interobserver agreement ( 0.699 ) . Conclusions HDWL i-Scan technology helps for characterization of polyps of the colon with good accuracy even if it can not replace , at the moment , the histopathological examination . Reproducibility among operators is supported by a moderate substantial interobserver and intraobserver agreement BACKGROUND Colonoscopy with narrow-b and imaging can allow real-time determination of polyp histology . OBJECTIVE To determine whether physicians with varying levels of experience can learn and apply endoscopic criteria to distinguish between adenomas and hyperplastic polyps . DESIGN Prospect i ve observational study . SETTING University teaching hospital . PARTICIPANTS This study involved 37 physicians ( medical residents , N = 12 ; gastroenterology fellows , N = 12 ; and gastroenterology faculty , N = 13 ) . INTERVENTION Small-group , 20-minute , didactic teaching sessions in which the endoscopic criteria for determining polyp histology by using narrow-b and imaging were described and demonstrated . MAIN OUTCOME MEASUREMENTS Learning outcomes were evaluated by using written pretests and posttests in which participants scored pathologically verified , high-definition polyp photographs as adenomas or hyperplastic polyps . RESULTS The mean overall scores increased significantly from 47.6 % correct on the pretest to 90.8 % correct on the posttest ( P = .0001 ) . The overall mean percentage of responses answered do n't know was significantly lower on the posttest ( 0.6 % ) compared with the pretest ( 20.5 % , P < .0001 ) . After training , the level of agreement was substantial ( kappa = 0.69 for all participants , kappa = 0.79 for fellows ) . LIMITATIONS Our study did not assess for sustained improvement with time or in vivo accuracy of histological prediction during live colonoscopy . Further validation in a sample of community physicians is required . CONCLUSION A short , didactic teaching session can achieve high accuracy and good interobserver agreement in the use of narrow-b and imaging for determining the histology of colorectal polyps BACKGROUND Experts are accurate in differentiating small adenomas from hyperplastic polyps at colonoscopy by using narrow-b and imaging ( NBI ) . OBJECTIVE To prospect ively evaluate the effectiveness of an NBI training module on individuals with varying colonoscopy experience . DESIGN Prospect i ve educational evaluation study . SETTING Academic endoscopy unit . PARTICIPANTS Twenty-one participants of varying colonoscopy experience ( novices , trainees , and experienced gastroenterologists ) and 5 experts in NBI . INTERVENTION Participants completed a computer-based test module consisting of 30 NBI polyp images . No feedback was given . They then completed a computer-based training module on the use of NBI in the differentiation of adenomas and hyperplastic polyps . The test module was then completed a second time . MAIN OUTCOME MEASUREMENTS Construct validity ( the difference in baseline accuracy on the test module between different groups of participants ) and content validity ( difference in accuracy achieved on the test module before and after training ) of the training module . RESULTS There was a significant difference in the baseline accuracy ( P < .001 ) between experts ( 0.95 ; 95 % confidence interval [ CI ] , 0.92 - 0.97 ) , experienced colonoscopists ( 0.68 ; 95 % CI , 0.68 - 0.74 ) , trainees ( 0.75 ; 95 % CI , 0.67 - 0.82 ) , and novices ( 0.62 ; 95 % CI , 0.46 - 0.77 ) . Accuracy increased significantly ( P < .001 ) for all 3 groups after training ( novices 0.84 ; 95 % CI , 0.78 - 0.88 , trainees 0.90 ; 95 % CI , 0.84 - 0.93 , and experienced colonoscopists 0.84 ; 95 % CI , 0.76 - 0.89 ) . After training , the agreement was moderate at least ( κ = 0.56 for novices , κ = 0.70 for trainees , and κ = 0.54 for experienced colonoscopists ) . LIMITATIONS This study did not assess the accuracy of optical diagnosis in routine clinical practice . CONCLUSION A short , computer-based training module can improve the diagnostic accuracy and interobserver agreement for the use of NBI to differentiate adenomas from hyperplastic polyps and could be used for the initial training in optical diagnosis BACKGROUND Accurate colonoscopic assessment of colorectal polyp histology could avoid resection of distal nonadenomatous polyps and reduce costs and risk . OBJECTIVE To assess the accuracy of predicting histology by using narrow-b and imaging ( NBI ) in real time for distal colorectal polyps . DESIGN Prospect i ve observational study . SETTING University hospital and ambulatory surgery center . PATIENTS This study involved 225 consecutive adults undergoing elective screening or surveillance colonoscopy . INTERVENTION We evaluated real-time histology of 235 distal ( rectosigmoid ) colorectal polyps from 31 patients by using high-definition colonoscopy and NBI without optical magnification . For each polyp , the endoscopist described size , Paris classification , and surface characteristics ( vascular and pit pattern , color , pseudodepression ) . Before resection , histology was predicted , and a level of confidence ( high or low ) was assigned . MAIN OUTCOME MEASUREMENTS Sensitivity and negative predictive value of high-confidence endoscopic predictions of adenomatous versus hyperplastic histology for polyps ≤ 5 mm . RESULTS The accuracy of a high-confidence endoscopic prediction was 97.7 % , sensitivity for adenomatous histology 93.9 % , specificity 98.4 % , negative predictive value 97.9 % , and positive predictive value 75.6 % . The performance characteristics for predicting diminutive distal polyps ( ≤ 5 mm ) with high confidence were sensitivity 96.0 % , specificity 99.4 % , negative predictive value 99.4 % , and positive predictive value 96.0 % . LIMITATIONS Single-center study with a single endoscopist . CONCLUSION NBI without optical magnification is sufficiently accurate to allow distal hyperplastic polyps to be left in place without resection and small , distal adenomas to be discarded without pathologic assessment . These findings vali date NBI criteria based on color , vessels , and pit characteristics for predicting real-time colorectal polyp histology BACKGROUND A simple endoscopic classification to accurately predict deep submucosal invasive ( SM-d ) carcinoma would be clinical ly useful . OBJECTIVE To develop and assess the validity of the NBI international colorectal endoscopic ( NICE ) classification for the characterization of SM-d carcinoma . DESIGN The study was conducted in 4 phases : ( 1 ) evaluation of endoscopic differentiation by NBI-experienced colonoscopists ; ( 2 ) extension of the NICE classification to incorporate SM-d ( type 3 ) by using a modified Delphi method ; ( 3 ) prospect i ve validation of the individual criteria by inexperienced participants , by using high-definition still images without magnification of known histology ; and ( 4 ) prospect i ve validation of the individual criteria and overall classification by inexperienced participants after training . SETTING Japanese academic unit . MAIN OUTCOME MEASUREMENTS Performance characteristics of the NICE criteria ( phase 3 ) and overall classification ( phase 4 ) for SM-d carcinoma ; sensitivity , specificity , predictive values , and accuracy . RESULTS We exp and ed the NICE classification for the endoscopic diagnosis of SM-d carcinoma ( type 3 ) and established the predictive validity of its individual components . The negative predictive values of the individual criteria for diagnosis of SM-d carcinoma were 76.2 % ( color ) , 88.5 % ( vessels ) , and 79.1 % ( surface pattern ) . When any 1 of the 3 SM-d criteria was present , the sensitivity was 94.9 % , and the negative predictive value was 95.9 % . The overall sensitivity and negative predictive value of a global , high-confidence prediction of SM-d carcinoma was 92 % . Interobserver agreement for an overall SM-d carcinoma prediction was substantial ( kappa 0.70 ) . LIMITATIONS Single Japanese center , use of still images without prospect i ve clinical evaluation . CONCLUSION The NICE classification is a valid tool for predicting SM-d carcinomas in colorectal tumors BACKGROUND The presence of meshed capillary ( MC ) vessels is highly sensitive ( 96 % ) and specific ( 92 % ) for diagnosing colorectal neoplasia on colonoscopy by using narrow-b and imaging ( NBI ) with optical magnification , which is not available in North America . However , the efficacy of NBI to identify an MC pattern without optical magnification has not been determined . OBJECTIVE To determine the diagnostic capabilities of NBI colonoscopy without optical magnification in differentiating neoplastic from non-neoplastic colorectal polyps by using the MC pattern . DESIGN Retrospective comparison of prospect ively collected colorectal polyp data . SETTING Large , academic medical center . PATIENTS This study involved 126 consecutive colorectal polyps ( median size 3 mm ) that were found in 52 patients ( 33 men ) with a median age of 59.5 years . INTERVENTION All lesions identified by white-light colonoscopy were prospect ively diagnosed in real-time by using the MC pattern as determined on high-definition NBI , with 1.5x zoom but without true optical magnification , and then endoscopically excised . Surgical pathology was used as the criterion st and ard . MAIN OUTCOME MEASUREMENTS Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of identifying neoplastic polyps were calculated . RESULTS NBI without optical magnification was found to have a sensitivity of 93 % , specificity of 88 % , positive predictive value of 90 % , negative predictive value of 91 % , and diagnostic accuracy of 91 % when all polyp sizes were considered . For lesions < or = 5 mm , sensitivity was 87 % , specificity was 93 % , positive predictive value was 89 % , negative predictive value was 91 % , and diagnostic accuracy was 90 % . LIMITATIONS Single-center , single-endoscopist experience . CONCLUSION Use of the MC pattern on NBI colonoscopy without optical magnification effectively distinguishes neoplastic from non-neoplastic colorectal polyps . NBI colonoscopy without optical magnification for neoplastic polyp diagnosis appears to be comparable with NBI with optical magnification when the MC pattern is used . A large , prospect i ve trial is needed for further validation BACKGROUND Colonoscopy is the preferred screening method for colorectal cancer . However , it has a substantial miss rate for colon polyps , and several techniques have been attempted to improve this limitation . Narrow-b and imaging ( NBI ) is a novel technology that enhances the visualization of surface mucosal and vascular patterns . OBJECTIVE The aim of this study was to determine the detection rate of additional polyps by NBI after removal of polyps visualized by st and ard white light colonoscopy ( WLC ) and to correlate the surface mucosal and vascular patterns with polyp histologic diagnosis . DESIGN This was a prospect i ve pilot feasibility study . SETTING Kansas City Veterans Affairs Medical Center . PATIENTS Subjects referred for screening colonoscopy were prospect ively enrolled . METHODS Subjects underwent colonoscopy after enrollment . After intubation of the cecum , colonic segments were sequentially examined , initially with WLC with removal of polyps followed by re-examination of the same segment with NBI . Additional polyps seen with NBI were photographed for their surface patterns and then removed . The total number of polyps visualized by WLC and NBI was calculated and the surface patterns were then correlated with polyp histologic features . RESULTS Forty patients were enrolled in the study , all men , 32 white . The mean age was 62 years . A total of 72 polyps were detected by WLC ( 43 tubular adenoma , 28 hyperplastic polyps ) , whereas NBI detected an additional 51 polyps , of which 29 were tubular adenomas and 22 were hyperplastic . Five different surface/vascular patterns were observed : fine capillary network with absent mucosal pattern , circular pattern with dots , round/oval pattern , tubular pattern , and gyrus pattern . The sensitivity , specificity , and overall accuracy of the first two patterns for hyperplastic polyps were 86 % , 96 % , and 92 % , respectively , and of the latter three patterns for tubular adenomas were 96 % , 86 % , and 92 % , respectively . CONCLUSIONS This pilot study demonstrates the feasibility of polyp detection and histologic correlation with NBI . These findings need to be confirmed in future r and omized controlled trials BACKGROUND & AIMS Accurate optical analysis of colorectal polyps ( optical biopsy ) could prevent unnecessary polypectomies or allow a " resect and discard " strategy with surveillance intervals determined based on the results of the optical biopsy ; this could be less expensive than histopathologic analysis of polyps . We prospect ively evaluated real-time optical biopsy analysis of polyps with narrow b and imaging ( NBI ) by community-based gastroenterologists . METHODS We first analyzed a computerized module to train gastroenterologists ( N = 13 ) in optical biopsy skills using photographs of polyps . Then we evaluated a practice -based learning program for these gastroenterologists ( n = 12 ) that included real-time optical analysis of polyps in vivo , comparison of optical biopsy predictions to histopathologic analysis , and ongoing feedback on performance . RESULTS Twelve of 13 subjects identified adenomas with > 90 % accuracy at the end of the computer study , and 3 of 12 subjects did so with accuracy ≥90 % in the in vivo study . Learning curves showed considerable variation among batches of polyps . For diminutive rectosigmoid polyps assessed with high confidence at the end of the study , adenomas were identified with mean ( 95 % confidence interval [ CI ] ) accuracy , sensitivity , specificity , and negative predictive values of 81 % ( 73%-89 % ) , 85 % ( 74%-96 % ) , 78 % ( 66%-92 % ) , and 91 % ( 86%-97 % ) , respectively . The adjusted odds ratio for high confidence as a predictor of accuracy was 1.8 ( 95 % CI , 1.3 - 2.5 ) . The agreement between surveillance recommendations informed by high-confidence NBI analysis of diminutive polyps and results from histopathologic analysis of all polyps was 80 % ( 95 % CI , 77%-82 % ) . CONCLUSIONS In an evaluation of real-time optical biopsy analysis of polyps with NBI , only 25 % of gastroenterologists assessed polyps with ≥90 % accuracy . The negative predictive value for identification of adenomas , but not the surveillance interval agreement , met the American Society for Gastrointestinal Endoscopy-recommended thresholds for optical biopsy . Better results in community practice must be achieved before NBI-based optical biopsy methods can be used routinely to evaluate polyps ; Clinical Trials.gov number , NCT01638091 Background Many authors have already reported the usefulness of narrow-b and imaging ( NBI ) for the differential diagnosis of non-neoplastic and neoplastic colorectal lesions . However , it is not clear whether magnification is required for differential diagnosis . The aim of this prospect i ve study was to clarify the clinical usefulness of a newly developed NBI system with a dual focus function ( dual-focus NBI ) compared with conventional white-light imaging ( WLI ) and NBI without magnification for distinguishing between non-neoplastic and neoplastic lesions . Patients and Methods Thirty-seven consecutive patients who underwent screening colonoscopy with the novel system between July and December 2013 were analyzed . Patients with polyps > 10 mm and those with polyps previously evaluated by histologic examination or colonoscopy were excluded . Lesions were diagnosed in real time with WLI , NBI without magnification , and dual-focus NBI , and then excised endoscopically . Each diagnosis was compared to that in the final histopathology reports . The primary endpoint was the diagnostic accuracy and the confidence level assigned to each modality by the endoscopists . The secondary endpoint was the differentiation ability according to the size of the lesion ( ≤5 and 6–10 mm ) . Results In all , 100 lesions including 76 adenomatous polyps and 24 hyperplastic polyps were analyzed in 37 patients . The overall diagnostic accuracy , sensitivity , and specificity for differentiating adenomatous from hyperplastic polyps were 87.0 , 89.5 , and 79.2 % for WLI , 93.0 , 94.7 , and 87.5 % for NBI without magnification , and 94.0 , 96.1 , and 87.5 % for dual-focus NBI , respectively . The level of confidence was significantly different between dual-focus NBI and WLI and NBI without magnification for diminutive ( ≤5 mm ) lesions ( p < 0.001 and p < 0.01 ) . Conclusion Dual-focus NBI is especially useful for differential diagnosis of diminutive colorectal lesions BACKGROUND AND AIMS Prospect i ve information on the use and yield of surveillance colonoscopy is limited . We examined the use and yield of surveillance colonoscopy among participants in the Polyp Prevention Trial ( PPT ) after the 4-year dietary intervention trial ended . METHODS We followed a cohort of 1297 participants . We calculated the cumulative probability of posttrial colonoscopy and investigated the yield and predictive factors for adenoma and advanced adenoma recurrence over a mean time of 5.9 years . RESULTS Seven-hundred seventy-four subjects ( 59.7 % ) had a repeat colonoscopy . Among 431 subjects with low-risk adenomas ( 1 - 2 nonadvanced adenomas ) at baseline and no adenoma recurrence at the end of the PPT ( lowest-risk category ) , 30.3 % underwent a repeat colonoscopy within 4 years . Among 55 subjects who had high-risk adenomas ( advanced adenoma and /or > or =3 nonadvanced adenomas ) at baseline and again at the final PPT colonoscopy ( highest-risk category ) , 41.3 % had a colonoscopy within 3 years and 63.5 % had an examination within 5 years . The cumulative yield of advanced adenoma through 6 years was 3.6 % for the lowest-risk category , 38.9 % for the highest-risk category , and ranged from 6.6 % to 13.8 % for intermediate-risk categories . An advanced adenoma at the final PPT colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance ( hazard ratio , 6.2 ; 95 % confidence interval , 2.5 - 15.4 ) . CONCLUSIONS Surveillance colonoscopy was overused for low-risk subjects and underused for high-risk subjects . Advanced adenoma yield corresponded with the adenoma risk category . Re source consumption can be better managed by aligning use with the risk of adenoma recurrence BACKGROUND Traditional white-light endoscopy can not reliably distinguish between small ( < 10 mm ) adenomatous and hyperplastic colon polyps . High-definition white-light ( HDWL ) endoscopy and i-Scan may improve in vivo characterization of small colon polyps . OBJECTIVE To compare HDWL endoscopy and HDWL plus i-Scan for the assessment of small colon polyps and to measure performance against the American Society for Gastrointestinal Endoscopy ( ASGE ) thresholds for assessment of diminutive colon polyps . DESIGN Prospect i ve cohort study . SETTING Single academic hospital . PATIENTS Patients undergoing bowel cancer screening colonoscopy . INTERVENTION In vivo assessment of all polyps < 10 mm by using HDWL and i-Scan image enhancement . MAIN OUTCOME MEASUREMENTS The primary outcome measure was overall diagnostic accuracy of in vivo assessment of colon polyps < 10 mm . Secondary outcome measures were sensitivity and specificity for adenomatous histology , negative predictive value for adenomatous histology of diminutive rectosigmoid polyps , and accuracy of prediction of polyp surveillance intervals . RESULTS A total of 209 polyps in 84 patients were included . There were no significant differences between HDWL endoscopy and i-Scan in characterization of polyps < 10 mm ( accuracy 93.3 % vs 94.7 % ; P = 1.00 ; sensitivity 95.5 % vs 97.0 % ; P = .50 ; specificity 89.3 % vs 90.7 % ; P = 1.00 ) . The negative predictive value for adenomatous histology of diminutive rectosigmoid polyps was 100 % with both HDWL endoscopy and i-Scan . U.K. and U.S. polyp surveillance intervals were predicted with 95.2 % accuracy with HDWL endoscopy and 97.2 % accuracy with i-Scan . LIMITATIONS Single-center study . CONCLUSION HDWL endoscopy may be as accurate as HDWL with i-Scan image enhancement for the in vivo characterization of small colon polyps . Both modalities fulfil the ASGE performance thresholds for the assessment of diminutive colon polyps . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01761279 . ) BACKGROUND & AIMS There are limited data describing the performance of Fuji Intelligent Color Enhancement ( FICE , EC 590 ZW ; Fujinon Inc , Saitama , Japan ) for differentiating polyp histologies during screening colonoscopy . We evaluated the ability of an endoscopist to diagnose small polyp histology during a screening colonoscopy using FICE . METHODS A prospect i ve study was performed on 763 consecutive , asymptomatic subjects who were undergoing screening colonoscopy . Pit patterns and vascular patterns were used to predict the histology of 525 polyps ( mean size , 4.5 ± 2.2 mm , 315 adenomas ) of less than 10 mm using FICE with high magnification and without . The performances of the FICE analyses were calculated and compared with the results from the histopathology . RESULTS The overall accuracy achieved by FICE with high magnification in the diagnosis of adenomas of less than 10 mm ( 87.0 % ) was significantly greater than that achieved without high magnification ( 80.4 % ; P < .05 ) . Moreover , the improvement of accuracy attained when using high-magnification FICE was most pronounced and significant compared without using high-magnification FICE in the diagnosis for diminutive polyps ( ≤5 mm ; 85.4 % vs 79.1 % ; P < .05 ) . Among all types of adenomas , the sensitivity of FICE was lowest for sessile serrated adenomas ( 38.5 % vs 89.4 % ; P < .01 ) , even when FICE was used with high magnification . CONCLUSIONS FICE with high magnification is better for differentiating the histology of small polyps during screening colonoscopy than FICE without high magnification , especially for diminutive polyps . Large-scale studies are needed to improve the identification of serrated adenomas and small diminutive polyps using FICE BACKGROUND There is no widely adopted , easily applied method for distinguishing between adenomatous and nonadenomatous polyps during real-time colonoscopy . OBJECTIVE To compare white light ( WL ) with narrow-b and imaging ( NBI ) for the differentiation of colorectal polyps in vivo and to assess for a learning curve . DESIGN A prospect i ve polyp series . PATIENTS AND SETTING A total of 302 patients referred for colonoscopy , between August 2006 and July 2007 , to a single tertiary-referral center in the United States . INTERVENTION St and ard WL colonoscopy was performed with Olympus 180-series colonoscopes . Each detected polyp was first characterized by WL and then by NBI . Modified Kudo pit pattern and vascular color intensity ( VCI ) were recorded , and the histology was predicted . Endoscopists were given feedback every 2 weeks . MAIN OUTCOME MEASUREMENTS Overall accuracy and sensitivity and specificity of endoscopic diagnosis by using WL alone and with NBI , as well as improvement in endoscopists ' performance . RESULTS A total of 265 polyps were found in 131 patients . Diagnostic accuracy was 80 % with NBI and 77 % with WL ( P = .35 ) . NBI performed better than WL in diagnosing adenomas ( sensitivity 80 % vs 69 % , P < .05 ) . Nonadenomatous polyps were more likely to have a " light " VCI compared with adenomas ( 71 % vs 29 % , P < .001 ) . During the second half of the study , NBI accuracy improved , from 74 % to 87 % , and outperformed an unchanged WL accuracy of 79 % ( P < .05 ) . CONCLUSIONS Overall , NBI was not more accurate than WL in differentiating colorectal polyps in vivo ; however , once a learning curve was achieved , NBI performed significantly better . Further refinements of an NBI pit-pattern classification and VCI scale are needed before broad application to clinical decisions regarding the necessity of polypectomy BACKGROUND Accurate optical diagnosis of small ( < 10 mm ) colorectal polyps in vivo , without formal histopathology , could make colonoscopy more efficient and cost effective . The aim of this study was to assess whether optical diagnosis of small polyps is feasible and safe in routine clinical practice . METHODS Consecutive patients with a positive faecal occult blood test or previous adenomas undergoing surveillance at St Mark 's Hospital ( London , UK ) , from June 19 , 2008 , to June 16 , 2009 , were included in this prospect i ve study . Four colonoscopists with different levels of experience predicted polyp histology using optical diagnosis with high-definition white light , followed by narrow-b and imaging without magnification and chromoendoscopy , as required . The primary outcome was accuracy of polyp characterisation using optical diagnosis compared with histopathology , the current gold st and ard . Accuracy of optical diagnosis to predict the next surveillance interval was also assessed and compared with surveillance intervals predicted by current guidelines using histopathology . This study is registered with Clinical Trials.gov , NCT00888771 . FINDINGS 363 polyps smaller than 10 mm were detected in 130 patients , of which 278 polyps had both optical and histopathological diagnosis . By histology , 198 of these polyps were adenomas and 80 were non-neoplastic lesions ( of which 62 were hyperplastic ) . Optical diagnosis accurately diagnosed 186 of 198 adenomas ( sensitivity 0.94 ; 95 % CI 0.90 - 0.97 ) and 55 of 62 hyperplastic polyps ( specificity 0.89 ; 0.78 - 0.95 ) , with an overall accuracy of 241 of 260 ( 0.93 , 0.89 - 0.96 ) for polyp characterisation . Using optical diagnosis alone , 82 of 130 patients could be given a surveillance interval immediately after colonoscopy , and the same interval was found after formal histopathology in 80 patients ( 98 % ) using British guidelines and in 78 patients ( 95 % ) using US multisociety guidelines . INTERPRETATION For polyps less than 10 mm in size , in-vivo optical diagnosis seems to be an acceptable strategy to assess polyp histopathology and future surveillance intervals . Dispensing with formal histopathology for most small polyps found at colonoscopy could improve the efficiency of the procedure and lead to substantial savings in time and cost . FUNDING Leigh Family Trust , London , UK BACKGROUND & AIMS Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk . METHODS We pooled individual data from 8 prospect i ve studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance . RESULTS During a median follow-up period of 47.2 months , advanced colorectal neoplasia was diagnosed in 1082 ( 11.8 % ) of the patients , 58 of whom ( 0.6 % ) had invasive cancer . Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas ( 24.1 % ; st and ard error , 2.2 ) and those with an adenoma 20 mm in size or greater ( 19.3 % ; st and ard error , 1.5 ) . Risk factor patterns were similar for advanced adenomas and invasive cancer . In multivariate analyses , older age ( P < .0001 for trend ) and male sex ( odds ratio [ OR ] , 1.40 ; 95 % confidence interval [ CI ] , 1.19 - 1.65 ) were associated significantly with an increased risk for metachronous advanced neoplasia , as were the number and size of prior adenomas ( P < .0001 for trend ) , the presence of villous features ( OR , 1.28 ; 95 % CI , 1.07 - 1.52 ) , and proximal location ( OR , 1.68 ; 95 % CI , 1.43 - 1.98 ) . High- grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics . CONCLUSIONS Occurrence of advanced colorectal neoplasia is common after polypectomy . Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas BACKGROUND The American Society for Gastrointestinal Endoscopy ( ASGE ) recently developed thresholds for the performance characteristics of technologies for real-time assessment of histology of diminutive ( ≤ 5 mm ) colon polyps . Narrow-b and imaging ( NBI ) has been shown to predict polyp histology with moderate to high accuracy in several studies . OBJECTIVE To determine whether in vivo optical diagnosis of polyp histology by using NBI can reach the 2 benchmarks set forth by the ASGE . DESIGN Retrospective analysis of data from 3 prospect i ve clinical trials . SETTING Two tertiary referral centers . PATIENTS Subjects undergoing screening or surveillance colonoscopy . INTERVENTIONS In vivo optical diagnosis of polyp histology by using NBI . MAIN OUTCOME MEASUREMENT Accuracy in predicting colonoscopy surveillance intervals , negative predictive value ( NPV ) for diagnosing adenomatous histology in the rectosigmoid . RESULTS A total of 410 patients met the inclusion /exclusion criteria and had at least 1 polyp seen and resected during colonoscopy . Using in vivo optical diagnosis instead of histopathology for all diminutive polyps predicted the correct colonoscopy surveillance interval in 86 % to 94 % patients . When optical diagnosis was limited to diminutive polyps in the rectosigmoid only , the NPV for diagnosing adenomatous histology with NBI was 95 % . LIMITATIONS Retrospective analysis from tertiary referral centers . CONCLUSIONS The threshold NPV for diagnosing adenomatous histology in diminutive rectosigmoid polyps recently set forth by the ASGE can be achieved by using NBI . The threshold accuracy rate for predicting surveillance interval recommendations can be reached by using NBI , but only if patients with 1 to 2 small adenomas without advanced features have a repeat colonoscopy in 10 years Aims Warfarin , a vitamin K antagonist ( VKA ) , has been the st and ard of care for stroke prevention in patients with atrial fibrillation ( AF ) . Aspirin is recommended for low-risk patients and those unsuitable for warfarin . Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies , respectively , and causes less bleeding than warfarin . We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective . Results and methods A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients , respectively . Clinical events considered in the model include ischaemic stroke , haemorrhagic stroke , intracranial haemorrhage , other major bleed , clinical ly relevant non-major bleed , myocardial infa rct ion , cardiovascular hospitalization and treatment discontinuations ; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model . Apixaban was projected to increase life expectancy and quality -adjusted life years ( QALYs ) compared with warfarin and aspirin . These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime . The estimated incremental cost-effectiveness ratio was £ 11 909 and £ 7196 per QALY gained with apixaban compared with warfarin and aspirin , respectively . Sensitivity analyses indicated that results were robust to a wide range of inputs . Conclusions Based on r and omized trial data , apixaban is a cost-effective alternative to warfarin and aspirin , in VKA suitable and VKA unsuitable patients with AF , respectively BACKGROUND & AIMS The ability to determine colorectal polyp pathology by endoscopy could reduce the risks of polypectomy and the cost of pathologic evaluation . This study evaluated the ability of the Olympus Exera 180 high-definition colonoscope ( Olympus America , Inc , Center Valley , PA ) , with narrow-b and imaging , to predict colorectal polyp histology . METHODS A library of 320 endoscopic photographs with correlated histologic information was used to identify endoscopic features associated with adenomatous and hyperplastic histology . These features were tested in a prospect i ve study of 451 consecutively identified colorectal polyps . Polyps were observed endoscopically and assigned a design ation of high or low confidence . The primary end points were the predictive value of high-confidence endoscopic interpretations of adenoma and hyperplastic histology for polyps 5 mm and smaller in size . RESULTS Endoscopic predictions of adenoma and hyperplastic histology were made with high confidence for 80 % and 83 % of cases , respectively . High-confidence predictions were more likely than low-confidence predictions to be correct ( P<.001 ) . High-confidence predictions of adenoma and hyperplastic histology were correct for 91 % and 95 % , respectively , of polyps 5 mm and smaller in size . CONCLUSIONS Introduction of confidence levels to the endoscopic interpretation of colorectal polyp histology allows sufficient accuracy for the use of the Exera narrow-b and imaging system in the identification of distal hyperplastic polyps that do not need resection , as well as to plan postpolypectomy surveillance without pathologic evaluation of polyps 5 mm in size or smaller BACKGROUND AND STUDY AIMS The resolution of endoscopes has increased in recent years . Modern Fujinon colonoscopes have a charge-coupled device ( CCD ) pixel density of 650,000 pixels compared with the 410,000 pixel CCD in st and ard-definition scopes . Acquiring high-definition scopes represents a significant capital investment and their clinical value remains uncertain . The aim of the current study was to investigate the impact of high-definition endoscopes on the in vivo histology prediction of colonic polyps . PATIENTS AND METHODS Colonoscopy procedures were performed using Fujinon colonoscopes and EPX-4400 processor . Procedures were r and omized to be performed using either a st and ard-definition EC-530 colonoscope or high-definition EC-530 and EC-590 colonoscopes . Polyps of < 10 mm were assessed using both white light imaging ( WLI ) and flexible spectral imaging color enhancement ( FICE ) , and the predicted diagnosis was recorded . Polyps were removed and sent for histological analysis by a pathologist who was blinded to the endoscopic diagnosis . The predicted diagnosis was compared with the histology to calculate the accuracy , sensitivity , and specificity of in vivo assessment using either st and ard or high-definition scopes . RESULTS A total of 293 polyps of < 10 mm were examined–150 polyps using the st and ard-definition colonoscope and 143 polyps using high-definition colonoscopes . There was no difference in sensitivity , specificity or accuracy between the two scopes when WLI was used ( st and ard vs. high : accuracy 70 % [ 95 % CI 62–77 ] vs. 73 % [ 95 % CI 65–80 ] ; P=0.61 ) . When FICE was used , high-definition colonoscopes showed a sensitivity of 93 % compared with 83 % for st and ard-definition colonoscopes ( P=0.048 ) ; specificity was 81 % and 82 % , respectively . CONCLUSIONS There was no difference between high- and st and ard-definition colonoscopes when white light was used , but FICE significantly improved the in vivo diagnosis of small polyps when high-definition scopes were used compared with st and ard definition Objectives At present , all colonic polyps are removed and sent for histopathological evaluation , result ing in laboratory and reporting costs . Recent American Society for Gastrointestinal Endoscopy ( ASGE ) guidelines have set st and ards for in-vivo diagnosis in place of conventional histopathology , and all future technologies will have to be tested against these st and ards . Data on flexible spectral imaging color enhancement ( FICE ) were very limited . This study aims to evaluate the accuracy of FICE and indigo carmine ( IC ) for in-vivo histology prediction for polyps of less than 10 mm in size and to assess the economic impact of this strategy . Methods In a screening population , polyps of less than 10 mm were assessed using white light ( WLI ) by FICE , by IC , and the predicted diagnosis was recorded . Polyps were then removed and sent for histological analysis . Accuracy of the predicted rescope interval was calculated using British Society of Gastroenterology and ASGE guidelines . Two models for using in-vivo diagnosis were proposed and savings in terms of histopathology costs calculated . Results A total of 232 polyps of less than 10 mm were examined . FICE improved the accuracy of in-vivo diagnosis of adenoma to 88 % compared with 75 % with WLI ( P<0.0001 ) . IC after FICE improved this further to 94 % . Rescope interval could be set correctly using FICE or IC in 97 % of cases by British Society of Gastroenterology guidelines or 97 % with FICE and 99 % with IC using ASGE guidelines . A saving of £ 678 253 ( & OV0556;762767 ) per annum could be made within the UK national screening population . Conclusion FICE and IC significantly improves the in-vivo diagnosis of colonic polyps over WLI and can lead to significant cost savings BACKGROUND AND STUDY AIMS The learning curve for optical diagnosis of colorectal polyps with the narrow-b and imaging ( NBI ) is unknown . To forego histological analysis of diminutive polyps diagnosed optically with high confidence , guidelines recommend ≥ 90 % negative predictive value ( NPV ) and concordance of ≥ 90 % for surveillance intervals predicted optically and histologically . We aim ed to study the learning of optical diagnosis for colorectal polyps . PATIENTS AND METHODS We studied five endoscopists as part of a r and omized multisite trial comparing near-focus and st and ard-focus views for optical diagnosis . They trained using a computer-based module , followed by 10 real-time colonoscopies with pathology correlation . Endoscopists then optically diagnosed and resected all the polyps found during 558 consecutive colonoscopies , and diagnoses were compared with pathology . Endoscopists repeated the training module at the study midpoint . NPV and concordance of surveillance intervals for diminutive polyps diagnosed optically with high confidence were measured over time . RESULTS Endoscopists showed high diagnostic performance , with a nonsignificant trend toward higher NPV in the second half of the study . For the 445 polyps in the st and ard-view arm , the NPV was 88.0 % ( 95 % CI 75.7 % - 95.5 % ) in the first half and 95.8 % ( 88.3 % - 99.1 % ) in the second ; P = 0.7 . Three endoscopists in the first half and four in the second achieved > 90 % NPV . Concordance of surveillance intervals was identical in the first and second halves at 98.1 % ( 95 % CI 93.3 % - 99.8 % ) . CONCLUSIONS High NPV for the prediction of non-neoplasms with NBI was achieved and maintained in this group of endoscopists who participated in st and ardized and continued training . Both NPV and surveillance interval agreement indicated high performance in the optical diagnosis of colorectal polyps and exceeded thresholds BACKGROUND Discriminating neoplastic from non-neoplastic polyps can significantly reduce the cost of colonoscopy . The American Society for Gastrointestinal Endoscopy ( ASGE ) recently set threshold levels for optical diagnostic accuracy to be acceptable for clinical use . OBJECTIVE In this study , we compare a novel colonoscope capable of dual-focus imaging with st and ard colonoscopy with respect to the ASGE guidelines . SETTING An academic medical center ambulatory surgical center . PATIENTS AND INTERVENTIONS Patients at average risk were r and omized to st and ard colonoscopy ( Olympus CF-H180 and Exera II 180 colonoscopes , Olympus America , Center Valley , Pa ) or dual-focus colonoscopy ( Olympus CF-HQ190 and Exera III 190 colonoscopes , Olympus America ) . All polyps were given an optical diagnosis and compared with histology . RESULTS A total of 600 patients were consented and 522 completed all aspects of the procedure . A total of 927 polyps were analyzed . Optical diagnostic accuracy was 79 % ( 95 % confidence interval , 74%-83 % ) for the 190 and 77 % ( 95 % confidence interval , 73%-81 % ) for the 180 colonoscope . Adenoma detection rates were also similar between the 2 groups ( 50 % for the 190 vs 52 % for the 180 colonoscope ) . For small distal rectosigmoid polyps with a high confidence diagnosis , the negative predictive value for adenoma was 96 % ( range 89%-99 % ) for the 180 in the narrow-b and imaging ( NBI ) mode and 97 % ( range 88%-99 % ) for the 190 colonoscope in NBI mode . Agreement of surveillance intervals by using optical diagnosis was 94 % to 95 % for all modalities ( 180 and 190 colonoscopes , white light imaging , NBI ) . LIMITATIONS Our study evaluated the accuracy of the 180 and 190 colonoscopes at a center with already-established expertise in endoscopic imaging . CONCLUSIONS Both traditional and new dual-focus colonoscopes provide highly accurate optical polyp discrimination . There was no difference between the 2 systems in terms of discrimination or adenoma detection . Both systems are consistent with ASGE guidelines for optical diagnosis of selected colorectal polyps without histological confirmation BACKGROUND Although microvascular vessels on the surface of colorectal polyps are observed by narrow-b and imaging ( NBI ) with magnification , its clinical usefulness is still uncertain . OBJECTIVE Our purpose was to evaluate the usefulness of meshed capillary ( MC ) vessels observed by NBI magnification for differentiating between nonneoplastic and neoplastic colorectal lesions . DESIGN Prospect i ve polyp study . SETTING National Cancer Center Hospital East , Chiba , Japan . PATIENTS A total of 702 consecutive patients who underwent total colonoscopy between September and December 2004 were prospect ively evaluated . Patients with polyps > 10 mm and those with polyps previously evaluated by histologic examination or colonoscopy were excluded . INTERVENTION Lesions were classified into 2 groups : polyps with invisible or faintly visible MC vessels as nonneoplastic and polyps with clearly visible MC vessels as neoplastic . Lesions judged as nonneoplastic were subjected to biopsy and those as neoplastic were removed endoscopically . Histologic analysis was performed in all lesions . MAIN OUTCOME MEASUREMENT Visible or invisible surface MC vessels , prediction of histologic diagnosis . RESULTS Of 92 eligible patients enrolled in this study , 150 lesions , including 39 ( 26 % ) hyperplastic polyps and 111 ( 74 % ) adenomatous polyps , were detected . Observation of MC vessels detected 107 of 111 neoplastic polyps and 36 of 39 nonneoplastic polyps . The overall diagnostic accuracy , sensitivity , and specificity were 95.3 % , 96.4 % , and 92.3 % , respectively . LIMITATIONS MC vessel judgment performed by a single colonoscopist with extensive experience in magnifying NBI . CONCLUSION Observation of surface MC vessels by magnifying NBI is a useful and simple method for differentiating colorectal nonneoplastic and neoplastic polyps BACKGROUND Polyps identified at colonoscopy are predominantly diminutive ( < 5 mm ) with a small risk ( > 1 % ) of high- grade dysplasia or carcinoma ; however , the cost of histological assessment is substantial . AIM The aim of this study was to determine whether prediction of colonoscopy surveillance intervals based on real-time endoscopic assessment of polyp histology is accurate and cost effective . METHODS A prospect i ve cohort study was conducted across a tertiary care and private community hospital . Ninety-four patients underwent colonoscopy and polypectomy of diminutive ( ≤5 mm ) polyps from October 2012 to July 2013 , yielding a total of 159 polyps . Polyps were examined and classified according to the Sano-Emura classification system . The endoscopic assessment ( optical diagnosis ) of polyp histology was used to predict appropriate colonoscopy surveillance intervals . The main outcome measure was the accuracy of optical diagnosis of diminutive colonic polyps against the gold st and ard of histological assessment . RESULTS Optical diagnosis was correct in 105/108 ( 97.2 % ) adenomas . This yielded a sensitivity , specificity and positive and negative predictive values ( with 95%CI ) of 97.2 % ( 92.1 - 99.4 % ) , 78.4 % ( 64.7 - 88.7 % ) , 90.5 % ( 83.7 - 95.2 % ) and 93 % ( 80.9 - 98.5 % ) respectively . Ninety-two ( 98 % ) patients were correctly triaged to their repeat surveillance colonoscopy . Based on these findings , a cut and discard approach would have result ed in a saving of $ 319.77 per patient . CONCLUSION Endoscopists within a tertiary care setting can accurately predict diminutive polyp histology and confer an appropriate surveillance interval with an associated financial benefit to the healthcare system . However , limitations to its application in the community setting exist , which may improve with further training and high-definition colonoscopes BACKGROUND AND STUDY AIMS Narrow b and imaging ( NBI ) can accurately characterize colonic polyps using microvascular appearances . We aim ed to assess whether the Kudo pit pattern classification is accurate when used with NBI ( without dye-spray ) , and if microvascular appearances or NBI pit patterns maintain accuracy for polyp characterization at sizes < 10 mm . PATIENTS AND METHODS 116 polyps < 10 mm in size were detected in 62 patients undergoing surveillance colonoscopy . The polyps were prospect ively assessed using NBI and magnification for Kudo pit pattern ( III-V neoplastic , I-II non-neoplastic ) and vascular pattern intensity ( VPI ) , a measure of microvascular density ( strong VPI , neoplastic ; normal or weak VPI , non-neoplastic ) . Sensitivity , specificity , and accuracy were calculated and compared with results from histopathology . RESULTS The mean polyp size was 3.4 mm ( range 1 - 9 mm ) . Overall , NBI pit pattern sensitivity , specificity , and accuracy were 0.88 , 0.91 , and 89.6 % , respectively . Equivalent values for VPI were 0.94 , 0.89 , and 91.4 % . Results were similar when polyps were subdivided into diminutive polyps ( size < or= 5 mm ) and flat polyps . Combining both pit pattern and VPI improved the sensitivity ( 0.98 , P = 0.06 versus NBI pit pattern alone ) . There was very good agreement between NBI pit pattern and VPI for prediction of dysplasia ( kappa = 0.83 ) . No evidence of a learning curve for VPI was found . The NBI pit pattern was better than the VPI at subclassifying hyperplastic from other non-neoplastic polyps ( sensitivity 0.79 versus 0.56 , respectively , P = 0.02 ) , but accuracy was poor . CONCLUSION The NBI pit pattern and VPI are both highly accurate in characterizing neoplastic colonic polyps of < 10 mm , with VPI appearing to be simple to learn . NBI has the potential to replace conventional histology for small polyps BACKGROUND Colonoscopy with spectral estimation technology and magnifying zoom imaging allows the characterization of the fine superficial capillary pattern of normal mucosa and of colorectal lesions . The endoscopic distinction of the capillary pattern of colorectal lesions might contribute to the differential diagnosis among normal , hyperplastic , and neoplastic lesions . OBJECTIVE By means of these latest technologic advances , the objective is to define a classification of the capillary-vessel pattern of colorectal lesions diagnosed during routine colonoscopy . DESIGN A total of 309 colorectal lesions endoscopically or surgically resected were prospect ively examined . The capillary pattern was divided into 5 subtypes according to the number , morphology , and distribution of the fine blood vessels . Capillary patterns types I and II were characterized by a few short , straight , and sparsely distributed vessels ; types III to V were of numerous , elongated , and tortuous capillaries irregularly distributed . RESULTS The overall accuracy of the capillary-vessel classification in determining the neoplastic or non-neoplastic nature of the colorectal lesions was 98.3 % ( 304/309 lesions ) . Among 59 non-neoplastic lesions , 56 ( 94.9 % ) that showed patterns I or II were diagnosed as normal , inflammatory , or hyperplastic polyps . Of the 250 neoplastic lesions , 248 ( 99.2 % ) that had capillary pattern types III , IV , and V were diagnosed as adenomatous or carcinoma . The sensitivity of the capillary pattern classification for distinguishing neoplasia was 99.2 % ( 95 % CI , 98.2%-100 % ) , and the specificity was 94.9 % ( 95 % CI , 92.5%-97.4 % ) . LIMITATION A single-center study . CONCLUSION The endoscopic classification of the superficial capillary-vessel pattern of colorectal lesions is an accurate method of predicting the histopathologic findings Background Accurate optical characterisation and removal of small adenomas ( < 10 mm ) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need for histopathology . Although accurate in specialist practice the performance of narrow b and imaging ( NBI ) , colonoscopy in routine clinical practice is poorly understood . Methods NBI-assisted optical diagnosis was compared with reference st and ard histopathological findings in a prospect i ve , blinded study , which recruited adults undergoing routine colonoscopy in six general hospitals in the UK . Participating colonoscopists ( N=28 ) were trained using the NBI International Colorectal Endoscopic ( NICE ) classification ( relating to colour , vessel structure and surface pattern ) . By comparing the optical and histological findings in patients with only small polyps , test sensitivity was determined at the patient level using two thresholds : presence of adenoma and need for surveillance . Accuracy of identifying adenomatous polyps < 10 mm was compared at the polyp level using hierarchical models , allowing determinants of accuracy to be explored . Findings Of 1688 patients recruited , 722 ( 42.8 % ) had polyps < 10 mm with 567 ( 78.5 % ) having only polyps < 10 mm . Test sensitivity ( presence of adenoma , N=499 patients ) by NBI optical diagnosis was 83.4 % ( 95 % CI 79.6 % to 86.9 % ) , significantly less than the 95 % sensitivity ( p<0.001 ) this study was powered to detect . Test sensitivity ( need for surveillance ) was 73.0 % ( 95 % CI 66.5 % to 79.9 % ) . Analysed at the polyp level , test sensitivity ( presence of adenoma , N=1620 polyps ) was 76.1 % ( 95 % CI 72.8 % to 79.1 % ) . In fully adjusted analyses , test sensitivity was 99.4 % ( 95 % CI 98.2 % to 99.8 % ) if two or more NICE adenoma characteristics were identified . Neither colonoscopist expertise , confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy . Interpretation This large multicentre study demonstrates that NBI optical diagnosis can not currently be recommended for application in routine clinical practice . Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training . Trial registration number The study was registered with clinical trials.gov ( NCT01603927 ) |
13,435 | 17,908,301 | Recent research on the causal relationship between the two disorders suggests that a subgroup of bipolar patients may develop a relatively milder form of affective illness that is expressed only after extended exposure to alcohol abuse .
Three open label medication trials provide limited evidence that quetiapine , aripiprazole , and lamotrigine may be effective in treating affective and substance use symptoms in bipolar patients with cocaine dependence and that aripiprazole may also be helpful in patients with alcohol use disorders .
The two placebo controlled trials to date suggest that valproate given as an adjunct to lithium in bipolar patients with co-occurring alcohol dependence improves both mood and alcohol use symptoms and that lithium treatment in bipolar adolescents improves mood and SUD symptoms . | The aim of this paper is to provide a systematic review of the literature examining the epidemiology , outcome , and treatment of patients with bipolar disorder and co-occurring substance use disorders ( SUDs ) .
Prior epidemiological research has consistently shown that substance use disorders ( SUDs ) are extremely common in bipolar I and II disorders .
The lifetime prevalence of SUDs is at least 40 % in bipolar I patients .
Alcohol and cannabis are the substances most often abused , followed by cocaine and then opioids .
Research has consistently shown that co-occurring SUDs are correlated with negative effects on illness outcome including more frequent and prolonged affective episodes , decreased compliance with treatment , a lower quality of life , and increased suicidal behavior .
There has been very little treatment research specifically targeting this population . | OBJECTIVE The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence . METHOD Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use . Patients were started on open-label divalproex . After stabilization on divalproex sodium , weekly assessment s were undertaken for 8weeks . Subjects also attended dual recovery counseling . RESULTS The results revealed significant improvement on % cocaine abstinent days , dollars spent on cocaine , ASI 's drug use severity index , % alcohol abstinent days , drinks per drinking day , marijuana use and cigarettes smoking . They also had significant improvement on manic , depressive , and sleep symptoms and on functioning . There were no reported adverse events or increases in liver function tests . CONCLUSION The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence . Double-blind , placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted BACKGROUND Substance abuse frequently complicates the course of bipolar illness , promotes mixed states , and contributes to poor outcome in mania . Preliminary open trials suggest that anticonvulsant mood stabilizers may enhance remission rates and outcome for bipolar patients with substance abuse . This study compared remission patterns for mixed or pure manic episodes among bipolar in patients with or without substance abuse histories . METHOD Hospital records were retrospectively review ed for 204 DSM-III-R bipolar I in patients . Clinical features were compared for those with or without substance abuse/dependence histories predating the index manic episode . Time until remission was analyzed by Kaplan-Meier survival analysis . Naturalistic treatment outcome with lithium or anticonvulsant mood stabilizers was compared for those with or without past substance abuse . RESULTS Past substance abuse was evident in 34 % of the bipolar sample and comprised most often alcoholism ( 82 % ) , followed by cocaine ( 30 % ) , marijuana ( 29 % ) , sedative-hypnotic or amphetamine ( 21 % ) , and opiate ( 13 % ) abuse . Substance abuse was more common among men ( p < .05 ) and those with mixed rather than pure mania ( p < .05 ) . Remission during hospitalization was less likely among patients with prior substance abuse ( p < .05 ) , especially alcohol or marijuana abuse , and among mixed manic patients with past substance abuse ( p < .05 ) . Bipolar patients with substance abuse histories who received divalproex or carbamazepine remitted during hospitalization more often than did those who received lithium as the sole mood stabilizer ( p < .05 ) . CONCLUSION These findings support previous reports suggesting that bipolar patients with past substance abuse have poorer naturalistic treatment outcomes , but may show a better response to anticonvulsant mood stabilizers than lithium OBJECTIVE To evaluate the prevalence of substance abuse dependence and /or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry . METHOD One hundred r and omly selected registrants in a voluntary case registry for bipolar disorder were interviewed , using the Structured Clinical Interview for DSM-IV Axis I Disorders , to vali date the diagnosis of this registry . Corroborative information was obtained from medical records , family members and the treating psychiatrist . Eighty-nine adults ( 18 - 65 years ) met criteria for bipolar disorder ( bipolar I = 71 , bipolar II = 18 ) and were included in this analysis . RESULTS Forty-one ( 57.8 % ) subjects with bipolar I disorder abused , or were dependent on one or more substances or alcohol , 28.2 % abused , or were dependent on , two substances or alcohol , and 11.3 % abused or were dependent on three or more substances or alcohol . Nearly 39 % of bipolar II subjects abused or were dependent on one or more substances , nearly 17 % were dependent on two or more substances or alcohol , and 11 % were dependent on three or more substances or alcohol . Alcohol was the most commonly abused drug among either bipolar I or II subjects . CONCLUSIONS Consistent with other epidemiologic and hospital population studies , this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and /or substance abuse dependence . Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects ; however , as the number of bipolar II subjects was rather small , this suggestion needs confirmation OBJECTIVE Substance abuse is extremely common in patients with bipolar disorders , although minimal data are available on the treatment of this important clinical population . Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action , acting as a dopamine-2 receptor partial agonist , thereby increasing dopamine release in some parts of the brain and decreasing dopa-mine release in other brain regions . Dopamine release is implicated in substance use , and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse . To our knowledge , dopa-mine receptor partial agonists have not been investigated for treatment of substance abuse in humans . METHOD Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripipra-zole using an overlap and taper method . At baseline , diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria . Psychiatric symptoms , side effects , and substance use and craving were assessed over 12 weeks . Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression ( HAM-D ) , Young Mania Rating Scale ( YMRS ) , and Brief Psychiatric Rating Scale ( BPRS ) . Substance craving was assessed with visual analogue scales , and side effects were monitored using the Abnormal Involuntary Movement Scale , Simpson-Angus Scale , Barnes Akathisia Scale , and patient report . Study enrollment was from April 2003 to February 2004 . RESULTS Significant baseline-to-exit improvement in HAM-D ( p = .002 ) , YMRS ( p = .021 ) , and BPRS ( p = .000 ) scores were observed without a significant change in antipsychotic-induced side effect scales . In 17 participants with current alcohol dependence , significant reductions in dollars spent on alcohol ( p = .042 ) and alcohol craving ( p = .003 ) were found . In 9 participants with cocaine-related disorders , significant reductions in cocaine craving ( p = .014 ) , but not use , were found . CONCLUSION A change to aripiprazole was associated with symptomatic improvement . Limitations of the study include a small sample size , high attrition , and an open-label design . Controlled trials in dual-diagnosis patients are needed to confirm these findings BACKGROUND Bipolar disorder is associated with the highest substance abuse rates of any psychiatric illness . Therefore , treatments that stabilize mood and decrease drug use or cravings are of great interest . Open-label lamotrigine was examined in 30 out patients with DSM-IV bipolar disorder and cocaine dependence . Lamotrigine was either added to existing medication regimens or used as monotherapy . METHOD Lamotrigine was started at a dose of 25 mg/day ( 12.5 mg/day in those taking valproic acid ) and titrated to a maximum dose of 300 mg/day . Subjects received a baseline evaluation including a structured clinical interview and weekly assessment s for 12 weeks with the Hamilton Rating Scale for Depression ( HAM-D ) , Young Mania Rating Scale ( YMRS ) , Brief Psychiatric Rating Scale ( BPRS ) , and Cocaine Craving Question naire ( CCQ ) . At each appointment , a urine sample was obtained , and participants reported drug use during the previous week . The subjects consisted of 13 men and 17 women with cocaine dependence and bipolar I disorder ( N = 22 ) , bipolar II disorder ( N = 7 ) , or bipolar disorder not otherwise specified ( N = 1 ) , with a mean + /- SD age of 35.4 + /- 7.2 years . Data were analyzed using the last observation carried forward on all subjects who completed the baseline evaluation and at least 1 postbaseline assessment . RESULTS Significant improvement was observed in HAM-D , YMRS , and BPRS scores ( p < or = .02 ) . Cravings also significantly decreased as measured by the CCQ ( p < .001 ) . Dollar amount spent on drugs decreased nonsignificantly . Lamotrigine was well tolerated , with no subjects discontinuing due to side effects . CONCLUSION Lamotrigine treatment was well tolerated in this sample and associated with statistically significant improvement in mood and drug cravings but not drug use . The findings suggest that larger controlled trials of lamotrigine are needed in this population OBJECTIVE Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric illness . Therefore , treatments that stabilize mood and decrease drug use or cravings are of great interest . Atypical antipsychotics are in widespread use in patients with bipolar disorder . However , minimal data are available on their use in bipolar patients with comorbid substance abuse . METHODS Open-label , add-on , quetiapine therapy was examined for 12 weeks in 17 out patients with bipolar disorder and cocaine dependence . Subjects were evaluated with a structured clinical interview ; Hamilton Depression Rating ( HDRS ) , Young Mania Rating ( YMRS ) , Brief Psychiatric Rating ( BPRS ) scales ; and Cocaine Craving Question naire ( CCQ ) . Urine sample s and self-reported drug use were also obtained . Data were analyzed using a last observation carried forward method on all subjects given medication at baseline . RESULTS Significant improvement from baseline to exit was observed in HDRS , YMRS , BPRS and CCQ scores ( p < or = 0.05 ) . Dollars spent on cocaine and days/week of cocaine use decreased non-significantly , and urine drug screens did not change significantly from baseline to exit . Quetiapine was well tolerated , with no subjects to our knowledge discontinuing because of side-effects . CONCLUSIONS The use of quetiapine was associated with substantial improvement in psychiatric symptoms and cocaine cravings . The findings are promising and suggest larger controlled trials of quetiapine are needed in this population Despite the availability of efficacious treatments for bipolar disorder , their effectiveness in general clinical practice is greatly attenuated , result ing in what has been called an ' efficacy-effectiveness gap ' . In design ing VA Cooperative Studies Program ( CSP ) Study # 430 to address this gap , nine principles for conducting an effectiveness ( in contrast to an efficacy ) study were identified . These principles are presented and discussed , with specific aspects of CSP # 430 serving as illustrations of how they can be implemented in an actual study . CSP # 430 hypothesizes that an integrated , clinic-based treatment delivery system that emphasizes ( 1 ) algorithm-driven somatotherapy , ( 2 ) st and ardized patient education , and ( 3 ) easy access to a single primary mental health care provider to maximize continuity-of-care , will address the efficacy-effectiveness gap and improve disease , functional , and economic outcome . It is an 11-site , r and omized controlled clinical trial of this multi-modal , clinic-based intervention versus usual VA care running from 1997 to 2003 . The trial has enrolled 191 subjects in each arm , using minimal exclusion criteria to maximize the external validity of the study . Subjects are followed for 3 years . The intervention is highly specified in a series of operations manuals for each of the three components . Several continuous quality improvement ( CQI ) interventions , process measures , and statistical techniques deal with drift of care in both the intervention and usual care arms to ensure the internal validity of the study . CSP # 430 is design ed to have impact well beyond the VA , since it evaluates a basic health care operational principle : that augmenting ambulatory access for major mental illness will improve outcome and reduce overall treatment costs . If results are positive , this study will provide a reason to reconsider the prevailing trend toward limitation of ambulatory services that is characteristic of many managed care systems today OBJECTIVE Although bipolar disorder and substance use disorder frequently co-occur , there is little information on the effectiveness of behavioral treatment for this population . Integrated group therapy , which addresses the two disorders simultaneously , was compared with group drug counseling , which focuses on substance use . The authors hypothesized that patients receiving integrated group therapy would have fewer days of substance use and fewer weeks ill with bipolar disorder . METHOD A r and omized controlled trial compared 20 weeks of integrated group therapy or group drug counseling with 3 months of posttreatment follow-up . Sixty-two patients with bipolar disorder and current substance dependence , treated with mood stabilizers for > or=2 weeks , were r and omly assigned to integrated group therapy ( N=31 ) or group drug counseling ( N=31 ) . The primary outcome measure was the number of days of substance use . The primary mood outcome was the number of weeks ill with a mood episode . RESULTS Intention-to-treat analysis revealed significantly fewer days of substance use for integrated group therapy patients during treatment and follow-up . Groups were similar in the number of weeks ill with bipolar disorder during treatment and follow-up , although integrated group therapy patients had more depressive and manic symptoms . CONCLUSIONS Integrated group therapy , a new treatment developed specifically for patients with bipolar disorder and substance dependence , appears to be a promising approach to reduce substance use in this population BACKGROUND Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder . However , few studies have utilized public sector sample s , and only one has attempted to separate contributions of each type of comorbidity . METHODS 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports . RESULTS Comorbidity was common ( current : 57.3 % ; lifetime : 78.4 % ) , with multiple current comorbidities in 29.8 % . Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient sample s ( 33.8 % current , 72.3 % lifetime ) . Selected anxiety comorbidity rates exceeded those in other inpatient sample s and appeared more chronic than episodic/recurrent ( 38.3 % current , 43.3 % lifetime ) . 49 % of PTSD was due to non-combat stressors . Major correlates of current substance comorbidity alone were younger age , worse marital status , and higher current employability . Correlates of current anxiety comorbidity alone were early age of onset , greater number of prior-year depressive episodes , higher rates of disability pension receipt , and lower self-reported mental and physical function . Combined comorbidity resembled anxiety comorbidity . LIMITATIONS This is a cross-sectional analysis of acutely hospitalized veterans . CONCLUSIONS Distinct patterns of substance and anxiety comorbidity are striking , and may be subserved by distinct neurobiologic mechanisms . The prevalence , chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted . Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built " from the patient out . Bipolar disorder remains a high morbidity and costly illness in general clinical practice , despite the availability of efficacious medications . This ' efficacy-effectiveness gap ' may be addressed by better organizing systems of care . One type of intervention is the ' collaborative practice model ' which can be defined as an organization of care that a ) emphasizes development in the patient of illness management skills , and b ) supports provider capability and availability in order to c ) engage patients in timely , joint decision-making regarding their illness . This article describes such a collaborative practice model for bipolar disorder , design ed to be widely adoptable and sustainable in general clinical practice . The first part of the article describes the theoretical background from which the collaborative practice approach developed , emphasizing its origins in the lithium clinics of the 1970s , in nursing theory and practice , and more recently in the management of chronic medical diseases . The second part describes the structure of one such intervention , the Bipolar Disorders Program ( BDP ) developed in the Veterans Affairs health care system . The third part summarizes results from single-site studies of the intervention . The fourth part describes several key issues in its implementation in an ongoing multi-site r and omized controlled trial , VA Cooperative Study Program ( CSP ) # 430 . Data to date indicate that such collaborative practice interventions may improve important process and intermediate outcome variables for bipolar disorder . The BDP provides an example of a multi-faceted collaborative practice model that can be manualized and implemented across multiple sites in a r and omized controlled trial OBJECTIVE To examine the potential impact of recovery from substance use disorder ( SUD ) on the course of bipolar disorder among patients diagnosed with both bipolar and substance use disorders according to DSM-IV criteria . METHOD As part of the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) , we examined bipolar disorder status ( i.e. , whether the patient is recovering or recovered ) , role functioning , and quality of life in the first 1000 patients to enter the STEP-BD study . We compared patients with no history of SUD , current SUD , and past SUD ( i.e. , lifetime SUD , but no current SUD ) on these parameters . Data were collected between November 1999 and April 2001 . RESULTS A current clinical status of recovering or recovered from bipolar disorder was less likely among patients with current or past SUD compared to patients with no SUD ( p < .002 ) . Recovering/recovered status did not differ significantly between patients with current SUD versus past SUD . All 3 groups differed significantly on measures of role functioning as assessed by the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool ( LIFE-RIFT ) , with poorest role functioning among patients with current SUD , followed by patients with past SUD ( p = .0002 ) . Patients with current or past SUD reported significantly lower quality of life as measured by the LIFE-RIFT and the Quality of Life Enjoyment and Satisfaction Question naire and more lifetime suicide attempts ( p < .001 ) than patients without an SUD ; patients with past versus current SUD did not differ significantly on these measures . CONCLUSION The results suggest that patients with bipolar disorder who experience sustained remission from an SUD fare better than patients with current SUD , but not as well as subjects with no history of SUD ; differences among the 3 groups appear greatest in the area of role functioning OBJECTIVE This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder . METHOD The authors evaluated substance use disorders , associated factors , and clinical course , prospect ively , in the first 2 years of DSM-IV bipolar I disorder with st and ardized methods . RESULTS Baseline substance use disorder was found in 33 % ( 37 of 112 ) of the patients at baseline and in 39 % at 24 months . Anxiety disorders were more frequent in the patients with than without substance use disorder ( 30 % and 13 % , respectively ) . Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested . Patients using two or more substances had worse outcomes . CONCLUSIONS Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome , early interventions for substance use disorder and anxiety might improve later outcome OBJECTIVE To detect risk factors for rapid cycling in bipolar disorder , the authors compared characteristics of rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective . METHOD Out patients with bipolar I disorder ( N=419 ) , bipolar II disorder ( N=104 ) , and bipolar disorder not otherwise specified ( N=16 ) were prospect ively evaluated with daily mood ratings for 1 year . Subjects were classified as having rapid cycling ( defined by the DSM-IV criterion of four or more manic or depressive episodes within 1 year ) or not having rapid cycling , and the two groups ' demographic and retrospective and prospect i ve illness characteristics were compared . Associated factors were also evaluated in relationship to episode frequency . RESULTS Patients with rapid cycling ( N=206 ; 38.2 % ) significantly differed from those without rapid cycling ( N=333 ) with respect to the following independent variables : history of childhood physical and /or sexual abuse , bipolar I disorder subtype , number of lifetime manic or depressive episodes , history of rapid cycling , and history of drug abuse . The prevalence of these characteristics increased progressively with episode frequency . The proportion of women was greater than the proportion of men only among patients with eight or more episodes per year . The average time spent manic/hypomanic increased as a function of episode frequency , but the average time spent depressed was comparable in patients with one episode and in those with more than one episode . Brief episodes were as frequent as full- duration DSM-IV-defined episodes . CONCLUSIONS A number of heterogeneous risk factors were progressively associated with increasing episode frequency . Depression predominated in all bipolar disorder patients , but patients with rapid cycling were more likely to be characterized by manic features . The findings overall suggest that rapid cycling is a dimensional course specifier arbitrarily defined on a continuum of episode frequency OBJECTIVE To perform a double-blind , placebo-controlled , r and om assignment , parallel group , pharmacokinetically dosed study of lithium for adolescents with bipolar disorders ( BP ) and temporally secondary substance dependency disorders ( SDD ) . METHOD Subjects were 16.3 + /- 1.2 years old and were comprehensively assessed during a 6-week outpatient protocol that included r and om weekly urine collection for drug assays and r and om and weekly serum collection for lithium levels . RESULTS Using both intent-to-treat ( N = 25 ) and completer ( n = 21 ) analyses , there were significant differences on continuous and categorical measures between the active and placebo groups for both psychopathology measures and weekly r and om urine drug assays . The mean scheduled weekly serum lithium level of active responders was 0.9 mEq/L. Addiction to both alcohol and marijuana was the most frequent category of SDD . Mean age at onset of BP was 9.6 + /- 3.9 years and of SDD was 15.3 + /- 1.3 years . There were multigenerational mood disorders in 96 % and multigenerational SDD in 56 % of families . CONCLUSIONS Lithium treatment of BP with secondary SDD in adolescents was an efficacious treatment for both disorders . These results warrant replication with a long-term maintenance phase . The mean 6-year interval between the onset of BP and onset of SDD strongly argues for earliest recognition of BP |
13,436 | 26,565,396 | No significant differences were found in the congenital malformation rate , prematurity rate , and Apgar scores .
Compared to control , lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4 - 8 weeks ' postpartum follow-up .
Tenofovir showed improvement in HBV DNA suppression at delivery .
No significant differences were found in postpartum hemorrhage , cesarean section , and elevated creatinine kinase rates .
CONCLUSIONS Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone ; the use of telbivudine , lamivudine , and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome | UNLABELLED Perinatal or mother-to-child transmission ( MTCT ) of hepatitis B virus ( HBV ) remains the major risk factor for chronic HBV infection worldwide .
In addition to hepatitis B immune globulin and vaccination , oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV .
We conducted a systematic review and meta- analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy . | This r and omized , double-blind , placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus ( HBV ) perinatal transmission in highly viraemic mothers . Mothers were r and omized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum . At birth , infants received recombinant HBV vaccine with or without HBIg and were followed until week 52 . One hundred and fifty mothers , with a gestational age of 26 - 30 weeks and serum HBV DNA > 1000 MEq/mL ( bDNA assay ) , were treated . A total of 141 infants received immunoprophylaxis at birth . In lamivudine-treated mothers , 56 infants received vaccine + HBIg ( lamivudine + vaccine + HBIg ) and 26 infants received vaccine ( lamivudine + vaccine ) . In placebo-treated mothers , 59 infants received vaccine + HBIg ( placebo + vaccine + HBIg ) . At week 52 , in the primary analyses where missing data was counted as failures , infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity ( 10/56 , 18%vs 23/59 , 39 % ; P = 0.014 ) and in detectable HBV DNA ( 11/56 , 20%vs 27/59 , 46 % ; P = 0.003 ) compared to infants in the placebo + vaccine + HBIg group . Sensitivity analyses to evaluate the impact of missing data at week 52 result ing from a high dropout rate ( 13 % in the lamivudine + vaccine + HBIg group and 31 % in the placebo + vaccine + HBIg group ) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers , but the differences were not statistically significant . No safety concerns were noted in the lamivudine-treated mothers or their infants . Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization The purpose of this study was to investigate the efficacy and safety of lamivudine ( LAM ) in stopping the vertical transmission of hepatitis B virus ( HBV ) . Pregnant women with normal alanine transaminase ( ALT ) ( n = 100 ) and with abnormal ALT ( n = 100 ) who were positive for hepatitis B e antigen ( HBeAg ) , and with HBV DNA ( deoxyribonucleic acid ) levels ≥1.0 × 107 copies/ml were enrolled in this study . One hundred volunteers ( 50 with normal ALT , 50 with abnormal ALT ) received 100 mg of LAM daily from the 24th to 32nd week of gestation and the untreated 100 volunteers served as controls . All infants received passive-active immunoprophylaxis . Compared to the control group , the study group got a marked reduction in serum levels ( P < 0.001 ) and high negativity ( P < 0.001 ) of HBV DNA before delivery . They also got normalization in ALT levels as much as controls received general medication ( P > 0.05 ) . The prenatal transmission rate in the study group was significantly lower than that of the control group ( P < 0.05 ) . There were no differences in incidences of congenital malformation between the two groups ( P > 0.05 ) . LAM treatment can effectively and safely stop vertical transmission of HBV and normalize the ALT levels of pregnant women BACKGROUND & AIMS Fetal safety of antiviral therapies is important given the long-term treatment of women with chronic hepatitis B ( CHB ) infection who may become pregnant . We analyzed neonatal safety data from the Antiretroviral Pregnancy Registry ( APR ) , the largest safety data base in pregnancy for antivirals used for HIV and CHB . METHODS Data were extracted from APR cases prospect ively enrolled between 1989 and 2011 . Primary outcomes were major birth defects rates with exposure to all antivirals , individual classes , and drugs compared to population -based controls . Relevant to CHB , only lamivudine ( LAM ) and tenofovir disoproxil fumarate ( TDF ) had sufficient individual data for review ( ≥200 cases ) . RESULTS Of 13,711 cases analyzed , the overall birth defect prevalence ( 2.8 % , 95 % CI 2.6 - 3.1 % ) was comparable to Centers for Disease Control population -based data ( 2.72 % , 2.68 - 2.76 % , p=0.87 ) and two prospect i ve antiretroviral exposed newborn cohorts ( 2.8 % , 2.5 - 3.2 % , p=0.90 and 1.5 % , 1.1 - 2.0 % , p<0.001 ) . The birth defects prevalence between first and second/third trimesters exposure was similar ( 3.0 % vs. 2.7 % ) . No increased risk of major birth defects with LAM or TDF exposure compared to population -based controls was observed . No specific pattern of major birth defects was observed for individual antivirals or overall . CONCLUSIONS No increased risk of major birth defects including in non-live births was observed for pregnant women exposed to antivirals relevant to CHB treatment overall or to LAM or TDF compared to population -based controls . Continued safety and efficacy reporting on antivirals in pregnancy are essential to inform patients on their risks and benefits during pregnancy OBJECTIVE To determine the rate of perinatal hepatitis B virus ( HBV ) transmission in an Australian setting and to identify maternal virological factors associated with highest risk of transmission . DESIGN , PARTICIPANTS AND SETTING A prospect i ve , observational study of perinatal transmission of HBV . Participants were pregnant women attending Sydney South West Area Health Service antenatal clinics who tested positive for hepatitis B surface antigen ( HBsAg ) , and their babies . All babies were routinely offered hepatitis B immunoglobulin ( HBIG ) and HBV vaccination . Babies positive for HBsAg at 9-month follow-up underwent further virological testing , including HBV DNA sequencing . The study was conducted between August 2002 and May 2008 . MAIN OUTCOME MEASURES HBV DNA levels and demographic characteristics of HBsAg-positive pregnant women ; proportion of their infants with active HBV infection at 9-month follow-up ; maternal characteristics affecting transmission rate ; HBV DNA sequencing of infected infants and their mothers . RESULTS Of 313 HBsAg-positive pregnant women , 213 ( 68 % ) were HBV DNA-positive and 92 ( 29 % ) were positive for hepatitis B " e " antigen ( HBeAg ) ; 138 babies born to HBV DNA-positive mothers were tested for HBV infection ( HBsAg positivity ) at about 9 months of age . Four cases of transmission were identified . All four mothers had very high HBV DNA levels ( > 10(8 ) copies/mL ) and were HBeAg-positive . Three of the four infants were infected with wild-type HBV strains , with identical maternal/infant isolates . The fourth mother-infant pair had an S gene variant , HBV D144E , which has been previously reported in association with vaccine/HBIG escape . ( Unfortunately , HBIG was inadvertently omitted from the immunisation schedule of this infant . ) Transmission rates were 4/138 ( 3 % ) from HBV DNA-positive mothers overall , 4/61 ( 7 % ) from HBeAg-positive mothers , and 4/47 ( 9 % ) from mothers with very high HBV DNA levels . No transmission was seen in 91 babies of mothers with HBV DNA levels < 10(8 ) copies/mL. CONCLUSION In this cohort , HBV perinatal transmission was restricted to HBeAg-positive mothers with very high viral loads OBJECTIVE To investigate the efficacy of telbivudine on intrauterine hepatitis B virus ( HBV ) infection during the last stage of pregnancy . METHODS 61 pregnant chronic hepatitis B ( CHB ) patients were enrolled and 31 patients were treated by telbivudine 600 mg once daily , 30 patients in the control group were not received antiviral treatment . Maternal HBV DNA level and the HBsAg positive rate in newborns were investigated . RESULTS The levels of serum HBV DNA in patients treated with Telbivudine were significantly reduced ( t = 19.09 , P less than 0.01 ) . Compared with the control group , serum HBV DNA levels were significantly lower in telbivudine treated patients than those in the control group before parturition ( t = 23.64 , P less than 0.01 ) . The infection rate of 7-month newborns were 0 and 13.33 % ( 4/30 ) , in telbivudine group and control group , respectively ( x2 = 4.29 , probability value less than 0.05 ) . CONCLUSIONS Telbivudine treatment can block intrauterine infection in pregnant chronic hepatitis B patients OBJECTIVE To investigate the effect of high viral loads ( HBV DNA concentration in blood > 2.0 copy/ml ) on the vertical transmission of hepatitis B virus in mothers with HBV DNA positivity . METHOD Forty pregnant women with HBV DNA positivity were divided r and omly , double-blindly into 2 groups : at 28 weeks of pregnancy , one group received oral lamivudine ( 100 mg/d ) and the other received oral placebo . The serum HBV DNA loads were tested at 28 and 40 weeks ' gestation in mothers , and serum HBV DNA , HBsAg , HBeAg and anti-HBs were examined in infants at 12 month follow up . RESULT Thirty-nine infants finished ( one twins ) the follow up , and 2 infants lost ( 5 % ) . Among them 4 infants were confirmed to be HBV infection ( 10 % , 4/39 ) , 2 in the treatment group ( 10 % , 2/20 ) and 2 in the control group ( 11 % , 2/19 ) ( P > 0.05 ) . The serum HBV DNA levels of 40 weeks ' gestation in the treatment group , compared with the levels of 28 weeks ' gestation in the treatment group and 40 weeks ' gestation in the control group , showed a significant decline ( P < 0.01 ) . The HBV DNA levels of the mothers whose infants were infected , were ( 3.1 + /- 3.4 ) copy/ml , ( 3.1 + /- 3.2 ) copy/ml during 28 and 40 weeks ' gestation , and for mothers whose infants were non-infected , the levels were ( 3.4 + /- 2.2 ) copy/ml , ( 2.6 + /- 1 . 5 ) copy/ml respectively ( P > 0.05 ) . The mean values of anti-HBs of 18 infants in the treatment group showed no significant difference as compared to 17 infants in the control group , ( 594 + /- 416 ) U/L vs ( 458 + /- 398 ) U/L ( P > 0.05 ) . CONCLUSION The pregnant women 's HBV DNA loads could be obviously decreased from high viral loads ( HBV DNA concentrations in blood > 2.0 copy/ml ) after they take lamivudine from 36 weeks ' gestation . But it might not reduce the maternal-fetal vertical transmission of HBV infection Little observational data exist describing telbivudine ( LdT ) or lamivudine ( LAM ) use in late pregnancy for preventing hepatitis B mother-to-child transmission ( MTCT ) in real-world setting s. During the period of January 2009 to March 2011 , we enrolled hepatitis B e antigen – positive mothers with HBV DNA > 6 log10 copies/mL in China . At gestation week 28 , the mothers received LdT or LAM until postpartum week 4 or no treatment ( NTx ) . The study endpoints were the safety of LdT/LAM use and MTCT rates . Of the 700 mothers enrolled , 648 ( LdT/LAM/NTx = 252/51/345 ) completed the 52-week study with 661 infants ( LdT/LAM/NTx = 257/52/352 ) . On treatment , viral rebound occurred in 1.6 % of mothers , all result ing from medication noncompliance . There was no genotypic mutation detected . At delivery , significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx . Alanine aminotransferase flares were observed in 17.1 % of treated mothers versus 6.3 % of untreated mothers ( P < 0.001 ) . At birth , hepatitis B surface antigen ( HBsAg ) was detected in 20 % and 24 % of newborns in the treated and NTx groups , respectively . At week 52 , an intention-to-treat analysis indicated 2.2 % ( 95 % confidence [ CI ] : 0.6 - 3.8 ) of HBsAg+ infants from the treated group versus 7.6 % ( 95 % CI : 4.9 - 10.3 ) in the NTx group ( P = 0.001 ) and no difference of HBsAg+ rate between infants in the LdT and LAM groups ( 1.9 % vs. 3.7 % ; P = 0.758 ) . On-treatment analysis indicated 0 % of HBsAg+ infants in the treated group versus 2.84 % in the NTx group ( P = 0.002 ) . There were no differences for gestational age or infants ' height , weight , Apgar scores , or birth defect rates between infants from the treated and untreated groups . Conclusions : LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT . The treatment was well tolerated with no safety concerns identified AIM To evaluate the efficacy of hepatitis B immunoglobulin ( HBIG ) in interrupting hepatitis B virus ( HBV ) intrauterine infection during late pregnancy . METHODS We allocated 112 HBsAg positive pregnant women into 2 groups r and omly . Fifty seven cases in the HBIG group received 200 IU ( unit ) HBIG intramuscularly every 4 wk from the 28 wk of gestation to the time of delivery , while 55 cases in the control group received no special treatment . HBsAg , HBeAg , HBcAb , HBeAb , HBsAb and HBV DNA levels were tested in the peripheral blood specimens from all of the mothers at 28 wk of gestation , just before delivery , and in blood from their newborns within 24 h before administration of immune prophylaxis . RESULTS The intrauterine infection rate in HBIG group and control group were 10.5 % and 27.3 % , respectively , with significant difference ( P<0.05 ) . It showed ascendant trend as HBV DNA levels in the peripheral blood increased before delivery . CONCLUSION HBIG is potent to cut down HBV intrauterine infection rate significantly when administered to pregnant women regularly during late pregnancy . The possibility of HBV intrauterine infection increases if maternal blood HBV DNA > or = 10(8 ) 宫内新生儿HBV感染主要与孕妇血清内HBV DNA的高载量有关 . 近年来临床上采用替比夫定进行HBV母婴阻断取得良好的疗效[1].本研究主要观察替比夫定阻断母婴垂直传播分娩后停药时间对母亲安全性的影响 , 以寻求临床最佳停药时间 . 关键词：肝炎病毒 , 乙型;垂直传播;替比夫定 BACKGROUND & AIMS Telbivudine reduces hepatitis B virus ( HBV ) DNA and normalizes levels of alanine aminotransferase ( ALT ) in patients with chronic hepatitis B ( CHB ) . We investigated its use in preventing vertical transmission . METHODS We performed an open-label , prospect i ve study of 88 hepatitis B ( HB ) e antigen (HBeAg)-positive pregnant women with CHB , levels of HBV DNA > 6 log(10 ) copies/mL , and increased levels of ALT . Women were given telbivudine ( n = 53 ) starting in the 2nd or 3rd trimester , or no treatment ( controls , n = 35 ) and followed until postpartum week ( PPW ) 28 . All infants received st and ard immunoprophylaxis after birth . RESULTS At 28 weeks , none of the infants whose mothers received telbivudine had immunoprophylaxis failure , whereas 8.6 % of the infants of control mothers did ( P = .029 ) . There were no differences between groups in mothers ' adverse events or infants ' congenital deformities , gestational age , height , and weight , or Apgar scores . At postpartum week 28 , significantly more telbivudine-treated mothers had levels of HBV DNA < 500 copies/mL , normalized levels of ALT , and hepatitis B e antigen seroconversion compared with controls ( 58 % vs none , P < .001 ; 92 % vs 71 % ; P = .008 ; and 15 % vs none ; P < .001 , respectively ) but none had loss of hepatitis B surface antigen . Telbivudine-treated mothers had no virologic breakthrough ( HBV DNA > 1 log(10 ) increase from < 500 copies/mL ) or discontinuations from adverse events . After delivery , 13/52 patients discontinued telbivudine due to preference . There were no episodes of severe hepatitis ( levels of ALT > 10 times the upper limit of normal ) in either group during 28 weeks of postpartum observation . CONCLUSIONS Women with CHB given telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission . Telbivudine produced no adverse events in mothers or infants by 28 weeks BACKGROUND & AIMS In the Asia-Pacific region , perinatal transmission of the hepatitis B virus ( HBV ) is the primary cause of chronic hepatitis B infection . Despite the use of HBIG and HBV vaccination , HBV perinatal transmission ( PT ) occurs in 10 - 30 % of infants born to highly viremic mothers . We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers . METHODS Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0 × 10(7 ) copies/ml mothers received telbivudine 600 mg/day from week 20 to 32 of gestation ( n=135 ) or served as untreated controls ( n=94 ) . All infants in both arms received 200 IU of HBIg within 12 h postpartum and recombinant HBV vaccine of 20 μg at 0 , 1 , and 6 months . HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate . All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry . RESULTS Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen ( HBeAg ) levels and normalization of elevated ALT levels before delivery . A striking decline of HBV DNA levels started from treatment onset to week 4 , and sustained in a low level since week 12 . Forty-four ( 33 % ) of the 135 telbivudine-treated mothers and none ( 0 % ) of the untreated controls had polymerase chain reaction-undetectable viremia ( DNA<500 copies/ml ) at delivery . Seven months after delivery , the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls ( 0 % vs. 8 % ; p=0.002 ) . HBV DNA levels were only detectable in HBsAg+infants . No significant differences in anti-HBs levels were observed during postnatal follow-up . No serious adverse events were noted in the telbivudine-treated mothers or their infants . CONCLUSIONS Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission . Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up . These data support the use of telbivudine in this special population BACKGROUND & AIMS Data on the long-term safety of lamivudine are limited . The aim of this analysis was to determine the incidence of hepatitis flares , hepatic decompensation , and liver-disease-related ( LDR ) serious adverse events ( SAE ) during long-term lamivudine treatment . METHODS We review ed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years ( median , 4 years ) and 200 patients who received placebo for 1 year . RESULTS Hepatitis flares occurred in 10 % of the lamivudine-treated patients in year 1 and in 18%-21 % in years 2 - 5 . A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43 % in year 1 to > 80 % in year 3 . Ten hepatic decompensation events occurred in 8 ( < 1 % ) lamivudine-treated patients . Fifty-three ( 5 % ) lamivudine-treated patients experienced a total of 60 LDR SAEs . Four patients died , 2 from liver-related causes . The proportion of patients with a documented lamivudine-resistant mutation increased from 23 % in year 1 to 65 % in year 5 . During each year of the study , patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations ( P < 0.005 ) . The occurrence of hepatic decompensation ( 0%-2 % ) and LDR SAEs ( 1%-10 % ) among patients with lamivudine resistance remained stable during the first 4 years with mutations and increased afterward to 6 % ( P = 0.03 ) and 20 % ( P = 0.009 ) , respectively . CONCLUSIONS This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease , but patients with long-st and ing lamivudine-resistant mutations may experience worsening liver disease Objective : To evaluate the association of tenofovir disoproxil fumarate ( TDF ) use during pregnancy with early growth parameters in HIV-exposed , uninfected ( HEU ) infants . Design : US-based prospect i ve cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure . Methods : We evaluated the association of maternal TDF use during pregnancy with small for gestational age ( SGA ) ; low birth weight ( LBW , < 2.5 kg ) ; weight-for-age z-scores ( WAZ ) , length-for-age z-scores ( LAZ ) , and head circumference-for-age ( HCAZ ) z-scores at newborn visit ; and LAZ , HCAZ , and WAZ at age 1 year . Logistic regression models for LBW and SGA were fit , adjusting for maternal and sociodemographic factors . Adjusted linear regression models were used to evaluate LAZ , WAZ , and HCAZ by TDF exposure . Results : Of 2029 enrolled children with maternal antiretroviral information , TDF was used by 449 ( 21 % ) HIV-infected mothers , increasing from 14 % in 2003 to 43 % in 2010 . There was no difference between those exposed to combination regimens with vs. without TDF for SGA , LBW , and newborn LAZ and HCAZ . However , at age 1 year , infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF ( LAZ : −0.17 vs. −0.03 , P = 0.04 ; HCAZ : 0.17 vs. 0.42 , P = 0.02 ) . Conclusion : TDF use during pregnancy was not associated with increased risk for LBW or SGA . The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy OBJECTIVE To evaluate the therapeutic efficacy and safety of lamivudine treatment in late pregnancy by analyzing the maternal-fetal outcomes of chronic hepatitis B ( CHB ) mothers featuring hepatitis B e antigen (HBeAg)-positivity and highly viremic status . METHODS A total of 256 pregnant women in the second or third trimester with monoinfected CHB , HBeAg-positivity , and HBV DNA more than 6 log10 copies/mL were divided into two groups : lamivudine ( lam ) treatment ( n=164 ) or no treatment ( controls ; n=92 ) . All infants were treated with hepatitis B immune globin ( HBIg ; 200 IU ) within 12 hrs of birth and 15 days later , and were given the recombinant HBV vaccine ( 20 mug ) at 0 , 1 and 6 months . All infants were followed-up to at least seven months and hepatitis B surface antigen ( HBsAg ) and HBV DNA levels were used to determine perinatal transmission ( PT ) rates . The mothers ' data from routine blood analysis , tests of hepatic and renal function , detection of HBV markers and HBV DNA were retrospectively analyzed to determine changes associated with the lam treatment . Correlations of lam treatment with HBV PT rate , alanine aminotransferase ( ALT ) normalization , adverse reactions , pregnancy complications , congenital deformities , and infants ' growth/development were determined by statistical analyses . RESULTS Prior to delivery , the lam-treated mothers had significantly lower HBV DNA levels ( 3.72+/-1.78 vs. controls : 7.83+/-0.67 log10 c/ml ; t=-22.359 , P less than 0.001 ) . The rate of virological response in the lam-treated group was 97.56 % ( 160/164 ) . The lam-treated group had significantly higher ALT normalization rate ( 90.20 % vs. controls : 55.88 % ; X2=13.349 , P less than 0.001 ) and significantly lower HBeAg titer ( 957.73+/-458.42 vs. controls : 1296.35+/-383.14 S/CO ; t=-5.410 , P less than 0.001 ) . At birth , the infants from lam-treated mothers had significantly lower HBsAg-positivity ( 15.24 % ( 25/164 ) vs. controls : 30.43 % ( 28/92 ) ; X2=8.284 , P=0.004 ) . By 7 - 12 months after birth , none of the infants born to lam-treated mothers tested positive for HBsAg , compared to 8.70 % ( 8/92 ) of the infants born to mothers in the control group ( X2=14.721 , P less than 0.001 ) . None of the lam-treated mothers required treatment discontinuation due to adverse events or lam-resistance . No congenital deformities were observed during the study and follow-up periods . There were no differences between the lam-treated and control groups for postpartum hemorrhage , gestational age , infants ' height/weight or Apgar scores . CONCLUSION In highly viremic HBsAg+ mothers with CHB , lam treatment in the second or third trimester of pregnancy is safe and effective for reducing HBV maternal-neonatal transmission Fifty-one asymptomatic Chinese hepatitis B surface antigen ( HBsAg ) carrier children ( 34 boys , 17 girls ) , age 1 to 15 years ( median : 10 years ) , were prospect ively followed for up to 4 years ( median : 30 months ) to determine the natural evolution of clinical , biochemical and virological features during the early phase of chronic hepatitis B virus infection . Hepatomegaly was the only abnormal finding on examination , being present in five children initially and four at follow-up . Serum ALT levels were normal in 80 % of the children at presentation and remained within the normal range during the study in 60 % . Fluctuations in ALT levels were mild . In four of 12 instances , transient elevations in ALT levels were associated with a fall in serum hepatitis B virus DNA levels . At presentation , 43 ( 84 % ) children were hepatitis B e antigen ( HBeAg ) positive ; only two ( 7 % ) cleared HBeAg on follow-up . None of the eight children who were initially positive for the antibody to HBeAg reverted back to HBeAg positivity . All the children remained HBsAg positive . In this study , we demonstrated that chronic hepatitis B virus infection in asymptomatic Chinese children is usually associated with a mild and stable liver disease despite high levels of hepatitis B virus replication . This may reflect an immunological tolerance to the hepatitis B virus induced by early exposure to the virus and accounts for the persistently high levels of hepatitis B virus replication on follow-up BACKGROUND & AIMS Persistence of hepatitis B e antigen ( HBeAg ) in chronic hepatitis B has been associated with increased risk for development of cirrhosis and hepatocellular carcinoma . Five hepatitis B virus genotypes were identified in Alaska Native persons ; we analyzed clearance of HBeAg by age and genotype . METHODS In this prospect i ve cohort study , 1158 Alaska Native persons throughout Alaska were tested serially for HBeAg for a median of 20.5 years and were genotyped . Initial and final HBeAg-positive specimens , time to clearance , age at clearance , and subsequent HBeAg results were analyzed for persons initially HBeAg-positive . Subsequent HBeAg results were analyzed for persons initially negative . RESULTS Genotypes A , B , C , D , and F were identified . Genotype C persons initially HBeAg-positive were more likely than those with other genotypes to be positive on initial and final specimens ( P < .001 for each ) and time to HBeAg clearance was longer ( P < .001 ) . Age at which 50 % of persons cleared HBeAg was < 20 years for those infected with genotypes A , B , D , and F and 47.8 years in genotype C ( P < .001 ) . After losing HBeAg , those with genotypes C and F were more likely to revert to the HBeAg-positive state ( P < .001 ) . CONCLUSIONS Genotype may have a strong effect on mode of transmission and outcome . Genotype C may have been responsible for most perinatal transmission , given that seroconversion from HBeAg occurs decades later than in other genotypes OBJECTIVE To evaluate the efficacy and safety of telbivudine use during the second and third trimester of pregnancy for reducing hepatitis B virus ( HBV ) transmission from highly viremic hepatitis B e antigen-positive ( HBeAg+ ) mothers to their fetuses . METHODS Pregnant women , between weeks 20 to 32 of gestation , who were HBeAg+ and had HBV DNA more than 1.0 * 10(7 ) copies/mL were enrolled in our study . The women were offered inclusion into one of two treatment arms , based upon their personal preference : telbivudine or no telbivudine . The patients in the telbivudine treatment arm were administered 600 mg/d telbivudine at least until postpartum week 4 . All delivered infants in both treatment arms were administered hepatitis B immune globulin ( HBIG ; 200 IU ) within 12 hours of delivery and recombinant HBV vaccine ( 20 mug ) at 0 , 1 and 6 months . The HBV perinatal transmission rate was determined by measuring HBsAg and HBV DNA in infants at postpartum week 28 . RESULTS A total of 220 pregnant women were enrolled in our study , 120 chose the telbivudine arm and 100 chose the control arm . All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry . Telbivudine treatment was associated with a marked reduction in the mothers ' serum HBV DNA , HBeAg and ALT levels before delivery . A striking decline of HBV DNA levels in treated mothers was observed at week 2 of treatment , which was followed by a gradual and steady decrease that continued until delivery . Thirty-seven ( 31 % ) of the telbivudine-treated mothers and none ( 0 % ) of the untreated controls had polymerase chain reaction-undetectable viremia at delivery . At week 28 , 0 % of the infants delivered from telbivudine-treated mothers were HBsAg+ or HBV DNA+ , as compared to 8 % HBsAg+ or HBV DNA+ in the untreated control arm ( P = 0.002 ) . No telbivudine discontinuations occurred from adverse events , and no congenital deformities were observed in the infants delivered to telbivudine-treated mothers . Eighty mothers discontinued telbivudine at week 4 postpartum , and there were no cases of severe hepatitis . There were no significant differences between the two treatment arms for postpartum hemorrhage , adverse events during pregnancy , cesarean section , gestational age , or infants ' height/weight or Apgar scores . CONCLUSIONS Telbivudine use during the second and third trimester of pregnancy in HBeAg+ highly viremic mothers can safely reduce perinatal HBV transmission rates . Telbivudine was well-tolerated by our patient group . Furthermore , no safety concerns were observed in either the telbivudine-treated mothers or their delivered infants in short term follow-up AIM To investigate the effect of hepatitis B virus ( HBV ) specific immunoglobin ( HBIG ) and lamivudine on HBV intrauterine transmission in HBsAg positive pregnant women . METHODS Each subject in the HBIG group ( 56 cases ) was given 200 IU HBIG intramuscularly ( i m . ) every 4 weeks from 28-week ( wk ) of gestation , while each subject in the lamivudine group ( 43 cases ) received 100 mg lamivudine orally ( po . ) every day from 28-wk of gestation until the 30(th ) day after labor . Subjects in the control group ( 52 cases ) received no specific treatment . Blood specimens were tested for HBsAg , HBeAg , and HBV-DNA in all maternities at 28-wk of gestation , before delivery , and in their newborns 24 hours before the administration of immune prophylaxis . RESULTS Reductions of HBV DNA in both treatments were significant ( P<0.05 ) . The rate of neonatal intrauterine HBV infection was significantly lower in HBIG group ( 16.1 % ) and lamivudine group ( 16.3 % ) compared with control group ( 32.7 % ) ( P<0.05 ) , but there was no significant difference between HBIG group and lamivudine group ( P>0.05 ) . No side effects were found in all the pregnant women or their newborns . CONCLUSION The risk of HBV intrauterine infection can be effectively reduced by administration of HBIG or Lamivudine in the 3(rd ) trimester of HBsAg positive pregnant women The efficacy and safety of maternal tenofovir disoproxil fumarate ( TDF ) in reducing mother‐to‐infant hepatitis B virus ( HBV ) transmissions is not clearly understood . We conducted a prospect i ve , multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen – positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication ( control group , n = 56 , HBV DNA 8.22 ± 0.39 log10 IU/mL ) or TDF 300 mg daily ( TDF group , n = 62 , HBV DNA 8.18 ± 0.47 log10 IU/mL ) from 30‐32 weeks of gestation until 1 month postpartum . Primary outcome was infant HBsAg at 6 months old . At delivery , the TDF group had lower maternal HBV DNA levels ( 4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL , P < 0.0001 ) . Of the 121/123 newborns , the TDF group had lower rates of HBV DNA positivity at birth ( 6.15 % versus 31.48 % , P = 0.0003 ) and HBsAg positivity at 6 months old ( 1.54 % versus 10.71 % , P = 0.0481 ) . Multivariate analysis revealed that the TDF group had lower risk ( odds ratio = 0.10 , P = 0.0434 ) and amniocentesis was associated with higher risk ( odds ratio 6.82 , P = 0.0220 ) of infant HBsAg positivity . The TDF group had less incidence of maternal alanine aminotransferase ( ALT ) levels above two times the upper limit of normal for ≥3 months ( 3.23 % versus 14.29 % , P = 0.0455 ) , a lesser extent of postpartum elevations of ALT ( P = 0.007 ) , and a lower rate of ALT over five times the upper limit of normal ( 1.64 % versus 14.29 % , P = 0.0135 ) at 2 months postpartum . Maternal creatinine and creatinine kinase levels , rates of congenital anomaly , premature birth , and growth parameters in infants were comparable in both groups . At 12 months , one TDF‐group child newly developed HBsAg positivity , presumably due to postnatal infection and inefficient humoral responses to vaccines . Conclusions : Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations . ( Hepatology BACKGROUND & AIMS Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9 % of children from highly viraemic mothers . Antiviral therapy in this setting has been suggested , however with limited evidence to direct agent choice . METHODS We conducted a multi-centre , prospect i ve , opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load ( > 7 log IU/ml ) ; lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate ( TDF ) from late 2010 . Outcomes of treated and untreated cohorts were compared . RESULTS 120 women with 130 pregnancies used TDF ( 58 ) , lamivudine ( 52 including four who switched due to TDF intolerance ) and no therapy ( 20 ) . 96 % were HBeAg positive , with baseline viral load mean 7.8 log IU/ml ( ±0.72 ) and ALT median 25 U/L ( 18.75 - 33 ) . Duration of antiviral theraphy before birth was mean 58 days ( ±19 ) TDF and 53 ( ±14 ) lamivudine . Viral load declined by 3.64 log IU/ml ( ±0.9 ) TDF and 2.81 log IU/ml ( ±1.33 ) lamivudine . Virologic failure ( birth viral load > 7 IU/ml ) occurred in 3 % and 18 % respectively . Congenital abnormality rate and neonatal growth centiles were similar across cohorts . Perinatal transmission reduced significantly to 2 % and 0 % in TDF and lamivudine cohorts , compared with 20 % in untreated . CONCLUSIONS TDF in this setting is safe , effective and more potent than lamivudine . Antiviral therapy did not adversely impact obstetric or infant parameters . More TDF intolerance occurred than expected . Perinatal transmission was significantly reduced in antiviral therapy cohorts |
13,437 | 27,266,275 | A high- quality meta- analysis with more RCTs was chosen , which suggested that there was no statistically significant difference between MIS and OS regarding rerupture rate , tissue adhesion , sural nerve injury , deep infection , and deep vein thrombosis .
However , MIS could decrease superficial infection rate , and had a better patient satisfaction for good to excellent outcomes in comparison to OS .
Conclusions Based on the best available evidence , MIS may be superior to OS for treating acute Achilles tendon rupture . | Background A number of meta-analyses have been carried out to evaluate the effects of minimally invasive surgery ( MIS ) versus open surgery ( OS ) for acute Achilles tendon rupture .
However , discordant findings were seen in these meta-analyses .
The present study , performing a systematic review of overlapping meta-analyses regarding MIS versus OS of acute Achilles tendon rupture , aim ed to assist decision-makers interpret and choose among conflicting meta-analyses , as well as to offer treatment recommendations based on current best evidence . | Purpose . To survey the management of acute Achilles tendon ruptures in the United Kingdom . Methods . A question naire with 4 different Achilles tendon rupture scenarios affecting patients of different ages and activity levels was sent to orthopaedic consultants specialised in sports trauma , foot and ankle surgery . Their treatment methods including surgical techniques , immobilisation and rehabilitation regimens were surveyed . Results . The response rate was 22 % ( 51/231 ) . Among the 51 respondents , 25 had managed less than 6 such patients in the preceding year . 26 ( 51 % ) used clinical examination ( e.g. calf squeeze test ) to make the diagnosis , 16 ( 31 % ) used ultrasonography , and 4 ( 8 % ) used magnetic resonance imaging . Surgical management was preferred for younger and more functionally dem and ing individuals . Open repairs were used more often than percutaneous repairs ( 72 vs 19 % ) . Across the 4 scenarios , the mean time to return to full activity was 17 ( range , 12–32 ) weeks for conservative to 19 ( range , 10–40 ) weeks for surgical management . Conclusion . Variation in opinion among respondents was wide . R and omised controlled trials are needed to assess optimal treatment BACKGROUND The treatment of Achilles tendon rupture has been controversial , and attempts are made to attenuate the complications arising from invasive procedures with minimally invasive techniques . This paper is a comparison between the results of Lynn 's traditional open technique and those of minimally invasive surgery assisted with the Achillon instrument guide . MATERIAL AND METHODS A prospect i ve , r and omized study was carried out in fifty-six patients with acute rupture of the Achilles tendon . Twenty-eight of them underwent surgery with Lynn 's technique and 28 underwent minimally-invasive surgery assisted with a mechanical guide . Patients were assessed at postoperative weeks 4 , 6 , 8 , 10 and 16 . They were examined for pain , muscle strength , presence or absence of Thomas sign , Merkel scale , ranges of motion , degree of amyotrophy , time to healing , degree of functional recovery , and complications . Data analysis was done with central trend measurements and nonparametric analyses . RESULTS The following were reported for Lynn 's technique ( LT ) and the minimally invasive approach ( MI ) : Mobility in extension : ( LT ) 40.3 + /- 0.59 degrees vs. ( MI ) 50.0 + /- 0.42 ( p < 0.01 ) ; flexion : ( LT ) 13.9 + /- 0.12 degrees vs. ( MI ) 18.2 + /- 18.2 degrees ( p < 0.01 ) ; amyotrophy : ( LT ) 2.9 + /- 0.09 cm vs. ( MI ) 1.5 + /- 0.13 ( p < 0.01 ) ; time to healing : ( LT ) 9.0 + /- 0.13 vs. ( MI ) 6.1 + /- 0.09 weeks ( p = 0.01 ) ; return to work : ( LT ) 9 weeks vs. ( MI ) 6 weeks . Postoperative complications were 19 for LT and 1 for MI . CONCLUSIONS The MI approach had statistically significant advantages over Lynn 's technique , which we attribute to a lesser tissue and neurovascular trauma OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review BACKGROUND We prospect ively analyzed and compared the functional and clinical results of patients with st and ard open and minimally invasive repair with the Achillon suture system at mid-term followup . MATERIAL S AND METHODS From February 2004 to May 2007 , 40 consecutive patients were operated for the treatment of acute Achilles tendon rupture with two different methods . None of the cases required adjunctive procedures like plantaris , flexor hallucis longus or gastrocnemius augmentation ( Lindholm , Bosworth ) to allow for acceptable end to end apposition . The patients were divided equally into two groups . In Group 1 , only Krakow end-to-end suturing technique and in Group 2 , Minimal invasive repair with Achillon suture system ( Integra Life Sciences Corporation , Plainsboro , NJ ) was used respectively . The average age of the patients was 40 years . Patients in study groups were followed up at mean of 22.4 ( range , 10 to 48 ) months after surgery . At the end of the followup time , functional outcome scores and complications were evaluated . RESULTS The AOFAS hindfoot clinical outcome scores were 98.7 in Group 1 , 96.8 in Group 2 . Although there was a numerical increase in AOFAS Scores in Group 1 , there was no significant difference . The surgical outcome concerning local tenderness , skin adhesions , scar and tendon thickness was better in Group 2 than in Group 1 with statistical significance . CONCLUSION Although functional outcomes of both treatment groups were the same , minimally invasive repair with the Achillon suture system provided safe , reliable and practical treatment with low risk of complications in the treatment of acute Achilles tendon ruptures The object of this study was to compare treatment of ruptured Achilles tendon by operative " end to end " surgery , percutaneous repair , or conservative therapy clinical ly ; a subject of considerable controversy in the literature . These three methods were compared in 73 patients in a r and omized trial between 1994 and 1996 . After 2.5 years ( 11 - 41 months ) , the actual activities were assigned to the Hannover Achilles tendon score and the ability of doing work or sport activities was assessed . After this period , 59.3 % of the patients showed good and excellent results on the Achilles tendon score , with over 79 points ( open surgery 59.1 % , percutaneous 60 % , conservative treatment 58.3 % ) . None of the patients reached the maximum score of 100 points . During the isometric strength tests , the patients with percutaneous repair had a lower weakening of the treated leg ( 8.9 % ) compared to the open-operated ( 12.7 % ) and non-operated patients ( 17.8 % ) . Of the patients who had percutaneous surgery , 88 % rated their treatment as good or excellent ; those who had open surgery 77.3 % , and those with conservative treatment 75 % . The percutaneous group were able to resume work and sport much sooner than the other two groups . Bearing in mind the literature and these results , we have developed an algorithm for treating Achilles tendon rupture to assist decision making in daily routine . In this way , the use of percutaneous Achilles tendon repair can be carried out in most of cases A prospect i ve r and omized controlled trial comparing open and percutaneous repair of closed ruptured Achilles tendons was performed over a period of 30 months . Sixty-six patients from seven district general hospitals were entered into the study with 33 patients r and omized into each group . A modification of the technique described by Ma and Griffith was used in the percutaneous group and a Kessler suture supplemented with interrupted sutures was used in the open group . Patients were followed up for a minimum of six months . The mean age was 38.5 years ( 26 to 53 years ) . Forty patients were male and 26 female . After the rupturing event but prior to surgery , it was noted that seven patients had paresthesia in the territory of the sural nerve . The mean duration of immobilization was 12.4 weeks ( 10 to 14 ) . The complications in the open group included seven wound infections ( 21 % ) , two adhesions ( 6 % ) and two cases of re-rupture ( 6 % ) . In the percutaneous group there were three cases of wound puckering ( 9 % ) , one re-rupture ( 3 % ) and one case with persistent paresthesia in the sural nerve territory ( 3 % ) . The difference in infective wound complications between the two groups was statistically significant ( Fisher 's exact test P = 0.01 ) . Percutaneous repair is advocated on the basis of the low rate of complications and improved cosmetic appearance Purpose To study the effects of early weightbearing and ankle mobilization after acute repair of ruptured Achilles tendon . Study Design Comparative longitudinal study . Methods Patients in group 1 were postoperatively immobilized with their ankle in gravity equinus , they were encouraged to bear weight on the operated limb as soon as possible to full weightbearing , and they received a single cast change at 2 weeks , with the ankle accommo date d in an anterior splint in a planti grade position , allowing the ankle to be plantar flexed fully but not dorsiflexed above neutral . Patients in group 2 were immobilized with their ankle in full equinus with a cast change at 2 weeks , when the ankle was immobilized in mid equinus , and at 4 weeks , when the ankle was immobilized in a planti grade position , and they were advised to bear weight . Results Patients in group 1 attended fewer outpatient visits , completely discarded their crutches at an average of 2.5 weeks , and more were satisfied with the results of surgery . At ultrasonography , the average thickness of the repaired tendon was 12.1 mm , with no difference in the thickness of the ruptured tendon regardless of postoperative management . There was no significant difference in isometric strength between the two groups . Conclusions Early weightbearing with the ankle planti grade is not detrimental to the outcome of repair after acute rupture of the Achilles tendon and shortens the time needed for rehabilitation . However , strength deficit and muscle atrophy are not prevented There is no agreement on the ideal type of surgical management for Achilles tendon rupture . The present r and omized prospect i ve study was performed to compare outcome data of open and percutaneous repair in the treatment of Achilles tendon rupture . Forty consecutive patients with acute rupture of Achilles tendon were recruited . Patients were r and omized to receive open ( group A ) or percutaneous repair with Tenolig ® ( group B ) . All patients followed the same rehabilitation protocol except for slight differences in the duration of immobilization . Follow-up included objective evaluation ( at 4 and 12 months ) , subjective evaluation using the SF-12 ® question naire ( at 24 months ) , and bilateral ultrasound scanning and isokinetic testing ( at 12 months ) . The differences in the parameters evaluated clinical ly were not significant except for ankle circumference , which was significantly greater in group B. There were two minor complications in the open repair group and one case of failed repair in the percutaneous group . SF-12 ® question naire , ultrasound and isokinetic test data did not show significant differences between the groups . The present study demonstrates that the open and the percutaneous technique are both safe and effective in repairing the ruptured Achilles tendon and that both afford the same degree of restoration of clinical , ultrasound and isokinetic patterns . Medium-term results were substantially comparable . Percutaneous repair is performed on a day-surgery basis , it reduces cutaneous complications and operation times , and enables faster recovery , enhancing overall patient compliance . To us , these characteristics make it preferable to open repair in managing subcutaneous ruptures of Achilles tendon in non-professional sports practicing adults Orthopaedic surgeons have always based their clinical care on evidence . Surgeons use evidence to make decisions tailored to an individual patient 's needs and circumstances . The primary sources of evidence for clinicians are studies published in the medical and surgical literature , such as The Journal of Bone and Joint Surgery . In June 2000 , The Journal introduced the quarterly Evidence -Based Orthopaedics section 1 . This section introduces orthopaedic surgeons to recent r and omized trials relevant to the practice of orthopaedic surgery published in forty-two journals other than The Journal of Bone and Joint Surgery . Structured abstract s of these studies are |
13,438 | 26,217,521 | There were no consistent associations in outcomes related to the mode of intervention delivery , the number or type of providers involved or the intensity of the intervention .
Conclusions There was evidence for the effectiveness of interventions that focussed on improving knowledge and skills ( health literacy ) for weight loss .
However , there was insufficient evidence to determine relative effectiveness of individual interventions . | Background Enhancing individual ’s health literacy for weight loss is important in addressing the increasing burden of chronic disease due to overweight and obesity .
We conducted a systematic review and narrative synthesis to determine the effectiveness of lifestyle interventions aim ed at improving adults ’ knowledge and skills for weight loss in primary health care . | Background R and omised controlled trials demonstrate a 60 % reduction in type 2 diabetes incidence through lifestyle modification programmes . The aim of this study is to determine whether such programmes are feasible in primary health care . Methods An intervention study including 237 individuals 40–75 years of age with moderate or high risk of developing type 2 diabetes . A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006 . Main outcome measures taken at baseline , three , and 12 months included weight , height , waist circumference , fasting plasma glucose and lipids , plasma glucose two hours after oral glucose challenge , blood pressure , measures of psychological distress and general health outcomes . To test differences between baseline and follow-up , paired t-tests and Wilcoxon rank sum tests were performed . Results At twelve months participants ' mean weight reduced by 2.52 kg ( 95 % confidence interval 1.85 to 3.19 ) and waist circumference by 4.17 cm ( 3.48 to 4.87 ) . Mean fasting glucose reduced by 0.14 mmol/l ( 0.07 to 0.20 ) , plasma glucose two hours after oral glucose challenge by 0.58 mmol/l ( 0.36 to 0.79 ) , total cholesterol by 0.29 mmol/l ( 0.18 to 0.40 ) , low density lipoprotein cholesterol by 0.25 mmol/l ( 0.16 to 0.34 ) , triglycerides by 0.15 mmol/l ( 0.05 to 0.24 ) and diastolic blood pressure by 2.14 mmHg ( 0.94 to 3.33 ) . Significant improvements were also found in most psychological measures . Conclusion This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care setting s , with reductions in risk factors approaching those observed in clinical trials . Trial NumberCurrent Controlled Trials IS RCT Background Rising levels of obesity coupled with the limited success of currently available weight control methods highlight the need for investigation of novel approaches to obesity treatment . This study aims to determine the effectiveness and cost-effectiveness of an Internet-based re source for obesity management . Methods A r and omised controlled trial conducted in a community setting , where obese volunteers ( n = 221 ) were r and omly assigned to Internet group ( n = 111 ) or usual care group ( n = 110 ) . Objective measures of weight and height were obtained . Question naires were used to collect dietary , lifestyle , physical activity and quality of life data . Data were collected at baseline , six months and 12 months . Results Data were collected on 54 ( 49 % ) participants in the Internet group and 77 ( 70 % ) participants in the usual care group at 12 months . Based on analysis conducted on all available data , the Internet group lost 1.3 kg , compared with 1.9 kg weight loss in the usual care group at 12 months , a non-significant difference ( difference = 0.6 kg ; 95 % CI : -1.4 to 2.5 , p = 0.56 ) . No significant differences in change in secondary outcome measures between the two groups at six or 12 months were revealed . Total costs per person per year were higher in the Internet group than the usual care group ( £ 992.40 compared to £ 276.12 ) , primarily due to the fixed costs associated with setting up the website , and QALYs were similar ( 0.78 and 0.77 ) for both groups . Conclusion This trial failed to show any additional benefit of this website in terms of weight loss or secondary outcome measures compared with usual care . High attrition and low compliance limits the results of this research . The results suggest that the Internet-based weight control re source was not a cost-effective tool for weight loss in the obese sample studied . Trail Registration IS RCT N Background : Research on the translation of efficacious lifestyle change programs to prevent type 2 diabetes into community or clinical setting s is needed . Objective : The objective of this study was to examine the reach , implementation , and efficacy of a 6-month lifestyle program implemented in primary care by nurse practitioners ( NPs ) for adults at risk of type 2 diabetes . Methods : The NP sites ( n = 4 ) were r and omized to an enhanced st and ard care program ( one NP and one nutrition session ) or a lifestyle program ( enhanced st and ard care and six NP sessions ) . These NPs recruited adults at risk of diabetes from their practice ( n = 58 ) , with an acceptance rate of 70 % . Results : The program reached a diverse , obese , and moderately low income sample . The NPs were able to successfully implement the protocol s. The average length of the program was 9.3 months . Attendance was high ( 98 % ) , and attrition was low ( 12 % ) . The NPs were able to adopt the educational , behavioral , and psychosocial strategies of the intervention easily . Motivational interviewing was more difficult for NPs . Mixed-model repeated- measures analysis indicated significant trends or improvement in both groups for nutrition and exercise behavior . Participants of the lifestyle program demonstrated trends for better high-density lipoprotein ( HDL ) and exercise behavior compared with the enhanced st and ard care participants . Twenty-five percent of lifestyle participants met treatment goals of 5 % weight loss compared with 11 % of st and ard care participants . Discussion : A lifestyle program can be implemented in primary care by NPs , reach the targeted population , and be modestly successful . Further research is indicated OBJECTIVE To measure the level of functional health literacy ( FHL ) in an Australian population , and to explore the level of risk associated with level of FHL . DESIGN , SETTING AND PARTICIPANTS Cross-sectional , r and om population survey administered to 2824 South Australians aged > or=15 years , September-October 2008 . MAIN OUTCOME MEASURES Newest Vital Sign as a measure of FHL , self-reported general health status , and use of health services . RESULTS 24 % of respondents were at risk of limited FHL , and 21 % had a high likelihood of inadequate FHL ; this increased with age ( > or=65 years , 50 % v 25 - 44 years , 11 % ) . In multiple logistic regression models , a high likelihood of inadequate FHL was significantly more common among those with lower education ( left school < or=15 years of age , odds ratio [ OR ] , 8.1 ; 95 % CI , 4.8 - 13.6 ) ; with lower annual income ( < $ 20 000 , OR , 4.1 ; 95 % CI , 2.3 - 7.4 ) ; who were born in countries other than Australia , New Zeal and , the United Kingdom and Irel and ; and with poorer health status ( OR , 1.6 ; 95 % CI , 1.2 - 2.2 ) . Inadequate FHL was significantly less common among females ( OR , 0.6 ; 95 % CI , 0.5 - 0.8 ) . People with inadequate or at-risk FHL were significantly more likely to report having diabetes , cardiac disease or stroke , and significantly less likely to have recently attended a doctor . Respondents aged > or=65 years with inadequate FHL were more likely to have been admitted to hospital ( OR , 2.2 ; 95 % CI , 1.1 - 4.5 ) . CONCLUSION Many Australians are likely to have limited health literacy , and this is a risk to effective health care delivery and health improvement across the community Most primary care providers ( PCPs ) , constrained by time and re sources , can not provide intensive behavioral counseling for obesity . This study evaluated the effect of using medical assistants ( MAs ) as weight loss counselors . The study was a r and omized controlled trial conducted in two primary care offices at an academic medical center . Patients ( n = 50 ) had a BMI of 27 - 50 kg/m(2 ) and no contraindications to weight loss . They were r and omized to quarterly PCP visits and weight loss material s ( Control group ) or to the same approach combined with eight visits with a MA over 6 months ( Brief Counseling ) . Outcomes included change in weight and cardiovascular risk factors ( glucose , lipids , blood pressure , and waist circumference ) . Patients in the Brief Counseling and Control groups lost 4.4 + /- 0.6 kg ( 5.1 + /- 0.7 % of initial weight ) and 0.9 + /- 0.6 kg ( 1.0 + /- 0.7 % ) , respectively , at month 6 ( P < 0.001 ) . There were no significant differences between groups for changes in cardiovascular risk factors . Brief Counseling patients regained weight between month 6 and month 12 , when MA visits were discontinued . Attrition was 10 % after 6 months and 6 % after 12 months . Brief Counseling by MAs induced significant weight loss during 6 months . Office-based obesity treatment should be tested in larger trials and should include weight loss maintenance counseling BACKGROUND The impact of overweight and nonmorbid obesity on health-related quality of life ( HRQL ) has not been widely research ed . The aim of this study was to evaluate the effects of a lifestyle modification program ( LMP ) focused on diet , exercise , and psychological support on HRQL in overweight and nonmorbidly obese patients treated in a primary healthcare setting . METHODS Sixty patients with grade II overweight and nonmorbid grade I-II obesity were included in this open pilot clinical trial ; subjects ' ages ranged from 18 to 50 years . They were provided with an LMP combining nutrition education , physical activity , and psychological support . Subjects attended group sessions every 2 weeks . The main outcome measures at baseline and 6 months were body composition parameters ( body mass index , body fat percentage , and waist circumference ) and HRQL using the 1.4 Spanish version of the SF-36 question naire . The question naire yields an 8-scale profile of physical functioning ( PF ) , role -- physical ( RP ) , bodily pain ( BP ) , vitality ( VT ) , social functioning ( SF ) , role -- emotional ( RE ) , mental health ( MH ) , and general health ( GH ) factors . RESULTS The LMP achieved improvements in SF-36 subscales at the end of the intervention : PF ( 80.37 ± 18.90 vs 89.40 ± 13.95 , P < .001 ) , RP ( 20.37 ± 9.10 vs 23.14 ± 6.67 , P < .05 ) , VT ( 58.71 ± 21.98 vs 70.91 ± 26.56 , P < .01 ) , SF ( 79.62 ± 27.76 vs 86.57 ± 25.45 , P < .03 ) , and GH ( 61.03 ± 19.13 vs 69.42 ± 18.80 , P < .001 ) . CONCLUSION An LMP focused on balanced and moderate energy-restricted diets , increased physical activity , and psychological support may improve the anthropometric parameters and the quality of life in moderately obese patients treated in a primary healthcare center BACKGROUND Around 10 - 15 % of adults aged over 40 years have pre-diabetes , which carries a high risk of progression to type 2 diabetes . Intensive lifestyle intervention reduces progression by as much as 58 % . However , the cost and personnel requirements of these interventions are major obstacles to delivery in NHS primary care . AIM To assess the effectiveness of a low-cost intervention , delivered in primary care by non-NHS staff , to reduce the risk of diabetes through weight loss and physical activity . DESIGN OF STUDY Pragmatic single-blind r and omised controlled trial with research ers and statistician blinded to group allocation . SETTING UK primary care . METHOD One-hundred and forty-one participants with a body mass index of 28 kg/m2 or more , but without diabetes or heart disease , received either information leaflets or individual behavioural counselling using motivational interviewing techniques . The intervention was delivered by five counsellors recruited from the local community . The primary outcomes were the proportions of participants meeting predefined targets for weight loss ( 5 % ) and moderate physical activity ( 150 minutes/week ) after 6 months . RESULTS Using intention-to-treat analysis , more people in the intervention group achieved the weight-loss target ( 24 % versus 7 % for controls ; odds ratio [OR]=3.96 ; 95 % confidence interval [Cl]=1.4 to 11.4 ; number needed to treat [NNT]=6.1 ( 95 % Cl=4 to 21 ) . The proportion achieving the physical activity target did not increase significantly ( 38 % versus 28 % for controls ; OR=1.6 ; 95 % Cl=0.7 to 3.8 ) . CONCLUSION Short-term weight loss , at a level which , if sustained , is clinical ly meaningful for reducing diabetes risk , is achievable in primary care , without excessive use of NHS monetary or personnel re sources |
13,439 | 25,764,405 | Transfusion threshold was not associated with differences in other outcomes .
Studies for most interventions recruited too few participants to determine effects on infections , mortality or function | null | null |
13,440 | 17,636,783 | Cryotherapy offers a potential alternative to st and ard therapies for the primary treatment of localised prostate cancer . | BACKGROUND Prostate cancer is a common cancer in elderly men and in some will prove fatal .
St and ard treatments for localised disease include surgery ( radical prostatectomy ) , radiotherapy and active monitoring .
New emerging therapies are being evaluated with the aim of reducing the complication rate associated with st and ard therapies , as well as developing an effective treatment .
One such modality is cryotherapy , a procedure that introduces probes directly into the prostate tumour and kills the malignant cells by a freezing process .
OBJECTIVES This review aims to evaluate the relative clinical and economic benefits of cryotherapy compared to st and ard therapies for the primary treatment of localised prostate cancer . | PURPOSE Cryosurgical ablation of the prostate is a novel therapeutic modality that induces cell lysis in the prostate by direct application of low temperatures . We have been conducting an ongoing prospect i ve pilot study of the use of cryosurgical prostate ablation in treating patients with nonmetastatic prostate adenocarcinoma since January 1993 . Results in 145 consecutive patients with mean 36 months and minimum 12 months of followup are presented . MATERIAL S AND METHODS Accrual was open to patients with clinical stages T1a to T3c prostate adenocarcinoma . Pelvic lymph node dissections were recommended but not required for patients with prostate specific antigen ( PSA ) greater than 15 ng./ml . before study entry . PSA changes , r and om prostate biopsy findings and morbidities after cryosurgical prostate ablation were recorded for each patient . RESULTS Overall actuarial rates at 42 months for maintaining PSA less than 0.3 and less than 1.0 were 59 % and 66 % , respectively . The overall actuarial progression-free rate at 60 months was 56 % . Among 160 biopsies performed 16 % showed some evidence of residual carcinoma . Overall crude rates of maintaining either a negative biopsy or PSA less than 0.3 at 6 and 24 months after cryosurgical prostate ablation were 87 % and 73 % , respectively . Significantly higher morbidities were seen in previously radiated patients undergoing cryosurgical prostate ablation compared to those with no prior radiation . Among nonradiated patients 85 % experienced no significant morbidity after cryosurgical prostate ablation . CONCLUSIONS Although preliminary , short-term outcomes after cryosurgical prostate ablation appear to be comparable to identical outcomes reported for external beam radiotherapy . Based on these results cryosurgical prostate ablation appears to be an effective therapeutic alternative for treating patients with localized prostate adenocarcinoma PURPOSE A phase I/II study was done to evaluate the efficacy and complications of salvage cryotherapy as a treatment for locally recurrent prostate cancer following full dose radiation therapy and /or systemic therapy . The efficacy of single and double freeze-thaw cycles was compared using posttreatment prostate specific antigen ( PSA ) levels and prostate biopsies as end points . MATERIAL S AND METHODS A total of 150 patients with locally recurrent prostate cancer following radiation , hormonal therapy and /or systemic chemotherapy underwent salvage cryotherapy using a single ( 71 men , mean followup 17.3 months ) or double ( 79 men , mean followup 10.0 months ) freeze-thaw cycle . PSA was measured approximately every 3 months postoperatively and sextant biopsies were repeated 6 months postoperatively . Complications were assessed by retrospective chart review and a mailed quality of life survey . RESULTS Overall , 45 patients ( 31 % ) had persistently undetectable PSA . Patients with a history of radiation therapy only who underwent a double freeze-thaw cycle had a higher negative biopsy rate ( 93 versus 71 % , p < 0.02 ) and lower biochemical failure rate ( defined as an increase in serum PSA of 0.2 ng./ml . above the nadir value , 44 versus 65 % , p < 0.03 ) than those who underwent a single freeze-thaw cycle . The main complications of salvage cryotherapy were urinary incontinence ( 73 % of the patients ) , obstructive symptoms ( 67 % ) , impotence ( 72 % ) and severe perineal pain ( 8 % ) . CONCLUSIONS Salvage cryotherapy impacts local tumor control as evident by the high frequency of negative posttreatment biopsies . A double freeze-thaw cycle appears more effective than a single cycle . Like salvage prostatectomy , salvage cryotherapy causes significant morbidity PURPOSE We examined the role of percutaneous cryoablation of the prostate in the treatment of prostate cancer . MATERIAL S AND METHODS We performed 95 percutaneous cryoablations of the prostate on 87 patients with prostate cancer . Of the patients 6 had positive lymph nodes preoperatively , radiation failed in 9 and 9 began postoperative hormonal therapy because of treatment failure . Mean patient age , prostate specific antigen ( PSA ) level ( ng./ml . ) and Gleason score were 65.4 , 12.60 and 6.03 , respectively . Median followup was 12 months ( mean 9.3 , range 1 to 24 ) . In 49 of the 87 patients ( 56 % ) the lymph nodes were evaluated before cryoablation based on the treatment protocol . RESULTS Median PSA level at 12 months was 0.55 ng./ml . ( mean 1.73 ) with a 17 % positive biopsy rate at 3 months . When the positive lymph node , radiation failure and postoperative hormonal therapy groups were removed from analysis , the median PSA level was 0.80 ng./ml . ( mean 1.86 ) with a 5 % positive biopsy rate . Of the patients in the radiation failure group 37 % had a positive biopsy at 3 months . Cases were classified according to stage , grade and PSA level , and the biopsy results were presented . The complications of percutaneous cryoablation of the prostate were review ed . CONCLUSIONS The low percentage of positive biopsies is encouraging but the significance of the persistent PSA levels remains uncertain OBJECTIVES To describe and assess the efficacy for increased gl and ular destruction by using 6 to 8 cryoprobes in place of the traditional 5 probes . METHODS In April 1996 , a revised method for cryosurgery was begun that uses 6 to 8 cryoprobes , and by July 1997 , 81 men had been treated . This group was compared retrospectively to our last 82 cases done before April 1996 using 5 cryoprobes . All cases were consecutive . To ensure that the groups were similar , comparison was performed of entrance prostate-specific antigen ( PSA ) , clinical stage , and Gleason score . Six months after cryosurgery , PSA and residual epithelial acini were compared between the two groups . RESULTS The two groups were comparable for all the above parameters ( P > 0.05 ) . The degree of overall gl and ular kill was greater for the 6 to 8-probe method ( P = 0.023 ) . Complete gl and ular ablation for the 5-probe and 6 to 8-probe methods was 39 % and 53 % , respectively , and the difference was not significant ( P = 0.072 ) . However , when one combined the complete gl and ular ablation group with the none to few residual acini group , 67.5 % for the 5-probe method and 88.9 % for the 6 to 8-probe method , a significant difference was found ( P = 0.001 ) . The odds of having many remaining acini versus having none to few were 3.5 times greater in the 5-probe group than in the 6 to 8-probe group . The mean and median PSA for the 5- and 6 to 8-probe groups were 0.19 and 0.1 versus 0.11 and 0.07 ng/mL , respectively , a significant difference ( P = 0.02 ) . No difference was found in rates of tumor persistence or complications . CONCLUSIONS A revised method for cryosurgery using 6 to 8 cryoprobes has proved to be more effective for near-gl and ular ablation than the traditional 5-probe method . It was easily applied , had a wide margin of safety , and even shortened learning time . These innovations have permitted a closer approach to the goal of complete gl and ular destruction OBJECTIVES Percutaneous cryosurgical ablation of the prostate ( CSAP ) was performed on patients with localized or locally advanced adenocarcinoma of the prostate . To assess local disease control , post-treatment biopsy and serum prostate-specific antigen ( PSA ) levels were obtained at 3 and 24 months post-treatment . METHODS From June 1990 through May 1994 , CSAP was performed 448 times on 383 patients under Institutional Review Board protocol s. A urethral warming catheter was used for all procedures . A total of 239 patients were followed for a minimum of 21 months after treatment . None of this group had received prior local treatment . The group consisted of patients who were newly diagnosed and treated solely with cryotherapy ( virgin ) ; the remainder had been on and rogen deprivation therapy ( ADT ) prior to CSAP . RESULTS Biopsies were obtained from 114 patients at 21 months or more after treatment . In the virgin group , 79 % had a negative biopsy after one or more treatments , and 88 % of the ADT group are negative after one or more treatments . Overall , 69 % had a negative biopsy after one treatment and 82 % had a negative biopsy following one or more CSAP treatments . Of a group of 163 patients , PSA data were evaluable at 21 months or more after treatment . In the virgin group , 60 % had a PSA 0.4 ng/mL or less , and 77 % had a PSA 1.0 ng/mL or less . In the ADT group , 40 % had a PSA 0.4 ng/mL or less , and 69 % had a PSA value of 1.0 ng/m Lor less . Complications were minimal , the most common one being urethral tissue sloughing , which occurred in 10 % of patients . CONCLUSIONS CSAP appears to be effective in obtaining local control as measured by biopsy and PSA 21 months or more post-treatment . When retrospectively comparing our results with recently published radiotherapy series , CSAP was more effective in obtaining nadir PSA values 1.0 ng/mL or less and negative biopsies at 21 months or more after treatment OBJECTIVE To study the complications and oncological outcome after cryosurgical ablation of the prostate ( CSAP ) . METHODS Fifty-four patients with prostate cancer were entered into this prospect i ve phase II trial of CSAP . Patients were followed with serum PSA determinations , follow-up biopsies at 3 - 6 months postoperatively and a question naire to assess complications . A PSA of > 1 ng/ml or a positive biopsy was interpreted as progression . RESULTS Mean follow-up was 58.5 months . Patients needed a suprapubic catheter postoperatively for in mean 18 days . Transient penile numbness occurred in 15 % . Bothersome sloughing of dead tissue was noticed by 15 % of patients and 15 % needed a transurethral resection . Nine patients ( 17 % ) developed strictures and five patients stone formation in the prostatic urethra . One patient developed a perennial fistula . Thirty-nine out of 43 patients reporting on potency become impotent , nine patients developed a slight stress incontinence and one severe incontinence . At median follow-up , the actuarial progression-free survival was 38.9 % . Fourteen out of 50 patients biopsied ( 28 % ) had remaining cancer in their prostates . CONCLUSION High complication rates in combination with poor oncological outcome has made us stop using this treatment modality OBJECTIVES To determine in a prospect i ve pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma . METHODS A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998 . All patients had histologically proved adenocarcinoma of the prostate , with prostate-specific antigen ( PSA ) readings of less than 30 ng/mL. Clinical evaluations , PSA determinations , and patient self-reported quality -of-life question naires ( functional assessment of cancer treatment-prostate ; FACT-P ) were used to determine biochemical and clinical disease-free status and complications . Patients had a mean follow-up of 50 months ( minimum 36 ) . RESULTS Follow-up biopsies were performed in 73 patients , and 72 were negative for malignancy after one or more treatments . Ten patients required two treatments and 1 patient required three treatments . The 5-year overall and cancer-specific survival rate was 89 % ( 95 % confidence interval , 83 % to 97 % ) and 98.6 % ( 95 % confidence interval , 96 % to 100 % ) , respectively . The undetectable PSA rate ( less than 0.3 ng/mL ) for low-risk patients ( n = 13 ) was 60 % at 5 years ; for moderate-risk patients ( n = 23 ) , it was 77 % , and for high-risk patients ( n = 40 ) , 48 % . The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75 % , 89 % , and 76 % . Sloughing occurred in 3 patients ( 3.9 % ) , incontinence in 1 ( 1.3 % ) , and testicular abscess in 1 ( 1.3 % ) . At 3 years , 18 ( 47 % ) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse , 5 spontaneously and 13 with sildenafil or prostagl and in . CONCLUSIONS The results of this prospect i ve evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer The current study was design ed to describe the long-term life quality and sexuality of men enrolled in a phase 2 clinical trial of cryosurgery for the treatment of localized prostate cancer . A total of 75 men were administered the Functional Assessment of Cancer Treatment-Prostate ( FACT-P ) before treatment and after treatment at 6 weeks , and at 3 , 6 , 12 , 24 , and 36 months . Additionally , these men completed a Sexuality Follow-Up Question naire ( SFQ ) 3 years after cryosurgery . By 12 months after cryosurgery , most FACT-P subscales had returned to pretreatment levels . Quality of life remained stable over the subsequent 2 years . The only exception to this general trend was persistent impairment in measures of social/family well-being . At 36 months , 13 % ( 5 of 38 ) of patients had regained erectile functioning , and an additional 34 % ( 13 of 38 ) of patients were sexually active with the help of aids . The 3-year quality -of-life outcomes support the renewed interest in cryosurgery . No late complications were observed . Whereas improvements in erectile function were observed between years 1 and 3 for some patients , most continue to experience erectile dysfunction . For these patients , aids are an important adjunct to the treatment of their erectile dysfunction |
13,441 | 25,854,522 | Based on mainly low to very low quality evidence from a limited number of studies , brief psychoeducation of any form appears to reduce relapse in the medium term , and promote medication compliance in the short term . | BACKGROUND Those with serious/severe mental illness , especially schizophrenia and schizophrenic-like disorders , often have little to no insight regarding the presence of their illness .
Psychoeducation may be defined as the education of a person with a psychiatric disorder regarding the symptoms , treatments , and prognosis of that illness .
Brief psychoeducation is a short period of psychoeducation ; although what constitutes ' brief psychoeducation ' can vary .
A previous systematic review has shown that the median length of psychoeducation is around 12 weeks .
In this current systematic review , we defined ' brief psychoeducation ' as programmes of 10 sessions or less .
OBJECTIVES To assess the efficacy of brief psychoeducational interventions as a means of helping severely mentally ill people when added to ' st and ard ' care , compared with the efficacy of st and ard care alone .
The secondary objective is to investigate whether there is evidence that a particular kind ( individual/ family/group ) of brief psychoeducational intervention is superior to others . | In a prospect i ve , r and omized clinical trial cognitive characteristics of schizophrenic patients were examined as predictors of the efficacy of a psychoeducational psychotherapeutic intervention . The aim of this study was to select adequate cognitive predictors . The reduction of the selected cognitive deficits by means of a psychoeducational psychotherapy was measured . Additionally , the prophylactic effects of the improvement of cognitive deficits were examined . Predictors of the course of illness were basic cognitive deficits and metacognitive constructs of 106 schizophrenic out patients . Additionally , the modification of the cognitive skills of these patients was taken into account . Relevant factors of the course of illness representing the therapeutic effect of the intervention were investigated within a five-year follow-up . By means of logistic regression analyses thought disorders ( AMDP system ) and idiosyncratic and fatalistic assumptions ( KK-scale ) were obtained as appropriate cognitive predictors of the long-term course of illness . Thought disorders and attentional deficits could not be improved significantly . Though , there was a correlation between the therapeutic improvement of idiosyncratic and fatalistic assumptions and the rehospitalization rate within the follow-up Within a controlled prospect i ve intervention study , schizophrenic out patients r and omly assigned to four treatment groups and one control group were assessed with regard to collaboration with drug treatment . In total , 39.3 % of 84 regular attenders of the psychoeducational training programme and 26.6 % of 64 control patients reported having persuaded their psychiatrists to modify their medication prescriptions . A total of 8.3 % and 7.8 % , respectively , modified their medication on their own initiative , although with subsequent approval by the psychiatrist , and 20.2 % and 15.6 % , respectively , modified their medication after consulting their psychiatrist . With regard to medication management , the groups did not differ either at post‐treatment or at follow‐up . At follow‐up , regular attenders showed a reduced fear of side‐effects , increased confidence in their medication and stable confidence in their physician . Among the control subjects , confidence in the medication and in their physician declined , and fear of side‐effects increased . Psychoeducational training therefore led to an optimization of patients ' attitudes toward treatment , but not to changes in medication management OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Abstract The study examines long-term effects on rehospitalization rates of a psychoeducationally and cognitive-behaviorally oriented intervention for schizophrenic out patients and their key-persons . 191 patients and their key-persons were allocated by r and om into four different treatment groups and one control group . Five years after completion of treatment 126 patients were reexamined by interviews or case notes . The rate of patients experiencing psychiatric rehospitalization during the follow-up was assessed in each respective treatment group . Concerning rehospitalization rates there was no significant difference between controls ( n = 35 ) and patients of the four treatment groups ( n = 91 ) . There were , however , fewer rehospitalized patients in the group with combined psychoeducational and cognitive treatment , including key-person counselling ( 42 % ) , than in the control group ( 69 % ) . Regarding the overall functioning , the patients in this treatment group did slightly better than those in the control group . These results are in accordance with the findings of comparable studies OBJECTIVE The present study examined whether psychoeducational groups for patients with schizophrenic disorders and for their families can reduce rehospitalization rates and improve compliance . METHOD 236 in patients who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and who had regular contact with at least 1 relative or other key person were r and omly assigned to 1 of 2 treatment conditions . In the intervention condition , patients and their relatives were encouraged to attend psychoeducational groups over a period of 4 to 5 months . The patients ' and relatives ' psychoeducational programs were separate , and each consisted of 8 sessions . Patients in the other treatment condition received routine care . Outcomes were compared over 12-month and 24-month follow-up periods . The study was conducted from 1990 to 1994 . RESULTS It was possible to significantly reduce the rehospitalization rate after 12 and 24 months in patients who attended psychoeducational groups compared with those receiving routine care ( p < .05 ) . Patients who attended psychoeducational groups showed better compliance than patients under routine care without psycho-education . CONCLUSIONS The results suggest that a relatively brief intervention of 8 psychoeducational sessions with systematic family involvement in simultaneous groups can considerably improve the treatment of schizophrenia . Psychoeducation should be routinely offered to all patients with schizophrenia and their families BACKGROUND A r and omised controlled trial was conducted in an acute treatment setting to examine the effectiveness of compliance therapy , a brief pragmatic intervention targeting treatment adherence in psychotic disorders , based on motivational interviewing and recent cognitive approaches to psychosis . METHOD Seventy-four patients with psychotic disorders according to DSM-III-R criteria recruited from consecutive admissions to an acute in-patient unit , received 4 - 6 sessions of either compliance therapy or non-specific counselling , and were followed-up over 18 months . The principal outcome measures were observer-rated compliance , attitudes to treatment , insight and social functioning . RESULTS Significant advantages were found for the compliance therapy group post-treatment on measures of insight , attitudes to treatment and observer-rated compliance which were retained over the follow-up period . Global social functioning improved relatively more over time in the compliance therapy group compared with the control group . Survival in the community prior to readmission was significantly longer in the compliance therapy group . CONCLUSIONS The results support the effectiveness of compliance therapy in improving functioning and community tenure after an acute psychotic episode OBJECTIVES To evaluate the effectiveness of a psychoeducation program for Chinese clients with schizophrenia and their family caregivers . METHODS A r and omized controlled trial was conducted . Seventy-three clients with a diagnosis of schizophrenia and their caregivers ( n=73 ) were recruited and r and omized into a study ( n=36 ) and control group ( n=37 ) . Ten psychoeducation sessions were provided to the study group . The outcomes were measured at the baseline , immediately after ( post-1 ) , six months ( post-2 ) , and 12 months after the intervention ( post-3 ) . RESULTS There were significant treatment effects across time for all client outcomes : adherence to medication ( p<0.01 ) , mental status ( p<0.01 ) , and insight into illness ( p<0.01 ) . However , no significant differences were found between groups at the post-3 measures for all client outcomes . For the caregivers , significant group differences were only detected in self-efficacy at the post-1 ( p=0.007 ) and post-2 ( p<0.001 ) measures , the level of satisfaction at the post-1 ( p=0.033 ) and post-2 ( p<0.021 ) measures , and the perception of family burden at the post-2 measures ( p=0.043 ) . CONCLUSION A psychoeducation intervention had positive effects on Chinese clients and their caregivers . However , these effects might not be sustained 12 months after the intervention . PRACTICE IMPLICATION S To substantiate its effects , psychoeducation should be an ongoing intervention , with its outcomes constantly evaluated BACKGROUND Family intervention in schizophrenia can reduce patient relapse and improve medication adherence , but few studies on this have involved a Chinese population . AIMS To examine the effects of a mutual support group for Chinese families of people with schizophrenia , compared with psychoeducation and st and ard care . METHOD R and omised controlled trial in Hong Kong with 96 families of out- patients with schizophrenia , of whom 32 received mutual support , 33 psychoeducation and 31 st and ard care . The psychoeducation group included patients in all the sessions , the mutual support group did not . Intervention was provided over 6 months , and patient- and family-related psychosocial outcomes were compared over an 18-month follow-up . RESULTS Mutual support consistently produced greater improvement in patient and family functioning and caregiver burden over the intervention and follow-up periods , compared with the other two conditions . The number of readmissions did not decrease significantly , but their duration did . CONCLUSIONS Mutual support for families of Chinese people with schizophrenia can substantially benefit family and patient functioning and caregiver burden Earlier studies of family psychoeducation and clinical reports on multiple family groups ( MFGs ) have reported substantial reductions in relapse rates for patients with schizophrenia . These groups offer an exp and ed social network and thereby may confer a margin of protection against relapse . However , to date , there has not been an empirical trial of this modality . The advent of family psychoeducational and behavioral management strategies provided the basis for an experimental , three-way comparison of psychoeducational MFGs to psychoeducation in a single-family format and to MFGs without psychoeducation , using symptomatic relapse as the outcome criterion . After 4 years , the psychoeducational MFGs were significantly more effective in extending remission than the single-family format , while the MFGs without psychoeducation approximated outcome in the psychoeducational MFGs . The respective relapse rates at 4 years were 50 % , 78 % , and 57 % ; MFGs averaged 12.5 % and 14 % per year . These results point toward an enhanced and independent , long-term therapeutic effect for multiple family groups , when combined with antipsychotic medication and psychoeducation , with especially promising cost-effectiveness Background The majority of patients with schizophrenia live with their relatives in Pakistan , thereby families experience a considerable burden . We aim ed to study the impact of psychoeducation on the burden of schizophrenia on the family in a r and omised controlled trial . Methods A total of 108 patients with schizophrenia and their family members from the outpatient department of a teaching hospital in Lahore , Pakistan were r and omised . Both groups received psychotropic drugs but one group received psychoeducation in addition . Family burden was assessed at the time of recruitment and at 6 months post intervention . Results In all , 99 patients and their relatives completed the treatment . There was significant reduction in burden at post-intervention assessment in the psychoeducation group based on intention to treat analysis . Conclusion Family psychoeducation can be an important intervention for patients with schizophrenia in Pakistan Family members of 55 patients with schizophrenia were r and omly assigned to a psychoeducational support group or to a control group . Support group participants showed greater knowledge of schizophrenia and greater satisfaction with health care services than did control group members . Psychological distress , coping behavior , and family satisfaction did not appear affected by support group participation ; nor were support groups associated with lower rehospitalization rates for patients Psychoeducational medication management training ( PMT ) , cognitive psychotherapy ( CP ) and key‐person counselling ( KC ) were carried out in various combinations in this r and omized , controlled intervention study of schizophrenic out‐ patients ( according to DSM‐III‐R ) . Special design characteristics of the study were a control group consisting of non‐specifically treated patients and a 2‐year follow‐up after completion of treatment in order to evaluate medium‐term effects . A total of 132 patients underwent a follow‐up examination 2 years after completion of treatment and were evaluated with an intention‐to‐treat approach . In the second follow‐up year , all treatment groups had lower but not significantly different relapse rates compared to the control group . The most intensive treatment ( PMT+CP+KC ) produces a clinical ly relevant reduction in rehospitalization rate ( a 26 % reduction compared to the control group ) . In comparison with the non‐specifically treated control group , whose original effect decreased , at least a medium‐term therapeutic effect was recorded in the treatment groups In this study we look into the question of whether , in addition to neuroleptic treatment , relapse rates among schizophrenic patients can be reduced by means of a combined psychoeducational and psychotherapeutic intervention strategy for patients and their relatives . In a r and omized controlled intervention study in an outpatient routine treatment setting , psychoeducational training for medication management , cognitive therapy and work with relatives ' groups were compared with each other and with a control group . The patients continued their st and ard treatment , including neuroleptic relapse prevention . The study comprised 191 chronic DSM-III-R schizophrenics . Data were collected before and after an 8-month intervention phase and at the 1-year follow-up . The group receiving all three treatments had the lowest relapse rates . Moreover , numerous gains recorded in subjective findings suggest that therapeutic work with schizophrenic patients and their relatives is of clinical ly significant benefit The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVES This study tested the effectiveness of a mutual support multiple-family-group intervention for schizophrenia in terms of improvements in patients ' psychosocial functioning , use of mental health services , and rehospitalization compared with a psychoeducation intervention and st and ard care . METHODS A controlled trial was conducted in a sample of 96 Chinese families who were caring for a relative with schizophrenia in Hong Kong . The families were r and omly assigned to one of three groups : mutual support ( N=32 ) , psychoeducation ( N=33 ) , and st and ard care ( N=31 ) . The interventions were delivered at two psychiatric outpatient clinics over a six-month period . The mutual support and psychoeducation interventions consisted of 12 group sessions every two weeks , each lasting about two hours . The mutual support group was a peer-led group design ed to provide information , emotional support , and coping skills for caregiving in stages . The psychoeducation group was a professional-led group design ed to educate families about the biological basis of schizophrenia and treatment and to improve illness management and coping skills . The st and ard care group and the other two groups received routine psychiatric outpatient care during the intervention . Data analyses of multiple outcomes over one-year follow-up were conducted on an intention-to-treat basis . RESULTS Multivariate analyses of variance showed that the mutual support intervention was associated with consistently greater improvements in patients ' functioning and rehospitalization and stable use of mental health services over the follow-up period compared with the other two interventions . CONCLUSIONS The study provides evidence that mutual support groups can be an effective family intervention for Chinese persons with mental illness in terms of improving patients ' functioning and hospitalization without increasing their use of mental health services OBJECTIVE To evaluate the feasibility of a telehealth psychoeducation intervention for persons with schizophrenia and their family members . STUDY DESIGN R and omized controlled trial . PARTICIPANTS 30 persons with schizophrenia and 21 family members or other informal support persons . INTERVENTIONS Web-based psychoeducation program that provided online group therapy and education . MAIN OUTCOME MEASURES Measures for persons with schizophrenia included perceived stress and perceived social support ; for family members , they included disease-related distress and perceived social support . RESULTS At 3 months , participants with schizophrenia in the intervention group reported lower perceived stress ( p = .04 ) and showed a trend for a higher perceived level of social support ( p = .06 ) . CONCLUSIONS The findings demonstrate the feasibility and impact of providing telehealth-based psychosocial treatments , including online therapy groups , to persons with schizophrenia and their families This paper focuses on the follow-up results of a r and omized clinical trial of inpatient family intervention ( IFI ) that emphasized psychoeducation . Results for the sample of 169 psychiatric patients suggested that adding family treatment to st and ard hospital treatment was effective ; however , the statistical interactions indicated that this therapeutic effect was restricted to female patients with schizophrenia or major affective disorder . The effect of family treatment on male patients with these diagnoses was minimal or slightly negative . In a group of patients with other diagnoses , the Treatment by Sex effect was reversed : male patients did better with the family treatment BACKGROUND The shortage of mental health care in rural China might be tackled by community care . This study tests the hypothesis that family intervention increases patients ' treatment compliance , which is crucial in community care . METHOD A cohort of psychiatric patients were r and omly selected to a controlled trial for four months . Compliance rates , clinical and social outcomes were measured double-blindly . RESULTS The compliance rate was increased significantly in the trial group , and they had better clinical and social outcomes . CONCLUSIONS Family intervention is an effective method of improving treatment compliance and should be an important part of community mental health care Objective To evaluate the effectiveness of multiple group family treatment for Schizophrenia . Method Relatives were r and omly provided with an informative programme ( n = 50 ) , or allocated to receive an additional support programme ( n = 26 ) . Patients did not attend the programme to overcome cultural and organizational implementation barriers . The 12 and 24 months clinical and family outcomes were assessed . Results Patients ’ compliance with st and ard care was greater at 12 months in the more intensive behavioural management group over a control group receiving treatment as usual ( TAU ) ( n = 25 ) . A reduction in levels of expressed emotion ( EE ) , significantly more frequent in those receiving the additional support programme than just the informative , occurred after treatment completion . Other clinical and family outcomes did not differ . However , treatment benefits declined at 24 months , when baseline high EE was again predictive of patient ’s admission and relatives were more vulnerable to objective burden . Baseline illness severity variables predicted a number of medium and long-term poor clinical outcomes . Conclusions Although family psychoeducation has been tested in a wide range of Anglo-Saxon setting s , there remains need to assess outcomes more internationally . Effective family interventions for people with schizophrenia probably require continued administration of key-elements or ongoing informal support to deal with the vicissitudes of illnesses In this study we investigated whether , in conjunction with neuroleptics , a psychoeducational and cognitively oriented treatment for schizophrenic out patients and their key-persons can improve the course of schizophrenic illness within a 2-year follow-up . This prospect i ve r and omized study covered a total of 191 schizophrenic patients ( according to DSM-III-R ) and comprised a psychoeducational training and cognitive psychotherapy for patients and counseling for their key persons in various combinations . Patients were examined before , immediately after and 2 years after the end of the intervention . Patients in the treatment groups reduced their overall psychopathology and their attention deficit . For patients receiving all three treatment conditions , there was a relevant preventive effect with regard to the rehospitalization rate appearing during the second year of the follow-up . We conclude that in the mid-term , a combination of psychoeducational and cognitively oriented therapy for patients and their keypersons can improve the course of schizophrenic illness Objective : Although the efficacy of cognitive‐behavioural therapy ( CBT ) in schizophrenia has been established in a number of studies , no information is available on the differential efficacy of CBT in comparison with patient psychoeduction ( PE ) BACKGROUND This study examined whether a program for relapse prevention ( PRP ) is more effective than treatment as usual ( TAU ) in reducing relapse and rehospitalization rates among out patients with schizophrenia . METHODS Eighty-two out patients with DSM-III-R schizophrenia or schizoaffective disorder were r and omly assigned to receive either PRP ( experimental group , n = 41 ) or TAU ( control group , n = 41 ) and were followed up for an 18-month prospect i ve controlled study . Patients in both groups were prescribed st and ard doses of maintenance antipsychotic medication . Treatment with PRP consisted of a combination of psychoeducation , active monitoring for prodromal symptoms with clinical intervention when such symptoms occurred , weekly group therapy for patients , and multifamily groups . The TAU consisted of biweekly individual supportive therapy and medication management . RESULTS Outcome rates over 18 months were 17 % for relapse ( 7 patients ) and 22 % for rehospitalization ( 9 patients ) in the PRP group , compared with 34 % for relapse ( 14 patients ) and 39 % for rehospitalization ( 16 patients ) in the TAU group ( P = .01 and P = .03 , respectively ) . Addition of age , sex , baseline Global Assessment Scale score , Positive and Negative Syndrome Scale scores ( 3 measures ) , and substance abuse to the proportional hazards regression models all yielded nonsignificant effects . The PRP teams were much more likely than the TAU psychiatrists to identify prodromal episodes before patients met objective relapse criteria or needed hospitalization . CONCLUSIONS The PRP was effective in detecting prodromal symptoms of relapse early in an episode . Crisis intervention including increased antipsychotic medication use during the prodromal phase reduced relapse and rehospitalization rates Abstract . Background : The aim of this study was to explore the characteristics and efficacy of psychoeducational family intervention for persons with schizophrenia in rural China . Methods : A cluster r and omised controlled trial of psychoeducational family intervention for families experiencing schizophrenia ( three groups , 326 cases ) was conducted in Xinjin County , Chengdu . Treatment groups consisted of family intervention and medication , medication alone , and a control . Results : The results showed a gain in knowledge , a change in the relatives ' caring attitudes towards the patients , and an increase in treatment compliance in the psychoeducational family intervention group ( p < 0.05 , 0.001 ) . Most importantly , the relapse rate over 9 months in this group ( 16.3 % ) was half that of the drug-only group ( 37.8 % ) , and just over one-quarter of that of the control group ( 61.5 % ) ( p < 0.05 ) . Antipsychotic drug treatment and families ' attitudes towards patients after the 9-month follow-up were significantly associated with clinical outcome ( p < 0.05 ) . Conclusions : In rural China , family intervention should focus on improving the relatives ' recognition of illness , the caring attitude towards the patients , treatment compliance , relapse prevention , and the training of the patients ' social functioning . This trial , one of the largest in the literature , has shown that psychoeducational family intervention is effective and suitable for psychiatric rehabilitation in Chinese rural communities ' TRIP ' ( Transforming Relapse and Instilling Prosperity ) is a ward-based illness management programme that aims to decrease treatment non-compliance and relapse rate by improving the insight and health of acute psychiatric patients with schizophrenia . Eighty-one stable male acute psychiatric patients with schizophrenia were r and omized to receive the TRIP programme ( n = 44 ) or the comparison group of traditional ward occupational therapy ( WOT ) programme ( n = 37 ) . Participants ' insights and health were assessed by the Unawareness of Mental Disorder Scale and the Hong Kong version of the Short Form-36 ( SF-36 ) health survey , respectively . Each group was then followed up for a 12-month period . One-way analysis of covariance ( ANCOVA ) showed that participants in the TRIP programme had significantly better insight and health than a comparison group during post- study measurement . Participants in the TRIP programme had significantly fewer re-admissions in the 12-month follow-up period than those who attended the WOT programme . In summary the TRIP programme , as led by an occupational therapist , was effective in improving insight , awareness of health and in having a lower re-admission rate than a traditional occupational therapy programme Objective : To evaluate the impact on outcome of a simple educational intervention in schizophrenic patients at risk of relapse BACKGROUND Various problems are associated with schizophrenia which may theoretically lead to impaired educability about treatment . METHOD The Underst and ing of Medication Question naire , design ed to measure knowledge about treatment in schizophrenia , is described and presented . An educational programme based on a specially design ed information booklet was developed . Sixty-four patients with DSM-III-R diagnosis schizophrenia were r and omly allocated to groups receiving none ( control ) , one session or three sessions of education . RESULTS Pre-intervention low levels of knowledge about illness and treatment increased significantly immediately after a st and ard education session . Three education sessions led to significantly greater knowledge gain than one session . There was no significant change in the control group . Only the PANSS negative syndrome score independently and consistently explained a significant proportion of the education effect . The influence on educability of attitudes to education , impaired insight , cognitive impairment and other variables were considered . Three sessions of education led to significantly increased insight , but no change in compliance . CONCLUSIONS Techniques appropriate for educating schizophrenic patients were discussed , and the value of involving patients in education emphasised . A series of patient education sessions is needed to consoli date learning , rather than a single informing process . The strong association between impaired learning and more severe negative schizophrenic syndrome emphasises the need for responsible prescribing of antipsychotic treatment in schizophrenia The study reported herein a r and omized controlled trial was conducted to test the effectiveness of a nurse-led , needs-based psycho-education program for Chinese patients with first-onset mental illness over a 6-month follow-up . Ninety-six families of Chinese patients with schizophrenia newly referred to one outpatient clinic in Hong Kong were r and omly assigned to a nurse-led psycho-education program or usual outpatient care , each comprising 48 subjects . The patients ' mental health , illness insight , self-efficacy , services utilization , and hospitalization rates were measured at recruitment and at one week and six months post-intervention . The patients in the psycho-education program reported significantly greater improvements in mental health , insights into treatment and illness , and hospitalization rates over the 6-month follow-up , when compared with those who received usual care . The findings provide evidence that the needs-based , nurse-led psycho-education program can improve the health conditions and treatment insights of Chinese out- patients with first-onset mental illness The purpose of this study was to evaluate the effectiveness of a psychoeducation program for Chinese family carers of members with schizophrenia in Hong Kong . The participants consisted of 64 carers of clients with schizophrenia who were recruited from a local mental hospital and r and omly assigned to the experimental and control arm ( 32 each ) . The experimental group received a psychoeducation program developed and implemented by mental health nurses based on Atkinson and Coia ’s framework . The control group received routine care . The outcome measures were family burden , self-efficacy , and perception of social support . The findings showed that the experimental group had more improvement on their perception of burden of care ( t = 5.25 , p < .01 ) , self-efficacy ( t = -7.16 , p < .01 ) , and social support ( t= -5.61 , p < .01 ) . This study supports psychoeducation as an effective nursing intervention for Chinese family carers Abstract There is increasing evidence of the efficacy and effectiveness of psychosocial interventions in schizophrenic patients . However , little research has been done on differential therapy effects . In a prospect i ve , r and omized clinical trial we carried out psychoeducational medication management training , cognitive psychotherapy , and key-person counseling . The patients of the control group participated in structured free-time activities for control of therapeutic commitment . Data from a total of 156 schizophrenic patients ( DSM-III-R , no first-admissions ) were available at 2-year follow-up . We analyzed in this study whether there are differential therapy effects of these interventions , depending on patient characteristics at baseline . There was a significant statistical interaction between treatment condition ( specific/non-specific ) and prognosis with respect to treatment outcome . Patients with a favorable prognosis and better social functioning had a better course under the specific treatment but a less favorable outcome in the non-specifically treated control group . These results suggest that more vulnerable patients are not sufficiently capable of learning and using coping strategies for relapse prevention . We need to learn more about differential indications for psychosocial treatment AIM This article outlines the rationale for a family-focused psychoeducational intervention for individuals at risk for psychosis and explains the design of a r and omized multisite trial to test its efficacy . METHODS Adolescents and young adults that meet criteria for a psychosis risk syndrome at eight participating North American Prodromal Longitudinal Study sites are r and omly assigned to a 6-month , 18-session family-focused treatment for prodromal youth or a 3-session psychoeducational enhanced care control intervention and followed over 1 year . RESULTS The results will determine whether the use of a family intervention is able to significantly improve functional outcomes , decrease the severity of positive symptoms and possibly prevent the onset of full psychosis , compared with enhanced care alone . Levels of familial criticism at baseline are hypothesized to moderate responses to family intervention . Improvements in knowledge about symptoms , family communication and problem solving will be tested as mediators in the pathways between treatment assignment and clinical or psychosocial outcomes in high-risk youth . CONCLUSIONS The ongoing trial evaluates whether a non-invasive psychosocial approach can significantly enhance functional outcomes and prevent the ultra high risk patients from developing psychosis . The results will provide an important stepping stone in the movement of the field from refining early detection strategies to developing efficacious preventative treatments Background : Family psychoeducation has a well-documented effect on the short-term prognosis in schizophrenia . Less is known about the effectiveness of shorter programmes with the main focus on information for patients ( patient education ) or for patients and relatives ( family education ) . Methods : A r and omized study of the effectiveness of an eight-session psychoeducational programme for patients with schizophrenia and for their relatives was conducted in two community mental health centres , in Århus and Viborg ( Denmark ) . Patient outcome measures were knowledge , relapse , compliance , insight and satisfaction , and relative outcome measures were knowledge and satisfaction . Postintervention outcome and follow-up evaluation 1 year after the start of the intervention are presented . Results : A statistically significant increase in knowledge of schizophrenia in both relatives and patients was demonstrated at postintervention and a non-significant trend at 1-year follow-up . Statistically significant changes in the Verona Service Satisfaction Scale Scores in the sub-dimension of satisfaction with Relatives involvement were demonstrated both for patients and relatives postintervention and for patients at 1-year follow-up . There was a tendency that time-to-relapse increased in the intervention group at postintervention and that the schizophrenia subscore of the Brief Psychiatric Rating Scale was reduced in the intervention group at 1-year follow-up . No differences were found between the groups regarding compliance , insight into psychosis , psychosocial function ( General Assessment of Function ) or in relatives ' expressed emotion scores postintervention or at 1-year follow-up . Conclusion : A short patient and relative education programme seems to be able to influence knowledge and some aspects of satisfaction , but does not seem to be sufficient to influence important variables such as relapse , compliance , psychopathology , insight or psychosocial functioning OBJECTIVE To evaluate the effect of a psychoeducational training , compliance , medication management , and illness-related attitudes were assessed among schizophrenic out patients . METHODS Study patients who attended at least 70 % of 10 psychoeducational sessions ( n = 74 ) and the 57 patients of the control group were reexamined 2 years after the end of intervention . RESULTS Attenders had better compliance , were more confident in medication codetermination and more satisfied with their knowledge about medication . Confidence in medication and physician increased whereas in the control both decreased . CONCLUSIONS Although there were no statistically significant differences the results show impressive longterm effects of psychoeducational training OBJECTIVE To test whether the statistically significant results of a r and omized clinical trial of an inpatient family intervention were clinical ly significant for hospital practice , the authors reanalyzed outcome data using a measure of clinical significance based on the extent to which patients had recovered during the course of the intervention . METHODS A total of 169 hospitalized subjects and their families were r and omly assigned to a psychoeducational inpatient family intervention or to a comparison group . Patient and family outcome measures were assessed at admission , discharge , and six and 18 months after admission . Analyses of statistically significant differences in outcome suggested that inpatient family intervention was effective for certain patient subgroups identified by gender and diagnosis . Global Assessment Scale scores two or more st and ard deviations above the pretreatment ( admission ) mean were used as indicators for clinical ly significant improvement . RESULTS The re analysis confirmed that inpatient family intervention was associated with clinical ly significant improvement at discharge , especially for female patients and patients with chronic schizophrenia and bipolar disorder . These effects were maintained six months after admission before attenuating at 18 months . CONCLUSIONS Inpatient family intervention results in clinical ly meaningful outcomes for certain subgroups of patients and their families OBJECTIVE In this study we aim ed to evaluate long-term effects of a community-based , quality of life oriented psychoeducational intervention for schizophrenia with and without booster sessions . METHOD One hundred and three out patients with a diagnosis of schizophrenia or schizoaffective disorder completed a 9-week psychoeducational programme . At the end of the programme groups were block-r and omised to either an extension programme comprising monthly booster sessions for a further nine months ( booster condition ) or routine clinical care with no further group meetings ( non-booster condition ) . Outcome measures were applied before and after the seminar and at 6 and 12 months . RESULTS Positive effects were observed after the short-term 9-week programme with regard to symptoms , knowledge about the illness , illness concept , control convictions and quality of life . These effects were retained over the 12-month period in both conditions . The only relevant difference between the booster and the non-booster conditions concerned external control convictions . CONCLUSION Overall this 9-week programme has shown encouraging effects still present at 12 months after baseline independent of booster or non-booster conditions . Further studies are needed to explore whether a subgroup of patients , those with impaired neurocognitive and social functioning , can benefit significantly from booster sessions OBJECTIVE According to most of the relevant guidelines , psychoeducation is considered a basic part of routine therapy for patients with schizophrenia ; scientific proofs of its efficacy are based mainly on the results of 1- and 2-year follow-ups . Therefore , the long-term effects of psychoeducation over a period of 7 years were investigated in regard to rehospitalization rates and hospital days . METHOD Of 101 patients with DSM-III-R or ICD-9 schizophrenia r and omly allocated to either an intervention group or a control group between 1990 and 1994 , 48 patients were available for follow-up after 7 years . During their index stay , the 24 patients of the intervention group and their key relatives each received a separate psychoeducational group therapy . The 24 patients of the control group received the usual treatment . After index discharge , all 48 patients received a comparable outpatient treatment . Main outcome measures were rehospitalization rate , number of intervening hospital days , compliance , and mean number of consumed chlorpromazine ( CPZ ) units . RESULTS Seven years after index discharge , the rate of rehospitalization was 54 % in the intervention group and 88 % in the control group . The rate of rehospitalization per patient was 1.5 in the intervention group and 2.9 in the control group ( p < .05 ) . In the intervening period , the mean number of hospital days spent in a psychiatric hospital was 75 in the intervention group and 225 days in the control group . ( p < .05 ) . The mean number of consumed CPZ units after 7 years was 354 in the intervention and 267 in the control group . CONCLUSIONS Seven years after psychoeducational group therapy , significant effects on the long-term course of the illness can be found . Therefore , the integration of psychoeducation into st and ard therapy for schizophrenia should become obligatory As neuroleptic therapy alone still fails to other effective relapse prevention in schizophrenic patients , psychoeducational therapeutic approaches have been developed as an additional aid for patients and their families . This article details the central characteristics of these approaches . A psychoeducational group program for schizophrenic out patients , the efficacy of which was investigated within the scope of a German controlled intervention study on 191 patients , is also presented . The article describes in detail the methods used and the therapeutic objectives , reporting on changes in the attitudes of patients to their medication . At the end of the training program , patients who had attended regularly showed significantly better medication compliance and were more reserved with respect to their medication self-management . After 1 year the positive effects had diminished . However , booster sessions or participation of the psychiatrist in charge as group therapist would have had longer lasting effects OBJECTIVE Korean Americans ' access to mental health services may be limited because of differences in their views of mental illness compared with Westerners , unfamiliarity with treatment methods , and cultural associations of social stigma with mental problems . This study used data from an urban outpatient clinic to assess the effects of a ten-week psychoeducational intervention for Korean Americans with chronic mental illness . METHODS Forty-eight Korean-American adults with a diagnosis of schizophrenia were r and omly assigned to either an experimental group that provided a culturally sensitive psychoeducational group program in addition to individual supportive therapy or a control group that offered only individual supportive therapy . The two groups were compared on pre- and posttreatment measures of psychiatric symptoms , attitudes about and underst and ing of mental illness , and coping skills . The experimental psychoeducational treatment group was expected to show lower symptom severity , greater underst and ing of mental illness leading to a decreased perception of stigma , and greater coping skills after the intervention than the control group . Comparisons were made with repeated- measures analysis of covariance with the effects of gender and education controlled for . RESULTS Compared with the control group , the psychoeducational group showed significantly reduced symptom severity and perception of stigma and greater coping skills immediately after treatment . CONCLUSIONS These findings suggest that a culturally sensitive psychoeducational intervention is a useful short-term treatment modality for Korean Americans with a diagnosis of schizophrenia BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials OBJECTIVES This study tested the effectiveness of a mindfulness-based psychoeducation program for Chinese out patients with schizophrenia over an 18-month follow-up . The program is a psychoeducational program that addresses patients ' awareness and knowledge of schizophrenia and builds skills for illness management . METHODS A multisite controlled trial was conducted with 96 Chinese patients with schizophrenia in Hong Kong . They were r and omly assigned to either the mindfulness-based psychoeducation program or usual psychiatric care . The patients ' mental and psychosocial functioning , insights into illness , and rehospitalization rates were measured at recruitment and at three and 18 months postintervention . RESULTS Compared with those in usual care , the patients in the mindfulness psychoeducation program showed significantly greater improvements in their illness insights , symptom severity , functioning , and number and length of rehospitalizations at the 18-month follow-up . CONCLUSIONS The findings provide evidence that the mindfulness-based education program can improve Chinese schizophrenia sufferers ' psychosocial functioning and reduce their illness relapse One of the main difficulties we find in psychopharmacologic treatment of schizophrenia is medication compliance . Following Kissling , only 40 - 50 % of patients adequately follow prescription directions . This phenomenon becomes one of the major factors of the high relapse rates in schizophrenia . Several studies have been made in recent oriented to improve medication compliance through psychoeducational groups involving patients and their closest relatives . Our results confirm the hypothesis . Statistically significant differences ( p < 0.0001 ) are found between readmission rates in control group ( 2.32 % ) and in group of patients participating in psychoeducational groups ( 0.30 % ) . Significant differences are also found when considering separately first episode patients ( 1.61 % controls vs. 0.04 % cases , p < 0.0001 ) and patients with previous history ( 3.05 % controls vs. 0.61 % cases , p < 0.0001 ) Objective : Although the clinical efficacy of cognitive behaviour therapy ( CBT ) has been established for patients with schizophrenia , the data on effects on quality of life ( QoL ) are lacking . The purpose of the present study was therefore to compare the effects of a brief group CBT and a group psychoeducational ( PE ) programme in patients with schizophrenia on QoL. Method : A total of 88 in patients with schizophrenia were r and omized to receive a therapy envelope of 8 weeks including either 16 sessions of group CBT or eight sessions of group PE treatment . QoL was assessed using the Modular System for Quality of Life at baseline , post-treatment assessment and 6 month follow up . Results : QoL improved significantly in both treatments in most QoL dimensions . Within-group effect sizes for general QoL at follow up were 0.25 for CBT and 0.29 for PE . No significant differences between CBT and PE were found at post-treatment and at 6 month follow up . Conclusions : Both brief group CBT and group PE improve subjective QoL in patients with schizophrenia UNLABELLED Earlier studies suggest that psychoeducation as a form of psychosocial care is of value in improving the patient 's attitude towards mental illness as well as in reducing and delaying the relapse rates of both -- psychotic and depressive disorders . AIM The aim of this study was the evaluation of influence of psychoeducation on clinical symptoms , quality of life and drug attitude in schizophrenic and depressive patients . METHOD 52 patients , aged 18 - 50 years , hospitalized in the Department of Psychiatry of Medical Academy in Białystok , were involved in the study . They were r and omly assigned into 2 groups : on medication without psychoeducation ( 12 schizophrenics , 12 depressive patients ) and on medication and psychoeducation ( 16 schizophrenics and 12 depressive patients ) . The patients were assessed by means of BPRS , BNS , IMHC 2000 , Raskin/Covi Scale , DAI-10 . The assessment was performed twice -- shortly after admission and before discharge from the hospital . RESULTS The patients in both groups showed improvement in symptoms and in quality of life . Patients on psychoeducation changed their drug attitude positively significantly more often . CONCLUSION Knowledge about the positive influence of medication on psychiatric symptoms helps to improve compliance and improves the course of disease BACKGROUND The aim of the study was to examine whether the efficacy of psychoeducation in patients with schizophrenia is dependent on their cognitive performance and if a preceding cognitive training can enhance the therapeutic effects of psychoeducation . PATIENTS AND METHODS A total of 116 in patients were r and omly assigned to either a st and ardized cognitive training ( COGPACK ) or to routine occupational therapy , followed by a psychoeducational group program of 8 sessions within 4 weeks for all study patients . The effects of cognitive training and psychoeducation were assessed directly afterwards and in a follow-up after 9 months . RESULTS The patient knowledge and compliance improved . Neurocognition and especially memory acquisition significantly predicted illness knowledge after psychoeducation , whereas psychopathology did not . No differential effects of the COGPACK training were found . After 9 months 75 % of the patients showed a very good compliance and the readmission rate was 18 % . The results were comparable under both study conditions . CONCLUSION Besides baseline illness knowledge neurocognition was the only significant predictor for illness knowledge after psychoeducation . Patients with cognitive deficits can profit from psychoeducation in the long run as well . In future it should be examined whether a modified cognitive training program could achieve a faster improvement of the illness knowledge |
13,442 | 29,929,525 | Across all population s , greater reductions in blood loss and operation time were observed for PFNA than for other treatments .
Conclusions The findings provide supporting evidence demonstrating the superiority of PFNA over other treatments for intertrochanteric femoral fracture .
PFNA treatment results in the lowest amount of blood loss and the shortest operation time .
These findings add to the existing knowledge of intertrochanteric femoral fracture treatment options | Background Multiple operative treatments are available for the fixation of intertrochanteric femoral fractures .
This analysis was conducted to provide guidance on the appropriate clinical choice to accommo date individual patients . | Purpose The purpose of this prospect i ve r and omised trial was to assess whether an intramedullary nail is superior to a sliding hip screw in the treatment of multifragmentary intertrochanteric fractures Methods Eighty patients with a 31-A2.2 or A2.3 Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association ( AO/OTA ) intertrochanteric fracture were r and omly allocated to fixation with either the Gamma nail or the AMBI sliding hip screw device . Results All patients were followed up at one , three , six and 12 months postoperatively , except for nine who died . There was no statistical difference in Parker mobility score between groups . The Gamma nail group had significantly higher Barthel Index and EuroQol-5D ( EQ-5D ) scores than the AMBI group at 12 months . At the same time , the EQ-5D score had returned to its pre-operative values in the Gamma nail group but not in the AMBI group . There were no differences in mortality , radiation time and hospital stay . Duration of the operation , incision length and hip pain occurrence were significantly less in the Gamma nail group . Conclusions Few failures occur when unstable 31-A2.2 and A2.3 AO/OTA fractures are fixed with a sliding hip screw . Nevertheless , an intramedullary nail seems superior in reconstituting patients to their pre-operative state OBJECTIVE To compare the efficacy of the gamma nail ( GN ) to the dynamic hip screw ( DHS ) in the management of intertrochanteric hip fractures . DESIGN R and omized , prospect i ve clinical trial with a mean follow-up of 52 weeks ( range from 11 to 82 weeks ) . SETTING A university teaching hospital . PATIENTS One hundred and one patients with 102 fractures : 49 fractures were treated with the DHS and 53 fractures were treated with the GN . INTERVENTIONS Fracture fixation with the DHS or the GN . MAIN OUTCOME MEASURES Comparison of duration of operation , blood loss , early and late complications , functional outcome and duration of hospital stay . RESULTS There was no significant difference between the two groups with respect to intraoperative blood loss , days in hospital , time to union and eventual functional outcome . The length of the procedure and fluoroscopy time were longer for the GN group . CONCLUSIONS Both the GN and the DHS can be used effectively for the treatment of intertrochanteric fractures . In this study the DHS was associated with a lower risk of local complications and should still be considered to be the implant of choice for patients with intertrochanteric fractures The Gamma nail was introduced for the treatment of peritrochanteric fractures with the theoretical advantage of a load-sharing femoral component which could be implanted by a closed procedure . We report a r and omised prospect i ve study of 186 fractures treated by either the Gamma nail or a dynamic hip screw . Gamma nails were implanted with significantly shorter screening times , smaller incisions , and less intraoperative bleeding . The Gamma nail group had a shorter convalescence and earlier full weight-bearing , but there was no significant difference in mortality within six months , postoperative mobility , or hip function at review . More intra-operative complications were recorded in the Gamma nail group , mainly due to the mismatching of the femoral component of the nail to the small femurs of Chinese people . Use of a smaller modified nail reduced these complications . We conclude that with careful surgical technique and the modified femoral component , the Gamma nail is an advance in the treatment of peritrochanteric fractures Summary : Achieving bony union and early weight bearing in peritrochanteric femur fractures poses a continuous challenge for the orthopedic surgeon . Current st and ards of surgical fixation for the myriad possible fracture patterns include the compression hip screw ( CHS ) , the 90 ° /95 ° blade plate , and locked intramedullary nails . The gamma nail ( GN ) was design ed as a “ hybrid ” of these devices , combining theoretical biomechanical advantages that should allow earlier postoperative weight bearing with surgical technique advantages that should decrease operative morbidity . Because these theoretical advantages were unproven in a clinical setting , we prospect ively r and omized 75 consecutive patients with peritrochanteric femur fractures into two groups to examine the fixation of these fractures with the GN as compared to the CHS . We found no significant differences in preoperative or intraoperative parameters . Postoperatively , the subtrochanteric fracture group treated with the GN achieved earlier weightbearing status , although this was not statistically significant . 72 patients were available for follow-up at a minimum of 6 months . All fractures had clinical ly and radiographically healed , and 94 % of the patients continued to be ambulatory . Major complications included missed distal locking screws ( one patient ) , cutting out of the lag screw superiorly in the femoral head ( two patients ) , and a femur fracture at the distal end of the GN ( one patient ) . In our series , the GN produced clinical results commensurate with current st and ards of fixation for peritrochanteric femur fractures . Although the GN allowed earlier independent weightbearing status in patients with subtrochanteric fractures , the procedure was technically more dem and ing and had a significant learning curve OBJECTIVES To present several alternative approaches to describing the range and functional outcomes of patients with hip fracture . DESIGN Prospect i ve study with concurrent medical records data collection and patient and proxy interviews at the time of hospitalization and 6 months later . SETTING Four hospitals in the New York metropolitan area . PARTICIPANTS Five hundred seventy-one hospitalized adults aged 50 and older with hip fracture between July 1997 and August 1998 . MEASUREMENTS Rates of return to function in four physical domains , mortality , and nursing home residence at 6 months . Cluster analysis was used to describe the heterogeneity among the sample and identify variations in 6-month mortality , nursing home residence , and level of functioning and to develop a patient classification tree with associated patient outcomes at 6 months postfracture . RESULTS In locomotion , transfers , and self-care , 33 % to 37 % of patients returned to their prior level of function by 6 months , including those needing assistance , but only 24 % were independent in locomotion at 6 months . Cluster analysis identified eight patient subgroups that had distinct baseline features and variable outcomes at 6 months . The patient classification tree used four variables : atypical functional status ( independent in locomotion but dependent in other domains ) ; nursing home residence ; independence/dependence in self-care ; and age younger than 85 or 85 and older that identified five subgroups with variable 6-month outcomes that clinicians may use to predict likely outcomes for their patients . CONCLUSION Patients with hip fracture are heterogeneous with respect to baseline and outcome characteristics . Clinicians may be better able to give patients and caregivers information on expected outcomes based on presenting characteristics used in the classification tree This prospect i ve r and omized study compared the outcome of elderly patients with an unstable pertrochanteric fracture , treated with a proximal femoral nail antirotation device ( PFNA ; n = 51 ) or a dynamic hip screw ( DHS ; n = 55 ) . All patients in the DHS group and nine in the PFNA group had open reductions . Incisions were significantly shorter for the PFNA than the DHS group . Blood loss and the number of patients requiring postoperative blood transfusions were significantly greater , but operation and fluoroscopy times were significantly shorter , for the DHS versus the PFNA group . Time to mobilization with a frame was significantly shorter in the PFNA group , and post-operative complications were more common in the DHS group . Poor fracture reduction led to three revisions . All fractures in both groups united during follow-up . The PFNA allowed earlier mobilization and faster recovery than the DHS . The PFNA is a highly acceptable , minimally invasive implant for unstable fractures Objectives : To compare the results between a new intramedullary Gamma nail and a compression hip screw in the treatment of trochanteric fractures . Design : Prospect i ve r and omized . Setting : Level 1 trauma center . Patients : Two hundred ten consecutive patients older than 65 years with trochanteric femoral fractures . Interventions : Treatment with a compression hip screw or a new design of the Trochanteric Gamma nail ( 180 mm in length with a mediolateral angle of 4 ° and available only with a proximal diameter of 17 mm and distal diameter of 11 mm ) . Main Outcome Measurements : Operative and fluoroscopy times , blood loss , functional outcome , complication rate , and failure of fixation . Results : The Trochanteric Gamma nail was used in 104 patients and the compression hip screw in 106 . The 2 groups were similar in terms of their preoperative data , with a median follow-up of 13.6 months ( range 12 - 30 ) . The results show no difference in operating time ( P = 0.21 ) , but the Trochanteric Gamma nail group had a significantly shorter fluoroscopy time ( P = 0.006 ) , and the number of patients transfused and the mean of units of blood transfused were significantly less in the Trochanteric Gamma nail group ( P = 0.013 , 0.046 , respectively ) . Mortality within 12 months was similar in both groups ( P = 0.83 ) . All fractures were radiographically healed at the last visit . There was no difference in intraoperative and postoperative complications or rate of fixation failure between the 2 groups , and no case of secondary shaft fracture of the femur was encountered in this study . In the entire series , there was no difference in the functional outcome ( P = 0.74 ) , but the postoperative walking ability was better in those patients with unstable fractures who were treated with the Trochanteric Gamma nail ( P = 0.017 ) . Conclusions : The new Trochanteric Gamma nail is an effective method for the treatment of trochanteric femoral fractures in elderly patients . The indication for either Trochanteric Gamma nail or compression hip screw is similar in stable fractures , but we recommend the use of the Trochanteric Gamma nail for unstable trochanteric fractures A prospect i ve , r and omised , controlled trial was performed to compare the outcome of treatment of unstable trochanteric fractures with either a short proximal femoral nail antirotation ( PFNA ) or dynamic hip screw ( DHS ) . Eighty one patients with unstable fracture of the proximal part of the femur were r and omised , at the time of admission , for fixation with either a short PFNA ( n=42 ) or DHS ( n= 39 ) . The primary outcome measure was reoperation within the first postoperative year and mortality at the end of one year . Operative time , fluoroscopy time , blood loss , and any intra-operative complication were recorded for each patient . Clinical and radiological follow-up was undertaken for a minimum of 36 months . Any changes in the position of the implant or fixation failure were recorded . Hip range of motion , pain in the hip or thigh and return to work were used to compare the outcomes . There was no significant difference between 1 year mortality rates for the two groups . The mean operative time was significantly less in PFNA group ( 25 min ) than in the DHS group ( 38 min ) . Patients treated with a PFNA experienced a shorter fluoroscopy time and less blood loss . Six patients in DHS group had implant failure while none experienced this in PFNA group . The PFNA group had a better functional outcome than the DHS group We report a prospect i ve , r and omized , controlled trial , comparing the results of treatment with a dynamic hip screw ( DHS ) and a gamma nail in 95 consecutive patients with peri-trochanteric fractures of the femur . The DHS was used in 48 patients , the gamma nail in 47 . Clinical and radiological outcomes were similar , but the gamma nail was associated with a higher incidence of complications , in particular fracture of the femur below the implant in eight cases . This is consistent with previous reports , and we do not recommend the gamma nail for the treatment of peri-trochanteric femoral fractures A prospect i ve , r and omized study comparing the compression hip screw with the Gamma nail in the treatment of 426 intertrochanteric fractures is reported . The median patient age was 80 years , and 71 % were women The compression hip screw operation took less time except in Evans Type 5 fractures . Blood loss generally was less in the compression hip screw group except in patients with Type 5 fractures . The most frequent surgical problem for patients in the Gamma group was problems with distal locking . Cephalic position of the femoral head screw and cut-out were seen more often in the Gamma nail group . The Gamma nail more frequently preserved the fracture position obtained perioperatively . Whether there was distal locking of the Gamma nail in unstable fractures did not seem to affect the healing rate . Additional fissures or fractures in the proximal femur occurred during five Gamma nail operations and two compression hip screw operations . Postoperative walking ability did not differ between the groups . At 6 months 88 % of the fractures were healed . In less comminuted fractures , the compression hip screw method is the preferred method of treatment whereas the Gamma nail is an alternative treatment for more comminuted Evans Type 5 fractures This prospect i ve , r and omized study compared the functional outcome and complications associated with a proximal femoral nail antirotation ( PFNA ) device with those of a traditional extramedullary device , the dynamic hip screw ( DHS ) , in patients with trochanteric fracture . A total of 121 patients were r and omized to the PFNA group ( n = 58 ) or the DHS group ( n = 63 ) . Perioperative information and complications were recorded , and assessment s of functional outcome were made . The DHS group required a longer operative time and was associated with greater blood loss than the PFNA group . The re-operation rate was lower in the PFNA group compared with the DHS group , especially in patients with unstable fractures , although there was no statistically significant difference in the overall complication rate between the two groups . There were no significant differences in functional outcome between the PFNA and the DHS groups . In conclusion , the PFNA device is useful in the treatment of trochanteric fractures BACKGROUND The Gamma nail has been introduced as an advance over the Ambi hip screw in intertrochanteric femoral fractures . Its efficacy in an Australasian setting has not been documented . METHODS A prospect i ve r and omized study was used to compare the Ambi hip screw and the Gamma nail for the treatment of 69 patients over the age of 50 years with intertrochanteric femoral fractures . The groups were similar with respect to age , sex , prefracture mobility and abode , anaesthetic risk grade , CT measured bone density and fracture pattern . RESULTS Those treated with the Gamma nail had a significantly longer image intensifier screening time ( P < 0.05 ) , greater blood loss ( P < 0.01 ) and more operative complications . There was no difference in the length of hospital stay but the level of mobility recovered was significantly better in the Ambi group at 6 months follow up . Urine retention was the most frequent complication but did not correlate with the implant or method of anaesthesia . Two implants cut out , one in each group . Limb shortening was similar in both groups and was not affected by leaving the Gamma nail unlocked distally in unstable fractures . Thirteen patients died from pre-existing medical conditions . CONCLUSIONS The Gamma nail proved technically more dem and ing with higher intra-operative complications and inferior return of mobility Limited access surgery is thought to reduce post-operative morbidity and provide faster recovery of function . The percutaneous compression plate ( PCCP ) is a recently introduced device for the fixation of intertrochanteric fractures with minimal exposure . It has several potential mechanical advantages over the conventional compression hip screw ( CHS ) . Our aim in this prospect i ve , r and omised , controlled study was to compare the outcome of patients operated on using these two devices . We r and omised 104 patients with intertrochanteric fractures ( AO/OTA 31.A1-A2 ) to surgical treatment with either the PCCP or CHS and followed them for one year postoperatively . The mean operating blood loss was 161.0 ml ( 8 to 450 ) in the PCCP group and 374.0 ml ( 11 to 980 ) in the CHS group ( Student 's t-test , p < 0.0001 ) . The pain score and ability to bear weight were significantly better in the PCCP group at six weeks post-operatively . Analysis of the radiographs in a proportion of the patients revealed a reduced amount of medial displacement in the PCCP group ( two patients , 4 % ) compared with the CHS group ( 10 patients , 18.9 % ) ; Fisher 's exact test , p < 0.02 . The PCCP device was associated with reduced intra-operative blood loss , less postoperative pain and a reduced incidence of collapse of the fracture |
13,443 | 31,412,057 | Except for agility tests , several tests for all categories with acceptable levels of validity and high levels of reliability for adult soccer players are available . | INTRODUCTION Speed is an important prerequisite in soccer .
Therefore , a large number of tests have been developed aim ing to investigate several speed skills relevant to soccer .
This systematic review aim ed to examine the validity and reliability of speed tests used in adult soccer players . | Abstract Shalfawi , SAI , Haugen , T , Jakobsen , TA , Enoksen , E , and Tønnessen , E. The effect of combined resisted agility and repeated sprint training vs. strength training on female elite soccer players . J Strength Cond Res 27(11 ) : 2966–2972 , 2013—The aim of this study was to compare the effects of in-season combined resisted agility and repeated sprint training with strength training on soccer players ' agility , linear single sprint speed , vertical jump , repeated sprint ability ( RSA ) , and aerobic capacity . Twenty well-trained elite female soccer players of age ± SD 19.4 ± 4.4 years volunteered to participate in this study . The participants were r and omly assigned to either the agility and repeated sprint training group or to the strength training group . All the participants were tested before and after a 10-week specific conditioning program . The pretest and posttest were conducted on 3 separate days with 1 day of low-intensity training in between . Test day 1 consisted of squat jump ( SJ ) , countermovement jump ( CMJ ) , and RSA . Test day 2 consisted of a 40-m maximal linear sprint and an agility test , whereas a Beep test was conducted on test day 3 to assess aerobic capacity . The agility and repeated sprint training implemented in this study did not have a significant effect on agility , although there was a tendency for moderate improvements from 8.23 ± 0.32 to 8.06 ± 0.21 seconds ( d = 0.8 ) . There was a significant ( p < 0.01 ) and moderate-positive effect on Beep-test performance from level 9.6 ± 1.4 to level 10.8 ± 1.0 , and only a trivial small effect on all other physical variables measured in this study . The strength training group had a positive , moderate , and significant ( p < 0.01 ) effect on Beep-test performance from level 9.7 ± 1.3 to level 10.9 ± 1.2 ( d = 1.0 ) and a significant ( p < 0.05 ) but small effect ( d = 0.5 ) on SJ performance ( 25.9 ± 2.7 to 27.5 ± 4.1 cm ) . Furthermore , the strength training implemented in this study had a trivial and negative effect on agility performance ( d = −0.1 ) . No between-group differences were observed . The outcome of this study indicates the importance of a well-planned program of conditioning that does not result in a decreased performance of the players , the great importance of strength and conditioning specialist in implementing the training program , and the importance of choosing the time of the year to implement such conditioning training programs . However , the fact that the present training program did not cause any decline in performance indicates that it is useful in maintaining the soccer players ' physical performance during the competition period ABSTRACT This study aim ed to investigate the effect of air pollution on diurnal variation of performance in anaerobic tests , cardiovascular and hematological parameters , and blood gases on soccer players following the Yo – Yo Intermittent Recovery Test Level-1 ( YYIRT1 ) . In a r and omized order , 11 healthy soccer players ( mean age : 21.8 [ range : 20–24 ] years ; height : 178.00 [ range : 1.64–1.83 ] cm ; body mass index [ BMI ] : 23.57 [ range : 20.45–28.03 ] kg.m−2 ) performed a YYIRT1 at two different times of day ( TOD ) ( 08:00 h and 18:00 h ) in two areas ( i.e. polluted ( PA ) and non-polluted ( NPA ) ) with a recovery period of ≥ 72 h in between , to determine the maximal oxygen uptake ( VO2max ) . In each test session : resting oral temperature is measured , anaerobic performances ( pre- and post-YYIRT1 ) were performed , cardiovascular parameters and blood sample s were collected at : rest , 3 min and 60 min after the YYIRT1 , to assess blood gases and hematological parameters . Our results showed that , agility performance , VO2max , red blood cells ( RBC ) , hemoglobin ( Hb ) , pH , and bicarbonate levels ( HCO3− ) decrease significantly ( p < 0.001 ) following the YYIRT1 in PA compared to NPA . Likewise , the heart rate ( HR ) , systolic blood pressure ( SBP ) , platelets ( PLT ) , white blood cells ( WBC ) , neutrophiles ( NEUT ) , lymphocytes ( LYM ) , and partial pressure of CO2 levels ( PvCO2 ) were significantly higher ( p < 0.001 ) in PA . This effect was slightly accentuated at 18:00 h for some parameters ( i.e. Agility , HCO3− , HR , PvCO2 , RBC , SBP ) . However , performances of sprint and Sargent jump test ( SJT ) , oral temperature , rate of perceived exertion scales ( RPE ) , partial pressure of O2 ( PvO2 ) , diastolic blood pressure ( DBP ) , and monocytes ( MON ) were not affected by pollution ( p > 0.05 ) . In conclusion , pollution seems to be critical for health stability and performance in response to YYIRT1 especially in the evening and the winter season . Therefore , coaches and athletes should draw attention to the potential importance of l and use planning in their training sessions and competitions in the morning in polluted area to minimize the risk of pollution exposure The purpose of this study was to compare the effects of combined strength and plyometric training with strength training alone on power-related measurements in professional soccer players . Subjects in the intervention team were r and omly divided into 2 groups . Group ST ( n = 6 ) performed heavy strength training twice a week for 7 weeks in addition to 6 to 8 soccer sessions a week . Group ST+P ( n = 8) performed a plyometric training program in addition to the same training as the ST group . The control group ( n = 7 ) performed 6 to 8 soccer sessions a week . Pretests and posttests were 1 repetition maximum ( 1RM ) half squat , countermovement jump ( CMJ ) , squat jump ( SJ ) , 4-bounce test ( 4BT ) , peak power in half squat with 20 kg , 35 kg , and 50 kg ( PP20 , PP35 , and PP50 , respectively ) , sprint acceleration , peak sprint velocity , and total time on 40-m sprint . There were no significant differences between the ST+P group and ST group . Thus , the groups were pooled into 1 intervention group . The intervention group significantly improved in all measurements except CMJ , while the control group showed significant improvements only in PP20 . There was a significant difference in relative improvement between the intervention group and control group in 1RM half squat , 4BT , and SJ . However , a significant difference between groups was not observed in PP20 , PP35 , sprint acceleration , peak sprinting velocity , and total time on 40-m sprint . The results suggest that there are no significant performance-enhancing effects of combining strength and plyometric training in professional soccer players concurrently performing 6 to 8 soccer sessions a week compared to strength training alone . However , heavy strength training leads to significant gains in strength and power-related measurements in professional soccer players OBJECTIVES This study investigated the acute effects of a currently implemented team-sport warm-up and two alternative , high-intensity , short- duration protocol s - 5 repetition maximum leg press and small-sided games . DESIGN Ten male soccer players participated in a r and omised , cross-over study . METHODS Participants performed a team-sport , a leg-press , or a small-sided game warm-up . Subsequent performance tests included counter-movement jump , reactive agility , and 15 × 20 m sprints embedded in an intermittent exercise task . Physiological measures included core temperature , blood lactate concentration , heart rate and rating of perceived exertion . Data were analysed using the effect size statistic with 90 % confidence intervals , and percentage change , to determine magnitude of effects . RESULTS Counter-movement jump height improved following the small-sided game ( 6 % , ES : 0.8±0.8 ) and leg-press warm-up ( 2 % , ES : 0.3±0.5 ) , but not after the team-sport warm-up ( ' unclear ' effect ) . Reactive agility improved after the small-sided game ( 4 % , ES : 0.8±0.7 ) and leg-press warm-ups only ( 5 % , ES : 1.1±0.7 ) , when compared to baseline . Mean 20-m sprint times during the intermittent exercise task improved following the leg-press warm-up , when compared with the small-sided game ( 9 % , ES : 0.9±0.3 ) and team-sport warm-ups ( 7 % , ES : 0.6±0.6 ) . Core temperature was lower following the leg-press warm-up compared to small-sided game ( 1 % , ES : 0.9±0.7 ) and the team-sport WUs ( 2 % , ES : 2.4±0.8 ) . Blood lactate was highest following the small-sided game ( 67 % , ES : 2.7±0.8 ) and team-sport warm-ups ( 66 % , ES : 2.9±0.9 ) . CONCLUSIONS A leg-press and small-sided game warm-up may improve acute team-sport performance tests when compared to a traditional warm-up protocol Sayers , AL , Farley , RS , Fuller , DK , Jubenville , CB , and Caputo , JL . The effect of static stretching on phases of sprint performance in elite soccer players . J Strength Cond Res 22(5 ) : 1416 - 1421 , 2008-The purpose of this study was to determine which phase of a 30-m sprint ( acceleration and /or maximal velocity ) was affected by preperformance static stretching . Data were collected from 20 elite female soccer players . On two nonconsecutive days , participants were r and omly assigned to either the stretch or no-stretch condition . On the first day , the athletes in the no-stretch condition completed a st and ard warm-up protocol and then performed three 30-m sprints , with a 2-minute rest between each sprint . The athletes in the stretch condition performed the st and ard warm-up protocol , completed a stretching routine of the hamstrings , quadriceps , and calf muscles , and then immediately performed three 30-m sprints , also with a 2-minute rest between each sprint . On the second day , the groups were reversed , and identical procedures were followed . One-way repeated- measures analyses of variance revealed a statistically significant difference in acceleration ( p < 0.0167 ) , maximal-velocity sprint time ( p < 0.0167 ) , and overall sprint time ( p < 0.0167 ) between the stretch and no-stretch conditions . Static stretching before sprinting result ed in slower times in all three performance variables . These findings provide evidence that static stretching exerts a negative effect on sprint performance and should not be included as part of the preparation routine for physical activity that requires sprinting Thomas , K , French , D , and Hayes , PR . The effect of two plyometric training techniques on muscular power and agility in youth soccer players . J Strength Cond Res 23(1 ) : 332 - 335 , 2009-The aim of this study was to compare the effects of two plyometric training techniques on power and agility in youth soccer players . Twelve males from a semiprofessional football club 's academy ( age = 17.3 ± 0.4 years , stature = 177.9 ± 5.1 cm , mass = 68.7 ± 5.6 kg ) were r and omly assigned to 6 weeks of depth jump ( DJ ) or countermovement jump ( CMJ ) training twice weekly . Participants in the DJ group performed drop jumps with instructions to minimize ground-contact time while maximizing height . Participants in the CMJ group performed jumps from a st and ing start position with instructions to gain maximum jump height . Posttraining , both groups experienced improvements in vertical jump height ( p < 0.05 ) and agility time ( p < 0.05 ) and no change in sprint performance ( p > 0.05 ) . There were no differences between the treatment groups ( p > 0.05 ) . The study concludes that both DJ and CMJ plyometrics are worthwhile training activities for improving power and agility in youth soccer players Spierer , DK , Petersen , RA , and Duffy , K. Response time to stimuli in Division I soccer players . J Strength Cond Res 25(4 ) : 1134 - 1141 , 2011-The purpose of this investigation was to examine the effect of auditory stimuli ( AS ) and visual stimuli ( VS ) on sprint time , sprint speed , and reaction time in National Collegiate Athletic Association Division I male soccer players . Fifteen healthy subjects ( mean age 22.1 ± 1.6 years ) volunteered for the study . This experiment was conducted on a regulation soccer field , using a wireless timing system . Subjects stood on a touch- and -release pad and were instructed a prompt ( AS : “ go ” comm and via a microphone interface , VS : movement of a player located 10 m from the start ) to run 20 m through the finish line timing gates without decelerating . After 3 submaximal sprint trials at 50 % , conditions ( AS and VS ) were r and omized and performed 3 times by each subject . The best sprint time , sprint speed , and reaction time were recorded . Paired t-tests were conducted on dependent variables to determine statistically significant differences . An alpha level was set at p ≤ 0.05 . Sprint time was reduced in response to VS as compared to AS ( 3.76 ± 0.16 seconds vs. 3.85 ± 0.15 seconds , p = 0.001 ) . Sprint speed ( distance covered ) was greater in VS compared to AS ( 5.3 ± 0.21 m·s−1 vs. 5.1 ± 0.19 m·s−1 , p < 0.001 ) , and reaction time was reduced in VS compared to AS ( 0.53 ± 0.048 seconds vs. 0.61 ± 0.044 seconds , p = 0.001 ) . These data show that VS rather than AS improve sprint response times in collegiate male soccer athletes . The data suggest that performance on the field may be improved if coaches and players strategize to integrate visual cues ( e.g. , gestures and signals ) during practice s and games Abstract It has been suggested that assessment of high-intensity activities during a match is a valid measure of physical performance in elite soccer . Recently , sprinting activities have been analysed in more depth . The aim of this study was to develop a detailed analysis of the sprinting activities of different playing positions during European Champions League and UEFA Cup competitions . Altogether , 717 elite outfield soccer players were evaluated throughout 2002–2006 using ProZone ® ( Leeds , UK ) . Sprinting ( explosive and leading ) was analysed for each playing position . To compare positional differences , a Kruskal-Wallis analysis was performed . Differences were found among positions for total number of sprints and total sprint distance covered : wide midfielders > ( attackers = wide defenders ) > central midfielders > central defenders ( P < 0.001 ) , as well as for explosive sprints : ( wide midfielders = attackers = wide defenders ) > central defenders , wide midfielders > central midfielders > central defenders and attackers = wide defenders = central midfielders ( P < 0.001 ) , and leading sprints : wide midfielders > ( attackers = wide defenders ) > central midfielders > central defenders ( P < 0.001 ) . For each group , there were no differences in ratio of explosive to leading sprints . Wide midfielders performed a higher number of sprints in all five distance categories than all other positions . This study showed that sprinting characteristics are influenced by position . Wide midfielders have to complete additional high-intensity activities during training sessions compared with the other positions to achieve the performance level required during the match Gelen , E. Acute effects of different warm-up methods on sprint , slalom dribbling , and penalty kick performance in soccer players . J Strength Cond Res 24(4 ) : 950 - 956 , 2010-Although pre-event static stretching is an accepted practice in most athletics program , pre-event dynamic exercise is becoming popular . The purpose of this study was to compare the acute effects of different warm-up methods on soccer performance . Twenty-six professional soccer players ( 23.3 ± 3.2 years , 178.2 ± 6.1 cm , and 73.0 ± 6.5 kg ) performed 4 different warm-up routines in r and om order on nonconsecutive days . The warm-up methods consisted of only 5 minutes of jogging ( Method A ) , 5 minutes of jogging and static stretching ( Method B ) , 5 minutes of jogging and dynamic exercise ( Method C ) , and 5 minutes of jogging and a combination of static stretching and dynamic exercise ( Method D ) . After each warm-up session , subjects were tested on the sprint , slalom dribbling , and penalty kick performance . Methods A-D were compared by repeated- measures analyses of variance and post hoc comparisons . In this study , existence of a significant drop in sprint , slalom dribbling , and penalty kick performances of Method C has been determined in comparison with that of Method A ( p < 0.05 ) . Again for sprint , slalom dribbling , and penalty kick performances of Method A in comparison with those of Method A , the existence of a significant increase has been determined ( p < 0.05 ) . In Method D in comparison with Method A , for sprint , slalom dribbling , and penalty kick performances , existence of no significant difference has been determined ( p > 0.05 ) . The results of this study suggest that it may be desirable for soccer players to perform dynamic exercises before the performance of activities that require a high power output Mujika , I , Santisteban , J , and Castagna , C. In-season effect of short-term sprint and power training programs on elite junior soccer players . J Strength Cond Res 23(9 ) : 2581 - 2587 , 2009-The aim of this study was to examine the effects of 2 in-season short-term sprint and power training protocol s on vertical countermovement jump height ( with or without arms ) , sprint ( Sprint-15 m ) speed , and agility ( Agility-15 m ) speed in male elite junior soccer players . Twenty highly trained soccer players ( age 18.3 ± 0.6 years , height 177 ± 4 cm , body mass 71.4 ± 6.9 kg , sum skinfolds 48.1 ± 11.4 mm ) , members of a professional soccer academy , were r and omly allocated to either a CONTRAST ( n = 10 ) or SPRINT ( n = 10 ) group . The training intervention consisted of 6 supervised training sessions over 7 weeks , targeting the improvement of the players ' speed and power . CONTRAST protocol consisted of alternating heavy-light resistance ( 15 - 50 % body mass ) with soccer-specific drills ( small-sided games or technical skills ) . SPRINT training protocol used line 30-m sprints ( 2 - 4 sets of 4 × 30 m with 180 and 90 seconds of recovery , respectively ) . At baseline no difference between physical test performance was evident between the 2 groups ( p > 0.05 ) . No time × training group effect was found for any of the vertical jump and Agility-15 m variables ( p > 0.05 ) . A time × training group effect was found for Sprint-15 m performance with the CONTRAST group showing significantly better scores than the SPRINT group ( 7.23 ± 0.18 vs. 7.09 ± 0.20 m·s−1 , p < 0.01 ) . In light of these findings CONTRAST training should be preferred to line sprint training in the short term in young elite soccer players when the aim is to improve soccer-specific sprint performance ( 15 m ) during the competitive season Foam rolling ( FR ) is a common strategy used after training and competition by players . However , no previous studies have assessed the effectiveness of FR as recovery tool in sports population s. The aim of this study was to examine the effectiveness of FR ( 20 minutes of foam rolling exercises on quadriceps , hamstrings , adductors , gluteals , and gastrocnemius ) and passive recovery ( 20 minutes sit on a bench ) interventions performed immediately after a training session on Total Quality Recovery ( TQR ) , perceived muscle soreness , jump performance , agility , sprint , and flexibility 24 hours after the training . During 2 experimental sessions , 18 professional soccer players ( age 26.6 ± 3.3 years ; height : 180.2 ± 4.5 cm ; body mass : 75.8 ± 4.7 kg ) participated in a r and omized fully controlled trial design . The first session was design ed to collect the pre-test values of each variable . After baseline measurements , the players performed a st and ardized soccer training . At the end of training unit , all the players were r and omly assigned to the FR recovery group and the passive recovery group . A second experimental session was carried out to obtain the posttest values . Results from the between-group analyses showed that FR had a large effect on the recovery in agility ( Effect Sizes [ES]= 1.06 ) , TQR ( ES= 1.08 ) , and perceived muscle soreness ( ES= 1.02 ) in comparison to passive recovery group at 24 h post-training . Thus , it is recommended soccer coaches and physical trainers working with high-level players use a structured recovery session lasting from 15 to 20 min based on FR exercises that could be implemented at the end of a training session to enhance recovery between training loads Does improved decision-making ability reduce the physiological dem and s of game-based activities in field sport athletes ? J Strength Cond Res 22(6 ) : 2027 - 2035 , 2008-This study investigated the effects of video-based perceptual training on pattern recognition and pattern prediction ability in elite field sport athletes and determined whether enhanced perceptual skills influenced the physiological dem and s of game-based activities . Sixteen elite women soccer players ( mean ± SD age , 18.3 ± 2.8 years ) were allocated to either a video-based perceptual training group ( N = 8) or a control group ( N = 8) . The video-based perceptual training group watched video footage of international women 's soccer matches . Twelve training sessions , each 15 minutes in duration , were conducted during a 4-week period . Players performed assessment s of speed ( 5- , 10- , and 20-m sprint ) , repeated-sprint ability ( 6 × 20-m sprints , with active recovery on a 15-second cycle ) , estimated maximal aerobic power ( & OV0312;o2 max , multistage fitness test ) , and a game-specific video-based perceptual test of pattern recognition and pattern prediction before and after the 4 weeks of video-based perceptual training . The on-field assessment s included time-motion analysis completed on all players during a st and ardized 45-minute small-sided training game , and assessment s of passing , shooting , and dribbling decision-making ability . No significant changes were detected in speed , repeated-sprint ability , or estimated & OV0312;o2 max during the training period . However , video-based perceptual training improved decision accuracy and reduced the number of recall errors , indicating improved game awareness and decision-making ability . Importantly , the improvements in pattern recognition and prediction ability transferred to on-field improvements in passing , shooting , and dribbling decision-making skills . No differences were detected between groups for the time spent st and ing , walking , jogging , striding , and sprinting during the small-sided training game . These findings demonstrate that video-based perceptual training can be used effectively to enhance the decision-making ability of field sport athletes ; however , it has no effect on the physiological dem and s of game-based activities UNLABELLED Agility is the player 's capability to perform rapid whole-body movement with change of velocity or direction in response to a stimulus . The aims of this study were as follows : 1 ) to assess the reliability of a reactive visual stimuli agility field test ( RVS-T ) ; and 2 ) to evaluate differences in RVS-T and planned ( PVS-T ) agility performances between female soccer and futsal players . MATERIAL AND METHODS Sixty-six female players belonging to Italian teams of regional level were recruited to the study . The experimental apparatus consisted of four lighted spherical visual stimuli connected to a computer able to r and omly generate three different sequences . Differences between RVS-T and PVS-T performances were calculated to evaluate the decision-making time ( DMT ) of players . RESULTS The intraclass reliability coefficient for RVS-T was 0.80 . Significant ( P<0.05 ) differences emerged only for RVS-T ( futsal , 17.3±0.5 s ; soccer , 18.8±1.1 s ) and DMT ( futsal , 2.6±0.6 s ; soccer , 4.1±1.2 s ) , whereas similar performances between groups result ed for PVS-T ( futsal , 14.7±0.6 s ; soccer , 14.6±0.6 s ) . CONCLUSIONS The RVS-T proved to be a reliable tool to evaluate agility in field conditions . Futsal players showed better RVS-T and DMT performances with respect to soccer counterparts , probably due to the higher velocity of actions and faster decision-making of their sport . The lack of difference in PVS-T performances confirms the importance to evaluate agility capabilities of players in both planned and reactive conditions Abstract In this study , we examined the reliability and construct validity of new soccer skills tests . Twenty soccer players ( 10 professional and 10 recreational ) repeated trials of passing , shooting , and dribbling skills on different days . Passing and shooting skills required players to kick a moving ball , delivered at constant speed , towards one of four r and omly determined targets . Dribbling required players to negotiate seven cones over 20 m. Each trial consisted of 28 passes , 8 shots , and 10 dribbles . Ball speed , precision , and success were determined for all tests using video analysis . Systematic bias was small ( < 9 % in all measures ) and all outcome measures were similar between trials . Test – retest reliability statistics were as follows : ball speed ( passing , shooting , dribbling ; coefficient of variation [ CV ] : 6.5 % , 6.9 % , 2.4 % ; ratio limits of agreement [ RLOA ] : 0.958 ×/÷ 1.091 , 0.990 ×/÷ 1.107 , 0.993 ×/÷ 1.039 ) , precision ( passing , shooting , dribbling ; CV : 10.0 % , 23.5 % , 4.6 % ; RLOA : 0.956 ×/÷ 1.147 , 1.030 ×/÷ 1.356 , 1.000 ×/÷ 1.068 ) , and success ( passing , shooting , dribbling ; CV : 11.7 % , 14.4 % , 2.2 % ; RLOA : 1.017 ×/÷ 1.191 , 0.913 ×/÷ 1.265 , 0.996 ×/÷ 1.035 ) . Professional players performed better than recreational players in at least one outcome measure for all skills . These findings demonstrate the reliability and validity of new soccer skill protocol The aim of the study was to investigate the reliability of a new test of soccer performance and evaluate the effect of carbohydrate ( CHO ) on soccer performance . Eleven university footballers were recruited and underwent 3 trials in a r and omized order . Two of the trials involved ingesting a placebo beverage , and the other , a 7.5 % maltodextrin solution . The protocol comprised a series of ten 6-min exercise blocks on an outdoor Astroturf pitch , separated by the performance of 2 of the 4 soccer-specific tests , making the protocol 90 min in duration . The intensity of the exercise was design ed to be similar to the typical activity pattern during soccer match play . Participants performed skill tests of dribbling , agility , heading , and shooting throughout the protocol . The coefficients of variation for dribbling , agility , heading , and shooting were 2.2 % , 1.2 % , 7.0 % , and 2.8 % , respectively . The mean combined placebo scores were 42.4 + /- 2.7 s , 43.1 + /- 3.7 s , 210 + /- 34 cm , and 212 + /- 17 points for agility , dribbling , heading , and kicking , respectively . CHO ingestion led to a combined agility time of 41.5 + /- 0.8 s , for dribbling 41.7 + /- 3.5 s , 213 + /- 11 cm for heading , and 220 + /- 5 points for kicking accuracy . There was a significant improvement in performance for dribbling , agility , and shooting ( p < .05 ) when CHO was ingested compared with placebo . In conclusion , the protocol is a reliable test of soccer performance , and ingesting CHO leads to an improvement in soccer performance Sjökvist , J , Laurent , CM , Richardson , M , Curtner-Smith , M , Holmberg , H-C , and Bishop , PA . Recovery from high-intensity training sessions in female soccer players . J Strength Cond Res 25(6 ) : 1726 - 1735 , 2011—This study quantified the performance recovery time requirements after training sessions using high-intensity soccer drills with and without the ball in National Collegiate Athletic Association Division I female soccer players . Recovery time periods ( 24 , 48 , 72 hours of rest ) from high-intensity soccer training sessions using drills with and without the ball were evaluated . Markers of recovery were each individual 's performance relative to baseline performance in countermovement jump ( CMJ ) height , 5 bound jumps for distance ( 5BT ) , 20-m sprint ( 20SP ) , session rating of perceived effort ( S-RPE ) , and heart rate ( HR ) . Repeated- measures analysis of variance revealed a significant difference in CMJ performance ( p < 0.04 ) and S-RPE ( p < 0.02 ) after 24 hours of rest but not at 48 or 72 hours compared to baseline . There were no significant differences in 20SP , 5BT , or HR after 24 , 48 , or 72-hour recovery ( p > 0.05 ) . Therefore , high-intensity training drills produced a sufficient conditioning stimulus with little chance of underrecovery for the performance measures we tested . Countermovement jump and S-RPE may be more sensitive performance recovery indicators |
13,444 | 19,160,232 | Use of rescue medication was significantly less common with naproxen than placebo .
Associated adverse events were generally of mild to moderate severity and rarely led to withdrawal .
Doses equivalent to 500 mg and 400 mg naproxen administered orally provided effective analgesia to adults with moderate to severe acute postoperative pain . | BACKGROUND Naproxen , a non-steroidal anti-inflammatory drug , is used to treat various painful conditions including postoperative pain , and is often administered as the sodium salt to improve its solubility .
This review up date s a 2004 Cochrane review showing that naproxen sodium 550 mg ( equivalent to naproxen 500 mg ) was effective for treating postoperative pain .
New studies have since been published .
OBJECTIVES To assess efficacy , duration of action , and associated adverse events of single dose oral naproxen or naproxen sodium in acute postoperative pain in adults . | DFP [ 3-(2-propyloxy)-(4-methyl-sulfonylphenyl)-(5,5-dimethyl)-fu ranone ] is a highly specific cyclooxygenase-2 inhibitor ( > 2500-fold selective in transfected Chinese hamster ovary cell assays ) that has demonstrated efficacy in pre clinical models of pain and inflammation . The present single-dose , r and omized , double-masked , double-dummy , placebo-controlled , parallel-group study was undertaken to compare DFP 5 , 25 , and 50 mg with naproxen sodium 550 mg and with placebo in 196 patients ( mean age , 25.8 years ; 187 [ 95.4 % ] males ) who experienced moderate-to-severe pain after surgical removal of > or = 2 third molars . Overall analgesic effect , duration of effect , time to onset of analgesic effect , peak analgesic effect , and tolerability were assessed over a 24-hour postdose period . Both DFP 25 and 50 mg , as well as the active comparator , naproxen sodium 550 mg , were significantly more effective than placebo . The onset of analgesic effect in the DFP 25-mg , DFP 50-mg , and naproxen sodium 550-mg groups did not differ significantly . DFP was generally well tolerated in single doses up to 50 mg . DFP 50 mg was efficacious in the treatment of postoperative dental pain and was indistinguishable from the active comparator , naproxen sodium 550 mg In a double-blind , parallel , placebo-controlled study , 203 patients with post-operative dental pain following the extraction of one or two bony impacted third molars were r and omized to receive a single dose of naproxen sodium 220 mg , ibuprofen 200 mg or placebo . Pain intensity and pain relief were assessed at intervals for 12 hours postdose . Both active drugs demonstrated superior analgesic efficacy over placebo . Naproxen sodium and ibuprofen were comparable both in onset of analgesic action and in pain relief . From 1 to 12 hours postdose , naproxen sodium showed a trend for superior analgesic efficacy compared with ibuprofen ; this trend reached statistical significance at the 12-hour time point . Both drugs were well-tolerated and effective analgesics for postoperative dental 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 Background Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions , including the treatment of postoperative pain . This review aims to assess the efficacy , safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults , compared with placebo . Methods The Cochrane Library ( issue 4 2002 ) , EMBASE , PubMed , MEDLINE and an in-house data base were search ed for r and omised , double blind , placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain . Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50 % pain relief over 4 to 6 hours . Relative benefit and number-needed-to-treat were then calculated . The percentage of patients with any adverse event , number-needed-to-harm , and time to remedication were also calculated . Results Ten trials with 996 patients in met the inclusion criteria . Six trials compared naproxen sodium 550 mg ( 252 patients ) with placebo ( 248 patients ) ; the NNT for at least 50 % pain relief over six hours was 2.6 ( 95 % confidence interval 2.2 to 3.2 ) . There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo . Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg ( 206 patients ) and 2.6 hours for placebo ( 205 patients ) . Four other trials used lower doses . Conclusion A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain . A low incidence of adverse events was found , although these were not reported consistently Abstract A multidisciplinary , double blind , parallel placebo controlled investigation was made to find an effective anti-inflammatory drug which prevents postoperative swelling , trismus and a general feeling of malaise . An additional aim was to evaluate objective ly the anti-inflammatory properties of anti-rheumatics . In 126 healthy patients , who were without complaints , the lower third molar was surgically removed . A drug had to be taken orally according to a fixed scheme for 4 days . Glafenine had to be taken in case of pain . The number of tablets taken was used to quantify pain . Swelling of the cheek was measured photographically and trismus was deducible from the maximal mouth-opening . The drugs investigated were betamethasone 14.5 mg decreasing over 4 days , ibuprofen 1200 mg/day , indomethacin 150 mg/day , naproxen 750 mg/day , niflumic acid 1000 mg/day , oxyphenylbutazone 600 mg/day and tranexamic acid 2000 mg/day . Oxyphenylbutazone and tranexamic acid were not significantly different from placebo in their pain-killing effects . Betamethasone prevents swelling and trismus significantly more than the placebo . Betamethasone is significantly better than the other drugs in the prevention of swelling . Reduction of the swelling by anti-rheumatics may be 10–15 % and a 20 % reduction of trismus is to be expected . The strongest analgesic is niflumic acid . Tranexamic acid may perhaps reduce the swelling by 28 % . The question naire and the blood- and urine-test showed that anti-rheumatics have to be considered to be acetylsalicylic acid-like drugs . Serious side effects have been reported previously for anti-rheumatics . When taken for a short time , corticosteroids are very safe drugs with a few mild side-effects . Many patients experience a slight euphoria . Betamethasone , in a dosage of 14.5 mg decreasingly divided over 4 days prevents pain by 80 % , swelling by 65 % and trismus by 40 % compared with the placebo group . This safe drug is recommended in elective surgery Oral naproxen in doses of 100 , 200 and 400 mg was compared with oral meperidine in doses of 25 and 75 mg , in a double-blind , single-dose , completely-r and omized study of patients with postoperative pain . One hundred patients were studied , twenty for each of the five treatments . The patients 1 subjective pain scores were recorded by an observer for four hours after administration of the treatment . Dose-effect trends were present with both naproxen and meperidine . Naproxen 400 mg performed the best of all treatments in the study ; on pain-score measurements it was significantly superior to meperidine 25 mg ; and in terms of the number of patients requiring re-medication for pain during the four-hour observation period , significantly fewer patients failed on naproxen 400 than on naproxen 100 mg . No appreciable excess of side effects occurred with naproxen A double-blind parallel r and omized study comparing naproxen 600 mg , naproxen 400 mg , and propoxyphene 65 mg was performed in 105 patients suffering from pain after orthopedic surgery . A significant difference in analgesic effectiveness was shown between the three drugs with successful analgesia recorded in 66 % of patients who received naproxen 600 mg , 37 % of those who received naproxen 400 mg , and 20 % of those who received propoxyphene 65 mg ( X2 2dt= 15.34 , p<0.005 ) . Naproxen 600 mg provided successful analgesia more often than did naproxen 400 mg . Complaints were mild but frequent with ail drugs ( 36 % of patients ) . No serious side effects were & 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 One hundred and eighty patients scheduled for day-care surgery were allocated r and omly to one of three groups to receive naproxen sodium 1100 mg 1 h prior to surgery , naproxen sodium 1100 mg immediately after surgery , or placebo . The pre-surgery naproxen sodium group had significantly lower pain scores 1 h post-operatively and at discharge than the placebo group . At discharge both treatment groups were better than placebo . At 24 h post-operatively only the post-operative naproxen sodium group had lower pain scores . There was no difference in post-operative analgesic requirements until discharge between the groups , but at 24 h post-operatively the placebo group had required significantly more analgesics than the treatment groups . A question naire concerning general acceptability of anaesthesia/analgesia showed similar results . Our conclusion is that naproxen is better than placebo for treatment of post-operative pain . The time of administration pre- or post-operatively is important for the immediate post-operative pain , but we found no support for the existence of ' pre-emptive analgesia ' 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 Pain after extraction of two antagonistic third molars was chosen to compare the analgesic effects of single doses of naproxen-sodium ( 825 mg ) and paracetamol ( 1 000 mg ) . 124 patients of both sexes , aged from 14 to 41 years , took part in the trial which was of the double blind double dummy type with r and omization into one or the other treatment . In all , 89 patients were acceptable for inclusion and followed the protocol correctly . The two treatment groups were statistically matched with regard to age , diagnosis , time of surgery and post-operative drug taking . The results were assessed by the patients on individual report-cards and by the clinician on the control visit . The analgesic effect began at the same time with naproxen-sodium and paracetamol but lasted longer ( over 12 hours ) with naproxen-sodium . During the 12-hour observation period , 43 % of patients on naproxen-sodium refrained from taking an escape drug , as against 23 % of patients on paracetamol , the difference being significant ( alpha = 5 % ) . Complete pain relief was obtained in 41 % of patients under naproxen-sodium and in only 18 % of patients under paracetamol . Two side-effects were noted in the paracetamol group and none in the naproxen-sodium group . In this particular pain model , the analgesic activity of naproxen-sodium proved statistically stronger and more durable than that of paracetamol We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials In a double-blind , r and omised , prospect i ve study of 139 patients undergoing arthroscopic meniscectomy , those receiving a prostagl and in inhibitor ( naproxen sodium ) had significantly less pain , less synovitis and less effusion . They had significantly more rapid return of movement and of quadriceps function ; their return to work and to sport also was significantly faster . It is recommended that , provided there are no contraindications , a prostagl and in inhibitor should be used after arthroscopic procedures Whereas nonsteroidal antiinflammatory drugs augment spinal morphine on Day l , the analgesia gained by simply combining these drugs with conventional “ on request ” oral regimens on Day 2 is less clear . In this trial , we r and omized 80 women undergoing elective cesarean delivery with spinal morphine ( 0.2 mg ) to receive naproxen ( 500 mg ) or placebo every 12 h after surgery . Both groups received conventional therapy with acetaminophen with codeine ( on request ) and rescue IM opioids . Incision pain on sitting ( IPS ) , incision pain at rest , uterine cramping , and gas pain were evaluated with visual analog scales ( 0–100 ) . Worst interval pain ( 0–10 ) , analgesic use , and side effects were measured over 72 h. At 36 h ( primary outcome ) , naproxen use was associated with reductions in IPS ( 38.2 ± 26.0 versus 51.4 ± 25.7;P = 0.05 ) , incision pain at rest , uterine cramping , and worst interval pain scores . Clinical ly modest , statistically significant reductions in IPS ( P = 0.0001 ) and opioid use were found over time ( P < 0.0l ) . Reductions in the incidence of inadequate analgesia and improvements in overall pain relief ( P = 0.0006 ) on Day l did not persist on Day 2 ( overall pain relief , P = 0.057 ; inadequate analgesia , 24 % naproxen versus 27 % controls;P = 1.00 ) . The addition of regular doses of naproxen to conventional oral pain therapy after cesarean delivery leads to reductions in IPS at 36 h and pain over Day 2 but does not reduce the incidence of inadequate analgesia A double-blind evaluation of the clinical effectiveness of a single dose of naproxen , ibuprofen , and acetaminophen was performed on 98 patients who had undergone periodontal surgery . A statistically significant difference was found when the effect of these medications was compared with that of a placebo , but no statistically significant difference was found among these three drugs . No side effects result ed from the use of these medications BACKGROUND Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death . Two regulatory review s in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs . The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery . METHODS This prospect i ve , r and omized multicentre trial evaluated the risks of death , increased surgical site bleeding , gastrointestinal bleeding , acute renal failure , and allergic reactions , with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment . Patients were followed for 30 days after surgery . RESULTS A total of 11,245 patients completed the trial at 49 European hospitals . Of these , 5634 patients received ketorolac and 5611 patients received one of the comparators . 155 patients ( 1.38 % ) had a serious adverse outcome , with 19 deaths ( 0 . 17 % ) , 117 patients with surgical site bleeding ( 1.04 % ) , 12 patients with allergic reactions ( 0.12 % ) , 10 patients with acute renal failure ( 0.09 % ) , and four patients with gastrointestinal bleeding ( 0.04 % ) . There were no differences between ketorolac and ketoprofen or diclofenac . Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac ( odds ratio=2.65 , 95 % CI=1.51 - 4.67 ) and the comparators ( odds ratio=3.58 , 95 % CI=1.93 - 6.70 ) . Other risk factors for serious adverse outcomes were age , ASA score , and some types of surgery ( plastic/ear , nose and throat , gynaecology , and urology ) . CONCLUSION We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery Objective : To compare the overall analgesic effect , including time to onset , peak and duration of effect for etoricoxib 120 mg , a new COX-2 selective inhibitor , in patients with acute pain to that of placebo . Naproxen sodium 550 mg and acetaminophen/codeine 600/60 mg were the active comparators . Methods : A total of 201 patients with moderate to severe pain following surgical extraction of ≥2 third molars , of which at least the m and ibular tooth was impacted , were r and omly allocated to receive single oral doses of placebo ( n = 50 ) , etoricoxib 120 mg ( n = 50 ) , naproxen sodium 550 mg ( n = 51 ) , or acetaminophen/codeine 600/60 mg ( n = 50 ) . The endpoints included total pain relief over 8 hours ( TOPAR8 , primary end point ) , sum of pain intensity difference over 8 hours , patient ’s global evaluation , onset , peak , and duration of analgesia . Results : Etoricoxib 120 mg had a significantly greater least squares ( LS ) mean TOPAR8 score than placebo ( 20.9 vs 5.4 ; P < 0.001 ) and acetaminophen/codeine 600/60 mg ( 20.9 vs 11.5 ; P < 0.001 ) , and a similar LS mean TOPAR8 score to naproxen sodium 550 mg ( 20.9 vs 21.3 ) . All three active treatments had rapid onset of analgesia , median time ~30 minutes . The duration of analgesic effect , defined as median time to rescue medication use , was > 24 hours for etoricoxib , 20.8 hours for naproxen sodium , 3.6 hours for acetaminophen/codeine , and 1.6 hours for placebo . Discussion : Etoricoxib is a new COX-2 selective inhibitor under development for treatment of osteoarthritis , rheumatoid arthritis , and acute pain . In this study , etoricoxib 120 mg provided rapid and long-lasting pain relief to patients with moderate-to-severe postdental surgery pain . Etoricoxib was generally well tolerated & 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 Objective To evaluate the efficacy and tolerability of nimesulide in the relief of postoperative pain after orthopedic surgery compared with naproxen and placebo . Methods In this multicenter , double-blind , double-dummy , r and omized , parallel group study , 94 patients with at least moderate postoperative pain after arthroscopy and meniscectomy were r and omized to receive nimesulide 100 mg b.i.d . , naproxen 500 mg b.i.d . , or placebo for a maximum of 3 days . Results Nimesulide was significantly more effective than placebo for the treatment of postoperative pain , as measured by the primary efficacy variable of summed pain intensity difference within 6 hours after first treatment ( 10.91 vs. 6.29 ) . Furthermore , nimesulide also provided significantly better pain relief than naproxen on this parameter . Overall , nimesulide demonstrated superior analgesic activity compared with naproxen and placebo for the majority of secondary efficacy variables . All 3 treatments were well tolerated , with a lower number of patients reporting adverse events in the nimesulide group . Nimesulide recipients reported no gastrointestinal disorders . Conclusions This study demonstrates that nimesulide is an effective , fast-acting and well-tolerated oral anti-inflammatory drug with a distinct analgesic activity after out-patient orthopedic surgery The aim of this study was to examine the clinical effect of naproxen sodium after knee arthroscopy . The design was r and omized , prospect i ve , and double-blind , with a placebo control group . Patients with preoperative synovial reaction were excluded . One hundred twenty consecutive arthroscopies were performed in 77 men and 43 women , median age 34 ( range 18 - 65 ) years . General anesthesia was used . Ninety-one arthroscopies were operative , whereas 29 were diagnostic . Postoperatively the patients received either 550 mg naproxen sodium twice daily or placebo for 10 days . Patients were given 500 mg acetaminophen to use if needed . Clinical examinations were performed 10 and 20 days postoperation . The results were analyzed using the Mann-Whitney test and chi 2 test . No operative complications were registered . All but two patients completed the study . Six patients had slight gastrointestinal symptoms . At 10 days ' follow-up , in patients who had undergone operative arthroscopy naproxen sodium demonstrated a statistically significant effect on synovial effusion ( p < 0.01 ) , range of motion ( p < 0.001 ) , quadriceps strength ( p < 0.05 ) , pain ( p < 0.001 ) , walking activity ( p < 0.05 ) , and use of crutches ( p < 0.01 ) . In patients who had undergone diagnostic arthroscopy naproxen sodium demonstrated a beneficial effect on pain ( p < 0.01 ) . At 20 days ' follow-up , in the operative group naproxen sodium affected synovial effusion ( p < 0.05 ) , range of motion ( p < 0.01 ) and pain ( p < 0.05 ) , and walking activity ( p < 0.05 ) . No effect was seen in the diagnostic group at 20 days ' follow-up A double-blind , controlled clinical trial is described in which a total of forty hospital in- patients suffering from severe post-operative pain were r and omly allocated to treatment with one of two non-steroidal anti-inflammatory drugs , namely , either indoprofen which has a short half-life ( two hours ) or naproxen which has a long half-life ( thirteen hours ) . The drugs were administered orally on a single-dose-only basis . The doses used in this way were 300 mg of indoprofen or 250 mg of naproxen . Patients scored the severity of their pain on a five-point scale and these scores were recorded prior to and at fixed time intervals up to eight hours following administration of medication . No significant differences emerged between the two test drugs and the duration of the response was also found to be similar for the two compounds despite their very different plasma half-life values The efficacy and safety of the analgesic drug ketorolac tromethamine in the treatment of moderate to very severe postoperative pain was assessed in five dose-ranging studies with single-dose , double-blind , r and omized , parallel-group design s. The drug was administered orally ( 2.5 - 200 mg , 352 patients in three trials ) and intramuscularly ( 5 - 90 mg , 395 patients in two trials ) , and compared with placebo and reference drugs . Patients subjectively evaluated pain intensity and relief using verbal categoric and visual analog scales ; efficacy values included pain intensity difference ( PID ) , summed PID , and total pain relief . Oral ketorolac 10 , 12.5 , 100 , and 200 mg were each statistically significantly superior to placebo in all efficacy measurements , and 10 mg was equivalent to intramuscular morphine 10 mg . Intramuscular ketorolac 90 mg was superior to and 10 and 30 mg were similar to intramuscular morphine 12 mg , and all of these ketorolac doses were superior to intramuscular morphine 6 mg . Intramuscular ketorolac 10 and 30 mg were superior to intramuscular meperidine 50 and 100 mg . Ketorolac was well tolerated , with rates of adverse events generally lower than those of the opiate comparators . Ketorolac doses of 2.5 and 5 mg were less effective than higher doses ; 10 mg or more result ed in faster onset of action and greater peak efficacy ; 90 mg or more gave more prolonged analgesic effects A controlled , r and omized , double-blind crossover study , in which the patients acted as their own controls , was carried out to test the efficacy of naproxen 500 mg x 2 versus acetaminophen 1000 mg x 4 for 3 days on the postoperative course following third molar surgery . Acetaminophen reduced the mean swelling on the 3rd postoperative day by 22.4 % ( p = 0.023 ) compared to that after naproxen . On the 6th postoperative day , there was 20.9 % less mean swelling with naproxen ( p = 0.44 ) , although the total swelling measurements were much less than those measured on the 3rd postoperative day . Summed pain intensity ( SUMPI3.5 - 11 ) on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen regimen with the exception of 0.5 hours ( p = 0.002 ) and 1 hour ( p = 0.009 ) after first medication when acetaminophen gave less pain than naproxen . Since the drug regimens were different , summed PI for the first acetaminophen dose interval ( SUMPI3.5 - 6 ) and the first naproxen dose interval ( SUMPI3.5 - 9 ) was calculated . There was a tendency toward a statistically significant difference in favor of acetaminophen for SUMPI3.5 - 6 ( p = 0.055 ) but no statistically significant difference ( p = 0.41 ) between the treatments with respect to SUMPI3.5 - 9 . Naproxen was statistically superior ( p < or = 0.002 ) to acetaminophen at 08:00 , 12:00 , and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day , when the pain intensity level was lower than that on the day of surgery . A 3-day acetaminophen regimen reduces acute postoperative swelling better than naproxen on the 3rd postoperative day after third molar surgery but not on the 6th postoperative day when the total swelling is less To determine the efficacy of rofecoxib in post-orthopedic surgery pain , we conducted a double-blind , r and omized , placebo- and active-comparator-controlled , parallel-group trial . Two hundred eighteen patients enrolled . Day 1 patients received placebo , rofecoxib 50 mg , or naproxen sodium 550 mg . Days 2 through 5 , the placebo and naproxen sodium groups received placebo , and the rofecoxib group received rofecoxib 25 or 50 mg . Rofecoxib 50 mg was superior to placebo ( P < .05 ) and similar to naproxen sodium for all single-dose measures of pain relief . Days 2 through 5 , the rofecoxib 50 mg group used less supplemental narcotic analgesia ( P = .005 ) and reported less pain on global evaluations ( P = .041 ) when compared with the placebo group ; the efficacy of rofecoxib 25 mg fell between that of placebo and rofecoxib 50 mg for these endpoints ( P < or = .267 ) . Rofecoxib 50 mg once daily effectively treated post-orthopedic surgery pain To establish the relative potency ofnaproxen and aspirinfor oral analgesia , a 4‐point , noncrossover bioassay with placebo control was undertaken with 197 patients . Subjective‐response methods were used to determine two measures of postoperative analgesia over aperiod of 6 hr . With reasonable confidence for an oral analgesic assay , we found 220 mg of naproxen to be equivalent to 600 mg of aspirin for pain relief and 330 mg of naproxen to be equivalent to 600 mg of aspirin for decreased pain intensity The purpose of the study was to evaluate the effect of na-naproxen after diagnostic arthroscopy and arthroscopic surgery of the knee joint . In a double-blind trial , 41 patients were r and omized to treatment with na-naproxen , and 46 patients were given placebo after surgery . For additional analgesia , patients got acetaminophen if necessary . In patients who underwent arthroscopic surgery , there were no differences between those treated with na-naproxen and those who received placebo in pain levels , but patients receiving na-naproxen had significantly less need for additional analgesia and returned significantly more quickly to work than patients receiving placebo ( median 10 versus 30 days ) . In patients who had only diagnostic arthroscopy , there were no differences between the na-naproxen and placebo groups OBJECTIVE To compare the analgesic requirement and pain scores in the postoperative period between closure and nonclosure of the peritoneum in women undergoing gynecological abdominal surgery . METHODS We conducted this study as a 2 parallel grouped , double blind , r and omized , controlled trial between February 2002 and March 2003 . The current study consists of 79 eligible women who were enrolled and completed baseline assessment s. We carried out this study at the Cumhuriyet University Hospital , Sivas , Turkey . RESULTS When the age , gravidity , parity , body mass index , type of surgery , operative time and length of hospital stay were compared , between the 2 groups , no statistically significant difference was found ( p>0.05 ) . The postoperative pain was found higher in the closure group than the nonclosure group ( p<0.05 ) when the pain with visual analogue scale ( VAS ) scores compared . CONCLUSION There was no significant difference in analgesic requirements between the 2 groups in the postoperative period . However , less pain and low VAS scores were evident especially after postoperative 2nd and 48th hours in the nonclosure group . We recommend non-closure of peritoneum at abdominal gynecologic procedure as the method of choice & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale In this r and omized , double-blind , placebo-controlled , multicenter study we assessed the analgesic effect of etoricoxib ( a new cyclooxygenase-2 inhibitor ) in patients having had knee or hip replacement surgery . A total of 228 patients with moderate or severe pain were r and omly allocated within 72 h after surgery to receive etoricoxib 120 mg , controlled-release naproxen sodium 1100 mg , or placebo ( 1:1:1 ) on day 1 followed by etoricoxib and placebo ( 1:2 ) on days 2 to 7 . Patients reported pain scores , rescue ( opioid-combination ) medication use , and the response to study drug . On day 1 , etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h , the primary end-point ; least-squares mean scores were 11.0 , 11.5 , and 5.6 , respectively ( P < 0.001 versus placebo ) . Similarly , a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiv-ing placebo reported good to excellent responses to study drug : 53 % , 60 % , and 26 % respectively . On days 2 - 7 , etoricoxib demonstrated a significant reduction of rescue medication use , 35 % ( P < 0.001 versus placebo ) . The clinical relevance of the decrease was confirmed by Patient ’s Global Evaluation ( P < 0.05 versus placebo ) . Patients receiving etoricoxib also experienced significantly less " worst " and " average " pain than did those on placebo . Etoricoxib was generally well tolerated in this study ; the incidence of adverse experiences was infrequent and similar across treatment groups . In summary , etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days A double-blind cross-over study comparing naproxen 400 mg and acetylsalicylic acid 325 mg with codeine 30 mg ( ASA-C ) was performed in 62 patients suffering severe or moderate pain after dental surgery . A significantly greater analgesic effectiveness was observed with naproxen , with 63 % of patients receiving the drug as first treatment recording successful analgesia while 33 % of patients receiving ASA-C recorded success ( p<0.025 ) . Complaints were mild but frequent with both drugs . No serious side effects were observed Naprelan ( Wyeth-Ayerst Laboratories , Philadelphia , Pennsylvania ) is a novel formulation of naproxen sodium design ed to offer both a rapid onset and a sustained duration of analgesia . Its onset of action was assessed in a double-blind , double-dummy , r and omized , parallel-group study of 129 patients who had just undergone oral surgery to remove impacted third molars . Patients received Naprelan ( 500 mg or 1,000 mg ) , naproxen ( 500 mg ) , codeine ( 30 mg ) , or placebo . Both doses of Naprelan compared favorably with the established Naprosyn ( formulation of naproxen ; Syntex Laboratories , Inc. , Palo Alto , California ) with respect to onset of action , which occurred within 30 minutes in the majority of patients . The relative adverse effect profile showed that both Naprelan doses were as well tolerated as Naprosyn , codeine , and placebo . Pharmacokinetic and pharmacodynamic analysis confirmed the findings of previous Phase I studies in healthy subjects OBJECTIVES To investigate pain relieving efficacy of six agents which are used in postoperative pain management after otolaryngologic operations . PATIENTS AND METHODS 120 adult patients ( 63 females , 57 males ; mean age 36 ; range 18 to 76 years ) were included in the study . The same intraoperative anesthesia was applied to all the patients . The following medications were r and omly given to the patients who declared pain in the sixth hour after the operation : naproxen sodium , meloxicam , rofecoxib , paracetamol , dipyrone , and etodolac in proper dosage to form groups of 20 for each medication . Before and after the application of pain reliever tablets , visual analog scale ( VAS ) and numerical rating scale ( NRS ) were used to inquire whether the agents were effective in relieving pain . ANOVA ( one way ) , paired t-test , Kruskal-Wallis , and Student 's t-test were used as statistical methods . p values < 0.05 were considered to indicate statistical significance . RESULTS All the groups had similar VAS values before medication ( p>0.05 ) . When VAS values of each group were assessed after medication , it was recorded that naproxen sodium ( p=0.020 ) and meloxicam ( p=0.001 ) were effective . When the difference of NRS values between " before medication " and " after medication " was compared among the groups , all the agents significantly changed NRS values , but no inter-group differences were found ( p>0.05 ) . CONCLUSION In terms of NRS scores , the effectiveness of six different analgesic agents which had been used to reduce postoperative pain was confirmed . Moreover , naproxen sodium and meloxicam were found to be more effective than the other agents when taken in the postoperative period for the adult patients according to VAS values |
13,445 | 31,908,858 | Conclusion Proactive case detection may provide promising benefits for child health , but evidence is insufficient to draw conclusions . | Introduction Identifying design features and implementation strategies to optimise community health worker ( CHW ) programmes is important in the context of mixed results at scale .
We systematic ally review ed evidence of the effects of proactive case detection by CHWs in low-income and middle-income countries ( LMICs ) on mortality , morbidity and access to care for common childhood illnesses . | OBJECTIVE To conduct the first rigorous evaluation of the long-term effect of the Comprehensive Rural Health Project on childhood mortality in rural Maharashtra . METHODS Background information and full birth histories were collected by conducting household surveys and interviewing women . Control villages resembling project villages in terms of population size were r and omly selected from an area enclosed by two ellipses centred around , but not including , the project area . An equal number of villages and approximately equal numbers of households and women were r and omly sample d from both areas . Cox models with robust st and ard errors were used to compare the hazard of death among children under 5 years of age in project and control villages . FINDINGS The hazard of death was reduced by 30 % ( 95 % confidence interval , CI : 6 % to 48 % ) after the neonatal period in the project villages compared with control villages after adjustment for caste and religion of subjects and for availability of irrigation in the villages . During the neonatal period there was an increase of 3 % in the hazard of death , but it was not statistically significant ( 95 % CI : -18 % to 29 % ) . CONCLUSION Our methods provide useful tools for evaluating long-running community-based primary health care programmes . Our findings add to the growing debate on the long-term sustainability of community-based interventions design ed to reduce child mortality The adage “ do n’t throw the baby out with the bathwater ” advises us not to discard the essential along with the unessential , whether due to impatience or frustration . 1 This issue of the journal includes reports on prospect i ve evaluations of the integrated community case management ( iCCM ) of childhood illness strategy in Burkina Faso , 2 Ethiopia , 3 and Malawi . 4 iCCM seeks to reduce child mortality by making effective treatment of pneumonia , diarrhea , and malaria available from trained health workers at community level . 5 In this commentary , we show results from the three countries , highlighting hard-won lessons about iCCM ’s potential to prevent unnecessary deaths among children . The independent iCCM evaluations were design ed in 2009– 2010 , as a part of the Catalytic Initiative to Save a Million Lives 6 spearheaded by Canada and involving the Bill & Melinda Gates Foundation , the U.K. Department for International Development , the United Nations Children ’s Fund , the World Health Organization , the Doris Duke Charitable Foundation , and others . The goal of the Catalytic Initiative was to support and measure the impact of strong , coordinated efforts to deliver high-impact interventions to reduce under-five mortality in low-income , high-burden countries , with a particular focus on providing treatment for childhood pneumonia , diarrhea , and malaria at community level using iCCM . The evaluation in each setting was conducted in collaboration with local research institutions , based on a locally adapted version of the common evaluation framework for maternal , newborn , and child health ( MNCH ) . 7 The evaluation design s were built on impact models reflecting the pathway to child survival . Beginning with policy and program inputs , the pathway moves to project implementation and intermediate outputs such as improved provision of quality services , strengthened health systems , and increased utilization . Continuing to coverage and behavioral outcomes , the pathway culminates in impact of under-five and postneonatal mortality . We focus on mortality among children aged 2–59 months here , because the iCCM strategy did not include guidelines for children under 2 months of age . Detailed methods are described in the individual papers ; Table 1 provides a summary . All sites documented program inputs and context ual factors that may have affected program implementation or effectiveness . The evaluation teams shared intermediate and final results with governments and partners as a basis for strengthening iCCM implementation . Selected results across the three countries are shown in Table 2 . We reanalyzed some variables to maximize comparability across countries ; in some instances , results presented here are not included in the series papers . iCCM was not associated with accelerated mortality declines in children aged 2–59 months during the 2- to 4-year evaluation periods in these three setting s. The reasons for this lack of association likely varied across setting s , as does the likelihood that these programs may achieve measureable impact after additional years of sustained implementation . In Burkina Faso , iCCM implementation did not reflect current best practice for design ing and implementing effective MNCH programs . The program relied on community health worker ( CHW ) lay volunteers . The initial training was organized as a “ cascade ” in which representatives from districts were trained and then requested to organize subdistrict-level training sessions to train over 3,000 CHWs in the space of a few months , with minimal support or supervision . The training included written material s even though many of the Objective To determine the effect of implementation of the Integrated Management of Neonatal and Childhood Illness strategy on treatment seeking practice s and on neonatal and infant morbidity . Design Cluster r and omised trial . Setting Haryana , India . Participants 29 667 births in nine intervention clusters and 30 813 births in nine control clusters . Main outcome measures The pre-specified outcome was the effect on treatment seeking practice s. Post hoc exploratory analyses assessed morbidity , hospital admission , post-neonatal infant care , and nutritional status outcomes . Interventions The Integrated Management of Neonatal and Childhood Illness intervention included home visits by community health workers , improved case management of sick children , and strengthening of health systems . Outcomes were ascertained through interviews with r and omly selected caregivers : 6204 , 3073 , and 2045 in intervention clusters and 6163 , 3048 , and 2017 in control clusters at ages 29 days , 6 months , and 12 months , respectively . Results In the intervention cluster , treatment was sought more often from an appropriate provider for severe neonatal illness ( risk ratio 1.76 , 95 % confidence interval 1.38 to 2.24 ) , for local neonatal infection ( 4.86 , 3.80 to 6.21 ) , and for diarrhoea at 6 months ( 1.96 , 1.38 to 2.79 ) and 12 months ( 1.22 , 1.06 to 1.42 ) and pneumonia at 6 months ( 2.09 , 1.31 to 3.33 ) and 12 months ( 1.44 , 1.00 to 2.08 ) . Intervention mothers reported fewer episodes of severe neonatal illness ( risk ratio 0.82 , 0.67 to 0.99 ) and lower prevalence of diarrhoea ( 0.71 , 0.60 to 0.83 ) and pneumonia ( 0.73 , 0.52 to 1.04 ) in the two weeks preceding the 6 month interview and of diarrhoea ( 0.63 , 0.49 to 0.80 ) and pneumonia ( 0.60 , 0.46 to 0.78 ) in the two weeks preceding the 12 month interview . Infants in the intervention clusters were more likely to still be exclusively breast fed in the sixth month of life ( risk ratio 3.19 , 2.67 to 3.81 ) . Conclusion Implementation of the Integrated Management of Neonatal and Childhood Illness programme was associated with timely treatment seeking from appropriate providers and reduced morbidity , a likely explanation for the reduction in mortality observed following implementation of the programme in this study . Trial registration Clinical trials NCT00474981 ; ICMR Clinical Trial Registry CTRI/2009/091/000715 OBJECTIVE To conduct an impact assessment of an intervention to enhance the provision of community-based integrated services for tuberculosis ( TB ) , human immunodeficiency virus ( HIV ) and prevention of mother-to-child transmission ( PMTCT ) . METHODS The intervention consisted of a combination of training of community care workers ( CCWs ) , structural adjustments , harmonisation of scope of practice and stipend of CCWs and enhanced supervision of CCWs to provide comprehensive TB-HIV/PMTCT services in a rural South African district . A before and after study design was used with a household survey to assess the operational effectiveness of the intervention . Six clusters were r and omised into intervention and control arms . Quantitative data were analysed using logistic regression , adjusting for cluster design . RESULTS Logistic regression analyses of the survey data show that CCWs from the intervention arm performed better in the provision of TB-HIV/PMTCT services , such as screening for TB and sexually transmitted infections , adherence to anti-tuberculosis treatment and antiretroviral therapy and counselling on infant feeding compared to the control CCWs ( P < 0.05 ) . However , intervention CCWs performed worse in the integrated management of childhood illnesses education and social welfare referrals ( P < 0.05 ) . The uptake of HIV testing increased significantly in the intervention arm , from 55 % to 78 % ( P < 0.001 ) . CONCLUSION The intervention was effective in enhancing the provision of community-based TB-HIV and PMTCT services . However , attention to other primary health care services is required to ensure that all key services are provided BACKGROUND Evidence suggests that community-based interventions that promote improved home-based practice s and care-seeking behaviour can have a large impact on maternal and child mortality in regions where rates are high . We aim ed to assess whether an intervention package based on the WHO Integrated Management of Childhood Illness h and book and community mobilisation could reduce under-5 mortality in rural Guinea-Bissau , where the health service infrastructure is weak . METHODS We did a non-masked cluster-r and omised controlled trial ( EPICS ) in the districts of Tombali and Quinara in Guinea-Bissau . Clusters of rural villages were stratified by ethnicity and distance from a regional health centre , and r and omly assigned ( 1:1 ) to intervention or control using a computerised r and om number generator . Women were eligible if they lived in one of the clusters at baseline survey prior to r and omisation and if they were aged 15 - 49 years or were primary caregivers of children younger than 5 years . Their children were eligible if they were younger than 5 years or were liveborn after intervention services could be implemented on July 1 , 2008 . In villages receiving the intervention , community health clubs were established , community health workers were trained in case management , and traditional birth attendants were trained to care for pregnant women and newborn babies , and promote facility-based delivery . Registered nurses supervised community health workers and offered mobile clinic services . Health centres were not improved . The control group received usual services . The primary outcome was the proportion of children dying under age 5 years , and was analysed in all eligible children up to final visits to villages between Jan 1 and March 31 , 2011 . This trial is registered with IS RCT N , number IS RCT N52433336 . FINDINGS On Aug 30 , 2007 , we r and omly assigned 146 clusters to intervention ( 73 clusters , 5669 women , and 4573 children ) or control ( 73 clusters , 5840 women , and 4675 children ) . From r and omisation until the end of the trial ( last visit by June 30 , 2011 ) , the intervention clusters had 3093 livebirths and the control clusters had 3194 . 6729 children in the intervention group and 6894 in the control group aged 0 - 5 years on July 1 , 2008 , or liveborn subsequently were analysed for mortality outcomes . 311 ( 4·6 % ) of 6729 children younger than 5 years died in the intervention group compared with 273 ( 4·0 % ) of 6894 in the control group ( relative risk 1·16 [ 95 % CI 0·99 - 1·37 ] ) . INTERPRETATION Our package of community-based interventions did not reduce under-5 mortality in rural Guinea-Bissau . The short timeframe and other trial limitations might have affected our results . Community-based health promotion and basic first-line services in fragile context s with weak secondary health service infrastructure might be insufficient to reduce child deaths . FUNDING Effective Intervention Objective To evaluate the Indian Integrated Management of Neonatal and Childhood Illness ( IMNCI ) programme , which integrates improved treatment of illness for children with home visits for newborn care , to inform its scale-up . Design Cluster r and omised trial . Setting 18 clusters ( population 1.1 million ) in Haryana , India . Participants 29 667 births in intervention clusters and 30 813 in control clusters . Intervention Community health workers were trained to conduct postnatal home visits and women ’s group meetings ; physicians , nurses , and community health workers were trained to treat or refer sick newborns and children ; supply of drugs and supervision were strengthened . Main outcome measures Neonatal and infant mortality ; newborn care practice s. Results The infant mortality rate ( adjusted hazard ratio 0.85 , 95 % confidence interval 0.77 to 0.94 ) and the neonatal mortality rate beyond the first 24 hours ( adjusted hazard ratio 0.86 , 0.79 to 0.95 ) were significantly lower in the intervention clusters than in control clusters . The adjusted hazard ratio for neonatal mortality rate was 0.91 ( 0.80 to 1.03 ) . A significant interaction was found between the place of birth and the effect of the intervention for all mortality outcomes except post-neonatal mortality rate . The neonatal mortality rate was significantly lower in the intervention clusters in the subgroup born at home ( adjusted hazard ratio 0.80 , 0.68 to 0.93 ) but not in the subgroup born in a health facility ( 1.06 , 0.91 to1.23 ) ( P value for interaction=0.001 ) . Optimal newborn care practice s were significantly more common in the intervention clusters . Conclusions Implementation of the IMNCI result ed in substantial improvement in infant survival and in neonatal survival in those born at home . The IMNCI should be a part of India ’s strategy to achieve the millennium development goal on child survival . Trial registration Clinical trials NCT00474981 ; ICMR Clinical Trial Registry CTRI/2009/091/000715 BACKGROUND No satisfactory strategy for reducing high child mortality from malaria has yet been established in tropical Africa . We compared the effect on under-5 mortality of teaching mothers to promptly provide antimalarials to their sick children at home , with the present community health worker approach . METHODS Of 37 tabias ( cluster of villages ) in two districts with hyperendemic to holoendemic malaria , tabias reported to have the highest malaria morbidity were selected . A census was done which included a maternity history to determine under-5 mortality . Tabias ( population 70,506 ) were paired according to under-5 mortality rates . One tabia from each pair was allocated by r and om number to an intervention group and the other was allocated to the control group . In the intervention tabias , mother coordinators were trained to teach other local mothers to recognise symptoms of malaria in their children and to promptly give chloroquine . In both intervention and control tabias , all births and deaths of under-5s were recorded monthly . FINDINGS From January to December 1997 , 190 of 6383 ( 29.8 per 1000 ) children under-5 died in the intervention tabias compared with 366 of 7294 ( 50.2 per 1000 ) in the control tabias . Under-5 mortality was reduced by 40 % in the intervention localities ( 95 % CI from 29.2 - 50.6 ; paired t test , p<0.003 ) . For every third child who died , a structured verbal autopsy was undertaken to ascribe cause of mortality as consistent with malaria or possible malaria , or not consistent with malaria . Of the 190 verbal autopsies , 13 ( 19 % ) of 70 in the intervention tabias were consistent with possible malaria compared with 68 ( 57 % ) of 120 in the control tabias . INTERPRETATION A major reduction in under-5 mortality can be achieved in holoendemic malaria areas through training local mother coordinators to teach mothers to give under-5 children antimalarial drugs We conducted a prospect i ve evaluation of the “ Rapid Scale-Up ” ( RSU ) program in Burkina Faso , focusing on the integrated community case management ( iCCM ) component of the program . We used a quasi-experimental design in which nine RSU districts were compared with seven districts without the program . The evaluation included documentation of program implementation , assessment s of implementation and quality of care , baseline and endline coverage surveys , and estimation of mortality changes using the Lives Saved Tool . Although the program trained large numbers of community health workers , there were implementation shortcomings related to training , supervision , and drug stockouts . The quality of care provided to sick children was poor , and utilization of community health workers was low . Changes in intervention coverage were comparable in RSU and comparison areas . Estimated under-five mortality declined by 6.2 % ( from 110 to 103 deaths per 1,000 live births ) in the RSU area and 4.2 % ( from 114 to 109 per 1,000 live births ) in the comparison area . The RSU did not result in coverage increases or mortality reductions in Burkina Faso , but we can not draw conclusions about the effectiveness of the iCCM strategy , given implementation shortcomings . The evaluation results highlight the need for greater attention to implementation of iCCM programs Background Efforts to improve access to treatment for common illnesses in children less than five years initially targeted malaria alone under the home management of malaria strategy . However under this strategy , children with other illnesses were often wrongly treated with anti-malarials . Integrated community case management of common childhood illnesses is now recommended but its effect on promptness of appropriate pneumonia treatment is unclear . Objectives To determine the effect of integrated malaria and pneumonia management on receiving prompt and appropriate antibiotics for pneumonia symptoms and treatment outcomes as well as determine associated factors . Methods A follow-up study was nested within a cluster-r and omized trial that compared under-five mortality in areas where community health workers ( CHWs ) treated children with malaria and pneumonia ( intervention areas ) and where they treated children with malaria only ( control areas ) . Children treated by CHWs were enrolled on the day of seeking treatment from CHWs ( 609 intervention , 667 control ) and demographic , illness , and treatment seeking information was collected . Further information on illness and treatment outcomes was collected on day four . The primary outcome was prompt and appropriate antibiotics for pneumonia symptoms and the secondary outcome was treatment outcomes on day four . Results Children in the intervention areas were more likely to receive prompt and appropriate antibiotics for pneumonia symptoms compared to children in the control areas ( RR = 3.51 , 95%CI = 1.75 - 7.03 ) . Children in the intervention areas were also less likely to have temperature ≥37.5 ° C on day four ( RR = 0.29 , 95%CI = 0.11 - 0.78 ) . The decrease in fast breathing between day one and four was greater in the intervention ( 9.2 % ) compared to the control areas ( 4.2 % , p-value = 0.01 ) . Conclusions Integrated community management of malaria and pneumonia increases prompt and appropriate treatment for pneumonia symptoms and improves treatment outcomes .Trial registration IS RCT N : IS RCT We conducted a cluster r and omized trial of the effects of the integrated community case management of childhood illness ( iCCM ) strategy on careseeking for and coverage of correct treatment of suspected pneumonia , diarrhea , and malaria , and mortality among children aged 2–59 months in 31 districts of the Oromia region of Ethiopia . We conducted baseline and endline coverage and mortality surveys approximately 2 years apart , and assessed program strength after about 1 year of implementation . Results showed strong iCCM implementation , with iCCM-trained workers providing generally good quality of care . However , few sick children were taken to iCCM providers ( average 16 per month ) . Difference in differences analyses revealed that careseeking for childhood illness was low and similar in both study arms at baseline and endline , and increased only marginally in intervention ( 22.9–25.7 % ) and comparison ( 23.3–29.3 % ) areas over the study period ( P = 0.77 ) . Mortality declined at similar rates in both study arms . Ethiopia 's iCCM program did not generate levels of dem and and utilization sufficient to achieve significant increases in intervention coverage and a result ing acceleration in reductions in child mortality . This evaluation has allowed Ethiopia to strengthen its strategic approaches to increasing population dem and and use of iCCM services Background Development of resistance to first line antimalarials led to recommendation of artemisinin based combination therapies ( ACTs ) . High adherence to ACTs provided by community health workers ( CHWs ) gave reassurance that community based interventions did not increase the risk of drug resistance . Integrated community case management of illnesses ( ICCM ) is now recommended through which children will access both antibiotics and antimalarials from CHWs . Increased number of medicines has been shown to lower adherence . Objective To compare adherence to antimalarials alone versus antimalarials combined with antibiotics under ICCM in children less than five years . Methods A cohort study was nested within a cluster r and omized trial that had CHWs treating children less than five years with antimalarials and antibiotics ( intervention areas ) and CHWs treating children with antimalarials only ( control areas ) . Children were consecutively sample d from the CHWs ' registers in the control areas ( 667 children ) ; and intervention areas ( 323 taking antimalarials only and 266 taking antimalarials plus antibiotics ) . The sample d children were visited at home on day one and four of treatment seeking . Adherence was assessed using self reports and pill counts . Results Adherence in the intervention arm to antimalarials alone and antimalarials plus antibiotics arm was similar ( mean 99 % in both groups ) but higher than adherence in the control arm ( antimalarials only ) ( mean 96 % ) . Forgetfulness ( 38 % ) was the most cited reason for non-adherence . At adjusted analysis : absence of fever ( OR = 3.3 , 95%CI = 1.6–6.9 ) , seeking care after two or more days ( OR = 2.2 , 95%CI = 1.3–3.7 ) , not underst and ing instructions given ( OR = 24.5 , 95%CI = 2.7–224.5 ) , vomiting ( OR = 2.6 , 95%CI = 1.2–5.5 ) , and caregivers ' perception that the child 's illness was not severe ( OR = 2.0 , 95%CI = 1.1–3.8 ) were associated with non-adherence . Conclusions Addition of antibiotics to antimalarials did not lower adherence . However , caregivers should be adequately counseled to underst and the dosing regimens ; continue with medicines even when the child seems to improve ; and re-administer doses that have been vomited Background Malaria is holo-endemic in Burkina Faso and causes approximately 40,000 deaths every year . In 2010 , health authorities scaled up community case management of malaria with artemisinin-based combination therapy . Previous trials and pilot project evaluations have shown that this strategy may be feasible , acceptable , and effective under controlled implementation conditions . However , little is known about its effectiveness or feasibility/acceptability under real-world conditions of implementation at national scale . Methods A panel study was conducted in two health districts of Burkina Faso , Kaya and Zorgho . Three rounds of surveys were conducted during the peak malaria-transmission season ( in August 2011 , 2012 and 2013 ) in a panel of 2,232 r and omly selected households . All sickness episodes in children under five and associated health-seeking practice s were documented . Community health worker ( CHW ) treatment coverage was evaluated and the determinants of consulting a CHW were analysed using multi-level logistic regression . Results In urban areas , less than 1 % of sick children consulted a CHW , compared to 1%–9 % in rural areas . Gaps remained between intentions and actual practice s in treatment-seeking behaviour . In 2013 , the most frequent reasons for not consulting the CHW were : the fact of not knowing him/her ( 78 % in urban areas ; 33 % in rural areas ) ; preferring the health centre ( 23 % and 45 % , respectively ) ; and drug stock-outs ( 2 % and 12 % , respectively ) . The odds of visiting a CHW in rural areas significantly increased with the distance to the nearest health centre and if the household had been visited by a CHW during the previous three months . Conclusions This study shows that CHWs are rarely used in Burkina Faso to treat malaria in children . Issues of implementation fidelity , a lack of adaptation to the local context and problems of acceptability/feasibility might have undermined the effectiveness of community case management of malaria . While some suggest extending this strategy in urban areas , total absence of CHW services uptake in these areas suggest that caution is required . Even in rural areas , treatment coverage by CHWs was considerably less than that reported by previous trials and pilot projects . This study confirms the necessity of evaluating public health interventions under real-world conditions of implementation OBJECTIVES We piloted a community-based proactive malaria case detection model in rural Senegal to evaluate whether this model can increase testing and treatment and reduce prevalence of symptomatic malaria in target communities . METHODS Home care providers conducted weekly sweeps of every household in their village throughout the transmission season to identify patients with symptoms of malaria , perform rapid diagnostic tests ( RDT ) on symptomatic patients and provide treatment for positive cases . The model was implemented in 15 villages from July to November 2013 , the high transmission season . Fifteen comparison villages were chosen from those implementing Senegal 's original , passive model of community case management of malaria . Three sweeps were conducted in the comparison villages to compare prevalence of symptomatic malaria using difference in differences analysis . RESULTS At baseline , prevalence of symptomatic malaria confirmed by RDT for all symptomatic individuals found during sweeps was similar in both sets of villages ( P = 0.79 ) . At end line , prevalence was 16 times higher in the comparison villages than in the intervention villages ( P = 0.003 ) . Adjusting for potential confounders , the intervention was associated with a 30-fold reduction in odds of symptomatic malaria in the intervention villages ( AOR = 0.033 ; 95 % CI : 0.017 , 0.065 ) . Treatment seeking also increased in the intervention villages , with 57 % of consultations by home care providers conducted between sweeps through routine community case management . CONCLUSIONS This pilot study suggests that community-based proactive case detection reduces symptomatic malaria prevalence , likely through more timely case management and improved care seeking behaviour . A r and omised controlled trial is needed to further evaluate the impact of this model BACKGROUND Progress towards MDG4 for child survival in South Africa requires effective prevention of mother-to-child transmission ( PMTCT ) of HIV including increasing exclusive breastfeeding , as well as a new focus on reducing neonatal deaths . This necessitates increased focus on the pregnancy and early post-natal periods , developing and scaling up appropriate models of community-based care , especially to reach the peri-urban poor . METHODS We used a r and omised controlled trial with 30 clusters ( 15 in each arm ) to evaluate an integrated , scalable package providing two pregnancy visits and five post-natal home visits delivered by community health workers in Umlazi , Durban , South Africa . Primary outcomes were exclusive and appropriate infant feeding at 12 weeks post-natally and HIV-free infant survival . RESULTS At 12 weeks of infant age , the intervention was effective in almost doubling the rate of exclusive breastfeeding ( risk ratio 1.92 ; 95 % CI : 1.59 - 2.33 ) and increasing infant weight and length-for-age z-scores ( weight difference 0.09 ; 95 % CI : 0.00 - 0.18 , length difference 0.11 ; 95 % CI : 0.03 - 0.19 ) . No difference was seen between study arms in HIV-free survival . Women in the intervention arm were also more likely to take their infant to the clinic within the first week of life ( risk ratio 1.10 ; 95 % CI : 1.04 - 1.18 ) . CONCLUSIONS The trial coincided with national scale up of ARVs for PMTCT , and this could have diluted the effect of the intervention on HIV-free survival . We have demonstrated that implementation of a pro-poor integrated PMTCT and maternal , neonatal and child health home visiting model is feasible and effective . This trial could inform national primary healthcare reengineering strategies in favour of home visits . The dose effect on exclusive breastfeeding is notable as improving exclusive breastfeeding has been resistant to change in other studies targeting urban poor families OBJECTIVE To describe a participatory approach to implement and evaluate ways to integrate and train community care workers ( CCWs ) to enhance collaborative TB/HIV/PMTCT activities , and home-based HIV counseling and testing ( HCT ) at community level . METHODS The intervention study was conducted in Sisonke , a rural district of KwaZulu Natal , South Africa . A baseline household ( HH ) survey was conducted in 11 villages . Six villages were r and omly selected into intervention and control clusters . Training was provided first to CCWs from the intervention cluster ( IC ) followed by the control cluster ( CC ) . Routine monthly data from CCWs were collected from March-December 2010 . The data was subjected to bivariate tests . RESULTS The baseline HH survey revealed that of 3012 HH members visited by CCWs in 2008 , 21 % were screened for TB symptoms , 7 % were visited for TB adherence support and 2 % for ART adherence , and 1.5 % were counselled on infant feeding options . A total of 89 CCWs were trained . Data show that during the study period in IC , 684 adults were offered HCT by CCWs , 92 % accepted HCT and tested and 7 % tested HIV-positive and were referred to the clinic for further care . Of 3556 adults served in IC , 44 % were screened for TB symptoms and 32 % for symptoms of sexually transmitted infections ( STIs ) and 37 % of children were traced as TB contact . Out of 6226 adults served in CC , 10 % were screened for TB symptoms and 7 % for STI symptoms . The differences in uptake of services between IC and CC were statistically significant ( p<0.05 ) . CONCLUSION The findings of this study suggest higher uptake of TB and STI symptoms screening , TB contact tracing and home based HCT in the intervention clusters . This study suggests that up-skilling CCWs could be one avenue to enhance TB/HIV case finding , TB contact tracing and linkages to care |
13,446 | 27,348,228 | Conclusion : Even when utilizing a stroke screening tool , the accuracy of stroke recognition by emergency dispatchers was suboptimal . | Background : Emergency dispatchers represent the first point of contact for patients activating an acute stroke response .
Accurate dispatcher stroke recognition is associated with faster emergency medical services response time ; however , stroke is often unrecognized during initial emergency calls .
Stroke screening tools such as the Cincinnati Prehospital Stroke Scale have been shown to improve on-scene stroke recognition and thus have been proposed as a means to improve dispatcher accuracy .
We conducted a systematic review of the accuracy of emergency dispatcher stroke recognition when employing stroke screening tools . | Background and Purpose — Recent innovations such as CT installation in ambulances may lead to earlier start of stroke-specific treatments . However , such technically complex mobile facilities require effective methods of correctly identifying patients before deployment . We aim ed to develop and vali date a new dispatcher identification algorithm for stroke emergencies . Methods — Dispatcher identification algorithm for stroke emergencies was informed by systematic qualitative analysis of the content of emergency calls to ambulance dispatchers for patients with stroke or transient ischemic attack ( N=117 ) and other neurological ( N=39 ) and nonneurological ( N=51 ) diseases ( Part A ) . After training of dispatchers , sensitivity and predictive values were determined prospect ively in patients admitted to Charité hospitals by using the discharge diagnosis as reference st and ard ( Part B ) . Results — Part A : Dysphasic/dysarthric symptoms ( 33 % ) , unilateral symptoms ( 22 % ) and explicitly stated suspicion of stroke ( 47 % ) were typically identified in patients with stroke but infrequently in nonstroke cases ( all < 10 % ) . Convulsive symptoms ( 41 % ) were frequent in other neurological diseases but not strokes ( 3 % ) . Pain ( 26 % ) and breathlessness ( 31 % ) were often expressed in nonneurological emergencies ( 6 % and 7 % in strokes ) . Part B : Between October 15 and December 16 , 2010 , 5774 patients were admitted by ambulance with 246 coded with final stroke diagnoses . Sensitivity of dispatcher identification algorithm for stroke emergencies for detecting stroke was 53.3 % and positive predictive value was 47.8 % for stroke and 59.1 % for stroke and transient ischemic attack . Of all 275 patients with stroke dispatcher codes , 215 ( 78.5 % ) were confirmed with neurological diagnosis . Conclusions — Using dispatcher identification algorithm for stroke emergencies , more than half of all patients with stroke admitted by ambulance were correctly identified by dispatchers . Most false-positive stroke codes had other neurological diagnoses Purpose — The aim of this guideline is to provide a focused up date of the current recommendations for the endovascular treatment of acute ischemic stroke . When there is overlap , the recommendations made here supersede those of previous guidelines . Methods — This focused up date analyzes results from 8 r and omized , clinical trials of endovascular treatment and other relevant data published since 2013 . It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations . Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council ’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee . Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process . Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence . Prerelease review of the draft guideline was performed by 6 expert peer review ers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee . Results — Evidence -based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment , for the endovascular procedure , and for systems of care to facilitate endovascular treatment . Conclusions — Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke . Systems of care should be organized to facilitate the delivery of this care Background and Purpose — Emergency medical dispatchers play an important role in optimizing stroke care if they are able to accurately identify calls regarding acute cerebrovascular disease . This study was undertaken to assess the diagnostic accuracy of the current national protocol guiding dispatcher question ing of 911 callers to identify stroke ( QA Guide version 11.1 of the National Academy Medical Priority Dispatch System ) . Methods — We identified all Los Angeles Fire Department paramedic transports of patients to University of California Los Angeles Medical Center during the 12-month period from January to December 2005 in a prospect ively maintained data base . Dispatcher-assigned Medical Priority Dispatch System codes for each of these patient transports were abstract ed from the paramedic run sheets and compared to final hospital discharge diagnosis . Results — Among 3474 transported patients , 96 ( 2.8 % ) had a final diagnosis of stroke or transient ischemic attack . Dispatchers assigned a code of potential stroke to 44.8 % of patients with a final discharge diagnosis of stroke or TIA . Dispatcher identification of stroke showed a sensitivity of 0.41 , specificity of 0.96 , positive predictive value of 0.45 , and negative predictive value of 0.95 . Conclusions — Dispatcher recognition of stroke calls using the widely employed Medical Priority Dispatch System algorithm is suboptimal , with failure to identify more than half of stroke patients as likely stroke . Revisions to the current national dispatcher structured interview and symptom identification algorithm for stroke may facilitate more accurate recognition of stroke by emergency medical dispatchers OBJECTIVE Early stroke recognition optimizes patients ' opportunities to benefit from therapeutic options . Prehospital stroke recognition is suboptimal . If 9 - 1 - 1 dispatchers used stroke- identification tools , prehospital stroke recognition might occur more rapidly and accurately . The Cincinnati Prehospital Stroke Scale ( CPSS ) is a brief , effective tool used by emergency medical services and hospital personnel to identify stroke . The study 's goal was to determine whether laypersons could be instructed to use the CPSS over the telephone . METHODS Adult visitors ( laypersons ) to a tertiary care emergency department were enrolled . Using a mock patient , laypersons were instructed to use the CPSS via telephone by an investigator simulating a 9 - 1 - 1 dispatcher . The patient r and omly portrayed clinical ly normal and abnormal patient types . The layperson 's ability to convey CPSS instructions to the patient and relay findings to the investigator was scored . RESULTS Seventy laypersons were enrolled ( 35 each for normal and abnormal patient types ) . Average age was 48 years , 63 % were female , and 40 % never attended college . Facial droop and speech instructions were administered with 100 % accuracy . Arm drift instructions were administered with 99 % accuracy . Layperson accuracies for interpreting findings were 93 % for facial droop , 93 % for arm drift , and 97 % for speech . Overall , stroke symptoms were detected with 94 % sensitivity ( 95 % CI 87 , 100 ) and 83 % specificity ( 95 % CI 70 , 95 ) . CONCLUSION Laypersons correctly administered and interpreted the CPSS when directed to do so over the telephone by a trained investigator . These findings suggest that the CPSS may be a useful tool in early prehospital detection of stroke by dispatchers BACKGROUND A number of emergency medical services ( EMSs ) performance measures for stroke have been proposed to promote early stroke recognition and rapid transportation to definitive care . This study examined performance measure compliance among EMS-transported stroke patients and the relationship between compliance and in-hospital stroke response . METHODS Eight quality indicators were derived from American Stroke Association guidelines . A prospect i ve cohort of consecutive , EMS-transported patients discharged from 2 large Midwestern stroke centers with a diagnosis of acute ischemic stroke was identified . Data were abstract ed from hospital and EMS records . Compliance with 8 prehospital quality indicators was calculated . Univariate and multivariable logistic regression analysis were performed to measure the association between prehospital compliance and a binary outcome of door-to-computed tomography ( CT ) time less than or equal to 25 minutes . RESULTS Over the 12 month study period , 186 EMS-transported ischemic stroke patients were identified . Compliance was highest for prehospital documentation of a glucose level ( 86.0 % ) and stroke screen ( 78.5 % ) and lowest for on-scene time less than or equal to 15 minutes ( 46.8 % ) , hospital prenotification ( 56.5 % ) , and transportation at highest priority ( 55.4 % ) . After adjustment for age , time from symptom onset , and stroke severity , transportation at highest priority ( odds ratio [ OR ] , 13.45 ) and hospital prenotification ( OR , 3.75 ) were both associated with significantly faster door-to-CT time . No prehospital quality metric was associated with tissue-plasminogen activator delivery . CONCLUSIONS EMS transportation at highest priority and hospital prenotification were associated with faster in-hospital stroke response and represent logical targets for EMS quality improvement efforts |
13,447 | 25,735,803 | Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocol s for HNSCC has a significant positive correlation with survival . | BACKGROUND The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocol s for nonmetastatic head and neck squamous cell carcinoma ( HNSCC ) has not been determined . | BACKGROUND To know the effectiveness and tolerance of weekly cisplatin added to radiotherapy ( RT ) in advanced carcinoma of oropharynx and nasopharynx . PATIENTS AND METHODS Stage II-IV cancer patients were r and omly assigned to either radical RT , 70 Gy/35 fractions over 7 weeks ( RT arm ) , or chemoradiotherapy ( CRT ) , cisplatin 40 mg/m² weekly for seven doses plus RT . Primary end points were ( i ) the responses , ( ii ) toxicity profile , and ( iii ) overall survival ( OS ) in two groups . Study period was from June 2003 to July 2005 . RESULTS One hundred and fifty-three patients were r and omly allocated to the study , 76 in RT arm and 77 in CRT arm . Seventy-one in each arm completed the planned treatment ; complete response ( CR ) : 67.1 % versus 80.5 % in RT and CRT arms ( P = 0.04 ) . Grade III and IV toxicity were 16 % and 40 % in RT and CRT arms , respectively ( P = 0.01 ) . There were frequent treatment interruptions ( 9.3 % versus 28.9 % ; P = 0.003 ) and hospitalization ( 20 % versus 40.8 % ) in the CRT group . OS was superior in the CRT arm ( P = 0.02 ) : 27 months [ 95 % confidence interval ( CI ) 15.2 - 36.8 ] for RT versus not reached for CRT . Three-year OS was 42 % for RT and 62 % for CRT group . CRT and CR were independent prognostic factors . CONCLUSION This trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone result ing in higher OS 5555 Background : In loco-regionally advanced head and neck squamous cell cancer ( HNSCC ) , concurrent 3-weekly cisplatin improves the overall survival ( OS ) of patients compared to radiotherapy ( RT ) alone , but is often associated with renal toxicity . METHODS Retrospective analysis of treatment outcome and nephrotoxicity frequency of intensity-modulated radiotherapy ( IMRT ) associated with either 3-weekly ( 100 mg/m2 on day 1 , 22 , 43 ) or weekly cisplatin ( 40 mg/m2 on day 1 , 8 , 15 , 22 , 29 , 36 , 43 ) in 94 patients with stage III/IV HNSCC . RESULTS Patients treated with weekly cisplatin ( N=40 ) were significantly older ( median age 65 vs. 58 years , p=0.0014 ) and received a significantly lower total cisplatin dose ( median 186 mg/m2 vs. 228 mg/m2 , p=0.0002 ) and these differences have likely contributed to the clinical outcome . At a median follow up of 2.8 years , the median progression-free survival ( PFS ) was 1.5 years with weekly and 2.1 years with 3-weekly cisplatin ( p= 0.47 ) . OS was significantly longer ( 4.3 vs. 1.9 years , p= 0.041 ) in patients treated with the 3-weekly regimen ( N=54 ) ; indeed cisplatin doses > 360 mg total or > 240 mg/m2 were associated with better OS but not better PFS . At univariate analysis , a history of alcohol abuse and /or smoking was associated with worse PFS ( p=0.013 ) . Multivariate analysis confirmed the impact of alcohol and smoking habits on both PFS and OS , while the treatment schedule only affected OS . Acute renal failure rate was 35 % with the weekly and 54 % with the 3-weekly regime ( p=0.07 ) ; chronic renal failure rate was 5 % and 30 % , respectively ( p=0.04 ) . No patient required renal replacement therapy . CONCLUSIONS Both schedules can be combined to IMRT , but weekly cisplatin is less nephrotoxic . PFS was not significantly different despite patients treated with the weekly schedule being significantly older and under-treated . The study suggests that cisplatin schedule may not be relevant when combined to IMRT . Controlled prospect i ve studies are needed to compare the clinical activity of different cisplatin schedules in combination with IMRT Background The aim of this study was to compare the outcomes of postoperative adjuvant concomitant chemoradiotherapy using two different schedules of cisplatin for patients with high-risk oral squamous cell carcinoma ( OSCC ) . Methods From Feb. 2008 to Aug. 2010 , 55 patients with high-risk OSCC were included in this study . Patients were r and omized into treatment groups that either received 100 mg/m2 cisplatin once every 3 weeks ( arm A ) or 40 mg/m2 cisplatin once per week ( arm B ) . All patients were irradiated with 66 Gy in 33 fractions . Results Of the 50 eligible patients , 26 were assigned to arm A , and 24 were assigned to arm B. Both groups of patients received the same mean doses of radiotherapy and cisplatin . However , 88.5 % of patients in arm A and 62.5 % of those in arm B ( p = 0.047 ) received ≥ 200 mg/m2 of cisplatin in total . The overall toxicity was significantly greater in arm B ( p = 0.020 ) , and all of the grade 4 toxicities occurred in patients in arm B. Conclusions Three-weekly high-dose cisplatin treatment showed higher compliance , and lower acute toxicity compared to weekly low-dose cisplatin treatment PURPOSE Although p16 protein expression , a surrogate marker of oncogenic human papillomavirus ( HPV ) infection , is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma ( OPSCC ) , its prevalence and significance have not been well established in cancer of the oral cavity , hypopharynx , or larynx , collectively referred as non-OPSCC , where HPV infection is less common than in the oropharynx . PATIENTS AND METHODS p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies were determined by immunohistochemistry ( IHC ) and in situ hybridization ( ISH ) . Hazard ratios from Cox models were expressed as positive or negative , stratified by trial , and adjusted for clinical characteristics . RESULTS p16 expression was positive in 14.1 % ( 12 of 85 ) , 24.2 % ( 23 of 95 ) , and 19.0 % ( 27 of 142 ) and HPV ISH was positive in 6.5 % ( six of 93 ) , 14.6 % ( 15 of 103 ) , and 6.9 % ( seven of 101 ) of non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies , respectively . Hazard ratios for p16 expression were 0.63 ( 95 % CI , 0.42 to 0.95 ; P = .03 ) and 0.56 ( 95 % CI , 0.35 to 0.89 ; P = .01 ) for progression-free ( PFS ) and overall survival ( OS ) , respectively . Comparing OPSCC and non-OPSCC , patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC , but patients with p16-negative OPSCC and non-OPSCC have similar outcomes . CONCLUSION Similar to results in patients with OPSCC , patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC , and HPV may also have a role in outcome in a subset of non-OPSCC . However , further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting PURPOSE Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months , the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head- and -neck carcinomas . With a minimum of 10 years of follow-up potentially now available for all patients , these results are up date d here to examine long-term outcomes . METHODS AND MATERIAL S A total of 410 analyzable patients who had high-risk resected head- and -neck cancers were prospect ively r and omized to receive either radiation therapy ( RT : 60 Gy in 6 weeks ) or identical RT plus cisplatin , 100 mg/m(2)i.v . on days 1 , 22 , and 43 ( RT + CT ) . RESULTS At 10 years , the local-regional failure rates were 28.8 % vs 22.3 % ( P=.10 ) , disease-free survival was 19.1 % vs 20.1 % ( P=.25 ) , and overall survival was 27.0 % vs 29.1 % ( P=.31 ) for patients treated by RT vs RT + CT , respectively . In the unplanned subset analysis limited to patients who had microscopically involved resection margins and /or extracapsular spread of disease , local-regional failure occurred in 33.1 % vs 21.0 % ( P=.02 ) , disease-free survival was 12.3 % vs 18.4 % ( P=.05 ) , and overall survival was 19.6 % vs 27.1 % ( P=.07 ) , respectively . CONCLUSION At a median follow-up of 9.4 years for surviving patients , no significant differences in outcome were observed in the analysis of all r and omized eligible patients . However , analysis of the subgroup of patients who had either microscopically involved resection margins and /or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy . The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT Background The dominant pattern of failure for squamous cell carcinoma of head and neck remains loco-regional , although distant metastases are now being increasingly documented . Radical radiotherapy with concurrent chemotherapy is contemporary st and ard of care in the non-surgical management of these loco-regionally advanced cancers , based on large r and omized controlled trials utilizing high-dose cisplatin ( 80–100 mg/m2 ) cycled every three-weekly during definitive radiotherapy . Although efficacious , this is associated with high acute morbidity necessitating intensive supportive care with attendant re source implication s. The aim of this retrospective study was to assess the efficacy and acute toxicity of an alternative schedule i.e. concurrent weekly cisplatin-based radical radiotherapy and it 's potential to be an optimal regimen in advanced head and neck cancers . Methods Outcome data of patients with Stage III & IV head and neck squamous cell carcinoma , excluding nasopharynx , planned for radical radiotherapy ( 66–70 Gy ) with concurrent weekly cisplatin ( 30 mg/m2 ) treated in a single unit between 1996–2004 was extracted . Results The data set consisted of 264 patients with a median age of 54 years . The median radiotherapy dose was 70 Gy ( range 7.2–72 Gy ) and median number of chemotherapy cycles was 6 ( range 1–7 ) . Two-thirds ( 65 % ) of patients received ≥85 % of planned cisplatin dose . With a mean follow-up of 19 months , the 5-year local control ; loco-regional control ; and disease free survival was 57 % ; 46 % ; and 43 % respectively . Acute grade 3 or worse mucositis and dermatitis was seen in 77 ( 29 % ) and 92 ( 35 % ) patients respectively , essentially in patients receiving doses ≥66 Gy and 6 or more cycles of chemotherapy . Other toxicities ( hematologic , nausea and vomiting ) were mild and self-limiting . Overall , the acute toxicity of this concurrent weekly chemo-radiation regimen though mildly increased did not m and ate intensive supportive care . Stage grouping , primary site , and intensity of treatment were significant predictors of loco-regional control and disease free survival . Conclusion Radical radiotherapy with concurrent weekly cisplatin has moderate efficacy and acceptable acute toxicity with potential to be an optimal regimen in loco-regionally advanced squamous cell carcinoma of the head and neck , particularly in limited-re source setting s. Stage grouping , primary site , and treatment intensity are important determinants of outcome BACKGROUND We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer . METHODS After undergoing surgery with curative intent , 167 patients were r and omly assigned to receive radiotherapy alone ( 66 Gy over a period of 6 1/2 weeks ) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area on days 1 , 22 , and 43 of the radiotherapy regimen . RESULTS After a median follow-up of 60 months , the rate of progression-free survival was significantly higher in the combined-therapy group than in the group given radiotherapy alone ( P=0.04 by the log-rank test ; hazard ratio for disease progression , 0.75 ; 95 percent confidence interval , 0.56 to 0.99 ) , with 5-year Kaplan-Meier estimates of progression-free survival of 47 percent and 36 percent , respectively . The overall survival rate was also significantly higher in the combined-therapy group than in the radiotherapy group ( P=0.02 by the log-rank test ; hazard ratio for death , 0.70 ; 95 percent confidence interval , 0.52 to 0.95 ) , with five-year Kaplan-Meier estimates of overall survival of 53 percent and 40 percent , respectively . The cumulative incidence of local or regional relapses was significantly lower in the combined-therapy group ( P=0.007 ) . The estimated five-year cumulative incidence of local or regional relapses ( considering death from other causes as a competing risk ) was 31 percent after radiotherapy and 18 percent after combined therapy . Severe ( grade 3 or higher ) adverse effects were more frequent after combined therapy ( 41 percent ) than after radiotherapy ( 21 percent , P=0.001 ) ; the types of severe mucosal adverse effects were similar in the two groups , as was the incidence of late adverse effects . CONCLUSIONS Postoperative concurrent administration of high-dose cisplatin with radiotherapy is more efficacious than radiotherapy alone in patients with locally advanced head and neck cancer and does not cause an undue number of late complications BACKGROUND Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the st and ard alternative to total laryngectomy for patients with locally advanced laryngeal cancer . The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown . METHODS We r and omly assigned patients with locally advanced cancer of the larynx to one of three treatments : induction cisplatin plus fluorouracil followed by radiotherapy , radiotherapy with concurrent administration of cisplatin , or radiotherapy alone . The primary end point was preservation of the larynx . RESULTS A total of 547 patients were r and omly assigned to one of the three study groups . The median follow-up period was 3.8 years . At two years , the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin ( 88 percent ) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy ( 75 percent , P=0.005 ) or radiotherapy alone ( 70 percent , P<0.001 ) . The rate of locoregional control was also significantly better with radiotherapy and concurrent cisplatin ( 78 percent , vs. 61 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 56 percent with radiotherapy alone ) . Both of the chemotherapy-based regimens suppressed distant metastases and result ed in better disease-free survival than radiotherapy alone . However , overall survival rates were similar in all three groups . The rate of high- grade toxic effects was greater with the chemotherapy-based regimens ( 81 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 82 percent with radiotherapy with concurrent cisplatin , vs. 61 percent with radiotherapy alone ) . The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of the other two treatments during radiotherapy . CONCLUSIONS In patients with laryngeal cancer , radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control PURPOSE The Head and Neck Intergroup conducted a phase III r and omized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer . PATIENTS AND METHODS Eligible patients were r and omly assigned between arm A ( the control ) , single daily fractionated radiation ( 70 Gy at 2 Gy/d ) ; arm B , identical radiation therapy with concurrent bolus cisplatin , given on days 1 , 22 , and 43 ; and arm C , a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy , 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle . Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and , if necessary , as salvage therapy on all three treatment arms . Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test . RESULTS Between 1992 and 1999 , 295 patients were entered on this trial . This did not meet the accrual goal of 362 patients and result ed in premature study closure . Grade 3 or worse toxicity occurred in 52 % of patients enrolled in arm A , compared with 89 % enrolled in arm B ( P < .0001 ) and 77 % enrolled in arm C ( P < .001 ) . With a median follow-up of 41 months , the 3-year projected overall survival for patients enrolled in arm A is 23 % , compared with 37 % for arm B ( P = .014 ) and 27 % for arm C ( P = not significant ) . CONCLUSION The addition of concurrent high-dose , single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival , although it also increases toxicity . The loss of efficacy result ing from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery PURPOSE To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and /or node-positive nonmetastatic carcinomas of the head and neck , compared with hyperfractionated radiotherapy alone . PATIENTS AND METHODS From July 1994 to July 2000 , 224 patients with squamous cell carcinomas of the head and neck ( excluding nasopharynx and paranasal sinus ) were r and omly assigned to hyperfractionated radiotherapy ( median dose , 74.4 Gy ; 1.2 Gy twice daily ) or the same radiotherapy combined with two cycles of concomitant cisplatin ( 20 mg/m2 on 5 days of weeks 1 and 5 ) . The primary end point was time to any treatment failure ; secondary end points were locoregional failure , metastatic relapse , overall survival , and late toxicity . RESULTS There was no difference in radiotherapy between both treatment arms ( 74.4 Gy in 44 days ) . The full cisplatin dose was applied in 93 % and 71 % of patients during the first and second treatment cycles , respectively . Acute toxicity was similar in both arms . Median time to any treatment failure was not significantly different between treatment arms ( 19 months for combined treatment and 16 months for radiotherapy only , respectively ) and the failure-free rate at 2.5 years was 45 % and 33 % , respectively . Locoregional control and distant disease-free survival were significantly improved with cisplatin ( log-rank test , P = .039 and .011 , respectively ) . The difference in overall survival did not reach significance ( log-rank test , P = .147 ) . Late toxicity was comparable in both treatment groups . CONCLUSION The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin PURPOSE To report the final results of a prospect i ve r and omized trial that aim ed to evaluate efficacy and toxicity of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV squamous cell carcinoma of the head and neck and histological evidence of extracapsular spread of tumor in lymph node metastase(s ) . METHODS AND MATERIAL S Radiotherapy was delivered using a daily dose of 1.7 Gy for the first 54 Gy and 1.8 to 2 Gy until the completion of the treatment . Cisplatin 50 mg i.v . with forced hydratation was given or not every week ( i.e. , seven to nine cycles ) concurrently with radiotherapy . A total of 44 patients were treated by irradiation only ( RT group ) and 39 by irradiation with chemotherapy ( CM group ) . RESULTS The RT group displayed a higher rate of loco-regional failures as compared to CM group ( 41 vs. 23 % ; p = 0.08 ) . The overall survival , the survival corrected for deaths by intercurrent disease , and the disease-free survival were better in CM group as compared to RT group with statistically significant differences . Survival without loco-regional treatment failure was better in the CM group , the difference being close to the level of significance ( p = 0.05 ) . Survival without distant metastases were comparable in the two therapeutic groups . Ten severe late complications were observed , four in the RT group ( 17 % ) and six in the CM group ( 22 % ) . Cox univariate analysis confirmed the importance of the therapeutic modality in predicting the overall survival , the survival corrected for deaths by intercurrent disease , and the disease-free survival . CONCLUSIONS The present final report of this phase III study confirms preliminary results . The concomitant use of 50 mg weekly Cisplatin infusion and postoperative radiation improved loco-regional control and survival . No significant increase of late radiation complications was observed in the CM group To determine toxicity and response , escalating dose levels of carboplatin were given simultaneously with accelerated radiation to 36 previously untreated patients with unresectable squamous cell carcinomas of the head and neck ( SCCHN ) ( 2 with stage III and 34 with stage IV disease ) . Twenty-three patients received a total radiation dose of 58.8 Gy with two daily fractions of 2.1 Gy on days 1 through 4 in weeks 1 , 2 , and 5 and on two additional days in week 6 . Simultaneous carboplatin was given intravenously at escalating dose levels : 20 mg/m2 in 3 patients , 30 mg/m2 in 5 patients , 40 mg/m2 in 5 patients , 50 mg/m2 in 6 patients , and 60 mg/m2 in 4 patients . Another 13 patients were treated with an escalated radiation dose of 67.2 Gy , which result ed in 2 more days of radiochemotherapy in week 6 . Six patients in this group received 60 mg/m2/d and 7 received 50 mg/m2/d carboplatin . All patients were evaluable for toxicity according to World Health Organization ( WHO ) criteria and 35 of 36 patients were evaluable for response . Dose-limiting toxicity was myelosuppression with WHO grade s 3 and 4 leukopenia in 5 of 6 patients treated with 60 mg/m2 carboplatin and 67.2 Gy . With radiochemotherapy doses of 67.2 Gy and 50 mg/m2 , no grade 4 myelosuppression occurred and toxicity was generally tolerable . Independent of the carboplatin dose , mucositis grade 3 or 4 was seen in 12 patients . No other toxicities above WHO grade 2 occurred , except in 2 patients with grade 3 nausea and vomiting . There were 19 complete responses ( 53 % ) and 16 partial responses ( 44 % ) . Our preliminary data suggest that 50 mg/m2 carboplatin together with a total radiation dose of 67.2 Gy might be the best combination for advanced , unresectable SCCHN Thirty-two patients with locally advanced head and neck cancer have been treated with concurrent weekly carboplatin and conventional radiation therapy ( RT ) ( 2 Gy fractions 4 - 5 days/week to a total dose of 64 - 70 Gy over 7 - 8 weeks ) in a Phase I/II study . Carboplatin was administered weekly during RT at doses of 75 - 150 mg/m2/wk as a 1-hour infusion . The maximum tolerated dose of carboplatin was 130 mg/m2/wk , with myelosuppression , predominantly neutropenia , being dose limiting . Other systemic toxicities were insignificant and no overlapping toxicity was evident . Ultimate locoregional control and survival probabilities were disappointing . It is suggested that either further studies using radiation and carboplatin at the dose 130 mg/m2/wk , or variations on dose and scheduling be performed prior to the instigation of Phase III studies A prospect i ve clinical trial was design ed to evaluate efficacy , toxicity , and patient compliance of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV S.C.C. of the head and neck and histological evidence of extra-capsular spread of tumor in lymph node metastase(s ) . Cisplatin 50 mg IV with forced hydration was given or not every week ( i.e. , 7 to 9 cycles ) concurrently with radiotherapy . Between 1984 and 1988 , 83 patients were r and omized : 44 were treated by irradiation without chemotherapy ( RT group ) and 39 by the combined modality ( CM group ) . There was no significant difference between the two groups in terms of patient characteristics , primary sites , tumor differentiation , T.N. stages , or postoperative prognostic factors . All patients completed the planned radiotherapy . There were seven severe toxicities ( greater than grade 3 ) in the RT group . In the CM group , 30 severe toxicities occurred in 16/39 ( 41 % ) patients but none was life-threatening . Seven of 39 ( 18 % ) patients received less than two-thirds of the scheduled Cisplatin courses because of intolerance , mainly nausea and vomiting . Preliminary results show a better disease-free survival for the CM group ( 65 % at 24 months ) than for the RT group ( 41 % at 24 months ) . This significant difference is largely due to increased loco-regional control in the CM group ( 79 % vs 59 % ) , the actuarial distant metastasis rates in patients controlled above the clavicles not being statistically different in the two groups BACKGROUND The current st and ard treatment for locoregionally advanced nasopharyngeal carcinoma ( NPC ) was conventional-fractionation radiotherapy plus concurrent-adjuvant chemotherapy as recommended by the Intergroup-0099 Study . This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors . METHODS Eligible patients with stage III-IVB non-keratinizing NPC were r and omly assigned to radiotherapy-alone ( RT(i ) group : 218 patients ) or chemoradiotherapy ( CRT(i ) group : 223 patients ) using cisplatin ( 100mg/m(2 ) ) for three cycles in concurrence with radiotherapy , followed by cisplatin ( 80 mg/m(2 ) ) plus fluorouracil ( 1000 mg/m(2)/day for 4 days ) for three cycles . The median follow-up was 6.1 years . FINDINGS Comparison by intention-to-treat showed that the CRT(i ) group achieved significant improvement in overall failure-free rate ( FFR ) , locoregional-FFR and cancer-specific survival ( p ≤ 0.019 ) ; but the improvements for distant-FFR and overall survival ( OS ) were statistically insignificant ( p ≥ 0.14 ) . Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS ( CRT(a ) versus RT(a ) group : 72 % versus 63 % at 5-year , p=0.037 ) . Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS , while that of fluorouracil during the adjuvant phase was significant for distant-FFR . The 5-year locoregional-FFR for patients who received 0 - 1 , 2 and 3 concurrent cycles were 79 % , 88 % and 88 % , respectively ; the corresponding distant-FFR by adjuvant cycles were 68 % , 78 % and 77 % , respectively . INTERPRETATION Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC . The concurrent phase is important for locoregional control and survival , cisplatin 200mg/m(2 ) in two concurrent cycles might be adequate . Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control PURPOSE To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91 - 11 study evaluating the contribution of chemotherapy added to radiation therapy ( RT ) for larynx preservation . PATIENTS AND METHODS Patients with stage III or IV glottic or supraglottic squamous cell cancer were r and omly assigned to induction cisplatin/fluorouracil ( PF ) followed by RT ( control arm ) , concomitant cisplatin/RT , or RT alone . The composite end point of laryngectomy-free survival ( LFS ) was the primary end point . RESULTS Five hundred twenty patients were analyzed . Median follow-up for surviving patients is 10.8 years . Both chemotherapy regimens significantly improved LFS compared with RT alone ( induction chemotherapy v RT alone : hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.59 to 0.95 ; P = .02 ; concomitant chemotherapy v RT alone : HR , 0.78 ; 95 % CI , 0.78 to 0.98 ; P = .03 ) . Overall survival did not differ significantly , although there was a possibility of worse outcome with concomitant relative to induction chemotherapy ( HR , 1.25 ; 95 % CI , 0.98 to 1.61 ; P = .08 ) . Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT ( HR , 0.58 ; 95 % CI , 0.37 to 0.89 ; P = .0050 ) and over RT alone ( P < .001 ) , whereas induction PF followed by RT was not better than treatment with RT alone ( HR , 1.26 ; 95 % CI , 0.88 to 1.82 ; P = .35 ) . No difference in late effects was detected , but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy ( 30.8 % v 20.8 % with induction chemotherapy and 16.9 % with RT alone ) . CONCLUSION These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS . Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone . New strategies that improve organ preservation and function with less morbidity are needed Between January 1988 and December 1991 , 159 patients with Stage III/IV ( M0 ) squamous cell carcinoma of the head and neck were r and omized to receive st and ard fraction RT ( 70 Gy ) ( group I ) or the same RT plus either 6 mg/m2 of cisplatin ( CDPP ) ( group II ) or 25 mg/ m2 of carboplatin ( CBDCA ) both given daily during RT ( group III ) . Patients in groups II and III had significantly higher overall response rates then those in group I ( P = 0.011 and P = 0.0025 , respectively ) with no difference between groups II and III ( P = 0.60 ) . They also had significantly longer median survival time ( MST ) and higher 5-year survival rates than those in group I ( MST , 32 months ( 32 % ) and 30 months ( 29 % ) versus 16 months ( 15 % ) , respectively ; P = 0.011 and P = 0.019 , respectively ) , with no difference between the two RT/CHT groups . Median time to local recurrence ( MTLR ) and 5-year local recurrence-free survival ( LRFS ) were significantly higher for both RT/CHT when compared to RT alone ( MTLR , not attained yet and 30 months versus 10 months , respectively ; 5-year LRFS , 51 % and 48 % versus 27 % , respectively ; P = 0.018 and P = 0.040 , respectively ) with no difference between the two RT/CHT groups . There was no difference between the three treatment groups regarding regional lymph node and distant metastasis control . Apart from acute high grade ( > or =3 ) hematological toxicity that was significantly more frequent in the two RT/CHT groups and no different between the two RT/CHT groups , other acute high grade toxicity was similar between the three treatment groups . Late high grade toxicity was infrequent and similar between the three treatment groups BACKGROUND Despite the use of resection and postoperative radiotherapy , high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed . We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control . METHODS Between September 9 , 1995 , and April 28 , 2000 , 459 patients were enrolled . After undergoing total resection of all visible and palpable disease , 231 patients were r and omly assigned to receive radiotherapy alone ( 60 to 66 Gy in 30 to 33 fractions over a period of 6 to 6.6 weeks ) and 228 patients to receive the identical treatment plus concurrent cisplatin ( 100 mg per square meter of body-surface area intravenously on days 1 , 22 , and 43 ) . RESULTS After a median follow-up of 45.9 months , the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone ( hazard ratio for local or regional recurrence , 0.61 ; 95 percent confidence interval , 0.41 to 0.91 ; P=0.01 ) . The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group , as compared with 72 percent in the radiotherapy group . Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group ( hazard ratio for disease or death , 0.78 ; 95 percent confidence interval , 0.61 to 0.99 ; P=0.04 ) , but overall survival was not ( hazard ratio for death , 0.84 ; 95 percent confidence interval , 0.65 to 1.09 ; P=0.19 ) . The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group ( P<0.001 ) . Four patients who received combined therapy died as a direct result of the treatment . CONCLUSIONS Among high-risk patients with resected head and neck cancer , concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival . However , the combined treatment is associated with a substantial increase in adverse effects In an attempt to improve local control of locally advanced head and neck cancer , radiation therapy was combined with cisplatin . Forty-eight patients entered into this study . All patients were irradiated with a 60Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck . Cisplatin was administered at a dose of 100 mg/m2 on days 2 , 22 and 42 . Thirty-seven ( 80 % ) patients received the total radiation dose as initially planned . Thirty-four ( 72 % ) patients achieved complete and 5 ( 10 % ) partial response . Grade 3 - 4 toxicities included vomiting ( 14 % ) , stomatitis ( 4 % ) , diarrhea ( 2 % ) , myelotoxicity ( 14 % ) , hoarseness ( 4 % ) , dysphagia ( 30 % ) , weight loss ( 32 % ) , nephrotoxicity ( 4 % ) and dermatitis ( 2 % ) . After a median follow-up of 26 ( range , 18 - 33 ) months , 16 patients have died . Among the 35 complete responders 6 later on relapsed . Median relapse-free survival has not yet been reached . Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned PURPOSE Primary chemoradiotherapy in patients with advanced laryngeal cancer can achieve high rates of organ preservation without sacrificing survival compared with radiation alone or conventional laryngectomy . Appropriate selection of patients for organ preservation approaches could enhance overall treatment outcome and quality of life . We conducted a phase II organ preservation trial for patients with stage III and IV larynx cancer to determine whether late salvage surgery rates could be decreased and survival improved by selecting patients for organ preservation based on response to a single cycle of induction chemotherapy . PATIENTS AND METHODS The chemotherapy was cisplatin 100 mg/m2 on day 1 and fluorouracil 1,000 mg/m(2)/d for 5 days . Patients who achieved less than 50 % response had immediate laryngectomy . Patients who achieved more than 50 % response went on to concurrent chemoradiotherapy . Histologic complete responders after chemoradiotherapy received two more cycles of chemotherapy . Patients with residual disease after chemoradiotherapy had planned salvage surgery . RESULTS Of 97 eligible patients , 73 ( 75 % ) achieved more than 50 % response and received chemoradiotherapy . A total of 29 patients ( 30 % ) had salvage surgery ; 19 patients ( 20 % ) had early salvage surgery after the single cycle of induction chemotherapy , three patients ( 3 % ) had late salvage surgery after chemoradiotherapy , six patients ( 6 % ) eventually had salvage surgery for recurrence , and one patient had laryngectomy for chondroradionecrosis . The median follow-up time was 41.9 months . The overall survival rate at 3 years is 85 % . The cause-specific survival rate was 87 % . Larynx preservation was achieved in 69 patients ( 70 % ) . CONCLUSION These results confirm excellent larynx preservation and improved overall survival rates compared with historical results The primary objective of the present r and omized phase III trial was to compare the 3-yr survival rate of patients treated with st and ard fractionated radiotherapy ( RT ) alone or with the same RT concomitantly with cisplatin ( DDP ) or carboplatin ( Cb ) . From January 1995 until July 1999 , 124 patients with histologically proven locally advanced non-nasopharyngeal head and neck cancer ( HNC ) were r and omized to receive either RT monotherapy ( 70Gy , Group A ) or the same RT concomitantly with DDP ( 100 mg/m2 on d 2 , 22 , 42 , Group B ) or Cb ( 7 AUC on d 2 , 22 , 42 , Group C ) . There were no significant differences in complete response rates between patients treated with RT alone or combined chemoradiotherapy . However , median time to progression ( TTP ) and overall survival ( OS ) were significantly longer in patients treated with concomitant chemoradiotherapy . Thus , median TTP was 6.3 , 45.2 , and 17.7 mo in groups A , B , and C respectively ( p=0.0002 ) . Similarly , median OS was 12.2 , 48.6 , and 24.5 mo , respectively ( p=0.0003 ) . At 3 yr follow-up , 17.5 % of patients in group A were alive compared to 52 % in group B and 42 % in group C ( p<0.001 ) . Patients treated with concomitant chemoradiotherapy experienced more frequently severe hematological toxicity . Also , severe nausea/vomiting was more pronounced in group B , as expected . The present study clearly demonstrated that concomitant chemoradiotherapy with platinum analogs significantly prolongs 3-yr survival and median OS in patients with locally advanced HNC compared to conventional RT alone BACKGROUND Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma ( HNSCC ) . We aim ed to assess the efficacy and safety of a combination of these approaches . METHODS In our open-label phase 3 r and omised trial , we enrolled patients with locally advanced , stage III and IV ( non-metastatic ) HNSCC and an Eastern Cooperative Oncology Group performance status of 0 - 2 . We r and omly allocated patients central ly with a computer program ( with centre , T stage , N stage , and localisation as minimisation factors ) in a 1:1:1 ratio to receive conventional chemoradiotherapy ( 70 Gy in 7 weeks plus three cycles of 4 days ' concomitant carboplatin-fluorouracil ) , accelerated radiotherapy-chemotherapy ( 70 Gy in 6 weeks plus two cycles of 5 days ' concomitant carboplatin-fluorouracil ) , or very accelerated radiotherapy alone ( 64·8 Gy [ 1·8 Gy twice daily ] in 3·5 weeks ) . The primary endpoint , progression-free survival ( PFS ) , was assessed in all enrolled patients . This trial is completed . The trial is registered with Clinical Trials.gov , number NCT00828386 . FINDINGS Between Feb 29 , 2000 , and May 9 , 2007 , we r and omly allocated 279 patients to receive conventional chemoradiotherapy , 280 to accelerated radiotherapy-chemotherapy , and 281 to very accelerated radiotherapy . Median follow-up was 5·2 years ( IQR 4·9 - 6·2 ) ; rates of chemotherapy and radiotherapy compliance were good in all groups . Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy ( HR 1·02 , 95 % CI 0·84 - 1·23 ; p=0·88 ) or very accelerated radiotherapy ( 0·83 , 0·69 - 1·01 ; p=0·060 ) ; conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy ( 0·82 , 0·67 - 0·99 ; p=0·041 ) . 3-year PFS was 37·6 % ( 95 % CI 32·1 - 43·4 ) after conventional chemoradiotherapy , 34·1 % ( 28·7 - 39·8 ) after accelerated radiotherapy-chemotherapy , and 32·2 % ( 27·0 - 37·9 ) after very accelerated radiotherapy . More patients in the very accelerated radiotherapy group had RTOG grade 3 - 4 acute mucosal toxicity ( 226 [ 84 % ] of 268 patients ) compared with accelerated radiotherapy-chemotherapy ( 205 [ 76 % ] of 271 patients ) or conventional chemoradiotherapy ( 180 [ 69 % ] of 262 ; p=0·0001 ) . 158 ( 60 % ) of 265 patients in the conventional chemoradiotherapy group , 176 ( 64 % ) of 276 patients in the accelerated radiotherapy-chemotherapy group , and 190 ( 70 % ) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment ( p=0·045 ) . INTERPRETATION Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy can not compensate for the absence of chemotherapy . We noted the most favourable outcomes for conventional chemoradiotherapy , suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules . FUNDING French Ministry of Health BACKGROUND AND PURPOSE Concurrent chemoradiotherapy ( CRT ) confers survival benefit over radiotherapy ( RT ) alone in the treatment of locoregionally advanced nasopharyngeal carcinoma ( NPC ) . This study explored the prognostic significance of the total dose of cisplatin delivered during CRT . MATERIAL S AND METHODS A retrospective analysis was performed in patients with stage II to IVB NPC ( AJCC 6th edition ) who participated in 3 prospect i ve studies . All patients received cisplatin at a fixed dose of 40 mg/m(2)/week during a 6 - 7-weeks course of CRT . Chi-square test was used in the univariate analysis . Relationship between prognostic factors , the total dose of cisplatin administered and time-to-event endpoints were analyzed with the Cox Hazards model . RESULTS Two hundred and forty-one patients were identified with the following stage distribution : Stage II=13.7 % , III=45.2 % , IV=41.1 % . The median total number of cycles of cisplatin administered per patient was 5 cycles ( range 1 - 8 cycles ) . At a median follow-up of 56.5 months ( range 4.2 - 200.2 months ) , 93 patients ( 38.6 % ) had relapsed and 85 patients ( 35.2 % ) died . For all patients , the total number of cycles of cisplatin delivered was significantly associated with survival in the univariate but not the multivariate analysis . In a sub-group analysis of 142 patients with stage II and III NPC , patients who received more than 5 cycles of cisplatin had significantly better overall survival than those who did not ( hazard ratio 0.44 ; 95 % confidence interval , 0.23 - 0.85 ; p=0.02 ) . CONCLUSION Number of cycles of cisplatin delivered is an independent prognostic factor in patients with stage II-III NPC undergoing CRT with weekly cisplatin Detailed information about how patients with head and neck carcinoma ( HNC ) are treated across practice setting s does not exist . The authors conducted a prospect i ve , observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses : 1 ) There is no difference in the pattern of care between community and academic setting s ; and 2 ) the results of major r and omized clinical trials will change the pattern of care in both practice setting s within 1 year of publication in peer‐ review ed journals PURPOSE To investigate whether the addition of cisplatin ( CDDP ) to hyperfractionation ( Hfx ) radiation therapy ( RT ) offers an advantage over the same Hfx RT given alone in locally advanced ( stages III and IV ) squamous cell carcinoma of the head and neck . PATIENTS AND METHODS One hundred thirty patients were r and omized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks ( group I , n = 65 ) or the same Hfx RT and concurrent low-dose ( 6 mg/m(2 ) ) daily CDDP ( group II , n = 65 ) . RESULTS Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone ( 68 % v 49 % at 2 years and 46 % v 25 % at 5 years ; P = .0075 ) . It also offered higher progression-free survival ( 46 % v 25 % at 5 years ; P = .0068 ) , higher locoregional progression-free survival ( LRPFS ) ( 50 % v 36 % at 5 years ; P = .041 ) , and higher distant metastasis-free survival ( DMFS ) ( 86 % v 57 % at 5 years ; P = .0013 ) . However , there was no difference between the two treatment groups in the incidence of either acute or late high- grade RT-induced toxicity . Hematologic high- grade toxicity was more frequent in group II patients . CONCLUSION As compared with Hfx RT alone , Hfx RT and concurrent low-dose daily CDDP offered a survival advantage , as well as improved LRPFS and DMFS |
13,448 | 28,809,653 | Strong evidence indicates that person-centered approaches can improve behavior .
Moderate evidence supports noise regulation , environmental design , unobtrusive visual barriers , and environmental relocation strategies to reduce problematic behaviors .
Evidence is insufficient for the effectiveness of mealtime ambient music , bright light , proprioceptive input , w and er gardens , optical strategies , and sensory devices in improving behavior or reducing w and ering and falls . | This systematic review evaluated the effectiveness of environment-based interventions that address behavior , perception , and falls in the home and other setting s for people with Alzheimer ’s disease ( AD ) and related major neurocognitive disorders ( NCDs ) . | Long-term effects of multisensory stimulation were assessed using a “ Snoezelen ” room on older residents with dementia . Thirty patients were r and omly assigned to 3 groups : multisensory stimulation environment ( MSSE ) group , individualized activities ( activity ) group , and control group . The MSSE and activity groups participated in two 30-minute weekly individualized intervention sessions over 16 weeks . Pre- , mid- , posttrial , and 8-week follow-up behavior , mood , cognitive , and functional impairment in basic activities of daily living were registered . Items included in the physically nonaggressive behavior factor improved significantly in post- versus pretrial in the MSSE group compared to the activity group , with no significant differences between MSSE and control groups . The MSSE and activity groups demonstrated behavior improvements and higher scores on the Cohen-Mansfield agitation inventory , verbal agitated behavior factor , and Neuropsychiatric Inventory – Nursing Home , with no significant differences between groups . The MSSE could have long-term positive effects on such neuropsychiatric symptoms in older people with dementia CONTEXT Optimal treatment to postpone functional decline in patients with dementia is not established . OBJECTIVE To test a nonpharmacologic intervention realigning environmental dem and s with patient capabilities . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve 2-group r and omized trial ( Care of Persons with Dementia in their Environments [ COPE ] ) involving patients with dementia and family caregivers ( community-living dyads ) recruited from March 2006 through June 2008 in Pennsylvania . INTERVENTIONS Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits ; obtained blood and urine sample s ; and trained families in home safety , simplifying tasks , and stress reduction . Control group caregivers received 3 telephone calls and educational material s. MAIN OUTCOME MEASURES Functional dependence , quality of life , frequency of agitated behaviors , and engagement for patients and well-being , confidence using activities , and perceived benefits for caregivers at 4 months . RESULTS Of 284 dyads screened , 270 ( 95 % ) were eligible and 237 ( 88 % ) r and omized . Data were collected from 209 dyads ( 88 % ) at 4 months and 173 ( 73 % ) at 9 months . At 4 months , compared with controls , COPE patients had less functional dependence ( adjusted mean difference , 0.24 ; 95 % CI , 0.03 - 0.44 ; P = .02 ; Cohen d = 0.21 ) and less dependence in instrumental activities of daily living ( adjusted mean difference , 0.32 ; 95 % CI , 0.09 - 0.55 ; P = .007 ; Cohen d = 0.43 ) , measured by a 15-item scale modeled after the Functional Independence Measure ; COPE patients also had improved engagement ( adjusted mean difference , 0.12 ; 95 % CI , 0.07 - 0.22 ; P = .03 ; Cohen d = 0.26 ) , measured by a 5-item scale . COPE caregivers improved in their well-being ( adjusted mean difference in Perceived Change Index , 0.22 ; 95 % CI , 0.08 - 0.36 ; P = .002 ; Cohen d = 0.30 ) and confidence using activities ( adjusted mean difference , 0.81 ; 95 % CI , 0.30 - 1.32 ; P = .002 ; Cohen d = 0.54 ) , measured by a 5-item scale . By 4 months , 64 COPE dyads ( 62.7 % ) vs 48 control group dyads ( 44.9 % ) eliminated 1 or more caregiver-identified problems ( chi(2/1 ) = 6.72 , P = . 01 ) . CONCLUSION Among community-living dyads , a nonpharmacologic biobehavioral environmental intervention compared with control result ed in better outcomes for COPE dyads at 4 months . Although no group differences were observed at 9 months for patients , COPE caregivers perceived greater benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00259454 CONTEXT Cognitive decline , mood , behavioral and sleep disturbances , and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers . Circadian rhythm disturbances have been associated with these symptoms . OBJECTIVE To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system : bright light and melatonin . DESIGN , SETTING , AND PARTICIPANTS A long-term , double-blind , placebo-controlled , 2 x 2 factorial r and omized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherl and s ; mean ( SD ) age , 85.8 ( 5.5 ) years ; 90 % were female and 87 % had dementia . INTERVENTIONS R and om assignment by facility to long-term daily treatment with whole-day bright ( + /- 1000 lux ) or dim ( + /- 300 lux ) light and by participant to evening melatonin ( 2.5 mg ) or placebo for a mean ( SD ) of 15 ( 12 ) months ( maximum period of 3.5 years ) . MAIN OUTCOME MEASURES St and ardized scales for cognitive and noncognitive symptoms , limitations of activities of daily living , and adverse effects assessed every 6 months . RESULTS Light attenuated cognitive deterioration by a mean of 0.9 points ( 95 % confidence interval [ CI ] , 0.04 - 1.71 ) on the Mini-Mental State Examination or a relative 5 % . Light also ameliorated depressive symptoms by 1.5 points ( 95 % CI , 0.24 - 2.70 ) on the Cornell Scale for Depression in Dementia or a relative 19 % , and attenuated the increase in functional limitations over time by 1.8 points per year ( 95 % CI , 0.61 - 2.92 ) on the nurse-informant activities of daily living scale or a relative 53 % difference . Melatonin shortened sleep onset latency by 8.2 minutes ( 95 % CI , 1.08 - 15.38 ) or 19 % and increased sleep duration by 27 minutes ( 95 % CI , 9 - 46 ) or 6 % . However , melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale , both for positive affect ( -0.5 points ; 95 % CI , -0.10 to -1.00 ) and negative affect ( 0.8 points ; 95 % CI , 0.20 - 1.44 ) . Melatonin also increased withdrawn behavior by 1.02 points ( 95 % CI , 0.18 - 1.86 ) on the Multi Observational Scale for Elderly Subjects scale , although this effect was not seen if given in combination with light . Combined treatment also attenuated aggressive behavior by 3.9 points ( 95 % CI , 0.88 - 6.92 ) on the Cohen-Mansfield Agitation Index or 9 % , increased sleep efficiency by 3.5 % ( 95 % CI , 0.8%-6.1 % ) , and improved nocturnal restlessness by 1.00 minute per hour each year ( 95 % CI , 0.26 - 1.78 ) or 9 % ( treatment x time effect ) . CONCLUSIONS Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia . To counteract the adverse effect of melatonin on mood , it is recommended only in combination with light . TRIAL REGISTRATION controlled-trials.com/is rct n Identifier : IS RCT N93133646 Background / Aims : Behavioural and psychological symptoms ( BPSD ) are frequent in people with Alzheimer ’s disease and cause considerable stress to patients and their carers . Antipsychotics have been widely used as a first-line treatment , result ing in an estimated 1,800 excess strokes and 1,600 excess deaths in the UK alone . Safe and effective alternatives are urgently needed . Based upon preliminary evidence from clinical trials , aromatherapy with melissa oil may be such an alternative , but initial studies have been modest in size , and adequate blinding has been problematic . Our objective was to assess the efficacy of melissa aromatherapy in the treatment of agitation in people with Alzheimer ’s disease in an adequately powered and robustly blinded r and omized controlled trial comparing it with donepezil , an anticholinesterase drug used with some benefit to treat BPSD . Methods and Findings : The study was a double-blind parallel-group placebo-controlled r and omized trial across 3 specialist old age psychiatry centres in Engl and . Participants had probable or possible Alzheimer ’s disease , were resident in a care home , had clinical ly significant agitation ( defined as a score of 39 or above on the Cohen Mansfield Agitation Inventory ) and were free of antipsychotics and /or anticholinesterase for at least 2 weeks . Participants were allocated to 1 of 3 groups : placebo medication and active aromatherapy ; active medication and placebo aromatherapy or placebo of both . Main Outcome : The primary outcome measure was reduction in agitation as assessed by the Pittsburgh Agitation Scale ( PAS ) at 4 weeks . This is an observational scale , and raters were required to wear nose clips to ensure that full blinding was maintained . The PAS , Neuropsychiatric Inventory ( NPI ; another measure of BPSD ) and other outcome measures were completed at baseline , 4-week and 12-week follow-ups . 114 participants were r and omized , of whom 94 completed the week 4 assessment and 81 completed the week 12 assessment . Aromatherapy and donepezil were well tolerated . There were no significant differences between aromatherapy , donepezil and placebo at week 4 and week 12 , but importantly there were substantial improvements in all 3 groups with an 18 % improvement in the PAS and a 37 % improvement in the NPI over 12 weeks . Conclusion : When assessed using a rigorous design which ensures blinding of treatment arms , there is no evidence that melissa aromatherapy is superior to placebo or donepezil , in the treatment of agitation in people with Alzheimer ’s disease . However , the sizeable improvement in the placebo group emphasizes the potential non-specific benefits of touch and interaction in the treatment of agitation in people with Alzheimer ’s disease OBJECTIVES A series of pre clinical studies have suggested that selective serotonin reuptake inhibitor antidepressants not only stimulate neurogenesis but also have neuroprotective effects . The present study primarily aim ed to investigate whether escitalopram would decelerate the brain atrophy of patients with mild-to-moderate Alzheimer 's disease ( AD ) . We also assessed the effects of escitalopram on the cognitive function and neuropsychiatric symptoms of these participants . METHODS Seventy-four probable AD patients without major depression were recruited from four dementia clinics of university hospitals and r and omly assigned in a 1:1 ratio . Each group received 20 mg/day of escitalopram or placebo for 52 weeks . The primary outcome measures were the change rates of hippocampal and whole brain volume on magnetic resonance imaging for 52 weeks . The Alzheimer 's Disease Assessment Scale-cognitive subscale , Mini-Mental State Examination , Neuropsychiatric Inventory , and Cornell Scale for Depression in Dementia ( CSDD ) were also applied . RESULTS We did not find any significant differences in the changes of hippocampal or whole brain volume between the groups . Escitalopram showed significant beneficial effects on the CSDD score at 28 weeks compared with placebo ( t = -2.17 , df = 50.42 , p = 0.035 ) , but this finding did not persist throughout the study . CONCLUSION The findings of the present study do not support the role of escitalopram as a progression-delaying treatment for AD . However , the negative results of the present trial should be interpreted cautiously because of the relatively small sample size . Further large-scale escitalopram trials targeting the earlier stages of AD , even prodromal AD , are still needed . Copyright © 2015 John Wiley & Sons , Objective : To assess the impact and the social rating of an active music condition ( in which 10 patients with Alzheimer 's disease regulated their music input ) vs. a passive music condition . Method : In the active condition , the patients used a simple h and response and a microswitch to activate music stimulation periods . In the passive condition , music stimulation was prearranged and continued through the sessions . The active and passive stimulation sessions were preceded and followed by control ( non-stimulation ) sessions . Results : The active condition sessions showed an increase in the patients ’ indices of positive participation ( e.g. , singing or music-related movements , and smiles ) similar to that observed in the passive condition sessions . Social raters ( 140 psychology students ) favored the active condition on a six-item question naire dealing , among others , with conditions ’ suitability , respect of patients ’ dignity and independence , and practicality . Conclusion : An active music stimulation condition can be viable , effective , and socially preferable BACKGROUND Agitation is common in people with dementia , is distressing to patients and stressful to their carers . Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate . Alternatives to drug treatment for agitation should be sought . The study aim ed to assess the effects of bright light therapy on agitation and sleep in people with dementia . METHODS A single center r and omized controlled trial of bright light therapy versus st and ard light was carried out . The study was completed prior to the m and atory registration of r and omized controls on the clinical trials registry data base and , owing to delays in writing up , retrospective registration was not completed . RESULTS There was limited evidence of reduction in agitation in people on active treatment , sleep was improved and a suggestion of greater efficacy in the winter months . CONCLUSIONS Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated OBJECTIVE To explore the impact of personal attributes , environmental attributes , and the presentation of 9 categories of stimuli on agitation in nursing home residents with dementia . METHOD Participants in this r and omized , controlled , observational cross-sectional study were 193 residents of 7 nursing homes , all with a diagnosis of dementia , for whom we obtained data pertaining to cognitive functioning ( via the Mini-Mental State Examination ) , performance of activities of daily living ( Minimum Data Set ) , and role-identity/activities of past interest ( Self-Identity Question naire ) . Environmental attributes ( eg , noise , lighting ) and direct observations of agitation ( primary outcome ) were recorded via the Agitation Behavior Mapping Inventory . Engagement was measured using the Observational Measurement of Engagement . Both agitation and engagement were assessed for each stimulus ( including a control condition ) . RESULTS Univariate findings ( ie , for 1 explanatory variable at a time ) showed agitation to be related to several personal attributes -- ie , female gender was related to verbal agitation ( P < .0001 ) ; low cognitive function was related to total , verbal , and physical agitation ( P < .001 for each ) ; low performance of activities of daily living was significantly related to all types of agitation ( P < .01 for total agitation and P < .05 for each type of agitation ) ; and unclear speech was significantly related to total agitation ( P < .01 ) . Eight of the 9 stimulus categories were significantly related to decreased levels of agitation , with ORs ranging from 0.37 ( live human stimuli , P < .001 ) to 0.79 ( inanimate social stimuli , P < .05 ) . Higher levels of engagement were related to lower levels of agitation ( P < .001 for total agitation ) . In the multivariate analyses , higher cognitive function ( P < .001 ) , male gender ( P < .05 ) , level of engagement with stimuli ( eg , duration of engagement for 3 minutes or longer , P < .05 ) , and all 9 stimulus categories , with the exception of music , were independently predictive of lower levels of agitation ( P < .001 ) . CONCLUSIONS The finding that both type of stimuli and engagement level with the stimuli were significant predictors of agitation underscores the importance of engagement as a determinant of agitation levels Thirteen older persons ( seven men and six women ) in residential care participated as subjects in this study . All participants had histories of confusion due to dementia and were identified by staff as being consistently resistant to medication administration as indicated by vocal outbursts , moving away , or physical combativeness . Subjects were exposed to four aroma interventions during medication administration : 1 ) lavender vera ( lavendula officinalis ) ; 2 ) sweet orange ( citrus aurantium ) ; 3 ) tea tree ( malaleuca alternifolia ) ; and 4 ) no aroma ( control ) . All medication administrations were videotaped for later data collection . Observers were trained to record frequency and duration of resistive behaviors during medication administration in all four interventions for each subject . Reliability between two observers was extremely high . Results showed no statistically significant differences across all aroma conditions for either resistive behavior or duration of administration . Also , there were no statistically significant differences based on gender . This study indicates that aromatherapy does not reduce combative , resistive behaviors in individuals with dementia . Research with a larger sample in future studies may yield other results Background : Alzheimer 's disease ( AD ) is known to increase the risk of falls . We aim to determine the effectiveness of home-based technologies coupled with teleassistance service ( HBTec-TS ) in older people with AD . Methods : A study of falls and the HBTec-TS system ( with a light path combined with a teleassistance service ) was conducted in the community . The 96 subjects , drawn from a r and om population of frail elderly people registered as receiving an allocation for lost autonomy from the county , were aged 65 or more and had mild-to-moderate AD with 1 year of follow-up ; 49 were in the intervention group and 47 in the control group . Results : A total of 16 ( 32.7 % ) elderly people fell in the group with HBTec-TS versus 30 ( 63.8 % ) in the group without HBTec-TS . The use of HBTec-TS was significantly associated with a reduction in the number of indoor falls among elderly people with mild-to-moderate AD ( OR = 0.37 , 95 % CI = 0.15 - 0.88 , p = 0.0245 ) . Conclusion : The use of the HBTec-TS significantly reduced the incidence of primary indoor falling needing GP intervention or attendance at an emergency room among elderly people with AD and mild-to-moderate dementia |
13,449 | 22,068,286 | CONCLUSIONS Exercise has modest positive effects on depressive symptoms with larger effects for programs that were supervised or partially supervised , not conducted at home , and at least 30 minutes in duration .
IMPACT Our results complement other studies showing that exercise is associated with reduced pain and fatigue and with improvements in quality of life among cancer survivors | BACKGROUND Depression is a distressing side effect of cancer and its treatment .
In the general population , exercise is an effective antidepressant .
OBJECTIVE We conducted a systematic review and meta- analysis to determine the antidepressant effect of exercise in cancer survivors . | PURPOSE / OBJECTIVES To evaluate the effects of 10 weeks of aerobic exercise on depressive and anxiety symptoms and self-esteem of breast cancer survivors . DESIGN Experimental , crossover . SETTING Midwestern university town . SAMPLE Twenty-four breast cancer survivors ( mean time following surgery 41.8 months ; ranging from 1 to 99 months ) recruited via mail and cancer support groups . The mean age of the sample was 48.9 years . METHODS Subjects were assigned r and omly into exercise ( EX ) , exercise-plus-behavior modification ( EX + BM ) , and control groups . EX and EX + BM groups exercised aerobically four days/week at > or = 60 % of age-predicted maximum heart rate for 10 weeks . Data were collected pretest , post-test , and crossover ( 12 weeks following post-test ) . Because pretest or post-test scores showed no statistical differences between EX and EX + BM groups , data were combined to form one group . MAIN RESEARCH VARIABLES Aerobic exercise ( four days/ week ; 30 - 40 minutes/session ) , depression , ( Beck Depression inventory ) , anxiety ( Speilberger State-Trait Anxiety Inventory ) , and self-esteem ( Rosenberg Self-Esteem Inventory ) . FINDINGS Pre- to post-test analyses revealed that women who exercised had significantly less depression and state and trait anxiety over time compared to controls . After the crossover , the control group demonstrated comparable improvements in both depressive and state anxiety scores . Self-esteem did not change significantly . Subjects who received exercise recommendations from their physicians exercised significantly more than subjects who received no recommendation . CONCLUSIONS Mild to moderate aerobic exercise may be of therapeutic value to breast cancer survivors with respect to depressive and anxiety symptoms but not to self-esteem . A physician 's recommendation to exercise appears to be an important factor in a patient 's exercise adherence . IMPLICATION S FOR NURSING PRACTICE To Improve depressive and anxiety symptoms following breast cancer surgery , healthcare professionals should consider recommending mild to moderate exercise Goals of workProstate cancer patients receiving and rogen deprivation therapy ( ADT ) are vulnerable to a number of potentially debilitating side effects , which can significantly impact quality of life . The role of alternate therapies , such as physical activity ( PA ) , in attenuating these side effects is largely understudied for such a large population . Thus , the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior , quality of life , and fitness measures . Patients and methods One hundred participants were r and omized into an intervention ( n = 53 ) or a wait-list control group ( n = 47 ) , with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing . The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions . PA , quality of life , fitness , and physiological outcomes were assessed pre and post the 16-week intervention . Results Significant increases in PA , supported by changes in girth measures and blood pressure , support the beneficial impact of the intervention . Positive trends were also evident for depression and fatigue . However , due to the high dropout rate , these results must be interpreted with caution . Conclusions PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy . Determining the maintenance of this behavior change will be important for underst and ing how the long-term benefits of increased activity levels may alleviate the late effects of ADT Background : Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment . Objective : The purpose of this study was to evaluate the effectiveness of a home-based exercise training intervention , the Pro-self Fatigue Control Program on the management of cancer-related fatigue . Interventions / Methods : Participants ( N = 119 ) were r and omized into 1 of 3 groups : group 1 received the exercise prescription throughout the study ; group 2 received their exercise prescription after completing cancer treatment ; and group 3 received usual care . Patients completed the Piper Fatigue Scale , General Sleep Disturbance Scale , Center for Epidemiological Studies -Depression Scale , and Worst Pain Intensity Scale . Results : All groups reported mild fatigue levels , sleep disturbance , and mild pain , but not depression . Using multilevel regression analysis , significant linear and quadratic trends were found for change in fatigue and pain ( ie , scores increased , then decreased over time ) . No group differences were found in the changing scores over time . A significant quadratic effect for the trajectory of sleep disturbance was found , but no group differences were detected over time . No significant time or group effects were found for depression . Conclusions : Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment . The optimal timing of exercise remains to be determined . Implication s for Practice : Clinicians need to be aware that some physical activity is better than none , and there is no harm in exercise as tolerated during cancer treatment . Further analysis is needed to examine the adherence to exercise . More frequent assessment s of fatigue , sleep disturbance , depression , and pain may capture the effect of exercise OBJECTIVE To determine the effect of exercise on quality of life in ( a ) a r and omized controlled trial of exercise among recently diagnosed breast cancer survivors undergoing adjuvant therapy and ( b ) a similar trial among post-treatment survivors . METHODS Fifty newly diagnosed breast cancer survivors were recruited through a hospital-based tumor registry and r and omized to a 6-month , home-based exercise program ( n=25 ) or a usual care group ( n=25 ) . In a separate trial , 75 post-treatment survivors were r and omized to a 6-month , supervised exercise intervention ( n=37 ) or to usual care ( n=38 ) . Participants in both studies completed measures of happiness , depressive symptoms , anxiety , stress , self-esteem , and quality of life at baseline and 6 months . RESULTS Forty-five participants completed the trial for newly diagnosed survivors and 67 completed the trial for post-treatment survivors . Good adherence was observed in both studies . Baseline quality of life was similar for both studies on most measures . Exercise was not associated with quality of life benefits in the full sample of either study ; however exercise was associated with improved social functioning among post-treatment survivors who reported low social functioning at baseline ( p<0.05 ) . CONCLUSIONS Exercise did not affect quality of life in either recently diagnosed or post-treatment breast cancer survivors ; however this may be due in part to relatively high baseline functioning among participants in both studies . Strategies for future research include limiting enrollment to survivors who report reduced quality of life on screening question naires and targeting survivor subgroups known to be at particular risk for quality of life impairment Objectives . This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer center . Methods . Eighty-eight stage II and III breast cancer out patients are r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to radiotherapy treatment . Assessment s include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety , depression , and stress collected before and after 6 weeks of radiotherapy . Results . Analysis of covariance reveals significant decreases in anxiety ( P < .001 ) , depression ( P = .002 ) , perceived stress ( P < .001 ) , 6 a.m. salivary cortisol ( P = .009 ) , and pooled mean cortisol ( P = .03 ) in the yoga group compared with controls . There is a significant positive correlation between morning salivary cortisol level and anxiety and depression . Conclusion . Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer , with six month follow-up . Design Pragmatic r and omised controlled prospect i ve open trial . Setting Three National Health Service oncology clinics in Scotl and and community exercise facilities . Participants 203 women entered the study ; 177 completed the six month follow-up . Interventions Supervised 12 week group exercise programme in addition to usual care , compared with usual care . Main outcome measures Functional assessment of cancer therapy ( FACT ) question naire , Beck depression inventory , positive and negative affect scale , body mass index , seven day recall of physical activity , 12 minute walk test , and assessment of shoulder mobility . Results Mixed effects models with adjustment for baseline values , study site , treatment at baseline , and age gave intervention effect estimates ( intervention minus control ) at 12 weeks of 129 ( 95 % confidence interval 83 to 176 ) for metres walked in 12 minutes , 182 ( 75 to 289 ) for minutes of moderate intensity activity reported in a week , 2.6 ( 1.6 to 3.7 ) for shoulder mobility , 2.5 ( 1.0 to 3.9 ) for breast cancer specific subscale of quality of life , and 4.0 ( 1.8 to 6.3 ) for positive mood . No significant effect was seen for general quality of life ( FACT-G ) , which was the primary outcome . At the six month follow-up , most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged . No adverse effects were noted . Conclusion Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later . Clinicians should encourage activity for their patients . Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services . Trial registration Current controlled trials IS RCT N12587864 PURPOSE To examine the effects of aerobic exercise therapy on quality of life ( QoL ) and associated outcomes in women treated for breast cancer . Evidence suggests that exercise may be beneficial , but no trial has included an exercise-placebo and a usual-care group to control for the attention effects that might be associated with aerobic exercise interventions in cancer patients . PATIENTS AND METHODS A total of 108 women who had been treated for breast cancer 12 to 36 months previously were r and omly assigned to supervised aerobic exercise therapy ( n = 34 ) , exercise-placebo ( body conditioning ; n = 36 ) , or usual care ( n = 38 ) . Exercise therapy and exercise-placebo sessions took place three times per week for 8 weeks . Outcomes included QoL , depression , exercise behavior , aerobic fitness ; outcomes were assessed at baseline and at the 8- and 24-week follow-up . RESULTS Analyses of covariance revealed a significant mean difference of 9.8 units in Functional Assessment of Cancer Therapy-General ( primary outcome ) favoring aerobic exercise therapy at 8 weeks , relative to usual care . Significant differences that favored aerobic exercise therapy relative to usual care were recorded for Functional Assessment of Cancer Therapy-Breast , social/family well-being , functional well-being , and breast cancer subscale scores at 8-week follow-up . Psychological health outcomes improved modestly for both intervention groups ; these improvements were sustained for several end points . CONCLUSION Exercise therapy had large , clinical ly meaningful , short-term beneficial effects on QoL in women treated for breast cancer ; this finding can not be attributable to attention , given that the exercise-placebo group did not report similar effects relative to usual care PURPOSE Breast cancer chemotherapy may cause unfavorable changes in physical functioning , body composition , psychosocial functioning , and quality of life ( QOL ) . We evaluated the relative merits of aerobic and resistance exercise in blunting these effects . PATIENTS AND METHODS We conducted a multicenter r and omized controlled trial in Canada between 2003 and 2005 that r and omly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care ( n = 82 ) , supervised resistance exercise ( n = 82 ) , or supervised aerobic exercise ( n = 78 ) for the duration of their chemotherapy ( median , 17 weeks ; 95 % CI , 9 to 24 weeks ) . Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale . Secondary end points were fatigue , psychosocial functioning , physical fitness , body composition , chemotherapy completion rate , and lymphedema . RESULTS The follow-up assessment rate for our primary end point was 92.1 % , and adherence to the supervised exercise was 70.2 % . Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem ( P = .015 ) , aerobic fitness ( P = .006 ) , and percent body fat ( adjusted P = .076 ) . Resistance exercise was superior to usual care for improving self-esteem ( P = .018 ) , muscular strength ( P < .001 ) , lean body mass ( P = .015 ) , and chemotherapy completion rate ( P = .033 ) . Changes in cancer-specific QOL , fatigue , depression , and anxiety favored the exercise groups but did not reach statistical significance . Exercise did not cause lymphedema or adverse events . CONCLUSION Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy , but they did improve self-esteem , physical fitness , body composition , and chemotherapy completion rate without causing lymphedema or significant adverse events PURPOSE / OBJECTIVES To compare the effectiveness of a prescribed home-based walking exercise intervention with usual care in older women receiving hormonal treatment for breast cancer , and to examine relationships among levels of the cortisol , serotonin , interleukin-6 , and bilirubin biomarkers and fatigue , sleep disturbances , and depressive symptoms . DESIGN Longitudinal r and omized clinical trial . SETTING A National Cancer Institute- design ated cancer center in the southeastern United States . SAMPLE 20 women ( aged 55 years or older ) with breast cancer receiving hormonal treatment . METHODS Participants were r and omized to a walking exercise intervention or usual care . Laboratory sample s and the Pittsburgh Sleep Quality Index ( PSQI ) , the Piper Revised Fatigue Scale , and the Center for Epidemiological Studies -Depression Scale were collected at the initial clinic visit and at 12 weeks from the groups . Question naires also were collected at weeks 2 and 14 . MAIN RESEARCH VARIABLES Fatigue , sleep disturbances , depressive symptoms , biomarkers , and exercise . FINDINGS Effect of the exercise intervention on sleep scores was highly significant between groups . Exercise group scores on the PSQI decreased significantly over time ( indicating improved sleep quality ) , although scores did not change significantly within the control group . Sleep actigraphy also showed significantly shorter actual wake time and less movement in the exercise group . Serotonin levels also were significantly affected by the intervention . CONCLUSIONS Data suggest that a walking exercise intervention improves sleep in older women receiving hormonal treatment for their breast cancer . Serotonin levels may be a useful biomarker when assessing sleep disturbances in this group . IMPLICATION S FOR NURSING Clinicians need to be aware that older women receiving hormonal treatment for their breast cancer may experience fatigue , sleep disturbances , and depressive symptoms . Homebased walking activity may reduce symptom severity in this group OBJECTIVE To show fatigue prevention and quality of life ( QOL ) improvement from cardiovascular exercise during radiotherapy . DESIGN Prospect i ve enrollment ( n=21 ) , r and omized to exercise ( n=11 ) and control groups ( n=10 ) , with pre- and post-radiotherapy between- and within-group comparisons . SETTING Academic medical center . PARTICIPANTS Localized prostate cancer patients undergoing radiotherapy . INTERVENTIONS The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise . MAIN OUTCOME MEASURES Pre- and post-radiotherapy differences in cardiac fitness , fatigue , depression , functional status , physical , social , and functional well-being , leg strength , and flexibility were examined within and between 2 groups . RESULTS No significant differences existed between 2 groups at pre-radiotherapy assessment . At post-radiotherapy assessment , the exercise group showed significant within group improvements in : cardiac fitness ( P<.001 ) , fatigue ( P=.02 ) , Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) ( P=.04 ) , physical well-being ( P=.002 ) , social well-being ( P=.02 ) , flexibility ( P=.006 ) , and leg strength ( P=.000 ) . Within the control group , there was a significant increase in fatigue score ( P=.004 ) and a decline in social well-being ( P<.05 ) at post-radiotherapy assessment . Between-group differences at post-radiotherapy assessment were significant in cardiac fitness ( P=.006 ) , strength ( P=.000 ) , flexibility ( P<.01 ) , fatigue ( P<.001 ) , FACT-P ( P=.006 ) , physical well-being ( P<.001 ) , social well-being ( P=.002 ) , and functional well-being ( P=.04 ) . CONCLUSIONS An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness , flexibility , muscle strength , and overall QOL and prevented fatigue 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 OBJECTIVES Restorative yoga ( RY ) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors . Study goals were : to determine the feasibility of implementing a RY intervention for women with breast cancer ; and to examine group differences in self-reported emotional , health-related quality of life , and symptom outcomes . METHODS Women with breast cancer ( n=44 ; mean age 55.8 years ) enrolled in this study ; 34 % were actively undergoing cancer treatment . Study participants were r and omized to the intervention ( 10 weekly 75-minute RY classes ) or a waitlist control group . Participants completed question naires at Week 0 ( baseline ) and Week 10 ( immediately post-intervention for the yoga group ) . RESULTS Group differences favoring the yoga group were seen for mental health , depression , positive affect , and spirituality ( peace/meaning ) . Significant baseline*group interactions were observed for negative affect and emotional well-being . Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group . The yoga group demonstrated a significant within-group improvement in fatigue ; no significant difference was noted for the control group . CONCLUSIONS Although limited by sample size , these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients . This study demonstrates that a RY intervention is feasible for women with breast cancer ; implication s for study design and implementation are noted with an emphasis on program adoption and participant adherence We conducted a r and omized controlled trial to determine the effects of a home-based exercise intervention on change in quality of life ( QOL ) in recently resected colorectal cancer survivors , most of whom were receiving adjuvant therapy . Participants were r and omly assigned in a 2:1 ratio to either an exercise ( n = 69 ) or control ( n = 33 ) group . The exercise group was asked to perform moderate intensity exercise 3 - 5 times per week for 20 - 30 min each time . The primary outcome was change in QOL as measured by the Functional Assessment of Cancer Therapy-Colorectal ( FACT-C ) scale . Adherence in the exercise group was good ( 75.8 % ) but contamination in the control group was problematic ( 51.6 % ) . Intention-to-treat analysis revealed no significant differences between groups for change in the FACT-C ( mean difference , -1.3 ; 95 % CI , -7.8 to 5.1 ; P = 0.679 ) . In an ' on-treatment ' ancillary analysis , we compared participants who decreased versus increased their cardiovascular fitness over the course of the intervention . This analysis revealed significant differences in favour of the increased fitness group for the FACT-C ( mean difference , 6.5 ; 95 % CI , 0.4 - 12.6 ; P = 0.038 ) . These data suggest that increased cardiovascular fitness is associated with improvements in QOL in colorectal cancer survivors but better controlled trials are needed Colorectal cancer constitutes a major health problem for elderly patients . The disease and its stage , treatment , and attendant symptoms can have significant negative impact on the mental functioning of these patients . As part of a larger longitudinal study , 158 patients 65 years of age or older with an incident diagnosis of colorectal cancer were recruited from 23 sites within a Midwestern state . R and om effects regression analysis techniques were used to analyze how age , gender , race , presence of a family caregiver , co-morbid conditions , stage of disease at diagnosis , and the time-dependent variables marital status , employment status , symptoms , physical functioning , social functioning , and treatment predict depressive symptomatology at four assessment s over the 1st year following diagnosis . Gender , race , co-morbid conditions , physical functioning , social functioning , and symptoms were significant predictors of depressive symptomatology over the four waves of the study . Female patients , African Americans , and patients with two or more co-morbid conditions exhibited more depressive symptomatology . Both more symptoms and more restricted physical and social functioning corresponded to higher levels of depressive symptomatology . At a clinical level of patient care , these findings m and ate early identification of psychosocial difficulties experienced , an individualized symptom management plan and the application of other interventions , such as information giving , reassurance and referral to other re sources , with particular attention to African American and female patients PURPOSE To evaluate the effectiveness of a supervised home-based flexible training program on cardiorespiratory fitness ( CRF ) , mental distress , and health-related quality of life ( HRQOL ) parameters in young and middle-aged cancer patients shortly after curative chemotherapy . PATIENTS AND METHODS One hundred eleven patients age 18 to 50 years who had received chemotherapy for lymphomas or breast , gynecologic , or testicular cancer completed the trial . These patients were r and omly allocated to either an intervention group ( n = 59 ) , which underwent a 14-week training program , or a control group ( n = 52 ) that received st and ard care . Primary outcome was change in CRF , as determined by Astr and -Rhyming indirect bicycle ergometer test ( maximum oxygen uptake [ VO(2max ) ] ) , between baseline ( T0 ) and follow-up ( T1 ) . Secondary outcomes were mental distress , as assessed by the Hospital Anxiety and Depression Scale , and HRQOL , as assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Question naire . Two-way analysis of covariance was used to analyze changes from T0 to T1 . RESULTS VO(2max ) increased by 6.4 mL/kg(-1)/min(-1 ) in patients in the intervention group and by 3.1 mL/kg(-1)/min(-1 ) in patients in the control group ( P < .01 ) . The fatigue score decreased by 17.0 points in the control group compared with only 5.8 points in the intervention group ( P < .01 ) . There were no intergroup differences in mental distress or HRQOL . CONCLUSION A supervised , home-based , flexible training program has significant effect on CRF in young and middle-aged cancer patients shortly after curative chemotherapy , but it has no favorable effect on patients ' experience of fatigue , mental distress , or HRQOL Background : Psychosocial interventions can improve psychological quality of life ( symptoms of depression and anxiety ) of both women with breast cancer and their partners , but are not offered routinely to women and their partners . Objective : To test the hypotheses that telephone-delivered psychosocial interventions decrease depression and anxiety in women with breast cancer and their partners . Methods : The design of the study was a three-wave repeated measures with a between-subjects factor ( treatment group ) . Ninety-six women and their 96 partners were assigned r and omly to participate in one of three different 6-week programs : ( a ) telephone interpersonal counseling ( TIP-C ) ; ( b ) self-managed exercise ; or ( c ) attention control ( AC ) . Results : The mixed-model analysis of variance for symptoms of depression among women with breast cancer revealed women 's depressive symptom scores decreased over time in all groups . For anxiety , women 's symptoms of anxiety decreased in the TIP-C and exercise groups over time , but not in the AC group . A parallel set of analyses was conducted on partners ' depression and anxiety data . Symptoms of depression and anxiety among the partners decreased substantially over the course of the investigation . Similar to the women , partners ' symptoms of anxiety decreased significantly in the TIP-C and exercise groups , but not in the AC group . Discussion : Findings from this study support that these telephone-delivered psychosocial interventions were effective for decreasing symptoms of depression and anxiety to improve psychological quality of life when compared to an AC group 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 . Prospect i ve data are limited on the course of anxiety and depression and their determinants in women with early breast cancer . These parameters were assessed before adjuvant radiotherapy ( RT ) and over 5 years follow-up . Of 2208 women recruited to the START QOL study , 35 % reported clinical ly relevant levels of anxiety and /or depression pre-RT ; there was no significant change in these proportions over time . However , 75 % women with high baseline anxiety recorded further high scores over time whilst one in six had high scores at every follow-up point . Depression showed a similar pattern with lower frequencies at all time points ; very few with initial normal scores developed clinical ly relevant anxiety or depression over time . Lower educational level predicted worse anxiety and depression over time ; younger age predicted worse anxiety and chemotherapy predicted worse depression . Scores in the borderline or case range for anxiety or depression at baseline were both significantly associated with worse mood states over 5 years . These findings indicate the course of anxiety and depression in women with specific risk factors . This subgroup of patients requires greater clinical attention PURPOSE Lymphoma patients commonly experience declines in physical functioning and quality of life ( QoL ) that may be reversed with exercise training . PATIENTS AND METHODS We conducted a r and omized controlled trial in Edmonton , Alberta , Canada , between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and r and omly assigned them to usual care ( UC ; n = 62 ) or 12 weeks of supervised aerobic exercise training ( AET ; n = 60 ) . Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia . Secondary end points were overall QoL , psychosocial functioning , cardiovascular fitness , and body composition . RESULTS Follow-up assessment for our primary end point was 96 % ( 117 of 122 ) at postintervention and 90 % ( 110 of 122 ) at 6-month follow-up . Median adherence to the supervised exercise program was 92 % . At postintervention , AET was superior to UC for patient-rated physical functioning ( mean group difference , + 9.0 ; 95 % CI , 2.0 to 16.0 ; P = .012 ) , overall QoL ( P = .021 ) , fatigue ( P = .013 ) , happiness ( P = .004 ) , depression ( P = .005 ) , general health ( P < .001 ) , cardiovascular fitness ( P < .001 ) , and lean body mass ( P = .008 ) . Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning . AET did not interfere with chemotherapy completion rate or treatment response . At 6-month follow-up , AET was still borderline or significantly superior to UC for overall QoL ( P = .054 ) , happiness ( P = .034 ) , and depression ( P = .009 ) without an increased risk of disease recurrence/progression . CONCLUSION AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response . Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients Physical exercise has been shown to enhance quality of life ( QOL ) in cancer survivors using pretest-posttest design s and compared to usual care ( i.e. no intervention ) . In the present study , we conducted a r and omized controlled trial to determine if exercise could improve QOL in cancer survivors beyond the known benefits of group psychotherapy ( GP ) . We matched 22 GP classes ( N=108 ) on content and then r and omly assigned 11 ( n=48 ) to GP alone and 11 ( n=60 ) to GP plus home-based , moderate-intensity exercise ( GP+EX ) . Participants completed a physical fitness test and QOL measures ( e.g. Functional Assessment of Cancer Therapy scales ) at the beginning and end of GP classes ( about 10 weeks ) . We had excellent recruitment ( 81 % ) , retention ( 89 % ) , and adherence ( 84 % ) rates and a modest contamination ( 22 % ) rate . Using intention-to-treat repeated measures analyses of variance , we found significant Time by Condition interactions for functional well-being , fatigue , and sum of skinfolds . We also found borderline significant interactions for physical well-being , satisfaction with life , and flexibility . All interactions favored the GP+EX condition . We conclude that a home-based , moderate intensity exercise program may im-prove QOL in cancer survivors beyond the benefits of GP , particularly in relation to physical and functional well-being |
13,450 | 15,495,047 | REVIEW ERS ' CONCLUSIONS Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin . | BACKGROUND In short acting insulin analogues the dissociation of hexamers is facilitated , achieving peak plasma concentrations about twice as high and within approximately half the time compared to regular human insulin .
According to these properties this profile resembles the shape of non-diabetic patients more than that of regular human insulins .
Despite this theoretical superiority of short acting insulin analogues over regular human insulin , the risk-benefit ratio of short acting insulin analogues in the treatment of diabetic patients is still unclear .
OBJECTIVES To assess the effect of treatment with short acting insulin analogues versus regular human insulin .
Due to fears of potentially carcinogenic and proliferative effects , most studies to date have excluded patients with advanced diabetic complications . | BACKGROUND AND AIM While lispro insulin has been reported to lower postpr and ial blood glucose concentrations , less consistent effects have been shown for glycosylated hemoglobin ( HbA1c ) levels . Aim of this study was to determine whether pre-meal association of NPH , an intermediate-acting insulin , with lispro improves overall glycemic control in type 1 diabetic patients . METHODS AND RESULTS Eighty-five type 1 diabetic patients were studied in a multicenter r and omized comparative ( human regular vs lispro insulin ) crossover ( 3-month ) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary . The number of injections was kept constant : 42 % and 58 % of patients injected insulin 3 and 4 times per day , respectively . Fasting and prepr and ial blood glucose levels were similar , while postpr and ial levels improved after lispro compared to human regular insulin ( breakfast : 8.28 + /- 2.39 vs 9.28 + /- 2.72 mmol/l ; lunch : 8.33 + /- 2.67 vs 9.06 + /- 2.67 mmol/l , dinner : 8.06 + /- 2.72 vs 9.28 + /- 2.44 mmol/l , ANOVA : p = 0.003 ) . HbA1c also improved after lispro : 8.1 + /- 0.9 vs 8.3 + /- 0.8 % , p < 0.05 . The rate of hypoglycemia was similar . Patients showed better acceptance of lispro treatment ( p < 0.001 ) . CONCLUSIONS Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia . This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long Summary The objective of this study was to identify possible risk factors of severe hypoglycaemia ( SH ) in a prospect i ve population based study of adult Type I ( insulin-dependent ) diabetic patients . A representative sample of 684 patients ( 41 % women , mean ± SD age 36 ± 11 , diabetes duration 18 ± 11 years ) , living in the district of Northrhine ( 9.5 million inhabitants ) , Germany , were examined in their homes using a mobile ambulance . A comprehensive baseline assessment of possible predictors of SH included sociodemographic and disease related variables , hypoglycaemia awareness , diabetes management , and attitudes and behavioural aspects as expressed by the patients . After a mean of 19 ± 6 months 669 ( 98 % ) patients were interviewed about events of SH since the baseline examination . Using the multiple Cox proportional hazards model , five risk factors of SH were identified : SH during the preceding year [ hazard ratio ( HR ) 2.7 , 95 % confidence intervals ( CI ) 1.8–4.2 ] , any history of SH ( HR 1.9 , CI 1.1–3.4 ) , C-peptide negativity ( HR 4.0 , CI 1.2–12.7 ) , social status ( HR 0.8 for a difference of 5 units for a value range of 0–24 , CI 0.6–0.9 ) , and patients ' determination to reach normoglycaemia ( HR 0.7 for a difference of 1 unit for a value range of 1–6 , CI 0.5–0.9 ) , indicating that the lower the social status and the higher the patients ' determination to reach normoglycaemia , the higher the risk of SH . After eliminating the history of hypoglycaemia from the model , impaired hypoglycaemia awareness and patients ' inappropriate denial of SH as their particular problem became additional significant risk factors of SH . In conclusion , in this population based study of adult Type I diabetic patients , C-peptide negativity , a previous event of SH , patients ' determination to reach normoglycaemia and social class were risk factors of SH . [ Diabetologia ( 1998 ) 41 : 1274–1282 Insulin lispro is an insulin analogue that has the advantages of being fast-acting , convenient , and less likely to lead to hypoglycaemic episodes . Previous studies have proven its value in treating both Type 1 and Type 2 diabetes both alone and in combination with different treatment regimens.1,2 However , diabetes is heterogeneous and differs in etiology and clinical characteristics in different ethnic groups . Even with the same insulin treatment , different diets will produce different glycaemic profiles . Diet patterns differ between different ethnic groups . Traditional oriental foods are characterized by a higher proportion of carbohydrates and a lower proportion of fat compared to Caucasian diets . To date , there has been no study on the use of insulin lispro in Chinese diabetic patients . Whether the Chinese dietary pattern will affect the efficacy of insulin lispro treatment remains unknown . Therefore , we conducted this trial to assess the efficacy of insulin lispro treatment in Chinese patients The short-acting insulin analogue lispro ( [ LYS(B28 ) , PRO(B29 ) ] is absorbed from the subcutis more rapidly than soluble insulin ( S ) . To compare the clinical effectiveness of lispro vs S , 11 Type 1 patients using continuous subcutaneous insulin infusion ( CSII ) therapy ( 6 F , 5 M , age 30 + /- 2.5 years , diabetes duration 14 + /- 1.0 years , BMI 24.0 + /- 0.8 kg m(-2 ) , HbA1c 6.5 + /- 0.2 % ) were studied in an open , r and omized , crossover study for 6 months ( 3 months lispro and 3 months S or vice versa ) . During lispro treatment mean fasting and 2 h postpr and ial blood glucose were lower compared to the S phase ( fasting 6.5 + /- 0.4 vs 7.5 + /- 0.4 mmol l(-1 ) ( NS ) , postpr and ial 6.8 + /- 0.3 vs 8.3 + /- 0.3 mmol l(-1 ) , p = 0.03 ) . In patients treated first with lispro HbA1c levels improved from 6.3 + /- 0.2 % to 5.7 + /- 0.3 % ; On reversion to S HbA1c increased to 6.2 + /- 0.2 % . In the group treated first with S , HbA1c fell ( 6.7 + /- 0.4 % vs 6.5 + /- 0.3 % ) and then improved further to 6.3 + /- 0.3 % with lispro . None of these changes were significant . There was no significant difference with respect to hypoglycaemic or other adverse events . It can be concluded that lispro in CSII therapy is safe and may improve postpr and ial glucose excursions BACKGROUND Although insulin lispro ( insulin LP ) has been shown to improve postpr and ial blood glucose ( BG ) control and reduce hypoglycemic episodes in adult patients with type I diabetes , there appear to have been few clinical studies focusing on its use in adolescents . OBJECTIVE This study compared the effects of insulin LP with those of regular human insulin ( insulin R ) on postpr and ial BG control and hypoglycemia in adolescents with type diabetes . METHODS In this crossover , open-label study , adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were r and omized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals , in addition to daily intermediate-acting insulin . After 4 months , patients were switched to the alternate treatment sequence . Eight-point BG profiles , hypoglycemia rate , and glycosylated hemoglobin ( HbA1c ) were measured at baseline and end point . RESULTS Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries ; 463 were r and omized to treatment ( 228 insulin LP , 235 insulin R ) , and 457 completed the study . Insulin LP given before breakfast result ed in significantly lower mean ( + /-SD ) 2-hour postpr and ial BG levels compared with insulin R ( 9.7 + /- 4.0 mmol/L vs 10.6 + /- 4.3 mmol/L , respectively ; P < 0.001 ) . Insulin LP given before dinner result ed in significantly lower 2-hour postpr and ial BG levels compared with insulin R ( 8.6 + /- 3.5 mmol/L vs 9.3 + /- 3.7 mmol/L ; P = 0.003 ) . No differences were seen between treatments in 2-hour postpr and ial BG levels after the midday meal . Mean baseline HbA1c values were similar between sequence groups , and no between-group difference in HbA1c was observed at end point ( insulin LP , 8.69 % + /- 1.52 % ; insulin R , 8.70 % + /- 1.65 % ) . Treatment with insulin LP result ed in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R ( 4.02 + /- 4.5 vs 4.37 + /- 4.5 , respectively ; P = 0.023 ) and significantly fewer hypoglycemic episodes between midnight and 6 AM ( 1.0 + /- 1.9 vs 1.7 + /- 2.6 ; P < 0.001 ) . CONCLUSIONS In adolescents with type 1 diabetes , insulin LP significantly improved postpr and ial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population OBJECTIVE The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart ( BIAsp 30 ) with the equivalent premixed biphasic human insulin ( BHI 30 ) , administered twice daily , in patients with type 2 diabetes mellitus . METHODS In this r and omized , double-blind , crossover trial , 13 patients ( mean age , 64 years ; baseline mean glycosylated hemoglobin , 7.7 % ; mean body mass index , 28.1 kg/m2 ) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast . At the end of each 2-week treatment period , 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays . All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance . RESULTS Total daily insulin exposure was similar between treatment periods . Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17 % greater than that of BHI 30 after dinner and 44 % greater after breakfast ; both differences were statistically significant . The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner ( 18 % ) and breakfast ( 35 % ) . Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group ; differences were significant only after breakfast . The mean daily pr and ial glucose excursion was significantly lower for BIAsp 30 ( 16.2 mmol x h x L(-1 ) ) than BHI 30 ( 17.9 mmol x h x L(-1 ) ) . Postpr and ial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast , but were significantly greater after lunch . Mean 24-hour and nocturnal serum glucose concentrations were similar , and both insulins were associated with < or = 7 minor and no major hypoglycemic events . CONCLUSIONS Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postpr and ial glucose excursions . This effect may be of importance when improvement in postpr and ial glucose control is desired Lispro ( LP ) and regular human ( HR ) insulins were compared in Type 1 diabetic ( T1DM ) patients on either a Mediterranean diet or normal diet . Twelve T1DM patients were recruited and r and omized into two groups of 6 , groups A and B. They were treated in different sequences ( in 3-month intervals for 1 year ) . Group A : LP insulin and normal diet , LP insulin and Mediterranean diet , regular insulin and Mediterranean diet , regular insulin and normal diet . Group B : regular insulin and normal diet , regular insulin and Mediterranean diet , LP insulin and Mediterranean diet , LP insulin and normal diet . Each patient was treated with rapid acting insulin , either LP insulin or HR insulin , before each main meal and a dose of slow acting insulin at bedtime . Every 15 days the glycemic control , the incidence and frequency of hypoglycemic episodes , and any adverse events were evaluated . Every 3 months , hematology and a chemistry panel , pre- and post-pr and ial glycemic and insulinemic profiles were evaluated in all patients . HbA1c levels significantly decreased in LP patients on normal diet , post-pr and ial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards , 15-min post-pr and ial insulin levels higher in LP- than in HR-treated patients , and hypoglycemic episodes were significantly less in LP- than in HR-treated patients . LP insulin , irrespective of the type of diet , results in more effective glycemic control , significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet Insulin lispro , an insulin analog recently developed particularly for mealtime therapy , has a fast absorption rate and a short duration of action . We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM . The study was a 6-month r and omized multinational ( 17 countries ) and multicenter ( 102 investigators ) clinical trial performed with an open-label crossover design . Insulin lispro was injected immediately before the meal , and regular human insulin was injected 30–45 min before the meal . Throughout the study , the postpr and ial rise in serum glucose was significantly lower during insulin lispro therapy . At the endpoint , the postpr and ial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro ( P < 0.001 ) . The rate of hypoglycemia was 12 % less with insulin lispro ( 6.4 ± 0.2 vs. 7.2 ± 0.3 episodes/30 days , P < 0.001 ) , independent of basal insulin regimen or HbA1c level . The reduction was observed equally in episodes with and without symptoms . When the total number of episodes for each patient was analyzed according to the time of occurrence , the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day ( P < 0.001 ) . The largest relative improvement was observed at night . In conclusion , insulin lispro improves postpr and ial control , reduces hypoglycemic episodes , and improves patient convenience , compared with regular human insulin , in IDDM patients OBJECTIVE To investigate the effects of a multiple injection regimen with a mixture of 75 % lispro and 25 % intermediate-acting insulin ( lispro high mixture [ HM ] ) before meals on glycemic control , physiological responses to hypoglycemia , well-being , and treatment satisfaction . RESEARCH DESIGN AND METHODS We studied 35 type 1 diabetes patients . After an 8- to 10-week lead-in period , patients were r and omized to HM or human regular insulin therapy for 12 - 14 weeks . During the lead-in and treatment periods , HbA1c levels and hypoglycemic frequencies were measured , and patients completed the Well-Being Question naire and the Diabetes Treatment Satisfaction Question naire . In 19 patients , responses to hypoglycemia were tested during stepped euglycemic-hypoglycemic clamps . RESULTS HM treatment improved postpr and ial glycemia but had no effect on HbA1c , frequency of hypoglycemia , well-being , or treatment satisfaction . During experimental hypoglycemia , HM therapy was associated with a slightly lower total adrenaline response and a higher autonomic symptom threshold ( i.e. , the autonomic symptom response occurred at a lower blood glucose level ) than human regular insulin therapy . We speculate that this effect result ed from an accumulation of insulin during the night . CONCLUSIONS Multiple injection therapy with HM rather than human regular insulin before meals does not offer advantages regarding glycemic control , frequency of hypoglycemia , well-being , or treatment satisfaction . In addition , this regimen causes an attenuation of the adrenaline and autonomic symptom responses to hypoglycemia The aim of the study was to compare lispro ( LP ) and Insuman(R ) ( I ) insulin in continuous subcutaneous insulin infusion ( CSII ) therapy with respect to blood glucose control as expressed by the st and ard deviation of blood glucose ( SD(BG ) ) and HbA(1c ) and to monitor the well-being ( WBQ ) and treatment satisfaction ( DTSQ ) parameters during such treatment . Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label , r and omized , cross-over , multicenter study for 4 months ( 2 months LP and 2 months I or vice versa ) . Boluses with LP were given 5 min before each meal and with I 30 min before each meal . During LP administration compared with I , the SD(BG ) of all blood glucose values ( 3.6 mmol/l vs. 3.9 mmol/l , p=0.012 ) , as well as the SD(BG ) of the postpr and ial , blood glucose values ( 3.6 mmol/l vs. 4.0 mmol/l , p=0.006 ) , were significantly reduced . The HbA(1c ) was significantly lower during LP administration ( 7.4 % vs. 7.6 % , p=0.047 ) . The incidence of hypoglycemic events per 30 days ( capillary blood glucose<3.0 mmol/l and /or symptoms ) did not significantly differ between LP and I ( 9.7 vs. 8.0 per month , p=0.23 ) . The total amount of daily insulin was slightly but significantly lower with LP , compared to I ( 38.0 IU vs. 40.3 IU , p=0.004 ) . There was no treatment effects of LP compared to I concerning WBQ and DTSQ . It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control , a lower HbA(1c ) , a less insulin requirement without increasing the frequency of hypoglycemia The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms . The insulin analogue insulin lispro has a weak self-association and a fast absorption rate . We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus . A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus ( IDDM ) and 295 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . The patients were r and omized to inject either regular human insulin 30 to 45 minutes before eating , or insulin lispro immediately before each meal , in addition to basal insulin . The postpr and ial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy . At end point the increment was significantly lower at 1 hour ( 35 % ) and at 2 hours ( 64 % ) after the meal in IDDM patients ; in NIDDM patients , the increment was nonsignificantly lower at 1 hour ( 19 % ) and significantly lower at 2 hours ( 48 % ) . IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin ( HbA1c ) levels in patients receiving regular human insulin ( 8.1 % vs 8.3 % ) . In NIDDM patients , HbA1c levels decreased equally in both treatment groups . Due to its fast absorption rate , insulin lispro improves postpr and ial control in diabetes . Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience OBJECTIVE Both rapid-acting insulin analogs , insulin aspart and lispro , attenuate pr and ial glucose excursion compared with human soluble insulin . This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on pr and ial blood glucose control . RESEARCH DESIGN AND METHODS A total of 24 type 1 diabetic patients ( age 36 + /- 8 years , 16 men and 8 women , BMI 24.3 + /- 2.6 kg/m(2 ) , diabetes duration 17 + /- 11 years , HbA(1c ) 7.9 + /- 0.8 % ) on intensified insulin therapy were recruited into a single-center , r and omized , double-blind , two-period , cross-over , glucose clamp trial . The subjects were given an individual need-derived dose of pr and ial insulin lispro or aspart immediately before a st and ard mixed meal . RESULTS With respect to blood glucose excursions from time 0 to 6 h ( Exc(glu(0 - 6 h ) ) ) and from time 0 to 4 h ( Exc(glu(0 - 4 h ) ) ) , the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent . This was supported by comparison with maximum postpr and ial blood glucose excursions ( C(max(glu ) ) ) ( estimated ratio aspart/lispro ANOVA [ 90 % CI ] : 0.95 [ 0.80 - 1.13 ] , 0.97 [ 0.82 - 1.17 ] , and 1.01 [ 0.95 - 1.07 ] for Exc(glu(0 - 6 h ) ) , Exc(glu(0 - 4 h ) ) , and C(max(glu ) ) , respectively ) . For pharmacokinetic end points ( maximum postpr and ial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h ) , equivalence was indicated . No difference concerning absorption or elimination for time to maximal insulin concentration , time to half-maximum insulin concentration , and time to decrease to 50 % of maximum insulin concentration was observed . CONCLUSIONS These data suggest that in type 1 diabetic patients , both insulin analogs are equally effective for control of postpr and ial blood glucose excursions AIMS To compare quality of life ( QoL ) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid-acting insulin analogue , insulin aspart ( IAsp ) , with that in patients receiving soluble human insulin ( HI ) . METHODS In this 6-month , multinational , r and omized , open-label trial , 424 patients from German-speaking countries were subjected to psychometric assessment before and after r and omization ( ratio 2 : 1 ) to basal-bolus treatment with either IAsp ( n = 283 ) or HI ( n = 141 ) . Patients on HI were advised to keep an injection-meal interval of 30 min , whereas patients on IAsp were advised to inject immediately before meals . Treatment satisfaction and diabetes-related QoL were assessed using vali date d instruments to measure the domains of patients ' individual treatment goals , physical complaints , worries about the future , social relations , leisure time flexibility , daily hassles , diet restrictions , burdens and fear of hypoglycaemia , blood glucose fluctuations , self-efficacy , and fear of insulin analogues . RESULTS After 6 months , IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales ( P < 0.01 ) , and in QoL with respect to diet restrictions ( P < 0.01 ) . Improved satisfaction was mainly due to increased dietary and leisure time flexibility ( P < 0.0001 ) . Twenty-three percent of the IAsp group vs. 14 % of the HI group achieved small but important improvements of total QoL ( between-group difference , P < 0.06 ) . The number needed to treat ( NNT ) with IAsp for an important increase in QoL was calculated to be 10 . Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength ( P < 0.01 ; NNT = 7 ) and patients feeling less protected against hypoglycaemia ( P < 0.005 ; NNT = 8) as being the most likely to benefit from IAsp . CONCLUSIONS Under these study conditions , IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin . The ' numbers needed to treat ' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial Summary Recombinant DNA technology allows the production of insulin analogues with faster absorption rates from subcutaneous tissue as compared to soluble human insulin . The human insulin analogue B10Asp ( mono/dimeric ) is absorbed twice as fast as soluble human insulin ( hexameric ) . A double blind , r and omised crossover study with a 1-month run-in period and two 2-month treatment periods was performed in 21 male insulin-dependent diabetic ( IDDM ) patients aged 18–40 years in order to compare the metabolic control obtained with equimolar doses of the analogue B10Asp vs soluble human insulin ( Actrapid ) given as mealtime insulin and intermediate acting isophane insulin ( Protaphane ) at bedtime . At the end of each 2-month study period , the patients were admitted to the metabolic ward . We found significantly higher plasma insulin/analogue levels after breakfast , lunch and dinner with B10Asp as compared to Actrapid ( p<0.05 ) . The plasma insulin/analogue levels were significantly lower before lunch and dinner with B10Asp as compared to Actrapid ( p<0.05 ) . Also , the plasma insulin/analogue level tended to be lower at bedtime when comparing B10Asp to Actrapid . The 24-h blood glucose profiles showed identical fasting blood glucose , significantly lower blood glucose after breakfast with the analogue ( p<0.05 ) , no differences in blood glucose after lunch and dinner but a significantly higher blood glucose at midnight using the analogue ( p<0.05 ) . The overall 24-h mean blood glucose concentrations , the daily insulin dose , HbA1c , diet , home blood glucose monitoring and frequency of hypoglycaemia were almost identical in the two treatment periods . In conclusion , the overall glycaemic control remained unchanged and quite good when Actrapid was exchanged dose for dose with the insulin analogue B10Asp in IDDM patients treated with a basal bolus regime Aim : It has been found that non‐fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes . The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels . In this study , we aim ed to assess the effects of three different insulin regimens ( group I : lispro insulin + NPH insulin , group II : lispro insulin + metformin and group III : regular insulin + NPH insulin ) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti‐diabetic drug failure OBJECTIVE Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes , this trial was performed to compare the efficacy and safety of prepr and ial insulin aspart with human soluble insulin ( HI ) and human premix ( 70 % NPH/30 % regular ) insulin ( MIX ) . RESEARCH DESIGN AND METHODS A total of 231 type 2 diabetic patients were r and omized to insulin aspart ( n = 75 ) , HI ( n = 80 ) , or MIX ( n = 76 ) for 3 months . Insulin aspart and HI were administered with or without bedtime NPH insulin . A total of 204 patients completed the trial according to protocol . HbA1c , 7-point blood glucose , insulin dosage , and hypoglycemic episodes were recorded . The primary end point was " change of HbA1c " from baseline to last visit . Analysis for equivalence was performed by t tests with three subtests . RESULTS HbA1c decreased 0.91 + /- 1.00 for insulin aspart , 0.73 + /- 0.87 for HI , and 0.65 + /- 1.10 for MIX with the following confidence intervals : insulin aspart HI ( -0.21 to 0.57 , P = 0.025 ) , insulin aspart MIX ( -0.17 to 0.69 , P = 0.092 ) , and HI-MIX ( -0.33 to 0.48 , P = 0.006 ) . Postpr and ial blood glucose decreased in the insulin aspart group : 0.44 mmol/l to > 1.67 mmol/l compared with HI and 1.1 mmol/l to > 1.67 mmol/l compared with MIX . Prepr and ial insulin doses were similar in the insulin aspart and HI groups ( 10 - 14.5 U ) . Hypoglycemic events per month were 0.56 HI , 0.40 insulin aspart , and 0.19 MIX . CONCLUSIONS Statistically , insulin aspart was not equivalent to another treatment in terms of HbA1c reduction . Insulin aspart treatment result ed in improved HbA1c and postpr and ial blood glucose . The application of insulin aspart was safe and well tolerated OBJECTIVE The purpose of this study was to compare the efficacy , safety and pump compatibility of insulin aspart ( a rapid-acting insulin analog ) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion ( CSII ) therapy . RESEARCH DESIGN AND METHODS This was a single-center r and omized open-label study Patients received CSII therapy with insulin aspart ( n = 19 ) or buffered regular human insulin ( n = 10 ) for 7 weeks . Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals . RESULTS Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels ( 8.2 + /- 1.9 and 8.5 + /- 2.1 mmol/l , respectively ) ( mean + /- SD ) and maintaining serum fructosamine ( 343 + /- 25.7 and 336 + /- 27.4 micromol/l ) and HbA1c ( 6.9 + /- 0.6 and 7.1 + /- 0.6 % ) levels . Possible obstructions and set leakages were infrequently reported in both groups . Similar numbers of patients experienced hypoglycemia ( blood glucose < 2.5 mmol/l ) : 14 ( 74 % ) insulin aspart patients versus 6 ( 60 % ) buffered regular human insulin patients . Patients receiving insulin aspart had fewer hypoglycemic events per patient ( 2.9 ) than those patients receiving buffered regular human insulin ( 6.2 ) . There were no differences between the two insulins in the occurrence of hyperglycemic events ( blood glucose > 19 mmol/l ) or in the number and type of adverse events . CONCLUSIONS Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy OBJECTIVE To compare the safety and efficacy of insulin aspart ( IAsp ) , buffered regular insulin ( BR ) , and insulin lispro administered by continuous subcutaneous insulin infusion ( CSII ) in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS After completing a 4-week run-in period with BR , 146 adult patients with type 1 diabetes ( with pretrial CSII experience ) were r and omly assigned ( 2:2:1 ) to CSII treatment with IAsp , BR , or lispro for 16 weeks in a multicenter , open-label , r and omized , parallel-group study . Bolus insulin doses were administered 30 min before meals ( BR ) or immediately before meals ( IAsp or lispro ) . RESULTS Treatment groups had similar baseline HbA(1c ) ( 7.3 % + /- 0.7 for IAsp , 7.5 % + /- 0.8 for BR , and 7.3 % + /- 0.7 for lispro ) . After 16 weeks of treatment , HbA1c values were relatively unchanged from baseline , and the mean changes in baseline HbA1c values were not significantly different between the three groups ( 0.00 + /- 0.51 , 0.15 + /- 0.63 , and 0.18 + /- 0.84 for the IAsp , BR , and lispro groups , respectively ) . The rates of hypoglycemic episodes ( blood glucose < 50 mg/dl ) per patient per month were similar ( 3.7 , 4.8 , and 4.4 for the IAsp , BR , and lispro groups , respectively ) . Clogs/blockages in pumps or infusion sets were infrequent ; most subjects ( 76 , 83 , and 75 % in the IAsp , BR , and lispro groups , respectively ) had < or = 1 clog or blockage per 4 weeks during the trial . CONCLUSIONS Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps OBJECTIVE To quantitate the contribution of postpr and ial blood glucose , which improves with the short-acting insulin analog lispro [ Lys(B28),Pro(B29 ) ] in type 1 diabetes , to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose . RESEARCH DESIGN AND METHODS A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin ( Hum-R ) and bedtime NPH were r and omly assigned to a continuation of Hum-R ( group 1 , n = 8) , lispro ( group 2 , n = 8) , or lispro + NPH ( in variable proportions ) administered at mealtime ( group 3 , n = 8) for 3 months , NPH administered at bedtime was continued in all three groups . Data from home blood glucose monitoring were collected , and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postpr and ial glucose curve ( 3.5 h after breakfast , 3.5 h after lunch , and 3.0 h after dinner for a total of 10.0 h ) and the postabsorptive blood glucose curve ( the remaining 14.0 h out of 24.0 h ) ( AUC ) . Eight nondiabetic subjects were also studied . RESULTS The substitution of Hum-R with lispro ( group 2 ) result ed in lower postpr and ial blood glucose , but greater postabsorptive blood glucose ( P < 0.05 vs. group 1 ) . The postpr and ial blood glucose AUC was lower ( 161 + /- 19 vs. 167 + /- 20 mg.100 ml-1.h-1 ) , but the postabsorptive blood glucose AUC was greater ( 155 + /- 22 vs. 142 + /- 19 mg.100 ml-1.h-1 ) ( P < 0.05 ) . Therefore , the 24-h blood glucose AUC was no different ( NS ) . Consequently , HbA1c was no different ( NS ) . This occurred because in group 2 , mealtime lispro result ed in normal pr and ial plasma insulin , but also result ed in lower interpr and ial concentration ( P < 0.05 vs. group 1 ) . When NPH was added to lispro ( 30 % at breakfast , 40 % at lunch , 10 % at dinner ) in group 3 , postabsorptive plasma insulin was similar to group 1 ( NS ) , in group 3 , the postpr and ial blood glucose AUC ( 153 + /- 17 mg.100 ml-1.h-1 ) was lower and the postabsorptive blood glucose AUC was no different , as compared with group 1 ( NS ) . Therefore , the 24-h blood glucose AUC was lower ( 147 + /- 17 vs. 155 + /- 21 and 158 + /- 20 mg.100 ml-1.h-1 ) , and HbA1c was lower ( 6.41 + /- 0.12 vs. 6.84 + /- 0.2 and 6.96 + /- 0.2 % ( groups 3 , 1 , and 2 respectively , P < 0.05 ) . Frequency of hypoglycemia was greater in group 2 ( P < 0.05 ) , but not in group 3 ( NS ) vs. group 1 In a r and omized , open-label , controlled cross-over trial , 107 patients with type 1 diabetes were treated with either regular human insulin or insulin lispro , a rapid-acting insulin analogue . After a lead-in period of 2 to 4 weeks , the patients were r and omized to receive intensified insulin treatment with one of the insulins . NPH-human insulin was used for basal substitution in both groups . The crossover took place after 3 months of treatment . Efficacy and safety of the drugs were established by the assessment of hemoglobin A1c , pretest blood glucose , 1 and 2-hour postpr and ial glucose excursions , number of hypoglycemic episodes , daily insulin doses , body weight , insulin antibodies , and the number and severity of adverse events . A question naire comprised of four primary domains was used to measure some quality of life aspects of the patients . Both treatment regimens were well tolerated . While no differences were seen in the hemoglobin A1c values , there was a trend for a decrease in the pretest blood glucose levels and significant decreases of the 1 and 2-hour postpr and ial glucose excursions in the patients treated with insulin lispro . The number of hypoglycemic episodes was also significantly lower in the insulin lispro treatment period . The evaluation of the quality of life question naire revealed an improvement in the patients treatment satisfaction for the insulin lispro group . During treatment with insulin lispro , the basal insulin doses increased slightly . However , the total daily insulin doses decreased to a greater extent with insulin lispro as compared to regular human insulin . Human insulin-specific antibody binding values at endpoint were not different for the two treatments . In conclusion , intensive insulin treatment with insulin lispro therapy results in improved postpr and ial glycemic control and HbA1c levels at least equal to the treatment with regular human insulin but with less hypoglycemia and more treatment satisfaction for the patient The present prospect i ve one-year r and omized study was conducted to compare soluble human insulin , with a new rapid-acting human insulin analogue , lispro , with respect to postpr and ial glucose excursions , frequency of hypoglycaemic episodes , glucose control , and long-term safety in 39 subjects ( 20 females , 19 males ) with Type 1 diabetes . The duration of diabetes , gender distribution , and age were similar in the two groups . The total number of hypoglycaemic episodes was significantly less ( p < 0.04 , Wilcoxon rank sum test ) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period . The 2-h postpr and ial glucose excursion at 1 year was also significantly less ( p < 0.05 , ANOVA ) in the group treated with insulin lispro . The reductions in the total number of hypoglycaemic episodes and in the postpr and ial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes . However , the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue AIMS Despite considerable experience with insulin lispro , few blinded comparisons with soluble insulin are available . This study compared insulin lispro with human soluble insulin in patients with Type 1 diabetes mellitus on multiple injection therapy who inject shortly before meals . METHODS Glucose control , frequency of hypoglycaemia and patient preference were examined in the course of a prospect i ve , r and omized , double-blind , crossover comparison , with a 6-week run-in period and 12 weeks on each therapy . Ninety-three patients took part , all on multiple daily doses of insulin , with soluble insulin before meals and NPH ( isophane ) insulin at night . The main outcome measures were self-monitored blood glucose profiles , glycated haemoglobin , frequency of hypoglycaemic episodes , patient satisfaction and well-being and patient preference . RESULTS Blood glucose levels were significantly lower after breakfast and lunch , but higher before breakfast , lunch and supper , in patients taking insulin lispro . Levels of HbA(1c ) were 7.4 + /- 1.1 % on Humulin S and 7.5 + /- 1.1 % on insulin lispro ( P = 0.807 ) . The overall frequency of symptomatic hypoglycaemia did not differ , but patients on insulin lispro were less likely to experience hypoglycaemia between midnight and 6 a.m. , and more likely to experience episodes from 6 a.m. to midday . Question naires completed by 84/87 patients at the end of the study showed that 43 ( 51 % ) were able to identify each insulin correctly , nine ( 11 % ) were incorrect , and 32 ( 38 % ) were unable to tell the insulins apart . No significant preference emerged : 35 ( 42 % ) opted for insulin lispro , 24 ( 29 % ) opted for Humulin S , while the remainder had no clear preference . CONCLUSIONS Substitution of insulin lispro for soluble insulin in a multiple injection regimen improved post-pr and ial glucose control at the expense of an increase in fasting and pre-pr and ial glucose levels . Patients who already injected shortly before meals expressed no clear preference for the fast-acting analogue , and did not improve their overall control as a result of using it . Nocturnal hypoglycaemia was however , less frequent on insulin lispro , and may emerge as a robust indication for its use OBJECTIVE To compare the effects of insulin lispro ( LP ) and human regular insulin ( HR ) when given twice daily with NPH insulin on glycemic control ( HbA1c ) , daily blood glucose profiles and rates of hypoglycemia in patients with type 2 diabetes mellitus after failure to respond to sulfonylurea drugs . RESEARCH DESIGN AND METHODS A 5.5-month r and omized , open-label , parallel study of 148 patients receiving either LP ( n = 70 ) or HR ( n = 78 ) . Eight-point blood glucose profiles and HbA1c measurements were collected at baseline , 1.5 , 3.5 and 5.5 months . RESULTS Two-hour post-breakfast and 2-hour post-supper blood glucose levels ( means [ and st and ard errors ] ) were significantly lower for LP than for HR at the end point ( 9.5 [ 0.4 ] mmol/L v. 10.9 [ 0.4 ] mmol/L and 8.4 [ 0.4 ] mmol/L v. 9.7 [ 0.4 ] mmol/L , respectively , p = 0.02 in both cases ) . HbA1c improved from 10.5 % ( 0.2 % ) ( LP ) and 10.3 % ( 0.2 % ) ( HR ) to 8.0 % ( 0.1 % ) . Hypoglycemia rates were similar during the day ; however , there was an overnight trend to reduced rates with LP ( 0.08 [ 0.03 ] episodes/30 d v. 0.16 [ 0.04 ] episodes/30 d , p = 0.057 ) . Quality -of life assessment showed significant improvement ( p < 0.05 ) in the diabetes-related worry scale for LP subjects whereas HR subjects slightly worsened . CONCLUSIONS With traditional twice-daily insulin administration algorithms , LP improves 2-hour postpr and ial glucose levels , quality of life and overnight hypoglycemia rates while delivering an equivalent level of glycemic control ( HbA1c ) compared with HR to insulin-naïve patients with type 2 diabetes who require insulin OBJECTIVE To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia . Research design and methods An open-label , r and omised , 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness . The efficacy of each treatment was evaluated by glycaemic control ( HbA(1c ) ) , eight-point home blood glucose profiles , and the frequency and severity of hypoglycaemic episodes and quality of life . RESULTS Eighteen ( 55 % ) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study . There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin ( 55 vs 84 episodes , p=0.087 ) . This result ed principally from a 47 % lower incidence of nocturnal severe hypoglycaemia with insulin lispro ( 25 vs 47 episodes , p=0.11 ) . The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments ( HbA(1c ) 9.1 % insulin lispro vs 9.3 % regular human insulin ) . CONCLUSIONS In individuals with type 1 diabetes , who have impaired awareness of hypoglycaemia , treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes . Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia , although a larger study is required to confirm these findings AIM To compare the efficacy and safety of premixed insulin aspart ( 30 % free and 70 % protamine-bound , BIAsp 30 ) with human insulin premix ( BHI 30 ) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes . METHODS People with Type 1 and Type 2 diabetes ( n = 294 ) using twice-daily insulin were r and omized to a 12-week open-label comparison of BIAsp 30 and BHI 30 . Efficacy was assessed by analysis of variance of 12-week data , adjusted for baseline level . RESULTS BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure , HbA1c , mean difference -0.01 ( 90 % confidence interval ( CI ) -0.14 ; 0.12 ) % Hb . Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group ( -0.68 ( -1.20 ; -0.16 ) mmol/l ; P < 0.02 ) . Significant improvements were observed after breakfast , before lunch , after dinner and at bedtime ( P < 0.02 - 0.05 ) , with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group . The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30 . However , the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments . CONCLUSION Post-pr and ial glycaemic control was significantly improved , without increasing the risk of hypoglycaemia , and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30 AIMS In intensified insulin therapy , the recent development of short-acting insulin analogues with a very rapid onset of action forces a new discussion in terms of the optimal injection-meal interval . This study evaluated pr and ial glycaemia in patients with Type 1 diabetes following the subcutaneous injection of soluble human insulin ( HI ) and the insulin analogue insulin aspart ( IAsp ) at different injection-meal intervals and investigated whether administration of IAsp after the meal might provide satisfactory metabolic control . METHODS In a r and omized , double-blind , double-dummy , four-period crossover study , 20 Type 1 diabetic patients were investigated . Pr and ial insulin was administered 15 min before the start of the meal ( HI(-15min ) ) , immediately before the meal ( HI(0min ) ; IAsp(0min ) ) and 15 min after the start of the meal ( IAsp(+15min ) ) . RESULTS Plasma glucose excursions from baseline levels during the 4 h ( PGexc ) were highest with HI(0min ) ( 17.9 mmol.l(-1).h ; P < 0.05 vs. other treatments ) and were not statistically different for HI(-15min ) , IAsp(0min ) and IAsp(15min ) ( 13.6 , 11.9 and 14.2 mmol.l(-1).h , respectively ) . Maximum concentration of plasma glucose ( PGmax ) was lowest with IAsp(0min ) ( 11.2 mmol/l ; P < 0.05 vs. other treatments ) . PGmax was comparable with HI(-15min ) , HI(0min ) and IAsp(+15min ) ( 13.3 , 14.1 and 13.2 mmol/l , respectively ) . CONCLUSIONS With regard to pr and ial glycaemia IAsp(+15min ) is as effective as HI(-5min ) and superior to HI(0min ) . Thus , post-pr and ial dosing of the insulin analogue IAsp offers an attractive and feasible therapeutic option for well-controlled patients with Type 1 diabetes mellitus AIMS To ascertain whether pre-meal administration of 50 % insulin lispro and 50 % neutral protamine lispro ( NPL ) , given as a fixed mixture ( Humalog Mix50 , human soluble ( regular ) insulin as a basal-bolus regimen in people with Type 1 diabetes . Both regimens included bedtime human isophane ( NPH ) insulin . METHODS This was a multinational , multicentre , r and omized , open-label , two-period crossover comparison of two insulin treatments for two 12-week periods in 109 patients with Type 1 diabetes . The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose ( BG ) values . Eight-point BG profiles , frequency of hypoglycaemia , HbA1c , insulin dose , time of injection , and frequency of snacking were assessed during each treatment . RESULTS Total daily insulin dose was similar for both treatments , but the total pre-meal doses were higher ( P < 0.001 ) and the bedtime dose of isophane was lower ( P < 0.001 ) with Mix50 . The pre-meal dose before breakfast and lunch , although statistically different ( P = 0.006 and P < 0.001 , respectively ) , was of similar magnitude , but the pre-evening meal dose was higher with Mix50 ( P < 0.001 ) . Median ( interquartile range ) time of insulin injection before meals was : Mix50 4.2 ( 25th percentile = 1.0 ; 75th percentile = 6.3 ) min , human soluble insulin 24.6 ( 25th percentile = 16.6 ; 75th percentile = 30.0 ) min . Pre-meal and bedtime BG concentrations did not differ between treatments . The BG 2 h after the evening meal was lower with Mix50 ( 8.40 + /- 2.95 mmol/l vs. 9.60 + /- 3.47 mmol/l ) ( P = 0.049 ) . BG after breakfast and lunch , mean HbA1c , frequency of hypoglycaemia , frequency of snacks , and body weight were not different . CONCLUSION The use of Mix50 in a basal-bolus regimen achieved similar control of pre-meal BG to human soluble insulin , and overall glycaemic control and hypoglycaemia risk were equivalent . This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals OBJECTIVE To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment . RESEARCH DESIGN AND METHODS This was a multicenter r and omized double-blind crossover study of 90 male subjects with type 1 diabetes . Insulin aspart or soluble human insulin was administered before meals , and NPH insulin was administered at bedtime as basal therapy . Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile . RESULTS The 24-h plasma glucose control obtained with insulin aspart , as assessed by excursions of blood glucose outside a predefined normal range ( 4.0 - 7.0 mmo/l ) , was superior ( 22 % reduction in excursion , P < 0.01 ) . Fructosamine levels remained unchanged with insulin aspart , with daytime glycemic control superior but nighttime glycemic control inferior . Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postpr and ial blood glucose control after lunch and dinner ( P < 0.05 ) without deterioration of prepr and ial blood glucose control . Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin ( 20 vs. 44 events , P < 0.002 ) . Insulin aspart was well tolerated . CONCLUSIONS In comparison with human insulin , insulin aspart can improve postpr and ial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes . For its full potential to be realized , it will need to provide better control of nighttime hyperglycemia OBJECTIVE To determine whether the long-term use of insulin lispro ( LP ) affects the counterregulatory hormone response to hypoglycemia . RESEARCH DESIGN AND METHODS Ten patients ( age range 26 - 51 years ; ratio of men to women 9:1 ; BMI 24.9 ± 0.48 ; mean HbA1c 7.84 ± 0.25 % ) with IDDM , treated with continuous subcutaneous insulin infusion ( CSII ; Disetronic H-TRON V100 ) were studied using a double-blind , crossover design . Patients were r and omized to LP or human regular insulin ( HR ) for 3 months and then crossed over to the other insulin for an additional 3 months . All meal boluses were given 0 - 5 min before breakfast , lunch , and dinner . Counterregulatory hormone responses to a stepped hypoglycemic clamp ( consecutive glucose levels in mmol/l : 4.2 ; 3.5 ; 2.8 , each for 1 h ) were evaluated at the end of each treatment period . RESULTS HbA1c was significantly lower with LP versus HR ( 7.47 ± 0.28 % vs. 7.9 ± 0.26 % , P = 0.04 ) . The incidence of hypoglycemia per 30 days ( capillary blood glucose < 3.0 mmol/l and /or symptoms ) during the last month of the study was significantly lower with LP versus HR ( 8.7 ± 2.9 vs. 11.8 ± 2.9 , P = 0.03 ) . The total daily insulin dosage was not different in the two treatment periods . There was no episode of severe hypoglycemia or diabetic ketoacidosis . The peak growth hormone , cortisol , glucagon , and epinephrine responses during the same period of hypoglycemia were not different for each treatment period . CONCLUSIONS The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia OBJECTIVE To compare the efficacy of the short-acting insulin analog lispro ( LP ) with that of regular insulin in IDDM patients treated with an external pump . RESEARCH DESIGN AND METHODS Thirty-nine IDDM patients ( age , 39.4 ± 1.5 years ; sex ratio , 22M/17W ; BMI , 24.4 ± 0.4 kg/m2 ; diabetes duration , 22.5 ± 1.6 years ) who were treated by external pump for 5.1 ± 0.5 years were involved in an open-label , r and omized , crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM , U-100 ( ACT ) . Boluses were given 0–5 min ( LP ) or 20–30 min ( ACT ) before meals . Blood glucose ( BG ) was monitored before and after the three meals every day . RESULTS The decrease in HbA1c was more pronounced with LP than with ACT ( −0.62 ± 0.13 vs. −0.09 ± 0.15 % , P = 0.01 ) . BG levels were lower with LP ( 7.93 ± 0.15 vs. 8.61 ± 0.18 mmol/l , P < 0.0001 ) , particularly postpr and ial BG levels ( 8.26 ± 0.19 vs. 9.90 ± 0.20 mmol/l , P < 0.0001 ) . St and ard deviations of all the BG values ( 3.44 ± 0.10 vs. 3.80 ± 0.10 mmol/l , P = 0.0001 ) and of postpr and ial BG values ( 3.58 ± 0.10 vs. 3.84 ± 0.10 mmol/l . P < 0.02 ) were lower with LP . The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT ( 7.03 ± 0.94 vs. 7.94 ± 0.88 per month , respectively ) , but the rate of occurrences of very low BG , defined as BG < 2.0 mmol/l , were significantly reduced with LP ( 0.05 ± 0.05 vs. 0.47 ± 0.19 per month , P < 0.05 ) . At the end of the study , all but two ( 95 % ) of the patients chose LP for the extension phase . CONCLUSIONS When used in external pumps , LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion ( CSII ) using an external insulin pump . In this 24-week multicenter , r and omized , two-way crossover , open-label trial , 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks , followed by the alternate treatment for another 12 weeks . Efficacy and safety measures included hemoglobin A(1c ) ( HbA(1c ) ) at baseline and endpoint , home blood glucose monitoring , hypoglycemia , and frequency of pump catheter occlusion . Patients consumed a st and ard test meal on three occasions , with determinations of fasting , 1- and 2-h postpr and ial glucose values . Insulin lispro use was associated with a significantly lower HbA(1c ) than was buffered regular human insulin ( 7.41+/-0.97 vs. 7.65+/-0.85 mmol/l ; P=.004 ) . Fasting serum glucose values before the test meal were similar between the two therapies . The 1-h ( 11.16+/-4.29 vs. 13.20+/-4.68 mmol/l ; P=.012 ) and 2-h ( 9.64+/-4.10 vs. 12.53+/-4.64 mmol/l ; P=.001 ) postpr and ial glucose concentrations were significantly lower during treatment with insulin lispro . No differences between treatments were observed in basal or bolus insulin doses , weight gain , or the incidence and rate of hypoglycemia , hyperglycemia , or pump occlusions . When used in external pumps , insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile OBJECTIVE Because of age-related developmental and cognitive issues , children < 10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision . The purpose of this study was to determine if insulin pump therapy at nighttime only , when children are at home , could improve fasting and nighttime blood glucose levels without adverse effects . RESEARCH DESIGN AND METHODS The study cohort consisted of 10 children aged 7 - 10 years . A r and omized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night , combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin , with 3 insulin injections per day . Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range ( 70 - 150 mg/dl ) before meals , at bedtime , and at 3:00 A.M. ; serum fructosamine levels ; and scores on measures of adherence and fear of hypoglycemia . RESULTS Compared with baseline levels , the use of the pump result ed in a significant decrease in the mean average ( P < 0.001 ) , breakfast ( P < 0.0001 ) , and 3:00 A.M. ( P < 0.003 ) blood glucose levels . There was a decrease in the percentage of blood glucose values less than the target range ( P < 0.01 ) and in fructosamine ( P < 0.01 ) values and an increase in the percentage of blood glucose levels within the target range ( P < 0.03 ) . CONCLUSIONS Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump The relationship between symptomatic ( subjective feelings ) and biochemical ( blood glucose concentration less than 3 mmol l-1 ) hypoglycaemia was studied in 66 r and omly selected insulin-dependent diabetic out- patients under normal conditions of daily life with conventional insulin injection regimens . The patients ( a ) collected 7-point diurnal blood glucose profiles at home on three consecutive days and then once weekly for 3 weeks , ( b ) indicated whether they felt hypoglycaemic at sampling times , and ( c ) collected extra sample s if they felt hypoglycaemic at any time during the study period . The weekly frequencies of symptomatic and biochemical hypoglycaemia were 0.99 and 1.75 per patient , respectively . Biochemical hypoglycaemia was present in 29 % of the symptomatic episodes , and symptomatic hypoglycaemia accompanied 16 % of the biochemical episodes . Symptomatic hypoglycaemia was experienced at a median blood glucose concentration of 3.4 mmol l-1 ( range 1.4 - 14.9 mmol l-1 ) . Fifty per cent of both symptomatic and biochemical episodes occurred before lunch , while the remainder were evenly distributed throughout the day . The occurrence of biochemical hypoglycaemia , but not of symptomatic hypoglycaemia , was inversely correlated with HbA1c and median blood glucose concentration . Thus symptomatic hypoglycaemia is an unreliable indicator of biochemical hypoglycaemia and of the degree of glycaemic control . Blood glucose measurements are a prerequisite for the diagnosis of hypoglycaemia Insulin aspart ( IAsp ) , is a rapid-acting analogue of human insulin ( HI ) , for use in the meal related treatment of diabetes mellitus . The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months . The prospect i ve , multicentre , r and omised , open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes . Main outcome measures were blood glucose control assessed by HbA1c , nine-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia and adverse events . An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin , particularly in the IAsp group . After 12 weeks of treatment , HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 ( 95 % CI 0.30 - 0.04 ) ( P<0.05 ) . Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast ( mean 8.4 vs 10.1 mmol/l ; P<0.0001 ) and dinner ( 8.2 vs 9.3 mmol/l ; P<0.01 ) . There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles . The WHO Diabetes Treatment Satisfaction Question naire score for perceived hyperglycaemia was lower with Iasp ( P=0.005 ) , and patients found the insulin aspart treatment more flexible ( P=0.022 ) . The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp Objective : To compare the safety , efficacy and management of insulin lispro ( LP ) with regular human insulin ( RH ) in young diabetic children treated with continuous subcutaneous insulin infusion ( CSII ) . Study Design : 27 very young diabetic children ( age 4.6 ± 2.2 years ) treated with CSII participated in an open-label , r and omized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH . Results : Mean daily basal rate was significantly higher during the LP period ( p = 0.04 ) . No differences were seen in changes in HbA1c levels , number of hypoglycemic events , cutaneous infections and catheter occlusions . There was no significant difference between the two treatments for prepr and ial and postpr and ial glucose values , although pr and ial glucose excursions tended to be lower with LP ( significant at dinner , p = 0.01 ) . Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy ( p < 0.05 ) . No episode of ketoacidosis occurred during LP treatment . More parents indicated that LP made their own and the child ’s daily life easier ( p = 0.02 ) and preferred LP ( p = 0.01 ) . Conclusions : LP in CSII therapy in children is safe , as effective as RH , improved postpr and ial excursions , met the needs of young children in their daily life well , and gained their parents ’ satisfaction and preference . However , a shorter duration of LP result ed in hyperglycemia during the first part of the night , which must be compensated for by increasing nocturnal basal rates during this time Insulin lispro was compared with regular human insulin with respect to glycaemic control in patients with diabetes mellitus on intensive insulin treatment . Sixty-two patients ( 55 type 1 ; 7 type 2 ) from eight study centres in the Czech Republic , Slovenia and the Slovak Republic participated in a 4-month , open-label , r and omized , crossover study . Patients administered insulin lispro immediately before meals or regular human insulin 30 min before meals . A test meal ( 220 - 400 kcal ) , based on local and individual dietary habits and consistent for each patient throughout the study was given at baseline and at the end of each treatment . At each test meal visit HbA1c , fasting blood glucose , 1-hour and 2-hour postpr and ial blood glucose levels were measured . The level of HbA1c ( 7.6 % + /- 1.5 % versus 7.4 % + /- 1.5 % ) , incidence of hypoglycaemia ( 41 - 66 % of patients --versus 39 - 63 % ) and daily insulin dose ( 0.67 + /- 0.11 U/kg versus 0.65 + /- 0.11 U/kg ) did not differ between treatment groups at endpoint ( insulin lispro versus regular human insulin , respectively ) . Mean 2-hour postpr and ial blood glucose excursion for the insulin lispro group ( 0.0 + /- 3.7 mmol/L ) was significantly lower ( p = 0.035 ) when compared with the regular human insulin group ( 1.3 + /- 3.7 mmol/L ) at endpoint . Therapy with insulin lispro was therefore associated with a significant improvement in postpr and ial blood glucose excursion control when compared with regular human insulin , without an increase in rate of hypoglycaemia OBJECTIVE To compare the efficacy and safety of prepr and ial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes . STUDY DESIGN Open r and omised multicentre study . Women were treated with multiple insulin injections aim ing at normoglycaemia . Blood glucose was determined six times daily , HbA(1c ) every 4 weeks . Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21 , 28 and 34 . PARTICIPANTS 33 pregnant women with type 1 DM were r and omised to treatment with lispro insulin ( n=16 ) or regular insulin ( n=17 ) . RESULTS Blood glucose was significantly lower ( P<0.01 ) after breakfast in the lispro group , while there were no significant group differences in glycemic control during the rest of the day . Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia ( blood glucose < 3.0 mmol/l ) was more frequent in the lispro than in the regular group ( 5.5 vs. 3.9 % , respectively ) . HbA(1c ) values at inclusion were 6.5 and 6.6 % in the lispro and regular group respectively . HbA(1c ) values declined during the study period and were similar in both groups . There was no perinatal mortality . Complications during pregnancy , route of delivery and foetal outcome did not differ between the groups . Retinopathy progressed in both groups , one patient in the regular group developed proliferative retinopathy . CONCLUSION The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies A common treatment regimen for patients with either insulin-dependent diabetes mellitus ( IDDM ) or non-insulin-dependent diabetes mellitus ( NIDDM ) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day . It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal . In practice , patients often inject regular human insulin closer to mealtime , causing a higher post-pr and ial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period . Insulin lispro , a rapid-acting insulin analogue , is best injected just before a meal because of its more rapid absorption and shorter duration of action . In 707 r and omized patients , 379 with IDDM and 328 with NIDDM , we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin ( isophane insulin ) on premeal , 2-hour postpr and ial , and bedtime glycemic control . Assessment s were based on the results of a seven-point blood glucose profile , the insulin dose ( by formulation and time of administration ) , the incidence and frequency of hypoglycemic episodes , and the glycated hemoglobin value . Treatment with insulin lispro result ed in lower postpr and ial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin . Overall glycemic control , frequency of hypoglycemic events , and total insulin dose were not different between the two groups . Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-pr and ial glycemic control without increasing the risk of hypoglycemia Aim : Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human‐soluble insulin but reduces rates of hypoglycaemia . We tested the hypothesis that the use of rapid‐acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy AIM Nonfasting plasma glucose is cl aim ed to be a better marker of diabetic control than fasting plasma glucose in type 2 diabetes . In this study we compared the efficacy and safety profile of two different intensive insulin treatment strategies in patients with uncontrolled type 2 diabetes despite using a twice-daily insulin regimen . METHODS We studied 60 insulin-treated patients who had uncontrolled type 2 diabetes . The study was a 6-month , open-label , r and omised , parallel clinical trial conducted in two diabetes centres . The main end-points for analysis were weekly self-monitored blood glucose readings , HbA1c levels , total daily insulin dose , weight gain and the number of hypoglycaemic episodes . RESULTS The breakfast 2-h , lunch 2-h and dinner 2-h postpr and ial glucose values and pre-dinner glucose values were significantly lower in the Lispro group than the regular insulin group . The HbA1c value at the end of the study was significantly lower in the Lispro group ( 7.3 + /- 0.7 % ) compared with the regular insulin group ( 7.7 + /- 0.7 % ; P<0.05 ) . Mean insulin doses were similar in the treatment groups initially and at the end . There was a statistically significant increase in insulin dose in both groups from baseline to the end of the study ( P<0.05 ) . Overall hypoglycaemia rates were comparably low and similar in both groups during the study . CONCLUSIONS We have shown that mealtime insulin Lispro plus additional lunch and bedtime NPH insulin is superior to premeal regular insulin plus bedtime NPH insulin for overall glycaemic regulation with similar weight gain and comparable rates of hypoglycaemia OBJECTIVE To compare the efficacy and safety of insulin glulisine ( GLU ) , a new rapid-acting insulin analogue , injected 0 to 15 minutes before or immediately after meals , with regular human insulin ( RHI ) , injected 30 to 45 minutes before meals . METHODS Patients with type 1 diabetes ( N = 860 ) received once-daily insulin glargine and subcutaneous injections of either GLU ( premeal or postmeal ) or premeal RHI in this open-label , r and omized , controlled , multicen-ter , parallel-group , 12-week study . RESULTS Baseline to endpoint changes in mean gly-cated hemoglobin ( as A1c equivalents ) ( A1c ) occurred in the premeal GLU , postmeal GLU , and premeal RHI groups ( -0.26 % , -0.11 % , and -0.13 % , respectively ) . The reduction in A1c was greater for the premeal GLU group in comparison with the RHI group ( P = 0.02 ) and the post-meal GLU group ( P = 0.006 ) ; no significant between-treatment difference was found for postmeal GLU versus RHI . Overall , blood glucose profiles were similar in all 3 treatment groups but were significantly lower for premeal GLU 2-hour postbreakfast measurements ( premeal versus postmeal GLU , P = 0.0017 ; premeal GLU versus RHI , P = 0.0001 ) and 2-hour postdinner measurements ( premeal GLU versus RHI , P = 0.0001 ; premeal versus postmeal GLU , P = 0.0137 ) . Severe hypoglycemic episodes were comparable for premeal GLU , postmeal GLU , and pre-meal RHI groups ( 8.4 % , 8.4 % , and 10.1 % , respectively ) . Body weight increased ( + 0.3 kg ) in the RHI and premeal GLU groups ; however , weight decreased in the postmeal GLU group ( -0.3 kg ; between-treatment difference , P = 0.03 ) . CONCLUSION Better A1c reductions were obtained with premeal GLU , but postmeal administration of GLU was as safe and effective as premeal GLU or RHI in combination with insulin glargine and was not associated with weight gain AIM To compare the therapeutic efficacy of the short-acting insulin analogue insulin lispro ( Humalog ) with that of buffered regular human insulin ( Velosulin ) in patients on insulin pump therapy . PATIENTS AND METHODS Sixty-two ( 45 women and 17 men ) young patients with type 1 diabetes using insulin pump therapy were compared while using buffered regular human insulin for a mean + /- s.e.m . of 20.1+/-1.2 months or insulin lispro for a mean + /- s.e.m . of 19.7+/-0.5 months . The initial mean + /- s.e.m . age and duration of diabetes were 29.1+/-0.9 and 17.7+/-0.9 years , respectively . The mean HbA1c values , basal insulin dosages , premeal insulin dosages and number of low blood sugars were recorded during treatment with both insulins . RESULTS Mean + /- s.e.m . HbA1c values were significantly lower ( p < 0.001 ; paired Wilcoxon t-test ) during insulin lispro treatment ( 7.4+/-0.1 % ) as compared to treatment with buffered regular human insulin ( 7.9+/-0.1 % ) . Total units of insulin ( mean + /- s.e.m.)/kg/day was significantly ( p = 0.03 ) lower ( 0.61+/-0.02 ) during the insulin lispro treatment period as compared to the buffered regular human insulin treated period ( 0.65+/-0.03 ) . Total mean + /- s.e.m . ( U/kg/day ) of basal insulin administered per day was higher when patients received insulin lispro treatment ( 0.44+/-0.02 vs. 0.42+/-0.01 for buffered regular human insulin treated period ; p = 0.002 ) . The premeal insulin boluses ( mean + /- s.e.m . ) for the two treatment groups were significantly different with less insulin required for the insulin lispro treatment period for all three meals ( p < 0.001 , t-test ) . The number of mild/moderate and severe hypoglycaemic episodes were similar in the two groups . CONCLUSION We conclude that use of insulin lispro in pump therapy significantly lowers HbA1c values in comparison to therapy with buffered regular human insulin insulin without increasing hypoglycaemic episodes OBJECTIVE To compare insulin lispro with regular human insulin with respect to blood glucose control and frequency of hypoglycaemia in patients with type 1 diabetes who wished to fast during the month of Ramadan . RESEARCH DESIGN AND METHODS Insulin lispro or regular human insulin was given together with NPH insulin , twice daily before the morning and evening meals , for two weeks each in an open-label , r and omised , cross-over design , and 64 patients completed the protocol . Blood glucose was self-monitored at fasting morning and evening , and 1-h and 2-h after the post-sunset meal on three consecutive days at the end of each treatment period . RESULTS The 2-h blood glucose excursion after the post-sunset meal was significantly ( p=0.026 ) lower with insulin lispro ( 2.50 + /- 0.46 mmol/l ) than with regular human insulin ( 3.47 + /- 0.49 mmol/l ) . Daily insulin doses did not differ between treatments but compliance with recommended time of injection was better with insulin lispro . Hypoglycaemia incidence ( insulin lispro , 15 ( 23.4 % ) patients ; regular human insulin 31 ( 48.4 % ) patients ; p=0.004 ) and frequency ( insulin lispro , 0.70 + /- 0.19 ; regular human insulin 2.25 + /- 0.36 episodes/patient/30 days ; p<0.001 ) were lower with insulin lispro . Five ( 22.7 % ) of the episodes during insulin lispro occurred during the nocturnal period compared with 27 ( 36.5 % ) of the episodes while on regular human insulin . CONCLUSIONS Glycaemic control , measured by postpr and ial glycemic excursions , was improved and hypoglycaemia was significantly reduced with insulin lispro compared with regular human insulin . Patients with type 1 diabetes who insist on fasting during Ramadan may be better managed with insulin lispro To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus ( DM ) in patients already in chronic good glycaemic control with conventional insulins , 69 patients on intensive therapy ( 4 daily s.c . insulin injections , soluble at each meal , NPH at bedtime , HbA1c < 7.5 % ) were studied with an open , cross-over design for two periods of 3 months each ( lispro or soluble ) . The % HbA1c and frequency of hypoglycaemia were assessed under four different conditions ( Groups I-IV ) . Lispro was always injected at mealtime , soluble 10 - 40 min prior to meals ( with the exception of Group IV ) . Bedtime NPH was continued with both treatments . When lispro replaced soluble with no increase in number of daily NPH injections ( Group I , n = 15 ) , HbA1c was no different ( p = NS ) , but frequency of hypoglycaemia was greater ( p < 0.05 ) . When NPH was given 3 - 4 times daily , lispro ( Group II , n = 18 ) , but not soluble ( Group III , n = 12 ) decreased HbA1c by 0.35 + /- 0.25 % with no increase in hypoglycaemia . When soluble was injected at mealtimes , HbA1c increased by 0.18 + /- 0.15 % and hypoglycaemia was more frequent than when soluble was injected 10 - 40 min prior to meals ( Group IV , n = 24 ) ( p < 0.05 ) . It is concluded that in intensive management of Type 1 DM , lispro is superior to soluble in terms of reduction of % HbA1c and frequency of hypoglycaemia , especially for those patients who do not use a time interval between insulin injection and meal . However , these goals can not be achieved without optimization of basal insulin OBJECTIVE To compare long-term glycemic control and safety of using insulin aspart ( IAsp ) with that of regular human insulin ( HI ) . RESEARCH DESIGN AND METHODS This was a multicenter r and omized open-label 6-month study ( 882 subjects ) with a 6-month extension period ( 714 subjects ) that enrolled subjects with type 1 diabetes . Subjects administered IAsp immediately before meals or regular HI 30 min before meals ; basal NPH insulin was taken as a single bedtime dose in the majority of subjects . Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals . RESULTS Mean postpr and ial blood glucose levels ( mg/dl + /- SEM ) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast ( 156 + /- 3.4 vs. 185 + /- 4.7 ) , lunch ( 137 + /- 3.1 vs. 162 + /- 4.1 ) , and dinner ( 153 + /- 3.1 vs. 168 + /- 4.1 ) , when assessed after 6 months of treatment . Mean HbA1c values ( % + /- SEM ) were slightly , but significantly , lower for the IAsp group ( 7.78 % + /- 0.03 ) than for the regular HI group ( 7.93 % + /- 0.05 , P = 0.005 ) at 6 months . Similar postpr and ial blood glucose and HbA1c values were observed at 12 months . Adverse events and overall hypoglycemic episodes were similar for both treatment groups . CONCLUSIONS Postpr and ial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment . The improvement was not obtained at an increased risk of hypoglycemia . HbA1c was slightly , but significantly , lower for IAsp compared with HI at 6 and 12 months OBJECTIVE To establish whether the short-acting insulin analog lispro can be successfully implemented in long-term intensive insulin therapy in type 1 diabetes , and if so , what its effects are on glycemic control and frequency and awareness of hypoglycemia . RESEARCH DESIGN AND METHODS We r and omized 56 type 1 diabetic patients to treatment with either lispro ( n = 28 ) or human regular insulin ( Hum-R ; n = 28 ) as mealtime insulin for 1 year ( open design , parallel groups ) . Lispro was injected at mealtime and Hum-R was given 10 - 40 min before meals ( bedtime NPH was continued on both occasions ) . With lispro , NPH was added at breakfast ( approximately 70/30 ) , lunch ( approximately 60/40 ) , and supper ( approximately 80/20 ) ( mixing percentage of lispro/NPH ) to optimize premeal and bedtime blood glucose . RESULTS Total daily insulin units were no different in the two treatment groups , but with lispro approximately 30 % less short-acting insulin at meals and approximately 30 % more NPH was needed versus Hum-R ( P < 0.05 ) . The bedtime NPH dosage was no different . With lispro + NPH , the mean daily blood glucose was lower than with Hum-R ( 8.0 + /- 0.1 vs. 8.8 + /- 0.1 mmol/l ; P < 0.05 ) , HbA1c was lower ( 6.34 + /- 0.10 vs. 6.71 + /- 0.11 % , mean value over 1 year ; P < 0.002 ) , and hypoglycemia ( blood glucose < or = 3.8 mmol/l ) was less frequent ( 7.4 + /- 0.5 vs. 11.5 + /- 0.7 episodes/patient-month ) and tended to occur more within 90 min after meals than in the postabsorptive state ( P < 0.05 vs. Hum-R ) . After 1 year , plasma adrenaline and symptom responses to experimental , stepped hypoglycemia improved with lispro and were closer to the responses of 12 nondiabetic control subjects versus Hum-R both in terms of thresholds and magnitude ( P < 0.05 ) . CONCLUSIONS We concluded that mealtime injection of lispro + NPH improves the 24-h blood glucose and the percentage HbA1c as compared with Hum-R. The improvement can be maintained long term . Intensive therapy with lispro + NPH results in less frequent hypoglycemia and better awareness and counterregulation of hypoglycemia AIMS Insulin aspart has been shown to improve post-pr and ial and overall glycaemic control in people with Type 1 diabetes . We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with st and ard basal NPH insulin . METHODS The trial was conducted in 43 centres in seven countries . People with Type 1 diabetes were r and omized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25 % increase in bedtime NPH dose ( n = 187 ) , or to mealtime human unmodified insulin with once or twice daily basal NPH insulin ( n = 181 ) . Efficacy and safety were evaluated at 12 weeks ( primary evaluation period ) and 64 weeks . RESULTS At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups : -0.09 ( 95 % confidence interval ( CI ) -0.23 , + 0.05)% and -0.14 ( -0.32 , + 0.04)% . Post-pr and ial glucose values were lower and the area under the 24-h self-monitored blood glucose curve above 7.0 mmol/l was 28 % smaller with insulin aspart ( 35.2 + /- 3.2 vs. 48.9 + /- 3.1 mmol/l h , P = 0.0015 ) . No significant differences were found in mild or severe hypoglycaemia , or adverse event rate . At 64 weeks treatment satisfaction was higher in the insulin aspart group ( difference 1.57 ( 95 % CI 0.49 , 2.64 ) points , P = 0.004 ) , while quality of life was not different . CONCLUSIONS Improved post-pr and ial glycaemic control and treatment satisfaction with insulin aspart were confirmed . Intensifying basal insulin supplementation result ed in a similar HbA1c decrement as previously found with the use of insulin aspart and st and ard NPH insulin supplementation . This does not support routinely basal NPH insulin intensification when using rapid-acting insulin analogues in daily practice AIMS To evaluate a multiple daily injections ( MDI ) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally . METHODS Twenty-five C-peptide negative Type 1 patients already trained to MDI were r and omized to lispro ( lispro + NPH 5 min before breakfast and lunch , lispro before dinner , NPH at bedtime ) or soluble insulin ( 20 - 30 min before each meal and NPH at bed-time ) for 3 months before crossing over to the other regimen for another 3 months . The mean initial HbA1c level was 8.32+/-1.5 % . RESULTS The variability of capillary blood glucose values was significantly lower with lispro ( MAGE 0.75+/-0.36 g/l vs. 0.99+/-0.50 , P<0.01 ; MODD 0.64+/-0.26 g/l vs. 0.80+/-0.40 , P<0.05 ) . There was a nonsignificant reduction in HbA1c with lispro : -0.40+/-0.86 vs. -0.08+/-0.71 . Mean daily blood glucose levels were significantly lower with lispro ( 1.53+/-0.48 g/l vs. 1.82+/-0.57 g/l , P<0.05 ) . The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro , P = 0.048 . At the end of the study , 75 % of the patients chose the lispro associated with multiple NPH regimen for their own treatment . The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro ( 53 % vs. 34 % ) . CONCLUSIONS An MDI regimen using lispro combined with multiple NPH compared to a st and ard MDI regimen using soluble insulin reduced day-to-day blood glucose fluctuations , was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control BACKGROUND Pregnancy outcome in diabetic women is strictly related to glycemic control during pregnancy . The aim of our study was to compare pregnancy outcome between patients subjected to intensive insulin therapy using regular human insulin and those treated with insulin lispro ( Humalog ) . MATERIAL / METHODS Group A ( n=25 ) was treated with Humalog , and the control group B ( n=46 ) with regular human insulin . Mean age , duration of diabetes , presence of chronic diabetic complications ( according to the White classification ) parity , and BMI did not differ between groups . RESULTS The mean HbA1c concentrations in groups A and B were respectively : 7.8+/-1.4 % vs. 7.5+/-1.5 % in the first trimester , 6.4+/-0.8 % vs. 6.5+/-1.6 % in the second , and 6.7+/-0.7 % vs. 6.3+/-1.2 % in the third ( no significant differences ) . The duration of pregnancy was 36.4+/-3.9 weeks in group A and 37.1+/-1.9 weeks in group B , while the mean neonatal birth weight was 3467+/-790 and 3367+/-666 g , respectively . Neither the frequency of preterm labor and cesarean section nor the frequency of fetal macrosomia and hypoglycemia differed between groups . There was only one malformed infant in the human insulin-treated group , and no statistical difference in the rate of spontaneous abortion between groups . Also , there were no differences in the frequencies of occurrence of hypertension ( essential and pregnancy induced ) and urinary tract infections . CONCLUSIONS The course of pregnancy and perinatal outcome is comparable in intensively treated diabetic women regardless of the short-acting insulin used . Humalog appears to be a safe alternative to human insulin in the treatment of diabetes during pregnancy OBJECTIVE To measure the effectiveness of insulin lispro , a fast-acting insulin analog , in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy . RESEARCH DESIGN AND METHODS In 11 diabetes outpatient clinics in the U.K. , 165 subjects with type 1 diabetes were enrolled in a r and omized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen . Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months . The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level . RESULTS A total of 135 patients were r and omized , with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months . The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction . Glycemic control was equally tight during treatment with human regular insulin ( HbA1c , 6.2 + /- 0.8 % ) and insulin lispro ( 6.0 + /- 0.9 % ) . A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro ( P = 0.04 ) . This difference was chiefly because of a reduced number of nocturnal episodes ( 181 vs. 52 , P = 0.001 ) in the insulin lispro group . CONCLUSIONS The use of a fast-acting insulin analog , insulin lispro , as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy Summary Objective : To compare the plasma glucose ( PG ) response with a fixed mixture of 25 % insulin lispro and 75 % NPL ( Mix25 ) , prior to a meal and 3 h before exercise , to human insulin 30/70 ( 30/70 ) in patients with type 2 diabetes . Research design and methods : Thirty-seven patients were treated in a r and omized , open-label , 8-week , two-period crossover study . Mix25 was injected 5 min before breakfast and dinner throughout the study , as was 30/70 on inpatient test days and on outpatient dose titration days . Following the 4-week outpatient phase , patients were hospitalized , and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min , separated by 30 min rest , starting 3 h after a 339 kcal breakfast . Results : The 2-h postpr and ial PG was significantly lower with Mix25 ( ( mean ± SEM ) 10.5 ± 0.4 mmol/lvs 11.6 ± 0.4 mmol/l ; p = 0.016 ) . Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 ( -3.6 ± 0.29 mmol/l vs -4.7 ± 0.31 mmol/l ; p = 0.001 ) . The maximum decrease in PG over 6 h , after exercise onset , was significantly less with Mix25 ( -4.3 ± 0.4 mmol/l vs -5.9 ± 0.4 mmol/l ; p < 0.001 ) . The frequency of hypoglycemia ( blood glucose ( BG ) < 3 mmol/l or symptoms ) during the inpatient test was not different between treatments . During the outpatient phase , the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 ( 0.7 ± 0.2 episodes/30d vs 1.2 ± 0.3 episodes/30 d ; p = 0.042 ) . Conclusions : Mix25 result ed in better postpr and ial PG control without an increase in exercise-induced hypoglycemia . The smaller decrease in PG during the postpr and ial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70 , especially for patients in tight glycemic control BACKGROUND Insulin lispro is an insulin analog that was recently developed particularly for a mealtime therapy . It has a fast absorption rate and short duration of action . The efficacy of insulin lispro in the clinical therapy of patients with non-insulin-dependent diabetes mellitus ( NIDDM ) has not been tested . OBJECTIVES To compare insulin lispro and human regular insulin in the mealtime treatment of patients with NIDDM . METHODS A 6-month , r and omized , multinational ( 16 countries ) , multicenter ( 80 sites ) clinical trial with an open-label , crossover design was performed in 722 patients with NIDDM . Insulin lispro was injected immediately before and human regular insulin 30 to 45 minutes before the meal . RESULTS Throughout the study , the postpr and ial rise in serum glucose levels was significantly lower during insulin lispro than human regular insulin treatment . At end point the rise ( mean + /- SEM ) in serum glucose levels was 30 % lower at 1 hour ( 2.6 + /- 0.1 mmol/L [ 46.8 + /- 1.8 mg/ dL ] for lispro vs 3.7 + /- 0.1 mmol/L [ 66.6 + /- 1.8 mg/dL ] for human regular insulin ) and 53 % lower 2 hours after the test meal ( 1.4 + /- 0.1 mmol/L [ 25.2 + /- 1.8 mg/dL ] for lispro vs 3.0 + /- 0.1 mmol/L [ 54.0 + /- 1.8 mg/dL ] for human regular insulin ) with insulin lispro compared with human regular insulin therapy ( P < .001 for both intervals ) . During insulin lispro therapy the rate of hypoglycemia overall ( P = .01 ) and overnight ( P < .001 ) was lower and the number of asymptomatic hypoglycemic episodes was smaller ( P = .03 ) than during human regular insulin therapy . Associated with a similar 13 % increase ( P < .001 ) in the total daily insulin dose , the glycosylated hemoglobin level decreased ( P < .001 ) equally in both treatment groups . Serum lipid and lipoprotein levels remained unchanged . There were no differences in the adverse events between the 2 treatment groups . CONCLUSIONS Compared with human regular insulin therapy , mealtime therapy with insulin lispro reduced postpr and ial hyperglycemia and may decrease the rate of mild hypoglycemic episodes in patients with NIDDM OBJECTIVE IGF‐I levels in patients with type 1 diabetes without endogenous insulin production are low . Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF‐I and IGFBP‐1 than that seen during treatment with conventional human insulin ( regular insulin ) Insulin lispro [ Lys ( B28 ) , Pro ( B29 ) human insulin ] is a rapidly absorbed analog that has diminished tendency to self-associate . In four open-label , 1-year-long international r and omized trials , we contrasted the immunogenicity of insulin lispro versus regular human insulin ( RHI ) in patients previously treated with insulin who had IDDM or NIDDM . Using a self-blank subtraction assay , we assessed sera for the presence of insulin-specific antibodies ( ISA ) , insulin lispro-specific antibodies ( LSA ) , and cross-reactive antibodies ( CRA ) . Basal insulin needs were provided either with human ultralente ( UL ) or NPH insulins . After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH , 50 % of patients were r and omly assigned to begin insulin lispro or continue on RHI . At baseline , few pretreated patients had LSA ( 0–4 % ) and ∼ 10 % had ISA , whereas 41–45 % of patients with IDDM and 23–27 % of patients with NIDDM had CRA ( IDDM vs. NIDDM , P < 0.001 ) . Within studies , no significant differences were noted over time in ISA , LSA , or CRA attributable to the type of short-acting insulin . When data were pooled , inconsistent changes were noted in ISA and LSA ( LSA were greater in NIDDM vs. IDDM at baseline , P = 0.001 , and ISA were greater in IDDM vs. NIDDM at 6 months , P = 0.007 ) . Significant levels of CRA were more common in IDDM at all times ( P < 0.001 , P = 0.022 , and P = 0.002 at baseline , 6 months , and 12 months , respectively ) . For patients receiving insulin lispro , no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study ( became positive , remained positive , became negative , or remained negative ) . IDDM patients were more likely to develop or maintain CRA levels ( P = 0.008 vs. NIDDM ) , whereas antibody levels were comparable among positive individuals . No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients The primary objectives of this study were to assess the efficacy and safety of Lys(B28 ) , Pro(B29 ) in the treatment of patients with diabetes mellitus and to compare Lys(B28 ) , Pro(B29 ) to currently available regular insulin with respect to quality of life . This study was design ed as an open-label , non-comparative one . The number of patients enrolled in the trial was 39 . At Visit 1 ( week 0 ) , blood sample s for fasting , 1- and 2-hour postpr and ial blood glucose , and HbA1c were taken . At Visit 2 ( week 6 ) and Visit 3 ( week 12 ) , fasting , 1- and 2-hour postpr and ial blood glucose , and HbA1c levels were measured again . There was no significant change in HbA1c , fasting blood glucose and 1- and 2-hour postpr and ial blood glucose levels . The 1- and 2-hour postpr and ial blood glucose excursions decreased significantly from Visit 1 to Visit 3 . There were no serious adverse events during the study . Half of the patients had less hypoglycemia with LysPro insulin , while 25 % had an increase in episodes . Thirty percent of patients were more satisfied with LysPro insulin than with the short-acting insulin that they had previously used . In conclusion , LysPro therapy can be regarded as safe , since there were no unexpected adverse events and no changes in the usual physical parameters AIMS To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy . METHODS In this multinational , double-blind , r and omised , crossover trial , 155 patients with Type 1 diabetes ( HbA(1c ) < 8.0 % ) were symmetrically r and omised to two 16-week treatment periods on either type of insulin , both injected 0 - 5 min before meals . NPH insulin was given as basal insulin once or twice daily as needed , and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control . Treatment periods were separated by a 4-week washout . RESULTS The rate of major nocturnal ( 24.00 - 06.00 h ) hypoglycaemic episodes was 72 % lower with insulin aspart than with human insulin ( 0.067 vs. 0.225 events/month ; P = 0.001 ) . Total rate of major hypoglycaemia did not differ significantly between treatments ( insulin aspart/human insulin relative risk 0.72 ; 95 % CI 0.47 - 1.09 , P = 0.12 ) . The rate of minor events was significantly reduced by 7 % with insulin aspart ( P = 0.048 ) . Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control : Mean HbA(1c ) remained constant , slightly below 7.7 % on both treatments . CONCLUSIONS The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinical ly significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control . Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy OBJECTIVE For intensified insulin therapy of type 1 diabetes , bolus injection of regular human insulin 30–15 min before a meal is currently recommended . This r and omized study is aim ed to determine whether insulin lispro ( LIS ) , a new insulin analog with a rapid onset of action , can provide comparable blood glucose ( BG ) control by injection after the meal . RESEARCH DESIGN AND METHODS Eighteen type 1 diabetic subjects injected regular insulin ( REG ) at 40 , 20 , or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a st and ardized test meal . BG excursions and area under the curve of BG excursions ( AUC ) at the six visits were compared by analysis of variance . Hypoglycemic events ( BG ≤2.78 mmol/1 ) were evaluated in relation to the achieved postpr and ial BG control . RESULTS Mean AUC values were 2.00 , 2.55 , and 3.33 mmol · h · 1−1 for REG given 40 , 20 , and 0 min before the test meal , respectively , and −2.19 , −2.15 , and 1.98 mmol · h · 1−1 for LIS given 20 and 0 min before and 15 min after the start of the test meal , respectively . LIS injected 20 min ( −20 ) or immediately ( 0 ) before the meal was significantly more effective in controlling postpr and ial BG excursion ( P < 0.001 ) than any REG treatment . Postpr and ial injection of LIS ( 15 ) did not compromise postpr and ial BG control and result ed in less hypoglycemia . REG −40 and LIS −20 were associated with early hypoglycemia , but other hypoglycemic events were equally distributed among groups . CONCLUSIONS The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS . LIS injected immediately after a st and ard meal provided postpr and ial BG control at least as good as REG injected from 40 to 0 min before the meal . Postpr and ial injection of LIS is an attractive new therapeutic option OBJECTIVE To compare health-related quality of life ( HRQOL ) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin ( Humulin R ) . RESEARCH DESIGN AND METHODS We performed two r and omized comparative studies over a 6-month period ( 3 months per treatment ) . Primary analyses used crossover baseline to 3-month changes in HRQOL scores . Ninety-three principal investigators in Canada , France , Germany , and the U.S. participated in these studies . One HRQOL crossover study included 468 patients with type I diabetes ; the other HRQOL crossover study included 474 patients with type II diabetes . In both studies , patients were taking insulin at least 2 months before enrollment . Primary outcomes included two generic HRQOL domains , energy/fatigue and health distress , and two diabetes-specific domains , treatment satisfaction and treatment flexibility . Thirty secondary outcomes included both generic and diabetes-specific measures . Secondary outcome domains were controlled for multiplicity in the analyses . RESULTS Primary analyses showed that treatment satisfaction scores ( P < 0.001 ) and treatment flexibility scores ( P = 0.001 ) were higher for insulin lispro in type I diabetic patients . No other significant treatment differences were detected using the data from these 6-month crossover studies . CONCLUSIONS Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro . Other HRQOL findings were comparable for insulin lispro and regular human insulin . Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes , as demonstrated by increased treatment satisfaction and treatment flexibility AIMS To compare the efficacy of insulin aspart , a rapid-acting insulin analogue , with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus . METHODS Prospect i ve , multi-centre , r and omized , open-labelled , parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes . Study patients were r and omized 2:1 to insulin aspart or unmodified human insulin before main meals , with NPH-insulin as basal insulin . Main outcome measures were blood glucose control as assessed by HbA1c , eight-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia , and adverse events . RESULTS After 6 months , insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 ( 95 % confidence interval 0.03 - 0.22 ) % Hb , P < 0.02 . Eight-point blood glucose profiles showed lower post-pr and ial glucose levels ( mean baseline-adjusted -0.6 to -1.2 mmol/l , P < 0.01 ) after all main meals , but higher pre-pr and ial glucose levels before breakfast and dinner ( 0.7 - 0.8 mmol/l , P < 0.01 ) with insulin aspart . Satisfaction with treatment was significantly better in patients treated with insulin aspart ( WHO Diabetes Treatment Satisfaction Question naire ( DTSQ ) baseline-adjusted difference 2.3 ( 1.2 - 3.3 ) points , P < 0.001 ) . The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 ( 0.59 - 1.18 , NS ) . Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart ( 1.3 vs. 3.4 % of patients , P < 0.05 ) , as were late post-pr and ial ( 4 - 6 h ) events ( 1.8 vs. 5.0 % of patients , P < 0.005 ) . CONCLUSIONS These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control , hypoglycaemia , and quality of life , in people with Type 1 diabetes mellitus AIMS To evaluate the acceptability and efficacy of an injection of insulin lispro , before an afternoon meal . METHODS The subjects , 43 patients with Type 1 diabetes , 16 boys and 27 girls , aged 12.4 + /- 2.4 years , were r and omly assigned to the treatment ( n = 20 ) or the untreated control group ( n = 23 ) . The treatment was an injection of insulin lispro immediately before the afternoon meal . The control group had no injection . The treatment and the control group consumed identical types of meals for 2 months . The mean before-dinner blood glucose was measured during the last 2 weeks of the study . RESULTS Injection of insulin lispro result ed in a significant reduction in the before-dinner blood glucose compared with the untreated control group ( 10.4 + /- 3.8 mmol/l vs. 14.7 + /- 3.9 mmol/l , respectively ) . The number of days on which the blood glucose was > 10 mmol/l was reduced by half in the insulin lispro group . The difference in HbA1c between baseline and endpoint differed slightly but significantly between the two groups , in boys . Treated patients ate the meal less frequently ( 11.4 + /- 3.0 times per 15 days ) than the control patients ( 14.4 + /- 0.6 times per 15 days ) and injected themselves with insulin 8.9 + /- 3.6 times per 15 days . The HbA1c increased significantly with the number of meals taken without injection . There was no statistically significant difference in the frequency of hypoglycaemia or changes in weight between the two groups . CONCLUSIONS We conclude that an injection of insulin lispro before the afternoon meal can effectively lower the before-dinner blood glucose , and in boys also lowers the HbA1c . Patients were satisfied with the lower blood glucose before dinner , and did not find the insulin lispro injection difficult . However , compliance with the protocol procedures decreased during a subsequent 6-month period OBJECTIVE Unmodified regular insulin has a long absorption tail , unlike the fast-acting insulin analog lispro , and may contribute to hypoglycemia in the early part of the night . A r and omized crossover double-blind study was performed to compare blood glucose concentrations in the early part of the night in type 1 diabetic patients receiving lispro or unmodified regular human insulin , in r and om order , on 2 separate study days . RESEARCH DESIGN AND METHODS We studied 23 C-peptide-negative patients ; 12 were using a premeal plus basal insulin regimen , and 11 were using twice-daily insulin injections . Patients were admitted to the investigation unit at 5:00 P.M. and received a single dose of lispro or unmodified regular human insulin before the evening meal . In both groups , the NPH insulin dose remained unchanged . Identical meals and snacks were eaten at the same time during both study days . RESULTS Average postpr and ial ( 6:00−10:00 P.M. ) blood glucose concentrations were significantly lower after lispro therapy compared with human insulin ( 7.1 ± 0.4 [ SE ] vs. 8.5 ± 0.4 mmol/l , P = 0.0002 ) . Nighttime ( midnight to 4:00 A.M. ) blood glucose concentrations were significantly higher after lispro compared with human insulin ( 10.3 ± 0.4 vs. 9.1 ± 0.4 mmol/l , P = 0.02 ) . This difference was greatest in patients on the premeal plus basal insulin regimen ( 11.6 ± 0.5 vs. 8.7 ± 0.4 mmol/l , P < 0.001 ) . The incidence of nocturnal hypoglycemia ( midnight to 4:00 A.M. , blood glucose < 3.5 mmol/l ) was less with lispro compared with unmodified insulin ( 1 vs. 6 patients , P = 0.04 ) . Nighttime ( midnight to 4:00 A.M. ) 3-hydroxybutyrate ( 102 ± 13 vs. 51 ± 7 mumol/l , P = 0.000 ) and glycerol ( 52 ± 3 vs. 42 ± 2 mumol/l , P < 0.01 ) were significantly higher after lispro therapy compared with human insulin in patients on the premeal plus bolus insulin regimen . CONCLUSIONS Lispro can improve postpr and ial blood glucose control and reduce the incidence of nocturnal hypoglycemia at the expense of nocturnal hyperglycemia and hyperketonemia in patients using a premeal plus basal insulin regimen OBJECTIVE Several studies have suggested that use of the short-acting insulin analog , insulin lispro , in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin . This effect might be more pronounced in well-controlled patients , since intensive treatment of IDDM increases the rate of severe hypoglycemic events . This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients . RESEARCH DESIGN AND METHODS This was an open , r and omized , 6-month crossover study of 199 IDDM patients . Glycemic control was evaluated by HbA1c , home blood glucose measurements , and rate and timing of hypoglycemic events . At the end of the study , patients completed an evaluation form regarding therapy-related quality of life . RESULTS HbA1c remained constant at ∼ 7.3 % throughout the study . Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin ( mean −0.8 ± 1.7 vs. 1.1 ± 1.6 mmol/l , P < 0.001 ) , as was the within-day variability ( M value 27.7 ± 19.7 vs. 30.2 ± 23.1 , P = 0.007 ) . The incidence of severe hypoglycemic events ( 58 vs. 36 , P = 0.037 ) including coma ( 16 vs. 3 , P = 0.004 ) was significantly lower with insulin lispro than with regular insulin . Patients felt that insulin lispro increased flexibility and freedom of lifestyle . CONCLUSIONS In well-controlled IDDM patients , insulin lispro is associated with a lower risk of severe hypoglycemia and coma The objective of this 6-month , open-label , r and omized , two-period crossover study was to compare glycemic control when patients were treated with ( 1 ) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation , neutral protamine lispro ( NPL ) , and ( 2 ) 2 manufactured premixed human insulin formulations , human insulin 50/50 and human insulin 30/70 . One hundred individuals , 37 with type 1 diabetes mellitus ( 12 females , 25 males ; mean age , 39.4 years ; mean body mass index [ BMI ] , 24.8 ; mean duration of diabetes , 12.9 years ) and 63 with type 2 diabetes mellitus ( 33 females , 30 males ; mean age , 59.0 years ; mean BMI , 28.4 ; mean duration of diabetes , 12.6 years ) , were treated with insulin lispro mixtures . Insulin lispro Mix50 ( 50 % insulin lispro/50 % NPL ) and human insulin 50/50 ( 50 % regular insulin/50 % neutral protamine Hagedorn [ NPH ] insulin ) were administered before breakfast ; insulin lispro Mix25 ( 25 % insulin lispro/75 % NPL ) and human insulin 30/70 ( 30 % regular insulin/70 % NPH ) were administered before dinner . Blood glucose ( BG ) , hypoglycemic episodes ( hypoglycemic signs or symptoms or BG < 3.0 mmol/L ) , insulin dose and timing of dose before meals , and hemoglobin A1c were measured . Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups . However , compared with human insulin mixtures , twice-daily administration of insulin lispro mixtures result ed in improved postpr and ial glycemic control , similar overall glycemic control , and less nocturnal hypoglycemia , as well as offering the convenience of dosing closer to meals Summary The aim of these studies was to compare the pharmacokinetics , pharmacodynamics , counterregulatory hormone and symptom responses , as well as cognitive function during hypoglycaemia induced by s. c. injection of 0.15 IU/kg of regular human insulin ( HI ) and the monomeric insulin analogue [ Lys(B28),Pro ( B29 ) ] ( MI ) in insulin-dependent-diabetic ( IDDM ) subjects . In these studies glucose was infused whenever needed to prevent decreases in plasma glucose below 3 mmol/l . After MI , plasma insulin increased earlier to a peak ( 60 vs 90 min ) which was greater than after HI ( 294±24 vs 255±24 pmol/l ) , and plasma glucose decreased earlier to a 3 mmol/l plateau ( 60 vs 120 min ) ( p<0.05 ) . The amount of glucose infused to prevent plasma glucose falling below 3 mmol/l was ∼three times greater after MI than HI ( 293±26 vs 90±25 μmol · kg−1 · 60–375 min−1 , p<0.05 ) . After MI , hepatic glucose production was more suppressed ( 0.7±1 vs 5.9±0.54 μmol · kg−1 · min−1 ) and glucose utilization was less suppressed than after HI ( 11.6±0.65 vs 9.1±0.11μmol · kg−1 · min−1 ) ( p<0.05 ) . Similarly , plasma NEFA , glycerol , and β-OH-butyrate were more suppressed after MI than HI ( p<0.05 ) , whereas plasma lactate increased only after MI , but not after HI . Responses of counterregulatory hormones , symptoms and deterioration in cognitive function during plasma glucose plateau of 3 mmol/l were superimposable after MI and HI ( p = NS ) . Post-hypoglycaemia hyperglycaemia was greater after MI than HI ( at 480 min 12.1±1 vs 11±1 mmol/l ) because of greater hepatic glucose production during insulin waning which occurred at least 135 min earlier with MI as compared to HI ( p<0.05 ) . It is concluded that counterregulatory hormones , symptoms and deterioration in cognitive function during hypoglycaemia respond similarly after MI and HI . The biological effect of MI appears greater than that of HI for at least 4 h after the s.c . injection and appears as a good c and i date for achieving optimal post-pr and ial glucose control in IDDM OBJECTIVE This study compared the glucose-lowering effect of insulin lispro , given before or after meals , with regular human insulin given before meals in prepubertal children with diabetes . RESEARCH DESIGN AND METHODS A 3-way crossover , open-label study involving 61 prepubertal children ( ages 2.9 - 11.4 years ) with type 1 diabetes . The children were r and omly assigned to receive regular human insulin 30 to 45 minutes before meals , insulin lispro within 15 minutes before or immediately after meals , combined with basal insulin . Each treatment lasted 3 months . Hemoglobin A(1c ) levels and home glucose monitoring profiles were measured at the end of each treatment period . RESULTS Treatment with insulin lispro before breakfast result ed in lower 2-hour postpr and ial glucose values than regular human insulin ( 11.7 + /- 4.4 mmol/L vs 15.0 + /- 5.4 mmol/L ) . Similarly , insulin lispro given before dinner result ed in lower blood glucose values 2 hours postpr and ially ( 8.8 + /- 5.0 mmol/L vs 10.8 + /- 5.4 mmol/L ) than regular human insulin . When insulin lispro was administered after meals , the 2-hour glucose levels were between those seen with either insulin lispro or regular human insulin given before meals . The number and types of adverse events , the rates of hypoglycemia , and the HbA(1c ) levels did not differ among the 3 therapies . CONCLUSIONS In prepubertal children , insulin lispro given before meals is safe and significantly lowers postpr and ial glucose levels after breakfast and dinner compared with regular human insulin , and insulin lispro given after the meal provides similar benefits as regular human insulin before the meal OBJECTIVE To compare the effects of Humalog Mix25 ( Humalog Mix75/25 in the USA ) ( Mix25 ) and human insulin 30/70 ( 30/70 ) on the 24-hour inpatient plasma glucose ( PG ) profile in patients with type 2 diabetes mellitus ( T2DM ) . DESIGN A r and omised , open-label , 8-week crossover study . Study insulins were injected twice daily , 5 minutes before breakfast and dinner . SETTING Four-week outpatient ( dose-adjustment ) treatment phase , and 3-day inpatient ( test ) phase . PATIENTS Twenty-five insulin-treated patients with T2DM ( ages 40 - 66 years ) , mean ( + /- st and ard error of the mean ) ( SEM ) HbA1c 7.7 % + /- 0.23 % , and body mass index ( BMI ) 29.3 + /- 0.83 kg/m2 . OUTCOME MEASURES 24-hour PG profiles , PG excursions after meals , PG area under the curve ( AUC ) , and 30-day hypoglycaemia rate . RESULTS The 2-hour PG excursions following breakfast ( 5.5 + /- 0.34 v. 7.2 + /- 0.34 mmol/l , p = 0.002 ) and dinner ( 2.4 + /- 0.27 v. 3.4 + /- 0.27 mmol/l , p = 0.018 ) were smaller with Mix25 than with 30/70 . PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 ( 77.6 + /- 3.8 v. 89.5 + /- 4.3 mmol/h/ml , p = 0.001 ) . PG AUC between lunch and dinner , dinner and bedtime , and bedtime and breakfast did not differ between treatments . Pre-meal and nocturnal PG were comparable . The postpr and ial insulin requirement for lunch meals was supplied equally by the two insulin treatments . The thirty-day hypoglycaemia rate was low ( Mix25 0.049 + /- 0.018 v. 30/70 0.100 + /- 0.018 episodes/patient/30 days , p = 0.586 ) for both treatments . CONCLUSION In patients with T2DM , Mix25 improved the 24-hour PG profile with lower postpr and ial PG excursions than with human insulin 30/70 BACKGROUND : In this study , we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 ( BIAsp30 ) with that of biphasic human insulin 30 ( BHI30 ) over a period of 24 months in patients with type 2 diabetes . METHODS : Patients with type 2 diabetes ( n=125 ) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a r and omized , controlled , multinational trial . RESULTS : No significant difference was found in mean HbA(1c ) after 24 months [ BIAsp30 , 8.35+/-0.20 % ; BHI30 8.13+/-0.16 % ; adjusted mean difference ( BIAsp30-BHI30 ) 0.03 ( 90 % CI -0.29 to 0.34)% , P=0.89 ] . The proportion of patients experiencing major hypoglycaemia was also similar during the first year ( BIAsp30 , 5 % ; BHI30 , 8 % ; P=0.72 ) , but it was significantly lower with BIAsp30 than with BHI30 during the second year ( BIAsp30 , 0 % ; BHI30 , 10 % ; P=0.04 ) . The proportion experiencing minor hypoglycaemia was not significantly different . No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months ( BIAsp30 , 4.87+/-1.92 % ; BHI30 ; 1.00+/-1.66 % ; P=0.13 ) . Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group ( P=0.07 ) . CONCLUSIONS : Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c ) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes OBJECTIVE Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin . Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion ( CSII ) treatment were assessed in an open r and omized crossover trial comparing insulin lispro and regular human insulin , both applied with insulin pumps . RESEARCH DESIGN AND METHODS A total of 113 type 1 patients ( 60 male , 53 female , age [ mean + /- SD ] 37 + /- 12 years , duration of diabetes 19 + /- 9 years ) participated in this open , r and omized crossover study . Both insulins were applied for 4 months each with the appropriate intervals between the pr and ial insulin bolus and the meal ( human insulin : 30 min ; lispro : 0 min ) . Observation parameters were HbA1c , daily and postpr and ial blood glucose profiles , adverse events , rate of hypoglycemic and hyperglycemic events , number of catheter obstructions , and treatment satisfaction as assessed with an international vali date d question naire . RESULTS The patients were well controlled with a mean HBA1c of 7.24 + /- 1.0 % at baseline . HbA1c decreased in both treatment periods , but it was better during insulin lispro treatment ( insulin lispro : 6.8 + /- 0.9 % , regular human insulin : 6.9 + /- 1.0 % , Friedman 's rank-sum test : P < 0.02 ) . In addition , the 1-h and 2-h postpr and ial rises in blood glucose were significantly lower ( P < 0.001 for each meal ) with insulin lispro , result ing in smoother daily glucose profiles as compared with regular human insulin . No significant differences were reported for the rate of hypoglycemia ( mean + /- SD [ median ] : insulin lispro 12.4 + /- 13.9 [ 8 ] , regular human insulin 11.0 + /- 11.2 [ 8 ] ) , for the rate of catheter obstructions ( 42 events in each treatment arm ) , and for the number and type of adverse events . No severe case of ketoacidosis was seen during insulin lispro treatment , whereas one case was reported during therapy with regular human insulin . Treatment satisfaction was better when patients were treated with insulin lispro . CONCLUSIONS Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment . Its safety profile does not differ from that of regular human insulin A total of 166 patients ( 102 type 1 , 64 type 2 ) were r and omised to insulin lispro ( LP ) combined with insulin lispro protamine suspension ( NPL ) , an intermediate-acting formulation of LP , or to regular human insulin ( HR ) combined with human NPH insulin ( NPH ) in this open-label , parallel study . Insulin doses were similar at endpoint . Blood glucose ( BG ) measurements ( before and two hours after meals , bedtime , 3 a.m.)(mmol/l ) were lower with LP/NPL two hours after breakfast ( 8.84 + /- 0.32 vs 10.29 + /- 0.41 , p < 0.001 ) , before lunch ( 6.21 + /- 0.20 vs 7.10 + /- 0.31 , p = 0.016 ) , two hours after the evening meal ( 10.18 + /- 0.36 vs 7.86 + /- 0.28 , p < 0.0.001 ) , and at bedtime ( 7.85 + /- 0.28 vs 9.43 + /- 0.40 , p = 001 ) . HbA1c was lower for LP/NPL at endpoint ( 7.54 + /- 0.11 % vs 7.92 + /- 0.10 % , p = 0.019 ) . There was no difference in hypoglycaemia or insulin antibody levels . LP/NPL result ed in better glycaemic control than HR/NPH without increasing the risk of hypoglycaemia OBJECTIVE Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation ( NPL ) in a ratio of 25:75 % . The objective of this study was to compare Humalog Mix25 to human insulin 30/70 ( 30 % regular insulin/70 % NPH ) with respect to glycemic control . RESEARCH DESIGN AND METHODS Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month r and omized open-label two-period crossover study . Each insulin was administered twice daily , before the morning and evening meals . Information regarding self-monitored blood glucose ( BG ) , hypoglycemic episodes ( hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l ) , insulin dose , and HbA1c was collected . RESULTS Treatment with Humalog Mix25 result ed in better postpr and ial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70 . Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments . CONCLUSIONS In comparison to treatment with human insulin 30/70 , twice daily administration of Humalog Mix25 result ed in improved postpr and ial glycemic control , similar overall glycemic control , and the convenience of dosing immediately before meals Aims The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus ( T1DM ) . We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen Transitioning safely to insulin therapy when oral antidiabetic agents fail to provide adequate glycemic control is a critical aspect of care for the patient with type 2 diabetes mellitus ( T2DM ) . We evaluated the clinical effectiveness of starting patients on a relatively simple regimen of once-daily injections of either biphasic insulin aspart 70/30 ( 10 min before dinner ) , NPH insulin ( at 10 p.m. ) , or biphasic human insulin 70/30 ( 30 min before dinner ) in combination with metformin . Enrolled patients had T2DM and inadequate glycemic control ( AlC>/=7.5 % ) on a previous regimen of metformin as monotherapy or in combination with a sulphonylurea . One hundred and forty ( 140 ) patients received metformin monotherapy for 4 weeks followed by 12 weeks of combination treatment with metformin and once-daily insulin injections . AlC levels decreased from baseline by 1.1 - 1.3 % for patients in each of the three treatment groups . Overall , FPG values decreased from baseline by 31 % ( biphasic insulin aspart ) , 37 % ( NPH insulin ) , and 28 % ( biphasic human insulin ) . Subjects whose final FPG level was < 126 mg/dl experienced the largest decreases in AlC values ( -2.3 % , -1.9 % , -1.8 % , respectively ) . All three treatment regimens were well tolerated . The results indicate that patients with T2DM can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart 70/30 , biphasic human insulin 70/30 , or NPH insulin in combination with metformin Aims To study whether post‐pr and ial insulin lispro ( PL ) could be used as a part of insulin therapy instead of premeal human regular insulin ( HR ) in prepubertal children with Type 1 diabetes mellitus ( Type 1 DM ) Intensive insulin management improves glycemic control and lowers the risks of long-term microvascular complications ( 1 ) . Several new insulin analogs ( 2 ) are in use to improve glycemic control in type 1 diabetes . Glargine in particular is a “ basal insulin ” ( 3 ) and found to be relatively peakless . Glargine is thought to provide glucose profiles similar to insulin pumps ( 4 ) . Although some clinical studies suggest that glargine lasts 24 h in children with diabetes ( 5 ) , to date there have been no formal pharmacokinetic and pharmacodynamic data to make that cl aim in the pediatric population . In fact , clinical observations in pediatric type 1 diabetes suggest that glargine action may be < 24 h. This would entail twice-daily glargine dosing and short-acting insulin analogs ( SAIs ) , such as lispro and aspart , given separately three to four times per day , result ing in improved glycemic control but compromising compliance and increasing complexity of management ( 6 ) . In this study , we tested the hypothesis that mixing glargine with SAIs and dividing the dose of glargine into twice- versus once-daily dosing would not adversely affect glycemic control as assessed by a continuous glucose monitoring system ( CGMS ) . The protocol was approved by the institutional review board of the Baylor College of Medicine , and consent was obtained before each study . Subjects were recruited from Texas Children ’s Hospital Diabetes Care Center , Houston , Texas . Subjects had type 1 diabetes for at least 1 year with no other chronic illness and were on Aim : To identify factors associated with nocturnal hypoglycaemia in patients with type 2 diabetes who were new ( < 2 months therapy ) to insulin therapy Insulin lispro is a human insulin analog that dissociates more rapidly than human regular insulin after subcutaneous injection , result ing in higher insulin levels at an earlier point in time and a shorter duration of action . The aim of the study was to evaluate if this pharmacokinetic difference would translate into better postpr and ial and overall control in 30 IDDM patients ( age , 35.1 ± 1.5 years ; male-female ratio , 17:13 ; BMI , 24.8 ± 0.5 kg/m2 ; HbA1c , 8.03 ± 0.13 % at baseline ) treated with continuous subcutaneous insulin infusion ( CSII ; Disetronic H-TRON V100 ) in a double-blind crossover clinical study . Patients were r and omized to insulin lispro or human regular insulin for 3 months before crossing over to the other insulin for another 3 months . All meal boluses were given immediately before breakfast , lunch , and supper . An eight-point blood glucose profile was measured once weekly , and HbA1c levels were measured monthly . At the end of the 3-month treatment period , HbA1c levels were significantly lower with insulin lispro , compared with human regular insulin : 7.66 ± 0.13 vs. 8.00 ± 0.16 % ( P = 0.0041 ) . While prepr and ial , bedtime , and 2:00 A.M. values for blood glucose were not significantly different , 1-h postpr and ial blood glucose was significantly improved after breakfast , lunch , and dinner with insulin lispro , compared with human regular insulin : 8.35 vs. 9.79 mmol/l ( P = 0.006 ) , 7.58 vs. 8.74 mmol/l ( P = 0.049 ) , and 7.85 vs. 9.01 mmol/l ( P = 0.03 ) . The incidence of hypoglycemia per 30 days ( blood glucose levels , < 3.0 mmol/l ) was 8.4 ± 1.3 before r and omization , decreasing to 6.0 ± 0.9 for insulin lispro and to 7.6 ± 1.3 for regular insulin during the last month of the study . Two patients in each group reported insulin precipitation . We conclude that insulin lispro improves glycemic control in CSII without increasing the risk of hypoglycemia |
13,451 | 22,177,461 | ( S ) Elective single embryo transfer is associated with decreased risks of PTB and LBW compared with DET but higher risks of PTB compared with spontaneously conceived singletons | OBJECTIVE To determine whether elective single embryo transfer ( eSET ) lowers the risk of poor perinatal outcomes associated with IVF , when [ 1 ] compared with double embryo transfer ( DET ) or multiple embryo transfer ( MET ) , and separately , [ 2 ] compared with spontaneous conceptions . | BACKGROUND We analysed the difference in maternal , neonatal and total costs after single ( SET ) versus double day 3 embryo transfer ( DET ) . METHODS We performed a two-centre prospect i ve study of women in their first IVF/ICSI cycle choosing between SET or DET . Infertility treatment data were gathered from a data base ; maternal and neonatal outcome data from a case report form ( CRF ) ; health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills . SET was performed in 206/367 ( 56.1 % ) and DET in 161/367 ( 43.9 % ) women . RESULTS In all , 367 transfers yielded 186 positive pregnancy tests , 148 ongoing pregnancies and 136 live deliveries ( 50.7 , 40.3 and 37.1 % per embryo transfer ) of which 15 ( 11.0 % ) were twins . Live birth rate was 37.4 % for SET , 36.6 % for DET . Intention-to-treat analysis showed differences for : duration of pregnancy ( SET : 39.0 + /- 1.4 versus DET : 38.3 + /- 2.2 weeks ; P = 0.055 ) , percentage prematurity ( 8.5 versus 23.8 % ; P = 0.033 ) , percentage of neonates hospitalized ( 5.7 versus 17.9 % ; P = 0.121 ) and duration of neonatal hospitalization ( 6.3 + /- 2.2 versus 10.3 + /- 10.1 days ; P = 0.01 ) . Total cost after DET was higher ( SET : 4700 + /- 3239 versus DET : 8613 + /- 10 105 ; P = 0.105 ) , due to significantly higher neonatal costs ( 451 + /- 957 versus 3453 + /- 8154 ; P < 0.001 ) and not to differences in maternal costs ( 4250 + /- 2882 versus 5160 + /- 4106 ; P = 0.152 ) . CONCLUSIONS This prospect i ve health economic study shows that transfer of a single top quality embryo is equally effective as , but substantially cheaper than , double embryo transfer in women < 38 years of age in their first IVF/ICSI cycle BACKGROUND Transfer of several embryos after IVF results in a high multiple birth rate associated with increased morbidity and high costs for the neonatal care . In a previous r and omized trial we demonstrated that a single embryo transfer ( SET ) strategy , including one fresh single embryo transfer and , if no live birth , one additional frozen-thawed SET , result ed in a live-birth rate that was not substantially lower than after double embryo transfer ( DET ) but markedly reduced the multiple birth rate . METHODS We compared costs for maternal health care and productivity losses and paediatric costs for the SET and DET strategies . In addition , maternal and paediatric outcomes between the two groups were compared . RESULTS The SET strategy result ed in lower average total costs from treatment until 6 months after delivery . There were a few more deliveries with at least one live-born child in the DET group . The incremental cost per extra delivery in the DET alternative was high , 71 940 . The rates of prematurely born and low birthweight children were significantly lower with the SET strategy . There were also markedly fewer maternal and paediatric complications in the SET group . CONCLUSIONS The SET strategy is superior to the DET strategy , when number of deliveries with at least one live-born child , incremental cost-effectiveness ratio and maternal and paediatric complications are taken into consideration . The findings do not support continuing transfers of two embryos in this group of patients Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT BACKGROUND Elective single embryo transfer ( eSET ) in a selected group of patients ( i.e. young patients with at least one good quality embryo ) reduces the number of multiple pregnancies in an IVF programme . However , the reduced overall multiple pregnancy rate ( PR ) is still unacceptably high . Therefore , a r and omized controlled trial ( RCT ) was conducted comparing eSET and double embryo transfer ( DET ) in an unselected group of patients ( i.e. irrespective of the woman 's age or embryo quality ) . METHODS Consenting unselected patients were r and omized between eSET ( RCT -eSET ) ( n = 154 ) or DET ( RCT -DET ) ( n = 154 ) . R and omization was performed just prior to the first embryo transfer , provided that at least two 2PN zygotes were available . Non- participants received our st and ard transfer policy [ SP-eSET in a selected group of patients ( n = 100 ) , otherwise SP-DET ( n = 122 ) ] . RESULTS The ongoing PR after RCT -eSET was significantly lower as compared with RCT -DET ( 21.4 versus 40.3 % ) and the twin PR was reduced from 21.0 % after RCT -DET to 0 % after RCT -eSET . The ongoing PRs after SP-eSET and SP-DET did not differ significantly ( 33.0 versus 30.3 % ) , with an overall twin PR of 12.9 % . CONCLUSION To avoid twin pregnancies result ing from an IVF treatment , eSET should be applied in all patients . The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients . The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9 % BACKGROUND The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies . The only strategy to avoid dizygotic twins is to transfer one embryo at a time . METHODS A total of 144 women , who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection ( ICSI ) and who had no more than one previous failed treatment cycle , were r and omized to have either one or two embryos transferred . The treatment outcomes including those after frozen embryo transfer were compared between these groups . RESULTS The clinical pregnancy rate per transfer was 32.4 % in the one embryo transfer group and 47.1 % in the two embryo transfer group , the difference being not significant . Eleven twin deliveries ( n = 39 ) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group . The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3 % in the one embryo transfer group and 58.6 % in the two embryo transfer group . CONCLUSIONS Our results indicate that among women who have good quality embryos in their first IVF/ICSI , good treatment results can be achieved . They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate , while dizygotic twins can be avoided BACKGROUND With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer ( SET ) and one cycle with double embryo transfer ( DET ) after IVF and calculated the cost-effectiveness of both strategies . METHODS A r and omized controlled trial was performed in 107 women , aged < 35 years , in their first IVF cycle , with at least one good quality embryo . They were r and omized to the SET ( n = 54 ) or DET ( n = 53 ) group using a computer-generated r and om block number table , stratified for primary or secondary infertility . RESULTS The cumulative live birth rates per woman r and omized of two consecutive cycles of SET [ 41 % ; 95 % confidence interval ( CI ) 27 - 54 ] versus one cycle of DET ( 36 % ; 95 % CI 23 - 49 ) were comparable , whereas the multiple pregnancy rate was significantly higher : 37 % ( 95 % CI 15 - 59 ) in the DET and 0 % in the in the SET group ( P = 0.002 ) . Combining the medical costs of the IVF treatments ( where 1.5 more SET cycles were required to achieve each live birth ) and of pregnancies up to 6 weeks after delivery , the total medical costs of DET per live birth were 13,680 and 13,438 for SET . CONCLUSIONS Two cycles with SET were equally effective as one cycle with DET , and the medical costs per live birth up to 6 weeks after delivery were the same . However , if lifetime costs for severe h and icaps are included , more than 7000 per live birth will be saved after implementing SET . Because of the high probability of multiple pregnancies in this group of IVF patients , only SET should be performed BACKGROUND The purpose of this study was to assess the effect of alternative ways of providing information about the risks of twins on couples ' perceptions about elective single embryo transfer ( eSET ) . METHODS Couples undergoing IVF were r and omized into three groups . Group 1 received a st and ard information pack , group 2 an extra information leaflet about twin pregnancy , and group 3 an additional discussion session . The primary outcome measure was acceptability of a hypothetical policy of eSET . Data were collected by means of a question naire . RESULTS eSET was acceptable to 17 ( 27 % ) , 20 ( 30 % ) and 24 ( 32 % ) couples in groups 1 , 2 and 3 , if it meant a slight reduction in pregnancy rates , and to 51 ( 82 % ) , 55 ( 83 % ) and 53 ( 87 % ) couples , respectively , if pregnancy rates were unchanged . A fixed charge for all fresh and frozen embryo transfers following a single oocyte retrieval led to acceptability rates of 35 ( 57 % ) , 36 ( 55 % ) and 38 ( 65 % ) . CONCLUSIONS Additional information , involving an extra information leaflet and face to face discussion , did not changes couples ' attitudes towards eSET . Maintaining existing rates of pregnancy and offering a fixed charge for all embryo transfers result ing from an oocyte recovery may encourage more couples to consider eSET OBJECTIVE To determine the extent to which embryo selection by blastulation and elective single blastocyst transfer , supported by efficient cryostorage of spare embryos , can reduce multiple pregnancies and maintain or improve on the live birth rate from IVF . DESIGN Prospect i ve , nonr and omized cohort study . SETTING Sydney IVF , a private clinic in Australia . PATIENT(S ) In vitro fertilization patients aged < 38 years with three or more usable blastocyst , recruited from April 2000 through December 2001 , with pregnancies followed up until August 2004 . INTERVENTION(S ) Blastocysts were cultured and cryostored with stage-specific culture medium and low oxygen conditions . MAIN OUTCOME MEASURE(S ) Fetal heart-positive twin pregnancy rate and accumulating " take-home baby " rate per retrieval leading to blastocyst transfer . RESULT ( S ) Among 121 women who elected single fresh blastocyst transfer ( but who could elect to have two frozen blastocysts transferred at once ) , 79 ( 65.3 % ) took home a baby , with a twin pregnancy rate of 7 % . Among 285 women who chose two blastocysts for fresh transfer , 184 ( 64.2 % ) took home at least one baby , with a twin pregnancy rate of 34 % and five perinatal deaths . CONCLUSION ( S ) With technically appropriate blastocyst culture and freezing , and elective single blastocyst transfer in the fresh cycle , the overall multiple pregnancy rate can be reduced by > 75 % , permitting in this series a slight increase in the chance of taking home a baby A prospect i ve r and omized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection ( IVF/ICSI ) was carried out . First , top quality embryo characteristics were delineated by retrospectively analysing embryos result ing in ongoing twins after double embryo transfer . A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination , the absence of multinucleated blastomeres and < 20 % cellular fragments on day 2 and day 3 after fertilization . Using these criteria , a prospect i ve study was conducted in women < 34 years of age , who started their first IVF/ICSI cycle . Of 194 eligible patients , 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospect ively r and omized . In all , 26 single embryo transfers result ed in 17 conceptions , 14 clinical and 10 ongoing pregnancies [ implantation rate ( IR ) = 42.3 % ; ongoing pregnancy rate ( OPR ) = 38.5 % ] with one monozygotic twin ; 27 double embryo transfers result ed in 20 ongoing conceptions with six ( 30 % ) twins ( IR = 48.1 % ; OPR = 74 % ) . We conclude that by using single embryo transfer and strict embryo criteria , an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI , while limiting the dizygotic twin pregnancy rate to its natural incidence of < 1 % of all ongoing pregnancies OBJECTIVE To assess the efficacy of elective single embryo transfer ( e-SET ) compared to a double embryo transfer ( DET ) in a selected population including obstetrical and neonatal outcome of fresh and frozen-thawed cycles . DESIGN Prospect i ve nonr and omized study . SETTING Department of reproductive medicine . PATIENT(S ) Elective single embryo transfer was proposed to women < 36 years with adequate ovarian function , in their first or second IVF or intracytoplasmic sperm injection ( ICSI ) attempt with ejaculated sperm , with at least 4 mature oocytes and 2 fertilized top quality embryos . Patients who refused e-SET had two top embryos transferred ( DET group ) . INTERVENTION(S ) Medical management and IVF-ICSI . MAIN OUTCOME MEASURE(S ) Cumulative delivery rate , twin delivery rate , obstetrical and neonatal outcome . RESULT ( S ) According to patients ' decision , 53 women had an e-SET and 98 a DET . The cumulative delivery rate per patient was 54.7 % in the e-SET group and 49.0 % in the DET group ( P>0.05 ) . Twin delivery rate was significantly different between the two groups ( 3.5 % versus 37.5 % respectively , P<0.05 ) . Neonatal outcome in twins result ing from IVF-ICSI was found to be poorer than in singletons , considering the mean gestational age , mode of delivery , birthweight , and risk of neonatal intensive care unit admission for the infants . CONCLUSION ( S ) In a selected population , the elective transfer of one embryo with high implantation potential helped to avoid twin pregnancies without decreasing delivery rate High numbers of embryos transferred during assisted reproduction have become implicated as the cause of higher than normal twinning and multiple gestation rates following this form of therapy . However , reducing the number to a single embryo transferred has been shown to carry unfavourable results in the first cycle , but with similar cumulative live birth rates . This study tested the theory by performing a r and omized controlled trial of elective single embryo transfer ( SET ) versus double embryo transfer ( DET ) in young women , and follow them up for 1 year to determine the result of cryo-embryo transfer cycles in the two cohorts . The results showed that the probability of a live birth was not significantly different between the two groups , but with a higher rate of twins in the DET group . In addition , during the 1-year follow-up period , the live birth , clinical pregnancy and multiple pregnancy rates were also similar , and in line with the results of the r and omized trial . In conclusion , the results of this prospect i ve r and omized trial and 1-year follow-up show that in young women , elective SET should be the first line of choice . Even so , these results should be confirmed by larger r and omized studies BACKGROUND Mild in-vitro fertilisation ( IVF ) treatment might lessen both patients ' discomfort and multiple births , with their associated risks . We aim ed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy result ing in term livebirth within 1 year compared with st and ard treatment , and can also reduce patients ' discomfort , multiple pregnancies , and costs . METHODS We did a r and omised , non-inferiority effectiveness trial . 404 patients were r and omly assigned to undergo either mild treatment ( mild ovarian stimulation with gonadotropin-releasing hormone [ GnRH ] antagonist co-treatment combined with single embryo transfer ) or a st and ard treatment ( stimulation with a GnRH agonist long- protocol and transfer of two embryos ) . Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after r and omisation ( with a non-inferiority threshold of -12.5 % ) , total costs per couple up to 6 weeks after expected date of delivery , and overall discomfort for patients . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Clinical Trial , number IS RCT N35766970 . FINDINGS The proportions of cumulative pregnancies that result ed in term livebirth after 1 year were 43.4 % with mild treatment and 44.7 % with st and ard treatment ( absolute number of patients = 86 for both groups ) . The lower limit of the one-sided 95 % CI was -9.8 % . The proportion of couples with multiple pregnancy outcomes was 0.5 % with mild IVF treatment versus 13.1 % ( p<0.0001 ) with st and ard treatment , and mean total costs were 8333 euros and 10745 euros , respectively ( difference 2412 euros , 95 % CI 703 - 4131 ) . There were no significant differences between the groups in the anxiety , depression , physical discomfort , or sleep quality of the mother . INTERPRETATION Over 1 year of treatment , cumulative rates of term livebirths and patients ' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for st and ard stimulation with two embryos transferred . However , a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs |
13,452 | 25,343,450 | Implementation strategies were shown to be effective with substantial heterogeneity of treatment effects across all investigated strategies .
Especially the cooperation of different health professionals in primary care practice s might increase efficacy and guideline implementation seems to be more difficult in tertiary prevention of cardiovascular diseases | This study is an in-depth- analysis to explain statistical heterogeneity in a systematic review of implementation strategies to improve guideline adherence of primary care physicians in the treatment of patients with cardiovascular diseases .
Primary aim of this study was to explain different effects of eligible trials and to identify method ological and clinical effect modifiers .
This study aim ed to identify effect modifiers of implementation strategies on physician adherence . | 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 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 Good blood pressure ( BP ) control reduces the risk of complications in people with type 2 diabetes , yet many do not achieve this . Guidelines for managing hypertension recommend increasing antihypertensive medications until control is achieved , but the effect of such recommendations in routine primary care is unknown . AIM To evaluate the effectiveness of a BP treatment algorithm in primary care patients with type 2 diabetes . DESIGN OF STUDY A cluster r and omised controlled trial of 1534 patients with type 2 diabetes . SETTING Forty-two practice s in Nottingham , UK . METHOD Practice s were r and omised to continue usual care or to use a treatment algorithm design ed so that practice nurses and GPs would increase antihypertensive treatment in steps until the target of 140/80 mmHg was reached . Participants were assessed by a clinical interview and case note review at recruitment and at 1 year . The primary outcome measure was the proportion of participants achieving target BP at 1 year . RESULTS At 1 year there was no difference between the proportions of participants with well controlled BP in the intervention and control arms ( 36.6 % versus 34.3 % ; P = 0.27 ) . Mean systolic and diastolic blood pressures were identical in the two arms ( 143/78 mmHg ) . There was some evidence that participants in the intervention arm were more likely to be receiving higher doses of their antihypertensive drugs , although there was no significant difference in the number of different antihypertensive drugs prescribed . Participants in the intervention arm had a higher rate of primary care BP-related consultations over 12 months than those receiving usual care ( rate ratio = 1.55 , 95 % confidence interval [ CI ] = 1.26 to 1.88 , P<0.001 ) . CONCLUSION Despite increased monitoring and possibly higher doses of medication there was no improvement in blood pressure control . Improvements achieved by specialist nurse-led clinics in secondary care may not translate to people with type 2 diabetes in primary care setting OBJECTIVE To measure the effect of faith community nurse referrals versus telephone-assisted physician appointments on blood pressure control among persons with elevated blood pressure at health fairs . METHODS R and omized community-based intervention trial conducted from October 2006 to October 2007 of 100 adults who had an average blood pressure reading equal to or above a systolic of 140 mm Hg or a diastolic of 90 mm Hg obtained at a faith community nurse-led church health event . Participants were r and omized to either referral to a faith community nurse or to a telephone-assisted physician appointment . The average enrollment systolic blood pressure ( SBP ) was 149 ± 14 mm Hg , diastolic blood pressure ( DBP ) was 87 ± 11 mm Hg , 57 % were uninsured and 25 % were undiagnosed at the time of enrollment . RESULTS The follow-up rate was 85 % at 4 months . Patients in the faith community nurse referral arm had a 7 ± 15 mm Hg drop in SBP versus a 14 ± 15 mm Hg drop in the telephone-assisted physician appointment arm ( p = 0.04 ) . Twenty-seven percent of the patients in the faith community nurse referral arm had medication intensification compared to 32 % in the telephone-assisted physician appointment arm ( p = 0.98 ) . CONCLUSIONS Church health fairs conducted in low-income , multiethnic communities can identify many people with elevated blood pressure . Facilitating physician appointments for people with elevated blood pressure identified at health fairs confers a greater decrease in SBP than referral to a faith community nurse at four months Address correspondence to : L.D. Saunders , Department of Health Services Administration and Community Medicine , 13 - 103 Clinical Sciences Building , University of Alberta , Edmonton , Alberta Canada T6 G 2G3 among patients attending a primary health care ( PHC ) clinic in Soweto for antihypertensive drug therapy . In a 1-year follow-up study of an inception cohort of newly treated hypertensives , only 27 % were compliant ( defined as attending frequently enough to receive 80 % or more of their required treatment ) , 42 % were not seen after the first 3 months ( early dropouts ) , and 22 % continued to attend until the last 3 PURPOSE Dyslipidemia treatment dramatically decreases coronary heart disease risk in diabetes , yet only a minority of these patients are screened or achieve optimal low-density lipoprotein ( LDL ) cholesterol levels . Our aim was to increase the percentage of diabetic patients in whom lipid management was achieved through electronic and direct educational detailing . METHODS The study cohort comprised 884 diabetic patients at 12 primary care practice s. Practice sites were r and omized to one of three intervention groups : electronic educational detailing , direct ( face-to-face ) educational detailing , or control . Direct and electronic detailing were performed over a 12-month period . All sites were notified of our goal to enhance lipid testing among diabetic patients . Chart abstract ion was performed 15 months after the start of the intervention . For the entire population ( n=884 ) , the proportion of patients with lipid testing was calculated , and changes from pre- to postintervention were compared across groups . We compared pre- and postintervention LDL-cholesterol changes between groups using least square means to account for site variation . RESULTS Favorable provider actions increased significantly with the intervention ( + 22 % compared with + 6 % in controls , P=.01 ) . By logistic regression , electronic detailing increased the likelihood of lipid testing ( odds ratio 3.0 , confidence interval 1.6 - 5.7 ) , as did direct detailing ( odds ratio 1.8 , confidence interval 0.9 - 3.7 ) in patients with no preintervention LDL test ( n=432 ) . Lipid testing tended to increase to a greater extent at intervention sites ( + 23 % for the combination of electronic and direct detailing vs + 11 % for controls , P=.06 ) . CONCLUSIONS Brief educational detailing either through direct or electronic communication favorably impacts provider behavior regarding dyslipidemia care for diabetic patients Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose BACKGROUND Although high blood pressure is associated with significant morbidity and mortality , the proportion reaching the goal blood pressures as outlined in the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , Treatment of High Blood Pressure ( JNC 7 ) is low . We conducted a r and omized trial in primary care practice s of a multifactorial intervention targeted to improve providers ' adherence to hypertension guidelines . METHOD A total of 61 primary care practice s in North Carolina were r and omized to receive either a multifactorial intervention ( guideline dissemination via a continuing medical education session , academic detailing sessions , audit and feedback on preintervention rates of adherence , and automated blood pressure machines ) or an attention control of similar magnitude but targeted at a different guideline . Outcomes were determined through review of patient charts conducted by an independent masked quality assurance organization . RESULTS We found no difference between the 2 groups in any of the adherence measures including no difference in the percentage of patients at goal ( intervention 49.2 % , control 50.6 % ) , with undiagnosed hypertension ( 18.1 % vs 13.6 % ) , average systolic ( 126 vs 125.1 mm Hg ) , or diastolic blood pressure ( 73.1 vs 73.4 mm Hg ) . Similarly , there was no difference in provider adherence to treatment recommendations ( use of thiazide-type diuretic as first-line therapy : 32 % vs 29.5 % ; use of 2-drug therapy in stage 2 hypertension : 11.3 % vs 10.4 % ) . CONCLUSION An intensive , multifactorial intervention did not improve adherence to national hypertension guidelines among community-based primary care . Efforts should be focused on other types of interventions to improve rates of control of hypertension Introduction We aim ed to assess whether hypertension management with a structured physician information program and a feedback system leads to improved blood pressure ( BP ) control and cardiovascular outcomes . Methods Cluster r and omized ( 3 : 1 ) , open , monitored , multicenter trial in Germany . Primary care-based physicians in the information group ( IG ) received detailed training on hypertension guidelines , feedback on target-level attainment , and a reminder to intensify treatment after each patient visit , whereas the observation/control group ( CG ) did not receive any such measures . A three-level mixed model was developed . Time-independent level differences between groups , group-independent changes , and nonparallel group-specific changes over time were tested . Results A total of 15 041 ( 78.1 % ) hypertensive patients were in the IG and 4213 ( 21.9 % ) in the CG . By 1-year follow-up , 82.9 % of patients in the IG and 81.5 % in the CG remained in the study . The guideline -oriented BP target was attained by 56.8 % in the IG and 52.5 % in the CG ( + 4.3 % , P = 0.03 ) , whereas the individual BP target was attained by 57.0 % in the IG and 51 % in the CG ( P = NS ) . BP control in the IG was achieved 2 months earlier on average . Clinical inertia , defined as the absence of medication changes , despite noncontrol of BP , occurred significantly less often in the IG group . One-year cardiovascular outcomes did not differ between groups . Conclusion The delivery of systematic information in connection with a feedback system reduces clinical inertia and improves guideline adherence . Although compared with earlier studies , the hypertension control rates obtained are higher , there is still considerable room for improvement . Eur J Cardiovasc Prev Rehabil 17:271 - 279 © 2010 The European Society of OBJECTIVE To determine whether enhanced access to primary care affects the diagnostic evaluation , pharmacologic management , or health outcomes of patients hospitalized with congestive heart failure ( CHF ) . DESIGN Multisite r and omized , controlled trial . SETTING Nine Veterans Affairs medical centers . PATIENTS 443 patients who were hospitalized with a diagnosis of CHF . INTERVENTION Enhanced access to primary care , including assignment of a primary care nurse and physician , increased telephone contact , additional outpatient visits , and patient education . MAIN OUTCOME MEASURES Diagnostic evaluation , pharmacologic management , health-related quality of life , and hospital readmission rates . RESULTS About 80 % of patients who had enhanced access to care and patients receiving usual care underwent recommended evaluation of left ventricular ejection fraction . Among the subset of patients for whom an angiotensin-converting enzyme ( ACE ) inhibitor was recommended ( i.e. , ejection fraction < 40 % ) , three quarters of the patients in both the enhanced access and usual care groups received the drug ( 75 % vs. 73 % ; P > 0.2 ) . Enhanced access to primary care did not improve quality of life and increased hospital readmissions , with an average of 1.5 + /- SD 2.0 readmissions per 6 months of follow-up for patients who had enhanced access compared with 1.1 + /- SD 1.8 for those who received usual care ( P = 0.02 ) . CONCLUSIONS Compliance with recommended CHF testing and treatment guidelines was equally high in both study groups . Enhanced access to primary care did not improve patients ' self-reported health status and was associated with more frequent hospitalizations 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 . ) BACKGROUND Studies have demonstrated that blood pressure ( BP ) control can be improved when clinical pharmacists assist with patient management . The objective of this study was to evaluate if a physician and pharmacist collaborative model in community-based medical offices could improve BP control . METHODS This was a prospect i ve , cluster r and omized , controlled clinical trial with clinics r and omized to a control group ( n = 3 ) or to an intervention group ( n = 3 ) . The study enrolled 402 patients ( mean age , 58.3 years ) with uncontrolled hypertension . Clinical pharmacists made drug therapy recommendations to physicians based on national guidelines . Research nurses performed BP measurements and 24-hour BP monitoring . RESULTS The mean ( SD ) guideline adherence scores increased from 49.4 ( 19.3 ) at baseline to 53.4 ( 18.1 ) at 6 months ( 8.1 % increase ) in the control group and from 40.4 ( 22.6 ) at baseline to 62.8 ( 13.5 ) at 6 months ( 55.4 % increase ) in the intervention group ( P = .09 for adjusted between-group comparison ) . The mean BP decreased 6.8/4.5 mm Hg in the control group and 20.7/9.7 mm Hg in the intervention group ( P < .05 for between-group systolic BP comparison ) . The adjusted difference in systolic BP was -12.0 ( 95 % confidence interval [ CI ] , -24.0 to 0.0 ) mm Hg , while the adjusted difference in diastolic BP was -1.8 ( 95 % CI , -11.9 to 8.3 ) mm Hg . The 24-hour BP levels showed similar effect sizes . Blood pressure was controlled in 29.9 % of patients in the control group and in 63.9 % of patients in the intervention group ( adjusted odds ratio , 3.2 ; 95 % CI , 2.0 - 5.1 ; P < .001 ) . CONCLUSIONS A physician and pharmacist collaborative intervention achieved significantly better mean BP and overall BP control rates compared with a control group . Additional research should be conducted to evaluate efficient strategies to implement team-based chronic disease management . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00201019 Bruno Giraudeau and Philippe Ravaud discuss the difficulties in preventing selection bias and applying intention-to-treat analysis in cluster r and omized trials , and propose some solutions OBJECTIVE To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a r and omized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton , Canada . Pharmacists performed medication assessment s and limited history and physical examinations and provided guideline -concordant recommendations to optimize medication management . Follow-up contact was completed as necessary . Control patients received usual care . The primary outcome was a ≥10 % decrease in systolic blood pressure at 1 year . RESULTS A total of 260 patients were enrolled , 57 % were women , the mean age was 59 years , diabetes duration was 6 years , and blood pressure was 129/74 mmHg . Forty-eight of 131 ( 37 % ) intervention patients and 30 of 129 ( 23 % ) control patients achieved the primary outcome ( odds ratio 1.9 [ 95 % CI 1.1–3.3 ] ; P = 0.02 ) . Among 153 patients with inadequately controlled hypertension at baseline , intervention patients ( n = 82 ) were significantly more likely than control patients ( n = 71 ) to achieve the primary outcome ( 41 [ 50 % ] vs. 20 [ 28 % ] ; 2.6 [ 1.3–5.0 ] ; P = 0.007 ) and recommended blood pressure targets ( 44 [ 54 % ] vs. 21 [ 30 % ] ; 2.8 [ 1.4–5.4 ] ; P = 0.003 ) . The 10-year risk of cardiovascular disease , based on changes to the UK Prospect i ve Diabetes Study Risk Engine , were predicted to decrease by 3 % for intervention patients and 1 % for control patients ( P = 0.005 ) . CONCLUSIONS Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams , which suggests that pharmacists can make important contributions to the primary care of these patients Although absolute risk of death associated with raised blood pressure increases with age , the benefits of treatment are greater in elderly patients . Despite this , the ' rule of halves ' particularly applies to this group . We conducted a r and omised controlled trial to evaluate different levels of feedback design ed to improve identification , treatment and control of elderly hypertensives . Fifty-two general practice s were r and omly allocated to either : Control ( n=19 ) , Audit only feedback ( n=16 ) or Audit plus Strategic feedback , prioritising patients by absolute risk ( n=17 ) . Feedback was based on electronic data , annually extracted from practice computer systems . Data were collected for 265,572 patients , 30,345 aged 65 - 79 . The proportion of known hypertensives in each group with BP recorded increased over the study period and the numbers of untreated and uncontrolled patients reduced . There was a significant difference in mean systolic pressure between the Audit plus Strategic and Audit only groups and significantly greater control in the Audit plus Strategic group . Providing patient-specific practice feedback can impact on identification and management of hypertension in the elderly and produce a significant increase in control ABSTRACT OBJECTIVE Evaluate the effectiveness of collaborative management of hypertension by primary care-pharmacist teams in community-based clinics . STUDY DESIGN A 12-month prospect i ve , single-blind , r and omized , controlled trial in the Providence Primary Care Research Network of patients with hypertension and uncontrolled blood pressure . METHODS As compared to usual primary care , intervention consisted of pharmacy practitioners participating in the active management of hypertension in the primary care office according to established collaborative treatment protocol s. At baseline , there was no significant difference in blood pressure between groups . Primary outcome measures were the differences in mean systolic and diastolic blood pressures between arms at study end . Secondary measures included blood pressure goal attainment ( < 140/90 mmHg ) , hypertension-related knowledge , medication adherence , home blood pressure monitoring , re source utilization , quality of life , and satisfaction . RESULTS A total of 463 subjects were enrolled ( n = 233 control , n = 230 intervention ) . Subjects receiving the intervention achieved significantly lower systolic ( p = 0.007 ) and diastolic ( p = 0.002 ) blood pressures compared to control ( 137/75 mmHg vs. 143/78 mmHg ) . In addition , 62 % of intervention subjects achieved target blood pressure compared to 44 % of control subjects ( p = 0.003 ) . The intervention group received more total office visits ( 7.2 vs. 4.9 , p < 0.0001 ) , however had fewer physician visits ( 3.2 vs. 4.7 , p < 0.0001 ) compared to control . Intervention subjects were prescribed more antihypertensive medications ( 2.7 vs. 2.4 , p = 0.02 ) , but did not take more antihypertensive pills per day ( 2.4 vs. 2.5 , p = 0.87 ) . There were minimal differences between groups in hypertension-related knowledge , medication adherence , quality of life , or satisfaction . CONCLUSIONS Patients r and omized to collaborative primary care-pharmacist hypertension management achieved significantly better blood pressure control compared to usual care with no difference in quality of life or satisfaction Abstract Objectives : To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk , blood pressure , and prescribing of cardiovascular drugs in hypertensive patients . Design : Cluster r and omised controlled trial . Setting : 27 general practice s in Avon . Participants : 614 patients aged between 60 and 79 years with high blood pressure . Interventions : Patients were r and omised to computer based clinical decision support system plus cardiovascular risk chart ; cardiovascular risk chart alone ; or usual care . Main outcome measures : Percentage of patients in each group with a five year cardiovascular risk≥10 % , systolic blood pressure , diastolic blood pressure , prescribing of cardiovascular drugs . Results : Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10 % than patients receiving usual care . Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk≥10 % than chart only patients , odds ratio 2.3 ( 95 % confidence interval 1.1 to 4.8 ) . The chart only group had significantly lower systolic blood pressure compared with the usual care group ( difference in means−4.6 mm Hg ( 95 % confidence interval−8.4 to−0.8 ) . Reduction of diastolic blood pressure did not differ between the three groups . The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups . Conclusions : The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended . Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure BACKGROUND Computerized decision support systems ( CDSSs ) linked with electronic medical records ( EMRs ) are promoted as an effective means of improving patient care . However , very few high- quality studies are set in routine , community-based clinical care , and no consistent evidence of an effect on patient outcomes has been found . METHODS A r and omized controlled trial among EMR-using primary care practice s in Ontario , Canada . Patients 55 years or older with previous vascular events , diabetes mellitus , hypertension , or hypercholesterolemia were r and omized to the Computerization of Medical Practice s for the Enhancement of Therapeutic Effectiveness ( COMPETE III ) CDSS intervention or to usual care . The intervention included personally tailored electronic vascular risk monitoring and treatment advice shared between the physician and patient , risk calculation , and a clinical re source . The primary outcome was a composite score of 8 recommended process outcomes at 1 year . Data collectors were blinded to group allocation . Analysis used the intention-to-treat principle with multiple imputation for missing data . RESULTS We r and omized and included in the analysis 1102 patients in 49 community-based physician practice s ( 53.4 % female ; mean age , 69.1 years ; 28.0 % with a previous vascular event ) . The intervention group ( 545 [ 49.5 % ] ) had a significantly greater improvement in mean process composite , with a difference of 4.70 ( P < .001 ) on a 27-point scale . Intervention patients had significantly higher odds of rating their continuity of care ( 4.18 ; P < .001 ) and their ability to improve their vascular health ( 3.07 ; P < .001 ) as improved . Despite this improvement , the clinical outcomes -vascular events , clinical variables , and quality of life-were not improved . CONCLUSION Despite favorable review s and important improvements in the complex processes required to reduce vascular risk , clinical outcomes remain unchanged BACKGROUND Poor long-term adherence is an important cause of uncontrolled hypertension . We examined whether monitoring drug adherence with an electronic system improves long-term blood pressure ( BP ) control in hypertensive patients followed by general practitioners ( GPs ) . METHODS A pragmatic cluster r and omised controlled study was conducted over one year in community pharmacists/GPs ' networks r and omly assigned either to usual care ( UC ) where drugs were dispensed as usual , or to intervention ( INT ) group where drug adherence could be monitored with an electronic system ( Medication Event Monitoring System ) . No therapy change was allowed during the first 2 months in both groups . Thereafter , GPs could modify therapy and use electronic monitors freely in the INT group . The primary outcome was a target office BP<140/90 mmHg . RESULTS Sixty-eight treated uncontrolled hypertensive patients ( UC : 34 ; INT : 34 ) were enrolled . Over the 12-month period , the likelihood of reaching the target BP was higher in the INT group compared to the UC group ( p<0.05 ) . At 4 months , 38 % in the INT group reached the target BP vs. 12 % in the UC group ( p<0.05 ) , and 21 % vs. 9 % at 12 months ( p : ns ) . Multivariate analyses , taking account of baseline characteristics , therapy modification during follow-up , and clustering effects by network , indicate that being allocated to the INT group was associated with a greater odds of reaching the target BP at 4 months ( p<0.01 ) and at 12 months ( p=0.051 ) . CONCLUSION GPs monitoring drug adherence in collaboration with pharmacists achieved a better BP control in hypertensive patients , although the impact of monitoring decreased with time Purpose To determine long-term adherence to evidence -based secondary preventive combination pharmacotherapy in survivors of acute myocardial infa rct ion ( AMI ) and to investigate the association between adherence to recommended therapy and all-cause mortality in cl aims data . Methods Prospect i ve cohort study based on cl aims data of an 18.75 % r and om sample of all persons insured with the local statutory health insurance fund AOK Hesse . Study population included patients with hospital discharge diagnoses of AMI between 2001 and 2005 excluding those who died within the first 30 days after AMI or who had been hospitalised with an AMI in the previous 2 years . A total of 3,008 patients were followed up until death , cancellation of insurance , or the end of the study period on 31 December 2007 , whichever came first ( median follow-up : 4.2 years ) . Results Drug adherence to single drug groups as determined by proportion of days covered ≥80 % was 21.8 % for antiplatelet drugs , 9.4 % for beta-blockers , 45.6 % for ACE inhibitors or angiotensin II receptor blockers and 45.1 % for lipid-lowering drugs . A total of 924 ( 39.7 % ) patients met our definition of guideline adherence : Drugs available from three of four relevant drug groups on the same day for at least 50 % of the observation time . Of the patients adhering to the guidelines , 17.3 % died and of the non-adherents , 32.4 % died . All-cause mortality was 28 % lower for guideline -adherent patients than for the non-adherent group ( adjusted HR 0.72 , 95 % CI 0.60–0.86 ) . Conclusions In everyday practice , post AMI patients benefit from guideline -oriented treatment , but the percentage of adherent patients should be improved The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s. Objective To evaluate the effectiveness of the community based Cardiovascular Health Awareness Program ( CHAP ) on morbidity from cardiovascular disease . Design Community cluster r and omised trial . Setting 39 mid-sized communities in Ontario , Canada , stratified by location and population size . Participants Community dwelling residents aged 65 years or over , family physicians , pharmacists , volunteers , community nurses , and local lead organisations . Intervention Communities were r and omised to receive CHAP ( n=20 ) or no intervention ( n=19 ) . In CHAP communities , residents aged 65 or over were invited to attend volunteer run cardiovascular risk assessment and education sessions held in community based pharmacies over a 10 week period ; automated blood pressure readings and self reported risk factor data were collected and shared with participants and their family physicians and pharmacists . Main outcome measure Composite of hospital admissions for acute myocardial infa rct ion , stroke , and congestive heart failure among all community residents aged 65 and over in the year before compared with the year after implementation of CHAP . Results All 20 intervention communities successfully implemented CHAP . A total of 1265 three hour long sessions were held in 129/145 ( 89 % ) pharmacies during the 10 week programme . 15 889 unique participants had a total of 27 358 cardiovascular assessment s with the assistance of 577 peer volunteers . After adjustment for hospital admission rates in the year before the intervention , CHAP was associated with a 9 % relative reduction in the composite end point ( rate ratio 0.91 , 95 % confidence interval 0.86 to 0.97 ; P=0.002 ) or 3.02 fewer annual hospital admissions for cardiovascular disease per 1000 people aged 65 and over . Statistically significant reductions favouring the intervention communities were seen in hospital admissions for acute myocardial infa rct ion ( rate ratio 0.87 , 0.79 to 0.97 ; P=0.008 ) and congestive heart failure ( 0.90 , 0.81 to 0.99 ; P=0.029 ) but not for stroke ( 0.99 , 0.88 to 1.12 ; P=0.89 ) . Conclusions A collaborative , multi-pronged , community based health promotion and prevention programme targeted at older adults can reduce cardiovascular morbidity at the population level . Trial registration Current controlled trials IS RCT N50550004 BACKGROUND Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines , but the effectiveness of mass dissemination of guidelines is unknown . AIM To study the effects of guideline dissemination on physicians ' prescribing practice s for the treatment of stable angina pectoris . DESIGN R and omized controlled trial . METHODS A sample of 3293 Quebec physicians were r and omly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina ( in February 1999 ) , to receive the summary and a reminder ( in February and March 1999 , respectively ) , or to receive no intervention ( controls ) . The prescribing profiles of participants , as well as sociodemographic characteristics of the physicians and their patients , were examined for June-December 1999 . RESULTS The intervention had no effect on prescription rates of beta-blockers , antiplatelet agents , or hypolipaemic drugs . Compared to 1997 data for the same physicians , there was an overall 10 % increase in appropriate prescription rates , irrespective of the intervention . DISCUSSION In-house production and dissemination of clinical practice guidelines may not improve physicians ' practice patterns if there is pre-existing substantial scientific consensus on the issue BACKGROUND No single quality improvement instrument has proved consistently effective , but multifaceted interventions are believed to have the greatest impact . However , only little is known regarding what combinations are likely to be successful . OBJECTIVE To evaluate the impact of a multifaceted intervention strategy combining GP registration s , outreach visits and feedback , targeting secondary prevention of ischemic heart disease in general practice . METHODS A r and omised controlled trial including 28 GPs in Ringkjøbing County , Denmark . Half of the GPs received outreach visits and feedback on their prescribing of heart disease drugs . Evaluation was based on registration of consultations with patients suffering from ischemic heart disease . RESULTS The intervention had a statistically significant impact on prescribing of lipid lowering drugs [ odds ratio 1.59 ; 95 % confidence interval ( CI ) 1.00 to 2.53 ] and acetylsalicylic acid ( odds ratio 2.54 ; 95 % CI 1.21 to 5.31 ) . CONCLUSION An intervention strategy combining outreach visits , feedback and GP registration s is a promising way of improving the quality of preventive treatment in general practice Aims We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease ( CHD ) risk could lower patients ' predicted Framingham CHD risk vs. usual care . Methods The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospect i ve , controlled , cluster-r and omised trial in nine European countries , among patients at moderate cardiovascular risk . Following baseline assessment s , physicians in the intervention group calculated patients ' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme . Usual care physicians did not calculate patients ' risk and provided usual care only . The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care . Results Of 1103 patients across 100 sites , 524 patients receiving intervention , and 461 receiving usual care , were analysed for efficacy . After 6 months , mean predicted risks were 12.5 % with intervention , and 13.7 % with usual care [ odds ratio = 0.896 ; p = 0.001 , adjusted for risk at baseline ( 17.2 % intervention ; 16.9 % usual care ) and other covariates ] . The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention ( 25.4 % ) than usual care ( 14.1 % ; p < 0.001 ) , and 29.3 % of smokers in the intervention group quit smoking vs. 21.4 % of those receiving usual care ( p = 0.04 ) . Conclusions A physician-implemented CHD risk evaluation/communication programme improved patients ' modifiable risk factor profile , and lowered predicted CHD risk compared with usual care . By combining this strategy with more intensive treatment to reduce residual modifiable risk , we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice Objective : To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners ( GPs ) in cardiovascular care . Design : Pragmatic cluster controlled trial with r and omisation of practice s to support ( intervention group ) or no special attention ( control group ) ; analysis after 2 years . Setting : 124 general practice s in The Netherl and s. Participants : 185 GPs . Main outcome measures : Compliance rates for 12 evidence -based indicators for the management of patients with hypertension , hypercholesterolaemia , angina pectoris , or heart failure . The evaluation relied on the prospect i ve recording of patient encounters by the participating GPs . Results : The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention . A significant improvement was seen for five of the 12 indicators : assessment of risk factors in patients with hypercholesterolaemia ( odds ratio 2.04 ; 95 % CI 1.44 to 2.88 ) or angina pectoris ( 3.07 ; 1.08 to 8.79 ) , provision of information and advice to patients with hypercholesterolaemia ( 1.58 , 1.17 to 2.13 ) or hypertension ( 1.55 , 1.35 to 1.77 ) , and checking for clinical signs of deterioration in patients with heart failure ( 4.11 , 2.17 to 7.77 ) . Single h and ed practice s , non-training practice s , and practice s with older GPs gained particular benefit from the intervention . Conclusions : Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care . The effect is small and the strategy needs further development Notwithst and ing the availability of antihypertensive drugs and practice guidelines , blood pressure control remains suboptimal . The complexity of current treatment guidelines may contribute to this problem . To determine whether a simplified treatment algorithm is more effective than guideline -based management , we studied 45 family practice s in southwestern Ontario , Canada , using a cluster r and omization trial comparing the simplified treatment algorithm with the Canadian Hypertension Education Program guidelines . The simplified treatment algorithm consisted of the following : ( 1 ) initial therapy with a low-dose angiotensin-converting enzyme inhibitor/diuretic or angiotensin receptor blocker/diuretic combination ; ( 2 ) up-titration of combination therapy to the highest dose ; ( 3 ) addition of a calcium channel blocker and up-titration ; and ( 4 ) addition of a non — first-line antihypertensive agent . The proportion of patients treated to target blood pressure ( systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg for patients without diabetes mellitus or systolic blood pressure < 130 mm Hg and diastolic blood pressure < 80 mm Hg for diabetic patients ) at 6 months was analyzed at the practice level . The proportion of patients achieving target was significantly higher in the intervention group ( 64.7 % versus 52.7 % ; absolute difference : 12.0 % ; 95 % CI : 1.5 % to 22.4 % ; P=0.026 ) . Multivariate analysis of patient-level data showed that assignment to the intervention arm increased the chance of reaching the target by 20 % ( P=0.028 ) , when adjusted for other covariates . In conclusion , the Simplified Treatment Intervention to Control Hypertension Study indicates that a simplified antihypertensive algorithm using initial low-dose fixed-dose combination therapy is superior to guideline -based practice for the management of hypertension OBJECTIVES To evaluate the efficacy of a healthcare education program for patients with hypertension . METHODS A multicenter , prospect i ve , cluster-r and omized trial was conducted . R and omization was by primary care center ; 18 of 36 urban primary care centers in Barcelona and its metropolitan area were r and omized to the intervention group ( IG ) and 18 to the control group ( CG ) . The study sample consisted of patients with hypertension ( n=996 ; 515 in the IG and 481 in the CG ) receiving outpatient treatment with antihypertensive drugs . The intervention consisted of personalized information by a trained nurse and written leaflets . Question naires on knowledge and awareness of hypertension and its medication , treatment adherence , healthy lifestyle habits , systolic and diastolic blood pressure , and body mass index were assessed at each visit , with a 12-month follow-up . An intention-to-treat analysis was applied . RESULTS Knowledge of hypertension increased by 27.8 % in the IG and by 18.5 % in the CG , while that of medication increased by 10.1 % in the IG and 5.5 % in the CG . Treatment adherence measured by the Morisky-Green test increased by 9.6 % ( 95 % CI : 5.5 - 13.6 ) in the IG and 8.8 % ( 95 % CI : 4.9 - 12.6 ) in the CG . There were no differences in adherence on the other tests used . No differences were observed between the IG and CG in clinical variables such as blood pressure or BMI at the end of the trial . CONCLUSIONS The educational intervention had no significant impact on patients ' adherence to the medication Abstract Objective : To study the efficacy of case method learning , for general practitioners , on patients ' lipid concentrations in the secondary prevention of coronary artery disease . Design : Prospect i ve controlled trial . Setting : Södertälje , Stockholm County , Sweden . Participants : 255 consecutive patients with coronary artery disease . Intervention : Guidelines were mailed to all general practitioners ( n=54 ) and presented at a common lecture . General practitioners who were r and omised to the intervention group participated in recurrent case method learning dialogues at their primary healthcare centres during a two year period . A locally well known cardiologist served as a facilitator . Main outcome measure : Concentration of low density lipoprotein cholesterol at baseline and after two years . Analysis according to intention to treat ( intervention and control groups ( n=88 ) ) was based on group affiliation at baseline . Results : Low density lipoprotein cholesterol was reduced by 0.5 mmol/l ( 95 % confidence interval 0.2 to 0.8 mmol/l ) ( 9.3 % ( 2.9 % to 15.8 % ) ) from baseline in patients in the intervention group and by 0.5 ( 0.1 to 0.9 ) mmol/l compared with controls ( P<0.05 ) . No change occurred in the control group ( 0.0 ( −0.2 to 0.2 ) mmol/l ) . Low density lipoprotein cholesterol decreased by 0.6 ( 0.4 to 0.8 ) mmol/l in a group of patients who received specialist care . Conclusion : Case method learning result ed in a lowering of low density lipoprotein cholesterol in the primary care patients with coronary artery disease comparable to that achieved at a specialist clinic . Conventional presentation of practice guidelines had no effect Background A gap exists between evidence and practice regarding the management of cardiovascular risk factors . This gap could be narrowed if systematic ally developed clinical practice guidelines were effectively implemented in clinical practice . We evaluated the effects of a tailored intervention to support the implementation of systematic ally developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease . Methods and Findings We conducted a cluster-r and omized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practice s in two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders linked to the medical record system . Pharmacists conducted the visits . Outcomes were measured for all eligible patients seen in the participating practice s during 1 y before and after the intervention . The main outcomes were the proportions of ( 1 ) first-time prescriptions for hypertension where thiazides were prescribed , ( 2 ) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs , and ( 3 ) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals . The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug . Thiazides were prescribed to 17 % of patients in the intervention group versus 11 % in the control group ( relative risk 1.94 ; 95 % confidence interval 1.49–2.49 , adjusted for baseline differences and clustering effect ) . Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals . Conclusions Our tailored intervention had a significant impact on prescribing of antihypertensive drugs , but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care BACKGROUND Control of blood pressure is a key component of cardiovascular disease prevention , but is difficult to achieve and until recently has been the sole preserve of health professionals . This study assessed whether self-management by people with poorly controlled hypertension result ed in better blood pressure control compared with usual care . METHODS This r and omised controlled trial was undertaken in 24 general practice s in the UK . Patients aged 35 - 85 years were eligible for enrolment if they had blood pressure more than 140/90 mm Hg despite antihypertensive treatment and were willing to self-manage their hypertension . Participants were r and omly assigned in a 1:1 ratio to self-management , consisting of self-monitoring of blood pressure and self-titration of antihypertensive drugs , combined with telemonitoring of home blood pressure measurements or to usual care . R and omisation was done by use of a central web-based system and was stratified by general practice with minimisation for sex , baseline systolic blood pressure , and presence or absence of diabetes or chronic kidney disease . Neither participants nor investigators were masked to group assignment . The primary endpoint was change in mean systolic blood pressure between baseline and each follow-up point ( 6 months and 12 months ) . All r and omised patients who attended follow-up visits at 6 months and 12 months and had complete data for the primary outcome were included in the analysis , without imputation for missing data . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N17585681 . FINDINGS 527 participants were r and omly assigned to self-management ( n=263 ) or control ( n=264 ) , of whom 480 ( 91 % ; self-management , n=234 ; control , n=246 ) were included in the primary analysis . Mean systolic blood pressure decreased by 12.9 mm Hg ( 95 % CI 10.4 - 15.5 ) from baseline to 6 months in the self-management group and by 9.2 mm Hg ( 6.7 - 11.8 ) in the control group ( difference between groups 3.7 mm Hg , 0.8 - 6.6 ; p=0.013 ) . From baseline to 12 months , systolic blood pressure decreased by 17.6 mm Hg ( 14.9 - 20.3 ) in the self-management group and by 12.2 mm Hg ( 9.5 - 14.9 ) in the control group ( difference between groups 5.4 mm Hg , 2.4 - 8.5 ; p=0.0004 ) . Frequency of most side-effects did not differ between groups , apart from leg swelling ( self-management , 74 patients [ 32 % ] ; control , 55 patients [ 22 % ] ; p=0.022 ) . INTERPRETATION Self-management of hypertension in combination with telemonitoring of blood pressure measurements represents an important new addition to control of hypertension in primary care . FUNDING Department of Health Policy Research Programme , National Coordinating Centre for Research Capacity Development , and Midl and s Research Practice s Consortium 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 : To assess the effect of a program that encourages teamwork between physicians and pharmacists on attempts to lower total cholesterol levels and to meet recommended goals proposed by the National Cholesterol Education Program ( NCEP ) . DESIGN A single-blind , r and omized , controlled trial lasting 6 months . SETTING : An ambulatory primary care center . PATIENTS : A sample of 94 patients with total cholesterol levels of 240 mg/dL ( 6.2 mmol/L ) or higher . INTERVENTION : Equal numbers of patients were r and omly assigned to a control arm in which st and ard medical care was received and an intervention arm which implemented close interaction between physicians and pharmacists . MEASUREMENTS AND MAIN RESULTS : Absolute change in total cholesterol levels from baseline values and the percentage of patients who achieved an NCEP goal after 6 months of intervention were determined . The rate of success in achieving NCEP goals in the intervention arm was double the rate in the control arm ( 43 % vs 21 % , p < .05 ) . Total cholesterol levels in the intervention arm declined 44 + /- 47 mg/dL ( 1.1 + /- 1.2 mmol/L ) versus 13 + /- 51 mg/dL ( 0.3 + /- 1.3 mmol/L ) in the control arm ( p < .01 ) . The effect of intervention on reducing total cholesterol levels was similar for men and women and did not appear to be altered by age . The effect of intervention was greatest in patients with coronary heart disease ( p < .01 ) followed by those without disease but with two or more coronary heart disease risk factors ( p < .05 ) . An effect of intervention was absent in patients without coronary heart disease and with fewer than two risk factors . CONCLUSIONS : Attempts to lower total cholesterol levels and achieve NCEP goals are likely to be more successful when combined with programs that include teamwork between physicians and pharmacists . Some programs , however , may be more successful for high-risk patients , for whom it is often easier to provide more aggressive therapies . Although altering adverse lipid profiles in lower-risk patients may be difficult , achieving optimal cholesterol levels could have an important impact on preventing movement to higher risk strata Many scientific and statistical issues are involved in generalizing the results of r and omized clinical trials . This paper examines the issues of heterogeneity of risk and heterogeneity of effect , as well as quantitative vs. qualitative heterogeneity . Generalization of quantitative results to population s at different risk is shown to be problematic , independent of any other considerations . Issues of heterogeneity as they relate to target population and choice of therapy are discussed . A few proposals are offered regarding the design and report of trials PURPOSE Patients ' lack of adherence to medical regimens frustrates many practicing physicians . This study was conducted to determine the effectiveness of a combined continuing medical education intervention in increasing physicians ' adherence-enhancing skills and improving hypercholesterolemic patients ' health . METHOD A prospect i ve , r and omized , controlled trial was design ed using a nested cohort of 28 community physicians throughout Alabama and 222 of their hypercholesterolemic out patients . The intervention , carried out in 1998 , consisted of three interactive case audio-conferences plus chart reminders . Physicians ' learning was measured by unannounced st and ardized patients , and patients ' health by serum cholesterol levels , weight , knowledge of hypercholesterolemia , self-reported dietary habits , and health status . RESULTS No significant difference was found in the numbers of physician adherence-enhancing strategies , although the number did increase within the treatment group . There were significant differences in the intervention group 's patients ' knowledge of cholesterol management ( p = .008 ) and significant reductions in their self-reported consumption of dietary fats ( p = .002 ) . A significant difference was found in the serum cholesterol level of men in the intervention group nine months after the intervention ( p = .02 ) . CONCLUSION Combining a series of interactive case audio-conferences with chart reminders shows promise in increasing physicians ' adherence-enhancing strategies . In chronic disease management , the problem of enhancing adherence remains complex 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 PURPOSE To compare group versus individual academic detailing to increase diuretic or beta-blocker use in hypertension . METHODS We conducted a cluster-r and omized controlled trial in a large health maintenance organization . Subjects ( N=9820 ) were patients with newly treated hypertension in the year preceding the intervention ( N=3692 ) , the 9 months following the intervention ( N=3556 ) , and the second year following intervention ( N=2572 ) . We r and omly allocated 3 practice sites to group detailing ( N=227 prescribers ) , 3 to individual detailing ( N=235 prescribers ) , and 3 to usual care ( N=319 prescribers ) . Individual detailing entailed a physician-educator meeting individually with clinicians to address barriers to prescribing guideline -recommended medications . The group detailing intervention incorporated the same social marketing principles in small groups of clinicians . RESULTS In the first year following the intervention , the rates of diuretic or beta-blocker use increased by 13.2 % in the group detailing practice s , 12.5 % in the individual detailing practice s , and 6.2 % in the usual care practice s. As compared with usual care practice s , diuretic or beta-blocker use was more likely in group detailing practice s ( adjusted odds ratio ( OR ) , 1.40 ; 95 % confidence interval ( CI ) , 1.11 - 1.76 ) and individual detailing practice s ( adjusted OR , 1.30 ; 95 % CI , 0.95 - 1.79 ) . Neither intervention affected blood pressure control . Two years following this single-visit intervention , there was still a trend suggesting a persistent effect of individual ( OR , 1.22 ; 95 % CI , 0.92 - 1.62 ) , but not group , detailing ( OR , 1.06 ; 95 % CI , 0.80 - 1.39 ) , as compared with usual care . CONCLUSION Both group and individual academic detailing improved antihypertensive prescribing over and above usual care but may require reinforcement to sustain improvements This article describes approaches for planning , dealing , and analyzing heterogeneity in a systematic review of complex interventions . Approaches aim to generate a priori hypotheses of the mechanism of action of a complex intervention to identify the key variables that might contribute to variation among studies and guide statistical analysis . In addition to characteristics related to the population , intervention , and outcomes , we describe study -related variables , such as the way the interventions have been implemented and the context and conduct of studies . These approaches will guide review ers planning a meta- analysis and provide a rationale for not meta-analyzing data if there is too much variability . Potential difficulties in applying meta-analytical techniques to examine statistical association among study results and sources of potential heterogeneity are described ; these include the selection of a fixed or r and om-effects model , the risk of multiple testing and confounding when studies include different aspects of a complex intervention or different sub sample s of the intended participant pool BACKGROUND Effective therapies for reducing mortality rates in persons with coronary heart disease ( CHD ) remain underused . We report the results of an effectiveness trial of a quality improvement effort to increase the use of 3-hydroxy-3methylglutaryl coenzyme A ( HMG CoA ) reductase inhibitors , beta-blockers , and angiotensin-converting enzyme ( ACE ) inhibitors in patients with CHD in a network-model managed-care setting . METHODS Patients with CHD were identified by search ing a cl aims data base . The use of therapies was assessed by linkage with a pharmacy data base . An intervention , consisting of a guideline summary , peer comparison performance feedback , and patient specific chart reminders was evaluated in a r and omized , practice -based effectiveness trial . RESULTS Data were available for > 700 patients per year ( 1999 - 2002 ) in 131 practice s. At baseline ( 1999 ) , 55 % of patients were receiving HMG CoA reductase inhibitors , 39 % of patients were receiving beta-blockers , and 24 % of patients were receiving ACE inhibitors . The use of all 3 types of medications increased steadily with time , with the exception of a decrease in the use of HMG CoA reductase inhibitors in the final year ( 2002 ) . No difference in medication use was observed between r and omized groups . CONCLUSIONS The observed pattern of care supports the contention that the quality of outpatient care for secondary prevention of CHD improved from 1999 to 2002 in this setting . The basis for the inconsistent pattern of use of HMG CoA reductase inhibitors is not certain , but may relate to concerns about toxicity . Central ized mailings of guideline summaries , performance feedback reports , and chart reminders had no observable impact on quality of care in this setting . More intensive intervention may be required to improve the quality of outpatient care for the secondary prevention of CHD AIMS To determine the effects of a nurse-led intervention design ed to improve self-management of patients with heart failure in a primary health care setting regarding health-related quality of life and depression . METHODS Patients at eight primary health care centres were screened by the Diagnosis Related Groups registry for the diagnosis of heart failure and eligibility for a cluster r and omised study . A total of 153 patients were included ( n=78 in the intervention group , 54 % males , mean age 79 years , 59 % in New York Heart Association class III-IV ) . The intervention involved patient and family education about heart failure and self-management and monthly telephone follow-up during 12 months by a primary health care nurse . RESULTS The effects of the nurse-led intervention were limited . Significant differences were found in the physical dimension measured by the SF-36 health survey , and in depression measured by the Zung Self-rating Depression Scale . In comparison within groups at the 3 and 12-month follow-up , the intervention group significantly maintained their health-related quality of life measured by the SF-36 health survey , and their experience of depression measured by the Zung Self-rating Depression Scale to a greater extent than in the control group , especially among women . CONCLUSION A nurse-led intervention directed toward patients with heart failure in a primary health care setting result ed in limited effects between the groups , although the physical and mental status were retained during 12 months of follow-up to a greater extent than in the control group BACKGROUND Cardiovascular risk reduction in ambulatory patients who survive myocardial infa rct ion ( MI ) is effective but underused . We sought to evaluate a provider-directed , Internet-delivered intervention to improve cardiovascular management for post-MI out patients . METHODS The Department of Veterans Affairs ( VA ) MI-Plus study was a cluster-r and omized trial involving 168 community-based primary care clinics and 847 providers in 26 states , the Virgin Isl and s , and Puerto Rico , from January 1 , 2002 , through December 31 , 2008 , with the clinic as the r and omization unit . We collected administrative data for 15,847 post-MI patients and medical record data for 10,452 of these . A multicomponent , Internet-delivered intervention included quarterly educational modules , practice guidelines , monthly literature summaries , and automated e-mail reminders delivered to providers for 27 months . Main outcome measures included percentage of patients who achieved each of 7 clinical indicators , a composite score of the 7 clinical indicators , and mean low-density lipoprotein cholesterol and hemoglobin A(1c ) levels . RESULTS Clinics had a median of 3 providers ( interquartile range , 2 - 6 ) , with a median of 50.0 % of providers ( 33.3%-66.7 % ) participating in the study . Patients in intervention clinics had greater improvements ( from 70.0 % to 85.5 % ) in the percentages prescribed β-blockers than patients in control clinics ( 71.9 % to 84.0 % ; adjusted improvement gain for intervention vs control , 2.6 % ; 95 % CI , 0.1%-4.1 % ) . We found nonsignificant differences in improvements favoring patients in intervention clinics for 5 of 6 remaining clinical indicators and levels of low-density lipoprotein cholesterol and hemoglobin A(1c ) . CONCLUSION A longitudinal , Internet-delivered intervention improved only 1 of 7 clinical indicators of cardiovascular management in ambulatory post-MI patients This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence CONTEXT Numbers of diagnostic tests ordered by primary care physicians are growing and many of these tests seem to be unnecessary according to established , evidence -based guidelines . An innovative strategy that focused on clinical problems and associated tests was developed . OBJECTIVE To determine the effects of a multifaceted strategy aim ed at improving the performance of primary care physicians ' test ordering . DESIGN Multicenter , r and omized controlled trial with a balanced , incomplete block design and r and omization at group level . Thirteen groups of primary care physicians underwent the strategy for 3 clinical problems ( arm A ; cardiovascular topics , upper and lower abdominal complaints ) , while 13 other groups underwent the strategy for 3 other clinical problems ( arm B ; chronic obstructive pulmonary disease and asthma , general complaints , degenerative joint complaints ) . Each arm acted as a control for the other . SETTING Primary care physician groups in 5 regions in the Netherl and s with diagnostic centers recruited from May to September 1998 . STUDY PARTICIPANTS Twenty-six primary care physician groups , including 174 primary care physicians . INTERVENTION During the 6 months of intervention , physicians discussed 3 consecutive , personal feedback reports in 3 small group meetings , related them to 3 evidence -based clinical guidelines , and made plans for change . MAIN OUTCOME MEASURE According to existing national , evidence -based guidelines , a decrease in the total numbers of tests ordered per clinical problem , and of some defined inappropriate tests , is considered a quality improvement . RESULTS For clinical problems allocated to arm A , the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 12 % among physicians in the arm A intervention , but was unchanged in the arm B control , with a mean reduction of 67 more tests per physician per 6 months in arm A than in arm B ( P = .01 ) . For clinical problems allocated to arm B , the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 8 % among physicians in the arm B intervention , and by 3 % in the arm A control , with a mean reduction of 28 more tests per physician per 6 months in arm B than in arm A ( P = .22 ) . Physicians in arm A had a significant reduction in mean total number of inappropriate tests ordered for problems allocated to arm A , whereas the reduction in inappropriate test ordered physicians in arm B for problems allocated to arm B was not statistically significant . CONCLUSION In this study , a practice -based , multifaceted strategy using guidelines , feedback , and social interaction result ed in modest improvements in test ordering by primary care physicians Using a large clinical multi‐site prospect i ve chronic heart failure registry , we sought to determine ( i ) implementation of guidelines over time and ( ii ) adjusted survival benefit there from RATIONALE , AIMS AND OBJECTIVES Evidence suggests that educational outreach ( ' academic detailing ' ) improves evidence -based prescribing . We evaluated the impact of an academic detailing programme intended to increase new statin prescriptions . METHODS In a 2 x 2 factorial design we evaluated the effect of an academic detailing programme with/without telephonic care management for patients . Eligible patients were continuously enrolled Medicaid members at high risk for cardiovascular disease utilization who were not receiving statin medication in the 18 months prior to the intervention . All primary care prescribers assigned to these patients were r and omized by clinic to academic detailing . Two trained nurses provided the detailing to prescribers , including specific discussion about the use of statins in this high-risk patient population . Nurses left the prescribers with a summary of clinical practice guidelines , a one-page detailing sheet and a list of patients under the care of the prescriber who were c and i date s for statins . The primary outcome was the incidence of a new statin prescription cl aim during the 6-month intervention period and the subsequent 6 months . Logistic regression models were used to estimate main effects of the interventions and to adjust for potential confounding variables in the study . RESULTS Forty-eight clinics were r and omized , effectively r and omizing a total of 284 patients and 128 prescribers . Among the 284 patients , 46 ( 16 % ) received a new statin cl aim during the evaluation period . Controlling for significant bivariate associations , the academic detailing intervention had no significant effect on new statin prescriptions compared with the control group ( odds ratio = 0.8 , 95 % confidence interval : 0.4 - 1.6 , P = 0.5 ) . CONCLUSION Among this Medicaid population at high risk for cardiovascular events , an academic detailing programme to increase statin prescriptions was not effective . To assist others to learn from our failed effort , we identify and discuss critical elements in the design and implementation of the programme that could account for these results BACKGROUND Sub-optimal management of cardiovascular disease ( CVD ) patients is widespread in primary and secondary care , with risk factors frequently unrecorded or untreated . AIM To investigate the effectiveness of educational interventions developed in primary care , on recording , prescribing and control of risk factors among all patients recorded by their general practitioner as having CVD . DESIGN OF STUDY Factorial , duster-r and omised controlled trial . SETTING Primary care teams representing the range of practice development in a geographically defined area in inner London . METHOD Participating practice s were r and omly allocated to one of the four intervention groups : information , evidence , both or neither . Interventions were tailored to suit individual practice needs . At a mean of 19 months after baseline , and three months after the end of intervention , practice s carried out the follow-up assessment of recording , treatment , and control of risk factors in the same CVD patients . RESULTS Adequate recording of all three risk factors , found inapproximately a third of patients at baseline , increased non-significantly by 10.5 % ( 95 % confidence interval [ CI ] = 3.9 to 24.9 ) in the information ( versus not information ) group and by 6.6 % ( 95 % [ CI ] = 8.9 to 22.0 ) in the evidence ( versus not evidence ) group . Factorial improvements in prescribing and control of risk factors tended not to be significant . Adequate recording of an three risk factors showed the greatest improvement in the information plus evidence group ( 19.9 % increase , P for heterogeneity across the four groups < or = 0.001 ) . Mean change from baseline to follow-up within the four intervention groups suggested improvements in the combined information plus evidence group in cholesterol recording ( 22.5 % increase ) , prescribing of lipid lowering drugs ( 4.4 % increase ) and mean cholesterol ( 0.7 mmol/l decrease ) . CONCLUSIONS Adequate risk factor recording did not differ between the information ( versus not information ) or the evidence ( versus not evidence ) intervention groups . Combined training in information systems and evidence -based medicine should be considered in the design of future interventions , to improve secondary prevention of CVD OBJECTIVE Evaluation of a structured hypertension treatment and teaching programme in general practice . DESIGN Prospect i ve controlled trial ; follow-up period 18 months . SETTING 10 primary health care practice s. PRACTICE S AND PATIENTS : From each practice 20 patients ( 30 to 60 years old , mean of the last two blood pressure measurements at or above 160 and /or 95 mmHg ) were r and omly selected ; in 5 practice s these patients were to participate in the treatment and teaching programme ; in the remaining 5 practice s hypertension care was continued without the availability of such a programme ( controls ) . INTERVENTION Structured treatment and teaching programme based upon four group sessions for patients mainly conducted by paramedical personnel . MAIN OUTCOME MEASURES Blood pressure , body weight , prescription of antihypertensive drugs - as documented in the patient 's records . MAIN RESULTS Of the 100 control patients 26 and of the 100 intervention patients 14 were lost to observation ; 46 patients had agreed to participate in the programme . The mean number of prescribed antihypertensive agents per patient decreased in the intervention group ( 1.8 + /- 1.3 at baseline , vs 1.2 + /- 1.2 at follow-up ) compared to the control group ( 1.6 + /- 1.3 vs 1.8 + /- 1.6 ) ; difference 0.8 ( 95 % CI 0.4 to 1.1 ) , p < 0.0001 . In the control group 9 % and in the intervention group 33 % of patients had documented reductions of body weight ( p < 0.0001 ) . Blood pressure decreased in the intervention group ( 162 + /- 14/100 + /- 7 mmHg at baseline , vs 154 + /- 16/95 + /- 9 mmHg at follow-up ) compared to the control group ( 161 + /- 13/98 + /- 7 mmHg vs 158 + /- 18/96 + /- 11 mmHg ) ; differences for systolic blood pressure 5 ( 95 % CI 0 to 10 ) mmHg , p = 0.071 ; for diastolic blood pressure 4 ( 1 to 7 ) mmHg , p = 0.018 . CONCLUSIONS The introduction of a structured hypertension treatment and teaching programme in general practice may lead to significant improvements of hypertension care BACKGROUND Most studies that have analysed the effect of secondary prevention of coronary heart disease come from hospitals . Those that are community-based have been conducted mainly by nurses and follow-up was generally too short to show impact on cardiovascular events . METHODS This is a multi-centre r and omised controlled clinical trial in which patients in the intervention group received periodic postal reminders to see their general practitioner every three months during a 3-year follow-up . General practitioners reinforced healthy lifestyle recommendations to patients and review ed drug therapies at these quarterly intervals . Patients in the control group received usual care . RESULTS A total of 983 patients aged 30 - 79 were included . During the 3-year follow-up , 67 patients died and 156 experienced a non-fatal cardiovascular event . The event rates and all-cause mortality were similar in the intervention and control groups ( 24.0 % and 23.5 % , and 8.1 % and 9.9 % , respectively ) . Improvement in quality of life was similar in both groups . Blood pressure and high-density lipoprotein cholesterol were more frequently within recommended levels in the intervention group than in controls : odds ratio 1.63 , 95 % confidence interval 1.05 - 2.51 , and odds ratio 2.61 , 95 % confidence interval 1.32 - 5.18 , respectively . CONCLUSIONS Intensive secondary prevention conducted by general practitioners may improve long-term blood pressure control and increase high-density lipoprotein cholesterol in patients with stable coronary disease BACKGROUND The Health Education and Research Trial ( HEART ) was a multicenter clinical trial design ed to test methods to improve primary care practice systems for heart disease prevention services . We present the trial methodology , the practice s ' use of medical record tools , and changes in documentation of cardiovascular risk factor screening and management . METHODS Primary care practice s were recruited from 4 Midwestern states . The factorial design result ed in 4 study groups : conference only , conference and quality improvement consultations , conference and prevention coordinator , and all interventions combined . Medical record audits and physician , staff , and patient surveys assessed practice change in cardiovascular disease risk factor documentation . RESULTS Practice s participated fully in this project , set goals to improve preventive services , and implemented recommended medical record tools . The number of goals set and the increase in the use of medical record tools were greatest in the combined intervention group , with improvements noted in all groups . The use of patient history question naires , problem lists , and flow sheets was significantly higher in the combined intervention group when compared with the conference-only group . Documentation of risk factor screening in a recommended-medical record location improved in all intervention groups , with significant sustained improvements in the practice s that received the combined intervention . Documented risk factor management significantly improved in all intervention groups compared with the conference-only control . CONCLUSION Primary care practice s are interested in improving prevention systems and can change these systems in response to supportive external interventions . Promoting organizational change to produce sustained improvement in preventive service clinical outcomes is a complex process that requires further research OBJECTIVE Concurrent peer review visits are structured office visits conducted by clinician peers of the primary care clinician that are specifically design ed to reduce competing dem and s , clinical inertia , and bias . We assessed whether a single concurrent peer review visit reduced clinical inertia and improved control of hypertension , hyperlipidemia , and diabetes control among underserved patients . METHODS We conducted a r and omized encouragement trial to evaluate concurrent peer review visits with a community health center . Seven hundred twenty-seven patients with hypertension , hyperlipidemia , and /or diabetes who were not at goal for systolic blood pressure ( SBP ) , low-density lipoprotein cholesterol ( LDL-C ) , and /or glycated hemoglobin ( A1c ) were r and omly assigned to an invitation to participate in a concurrent peer review visit or to usual care . We compared change in these measures using mixed models and rates of therapeutic intensification during concurrent peer review visits with control visits . RESULTS One hundred seventy-one patients completed a concurrent peer review visit . SBP improved significantly ( p < .01 ) more among those completing concurrent peer review visits than among those who failed to respond to a concurrent peer review invitation or those r and omized to usual care . There were no differences seen for changes in LDL-C or A1c . Concurrent peer review visits were associated with statistically significant greater clinician intensification of blood pressure ( p < .001 ) , lipid ( p < .001 ) , and diabetes ( p < .005 ) treatment than either for control visits for patients in either the nonresponse group or usual care group . CONCLUSIONS Concurrent peer review visits represent a promising strategy for improving blood pressure control and improving therapeutic intensification in community health centers RATIONALE , AIMS AND OBJECTIVES The objective of this study was to apply a paper-based clinical reminder to improve the adherence to lipid guidelines . METHODS Patients with coronary heart disease ( CHD ) without lipid-lowering therapy ( LLT ) were recruited , and medical records were review ed . Eligible subjects were r and omized ; a clinical reminder stating current st and ards and local insurance policy was stamped on the paper chart in the study group but not in the control . The primary outcome was new LLT subscription in the 6-month follow-up period , and the secondary end point was the composite result of LLT or lipid profile check-up . RESULTS Ninety-two patients were assigned to the study group and 102 to the control group . The primary outcome showed no difference at the end of 6 months ( OR : 1.70 , P = 0.248 , 95 % CI : 0.69 - 4.19 ) . The secondary end point was significantly higher in the reminder group ( OR : 2.81 , P = 0.001 , 95 % CI : 1.57 - 5.04 ) . CONCLUSION A paper chart based clinical reminder providing up date clinical recommendations could modify the doctor 's behaviour and improve the attention to lipid levels . However , its effect can not be transformed into an increase in LLT or a decrease in low-density lipoprotein level owing to local policy constraint BACKGROUND Despite increasing evidence that treating dyslipidemia reduces cardiovascular events , many patients do not achieve recommended lipid targets . METHODS To determine whether showing physicians and patients the patient 's calculated coronary risk can improve the effectiveness of treating dyslipidemia in a primary care setting , patients were r and omized to receive usual care or ongoing feedback regarding their calculated coronary risk and the change in this risk after lifestyle changes , pharmacotherapy , or both to treat dyslipidemia . Outcomes , based on intention-to-treat analysis , included changes in blood lipid levels , coronary risk , and the frequency of reaching lipid targets . RESULTS Two hundred thirty primary care physicians enrolled 3,053 patients . After 12 months of follow-up , 2,687 patients ( 88.0 % ) remained in the study . After adjustment for baseline lipid values , significantly greater mean reductions in low-density lipoprotein cholesterol levels and the total cholesterol to high-density lipoprotein cholesterol ratio were observed in patients receiving risk profiles ( 51.2 mg/dL [ to convert to millimoles per liter , multiply by 0.0259 ] and 1.5 , respectively ) vs usual care ( 48.0 mg/dL and 1.3 , respectively ) , but the differences were small ( -3.3 mg/dL ; 95 % confidence interval [ CI ] , -5.4 to -1.1 mg/dL ; and -0.1 ; 95 % CI , -0.2 to -0.1 , respectively ) . Patients in the risk profile group were also more likely to reach lipid targets ( odds ratio , 1.26 ; 95 % CI , 1.07 to 1.48 ) . A significant dose-response effect was also noted when the impact of the risk profile was stronger in those with worse profiles . CONCLUSIONS Discussing coronary risk with the patient is associated with a small but measurable improvement in the efficacy of lipid therapy . The value of incorporating risk assessment in preventive care should be further evaluated Background : Medical record audits have been used to provide physicians with feedback about their compliance with preventive health and disease management recommendations . Purpose : To determine if report cards summarizing medicine residents ' preventive health and disease management practice s can be used as a feedback tool to improve practice performance . Methods : R and omized , blinded , controlled study of 44 internal medicine residents using an individualized 78-item report card based on outpatient record audits . Results : Four hundred ninety-seven charts were retrospectively audited at baseline and 284 charts in follow-up . There were no significant differences in baseline performance between the residents in the intervention and control group . There were no differences in performance scores between residents receiving report cards and those who had not in immunizations , counseling , total preventive health , diabetes , hypertension , and total disease management . Conclusions : Intensive data -based feedback using report cards may not be a successful way to improve ambulatory performance of medical house officers 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 BACKGROUND Accumulating evidence suggests that collaborative models of care enhance communication among primary care providers , improving quality of care and outcomes for patients with chronic conditions . We sought to determine whether a multifaceted intervention that used a collaborative care model and was directed through primary care providers would improve symptoms of angina , self-perceived health , and concordance with practice guidelines for managing chronic stable angina . METHODS We conducted a prospect i ve trial , cluster r and omized by provider , involving patients with symptomatic ischemic heart disease recruited from primary care clinics at 4 academically affiliated Department of Veterans Affairs health care systems . Primary end points were changes over 12 months in symptoms on the Seattle Angina Question naire , self-perceived health , and concordance with practice guidelines . RESULTS In total , 183 primary care providers and 703 patients participated in the study . Providers accepted and implemented 91.6 % of 701 recommendations made by collaborative care teams . Almost half were related to medications , including adjustments to β-blockers , long-acting nitrates , and statins . The intervention did not significantly improve symptoms of angina or self-perceived health , although end points favored collaborative care for 10 of 13 prespecified measures . While concordance with practice guidelines improved 4.5 % more among patients receiving collaborative care than among those receiving usual care ( P < .01 ) , this was mainly because of increased use of diagnostic testing rather than increased use of recommended medications . CONCLUSION A collaborative care intervention was well accepted by primary care providers and modestly improved receipt of guideline -concordant care but not symptoms or self-perceived health in patients with stable angina 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 BACKGROUND There have been recent moves to extend the role of the community pharmacist to include medicine management . METHODS A r and omized controlled trial was conducted in nine sites in Engl and . Patients with coronary heart disease were identified from general practice computer systems , recruited and r and omized ( 2:1 ) to intervention or control . The 12-month intervention comprised an initial consultation with a community pharmacist to review appropriateness of therapy , compliance , lifestyle , social and support issues . Control patients received st and ard care . The primary outcome measures were appropriate treatment [ derived from the National Service Framework ( NSF ) ] , health status ( SF-36 , EQ-5D ) and an economic evaluation . Secondary outcome measures were patient risk of cardiovascular death and satisfaction . RESULTS The study involved 1493 patients ( 980 intervention and 513 control ) , 62 pharmacists and 164 GPs . No statistically significant differences between intervention and control groups were shown at follow-up for any of the primary outcome measures such as numbers on aspirin or lifestyle measures . There were few differences in quality of life ( SF-36 ) between the intervention and control groups at baseline or follow-up or with overall EQ-5D score over time . The total National Health Service cost increased between baseline and at 12 months in both groups but to a greater extent in the intervention group . Significant improvements were found in the satisfaction score for patients ' most recent pharmacy visit for prescription medicines among the intervention group , compared with control group . Self-reported compliance was good for both groups at baseline and no significant differences were shown at follow-up . CONCLUSION There was no change in the proportion of patients receiving appropriate medication as defined by the NSF . The pharmacist-led service was more expensive than st and ard care To overcome shortcomings in the delivery of care for hypertension various approaches have been developed including a system whereby care of hypertension is shared in a formal manner between general practitioners and hospital specialists . The feasibility , acceptability and cost-effectiveness of a computerised model of shared care were investigated in three matched groups of patients attending hypertension clinics in Glasgow . Glasgow Blood Pressure Clinic attenders considered suitable for shared care by their consultants were r and omised to shared care ( n = 277 ) or continued clinic follow-up ; a further control group ( n = 277 ) was identified from an independent nurse-practitioner clinic . After 2 years of follow-up , feasibility was estimated by the proportion of patients who had undergone an adequate review ( blood pressure , serum creatinine and electrocardiograph ) ; acceptability to general practitioners and patients was assessed by question naires ; cost-effectiveness was calculated as the cost ( to National Health Service and patient ) per adequate review . The drop-out rate for shared care over 2 years was 3 % compared with 14 % for the outpatient clinic and 9 % for the nurse-practitioner clinic . In year 2 , rates of adequate review s were 82 % , 52 % and 75 % , respectively . Blood pressure control was similar in the groups . Of 297 general practitioners invited to participate , 85 % agreed and 68 % wished to continue participation after 2 years . About 50 % of shared care patients preferred this method of follow-up compared with their earlier experience of clinic attendance . Shared care was more cost-effective than either conventional or nurse-practitioner clinic follow-up , especially with respect to cost to the patient ; costs per adequate review ( pound sterling ) were 28.96 , 50.55 and 30.95 , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS Background Self blood pressure monitoring at home may improve blood pressure control and patients ' compliance with treatment , but its implementation in daily practice faces difficulties . Teletransmission facilities may offer a more efficient approach to long-term home blood pressure monitoring . Methods Twelve general practitioners screened 391 consecutive uncontrolled mild – moderate hypertensive patients ( 80 % treated ) , 329 of whom ( 58 ± 11 years , 54 % men ) were r and omized to either usual care on the basis of office blood pressure ( group A , n = 113 ) or to integrated care on the basis of teletransmitted home blood pressure ( group B , n = 216 ) . Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline and after 6 months , during which treatment was optimized according to either office ( group A ) or home ( group B ) blood pressure values . We compared differences between groups in the rate of daytime ambulatory blood pressure normalization ( < 130/80 mmHg ) , need of treatment changes during follow-up , quality of life scores , and healthcare costs . Results Baseline office blood pressures were 149 ± 12/89 ± 9 and 148 ± 13/89 ± 7 mmHg in groups A ( n = 111 ) and B ( n = 187 ) respectively , the corresponding daytime values being 140 ± 11/84 ± 8 and 139 ± 11/84 ± 8 mmHg . The percentage of daytime blood pressure normalization was higher in group B ( 62 % ) than in group A ( 50 % ) ( P < 0.05 ) . There were less frequent treatment changes in group B than in group A ( 9 vs. 14 % , P < 0.05 ) . Quality of life tended to be higher and costs lower in group B. Conclusion Patients ' management based on home blood pressure teletransmission led to a better control of ambulatory blood pressure than with usual care , with a more regular treatment regimen BACKGROUND There is a lack of evidence regarding the value of tools design ed to aid decision making in patients with newly diagnosed hypertension . AIM To evaluate two interventions for assisting newly diagnosed hypertensive patients in the decision whether to start drug therapy for reducing blood pressure . DESIGN OF STUDY Factorial r and omised controlled trial . SETTING Twenty-one general practice s in south-west Engl and , UK . METHOD Adults aged 32 to 80 years with newly diagnosed hypertension were r and omised to receive either : ( a ) computerised utility assessment interview with individualized risk assessment and decision analysis ; or ( b ) information video and leaflet about high blood pressure ; or ( c ) both interventions ; or ( d ) neither intervention . Outcome measures were decisional conflict , knowledge , state anxiety , intentions regarding starting treatment , and actual treatment decision . RESULTS Of 217 patients r and omised , 212 ( 98 % ) were analysed at the primary follow-up ( mean age = 59 years , 49 % female ) . Decision analysis patients had lower decisional conflict than those who did not receive this intervention ( 27.6 versus 38.9 , 95 % confidence interval [ CI ] for adjusted difference = -13.0 to -5.8 , P < 0.001 ) , greater knowledge about hypertension ( 73 % versus 67 % , adjusted 95 % CI = 2 % to 9 % , P = 0.003 ) and no evidence of increased state anxiety ( 34.8 versus 36.8 , adjusted 95 % CI = -5.6 to 0.1 , P = 0.055 ) . Video/leaflet patients had lower decisional conflict than corresponding controls ( 30.3 versus 36.8 , adjusted 95 % CI = -7.4 to -0.6 , P = 0.021 ) , greater knowledge ( 75 % versus 65 % , adjusted 95 % CI = 6 % to 13 % , P < 0.001 ) and no evidence of increased state anxiety ( 35.7 versus 36.1 , adjusted 95 % CI = -3.9 to 1.7 , P = 0.46 ) . There were no differences between either of the interventions and their respective controls in the proportion of patients prescribed antihypertensive medication ( 67 % ) . CONCLUSIONS This trial demonstrates that , among patients facing a real treatment decision , interventions to inform patients about hypertension and to clarify patients ' values concerning outcomes of treatment are effective in reducing decisional conflict and increasing patient knowledge , while not result ing in any increases in state anxiety Aims We tested the hypothesis that enhanced care for diabetes , tailored to the needs of the South Asian community with Type 2 diabetes , would improve risk factors for diabetic vascular complications and ultimately reduce morbidity and mortality Background : Proven efficacious therapies are sometimes underused in patients with chronic cardiac conditions , result ing in suboptimal outcomes . We evaluated whether evidence summaries , which were either unsigned or signed by local opinion leaders , improved the quality of secondary prevention care delivered by primary care physicians of patients with coronary artery disease . Methods : We performed a r and omized trial , clustered at the level of the primary care physician , with 3 study arms : control , unsigned statements or opinion leader statements . The statements were faxed to primary care physicians of adults with coronary artery disease at the time of elective cardiac catheterization . The primary outcome was improvement in statin management ( initiation or dose increase ) 6 months after catheterization . Results : We enrolled 480 adults from 252 practice s. Although statin use was high at baseline ( n = 316 [ 66 % ] ) , most patients were taking a low dose ( mean 32 % of the guideline -recommended dose ) , and their low-density lipoprotein ( LDL ) cholesterol levels were elevated ( mean 3.09 mmol/L ) . Six months after catheterization , statin management had improved in 79 of 157 patients ( 50 % ) in the control arm , 85 of 158 ( 54 % ) patients in the unsigned statement group ( adjusted odds ratio [ OR ] 1.18 , 95 % CI 0.71–1.94 , p = 0.52 ) and 99 of 165 ( 60 % ) patients in the opinion leader statement group ( adjusted OR 1.51 , 95 % CI 0.94–2.42 , p = 0.09 ) . The mean fasting LDL cholesterol levels after 6 months were similar in all 3 study arms : 2.35 ( st and ard deviation [ SD ] 0.86 ) mmol/L in the control arm compared with 2.24 ( SD 0.73 ) among those in the opinion leader group ( p = 0.48 ) and 2.19 ( SD 0.68 ) in the unsigned statement group ( p = 0.32 ) . Interpretation : Faxed evidence reminders for primary care physicians , even when endorsed by local opinion leaders , were insufficient to optimize the quality of care for adults with coronary artery disease . Clinical Trials.gov trial register no. NCT00175240 RATIONALE , AIMS AND OBJECTIVES Peer review groups are considered helpful for quality improvement in primary care . An interactive educational programme for small peer groups was developed , focusing on the implementation of newly developed treatment guidelines . The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice . METHODS A cluster r and omized trial using a balanced incomplete block design was used ; one arm received a programme on treatment of chronic heart failure ( CHF ) , the other on hypertension treatment in diabetes mellitus type 2 ( T2DM ) . A r and om sample of 10 CHF and 10 T2DM patients per GP was drawn , for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention . The outcomes were prescribing of ACE inhibitors , and antihypertensive treatment in T2DM . The effect was analysed separately for both programmes using multilevel regression models . RESULTS All 27 peer review groups in one region in the Netherl and s were r and omized , of which 16 participated . No significant effects were observed in the CHF group or in the T2DM group . The opportunity for change was limited , as only 53 % of the CHF patients and 60 % of the T2DM patients had a contact with their GP between the intervention and follow-up measurement . CONCLUSION The peer review programme was not successful for changing the treatment of chronic patients , although the programme focused on dealing with barriers perceived by the participants . Not all problems perceived can be solved in a peer group discussion BACKGROUND Adequate care for patients with cardiovascular risks requires an adequate practice organization . Educational outreach visits are a promising approach to modifying professional behavior . We aim ed to assess whether the quality of cardiovascular preventive care in general practice can be improved through a comprehensive intervention implemented by an educational outreach visitor . METHODS After baseline measurements , general practice s ( n = 124 ) in the southern half of The Netherl and s were r and omly allocated to either intervention or control group . The intervention , based on the educational outreach model , comprised 15 practice visits over a period of 21 months and addressed a large number of issues around task delegation , availability of instruments and patient leaflets , record-keeping , and follow-up routines . Twenty-one months after the start of the intervention , postintervention measurements were performed . The difference between ideal and actual practice in each aspect of organizing preventive care was defined as a deficiency score . Primary outcome measure was the difference in deficiency scores before and after the intervention . RESULTS All practice s completed both baseline and postintervention measurements . The difference in change between intervention and control group adjusted for baseline was statistically significant ( P < 0.001 ) for each aspect of organizing preventive care . The largest absolute improvement was found for the number of preventive tasks performed by the practice assistant . CONCLUSIONS This study showed that a comprehensive intervention implemented by outreach visitors was effective in improving organization of cardiovascular preventive care in general practice 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 Despite evidence from r and omized trials and national guidelines that recommend the use of aspirin , β-blockers , and cholesterol-lowering agents for patients with coronary artery disease , many patients are not treated appropriately.1,2,3 Several types of fixed-message physician reminder systems — including checklists , chart tags , and computer-generated reminders — have improved physician compliance with cancer screening guidelines , 4 but it is less clear whether they are effective at improving disease management . We examined whether the combination of a computer-generated and written reminder system provided during patient visits could increase patient receipt of aspirin , β-blockers , and cholesterol-lowering agents Abstract Objectives To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting , and to assess the impact of these on health behaviours , anxiety , prescribed antihypertensive drugs , patients ' preferences , and costs . Design R and omised controlled trial . Setting Eight general practice s in south Birmingham . Participants 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg . Interventions Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice ; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level . Patients in the control group received usual care ( blood pressure monitoring by their practice ) . Main outcome measures Primary outcome : change in systolic blood pressure at six months and one year in both intervention and control groups . Secondary outcomes : change in health behaviours , anxiety , prescribed antihypertensive drugs , patients ' preferences of method of blood pressure monitoring , and costs . Results 400 ( 91 % ) patients attended follow up at one year . Systolic blood pressure in the intervention group had significantly reduced after six months ( mean difference 4.3 mm Hg ( 95 % confidence interval 0.8 mm Hg to 7.9 mm Hg ) ) but not after one year ( mean difference 2.7 mm Hg ( – 1.2 mm Hg to 6.6 mm Hg ) ) . No overall difference was found in diastolic blood pressure , anxiety , health behaviours , or number of prescribed drugs . Patients who self monitored lost more weight than controls ( as evidence d by a drop in body mass index ) , rated self monitoring above monitoring by a doctor or nurse , and consulted less often . Overall , self monitoring did not cost significantly more than usual care ( £ 251 ( $ 437 ; 364 euros ) ( 95 % confidence interval £ 233 to £ 275 ) versus £ 240 ( £ 217 to £ 263 ) . Conclusions Practice based self monitoring result ed in small but significant improvements of blood pressure at six months , which were not sustained after a year . Self monitoring was well received by patients , anxiety did not increase , and there was no appreciable additional cost . Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care Objective - A lack of global cardiovascular ( CV ) risk approach is often observed in the clinical practice . Having conceived a clinical strategy aim ed at helping general practitioners ( GPs ) to assess and manage global CV risk in the daily practice , we wanted to evaluate the impact of a training promoting this strategy . Methods - R and omised controlled trial involving GPs registered in a continual medical education ( CME ) group . The intervention and control arms included 7 ( 123 GPs ) and 13 ( 220 GPs ) groups , respectively . The intervention was a training in CV prevention provided during a CME meeting . GPs answered a question naire four months after the training . The main outcome was the use of a global CV risk assessment tool . Secondary outcomes were the GPs ’ awareness of the CV diseases burden , knowledge of the CV risk factors , and CV therapeutic attitudes . Results - More trained GPs ( 76 % vs. 52 % ) used a global CV risk assessment tool ( p??=??0.003 ) . Significant differences were also observed for secondary outcomes : ( a ) awareness of CV diseases burden : more trained GPs were aware of the lethality from myocardial infa rct ion ( 37 % vs. 21 % , p??=??0.047 ) and considered it as the main cause of sudden death in adults ( 78 % vs. 59 % , p??=??0.018 ) ; ( b ) knowledge of risk factors : more trained GPs considered familial CV history ( 89 % vs. 73 % , p??=??0.021 ) and HDL-cholesterol ( 82 % vs.62 % , p??=??0.013 ) as important CV risk factors ; ( c ) therapeutic attitudes : fewer trained GPs used to prescribe a lipid-lowering drug based on a total cholesterol value without considering the other risk factors ( 44 % vs.65 % , p??=??0.013 ) . Conclusions - The global CV risk approach in the general practice was favourably influenced by this training provided during a CME meeting . The impact of the training on patients ’ outcomes should be addressed in a prospect i ve trial Electronic decision-support tools may help to improve management of hyperlipidemia and other chronic diseases . This study examined the impact of lipid management tools integrated into an electronic medical record ( EMR ) in primary care practice s. This r and omized controlled trial was conducted in a national network of physicians who use an outpatient EMR . Adult primary care physicians were r and omized by office to receive an electronic form that was embedded in the EMR . The form contained prompts regarding suboptimal care based on Adult Treatment Panel-III ( ATP-III ) guidelines , as well as reporting tools to identify patients outside of office visits whose lipid management was suboptimal . All active patients , ages 20 - 79 years , whose physicians participated in the study , were categorized as high , moderate , or low cardiovascular risk , and the proportion who were tested for hyperlipidemia , at lipid goal , and on lipid-lowering medications if not at goal were measured according to ATP-III guidelines . A total of 105 physicians from 25 offices and 64,150 patients were included in the study . Outcomes improved for most measures from before to 1 year after the intervention ( November 1 , 2005 to October 31 , 2006 ) . However , after controlling for confounding variables and for clustering in multilevel modeling , only up-to- date lipid testing for high-risk patients was statistically better in the intervention group as compared to the control group ( adjusted odds ratio 15.0 , P < 0.05 ) . This study showed few differences in quality of lipid management after implementing an EMR-based disease management intervention in primary care setting s. Future studies may need to examine more comprehensive interventions that include office staff in a team approach to care BACKGROUND Lowering plasma lipid levels in patients in the months following hospital discharge for a myocardial infa rct ion ( MI ) is clearly beneficial if recurrent cardiac events and mortality are to be prevented ; traditionally , however , there has been a large gap between guidelines and levels achieved in routine practice . OBJECTIVES AND METHODS A r and omized , open-label clinical trial was conducted to assess the impact of nurse-centred surveillance and treatment in achieving nationally recognized lipid targets in post-MI patients . This program had the following features : systematic telephone follow-up of patients discharged from the University of Sherbrooke ( Sherbrooke , Quebec ) after an MI ; systematic lipid testing three months after discharge ; close liaison with , and guidance of , patients ' primary care physicians to intervene on results of this test if targets were not obtained ; and continued monitoring of patients until lipid profiles consistent with consensus targets were achieved . The impact of this approach was tested and compared with that of a control group that continued to be followed by a primary care physician for up to 18 months . RESULTS A total of 127 patients were r and omly assigned into an intervention group ( n=64 ) or a control group ( n=63 ) . The intervention group was followed by telephone for an average ( + /-SD ) of 4.4+/-2.0 months post-MI . At this point , when intervention was optimized , the mean low-density lipoprotein cholesterol ( LDL-C ) level was 2.19+/-0.65 mmol/L in the intervention group , and 87.3 % of patients had LDL-C levels of less than 2.5 mmol/L. Patients from both experimental groups returned at 12 months and 18 months post-MI for a new blood lipid assessment . In total , 12.5 % of patients in each group were lost to follow-up . At 12 months and 18 months , the mean LDL-C level was not different between the two groups , nor was there a significant difference in the proportion of patients achieving LDL-C levels of less than 2.5 mmol/L ( 51.6 % in the intervention group and 65 % in the control group at 18 months ; P>0.05 ) . When the combined end point of an LDL-C level of less than 2.5 mmol/L , a triglyceride level of less than 2.0 mmol/L and a total cholesterol to high-density lipoprotein cholesterol ratio of less than 4.0 was considered , the proportion of patients achieving this composite at 18 months was low and not different between the two groups ( 23.4 % in the intervention group and 38.3 % in the control group ; P>0.05 ) . Over 95 % of patients in both groups were on a lipid-lowering medication , and more than 90 % had complied with their medication regimen at 18 months . CONCLUSIONS This trial did not support the role of nurse-managers and a system of telephone-based contacts to ensure the continuity of care and aggressive intervention when considering cardiovascular risk factors in post-MI patients . This trial also re-emphasized the important remaining treatment gap in secondary prevention of coronary artery disease , particularly if composite lipid end points are to be targeted BACKGROUND The availability of clinical guidelines in isolation has generally failed to promote voluntary change in practice patterns . Accordingly , a r and omized controlled trial was conducted to determine the effectiveness of academic detailing ( AD ) techniques and continuous quality improvement ( CQI ) teams in increasing compliance with national guidelines for the primary care of hypertension and depression . METHODS Fifteen small group practice s at four Seattle primary care clinics were assigned to one of three study arms -- AD alone , AD plus CQI teams , or usual care . The activity of 95 providers and 4,995 patients was monitored from August 1 , 1993 , through January 31 , 1996 . Twelve-month baseline and study periods were separated by a six-month " wash-in " period during which training sessions were held . Changes in hypertension prescribing , blood pressure control , depression recognition , use of older tricyclics , and scores on the Hopkins Symptom Checklist depression scale were examined . RESULTS Clinics varied considerably in their implementation of both the AD and the CQI team interventions . Across all sites , AD was associated with change in a single process measure , a decline in the percentage of depressives prescribed first-generation tricyclics ( -4.7 percentage points versus control , p = 0.04 ) . No intervention effects were demonstrated for CQI teams across all sites for either disease condition . Within the clinic independently judged most successful at implementing both change strategies , the use of CQI teams and AD in combination did increase the percentage of hypertensives adequately controlled ( 17.3 percentage points versus control , p = 0.03 ) . SUMMARY AND CONCLUSIONS The AD techniques and the CQI teams evaluated were generally ineffective in improving guideline compliance and clinical outcomes regarding the primary care of hypertension and depression Background : Few studies have reported the efficacy of collaborative care involving family physicians and community pharmacists for patients with dyslipidemia . Methods : We r and omly assigned clusters consisting of at least two physicians and at least four pharmacists to provide collaborative care or usual care . Under the collaborative care model , pharmacists counselled patients about their medications , requested laboratory tests , monitored the effectiveness and safety of medications and patients ’ adherence to therapy , and adjusted medication dosages . After 12 months of follow-up , we assessed changes in low-density lipoprotein ( LDL ) cholesterol ( the primary outcome ) , the proportion of patients reaching their target lipid levels and changes in other risk factors . Results : Fifteen clusters representing a total of 77 physicians and 108 pharmacists were initially recruited , and a total of 51 physicians and 49 pharmacists were included in the final analyses . The collaborative care teams followed a total of 108 patients , and the usual care teams followed a total of 117 patients . At baseline , mean LDL cholesterol level was higher in the collaborative care group ( 3.5 v. 3.2 mmol/L , p = 0.05 ) . During the study , patients in the collaborative care group were less likely to receive high-potency statins ( 11 % v. 40 % ) , had more visits with health care professionals and more laboratory tests , were more likely to have their lipid-lowering treatment changed and were more likely to report lifestyle changes . At 12 months , the crude incremental mean reduction in LDL cholesterol in the collaborative care group was −0.2 mmol/L ( 95 % confidence interval [ CI ] −0.3 to −0.1 ) , and the adjusted reduction was −0.05 ( 95 % CI −0.3 to 0.2 ) . The crude relative risk of achieving lipid targets for patients in the collaborative care group was 1.10 ( 95 % CI 0.95 to 1.26 ) , and the adjusted relative risk was 1.16 ( 95 % CI 1.01 to 1.34 ) . Interpretation : Collaborative care involving physicians and pharmacists had no significant clinical impact on lipid control in patients with dyslipidemia . International St and ard R and omized Controlled Trial register no. IS RCT N66345533 |
13,453 | 26,689,942 | Our main outcomes of interest were important changes in ( i ) mental state , ( ii ) behaviour , ( iii ) dose of medication used , ( iv ) adverse events , ( v ) satisfaction with care and ( iv ) cost of care . | BACKGROUND Drugs used to treat psychotic illnesses may take weeks to be effective .
In the interim , additional ' as required ' doses of medication can be used to calm patients in psychiatric wards .
The practice is widespread , with 20 % to 50 % of people on acute psychiatric wards receiving at least one ' as required ' dose of psychotropic medication during their admission .
OBJECTIVES To compare the effects of ' as required ' medication regimens with regular patterns of medication for the treatment of psychotic symptoms or behavioural disturbance , thought to be secondary to psychotic illness .
These regimens may be given alone or in addition to any regular psychotropic medication for the long-term treatment of schizophrenia or schizophrenia-like illnesses . | Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly . However , patients view intramuscular administration as coercive , and conventional antipsychotics are often associated with adverse events . In this open study , consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2 - 6 mg/day ( n = 48 ) or oral zuclopenthixol 20 - 50 mg/day ( n = 27 ) for 7 - 14 days . Lorazepam ( either oral or intramuscular ) was administered to both groups as needed . Patients were assessed regularly until day 14 or discharge . Mean Positive And Negative Syndrome Scale ( PANSS ) aggression scores ( sum of item scores on excitement , poor impulse control , hostility and uncooperativeness ) decreased steadily and similarly in both groups ; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point . The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group , but not in the zuclopenthixol group . Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups . Overall , 18.7 % of patients showed minor extrapyramidal symptoms during the study , but only 16.7 % of risperidone-treated patients , compared to 59.3 % of zuclopenthixol-treated patients , received anti-parkinsonian medication ( p < 0.001 ) . Lorazepam was administered to all of the patients assigned to risperidone and to 89 % of those assigned to zuclopenthixol . Oral risperidone plus lorazepam is a convenient , effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Abstract Intramuscular ( IM ) antipsychotics are preferred for efficient control of agitation symptoms . Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia . However , clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability . This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia . Subjects with acute schizophrenia were r and omized to either ziprasidone ( n = 189 , 10 to 20 mg as required up to a maximum of 40 mg/d ) or haloperidol ( n = 187 , 5 mg every 4 to 8 hours to a maximum of 20 mg/d ) for 3 days . Psychiatric assessment s and adverse events were assessed at baseline , 2 , 4 , 24 , 48 , and 72 hours . In the ziprasidone group , 2.1 % of subjects discontinued versus 3.7 % in the haloperidol group . The least squares mean change ( SE ) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was −17.32 ( 0.7 ) for ziprasidone ( n = 167 ) and −18.44 ( 0.7 ) for haloperidol ( n = 152 ) , with a 95 % confidence interval treatment difference of −0.7 to 2.9 . Fewer subjects experienced adverse events after ziprasidone ( n = 54 , 28.6 % ) than haloperidol ( n = 116 , 62.0 % ) , with a notably higher incidence of extrapyramidal symptoms in the haloperidol group ( n = 69 , 36.9 % ) compared to the ziprasidone group ( n = 4 , 2.1 % ) . For controlling agitation in schizophrenia in this Chinese study , ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol OBJECTIVE The objective of this study was to compare the efficacy and side effects of sodium cromoglycate eye drops ( Opticrom 2 % ) used regularly versus as needed in the treatment of seasonal ( ragweed ) allergic conjunctivitis . METHODS A r and omized , unblinded , parallel group comparison was performed during the 6 weeks of the ragweed pollen season . Sixty-two adults with ragweed pollen-induced conjunctivitis were recruited for the study from previous ragweed studies and notices in the local media . Two drops of sodium cromoglycate were placed in each eye either four times daily ( regular treatment group ) or when needed , up to four times daily ( prn group ) , from 1 week before and throughout the ragweed pollen season . Uncontrolled eye symptoms were treated with terfenadine 60 mg as needed , up to 120 mg daily . Subjects kept daily diaries for symptoms and medication requirements throughout the 6 weeks of treatment . The Rhinoconjunctivitis Quality of Life Question naire was administered and adverse experiences were reported after 1 , 3 , and 6 weeks of treatment . RESULTS Diary eye symptoms were similar in the two treatment groups , but quality of life was better in the regular treatment group . There was a trend for the prn group to require more terfenadine for uncontrolled eye symptoms . CONCLUSIONS There may be some additional therapeutic benefit from using sodium cromoglycate eye drops regularly throughout the ragweed pollen season OBJECTIVE This study compared the effects of atypical antipsychotics ( risperidone or quetiapine ) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization . METHODS This international , r and omized , double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase . Recently exacerbated patients with schizophrenia or schizoaffective disorder ( DSM-IV ) were r and omized ( 2:2:1 ) to risperidone ( n = 153 ) , quetiapine ( n = 156 ) , or placebo ( n = 73 ) . Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5 , with the ability to increase to 600 or 800 mg/day of quetiapine on day 8 . The main outcome measures were the total Positive and Negative Syndrome Scale ( PANSS ) and need for additional psychotropic medications . RESULTS Monotherapy Phase : The combined atypical antipsychotic group ( n = 308 ) reached borderline superiority to placebo ( n = 71 ) at the 2-week endpoint on mean change in total PANSS score ( -24.1 + /- 1.2 and -20.2 + /- 2.0 , respectively ; p = 0.067 ) . The change in the atypical group was driven by the improvement with risperidone ( -27.7 + /- 1.5 vs. -20.2 + /- 2.0 with placebo , p < 0.01 ; and vs. -20.5 + /- 1.5 with quetiapine , p < 0.01 ) ; the improvement with quetiapine was similar to placebo , p = 0.879 . Results were similar on other efficacy endpoints . Additive Therapy Phase : Additional psychotropics were prescribed to fewer ( p < 0.01 ) risperidone ( 36 % ) than quetiapine ( 53 % ) or placebo patients ( 59 % ) . The overall discontinuation rate was 18 % , 26 % , and 38 % , respectively . Risperidone , compared with placebo , was associated with more parkinsonism , akathisia , plasma prolactin changes , and weight gain ; while quetiapine was associated with more somnolence , sedation , dizziness , constipation , tachycardia , thyroid dysregulation , and weight gain . CONCLUSION While the combined atypical antipsychotic group did not experience greater improvements than the placebo group , risperidone , but not quetiapine , was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder , with no unexpected tolerability findings We conducted a prospect i ve double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia . Patients were r and omized to either oral olanzapine ( 10 mg per day ) or oral haloperidol ( 10 mg per day ) , plus lorazepam as needed ( up to 12 mg per day ) . Antipsychotic dosage was increased to 20 mg per day as early as day 3 . Patients were evaluated with the Positive and Negative Syndrome Scale ( PANSS ) Agitation subscale during the first 24 hours of treatment , daily for the first week , then weekly until study completion . Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy ( -5.79 + /- 6.30 for olanzapine and -4.89 + /- 6.05 for haloperidol , P < .001 ) . This study demonstrated that accelerated dose titration of oral olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia Background Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state . Agitation presents a barrier to therapy , interrupting the typical physician-patient alliance and creating a disruptive , even hazardous , environment . Rapid assessment and effective treatment are necessary to manage agitation and , potentially , to shorten the time to recovery . Methods One hundred forty-eight acutely agitated patients received either : rapid initial dose escalation ( RIDE ) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2 , up to 30 mg on days 3 and 4 , and 5 to 20 mg thereafter ; or usual clinical practice ( UCP ) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2 , up to 2 mg on days 3 and 4 , and olanzapine 5 to 20 mg/d thereafter . The Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC : poor impulse control , tension , hostility , uncooperativeness , and excitement ) measured at 24 hours was the primary measure . Secondary assessment s of agitation and safety were also performed . Results Agitation improved significantly from baseline for both treatment groups ; however , improvement with the RIDE strategy was superior to UCP . The RIDE group improvement was superior on the primary efficacy measure ( PANSS-Excited ) at 24 hours ; it was superior on all agitation measures at the end of double-blind treatment . Both treatments were well tolerated , with no clinical ly significant differences in safety measures . Treatment was not limited by oversedation and attention improved from baseline in both groups . Conclusions This study demonstrates the value of olanzapine in the treatment of acutely agitated patients . A new approach to olanzapine dosing that exp and s the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation BACKGROUND There is a clear need for effective , well-tolerated intramuscular ( i.m . ) agents for the acute control of agitated psychotic patients . Currently used agents , including conventional antipsychotics and /or benzodiazepines , may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation . OBJECTIVE The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m . formulation of the novel antipsychotic ziprasidone in the treatment of in patients with psychosis and acute agitation ( DSM-IV diagnoses ) . METHOD In a 24-hour , double-blind , fixed-dose clinical trial , patients were r and omly assigned to receive up to 4 injections ( every 2 hours p.r.n . ) of 2 mg ( N = 54 ) or 10 mg ( N = 63 ) of ziprasidone i.m . The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m . injection . RESULTS Ziprasidone i.m . , 10 mg , rapidly reduced symptoms of acute agitation and was significantly more effective ( p < .01 ) than the 2-mg dose up to 4 hours after the first injection . Patients were calmed but not excessively se date d , and over half were classed as responders 2 hours after the 10-mg dose . No acute dystonia or behavioral disinhibition was reported . One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia . CONCLUSION Ziprasidone i.m . , 10 mg , is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient . Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m . is significant and dose related In a double-blind controlled study , 20 acutely psychotic in patients were treated with different haloperidol dosage regimens . Over a 24-hour period , 10 of the patients were treated with rapid intramuscular neuroleptization at 10 mg per dose and 10 at 2 mg per dose . The patients were then treated for 6 more days with an oral dose equivalent to that given over the first 24 hours of treatment , with doctor 's choice adjustments as needed . Behavioral change was rated using the Brief Psychiatric Rating Scale ( BPRS ) . Blood sample s drawn at baseline and late in the treatment were assayed for plasma and red blood cell haloperidol levels . Although neither of these variables showed a significant correlation with behavioral improvement , the ratio of plasma/RBC haloperidol levels significantly correlated with improvement The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service . Thirty-seven highly agitated patients exhibiting psychotic symptoms were r and omly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate . Symptom ratings were conducted each hour using double-blind procedures . Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale . Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study . However , Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings . The groups did not differ on the Brief Psychiatric Rating Scale at any rating time . No differences were found either in the number of doses administered or in the administration route selected . Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol , lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting Nine patients receiving a low dose ( 25 mg ) and ten receiving a st and ard dose ( 150 mg ) of depot haloperidol every four weeks were assessed every three months for two years . Patients also received targeted oral neuroleptics as needed . No significant between-group differences were found in clinical outcome as measured by number of hospital admissions , days hospitalized , scores on the Brief Psychiatric Rating Scale and the Global Assessment Scale , and level of extrapyramidal symptoms . Combining low-dose depot and targeted oral neuroleptics was at least as effective as using a st and ard depot dose and for many patients may provide the best way to reach the minimal effective dose for maintenance treatment BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials 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 |
13,454 | 28,713,272 | Conclusion : The studies discussed in this review strongly corroborate the role of Citrus juices and their derivatives as potential re source against cancer | Background : During the last decades , a huge body of evidence has been accumulated suggesting that Citrus fruits and their juices might have a role in preventing many diseases including cancer .
Objective : To summarize the numerous evidence s on the potential of Citrus juices and their extracts as anticancer agents . | IMPORTANCE Resveratrol , a polyphenol found in grapes , red wine , chocolate , and certain berries and roots , is considered to have antioxidant , anti-inflammatory , and anticancer effects in humans and is related to longevity in some lower organisms . OBJECTIVE To determine whether resveratrol levels achieved with diet are associated with inflammation , cancer , cardiovascular disease , and mortality in humans . DESIGN Prospect i ve cohort study , the Invecchiare in Chianti ( InCHIANTI ) Study ( " Aging in the Chianti Region " ) , 1998 to 2009 conducted in 2 villages in the Chianti area in a population -based sample of 783 community-dwelling men and women 65 years or older . EXPOSURES Twenty-four-hour urinary resveratrol metabolites . MAIN OUTCOMES AND MEASURES Primary outcome measure was all-cause mortality . Secondary outcomes were markers of inflammation ( serum C-reactive protein [ CRP ] , interleukin [IL]-6 , IL-1β , and tumor necrosis factor [ TNF ] ) and prevalent and incident cancer and cardiovascular disease . RESULTS Mean ( 95 % CI ) log total urinary resveratrol metabolite concentrations were 7.08 ( 6.69 - 7.48 ) nmol/g of creatinine . During 9 years of follow-up , 268 ( 34.3 % ) of the participants died . From the lowest to the highest quartile of baseline total urinary resveratrol metabolites , the proportion of participants who died from all causes was 34.4 % , 31.6 % , 33.5 % , and 37.4 % , respectively ( P = .67 ) . Participants in the lowest quartile had a hazards ratio for mortality of 0.80 ( 95 % CI , 0.54 - 1.17 ) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders . Resveratrol levels were not significantly associated with serum CRP , IL-6 , IL-1β , TNF , prevalent or incident cardiovascular disease , or cancer . CONCLUSIONS AND RELEVANCE In older community-dwelling adults , total urinary resveratrol metabolite concentration was not associated with inflammatory markers , cardiovascular disease , or cancer or predictive of all-cause mortality . Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study BACKGROUND & AIMS Blond orange juice is the most consumed fruit juice in the world . It is a source of hesperidin , a bioavailable flavonoid reported to exhibit potential vascular protective actions . However , the specific impact on vascular function of Citrus phytomicronutrients , is unknown . For the first time , we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice ( including Vitamin C but no phytomicronutrients ) , on antioxidant markers , cardiovascular risk factors and endothelial function . METHODS Twenty five male volunteers with two cardiovascular risk factors ( age over 50 years and LDL-cholesterol between 130 and 190 mg/L ) were enrolled in a r and omized cross-over study . They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks , spaced by a 5-week wash-out . Endothelial function ( flow mediated dilatation and plasma markers ) , oxidative status , lipid profile and inflammatory markers were assessed . RESULTS Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species . A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed . This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice . CONCLUSIONS These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in . Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function . This study is recorded in Clinical Trials.com as NCT00539916 BACKGROUND Oxidative and inflammatory stresses are involved in the pathogenesis of atherosclerosis . The consumption of fruit and vegetables is associated with improved health and reduced cardiovascular risk . Red oranges have a high content of antioxidant and antiinflammatory substances , but there is a paucity of data concerning their effects on cardiovascular biomarkers in subjects with increased cardiovascular risk . OBJECTIVE We investigated the effect of red orange juice intake on endothelial function , oxidative stress , and markers of inflammation in subjects with increased cardiovascular risk . DESIGN Nineteen nondiabetic subjects with increased cardiovascular risk ( aged 27 - 56 y ) were included in a r and omized , placebo-controlled , single-blind crossover study and compared with 12 healthy , nonobese control subjects . In 2 periods of 7 d each with a 3-d interval , each participant alternatively received 500 mL red orange juice/d and 500 mL placebo/d in a r and om sequence . All measurements were performed in the morning after overnight fasting . RESULTS Endothelial function , which was measured as flow-mediated dilation , significantly improved and was normalized ( 5.7 % compared with 7.9 % ; P < 0.005 ) after 1 wk of red orange juice consumption . Similarly , concentrations of high-sensitivity C-reactive protein , IL-6 , and TNF-α significantly decreased ( P < 0.001 ) . Red orange juice had no significant effect on nitric oxide plasma concentrations . CONCLUSION A 7-d consumption of red orange juice ameliorates endothelial function and reduces inflammation in nondiabetic subjects with increased cardiovascular risk . This trial was registered at biomed central .com as IS RCT N39987296 The authors prospect ively evaluated fruit and vegetable consumption and the incidence of oral premalignant lesions among 42,311 US men in the Health Professionals Follow-up Study . Diet was assessed every 4 years by food frequency question naires . The authors confirmed 207 cases of clinical ly or histopathologically diagnosed oral premalignant lesions occurring between 1986 and 2002 . Multivariate-adjusted relative risks were calculated from proportional hazards models . Significant inverse associations were observed with citrus fruits , citrus fruit juice , and vitamin-C-rich fruits and vegetables , indicating 30 - 40 % lower risks with greater intakes ( e.g. , citrus fruit juice quintile 5 vs. quintile 1 relative risk = 0.65 , 95 % confidence interval : 0.42 , 0.99 ) . Inverse associations with fruits did not vary by smoking status and were stronger in analyses of baseline consumption , with a 10-year lag time to disease follow-up ( quintile 5 vs. quintile 1 relative risk = 0.41 , 95 % confidence interval : 0.20 , 0.82 ; p = 0.01 ) . No associations were observed with total vegetables or with beta-carotene-rich or lycopene-rich fruits and vegetables . For current smokers , green leafy vegetables ( ptrend = 0.05 ) and beta-carotene-rich fruits and vegetables ( ptrend = 0.02 ) showed significant linear trends of increased risk ( one additional serving/day relative risk = 1.7 ) . The risk of oral premalignant lesions was significantly reduced with higher consumption of fruits , particularly citrus fruits and juices , while no consistent associations were apparent for vegetables |
13,455 | 28,913,645 | This reported inferior alveolar nerve block to be more effective than buccal infiltration for dental treatment of m and ibular molars , while no differences were found regarding pharmacological agents .
Conclusions At present , there is insufficient evidence in support of any pharmacologic agent or injection technique as being superior compared to others . | Purpose To evaluate the evidence supporting effects and adverse effects of local analgesia using different pharmacological agents and injection techniques during dental treatment in children and adolescents aged 3–19 years . | Clinical effectiveness of the double-blind administration of 1 and 2 % lidocaine solutions was evaluated for restorative and surgical procedures on primary molars of children 4.5 to 10.5 years old . This effectiveness was measured by changes in the child 's heart rate , the child 's self report of pain , and the operator 's assessment of the anesthesia 's effectiveness . Although the incidence of anesthetic failure was higher for the 1 % solution ( 31.3 % ) than for the 2 % solution ( 11.1 % ) , no statistically significant difference between the solutions was found . During the performance of pulpotomies and extraction s , a higher failure rate was recorded for the 1 % solution ( 62.5 % ) than for the 2 % solution ( 28.6 % ) , but these differences were not statistically significant . For minor restorative procedures , the 1 % solution was equally successful in achieving anesthesia . The results suggested that 1 % lidocaine should be used when multiple minor procedures are performed and potential toxicity in the young dental patient is a concern In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES The purpose of the study was to compare children 's reactions to inferior alveolar nerve injection with traditional syringe and periodontal ligament injection with a computerized device ( W and ) ; and to assess the efficacy of the anesthesia and their reaction after treatment . METHOD AND MATERIAL S Twenty-five children , aged 6 to 10 years , participated in the study . The contralateral primary m and ibular second molars were treated in 2 separate visits with r and om use of either the W and or traditional syringe injection . The pain perception levels for each step were assessed with El and Color Scale during the preparation . A Mann-Whitney U test was performed to compare the results . The patients were asked their preference of technique after the treatment . RESULTS When pain was measured immediately after injection , the traditional syringe was found to be more painful than injections with the W and ( P < .05 ) . Pain scores with the W and injections were found to be significantly ( P < .05 ) higher than those with traditional inferior alveolar nerve injections at the end of the restoration . The overwhelming majority of patients favored the periodontal ligament injection with the W and . CONCLUSION The W and technique provided significantly lower pain scores during the periodontal ligament injection . However , the pain scores during the treatment were significantly higher compared with the inferior alveolar nerve injections . Most of the patients stated that they preferred the periodontal ligament injection with the W and to the traditional inferior alveolar nerve injection PURPOSE Three identical single-dose , r and omized , double-blind , parallel-group , active-controlled multicenter studies were conducted to compare the safety and efficacy of articaine HCl ( 4 % with epinephrine 1:100,000 ) to that of lidocaine HCl ( 2 % with epinephrine 1:100,000 ) in patients aged 4 years to 79 years , with subgroup analysis on subjects 4 to < 13 years . METHODS Fifty subjects under the age of 13 years were treated in the articaine group and 20 subjects under the age of 13 were treated with lidocaine . Subjects were r and omized in a 2:1 ratio to receive articaine or lidocaine . Efficacy was determined on a gross scale immediately following the procedure by having both the subject and investigator rate the pain experienced by the subject during the procedure using a visual analog scale ( VAS ) . Safety was evaluated by measuring vital signs before and after administration of anesthetic ( 1 and 5 minutes post-medication and at the end of the procedure ) and by assessing adverse events throughout the study . Adverse events were elicited during telephone follow-up at 24 hours and 7 days after the procedure . RESULTS Pediatric patients received equal volumes , but higher mg/kg doses , of articaine than lidocaine during both simple and complex dental procedures . Pain ratings : Articaine : VAS ( Visual Analogue Scale ) scores ( from 0 to 10 cm ) by patients 4 to < 13 years of age were 0.5 for simple procedures and 1.1 for complex procedures , and average investigator scores were 0.4 and 0.6 for simple and complex procedures , respectively . Lidocaine : patients 0.7 ( simple ) and 2.3 ( complex ) ; investigators 0.3 ( simple ) and 2.8 ( complex ) . Adverse events : No serious adverse events related to the articaine occurred . The only adverse event considered related to articaine was accidental lip injury in one patient . CONCLUSIONS VAS scores indicate that articaine is an effective local anesthetic in children and that articaine is as effective as lidocaine when measured on this gross scale . Articaine 4 % with epinephrine 1:100,000 is a safe and effective local anesthetic for use in pediatric dentistry . Time to onset and duration of anesthesia are appropriate for clinical use and are comparable to those observed for other commercially available local anesthetics BACKGROUND Lidocaine is the gold st and ard anaesthetic solution that has been used since its inception into dentistry till date . Around 80 % of failures have been reported when lignocaine has been used for inferior alveolar nerve block in children and adults with irreversible pulpitis . There is a need to use newer drugs which are available which have been reported to be effective like lignocaine , such as articaine . Although articaine has been used in adults , literature supporting its use in children is sparse . AIM The purpose of this study is to compare the anaesthetic efficacy of 4 % articaine buccal infiltration and 2 % lignocaine inferior alveolar nerve block in children with irreversible pulpitis . It also aims to assess the need for supplemental intrapulpal injections . MATERIAL S AND METHODS This study was design ed as a r and omized double-blind cross over trial comparing the anaesthetic effectiveness of 4 % articaine with 1:100,000 epinephrine in buccal infiltration and 2 % lignocaine IAN block anaesthesia . The study subject and the pediatric dentist performing the pulpectomy procedures were blinded to the study . A sample size of 40 subjects in the age group of 5 - 8 y was included in the study . RESULTS The onset of anaesthesia with 4 % articaine was faster as compared to 2 % lignocaine . The duration of anaesthesia with articaine infiltration was shorter . The need for supplemental injection in the articaine group was less . CONCLUSION Four percent articaine infiltration can be used in children with irreversible pulpitis . It can be used to replace the IAN block in children thereby reducing the post anaesthetic complications like lip biting BACKGROUND The authors compared the safety and efficacy of 4 percent articaine with epinephrine 1:100,000 with 2 percent lidocaine with epinephrine 1:100,000 . METHODS In three identical r and omized , double-blind , multicenter trials , subjects 4 to 80 years of age received either 4 percent articaine with epinephrine 1:100,000 or 2 percent lidocaine with epinephrine 1:100,000 for simple or complex dental procedures . In each trial , the authors r and omized the subjects in a 2:1 ratio to receive articaine or lidocaine . Efficacy was determined by both subject and investigator using a visual analog scale , or VAS . The authors used the Kruskal-Wallis test to analyze the data . RESULTS A total of 882 subjects received articaine , and 443 received lidocaine . The authors found no statistical differences between the groups ( P = .05 ) . They also compared drug volumes for both articaine and lidocaine groups ( 2.5 milliliters + /- 0.07 st and ard error of mean , or SEM , vs. 2.6 mL + /- 0.09 SEM for simple procedures and 4.2 mL + /- 0.15 SEM vs. 4.5 mL + /- 0.21 SEM for complex procedures ) . The procedures ' duration s were comparable for both the articaine and lidocaine groups . The authors found no statistical difference between the two treatment groups ( P = .05 ) with respect to subject or investigator pain ratings using the VAS ; the mean pain scores determined by both patients and investigators for all groups tested were less than 1.0 . CONCLUSIONS The authors found that 4 percent articaine with epinephrine 1:100,000 was well-tolerated in 882 subjects . It also provided clinical ly effective pain relief during most dental procedures and had a time to onset and duration of anesthesia appropriate for clinical use and comparable to those observed for other commercially available local anesthetics . CLINICAL IMPLICATION S Pain control is a major component of patient comfort and safety . Local anesthetics form the backbone of pain control techniques in dentistry . Four percent articaine with epinephrine is an amide local anesthetic that will meet the clinical requirements for pain control of most dental procedures in most patients BACKGROUND Articaine administered through buccal infiltration ( BI ) has been suggested as providing adequate posterior m and ibular analgesia . This study compared the efficacy of articaine 4 % with 1:100 000 adrenaline ( test ) and lignocaine 2 % with 1:80 000 adrenaline ( control ) , delivered either through an inferior alveolar nerve block ( IANB ) or BI for routine restorative procedures in m and ibular posterior teeth among children . METHODS Children enrolled within the Western Australian School Dental Service and in need of restorative care on contralateral m and ibular posterior teeth were eligible . Consenting children were r and omly allocated to test and control techniques , and to type of local anaesthetic . Using the faces pain scale , pain reports from analgesia administration and from dental treatment were elicited . Analgesia success and pain reports were compared by anaesthetic technique and type . RESULTS Fifty-seven children were recruited into the study ; 29 allocated to IANB . Analgesia success for IANB 100 % ; BI 67 % ; p < 0.001 . Analgesia success for BI with articaine 71 % ; lignocaine 64 % , p > 0.05 . Analgesia success was associated with fewer reports of painful dental treatment , p = 0.005 . CONCLUSIONS There was higher success and less painful treatment with IANB . There was no statistically significant difference in local analgesia success between articaine and lignocaine when delivered via BI This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence PURPOSE The purpose of this study was to compare pain , efficacy and postoperative complications of anesthesia in first primary m and ibular molars anesthetized with either intraligamentary ( IL ) or supraperiosteal ( SP ) anesthesia using a computer-controlled delivery system ( CCDS ) . STUDY DESIGN This r and omized , controlled-crossover , blind clinical trial was conducted with 90 children requiring bilateral extraction , pulpotomy or restorative treatment of first m and ibular primary molars . A CCDS was used to deliver IL anesthesia to 1 deciduous tooth and SP anesthesia to the contralateral tooth in each patient . Severity of pain and efficacy of anesthesia during the treatments were evaluated using the Wong-Baker Faces Pain Rating Scale ( PRS ) and comfort and side effects were assessed using post-injection and post-treatment question naires . Data were analyzed using χ2 and Mann-Whitney U tests . RESULTS According to PRS scores , pain levels during extraction were significantly higher with IL when compared to SP . Patients reported significantly less pain during needle insertion with SP when compared to IL ; however , rates of postoperative complications were significantly higher with SP when compared to IL . CONCLUSIONS CCDS-administered IL anesthesia and SP anesthesia were similarly effective when used during restorative treatment and pulpotomy of primary m and ibular molars ; however , SP was more effective than IL when used during extraction procedures AIM Articaine and bupivacaine are both amide-type local anesthetic ( LA ) agents , of almost equal potency . However , lidocaine is considered the gold st and ard and is the most widely used anesthetic agent because of its potency , safety , and efficiency . Articaine is fast acting and bupivacaine is a long-lasting LA . The aim of this r and omized controlled crossover clinical study was to evaluate and compare the clinical anesthetic efficacy of 4 % articaine and 0.5 % bupivacaine in orthodontic extraction s models . METHODS Forty systemically healthy patients ( age range : 10 - 18 years ) , requiring premolar extraction for orthodontic reasons ( all 4 premolars ) were included . Patients were categorized into two groups ( 4 % articaine and 0.5 % bupivacaine ) in a crossover manner ( 160 premolars ) . Parameters recorded included : time of anesthetic onset , duration of postoperative analgesia , time to first rescue analgesic medication , and visual analog scale ( VAS ) . At the first appointment , both upper and lower premolars were extracted on one side of the jaws ( right or left ) . A fixed volume of 1.4 mL of 4 % articaine or 0.5 % bupivacaine ( based on a computer-generated list ) was infiltrated in the buccal vestibule ( local infiltration ) for extraction . At the second appointment , after a washout period of 15 days , the anesthetic agent that was not administered at the first appointment was administered in a crossover manner . Each patient was evaluated using a 100-mm VAS during and after extraction . RESULTS The results showed that 4 % articaine had significantly faster onset of action and lower VAS scores when compared with bupivacaine . However , the duration of analgesia and time to first rescue analgesic medication was longer in the bupivacaine group . CONCLUSION Articaine seemed to have better potency and efficacy in terms of onset of action and lower pain scores compared to the bupivacaine group . Further studies are required to confirm these results OBJECTIVE Failure of inferior alveolar nerve block in achieving profound anesthesia of the pulp due to various reasons has led to the introduction of more potent local anesthetic agents like articaine . This study was conducted to compare the efficacy of buccal infiltration with articaine in achieving pulpal anesthesia of primary molars as compared to inferior alveolar nerve block with lignocaine . STUDY DESIGN 30 patients ( 4 - 8 years ) with indication of pulp therapy in at least two m and ibular primary molars were selected . Patients were r and omly assigned to receive nerve block with lignocaine or infiltration with articaine on first appointment and the other solution on second appointment . All the pulpotomies and pulpectomies were performed by a pediatric dentist . Two research ers st and ing at a distance of 1.5 m recorded the Pain Scores and Sound , Eye , Motor ( SEM ) scores . After the completion of procedure , the patient was asked to record the Facial Image score and Heft-Parker Visual Analogue Score ( HP-VAS ) . RESULTS Pain Score recorded at the time of injection showed significantly more movements with block as compared to infiltration ( p<0.001 ) . SEM scores at time of pulp extirpation were also higher for block than infiltration ( p<0.001 ) . CONCLUSION Articaine infiltration has the potential to replace inferior alveolar nerve block for primary m and ibular molars |
13,456 | 22,071,841 | Consequently , there are insufficient data to draw any conclusions on exercise capacity , symptoms and HRQoL for this comparison .
For comparisons between continuous and interval training , both appear to be equally effective in improving exercise capacity , symptoms and | BACKGROUND Intensity of exercise is considered a key determinant of training response , however , no systematic review has investigated the effects of different levels of training intensity on exercise capacity , functional exercise capacity and health-related quality of life ( HRQoL ) in people with chronic obstructive pulmonary disease ( COPD ) .
As type of training ( continuous or interval ) may also affect training response , the effects of the type of training in COPD also require investigation .
OBJECTIVES To determine the effects of training intensity ( higher versus lower ) or type ( continuous versus interval training ) on primary outcomes in exercise capacity and secondary outcomes in symptoms and HRQoL for people with COPD . | Abstract The evaluation of a 13-month maintenance program ( MP ) for 39 severe COPD patients with FEV1%pred 44(7)% who , as result of two different 8-week leg exercise training ( LET ) programs , one supervised at the hospital ( group S ; n = 20 ) and the other self-monitored ( SM ; n = 19 ) , had achieved different levels of exercise tolerance . After LET , patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O2max 1.43(0.30 ) l · min−1 ] vs l.25(0.27 ) l · min−1 and endurance-time 16(4 ) min vs 12 ( 5 ) min , respectively ) . During the MP patients were advised to walk vigorously at least 4 km/day , 4 times/wk . After the MP , while endurance time remained higher than at baseline , it had decreased ( p < 0.01 ) immediately after LET in both groups and no differences were evident between groups ( 11(4 ) min and 10(4 ) , respectively ) . In contrast , Chronic Respiratory Diseases Question naire scores , which had improved significantly after LET in both groups , remained high . Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET . SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance , though “ quality of life ” can be maintained Limited information is available regarding the physiological responses to different types of exercise training in patients with severe chronic obstructive pulmonary disease ( COPD ) . The aim of this study was two fold : firstly , to investigate the physiological response to training at 60 % of achieved peak load in patients with severe COPD ; and secondly to study the effects of interval ( I ) versus continuous ( C ) training in these patients . Twenty-one patients with COPD ( mean+/-SD forced expiratory volume in one second : 37+/-15 % of predicted , normoxaemic at rest ) were evaluated at baseline and after 8 weeks ' training . Patients were r and omly allocated to either I or C training . The training was performed on a cycle ergometer , 5 days a week , 30 min daily . The total work load was the same for both training programmes . C training result ed in a significant increase in oxygen consumption ( V'O2 ) ( 17 % , p<0.05 ) and a decrease in minute ventilation (V'E)/V'O2 ( p<0.01 ) and V'E/carbon dioxide production ( V'CO2 ) ( p<0.05 ) at peak exercise capacity , while no changes in these measures were observed after interval training . During submaximal exercise a significant decrease was observed in lactic acid production , being most pronounced in the C-trained group ( -31 % , p<0.01 versus -20 % , p<0.05 ) . Only in the I-trained group did a significant increase in peak work load ( 17 % , p<0.05 ) and a decrease in leg pain ( p<0.05 ) occur . Training did not result in a significant improvement in lung function , but maximal inspiratory mouth pressure increased in both groups by 10 % ( C : p<0.05 ) and 23 % ( I : p<0.01 ) . The present study shows a different physiological response pattern to interval or continuous training in chronic obstruction pulmonary disease , which might be a reflection of specific training effects in either oxidative or glycolytic muscle metabolic pathways . Further work is required to determine the role of the different exercise programmes and the particular category of patients for whom this might be beneficial We studied the impact of a 6-wk supervised , multimodality endurance exercise training program ( EXT ) on strength and endurance of ventilatory and peripheral muscles in patients with chronic airflow limitation ( CAL ) , and determined whether potential improvements contributed to relief of exertional breathlessness ( B ) and perceived leg effort/discomfort ( LE ) , respectively . Twenty breathless patients with stable CAL ( FEV1 = 41 + /- 3 % predicted ; mean + /- SEM ) were tested at 6-wk intervals at baseline , after a nonintervention control period ( pre-EXT ) , and post-EXT . Measurements included : pulmonary function tests ( PFTs ) , maximal inspiratory/expiratory pressures ( MIP , MEP ) , inspiratory muscle endurance ( V(LIM ) ) , quadriceps strength and endurance , exercise endurance , and submaximal cycle exercise with cardioventilatory and symptom responses . Measurements at baseline and pre-EXT were identical . Post-EXT , PFTs did not change ; exercise endurance measured on the treadmill , cycle ergometer , arm ergometer , and by 6-min walk distance increased 40 + /- 8 % , 43 + /- 10 % , 12 + /- 5 % , and 34 + /- 9 % , respectively ( p < 0.05 ) ; quadriceps strength increased 21 + /- 5 % ( p < 0.01 ) ; MIP and MEP increased 29 + /- 11 % and 27 + /- 11 % , respectively ( p < 0.05 ) ; V(LIM ) increased almost threefold ( p < 0.05 ) . At isotime near end-exercise , B , LE , carbon dioxide production ( VCO2 ) , oxygen consumption ( VO2 ) , ventilation , and breathing frequency ( F ) all fell after EXT ( p < 0.05 ) : deltaB correlated with deltaF ( r = 0.58 , p < 0.01 ) . Increased MIP and V(LIM ) did not correlate with improved breathlessness or exercise endurance . Similarly , changes in quadriceps strength and endurance did not correlate with changes in LE or exercise endurance . In conclusion , general nonspecific EXT improved ventilatory and peripheral muscle function in severe CAL , but such improvements did not appear to contribute significantly to reduced exertional symptoms and enhanced exercise performance In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials QUESTIONS Does an eight-week program of walk training improve endurance walking capacity in people with COPD compared to cycle training ? Does walk training improve peak walking capacity , cycle capacity , and quality of life compared to cycle training ? Is the endurance shuttle walk test ( ESWT ) responsive to change in walking capacity elicited by exercise training ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 36 people with stable COPD recruited with four dropouts . INTERVENTION Participants were r and omised into either a walk or cycle training group . Both groups trained indoors for 30 to 45 minutes per session , three times weekly over eight weeks at Concord Hospital . Training intensities were based on baseline peak exercise tests and progressed as able . OUTCOME MEASURES The primary outcome was endurance walking capacity measured by the ESWT . Secondary outcomes included peak walking capacity , peak and endurance cycle capacity , and health-related quality of life . Measures were taken at baseline ( Week 0 ) and following training ( Week 8) . RESULTS The walk training group increased their endurance walking time by 279 seconds ( 95 % CI 70 to 483 ) more than the cycle training group . No significant differences between the groups were found for any other outcome . CONCLUSION Ground walk training increased endurance walking capacity more than cycle training and was similar to cycle training in improving peak walking capacity , peak and endurance cycle capacity and quality of life . This study provides evidence for ground walking as a mode of exercise training in pulmonary rehabilitation programs We studied high intensity , symptom-limited , endurance exercise training in 52 patients with COPD participating in a pulmonary rehabilitation program . The patients had moderate to severe airway obstruction and reduced exercise tolerance with ventilatory limitation . The target workload for endurance exercise testing was 95 percent of the baseline maximum treadmill work load . At training weeks 1 , 4 and 8 , they were training at 85 , 84 , and 86 percent respectively , of baseline maximum . After rehabilitation , there was an increase in maximal treadmill work load , VO2max , and endurance exercise time , and a decrease in perceived symptoms . Patients who did not reach anaerobic threshold ( group 2 ) were able to train at a higher percentage of maximum exercise tolerance than patients who reached anaerobic threshold ( group 1 ) . The increase in exercise performance of both groups , however , was similar . We conclude that patients with moderate to severe COPD can perform exercise training successfully at intensity targets which represent higher percentages of maximum than typically recommended in normal individuals or other patients Our objective was to compare the effect of a 4−week homebased low and middle intensity and frequency training program in patients with moderate to severe chronic obstructive pulmonary disease . From 124 patients hospitalized with chronic obstructive lung disease ( COPD ) in an 18-month period 65 fulfilled the inclusion criteria and were invited to participate . Only 31 ( 48 % ) accepted and among these only 20 patients ( 31 % of invited ) completed the 4-week study period . The walking time in seconds in a st and ardized treadmill walking test was unchanged after 4 weeks of low intensity training 60 minutes per week for two weekly training sessions . In contrast , the walking time in seconds increased 55 % ( p < 0.001 ) from 321 seconds to 499 seconds in 9 patients who completed 4 weeks of middle intensity training which comprised 21/2 hours of training per week for 5 weekly training sessions . There was no change in lung function over the 4 weeks but the combined score for physical quality of life ( physical component summary ) measured by SF-36 increased ( p < 0.05 ) with both low intensity and middle intensity physical training . In conclusion , homebased physical training , which aims at improvements in patient performance and quality of life as part of pulmonary rehabilitation programs , is only accepted by about one-third of unselected patients with moderate to severe COPD . The minimum training time necessary to improve physical performance is 2–3 hours per week of middle intensity training AIM In this study , the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program ( HRP ) are compared with those of a 12-week home-care rehabilitation program ( HCRP ) in COPD patients . A control group received no rehabilitation therapy . METHODS After r and omization and stratification , effects on lung function , exercise performance ( 4-min walking test and cycle ergometer test ) , dyspnea , and leg effort during exercise , and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation ( mean [ SD ] FEV1 percent predicted , 42.8 [ 8.4 ] ) . RESULTS After HRP and HCRP , at 3 to 6 months after the start of the study , equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test . However , whereas after HRP at longer term values tended to return to baseline outcome , after HCRP a further ongoing significant improvement in exercise capacity was observed , while Borg dyspnea scores remained significantly improved over 18 months . Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP . Lung function , arterial oxygen saturation , and heart frequency during exercise did not change . A significant improvement in well-being was maintained over 18 months in both rehabilitation groups . CONCLUSION Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation . Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting This r and omized , controlled study investigated the physiological effects of a specially design ed 12 week programme of isolated conditioning of peripheral skeletal muscle groups . The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital . Forty eight patients , aged 40 - 72 yrs with chronic obstructive pulmonary disease ( COPD ) ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 61 (27)% of predicted normal ) were r and omly allocated into training ( n = 32 ) and control ( n = 16 ) groups . Physiological assessment s were performed before and after the 12 week study period , and included peripheral muscle endurance and strength , whole body endurance , maximal exercise capacity ( maximum oxygen consumption ( V'O2,max ) ) and lung function . The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance , with no additional breathlessness . Whole body endurance measured by free arm treadmill walking increased by 6,372 ( 3,932 - 8,812 ) 3 ( p < 0.001 ) . Symptom-limited maximal V'O2 was unchanged . However , the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide , both at peak exercise and at equivalent work rate ( Wmax ) . In summary , low intensity isolated peripheral muscle conditioning is well-tolerated , simple and easy to perform at home . The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning OBJECTIVES To have a group of COPD patients undergo a simple program of home-based exercise training , using the shuttle walking test ( SWT ) to st and ardize the intensity of training . METHODS Sixty patients participated , r and omly distributed into two groups ( rehabilitation and control ) of 30 patients each . The following evaluations were carried out at baseline and at 12 weeks : ( 1 ) pulmonary function studies ; ( 2 ) SWT ; ( 3 ) submaximal intensity resistance test ; ( 4 ) cycle ergometer test ; ( 5 ) quality of life ; and ( 6 ) dyspnea . The rehabilitation group underwent a lower-extremity training program . Walking was selected as the type of exercise . The intensity of training was set at 70 % of the maximum speed attained on the SWT . Divided sessions were held , lasting 1 h , 6 days/wk , at home , with a checkup every 2 weeks . The duration of the program was 12 weeks . RESULTS The following patients completed the study : 20 patients ( 66.6 % ) from the rehabilitation group ( mean [ + /- SD ] ) age , 64.3 + /- 8.3 years ; mean FEV(1 ) , 41.7 + /- 15.6 % of predicted ) ; and 17 patients ( 56.6 % ) from the control group ( mean age , 63.1 + /- 6.9 years ; mean FEV(1 ) , 40 + /- 16.4 % of predicted ) . We found no changes in pulmonary function or effort parameters ( SWT or cycle ergometer ) in the rehabilitation group at 12 weeks . A twofold increase ( 1,274 + /- 980 to 2,651 + /- 2,056 m ; p < 0.001 ) was achieved in the submaximal intensity resistance test , with less dyspnea at the conclusion of the test ( p = 0.05 ) . Significant improvement also was achieved in basal dyspnea and , both statistically and clinical ly , in the quality of life . Significant changes were not achieved in the control group patients . CONCLUSIONS A simple home-based program of exercise training achieved improvement in exercise tolerance , posteffort dyspnea , basal dyspnea , and quality of life in COPD patients The effects of two 8-week programmes of exercise reconditioning on the time constants ( tau ) of the pulmonary gas exchange , ventilatory and heart rate responses to moderate intensity exercise in patients with chronic obstructive pulmonary disease ( COPD ) were studied . Thirty-five subjects ( mean+/-SD 64+/-5 yrs ; forced expiratory volume in one second ( FEV1 ) 1.09+/-0.17 L ; 41+/-6.2 % predicted ) were r and omly assigned either to supervised ( s ) training on a treadmill , 4 days x week(-1 ) ( group S ; n=21 ) or self-monitored ( SM ) walking 3 or 4 km in 1 h 4 days x week(-l ) ( group SM ; n=20 ) . The different levels of supervision result ed in a different estimated intensity of training ( 35+/-10 W in the SM group and 70+/-22 W in the S group ) . The kinetics were evaluated with a constant-load exercise test on a cycle-ergometer at a work rate corresponding to 80 % the highest oxygen consumption ( V'O2 ) that can be achieved without blood lactic acidosis ( V'O2,LAT ) or 50 % of V'O2,max , if maximum oxygen consumption V'O2,LAT was not found . Mean endurance time at a work rate equivalent to 70 % of the pretraining V'O2,max increased by 493+/-281 s in the S group and 254+/-283 s in the SM group ( p<0.001 ) . Mean tauV'O2 decreased from 83+/-17 s to 67+/-11 s ( p<0.0001 ) in the S group and from 84+/-12 to 79+/-16 ( p=0.04 ) in the SM group . Mean tau for carbon dioxide output minute ventilation and heart rate were also speeded after training , again more markedly in the S group . In the S group there was a significant correlation between the decrease in tauV'O2 and the increase in endurance time ( r=-0.56 , SEM=0.21 ) . It is concluded that training speeds the kinetic response of oxygen consumption , carbon dioxide production , minute ventilation and heart rate to moderate exercise and that the effect is greater after supervised , more intense training STUDY OBJECTIVES We hypothesized that endurance exercise training would reduce the degree of hyperinflation for a given level of exercise and thereby improve submaximal exercise endurance . METHODS Twenty-four patients with COPD ( mean FEV(1 ) , 36.4 + /- 8.5 % of predicted [ + /- SD ] ) undertook a high-intensity cycle ergometer exercise training program for 45 min , three times a week for 7 weeks . Before and after training , the patients performed both an incremental exercise test to maximum and a constant work rate ( CWR ) test on a cycle ergometer at 75 % of the peak work rate obtained in the pretraining incremental test . Ventilatory variables were measured breath-by-breath , and inspiratory capacity ( IC ) was measured every 2 min to assess changes in end-expiratory lung volume . RESULTS After training , the increase in peak oxygen uptake was not statistically significant ; however , the peak work rate increased by 12.9 + /- 10.3 W ( p < 0.01 ) . For the CWR test performed at the same work rate both before and after training , ventilation and breathing frequency ( f ) were lower after training ( average , 1.97 L/min and 3.2 breaths/min , respectively ; p < 0.01 ) and IC was greater ( by an average of 133 mL , p < 0.05 ) , signifying decreased hyperinflation . The increase in IC at the point of termination in the shortest CWR test for each individual ( defined as isotime ) correlated well with both the decreased f ( r = 0.63 , p = 0.001 ) and with the increase in CWR exercise endurance ( average , 13.1 min , r = 0.46 , p = 0.023 ) . CONCLUSIONS Exercise training in patients with severe COPD dramatically improves submaximal exercise endurance . Decreased dynamic hyperinflation may , in part , mediate the improvement in exercise endurance by delaying the attainment of a critically high inspiratory lung volume The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment , and a 3 month control period of drug treatment only , for asthmatic patients and patients with chronic obstructive pulmonary disease ( COPD ) . The programme was run by physiotherapists in eight local practice s , and included exercise training , patient education , breathing retraining , evacuation of mucus , relaxation techniques , and recreational activities . In a r and omized controlled trial with a cross-over design , the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life ( QOL ) . Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests . QOL was evaluated by means of the Chronic Respiratory Disease Question naire ( CRDQ ) . After 3 months , the patients who started with rehabilitation showed significant improvements in endurance time ( 421 s ) and cardiac frequency ( 6 beats.min-1 ) during cycling , walking distance ( 39 m ) , and total CRDQ score ( 17 points ) compared to the control group . These improvements were still significant after 6 months . Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way , with the exception that there was a greater improvement in walking distance for asthmatics . Improvements in exercise tolerance were not significantly correlated with improvements in QOL . Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practice s improves exercise tolerance and quality of life PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program Context Exercise training improves quality of life in patients with chronic obstructive pulmonary disease , but many of these patients can not tolerate continuous exercise . The effects of intermittent exercise are not known . Contribution The authors r and omly assigned 100 in patients with chronic obstructive pulmonary disease in a 3-week respiratory rehabilitation program to receive either high-intensity continuous exercise or high-intensity exercise alternating with low-intensity exercise ( interval exercise ) . After 5 weeks , the 2 groups had similar respiratory symptoms in daily activities and 6-minute walking distance , but the interval exercise group adhered better to the exercise protocol . Caution s The study focused on initiation of exercise and not on outpatient or home-based maintenance of exercise . Implication s For pulmonary rehabilitation , interval exercise is as effective as continuous high-intensity exercise and is better tolerated . The Editors Low exercise capacity is an important systemic manifestation of advanced chronic obstructive pulmonary disease ( COPD ) associated with poor health-related quality of life , exacerbations , and death ( 14 ) . Physical exercise , therefore , represents an important element of COPD management ( 5 , 6 ) . If performed under supervision during respiratory rehabilitation , exercise training improves health-related quality of life and may improve prognosis ( 79 ) . Dyspnea and leg fatigue limit the ability of patients with COPD to exercise , and patient response to exercise is highly variable ( 10 ) . It is challenging to find endurable exercise programs that are still effective . Current guidelines recommend endurance exercise at constant and high intensity ( 70 % of maximum exercise capacity ) ( 11 , 12 ) . For example , if a patient achieves 100 watts in an incremental exercise test , workload would be set at 70 watts for the entire exercise session of at least 20 minute 's duration . Strong evidence from r and omized trials shows that patients achieve clinical ly important improvements of health-related quality of life and exercise capacity with a continuous exercise protocol ( 1316 ) . However , patients with severe COPD are often unable to tolerate continuous exercise ( 17 ) , which can be frustrating for them and can limit their long-term adherence to exercise programs . Effective alternatives to continuous exercise are required to offer this important intervention to more patients with COPD . The American Thoracic Society and the European Respiratory Society state , on the basis of 2 r and omized trials ( 18 , 19 ) , that interval exercise may be an alternative . The benefits of interval exercise may be similar to those of continuous training , but this method is associated with less dyspnea ( 11 , 12 ) . Although studies indicated that interval exercise is well tolerated ( 1821 ) , evidence about its effectiveness relative to continuous exercise is inconclusive ; previous trials had method ological limitations and were small ( 22 ) . Because of perceived better tolerability of interval exercise , r and omized trials should be explicitly design ed to show that interval exercise is no less effective ( clinical noninferiority ) ( 22 ) . Thus , the aim of our trial was to assess whether interval exercise is no less effective than high-intensity continuous exercise in patients with severe COPD and whether patient tolerance of the interval exercise protocol is superior to that of continuous exercise . Methods Design Overview We conducted a r and omized , controlled noninferiority trial to compare the effects of interval exercise with those of high-intensity continuous exercise in patients with severe COPD . We previously described the detailed study protocol ( 23 ) and report this trial following the recommendations of the extended Consoli date d St and ards of Reporting Trials ( CONSORT ) statement for noninferiority and equivalence trials ( 24 ) . Setting The trial took place in a public rehabilitation clinic , Klinik Barmelweid , in Aargau , Switzerl and . The ethics committee of the Kantonsspital Aarau , Aargau , Switzerl and , approved the study protocol , and all study participants provided written informed consent . Participants We screened patients admitted to the respiratory medicine unit and included consecutive patients following inclusion criteria similar to those of previous respiratory rehabilitation trials ( 7 ) : COPD as defined by FEV1FVC ratio less than 70 % of predicted , FEV1 less than 50 % of predicted after bronchodilation corresponding to Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stage III to IV ( 5 ) , and German as first or daily language . Exclusion criteria included cardiovascular , musculoskeletal , or neurologic disorders that inhibited physical exercise or the performance of exercise tests ( 6 ) . We also excluded patients who had received a diagnosis of cancer ( excluding skin cancer ) within the past 2 years and were undergoing treatment . R and omization and Interventions A third party not involved in the execution of the trial ( DatInf GmbH , Tuebingen , Germany ) provided online central r and omization using a computerized minimization procedure , thereby ensuring concealment of r and omization ( 25 ) . Stratification variables were exercise capacity ( 6-minute walking distance < 300 or 300 meters ) , the presence of affective disorders ( Hospital Anxiety Depression Scale scores < or 8) , stability of pulmonary condition ( stable or exacerbation within the last 8 weeks ) , and the need for oxygen at rest ( Pao 2 < 55 mm Hg or 55 mm Hg ) . Patients followed an inpatient respiratory rehabilitation of approximately 3 week 's duration that included 12 to 15 exercise sessions . On weekdays , patients usually participated in 1 exercise session . Twelve physical therapists worked with an approximately equal number of patients from both treatment groups . Apart from exercise , the rehabilitation program was identical for both groups and included breathing therapy , relaxation therapy , guided walking tours , and patient education ( 23 ) . At discharge , physiotherapists prescribed home-based exercise for each patient . Patients with cycle ergometers at home were instructed to exercise for at least 20 minutes per day . If no cycle ergometers were available , daily walking , swimming , or stair climbing was prescribed . High-Intensity Continuous Exercise Patients r and omly assigned to this intervention exercised on electromagnetically braked cycle ergometers ( Ergometrics 900S , Ergoline , Bitz , Germany ) with a target workload of 70 % or more of maximum exercise capacity ( Figure 1 ) . This exercise protocol has been used in earlier respiratory rehabilitation trials ( 7 ) . To determine maximum exercise capacity , patients pedaled unloaded for 3 minutes at 20 watts to warm up . Then , we used increments of 7.5 watts per minute until patients had to stop because of symptoms or cardiovascular stopping criteria . In each exercise session , patients completed a warm-up period of 2 minutes at 20 % of maximum exercise capacity , high-intensity exercise for 20 minutes , and a run-out phase of 2 minutes ( gradual decrease from 70 % to 0 % ) . If patients could not sustain the workload because of perceived dyspnea ( modified Borg [ 26 ] ratings > 5 on a scale from 0 to 10 ) or because heart rate exceeded safety limits , physical therapists let patients rest for 1 minute before continuing in the assigned phase . If patients had to rest more than twice per session , physical therapists lowered the workload by steps of 10 % of baseline maximum exercise capacity for the following exercise sessions . If workload was too low ( modified Borg ratings < 3 or patients or physical therapists considered the workload to be too low ) , physical therapists increased the workload by steps of 10 % of baseline maximum exercise capacity . Figure 1 . Exercise protocol s. Interval Exercise The target workload for this group was 50 % ( high-intensity intervals ) and 10 % ( low-intensity intervals ) of short-term maximum exercise capacity as determined by a steep ramp test ( 27 , 28 ) . The steep ramp test is an incremental cycle ergometer test in which patients pedal cycle ergometers unloaded for 2 minutes and then at increments of 25 watts every 10 seconds until they can not maintain a pedaling frequency above 50 pedals per minute or their heart rate exceeds the limit set by the normal incremental exercise test . We used the steep ramp test because workload for interval exercise can be underestimated if it is based on normal incremental exercise tests ( 28 ) . Fifty percent of short-term maximum exercise capacity corresponds , on average , to 90 % to 100 % of normal maximum exercise capacity ( 27 ) . We chose a workrecovery ratio of 1:2 that prevents high lactate accumulation and is well tolerated by patients ( 28 ) . In each session , patients had a warm-up period of 2 minutes at 10 % of the short-term maximum exercise capacity and then exercised for 20 minutes alternating between high-intensity intervals for 20 seconds and low-intensity intervals for 40 seconds ( Figure 1 ) . Patients also had a slowdown period of 2 minutes before completing the training session . We adjusted the exercise load for each patient individually if workload was too high or too low as described earlier ; physiotherapists lowered or increased the workload by steps of 10 % of short-term maximum exercise capacity , but the length of intervals remained constant ( 23 ) . Outcomes and Measurements Our primary outcome for effectiveness was the difference from baseline in Chronic Respiratory Question naire ( CRQ ) scores 5 weeks after r and omization as measured by the self-administered German- language version ( 29 , 30 ) with st and ardized dyspnea questions ( 31 ) . The CRQ is a widely used instrument in respiratory rehabilitation and measures dyspnea , fatigue , emotional functioning , and ability to cope with COPD ( 7 , 32 ) . Domain and total ( average of domains ) scores are presented on a Likert-type scale from 1 ( most severe impairment ) to 7 ( no impairment ) . We selected assessment at 5 weeks after r and omization as the primary outcome STUDY OBJECTIVES To compare the effectiveness of two forms of exercise training in pulmonary rehabilitation . DESIGN A prospect i ve , r and omized , unblinded , 8-week trial . SETTING A hospital-based outpatient pulmonary rehabilitation program . PATIENTS Forty patients ( 20 patients in each group ) with COPD who were referred for pulmonary rehabilitation . INTERVENTIONS We compared the short-term effectiveness of a high-intensity , lower-extremity endurance program with a low-intensity , multicomponent calisthenics program for the rehabilitation of patients with COPD . The high-intensity group trained predominately on the stationary bicycle and treadmill , with a goal of exercising at > or = 80 % of maximal level determined from incremental testing for 30 min per session . The low-intensity group performed predominately classroom exercises for approximately 30 min per session . For both groups , twice-weekly sessions were held for 8 weeks . The primary outcome measure was health status , measured using the Chronic Respiratory Disease Question naire . Other outcomes included peak oxygen consumption on incremental treadmill exercise testing , exertional dyspnea , treadmill endurance time , the number of sit-to-st and repetitions and arm lifts in 1 min , overall dyspnea , and question naire-rated functional status . MEASUREMENTS AND RESULTS Both groups showed significant postrehabilitation improvement in exercise variables , exertional and overall dyspnea , functional performance , and health status . Patients in the high-intensity group showed greater increases in treadmill endurance and greater reductions in exertional dyspnea , whereas those in the low-intensity group showed greater increases in arm-endurance testing . Both groups had similar improvements in overall dyspnea , functional performance , and health status . CONCLUSIONS Despite differences in exercise performance , both high-intensity , lower-extremity endurance training and low-intensity calisthenics led to similar short-term improvements in question naire-rated dyspnea , functional performance , and health status Underst and ing of what constitutes a training load adequate to induce training effects in patients with chronic obstructive pulmonary disease ( COPD ) is still evolving . The present study investigated whether interval training ( IT ) is effective in terms of inducing measurable improvements in physiological response and compared its effects on exercise tolerance ( ET ) and quality of life to those of continuous training ( CT ) . Thirty-six COPD patients , with a forced expiratory volume in one second of 45±4 % of the predicted value ( mean±sem ) , were r and omly assigned to CT ( exercise at 50 % of baseline peak work-rate ) or IT ( work for 30 s at 100 % of peak work-rate alternating with 30‐s rest intervals ) groups that cycled 40 min·day−1 and 2 days·week−1 for 12 weeks . After training , both groups showed significantly improved ET ( IT , 57±6 to 71±8 W ; CT , 57±5 to 70±6 W ) and total quality -of-life score of the Chronic Respiratory Disease Question naire ( IT , 77±3 to 88±2 ; CT , 78±3 to 93±2 ) . At identical levels of exercise , minute ventilation was significantly reduced ( IT , 35.8±2.5 to 31.7±2.5 L·min−1 ; CT , 36.4±2.7 to 32.5±2.7 L·min−1 ) . The magnitude of improvement in these variables was not significantly different among groups . The present data exp and on the principles of exercise prescription for chronic obstructive pulmonary disease patients by demonstrating that interval training elicits substantial training effects , which are similar in magnitude to those produced by continuous training at half the exercise intensity but double the exercise time During constant-work-rate exercise in chronic obstructive pulmonary disease , dyspnea increases steeply once inspiratory reserve volume ( IRV ) falls to a critical level that prevents further expansion of tidal volume ( Vt ) . We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator . In a r and omized , double-blind , crossover study , 18 patients with chronic obstructive pulmonary disease ( forced expiratory volume in 1 s = 40 + /- 3%predicted ; mean + /- SE ) inhaled tiotropium 18 mug or placebo once daily for 7 - 10 days each . Pulmonary function tests and symptom-limited cycle exercise at 75 % of each patient 's maximal work capacity were performed 2 h after dosing . Dyspnea intensity ( Borg scale ) , operating lung volumes , breathing pattern , and esophageal pressure ( n = 11 ) were measured during exercise . Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio , which is defined as the ratio between tidal swings of esophageal pressure ( expressed relative to maximum inspiratory pressure ) and Vt ( expressed relative to predicted vital capacity ) . After a minimal IRV of 0.5 + /- 0.1 liter was reached , both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached . Tiotropium did not alter dyspnea-IRV relationships , but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise . Once a critically low IRV was reached during exercise , dyspnea rose with the disparity between respiratory effort and the Vt response . Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling BACKGROUND AND OBJECTIVES The benefits of pulmonary rehabilitation for patients with COPD depend on the intensity of training . Traditional pulmonary rehabilitation programmes ( PRPs ) do not consistently achieve high-intensity training and have variable training effects . This study examined the effects of high-intensity exercise training on cardiac and pulmonary function in COPD patients . METHODS Patients with COPD participated in a 6-week , cardiopulmonary exercise test-based PRP . Spirometry , 6-min walking distance and cardiopulmonary exercise test were used to evaluate cardiopulmonary function , respiratory muscle strength and endurance at rest , during exercise and before and after the programme . Patients were encouraged to complete high-intensity exercise with a targeted training intensity of at least 75 % maximum oxygen uptake ( VO(2 ) ) . RESULTS Thirty-four COPD patients were enrolled into the study ; 16 completed the high-intensity training , 18 did not . At the end of the 12-session PRP , submaximal exercise capacity ( 6-min walking distance , 461.8 + /- 77.2 - 502.7 + /- 66.9 m , P < 0.001 ) improved in both the patients who completed high-intensity training and those who did not . Only the patients who completed high-intensity training had significant improvements in FVC ( 2.47 + /- 0.70 - 2.70 + /- 0.62 L , P = 0.024 ) at rest , maximal exercise capacity ( peak VO(2 ) , 1001.6 + /- 286.4 - 1116.1 + /- 320.4 mL/min , P = 0.020 ) and work efficiency ( 7.3 + /- 1.4 - 8.4 + /- 1.8 mL/min/watt , P = 0.026 ) . There was no statistically significant difference between the two groups in the change in the physiological parameters before and after exercise . CONCLUSIONS Exercise training in a PRP improved submaximal exercise capacity . Only patients who completed high-intensity exercise training showed improvements in maximal exercise capacity , FVC and work efficiency OBJECTIVES Autonomic modulation is adversely impacted in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of the present investigation is to assess the effects of a 6-week aerobic exercise training program on autonomic modulation of heart rate in patients with COPD . METHODS Forty patients of both sexes with moderate-to-severe COPD were r and omly allocated to aerobic exercise training ( PT , n=20 ) or to usual care ( Control , n=20 ) . The training program consisted of lower and upper limb stretching and 30 min of treadmill exercise , 3 times per week for a 6-week period . Physiological data during symptom-limited exercise testing and the six-minute walk test ( 6MWT ) were assessed . In addition , R-R intervals were obtained at rest and during the 6MWT . Heart rate variability was analyzed by time ( rMSSD and SDNN index ) and frequency domains ( high frequency -- HF , low frequency -- LF and HF/LF ratio ) . RESULTS Peak oxygen consumption significantly improved in the training group only ( p<0.05 ) . Moreover , the training group demonstrated significant improvements ( p<0.05 ) in blood lactate , minute ventilation , dyspnea at peak exercise , sympathetic activity , and parasympathetic activity at rest and during submaximal exercise . Lastly , a positive and significant correlation was found between change in 6MWT distance and rMSSD index ( r=0.65 and p=0.001 ) . CONCLUSIONS Neural control of heart rate , in addition to other clinical ly valuable measures , is positively altered in moderate-severe COPD patients following 6 weeks of aerobic exercise training . The improvement in submaximal performance after exercise training was associated with parasympathetic activity This study tested the effect of two methods of training , one individualized at the heart rate corresponding to the gas exchange threshold ( GET ) and the other at the heart rate corresponding to 50 % of maximal heart rate reserve , on maximal and submaximal cardiorespiratory response in 24 patients with chronic airway limitation ( CAL ) . The patients were r and omly assigned to either the individualized training group ( IT ; n = 12 ) or the st and ardized training group ( ST ; n = 12 ) . The training programme consisted of 4 weeks of stationary bicycle exercise , 5 days.week-1 . Before reconditioning began , the target level based on heart rate was not significantly different between groups ( 109 + /- 4 versus 110 + /- 3 beats.min-1 , in IT and ST , respectively ) . Post-training , a significant increase in symptom-limited oxygen uptake ( V'O2.sl ) and maximal O2 pulse was found in IT , whereas ST exhibited no significant change . In each group , GET was statistically increased in much the same way as V'O2,sl , with a higher increase in IT ( p < 0.01 ) than ST ( p < 0.05 ) . Nevertheless , IT exhibited a concomitant and gradual decrease in minute ventilation ( V'E ) , carbon dioxide production ( V'CO2 ) , and venous lactate concentration ( [ La ] ) , whereas ST presented no significant change in these parameters ( intergroup p < 0.01 ) . Breathing pattern was also altered after IT , at the same metabolic level and at the same ventilation level ( intergroup p < 0.05 ) . Cardiac responses were modified in the two groups . At the same metabolic level , a significantly lower cardiac frequency was found both for IT and ST ( intragroup p < 0.05 after training ) . In contrast , the increase in O2 pulse was only significantly higher in It after training . These data show the greater efficiency of an individualized training protocol based on determination of gas exchange threshold as compared to a st and ardized protocol , in improving exercise performance , when applied to a patient group . Despite an apparently similar target training level , the individualized method clearly optimized the physiological training effects in patients with chronic airway limitation and , more particularly , decreased their ventilatory requirement Endurance time on submaximal exercise tests is a sensitive measure in detecting changes after medical intervention and is used as an outcome in clinical trials , although there has been little discussion regarding the appropriate intensity . Therefore , we investigated whether there were differences in exercise responses between endurance tests at high versus moderate intensity , and analyzed which test was more appropriate . Thirty-seven patients with chronic obstructive pulmonary disease participated in the study . They performed cycle endurance tests at high and moderate submaximal workloads representing 80 % and 60 % of the maximum work rate reached on progressive cycle ergometry , respectively . Each type of exercise test was performed after inhaling salbutamol 400 microg , ipratropium bromide 80 microg or an identical placebo . Endurance time on the 80 % endurance test was much shorter than on the 60 % endurance test . The coefficients of variation for the endurance time were lower on the 80 % test . Statistically significant improvements in the endurance time after bronchodilators in comparison to placebo were found only on the 80 % test . When using the endurance time as an outcome , the high intensity endurance test is preferable to the moderate intensity endurance test , as the high intensity test demonstrated shorter exercise time , less variability and higher sensitivity PURPOSE Endurance training is an important component of rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) . In our study , we investigated the pulmonary hemodynamics ' adaptation during a high-intensity intermittent exercise in such patients . METHODS Eight patients underwent a 30-min exercise , alternating a 4-min work set at their first ventilatory threshold with a 1-min exercise set at 90 % of their maximal tolerated power output . Pulmonary arterial pressure was measured by means of a right heart catheter . Cardiac output was calculated using the Fick 's principle applied to oxygen . RESULTS VO(2 ) , cardiac output , and ventilation increased during the first minutes of exercise and remained stable thereafter . Heart rate increased significantly and progressively to its maximal value from rest to the end of the test ( P < 0.001 ) . After an initial increase , stroke volume decreased significantly ( P < 0.05 ) . Pulmonary arterial pressure increased from rest ( mean + /- SEM 23.9 + /- 2.1 mm Hg ) to the fifth minute of exercise ( 41.6 + /- 2.8 mm Hg ) , and decreased significantly thereafter ( 35.2 + /- 3.3 mm Hg at the 30th minute ) ( P < 0.001 ) . Total pulmonary vascular resistance decreased from rest to the end of the test ( P < 0.001 ) . CONCLUSION The high-intensity 1-min bouts of work of our intermittent work exercise are well tolerated without pushing the pulmonary arterial pressure dramatically high in COPD patients BACKGROUND : A study was carried out to determine whether rating of dyspnoea by means of a visual analogue scale during a progressive exercise test is affected by the subject 's awareness of the progressive nature of the protocol . METHODS : Nineteen patients with chronic obstructive lung disease ( FEV1 mean ( SE ) 1.06 ( 0.07 ) 1 ) were studied . A preliminary incremental test was carried out with a work rate increasing by 10 watts every minute until the subject could no longer exercise , to determine the maximum work load ( Wmax ) and to anchor the upper end of the visual analogue scale . This was followed by two exercise tests performed one day apart in r and omised sequence , with two different protocol s. One was a 12 minute protocol that included two sudden bursts of three minute high intensity exercise , up to the subject 's Wmax , each preceded by three minutes of low level exercise . The other test was a conventional three minute incremental test lasting 12 minutes . On both study days the only information given to the subject about the temporal profile of load was that a change would be made every three minutes . The relation between dyspnoea , as assessed by the visual analogue scale , and ventilation , measured during high intensity or progressive exercise , was studied . RESULTS : The mean ( SE ) rates of increase of dyspnoea with increasing ventilation ( % of line length 1(-1 ) min ) obtained by linear regression analysis were similar for the two tests ( 2.86 ( 0.20 ) for progressive exercise and 2.87 ( 0.25 ) for high intensity exercise ) ; it was 2.59 ( 0.25 ) for the initial burst of high intensity exercise when the data on this were analysed separately . In six subjects with stable disease studied again two months later the reproducibility of the rating of dyspnoea was reasonably good for both protocol s. CONCLUSION : The results suggest that in most patients with chronic obstructive lung disease the assessment of exercise induced dyspnoea by means of a visual analogue scale during a progressive exercise test is not affected by the subject 's awareness of the progressive increase in work intensity PURPOSE The purpose of this study was to compare the effects of interval training ( IT ) and continuous steady-pace training ( CT ) in patients with COPD . METHODS Patients ( n = 21 ) ( mean forced expiratory volume in 1 second ( [ FEV1 ] = 44.6 % ± 13.9 % ) were r and omized to IT , and 20 patients ( mean FEV1 = 41.7 % ± 12.6 % ) to CT . Outcome measures included 6-minute walk distance , maximal work capacity , endurance exercise time during constant workload exercise at 60 % to 70 % of maximal work capacity , and quality of life including fatigue and dyspnea . Participants exercised 3 times per week for 8 weeks , and total work was the same for both training regimens . RESULTS Significant improvement in mean score was observed in each variable within each of the 2 groups : 6-minute walk distance ( IT = 158 ± 178 ft , CT = 106 ± 165 ft ) ; maximal work capacity ( IT = 10.0 ± 13.0 W , CT = 11.5 ± 13.1 W ) ; endurance exercise time ( IT = 15.0 ± 12.5 minutes , CT = 18.7 ± 10.6 minutes ) ; and quality of life domains , fatigue ( IT = 3.1 ± 3.0 , CT = 2.8 ± 4.7 ) , and dyspnea ( IT = 4.4 ± 5.3 , CT = 5.4 ± 5.1 ) . There was no significant difference in the extent of improvement between the 2 training regimens for any of the outcome variables . CONCLUSION Compared with CT , IT was well tolerated and produced similar improvements in exercise performance and quality of life OBJECTIVE The optimum method for sustaining the benefits gained from pulmonary rehabilitation ( PR ) has not been determined . In this report the authors describe the 4-year referral and uptake patterns to a hospital-based outpatient PR programme , and the sustained benefits of PR in patients with COPD attending a community-based maintenance exercise programme . METHODS Entry and exit data were mapped for all patients referred to the PR service over the review period . All eligible patients were offered a community-based maintenance exercise programme upon completion of PR . A total of 21 patients underwent follow-up assessment of functional exercise capacity , quality of life ( QOL ) and health-care utilization . RESULTS Over a 4-year period , 467 patients ( 80 % with COPD ) were referred to the programme , of whom 230 entered PR . In total , 172 patients completed PR , with attrition ( 25 % ) being mostly due to medical problems . Of the 84 patients who elected for the community-based programme , 46 were still attending at follow up and 21 patients with moderate-to-severe COPD ( 44.9 + /- 12.6 ( mean + /- SD ) FEV(1)% predicted ) were reassessed at 18.4 + /- 11.9 months post PR . Significant improvements ( mean change ( 95 % confidence interval ) ) persisted in 6-min walk distance ( 41.1 m ( 15.7 - 66.5 ) ) , distance walked in 20 min ( 195.1 m ( 82.3 - 308 ) ) and in QOL ( Chronic Respiratory Disease Question naire ) ( 11.0 points ( 4.4 - 17.6 ) ) ( P < 0.01 ) . The QOL improvements exceeded the minimum clinical ly important difference . A trend towards a reduction in COPD -related hospital admissions , bed-days and emergency department presentations was observed in the 12 months following PR . Self-reported adherence with the home exercise programme indicated that 67 % of patients were exercising at least 3 - 5 days each week in addition to attending a class . CONCLUSION For patients with moderate-to-severe COPD , a weekly community-based maintenance exercise class , supervised by a physiotherapist , combined with a home exercise programme is an effective intervention for maintaining improvements following PR PURPOSE To create a maximum tolerated 45-minute aerobic training program for patients with chronic obstructive pulmonary disease ( COPD ) and to compare its outcomes with those of commonly prescribed moderate exercise . DESIGN Prospect i ve , r and omized trial . SETTING A work physiology laboratory . PATIENTS AND METHODS The maximum exercise intensities that 7 COPD patients could sustain for 45 minutes were determined on a bilevel exercise ergometer . The patients then exercised 45 minutes daily , 5 days a week for 6 weeks , working 2.03+/-0.4 kJ/kg per session . They were matched with 6 COPD patients who pushed an O2 cart for 45 minutes daily , 5 days a week for 6 weeks , working 1.44+/-.35 kJ/kg per session . RESULTS A 45 minute maximal regimen was established by alternating 1-minute peak exercise at peak VO2-levels with 4 minutes at the ventilatory anaerobic threshold or at 40 % of peak VO2 . Maximal bilevel training significantly decreased dyspnea at rest ( p < or = .01 ) and the blood lactate level during submaximal exercise ( p<.001 ) , and increased peak VO2 and total physical work ( p<.01 ) , maximum inspiratory and expiratory pressures ( p<.01 ) , and grip and forearm strength and endurance ( p<.01 ) . The training also increased maximum voluntary ventilation while decreasing the ventilatory equivalent during exercise ( p<.001 ) . The O2 cart pushers significantly improved only on the 12-minute walk ( p<.05 ) . CONCLUSIONS A maximally intense anaerobic exercise program can be created for most COPD patients that can significantly improve both skeletal and respiratory muscle strength and endurance as well as dyspnea and physiologic parameters OBJECTIVE To compare the effects of a simple home pulmonary rehabilitation program and an intensive hospital-based program in terms of the exercise tolerance and health-related quality of life ( HRQL ) of patients with severe chronic obstructive pulmonary disease ( COPD ) . PATIENTS AND METHODS Patients in this prospect i ve , multicenter trial were r and omized to 2 groups to receive hospital or home pulmonary rehabilitation . Patients in both groups attended 2 informative sessions about the disease and 4 physical therapy sessions . Patients in the hospital group then carried out a structured exercise program while home group patients performed low intensity exercises at home without supervision . RESULTS Twenty-eight patients were r and omized to the hospital rehabilitation group and 23 to the home group . Both groups showed a similar improvement on the 6-minute walk test ( mean difference , 8.7 m ; P=.61 ) . HRQOL measured with the Chronic Respiratory Question naire also improved in both groups , but the change was greater on the emotional function domain in the hospital rehabilitation group ( mean difference between groups , 0.58 on a scale for which the smallest clinical ly relevant difference is 0.5 points ) . The benefits were maintained in both groups 6 months after the programs ended . CONCLUSIONS This study demonstrates that the improvement in exercise tolerance achieved by COPD patients with an unsupervised home pulmonary rehabilitation program is similar to the gains of patients in an intensive hospital-based program . However , the hospital program afforded greater benefit on the HRQOL emotional function domain STUDY OBJECTIVES To investigate the response to interval exercise ( IE ) training by looking at changes in morphologic and biochemical characteristics of the vastus lateralis muscle , and to compare these changes to those incurred after constant-load exercise ( CLE ) training . DESIGN R and omized , controlled , parallel , two-group study ( IE vs CLE training ) . SETTING Multidisciplinary , outpatient , hospital-based , pulmonary rehabilitation program . PATIENTS Nineteen patients with stable advanced COPD ( mean + /- SEM FEV1 , 40 + /- 4 % predicted ) . INTERVENTIONS Patients ( n = 10 ) assigned to IE training exercised at a mean intensity of 124 + /- 15 % of baseline peak exercise capacity ( peak work rate [ Wpeak ] ) with 30-s work periods interspersed with 30-s rest periods for 45 min/d . Patients ( n = 9 ) allocated to CLE training exercised at a mean intensity of 75 + /- 5 % Wpeak for 30 min/d . Patients exercised 3 d/wk for 10 weeks . MEASUREMENTS AND RESULTS Needle biopsies of the right vastus lateralis muscle were performed before and after rehabilitation . After IE training , the cross-sectional areas of type I and IIa fibers were significantly increased ( type I before , 3,972 + /- 455 microm2 ; after , 4,934 + /- 467 microm2 [ p = 0.004 ] ; type IIa before , 3,695 + /- 372 microm2 ; after , 4,486 + /- 346 microm2 [ p = 0.008 ] ) , whereas the capillary-to-fiber ratio was significantly enlarged ( from 1.13 + /- 0.08 to 1.24 + /- 0.07 [ p = 0.013 ] ) . Citrate synthase activity increased ( from 14.3 + /- 1.4 to 20.5 + /- 4.2 micromol/min/g ) , albeit not significantly ( p = 0.097 ) . There was also a significant improvement in Wpeak ( by 19 + /- 5 % ; p = 0.04 ) and in lactate threshold ( by 17 + /- 5 % ; p = 0.02 ) . The magnitude of changes in all the above variables was not significantly different compared to that incurred after CLE training . During training sessions , however , ratings of dyspnea and leg discomfort , expressed as fraction of values achieved at baseline Wpeak , were significantly lower ( p < 0.05 ) for IE training ( 73 + /- 9 % and 60 + /- 8 % , respectively ) compared to CLE training ( 83 + /- 10 % and 87 + /- 13 % , respectively ) . CONCLUSIONS High-intensity IE training is equally effective to moderately intense CLE training in inducing peripheral muscle adaptations ; however , IE is associated with fewer training symptoms PURPOSE This study investigated the possible mechanisms for the expected improvement in dyspnea with pulmonary rehabilitation . METHODS Lung function , clinical ratings of dyspnea , and exercise responses were studied in 44 patients with chronic obstructive pulmonary disease who participated in an outpatient program consisting of 1.5 hours per week of supervised education , breathing training , and upper/lower extremity exercise . RESULTS After rehabilitation , there were significant increases in forced expiratory volume in 1 second ( FEV1 , 7 % ; P = .02 ) , maximal inspiratory mouth pressure ( PImax , 17 % ; P < .001 ) , and the transition dyspnea index focal score ( 3.4 ; P < .001 ) and a significant decrease in the slope of dyspnea/power ( 0.12 versus 0.09 ; P = .001 ) during exercise . Patients who demonstrated > or = 0 mL of change in FEV1 or > or = 5 cm H2O of change in PImax exhibited significant decreases in the slopes for dyspnea/power . CONCLUSIONS After pulmonary rehabilitation , there was a significant improvement in dyspnea . Although there was no evidence of a physiologic training response or enhanced mechanical efficiency , the modest increase in FEV1 and the increase in respiratory muscle strength appeared to contribute to the reduction in dyspnea Limitation of physical activity occupies a central role in the symptom complex of patients with chronic obstructive pulmonary disease ( COPD ) , and improvement in exercise capacity is a key outcome of response to COPD therapy . Maximum exercise capacity testing facilitates assessment of physiologic mechanisms of exercise and allows quantitation of the degree of limitation . This manuscript utilizes published data from the National Emphysema Treatment Trial to investigate the minimal clinical ly important difference ( MCID ) in maximum exercise capacity in patients with severe emphysema . Distribution- and opinion-based methods were used to estimate MCID . Expert clinician opinion yielded a value of 10 Watts as the MCID for change in maximum exercise capacity . Baseline st and ard deviation and error data yielded a one-half st and ard deviation-based estimate of 10.5 Watts and a st and ard error-based estimate of 4.2 Watts . In subjects r and omized to medical therapy , the mean ( ± SD ) 24-month change in maximum exercise capacity following medical therapy was − 9.2 ± 1.2 Watts , whereas among those r and omized to lung volume reduction surgery , mean 24-month change in maximum exercise capacity was 1.7 ± 17.7 Watts , with a mean difference between the groups of 10.9 Watts . The observed difference in maximum exercise capacity after 24 months between subjects r and omized to medical versus surgical therapy conforms to both opinion- and distribution-based estimates of MCID . Further investigation is needed to develop and vali date estimates of MCID for maximum exercise capacity and other key clinical outcomes in COPD STUDY OBJECTIVE We undertook the present study to investigate the perception of dyspnea ( with respect to changes in end-inspiratory and end-expiratory lung volumes ) , during four different levels of high-intensity constant work rate exercise ( CWRE ) in patients with severe COPD . DESIGN Crossover descriptive study with consecutively recruited subjects . SETTING Tertiary university hospital . PATIENTS Twenty-seven subjects with severe COPD ( mean [ + /- SD ] age , 65 + /- 5 years of age ; mean FEV1 , 43 + /- 8 % predicted ; and mean inspiratory capacity [ IC ] ; 74 + /- 14 % predicted ) . MEASUREMENTS AND RESULTS Subjects r and omly performed four high-intensity CWRE tests ( conducted at 65 % , 75 % , 85 % , and 95 % of their symptom-limited peak work rate ) . Dyspnea , leg fatigue , and IC were determined every 2 min during exercise with breath-by-breath gas exchange and ventilatory measurements . There was a good correlation between the resting IC percent predicted and the oxygen uptake ( V(O2 ) ) peak ( r = 0.64 to 0.69 between the IC percent predicted and V(O2 ) peak at the four work rates ) . There were significant differences ( p < 0.01 ) in mean respiratory rate ( 33 + /- 6 , 35 + /- 6 , 37 + /- 6 , and 38 + /- 6 min ) , peak dyspnea score ( 5.9 + /- 1.3 , 6.3 + /- 1.4 , 6.8 + /- 1.2 , and 6.9 + /- 1.6 ) , minute ventilation ( 45.0 + /- 8.7 , 43.8 + /- 7.7 , 43.1 + /- 8.7 , and 42.8 + /- 8.0 L/min ) , leg fatigue ( 4.8 + /- 1.3 , 5.1 + /- 1.3 , 5.7 + /- 1.4 , and 5.8 + /- 1.4 ) , and end-tidal carbon dioxide partial pressure ( 4.41 + /- 0.36 , 4.53 + /- 0.33 , 4.66 + /- 0.31 , and 4.76 + /- 0.24 kPa ) , respectively , for tests conducted at 65 % , 75 % , 85 % , and 95 % of their symptom-limited peak work rate , and in mean end-expiratory lung volume ( [ EELV ] 4.55 + /- 0.44 , 4.69 + /- 0.43 , and 4.79 + /- 0.43 L ) , respectively , for tests conducted at 65 % , 75 % , and 85 % of their symptom-limited peak work rate . In multivariable analysis , the factors that were independently correlated with dyspnea ( p < 0.05 ) were EELV , peak inspiratory flow , and leg fatigue/discomfort . CONCLUSION In COPD subjects with flow limitation at rest , the perception of dyspnea increased nonlinearly with the magnitude of high-intensity CWRE in association with a faster respiratory pattern and an increase in EELV . At the highest work rates , it appeared that a reduction in tidal volume and ventilation peak may have limited the tolerance to exercise Clinical experience suggests that exercise is beneficial for recovery after an acute exacerbation in patients with severe chronic obstructive pulmonary disease ( COPD ) . The aim of this study was to quantify the clinical benefit of exercise in these patients . Twenty-nine in patients were r and omly assigned to a training group ( n = 15 , FEV1 34 % pred ) or a control group ( n = 14 , FEV1 38 % pred ) . On ten consecutive days , patients in the training group performed a 6-min treadmill walking test and , in addition , five walking sessions per day at > or = 75 % of the respective treadmill walking distance . Patients in the control group performed only treadmill walking tests on days 1 , 5 , and 10 . To directly compare the possible benefit of exercise training all patients had an exercise test on day 11 at the same work load as on day 1 . In the training group , 6-min walking distance increased from 237 to 420 m , in the control group from 230 to 255 m over the 10 day period which was significantly different ( P < 0.0001 ) . Minute ventilation and oxygen uptake increased significantly ( P < 0.05 ) in the training but not in the control group . When comparing exercise tests on days 1 and 11 , minute ventilation , oxygen uptake , PaCO2 , lactic acid concentration , and Borg scale were significantly reduced to achieve the same work load ( P < 0.01 ) only in the training group . Intrathoracic gas volume and residual volume decreased , and FEV1 and vital capacity increased in the training ( P < 0.05 ) but not in the control group . Our data demonstrate that exercise training significantly improves the exercise capacity in patients with severe COPD after an acute exacerbation of their disease The BODE index is frequently used to assess functional capacity in patients with COPD . The aim of this study was to investigate the effectiveness of interval-load training ( ILT ) to improve the BODE index in comparison to the commonly implemented constant-load training ( CLT ) . Forty-two patients with COPD [ FEV(1 ) : ( mean+/-SEM ) 42+/-3 % predicted ] were r and omly allocated to either ILT ( n=21 ) or CLT ( n=21 ) . The training program consisted of cycling exercise 3 days/week for 10 weeks . Patients assigned to ILT exercised at a mean intensity of 126+/-4 % of baseline peak work rate ( Wpeak ) with 30-s work periods alternated with 30-s rest periods for 45 min per day , whereas patients allocated to CLT exercised at a mean intensity of 76+/-5 % of baseline Wpeak for 30 min per day . The BODE index and its components : body mass index , FEV(1 ) , MMRC dyspnea score and the 6-min walk test ( 6-MWT ) as well as cycling Wpeak were assessed before and after both exercise training regimes . Both ILT and CLT significantly ( p<0.001 ) decreased the BODE index ( from 4.8+/-0.5 to 4.0+/-0.5 units and from 4.4+/-0.5 to 3.8+/-0.5 units , respectively ) . In addition , both ILT and CLT significantly decreased the MMRC dyspnea score by 0.4+/-0.1 units and increased the 6-MWT ( by 52+/-16 and 44+/-12 m , respectively ) as well as cycling Wpeak ( by 14+/-2 and 10+/-2W , respectively ) . The magnitude of these changes was not significantly different between ILT and CLT . Consequently , ILT is equally effective to CLT in terms of improving the BODE index in patients with COPD and as such it may constitute an alternative rehabilitative modality in COPD The aim of this study was to compare the effects of interval training ( 3-min intervals ) with continuous training on peak exercise capacity ( W peak ) , physiological response , functional capacity , dyspnoea , mental health and health-related quality of life ( HRQoL ) in patients with moderate or severe COPD . Sixty patients exercised twice weekly for 16 weeks after r and omisation to interval- or continuous training . Target intensity was 80 % of baseline W peak in the interval group ( I-group ) and 65 % in the continuous group ( C-group ) . Patients were tested by spirometry , ergometer cycle test , cardiopulmonary test and a 12 min walk test . Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease Question naire ( CRDQ ) , mental health by Hospital Anxiety and Depression scale ( HAD ) and HRQoL by the Medical Outcomes Survey Short Form 36 ( SF-36 ) . After training , W peak , peak oxygen uptake ( VO(2 ) peak ) and exhaled carbon dioxide ( VCO(2 ) peak ) increased significantly in both groups , no significant differences between the groups . Minute ventilation ( V(E ) peak ) increased only in the C-group . At identical work rates ( isotime ) VO(2 ) , VCO(2 ) and V(E ) were significantly more decreased in the I-group than in the C-group ( p<0.05 ) . Functional capacity , dyspnoea , mental health , and HRQoL improved significantly in both groups , no difference between the groups . Interval training and continuous training were equally potent in improving peak exercise capacity , functional exercise capacity , dyspnoea , mental health and HRQoL in patients with moderate or severe COPD . At isotime , the physiological response to training differed between the groups , in favour of the interval training We investigated the physiological responses in older men to continuous ( CEx ) and intermittent ( IEx ) exercise . Nine men [ 70.4 ( 1.2 ) years , V̇O2peak : 2.21 ( 0.20 ) l min−1 ; mean ( SE ) ] completed eight exercise tests ( two CEx and six IEx ) on an electronically braked cycle ergometer in r and om order . CEx and IEx were performed at 50 % and 70 % V̇O2peak . IEx was performed using 60sE:60sR , 30sE:30sR and 15sE:15sR exercise to rest ratios . The duration of exercise was adjusted so that the total amount of work completed was the same for each exercise test . Oxygen uptake ( V̇O2 ) , minute ventilation ( V̇E ) and heart rate ( HR ) were measured at the mid-point of each exercise test . Arterialised blood sample s were obtained at rest and during exercise and analysed for pH and PCO2 . At the same relative intensity ( 50 % or 70 % V̇O2peak ) , IEx result ed in a significantly lower ( P<0.01 ) V̇O2 , V̇E and HR than CEx . There were no significant differences ( P>0.05 ) in V̇O2 , V̇E and HR measured at the mid point of the three exercise to rest ratios at 50 % and 70 % V̇O2peak . pH and PCO2 during CEx and IEx at 50 % V̇O2peak were not significantly different from rest . CEx performed at 70 % V̇O2peak result ed in significant decreases ( P<0.05 ) in pH and PCO2 . There was a significant decrease ( P<0.05 ) in pH only during the 60sE:60sR IEx at 70 % V̇O2peak . Changes in arterialised PCO2 during the 60sE:60sR , 30sE:30sR and 15sE:15sR at both 50 % and 70 % V̇O2peak exercise tests were not significant . When exercising at the same percentage of V̇O2peak and with the total amount of work fixed , IEx results in significantly lower physiological responses than CEx in older men . All results are given as mean ( SE ) The effect of endurance training on muscle electrical activity during general exercise testing was investigated in physically active patients with chronic obstructive pulmonary disease ( COPD ) . Before and after rehabilitation , patients performed identical incremental exercise tests . Pulmonary gas exchange , venous lactate and pyruvate concentrations , and the quadriceps electromyographic signal were sample d every minute throughout exercise testing . Three weeks of rehabilitation increased exercise capacity without modifying pulmonary function . M-wave amplitude , root mean square ( RMS ) of electromyographic activity , and RMS/oxygen uptake were increased significantly during post-rehabilitation testing at the same exercise intensity compared to pre-rehabilitation . Median frequency was significantly lower after training . These modifications reflect greater muscle excitability , greater muscle activation for the same level of exercise , and higher recruitment of slow-twitch fibers . Pulmonary rehabilitation in active COPD patients may normalize the electrical activity of skeletal muscles during incremental dynamic exercise . The electromyographic signal confirms neuromuscular changes after endurance training BACKGROUND In addition to the respiratory limitation in patients with chronic obstructive pulmonary disease ( COPD ) , skeletal muscle abnormalities may occur and contribute to the exercise intolerance . This study assessed the ability of the skeletal muscle of patients with COPD to adapt to individualized exercise training at the gas exchange threshold ( GET ) METHODS : Fourteen patients ( 8 in a training group and 6 controls ) performed the following exercise tests before and after a 3-week training period : an incremental exercise test , maximal voluntary contraction of the quadriceps , and three endurance tests consisting of dynamic contractions of the quadriceps until exhaustion . These endurance tests , characterized by three different power outputs , were used to determine muscle limit times and critical power . RESULTS The results showed that training increased exercise tolerance ( + 11 % for symptom limited peak oxygen consumption ( VO2 sl ] , P < 0.05 ) , maximum voluntary contraction ( + 8 % , P < 0.05 ) , limit times ( from + 45 % to + 161 % , P < 0.05 ) and critical power ( + 39 % , P < 0.05 ) . CONCLUSIONS These findings indicate greater muscle strength and endurance after training in COPD patients and suggest better muscular recruitment and improved oxidative capacity in the exercising muscles . The sharp differences in the magnitude of VO2 sl and limit times suggest that the kinetics of peripheral and central changes in response to training are different . In conclusion , peripheral muscle performance can be increased rapidly in response to an individualized training program at the GET in COPD patients Context Pulmonary rehabilitation programs improve outcomes , but access to outpatient , hospital-based programs is very limited . Contribution In a 10-center , r and omized , noninferiority trial in Canada , investigators r and omly assigned 252 patients to home-based or outpatient , hospital-based exercise training for 8 weeks . At 1 year , the 2 interventions had reduced dyspnea by the same amount , as measured on the dyspnea subscale of the Chronic Respiratory Question naire . The difference between the programs in dyspnea at 1 year was statistically very unlikely to be clinical ly important . Caution The study was unblinded , and its primary outcome was self-reported . Implication Home-based pulmonary rehabilitation is a reasonable alternative to hospital-based programs . The Editors Chronic obstructive pulmonary disease ( COPD ) is a major cause of morbidity and mortality throughout the world . It is currently the fourth leading cause of death , and prevalence is expected to increase ( 1 ) . By focusing on the multiple needs of patients with COPD , pulmonary rehabilitation offers the best chance to address the disability associated with this chronic , progressive disease . This therapeutic approach typically combines exercise training and patient education to achieve the goals of alleviating dyspnea , improving health status , and reducing health care utilization . Despite documented efficacy in a meta- analysis of r and omized trials ( 2 ) and strong recommendations to use it routinely for COPD care ( 3 ) , pulmonary rehabilitation is largely underutilized ( 4 ) . For instance , in 2005 , only an estimated 1 % to 2 % of the Canadian COPD population had access to pulmonary rehabilitation (4)a statistic similar to that reported from other countries ( 5 , 6 ) . We need strategies to increase access to pulmonary rehabilitation . Outpatient , hospital-based programs ( 2 ) are the st and ard against which to compare new forms of pulmonary rehabilitation . The major shortcoming of outpatient , hospital-based pulmonary rehabilitation is limited availability . Self-monitored , home-based rehabilitation is an alternative to outpatient rehabilitation ( 7 , 8) , but only a few small trials have compared it with outpatient , hospital-based rehabilitation ( 9 , 10 ) . We hypothesized that self-monitored , home-based rehabilitation would be as effective as outpatient , hospital-based rehabilitation for improving dyspnea at 1 year . Our secondary objectives were to compare the effects of home-based rehabilitation on health status and exercise tolerance and to evaluate its safety . Methods Design This study was a parallel-group , r and omized , noninferiority , multicenter clinical trial . Eight university-based centers and 2 community-based centers participated . All but 2 centers had experience in providing pulmonary rehabilitation . All patients first participated in a 4-week , st and ardized , comprehensive , self-management education program delivered by a trained health professional acting as a case manager in collaboration with the treating physician . Then , we r and omly assigned participants either to self-monitored , home-based exercise training or to outpatient , hospital-based exercise training for 8 weeks . After the 12-week intervention , we encouraged patients in both groups to continue exercising at home , and we followed them for 40 weeks to complete the 1-year study . We provided an identical educational intervention to both study groups so that we could compare home-based and outpatient exercise-training interventions . During the maintenance phase ( 3 to 12 months ) , contacts with study personnel were limited to telephone interviews to reinforce the importance of exercise and to ask about adverse events . We assessed patients at baseline ( before the educational program ) , immediately after the exercise program , and at 1 year . Each institutional research ethics board approved the study , and each patient provided informed consent . Patient Selection We recruited patients from the pulmonary clinics of the participating centers . Patients were eligible for participation if they had stable COPD , that is , no change in medication and symptoms ( dyspnea , volume , or color of sputum ) for at least 4 weeks before the study ; were 40 years or older ; were current or former smokers of at least 10 pack-years ( 20 cigarettes per pack ) ; had an FEV1 less than 70 % of the predicted value and FEV1FVC ratio less than 0.70 ; and had a Medical Research Council dyspnea score of at least 2 ( 11 ) . No participants had previously been involved in pulmonary rehabilitation or had lived in a long-term care facility . Everyone understood , read , and wrote French or English . Exclusion criteria included a previous diagnosis of asthma , congestive left heart failure as the primary disease , a terminal disease , dementia , or an uncontrolled psychiatric illness . We sought to study a broad COPD population and did not exclude patients with oxygen dependence or other comorbid conditions . Interventions Educational Program Both study groups received the same educational intervention . The self-management educational program Living Well with COPD consisted of an educational flipchart and 6 skill-oriented , self-help , patient workbook modules . The program was provided in the hospital on an outpatient basis . A health professional gave 8 lectures to small groups of 4 to 8 study participants at a rate of 2 sessions per week for 4 weeks . A qualified exercise trainer presented the exercise module . Another study gives a detailed description of the program and confirms its efficacy ( 12 ) . The program is available at www.livingwellwith copd .com ( password : copd ) . Outpatient Hospital-Based Exercise Program Exercise training began after the educational program ended . The training program combined aerobic and strength exercises ( 3 ) at a rate of 3 sessions per week for 8 weeks . Briefly , the aerobic training consisted of stationary leg cycling for 25 to 30 minutes in each session . The target training intensity was 80 % of peak work capacity during incremental exercise . Patients used supplemental oxygen if they had exercise-induced oxygen desaturation during the initial exercise session ( SpO2 < 88 % ) or if they were already receiving home oxygen . The study protocol permitted therapists to adjust the training intensity according to the level of dyspnea and heart rate and in cases of severe dyspnea ( Borg scale score 7 ) , dizziness , or unusually severe chest or leg discomfort . The strength-training exercises lasted 30 minutes , starting with 1 set of 10 repetitions per exercise for a maximum of 3 sets . When the patient reached this goal , we increased resistance through use of elastic b and s , s and bags , and weight against gravity . During training , a qualified exercise specialist closely supervised patients in a ratio of 4 to 5 participants for 1 trainer ( 13 ) . The exercise specialists recorded attendance at the exercise sessions . Home-Based Exercise Program The home program was self-monitored and included aerobic and strength exercises 3 times a week for 8 weeks ( 14 ) . A qualified exercise specialist initiated the program in the patient 's home to ensure full underst and ing . During the 8 weeks , the exercise trainer made weekly telephone calls to reinforce the importance of the exercises and to detect problems . The patients did aerobic training with portable ergocycles with manually adjustable resistance , which we loaned to participants for the 8-week exercise program . The target intensity was 60 % of the maximum work rate achieved during a test of peak exercise capacity for 40 minutes per day , 3 times a week . We instructed patients to reduce intensity in case of severe dyspnea . We recommended a lower training intensity at home than in the outpatient , hospital-based program to ensure participants ' safety , but the sessions were 40 minutes , as opposed to 30 minutes in the outpatient , hospital-based program , to obtain a similar amount of training . The strengthening exercises and use of supplemental oxygen were the same as in the outpatient program . We asked patients to keep a diary of each completed training session . Exercise Maintenance Strategy The maintenance program was identical in both interventions it did not include supervised training sessions . We encouraged patients to buy their own exercise equipment and gave personalized exercise-training recommendations . The case manager contacted patients of both groups every 2 months to reinforce mastery of the intended behavior ( home exercises 3 times per week ) . The case manager was also available to take calls for advice during business hours through a pager or dedicated telephone line . R and omization We r and omly assigned patients to an intervention after they completed the 4-week educational program . Neither research staff nor patients were aware of treatment assignments before patients received them . We used a central ly administered , computer-generated permuted block r and omization scheme using blocks of 2 , stratified according to sex and participating site . We communicated assignments by e-mail to research staff who were not otherwise involved in the trial . The case manager subsequently informed patients of their group allocation . Study personnel were unaware of the permuted block size . Measurements and Outcomes We scheduled evaluation visits at the study center at enrollment ( initial visit ) , 3 months ( immediately after completion of the exercise-training program ) , and 12 months ( end of study ) . Patients in both groups kept a diary to help collect information on medical events . An independent research assistant , unaware of the patient 's group assignment , conducted a st and ardized telephone interview every 4 weeks to identify adverse events . To minimize bias , we asked patients not to discuss their group assignment with the research assistant . Research assistants had no contact with participants other than during the evaluations . Primary Outcome Variable The prespecified primary outcome was the change in the dyspnea domain of the Chronic OBJECTIVE Investigate the effect of lower extremity exercise on maximum lower extremity muscle strength and physical capacity in COPD patients . MATERIAL AND METHOD Twenty moderate to very severe COPD patients were allocated into trained and control groups . The trained group received eight weeks of lower extremity functional exercise including forward step up , lateral step up , heel raise , and lunge at home . Maximum muscle strength and Six Minute Walk Distance ( 6MWD ) assessment s were performed at pre-training , week 4 , and week 8 in hospital setting s. RESULTS There was no significant difference between trained and control groups in maximum muscle strength and 6MWD at the beginning of the program . However , there was a significant improvement in 6MWD after eight weeks of training , whereas there were no significant differences in the control group . CONCLUSION Functional exercise may improve physical capacity in moderate to very severe COPD patients . It is beneficial and easy to perform at home PURPOSE To evaluate the differences in the long-term outcomes of dyspnea , exercise performance , health-related quality of life , and health re source utilization following a dyspnea self-management program with 3 different " doses " of supervised exercise . PATIENTS AND METHODS In a prospect i ve , r and omized , single-blind , 1-year trial , patients with stable chronic obstructive pulmonary disease ( N = 103 ; age 66 + /- 8 , females 57 ; FEV1 44.8 % + /- 14 % predicted ) were r and omly assigned to either : ( 1 ) Dyspnea self-management program ( DM ) ; ( 2 ) DM plus 4 supervised exercise sessions ( DM-exposure ) ; or ( 3 ) DM plus 24 supervised exercise sessions ( DM-training ) . The dyspnea self-management program included individualized education and demonstration of dyspnea self-management strategies , an individualized home walking prescription , and biweekly nurse telephone calls . Outcomes were measured at baseline and every 2 months for 1 year . RESULTS The DM-training group had significantly greater improvements in dyspnea during incremental treadmill test and in exercise performance on the incremental and endurance treadmill tests at 6 and 12 months compared with the other 2 groups . Dyspnea with activities of daily living and self-reported physical functioning significantly improved for all groups over time . The dose-response relationship between supervised exercise and improvement in dyspnea present at 2 months was not sustained over the year . CONCLUSION Consistent with previous findings from evaluation studies of pulmonary rehabilitation programs , the greater number of supervised exercise training sessions improved laboratory dyspnea and performance more than the other two doses of exercise . In the long term , the improvement in dyspnea with activities of daily living and physical functioning was similar for all 3 groups Background : There has been no systemic investigation of the effects of training on endurance at different high-intensity work rates in patients with COPD to date . Objectives : We wanted to determine the effects of intense endurance training on tolerance to several high-intensity work rates and to establish the relationship between power ( WR ) and its tolerable duration ( t ) ( t = W’/(WR – CP ) , being W ’ , the curvature constant , thought to be reflective of anaerobic energy availability and /or tolerance to the uncomfortable sensations associated with the high-intensity exercise , and CP the critical power . Methods : We studied 27 patients : age 62 ± 5 years ; FEV1 1.2 ± 0.2 liters . Before and after the intervention , the subjects r and omly underwent 4 high-intensity constant WR exercise tests . The endurance times of the highest 3 tests were used . Results : Ventilation reached approximately the same level in each of the tests . In response to the training , the average peak increased by 9 ± 5 % ( p < 0.0001 ) , CP by 14 ± 12 % ( p < 0.0001 ) and W ’ 18 ± 22 % ( p = 0.002 ) . In 67 % of the patients , CP increased , accompanied by changes in other related physiological variables of aerobic capacity . In the remaining 33 % , W ’ increased but not CP . Smaller or no changes in the other variables of aerobic capacity were found in those subjects . This latter group was significantly older and had more hyperinflation ( i.e. higher RV/TLC% ) . Conclusions : Our results suggest that neither an incremental nor a single endurance test at constant WR provides an adequate characterisation of exercise tolerance at other WRs . CP and W ’ appear to be important parameters characterizing exercise tolerance over a range high-intensity work rates and identifying two distinct types of response to training UNLABELLED Pulmonary rehabilitation has become a part of the integrated management of patients with chronic obstructive pulmonary disease ( COPD ) . The lower extremity dynamic training has been proved to be the most effective element of the program . OBJECTIVE Does the supervised training have more favorable effect in case of similar program ? PATIENTS AND METHODS In two groups : 54 patients , supervised ( group K , n = 22 ) and not supervised ( group NK , n = 32 ) by physiotherapists , chosen at r and om have been investigated . Both groups consisted of hospitalized patients of the same severity ( forced expiratory volume in one second ) [ FEV1 ( average + /- SD ) ] : K : 51.0 + /- 16.1 vs. NK : 51.9 + /- 15.6 % pred ) . Group K performed physiotherapist-supervised cycling training in the Pulmonology Ambulance Unit 3 - 4 times a week for 45 minutes doing an 8-week period and group NK performed training in the form of cycling , stepping on stairs or dynamic walking at home with the same duration , weekly periodicity and time interval . RESULTS After rehabilitation vital capacity ( VC ) ( K : 3.0 + /- 0.8 vs. 3.3 + /- 0.7 l , p < 0.05 ) , emphysema ratio ( RV/TLC ) : K : 53.5 + /- 10.1 vs. 51.6 + /- 9.9 , p < 0.05 ) in the supervised group , and alveolar volume ( VA ) in the not supervised group ( NK : 4.3 + /- 0.9 vs. 4.7 + /- 0.9 l , p < 0.05 ) significantly improved . Improvement of exercise capacity was more effective in group K ( K : 92.7 + /- 33.9 vs. 106.4 + /- 34.5 W , p < 0.001 ; NK : 95.8 + /- 36.7 vs. 99.9 + /- 35.1 W , p < 0.05 ) . In both groups aerobic capacity ( VO2 : K : 1.2 + /- 0.4 vs. 1.3 + /- 0.4 l/min , p < 0.01 , NK : 1.1 + /- 0.4 vs. 1.2 + /- 0.4 l/min , p < 0.01 ; VO2/kg : K : 16.1 + /- 5.5 vs. 17.5 + /- 5.8 ml/kg/mm , p < 0.01 , NK : 16.2 + /- 5.3 vs. 16.7 + /- 4.8 ml/kg/ min , p < 0.01 ) and anaerobic threshold level [ AT ( pred VO2 % ) ] ( K : 36.6 + /- 9.8 vs. 42.8 + /- 10.2 % , p < 0.001 ; NK : 40.8 + /- 12.0 vs. 44.6 + 11.6 % , p < 0.001 ) significantly improved . Heart rate reserve : ( K : 17.7 + /- 22.7 vs. 28.8 + /- 31.5 l/min , p < 0.01 ; NK : 20.4 + /- 21.2 vs. 25.0 + /- 21.6 l/min , p < 0.01 ) improved at the same level of exercise . The Borg scale of dyspnea ( 0 - 10 ) : ( K : 6.4 + /- 2.5 vs. 5.7 + /- 2.7 , p < 0.05 ; NK : 7.5 + /- 1.8 vs. 6.9 + /- 2.2 , p < 0.05 ) was reduced and quality of life score ( 0 - 24 ) : K : 11.5 + /- 0.7 vs. 9.0 + /- 2.8 , p < 0.005 ; NK : 11.6 + /- 2.3 vs. 7.0 + /- 1.9 , p < 0.005 ) was improved . CONCLUSION In both group dynamic lower extremity training caused improvement in exercise capacity . The favorable metabolic effect of training was shown by the change of anaerobic threshold result ing in less carbon dioxide production during analogous exercise . This reduction led to less ventilation reducing the work of breathing in supervised group . The more favorable adaptation taking place in the group supervised by physiotherapists might have result ed from the controlled higher intensity of the training Background : Pulmonary rehabilitation ( PR ) programs are beneficial to patients with chronic obstructive pulmonary disease ( COPD ) , and lower-extremity training is considered a fundamental component of PR . Nevertheless , the isolated effects of each PR component are not well established . Objective : We aim ed to evaluate the effects of a cycle ergometry exercise protocol as the only intervention in a group of COPD patients , and to compare these results with a control group . Methods : 25 moderate-to-severe COPD patients were evaluated regarding pulmonary function , respiratory muscle strength , exercise capacity , quality of life and body composition . Patients were allocated to one of two groups : ( a ) the trained group ( TG ; n = 13 ; 6 men ) was su bmi tted to a protocol of 24 exercise sessions on a cycle ergometer , with training intensity initially set at a heart rate ( HR ) close to 80 % of maximal HR achieved in a maximal test , and load increase based on dyspnea scores , and ( b ) the control group ( CG ; n = 12 ; 6 men ) with no intervention during the protocol period . Results : TG showed within-group significant improvements in endurance cycling time , 6-min walking distance test , maximal inspiratory pressure and in the domain ‘ dyspnea ’ related to quality of life . Despite the within-group changes , no between-group significant differences were observed . Conclusion : In COPD patients , the results of isolated low-to-moderate intensity cycle ergometer training are not comparable to effects of multimodality and high-intensity training programs AIM To verify the outcome of different physical therapy interventions in activities of daily living of individuals with chronic obstructive pulmonary disease ( COPD ) . METHODS Twenty-two COPD individuals were r and omly divided into three groups : the Lower Limb Training Group ( LLTG , n=8 ) performed treadmill exercise , Upper Limb Training Group ( ULTG , n=8 ) performed upper limb ( UL ) training , and Control Group ( CG , n=6 ) underwent bronchial hygiene therapy for 6 weeks , three times per week . The following were simulated in the activities of the daily living test : blackboard erasing , weight lifting exercise , stair climbing and treadmill walking . The duration of these tasks was 5 min of blackboard erasing and weight lifting , and 6 min of stair climbing and treadmill walking . RESULTS Intragroup analysis presented a significant post-treatment ventilatory dem and ( V(E)/MVV ) decrease for the LLTG during basal conditions and walking , and significant decrease during blackboard erasing and walking for the ULTG , with similar metabolic dem and ( VO(2)/VO(2)max ) for both groups . Dyspnoea decreased significantly in the LLTG during post-treatment walking and increased for CG . The number of stairs climbed decreased significantly for the CG and increased for LLTG and ULTG post treatment , along with the walked distance for LLTG . The intergroup analysis presented significant differences in post-treatment dyspnoea with greater values observed for the CG during walking . CONCLUSION The different protocol s utilized promoted benefits towards physical exercise tolerance , particularly in the ULTG that presented better performance in sustained UL tasks , which may suggest better conditioning and coordination of the muscles involved in UL elevation |
13,457 | 21,509,219 | In the natural history of neurocysticercosis , the following stages of evolution of parenchymal larval cysts can be observed on neuroimaging : viable cyst , granulomatous cysticercosis and disappearance of cyst with or without residual calcification.2 In the viable cyst stage , the cyst wall is not visible on imaging and the cyst demonstrates little or no perilesional oedema .
Ring-like or nodular areas of enhancement with prominent perilesional oedema mark the phase of granulomatous cysticercosis .
The image shown here demonstrates the granulomatous cysticercosis as a ring-enhancing lesion with scolex and peri-lesional oedema .
Ultimately , the remnant of the cyst is either not visible on the imaging or observed as calcified lesion(s ) .
A single day course of praziquantel has also been employed.7 Surgery is usually reserved for extraparenchymal neurocysticercosis such as an intraventricular cyst , spinal cysticercosis causing spinal cord compression , for hydrocephalus , or for ophthalmic cysticercosis.8 In general , the seizure outcome in solitary cerebral cysticercosis is good in view of the symptomatic nature of the seizure . | A 7-year-old boy from South India presented with recurrent left motor seizure with secondary generalisation .
The computed tomography scan of his brain [ Figure 1 ] demonstrated a solitary enhancing cystic lesion with eccentric mural nodule ( scolex ) in the right frontal region .
Solitary cysticercal cysts are an important cause of symptomatic seizure in endemic areas .
Other clinical manifestations include headache and focal neurological deficits .
Antiparasitic therapy for solitary cysticercus granuloma is shrouded in controversy for the following reasons : 1 ) solitary cysticercus granuloma may resolve spontaneously without antihelminthic treatment ; 2 ) the parasite can not grow and develop further in the cerebral parenchymal location , and 3 ) antihelminthic treatment kills the parasite that can potentially cause neurological complications such as a transient increase in seizure frequency , headaches , and raised intracranial pressure .
The latter complication is observed especially in patients with multiple cysticercus granulomata .
The arguments for cysticidal therapy include rapid disappearance of cyst(s ) and the possibility of less residual calcification.2 Albendazole in a dose of 15 mg/kg/day divided into two doses is the antihelminthic drug widely employed .
The duration of treatment was 1 month in older studies , 3 but this has been reduced to 15 days and even 1 week in later studies .4,5 It is usually administered along with corticosteroids to prevent the neurological complications associated with the degeneration and death of the parasite as mentioned above .
Some authors favour anticonvulsant prophylaxis for 6 months and repeat the neuroimaging scan ( by CT or magnetic resonance imaging ) to look for resolution of the lesion with a view to tapering anticonvulsants in patients who are fit free,8 while others have continued anticonvulsant therapy for 2 years.9 Patients with residual calcification may be at risk of recurrent seizures . | Background : Single small enhancing CT lesions ( SSECTL ) of the brain with or without perifocal oedema are common in patients with symptomatic epilepsy in India . Solitary cysticercus granuloma , a benign form of parenchymal neurocysticercosis , is considered to be the most common aetiology for SSECTL . Definite information is lacking regarding the effectiveness of antiparasitic treatment on resolution of these lesions and on long term seizure recurrence . Objective : To evaluate the response to albendazole treatment in patients who had SSECTL and new onset seizures treated with antiepileptic drugs ( AED ) in a prospect i ve clinical trial . Methods : 43 patients who presented with new onset seizures and were documented to have SSECTL were alternatively allocated to receive albendazole 15 mg/kg/day for 2 weeks or no cysticidal therapy . All patients were treated with AED and followed for at least 6 months for seizure recurrence , and serial CT scans were obtained at 4 weeks , 3 months and at study completion . Results : 28 ( 65 % ) patients were aged 5–25 years and 31 ( 72 % ) presented clinical ly with partial motor seizures with or without generalisation . Most of the SSECTL were ring lesions ( 75 % ) and located in and around the sensory – motor cortex at the gray – white junction ( 65 % ) . In the albendazole group , 56 % of patients compared with 35 % in the control group showed resolution of SSECTL ( p = 0.154 ) at 1 month . 22 of 23 patients ( 95.6 % ) , who received albendazole , compared with 14 of 20 patients ( 70 % ) in the control group , demonstrated radiological resolution on study completion ( p = 0.03 ) . Punctate residual calcification and seizure recurrence were observed in four patients ( 9.3 % ) in the control group and in three ( 7 % ) patients in the albendazole group ( p = 0.47 ) . Conclusions : In patients presenting with seizures due to single viable parenchymal neurocysticercosis , albendazole hastens the resolution of SSECTL if treatment is given in the early phase of the illness Twenty-six patients with single enhancing brain lesion ( SEL ) were openly assigned to receive single-day praziquantel therapy ( n=14 ) , or not ( n=12 ) . From 14 treated patients , complete resolution was found in 11 , partial resolution in two , and the remaining case was later diagnosed as an arteriovenous malformation . Side effects presented in only one patient and remitted in the same day with symptomatic treatment . Conversely , the lesions persisted unchanged in six of 12 patients in the non-treatment group . Untreated patients with persisting lesions were prescribed praziquantel treatment . After this , SELs disappeared in three cases , other diagnoses ( brain tuberculoma and arteriovenous malformation ) were made in two , and one was not evaluated . When analyzed in regard to the baseline serology , resolution of lesions on computed tomography was found in 13 ( complete=12 , partial=1 ) of 14 seropositive patients , whereas it only happened in six ( complete=5 , partial=1 ) of 12 seronegative patients . Serological screening defines a subset of SEL patients with good prognosis . If antiparasitic therapy is to be used in patients with SEL , and we can not find a strong argument against it , single-day praziquantel is the regimen of choice based on duration , costs , and minimal side effects No trials to date have focused on long-term seizure outcome in solitary cerebral cysticercal lesion ( SCCL ) , which is believed to produce a relatively benign form of epilepsy . This is a prospect i ve r and omized controlled study to evaluate the effect of Albendazole on long-term seizure outcome in patients with MRI-confirmed solitary cerebral cysticercal lesion ( SCCL ) . One hundred and twenty-three patients with new-onset seizures and SCCL on contrast MRI were r and omized to treatment with albendazole and followed for up to five years with serial MRI and clinical evaluation . At final analysis 103 patients ( M-54 , F-49 ) with a mean age of 18.6+/-10.7 years and follow-up period more than 12 months were included . The mean follow-up duration was 31.4+/-14.8 months ( 12 - 64 ) . At one month follow-up more patients receiving albendazole were seizure-free ( 62 % versus 49 % for controls ) . Subsequently there was no significant difference in overall seizure outcome between the two groups . There was no correlation between seizure semiology , albendazole therapy and long-term seizure outcome . Baseline MRI showed active lesions in all ; 23 % remained active at 12 months with no difference between the albendazole and control groups . Patients whose lesions resolved at 12 months showed better seizure outcome . Reduction in mean cyst area was greater in the albendazole group as compared to the controls and the difference at six months was significant ( p<0.05 ) . At three months follow-up perilesional edema also resolved faster in albendazole group ( p<0.05 ) . Thus , albendazole did not alter the long-term seizure outcome in patients with SCCL and epilepsy . However , albendazole hastened resolution of SCCL on MRI , but interestingly 23 % of lesions were still active 12 months after treatment Objectiue To compare the effectiveness of two regimens of albendazole therapy for neurocysticercosis . Design R and omized , double-blind clinical trial . Setting s Patients admitted to neurologic wards in Lima , Peru . Patients Adult patients with active neurocysticercosis demonstrated by CT and Western blot ( immunoblot ) . Intervention One week ( n = 25 ) versus 2 weeks ( n = 25 ) of albendazole therapy . Measurements Decrease in the number of cysts on CT . Results Effectiveness of albendazole was 78 % , with no difference between the groups when compared 3 months after therapy . Complete cure was obtained in only 38 % of patients . Patients with more than 20 cysts had poorer responses to therapy . The clinical course and EEG evolution improved in most patients . Side effects were present in 38 % of patients , mainly mild , transient gastrointestinal symptoms . Therapy was also associated with exacerbation of neurologic symptoms . Two patients died in the first year after therapy , both because of aggregated infections of ventricle-peritoneal shunts . One-year follow-up CT showed lesions in three of 10 patients presumed to be cured 3 months after therapy . Conclusions Extension of albendazole therapy for more than 7 days adds no benefits for the patients KEY WORDS : Neurocysticercosis : Albendazole ; Dextrochloropheniramine ; Treatment . The clinical variability of neurocysticercosis is due to a series of factors such as number , location , form , dimensions and stage of development of the parasite , the nature of its action on the organism and the individual immunological response of the hosu.4,6 . Thus , diagnosis is very difficult , especially in not highly endemic areas or in regions were laboratory support is lacking . Another important feature to be considered in the approach to neurocysticercosis is the lack of an alternative program of antiparasitic treatment . The high coast of treatment with praziquantel and the side effects ' of |
13,458 | 29,949,894 | The DASH pattern showed improvement in cardiac function , functional capacity , blood pressure , oxidative stress and mortality .
The Mediterranean diet had a correlation with inflammation , quality of life and cardiac function but just on cross-sectional studies .
Conclusions : DASH pattern may have benefits in the secondary prevention of HF .
In addition , the Hyperproteic and Low-carb diets , despite the lack of studies , also demonstrated positive effects on the functional capacity in patients with HF | Background : Diet is an important factor in secondary prevention of heart failure ( HF ) but there is still no consensus as to which dietary model should be adopted by this population .
This systematic review aims to clarify the relationship between dietary patterns and secondary prevention in HF . | Background / Objectives : Evidence about the relation between dietary patterns and cardiovascular disease ( CVD ) is scarce in Middle Eastern countries . This study was performed to examine the association between major dietary patterns and CVD mortality in Iranian adults . Subjects/ Methods : This population -based prospect i ve cohort study was conducted among 4834 r and omly selected participants aged ⩾35 years from urban and rural areas of central Iran ( 2001–2009 ) ( the Isfahan Cohort Study ) . Dietary intakes were assessed using a food frequency question naire , and major dietary patterns were identified by means of exploratory factor analysis . Subjects or their next of kin were interviewed biannually looking for possible occurrence of events . Cardiovascular mortality was defined as fatal myocardial infa rct ion , fatal stroke and sudden cardiac death . Results : During the median follow-up of 9.0 years and 50 282 person-years , we found a total of 118 CVD mortalities . Four major dietary patterns were identified : ' Western ' , ' Mediterranean ' , ' Animal fat ' and ' Fast food ' . Adherence to the Mediterranean dietary pattern was protectively associated with CVD mortality , such that those in the highest quartile were 46 % ( hazard ratio ( HR ) : 0.54 ; 95 % confidence interval ( CI ) : 0.32–0.91 ; P-value for trend=0.03 ) less likely to have incident CVD mortality than those in the lowest quartile . Further adjustment for potential confounders strengthened this association ( HR : 0.42 ; 95 % CI : 0.19–0.96 ; P-value for trend=0.02 ) . We found no significant association between adherence to the Western , animal fat and fast food dietary patterns and CVD mortality . Conclusions : Adherence to a Mediterranean dietary pattern was associated with reduced risk for cardiovascular mortality even in a developing country setting Diet rich in fruits , vegetables , and dairy products , known as the Dietary Approaches to Stop Hypertension ( DASH ) diet , is known to reduce blood pressure ( BP ) in hypertensive patients . More recently , the DASH diet was shown to reduce oxidative stress in hypertensive and nonhypertensive humans . However , the main nutritional components responsible for these beneficial effects of the DASH diet remain unknown . Because the DASH diet is rich in potassium ( K ) , magnesium ( Mg ) , and alkali , we performed a r and omized , double-blinded , placebo-controlled study to compare effects of potassium magnesium citrate ( KMgCit ) , potassium chloride ( KCl ) , and potassium citrate ( KCit ) to allow dissociation of the three components of K , Mg , and citrate on 24-hour ambulatory BP and urinary 8-isoprostane in hypertensive and prehypertensive subjects , using a r and omized crossover design . We found that KCl supplementation for 4 weeks induced a significant reduction in nighttime SBP compared with placebo ( 116 ± 12 vs 121 ± 15 mm Hg , respectively , p < 0.01 vs placebo ) , whereas KMgCit and KCit had no significant effect in the same subjects ( 118 ± 11 and 119 ± 13 mm Hg , respectively , p > 0.1 vs placebo ) . In contrast , urinary 8-isoprostane was significantly reduced with KMgCit powder compared with placebo ( 13.5 ± 5.7 vs 21.1 ± 10.5 ng/mgCr , respectively , p < 0.001 ) , whereas KCl and KCit had no effect ( 21.4 ± 9.1 and 18.3 ± 8.4 , respectively , p > 0.1 vs placebo ) . In conclusion , our study demonstrated differential effects of KCl and KMgCit supplementation on BP and the oxidative stress marker in prehypertensive and hypertensive subjects . Clinical significance of the antioxidative effect of KMgCit remains to be determined in future studies OBJECTIVES This study sought to determine the efficacy of dietary sodium restriction ( DSR ) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure ( SBP ) ( 130 - 159 mm Hg ) and the associated physiological mechanisms . BACKGROUND Vascular endothelial dysfunction develops with advancing age and elevated SBP , contributing to increased cardiovascular risk . DSR lowers BP , but its effect on vascular endothelial function and mechanisms involved are unknown . METHODS Seventeen subjects ( 11 men and 6 women ; mean age , 62 ± 7 years ) completed a , r and omized crossover study of 4 weeks of both low ( DSR ) and normal sodium intake . Vascular endothelial function ( endothelium-dependent dilation ; EDD ) , nitric oxide (NO)/tetrahydrobiopterin ( BH(4 ) ) bioavailability , and oxidative stress-associated mechanisms were assessed following each condition . RESULTS Urinary sodium excretion was reduced by ≈ 50 % ( to 70 ± 30 mmol/day ) , and conduit ( brachial artery flow-mediated dilation [ FMD(BA ) ] ) and resistance ( forearm blood flow responses to acetylcholine [ FBF(ACh ) ] ) artery EDD were 68 % and 42 % ( peak FBF(ACh ) ) higher following DSR ( p < 0.005 ) . Low sodium markedly enhanced NO-mediated EDD ( greater ΔFBF(ACh ) with endothelial NO synthase inhibition ) without changing endothelial NO synthase expression/activation ( Ser 1177 phosphorylation ) , restored BH(4 ) bioactivity ( less ΔFMD(BA ) with acute BH(4 ) ) , abolished tonic superoxide suppression of EDD ( less ΔFMD(BA ) and ΔFBF(ACh ) with ascorbic acid infusion ) , and increased circulating superoxide dismutase activity ( all p < 0.05 ) . These effects were independent of ΔSBP . Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged . CONCLUSIONS DSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH(4 ) bioavailability and reducing oxidative stress . Our findings support the emerging concept that DSR induces " vascular protection " beyond that attributable to its BP-lowering effects BACKGROUND The incidence of congestive heart failure ( CHF ) has been increasing steadily in the United States during the past 2 decades . We studied risk factors for CHF and their corresponding attributable risk in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study . PARTICIPANTS AND METHODS A total of 13 643 men and women without a history of CHF at baseline examination were included in this prospect i ve cohort study . Risk factors were measured using st and ard methods between 1971 and 1975 . Incidence of CHF was assessed using medical records and death certificates obtained between 1982 and 1984 and in 1986 , 1987 , and 1992 . RESULTS During average follow-up of 19 years , 1382 CHF cases were documented . Incidence of CHF was positively and significantly associated with male sex ( relative risk [ RR ] , 1.24 ; 95 % confidence interval [ CI ] , 1.10 - 1.39 ; P<.001 ; population attributable risk [ PAR ] , 8.9 % ) , less than a high school education ( RR , 1.22 ; 95 % CI , 1.04 - 1.42 ; P = .01 ; PAR , 8.9 % ) , low physical activity ( RR , 1.23 ; 95 % CI , 1.09 - 1.38 ; P<.001 ; PAR , 9.2 % ) , cigarette smoking ( RR , 1.59 ; 95 % CI , 1.39 - 1.83 ; P<.001 ; PAR , 17.1 % ) , overweight ( RR , 1.30 ; 95 % CI , 1.12 - 1.52 ; P = .001 ; PAR , 8.0 % ) , hypertension ( RR , 1.40 ; 95 % CI , 1.24 - 1.59 ; P<.001 ; PAR , 10.1 % ) , diabetes ( RR , 1.85 ; 95 % CI , 1.51 - 2.28 ; P<.001 ; PAR , 3.1 % ) , valvular heart disease ( RR , 1.46 ; 95 % CI , 1.17 - 1.82 ; P = .001 ; PAR , 2.2 % ) , and coronary heart disease ( RR , 8.11 ; 95 % CI , 6.95 - 9.46 ; P<.001 ; PAR , 61.6 % ) . CONCLUSIONS Male sex , less education , physical inactivity , cigarette smoking , overweight , diabetes , hypertension , valvular heart disease , and coronary heart disease are all independent risk factors for CHF . More than 60 % of the CHF that occurs in the US general population might be attributable to coronary heart disease Background Despite convincing evidence in the Mediterranean region , the cardiovascular benefit of the Mediterranean diet is not well established in non-Mediterranean countries and the optimal criteria for defining adherence are unclear . The population attributable fraction ( PAF ) of adherence to this diet is also unknown . Methods In the UK-based EPIC-Norfolk prospect i ve cohort , we evaluated habitual diets assessed at baseline ( 1993–1997 ) and during follow-up ( 1998–2000 ) using food-frequency question naires ( n = 23,902 ) . We estimated a Mediterranean diet score ( MDS ) using cut-points projected from the Mediterranean dietary pyramid , and also three other pre-existing MDSs . Using multivariable-adjusted Cox regression with repeated measures of MDS and covariates , we examined prospect i ve associations between each MDS with incident cardiovascular diseases ( CVD ) by 2009 and mortality by 2013 , and estimated PAF for each outcome attributable to low MDS . Results We observed 7606 incident CVD events ( 2818/100,000 person-years ) and 1714 CVD deaths ( 448/100,000 ) . The MDS based on the Mediterranean dietary pyramid was significantly associated with lower incidence of the cardiovascular outcomes , with hazard ratios ( 95 % confidence intervals ) of 0.95 ( 0.92–0.97 ) per one st and ard deviation for incident CVD and 0.91 ( 0.87–0.96 ) for CVD mortality . Associations were similar for composite incident ischaemic heart disease and all-cause mortality . Other pre-existing MDSs showed similar , but more modest associations . PAF due to low dietary pyramid based MDS ( < 95th percentile ) was 3.9 % ( 1.3–6.5 % ) for total incident CVD and 12.5 % ( 4.5–20.6 % ) for CVD mortality . Conclusions Greater adherence to the Mediterranean diet was associated with lower CVD incidence and mortality in the UK . This diet has an important population health impact for the prevention of CVD BACKGROUND The possible advantage for weight loss of a diet that emphasizes protein , fat , or carbohydrates has not been established , and there are few studies that extend beyond 1 year . METHODS We r and omly assigned 811 overweight adults to one of four diets ; the targeted percentages of energy derived from fat , protein , and carbohydrates in the four diets were 20 , 15 , and 65 % ; 20 , 25 , and 55 % ; 40 , 15 , and 45 % ; and 40 , 25 , and 35 % . The diets consisted of similar foods and met guidelines for cardiovascular health . The participants were offered group and individual instructional sessions for 2 years . The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content . RESULTS At 6 months , participants assigned to each diet had lost an average of 6 kg , which represented 7 % of their initial weight ; they began to regain weight after 12 months . By 2 years , weight loss remained similar in those who were assigned to a diet with 15 % protein and those assigned to a diet with 25 % protein ( 3.0 and 3.6 kg , respectively ) ; in those assigned to a diet with 20 % fat and those assigned to a diet with 40 % fat ( 3.3 kg for both groups ) ; and in those assigned to a diet with 65 % carbohydrates and those assigned to a diet with 35 % carbohydrates ( 2.9 and 3.4 kg , respectively ) ( P>0.20 for all comparisons ) . Among the 80 % of participants who completed the trial , the average weight loss was 4 kg ; 14 to 15 % of the participants had a reduction of at least 10 % of their initial body weight . Satiety , hunger , satisfaction with the diet , and attendance at group sessions were similar for all diets ; attendance was strongly associated with weight loss ( 0.2 kg per session attended ) . The diets improved lipid-related risk factors and fasting insulin levels . CONCLUSIONS Reduced-calorie diets result in clinical ly meaningful weight loss regardless of which macronutrients they emphasize . ( Clinical Trials.gov number , NCT00072995 . OBJECTIVE Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk . Low-carbohydrate , high-fat diets are advocated as an alternative , but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction . RESEARCH DESIGN AND METHODS We investigated a low-fat ( 20 % fat , 60 % carbohydrate ) versus a low-carbohydrate ( 60 % fat , 20 % carbohydrate ) weight reduction diet in 24 overweight/obese subjects ( [ mean ± SD ] BMI 33.6 ± 3.7 kg/m2 , aged 39 ± 10 years ) in an 8-week r and omized controlled trial . All food was weighed and distributed , and intake was calculated to produce a 500 kcal/day energy deficit . Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test . Body composition , adipokine levels , and vascular compliance by pulse-wave analysis were also measured . RESULTS Significant weight loss occurred in both groups ( P < 0.01 ) , with no difference between groups ( P = 0.40 ) . Peripheral glucose uptake increased , but there was no difference between groups ( P = 0.28 ) , and suppression of endogenous glucose production was also similar between groups . Meal tolerance – related insulin secretion decreased with weight loss with no difference between groups ( P = 0.71 ) . The change in overall systemic arterial stiffness was , however , significantly different between diets ( P = 0.04 ) ; this reflected a significant decrease in augmentation index following the low-fat diet , compared with a nonsignificant increase within the low-carbohydrate group . CONCLUSIONS This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content . The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk Abstract — Evidence suggests that obesity may raise blood pressure ( BP ) through oxidative stress – sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet ( DASH-CD ) may decrease BP by enhancing antioxidant capacity . To address this question , 12 obese patients with high-normal – to – stage 1 hypertension ( hypertensives ) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in r and om sequence for 4 weeks each . Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin . Ferric-reducing activity of plasma ( FRAP ) and plasma F2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress , respectively . BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets ( −8.1±1.5/−7.4±1.6 mm Hg , P < 0.05 ) . BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet . FRAP on usual diets was higher in lean subjects than in obese subjects . FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet , and the group difference disappeared . F2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD . Among free-living obese hypertensives , the DASH-CD raises antioxidant capacity , lowers BP , and reduces oxidative stress induced by acute hyperlipidemia . The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD Endothelial dysfunction has been recognized as a pathophysiologic mechanism in the progression of heart failure ( HF ) . However , little attention has been given to the ability of dietary approaches to improve endothelial function . This study examined the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on endothelial function , exercise capacity , and quality of life in patients with chronic symptomatic ( stage C ) HF . Forty-eight patients were r and omized to follow the DASH diet ( n = 24 ) or the general HF dietary recommendations ( n = 24 ) . Endothelial function was assessed by measuring large and small arterial elasticity ( LAE and SAE ) at rest . Exercise capacity ( measured with the 6-minute walk test ) and quality of life ( measured with the Minnesota Living with Heart Failure Question naire ) at baseline and 3 months were also evaluated . Patients were older adults with an average HF duration of 5 years . LAE at 1 month improved significantly in the DASH diet group ( P < 0.01 ) . Overall LAE and SAE scores at 3 months also improved ; however , the net changes were not statistically significant . The DASH group had better exercise capacity ( 292 m vs 197 m ; P = 0.018 ) and quality of life scores ( 21 vs 39 ; P = 0.006 ) over time , while sodium intake levels at 1 , 2 , and 3 months were comparable between the groups . Adhering to the DASH diet improved arterial compliance initially and improved exercise capacity and quality of life scores at 3 months . The DASH diet may be an important adjunctive therapy for patients with symptomatic H We determined the temporal effects of dietary sodium restriction on large elastic artery compliance and systolic blood pressure ( SBP ) in 12 untreated , older ( 64±2 years ) men and women ( 6 each ) with stage 1 systolic hypertension . After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake ( r and omized , crossover design ) . Urinary sodium excretion was reduced by 60 % by the end of week 1 of sodium restriction ( 54±11 mmol/d , P < 0.01 ) versus baseline ( 135±14 ) . Compared with baseline ( 0.11±0.01 mm/mm Hg ) , carotid artery compliance was increased by 27 % ( to 0.14±0.02 , P < 0.05 ) at the end of week 1 of sodium restriction , attaining peak levels by week 2 ( + 46 % , to 0.16±0.02 , P < 0.01 ) . Similarly , supine resting brachial artery SBP was reduced by > 5 mm Hg by week 1 of sodium restriction , attaining peak reductions by week 2 ( −12 mm Hg , P < 0.01 versus baseline ) . The 24-hour ambulatory SBP was ≈3 mm Hg lower at week 1 of sodium restriction and ≈6 mm Hg lower by week 2 ( P < 0.01 versus baseline ) . The reductions in resting SBP from baseline to week 2 of sodium restriction were strongly related to the corresponding increases in carotid compliance ( r = 0.80 , P < 0.01 ) . Urinary sodium excretion , carotid artery compliance , and SBP were not different during normal sodium intake versus baseline . Other subject characteristics were not different across conditions . Sodium restriction rapidly improves large elastic artery compliance in older adults with stage 1 systolic hypertension . These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by sodium restriction in these patients Objective The aim of this study was to evaluate adherence to the Mediterranean Diet ( MD ) and its association with all-cause mortality in an elderly Italian population . Design Data analysis of a longitudinal study of a representative , age stratified , population sample . Setting Study data is based upon the Italian Longitudinal Study on Aging ( ILSA ) a prospect i ve , community-based cohort study . The baseline evaluation was carried out in 1992 and the follow-up in 1996 and 2000.ParticipantParticipant food intake assessment was available at baseline for 4,232 subjects ; information on survival was available for 2,665 at the 2000 follow-up . Measurements Adherence to the MD was evaluated with an a priori score based on the Mediterranean pyramid components . Cox proportional hazard models were used to assess the relationship between the MD score and all-cause mortality . Six hundred and sixty five subjects had died at the second follow-up ( identified up to the first and second follow-up together ; mean follow-up : 7.1±2.6 years ) . Results At the 2000 follow-up , adjusting for other confounding factors , participants with a high adherence to MD ( highest tertile of the MD score distribution ) had an all-cause mortality risk that was of 34 % lower with respect to the subjects with low adherence ( Hazard Ratio=0.66 ; 95 % CI : 0.49 - 0.90 ; p=0.0144 ) . Conclusion According to study results , a higher adherence to the MD was associated with a low all-cause mortality risk in an elderly Italian population Background Adherence to the Mediterranean diet is associated with lower mortality in a general population but limited evidence exists on the effect of a Mediterranean diet on mortality in subjects with diabetes . We aim to examine the association between the Mediterranean diet and mortality in diabetic individuals . Design Prospect i ve cohort study on 1995 type 2 diabetic subjects recruited within the MOLI-SANI study . Methods : Food intake was recorded by the European Project Investigation into Cancer and Nutrition food frequency question naire . Adherence to the Mediterranean diet was appraised by the Greek Mediterranean diet score . Hazard ratios were calculated using multivariable Cox-proportional hazard models . Results During follow-up ( median 4.0 years ) , 109 all-cause including 51 cardiovascular deaths occurred . A 2-unit increase in Mediterranean diet score was associated with 37 % ( 19%–51 % ) lower overall mortality . Data remained unchanged when restricted to those being on a hypoglycaemic diet or on antidiabetic drug treatment . A similar reduction was observed when cardiovascular mortality only was considered ( hazard ratio = 0.66 ; 0.46–0.95 ) . A Mediterranean diet-like pattern , originated from principal factor analysis , indicated a reduced risk of overall death ( hazard ratio = 0.81 ; 0.62–1.07 ) . The effect of Mediterranean diet score was mainly contributed by moderate alcohol drinking ( 14.7 % in the reduction of the effect ) , high intake of cereals ( 12.2 % ) , vegetables ( 5.8 % ) and reduced consumption of dairy and meat products ( 13.4 % and 3.4 % respectively ) . Conclusions The traditional Mediterranean diet was associated with reduced risk of both total and cardiovascular mortality in diabetic subjects , independently of the severity of the disease . Major contributions were offered by moderate alcohol intake , high consumption of cereals , fruits and nuts and reduced intake of dairy and meat products Background : The effectiveness of high-protein ( HP ) diets in reducing body weight and adiposity and potentially improving clinical outcomes in heart failure ( HF ) is not known . Objective : This feasibility study was conducted to evaluate the impact of 3 dietary interventions on body weight and adiposity , functional status , lipid profiles , glycemic control , and quality of life ( QOL ) in overweight and obese patients with HF and type 2 diabetes mellitus . Design : Fourteen patients with HF with a body mass index greater than 27 kg/m2 were r and omized to an HP diet , a st and ard protein diet , or a conventional diet . Data were obtained at baseline and 12 weeks . Results : There were no significant differences in age ( 59 ± 10 years ) , sex ( 78 % male ) , New York Heart Association class ( 43 % class II , 57 % class III ) , and HF etiology or left ventricular ejection fraction ( 26 ± 7 ) between the groups at baseline . Patients on the HP diet demonstrated significantly greater reductions in weight ( P = .005 ) , percent body fat ( P = .036 ) , total cholesterol ( P = .016 ) , triglyceride concentrations ( P = .034 ) , and low-density lipoprotein cholesterol ( P = .041 ) and greater improvements in functional status ( 6-minute walk [ P = .010 ] and VO2 peak [ P = .003 ] ) , high-density lipoprotein cholesterol ( P = .006 ) , and physical QOL scores ( P = .022 ) compared with those on st and ard protein and conventional diets . Conclusion : A 12-week HP diet result ed in moderate weight loss and reduced adiposity in a small sample of overweight and obese patients with HF that were associated with improvements in functional status , lipid profiles , glycemic control , and QOL . However , these preliminary findings must be confirmed in studies with more participants and long-term follow-up The prognostic value of exercise peak VO2 is still controversial . We therefore prospect ively studied 75 patients in New York Heart Association functional class II or III with chronic heart failure stabilized by drug treatment . The patients ( mean age of 58 + /- 10 years ) were su bmi tted to a clinical examination , a radionuclide determination of left ventricular ejection fraction , and a haemodynamic study at rest ( right side catheterization ) ; their plasma sodium , plasma creatinine and blood urea nitrogen levels were measured in addition to exercise peak VO2 . An exercise peak VO2 threshold value of 14 ml.kg-1.min-1 was used to define two groups : GI ( 23 patients ) , with an exercise peak VO2 < or = 14 ml.kg-1.min-1 and G2 ( 52 patients ) with an exercise peak VO2 > 14 m.kg-1.min-1 . G1 and G2 were comparable in terms of age , heart rate , left ventricular ejection fraction , cardiac index and mean arterial pressure . Apart from exercise peak VO2 , G1 and G2 also showed differences in right and left ventricular filling pressures , plasma sodium , plasma creatinine , blood urea nitrogen levels and exercise duration ( all P < 0.01 ) . Moreover the prognosis was worse in G1 than in G2 : nine deaths vs 0 , and seven major events -- major events being defined as pulmonary oedema , hospitalization for heart failure , or severe ventricular arrhythmias -- vs three ( P < 0.001 ) . A sub-group analysis ( deceased patients , living patients with and without major events ) was performed . Out of 20 clinical and para clinical parameters , exercise peak VO2 proved to have the greatest prognostic value . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE The aim of this study was to assess the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on lipid profiles and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome ( PCOS ) . METHODS This r and omized controlled clinical trial was conducted with 48 women diagnosed with PCOS . The women were r and omly assigned to consume either the control ( n = 24 ) or DASH diet ( n = 24 ) for 8 wk . Both diets were design ed to be calorie-restricted . Both diets consisted of 52 % carbohydrates , 18 % proteins , and 30 % total fats . The DASH diet was design ed to be rich in fruits , vegetables , whole grains , and low-fat dairy products and to be low in saturated fats , cholesterol , and refined grains . Fasting blood sample s were taken at baseline and after 8-wk intervention to measure lipid profiles and biomarkers of oxidative stress including plasma total antioxidant capacity ( TAC ) and total glutathione ( GSH ) . RESULTS Adherence to the DASH diet , compared with the control diet , result ed in a significant decrease in weight ( -4.4 versus -1.5 kg ; P < 0.001 ) and body mass index ( -1.7 versus -0.6 kg/m(2 ) ; P < 0.001 ) , decreased serum triglycerides ( -10.0 versus + 19.2 mg/dL ; P interaction = 0.005 ) and very-low-density lipoprotein cholesterol levels ( -2.0 versus + 3.9 mg/dL ; P interaction = 0.005 ) . Increased concentrations of TAC ( + 98.6 versus -174.8 mmol/L ; P interaction < 0.001 ) and GSH ( + 66.4 versus -155.6 μmol/L ; P interaction = 0.005 ) also were found in the DASH group compared with the control group . CONCLUSION Consumption of DASH diet for 8 wk led to a significant reduction in serum insulin , triglycerides and very-low-density lipoprotein cholesterol and a significant increase in TAC and GSH levels BACKGROUND Olive oil polyphenols have been associated with several cardiovascular health benefits . This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure ( BP ) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension . METHODS We conducted a double-blind , r and omized , crossover dietary-intervention study . After a run-in period of 4 months ( baseline values ) , two diets were used , one with polyphenol-rich olive oil ( ∼30 mg/day ) , the other with polyphenol-free olive oil . Each dietary period lasted 2 months with a 4-week washout between diets . Systolic and diastolic BP , serum or plasma biomarkers of endothelial function , oxidative stress , and inflammation , and ischemia-induced hyperemia in the forearm were measured . RESULTS When compared to baseline values , only the polyphenol-rich olive oil diet led to a significant ( P < 0.01 ) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP . A similar finding was found for serum asymmetric dimethylarginine ( ADMA ) ( -0.09 ± 0.01 µmol/l , P < 0.01 ) , oxidized low-density lipoprotein ( ox-LDL ) ( -28.2 ± 28.5 µg/l , P < 0.01 ) , and plasma C-reactive protein ( CRP ) ( -1.9 ± 1.3 mg/l , P < 0.001 ) . The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates ( + 4.7 ± 6.6 µmol/l , P < 0.001 ) and hyperemic area after ischemia ( + 345 ± 386 perfusion units (PU)/sec , P < 0.001 ) . CONCLUSIONS We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension BACKGROUND Global and national dietary guidelines have been created to lower chronic disease risk . The aim of this study was to assess whether greater adherence to the WHO guidelines ( Healthy Diet Indicator ( HDI ) ) ; the Dutch guidelines for a healthy diet ( Dutch Healthy Diet-index ( DHD-index ) ) ; and the Dietary Approaches to Stop Hypertension ( DASH ) diet was associated with a lower risk of cardiovascular disease ( CVD ) , coronary heart disease ( CHD ) or stroke . METHODS A prospect i ve cohort study was conducted among 33,671 healthy Dutch men and women aged 20 - 70 years recruited into the EPIC-NL study during 1993 - 1997 . We used Cox regression adjusted for relevant confounders to estimate the hazard ratios per st and ard deviation increase in score and 95 % confidence intervals ( CI ) of the associations between the dietary guidelines and CVD , CHD and stroke risk . RESULTS After an average follow-up of 12.2 years , 2752 CVD cases were documented , including 1630 CHD cases and 527 stroke cases . We found no association between the HDI ( 0.98 , 95 % CI 0.94 ; 1.02 ) or DHD-index ( 0.96 , 95 % CI 0.92 ; 1.00 ) and CVD incidence . Similar results were found for these guidelines and CHD or stroke incidence . Higher adherence to the DASH diet was significantly associated with a lower CVD ( 0.92 , 95 % CI 0.89 ; 0.96 ) , CHD ( 0.91 , 95 % CI 0.86 ; 0.95 ) , and stroke ( 0.90 , 95 % CI 0.82 ; 0.99 ) risk . CONCLUSION The HDI and the DHD-index were not associated with CVD risk , while the DASH diet was significantly associated with a lower risk of developing CVD , CHD and stroke |
13,459 | 30,229,671 | At present , there is a lack of clear evidence concerning the efficacy of multisession anodal tDCS due to the small number of studies and different measures used . | There have been increasing efforts to investigate the effects of neuromodulation techniques , such as transcranial direct current stimulation ( tDCS ) , on cognitive impairment in dementia and related conditions .
In this systematic review and meta- analysis , we assessed the efficacy of multisession anodal tDCS compared with sham stimulation for improving global cognition and specific cognitive domains in both Alzheimer ’s disease and mild cognitive impairment . | Computer-administered cognitive training ( CT ) tasks are a common component of cognitive remediation treatments . There is growing evidence that transcranial direct current stimulation ( tDCS ) , when given during cognitive tasks , improves performance . This r and omized , controlled trial explored the potential synergistic effects of CT combined with tDCS in healthy participants . Altogether , 60 healthy participants were r and omized to receive either active or sham tDCS administered during training on an adaptive CT task ( dual n-back task ) , or tDCS alone , over 10 daily sessions . Cognitive testing ( working memory , processing speed , executive function , reaction time ) was conducted at baseline , end of the 10 sessions , and at 4-wk follow-up to examine potential transfer effects to non-trained tasks . Altogether , 54 participants completed the study . Over the 10 ' online ' sessions , participants in the active tDCS+CT condition performed more accurately on the CT task than participants who received sham tDCS+CT . The performance enhancing effect , however , was present only during tDCS and did not result in greater learning ( i.e. improvement over sessions ) on the CT task . These results confirm prior reports of enhancement of cognitive function during tDCS stimulation . At follow-up , the active tDCS+CT group , but not the sham tDCS+CT group , showed greater gains on a non-trained test of attention and working memory than the tDCS-only group ( p < 0.01 ) . Although this gain can mainly be attributable to training , this result suggests that active tDCS may have a role in further enhancing outcomes BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Objective : Given the limited effectiveness of pharmacological treatments , non-pharmacological interventions to treat Alzheimer 's disease ( AD ) have gained attention in recent years . The aim of the present study is to investigate the effects of anodal tDCS ( AtDCS ) combined with memory training on face-name associations in an AD patient sample . Methods : Thirty six AD patients were r and omly assigned to one of three study groups : Group 1 , AtDCS plus individualized computerized memory training ; Group 2 , placebo tDCS plus individualized computerized memory training ; Group 3 , AtDCS plus motor training . Results : A general improvement in performance was observed after 2 weeks of memory training . Both the anodal tDCS plus individualized computerized memory training and the placebo tDCS plus individualized computerized memory training groups had significantly improved performances at 2 weeks compared with the AtDCS plus motor training group . Conclusion : Our findings suggest a beneficial effect of individualized memory rehabilitation in AD patients The capacity for transcranial direct current stimulation ( tDCS ) to increase learning and cognition shows promise for the development of enhanced therapeutic interventions . One potential application is the combination of tDCS with cognitive training ( CT ) , a psychological intervention which aims to improve targeted cognitive abilities . We have previously shown that tDCS enhanced performance accuracy , but not skill acquisition , on a dual n-back working memory ( WM ) CT task over repeated sessions . In the current study , we investigated the optimal timing for combining tDCS with the same CT task to enhance within and between session performance outcomes across two daily CT sessions . Twenty healthy participants received in a r and omised order 30 min of anodal tDCS to the left dorsolateral prefrontal cortex immediately before ( ‘ offline ’ tDCS ) and during performance ( ‘ online ’ tDCS ) on a dual n-back WM CT task , in an intra-individual crossover design . Analyses examined within and between session consolidation effects of tDCS on CT performance outcomes . Results showed that ‘ online ’ tDCS was associated with better within session skill acquisition on the CT task , with a significant difference found between conditions the following day . These results suggest that ‘ online ’ tDCS is superior to ‘ offline ’ tDCS for enhancing skill acquisition when combining anodal tDCS with CT . This finding may assist with the development of enhanced protocol s involving the combination of tDCS with CT and other rehabilitation protocol Background : The purpose of this study was to investigate the long-term efficacy of transcranial direct current stimulation ( tDCS ) in the neurorehabilitation of Alzheimer ’s disease ( AD ) . Methods : Thirty-four AD patients were r and omly assigned to three groups : anodal , cathodal , and sham tDCS . Stimulation was applied over the left dorsolateral prefrontal cortex for 25 min at 2 mA , daily for 10 days . Each patient was su bmi tted to the following psychometric assessment s : mini-mental state examination ( MMSE ) and Wechsler adult intelligence scale-third edition at base line , at the end of the 10th sessions and then at 1 and 2 months after the end of the sessions . Motor cortical excitability and the P300 event-related potential were assessed at baseline and after the last tDCS session . Results : Significant treatment group × time interactions were observed for the MMSE and performance IQ of the WAIS . Post hoc comparisons showed that both anodal and cathodal tDCS ( ctDCS ) improved MMSE in contrast to sham tDCS . Whereas , this was only true for ctDCS in the performance IQ . Remarkably , tDCS also reduced the P300 latency , but had no effect on motor cortex excitability . Conclusion : Our findings reveal that repeated sessions of tDCS could not only improve cognitive function but also reduce the P300 latency , which is known to be pathologically increased in AD Background There has been longst and ing interesting in cognitive training for older adults with cognitive impairment . In this study , we will investigate the effects of working memory training , and explore augmentation strategies that could possibly consoli date the effects in older adults with mild neurocognitive disorder . Transcranial direct current stimulation ( tDCS ) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance . As tDCS may also modulate cognitive function through changes in neuroplastic response , it would be adopted as an augmentation strategy for working memory training in the present study . Methods / Design This is a 4-week intervention double-blind r and omized controlled trial ( RCT ) of tDCS . Chinese older adults ( aged 60 to 90 years ) with mild neurocognitive disorder due to Alzheimer ’s disease ( DSM-5 criteria ) would be r and omized into a 4-week intervention of either tDCS-working memory ( DCS-WM ) , tDCS-control cognitive training ( DCS-CC ) , and sham tDCS-working memory ( WM-CD ) groups . The primary outcome would be working memory test – the n-back task performance and the Chinese version of the Alzheimer ’s Disease Assessment Scale – Cognitive Subscale ( ADAS-Cog ) . Secondary outcomes would be test performance of specific cognitive domains and mood . Intention-to-treat analysis would be carried out . Changes of efficacy indicators with time and intervention would be tested with mixed effect models . Discussion This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation , working memory training and dual stimulation in older adults at risk of cognitive decline . It would also examine the tolerability , program adherence and adverse effects of this novel intervention . Information would be helpful for further research of dementia prevention studies .Trial registration ChiCTR-TRC-14005036 Date of registration : 31 July 2014 Background The purpose of this study was to assess the efficacy of transcranial direct current stimulation ( tDCS ) on verbal memory function in patients with Alzheimer ’s disease . Methods We conducted a r and omized , placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days . tDCS was delivered to the left temporal cortex with 2-mA intensity . A total of 25 patients with Alzheimer ’s disease were enrolled in the study . All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer ’s Disease and Related Disorders Association criteria . Twelve patients received active stimulation , and thirteen patients received placebo stimulation . The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test – Second Edition , a st and ardized neuropsychological memory test normalized by age and gender . The secondary outcome measures were the Mini Mental State Examination , clock-drawing test , and Trail Making Test A and B. Results Changes in the California Verbal Learning Test – Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall ( p = 0.270 ) , delayed recall ( p = 0.052 ) , or recognition ( p = 0.089 ) . There were nonsignificant differences in score changes on the Mini Mental State Examination ( p = 0.799 ) , clock-drawing test ( p = 0.378 ) , and Trail Making Test A ( p = 0.288 ) and B ( p = 0.093 ) . Adverse effects were not observed . Conclusions Compared with placebo stimulation , active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer ’s disease . This study differs from previous studies in terms of the stimulation protocol , trial design , and application of st and ardized neuropsychological memory assessment .Trial registration Clinical Trials.gov identifier NCT02518412 . Registered on 10 August 2015 Background and Purpose To investigate whether transcranial direct-current stimulation ( tDCS ) can improve cognition in stroke patients . Methods Forty-five stroke patients ( 20 males and 25 females , average age : 62.7 years ) with cognitive dysfunction were included in this prospect i ve , double-blinded , r and omized case – control study . All patients were right-h and ed and the mean elapsed time after stroke was 39.3 days . Three different treatments groups were used : ( 1 ) anodal stimulation of the left anterior temporal lobe , ( 2 ) anodal stimulation of the right anterior temporal lobe , and ( 3 ) sham stimulation . tDCS was delivered for 30 minutes at 2 mA with 25 cm2 electrodes , five times/week , for a total of 3 weeks , using a Phoresor II Auto Model PM 850 ( IOMED ® ) . The evaluation of cognitive impairment was based on a Computerized Neuropsychological Test ( CNT ) , Korean Mini-Mental State Examination ( K-MMSE ) . The Korean version of the Modified Barthel Index ( K-MBI ) was used to assess activities of daily living functionality . These evaluations were conducted in all patients before and after treatment . Results Each group included 15 patients . Pre-treatment evaluation showed no significant differences between the three groups for any of the parameters . There was significant improvement in the verbal learning test on the CNT in the left anodal stimulation group ( P < 0.05 ) . There were , however , no significant differences in the K-MMSE or K-MBI scores among the three groups . Conclusions These results demonstrated the beneficial effects of anodal tDCS on memory function . Thus , tDCS can successfully be used as a treatment modality for patients with cognitive dysfunction after stroke Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background In spite of treatment advances , HIV infection is associated with cognitive deficits . This is even more important as many persons with HIV infection age and experience age-related cognitive impairments . Both computer-based cognitive training and transcranial direct current stimulation ( tDCS ) have shown promise as interventions to improve cognitive function . In this study , we investigate the acceptability and efficacy of cognitive training with and without tDCS in older persons with HIV . Patients and methods In this single-blind r and omized study , participants were 14 individuals of whom 11 completed study procedures ( mean age = 51.5 years ; nine men and two women ) with HIV-related mild neurocognitive disorder . Participants completed a battery of neuropsychological and self-report measures and then six 20-minute cognitive training sessions while receiving either active or sham anodal tDCS over the left dorsolateral prefrontal cortex . After training , participants completed the same measures . Success of the blind and participant reactions were assessed during a final interview . Assessment s were completed by an assessor blind to treatment assignment . Pre- and post-training changes were evaluated via analysis of covariance yielding estimates of effect size . Results All participants believed that they had been assigned to active treatment ; nine of the 11 believed that the intervention had improved their cognitive functioning . Both participants who felt the intervention was ineffective were assigned to the sham condition . None of the planned tested interactions of time with treatment was significant , but 12 of 13 favored tDCS ( P=0.08 ) . All participants indicated that they would participate in similar studies in the future . Conclusion Results show that both cognitive training via computer game playing and tDCS were well accepted by older persons with HIV infection . Results are suggestive that tDCS may improve cognitive function in persons with HIV infection . Further study of tDCS as an intervention for HIV-related cognitive dysfunction is warranted BACKGROUND Apathy is the most common neuropsychiatric symptom in Alzheimer 's disease ( AD ) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions . To date no effective treatment for apathy has been demonstrated . OBJECTIVE We aim ed to investigate the effects and safety of repetitive transcranial direct current stimulation ( tDCS ) on apathy in moderate AD patients . METHODS Forty patients were r and omized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex ( DLPFC ) . Patients received six sessions of intervention during 2 weeks and were evaluated at baseline , at week 1 and 2 , and after 1 week without intervention . Clinical raters , patients , and caregivers were blinded . The primary outcome was apathy . Global cognition and neuropsychiatric symptoms were examined as secondary outcomes . RESULTS The mean MMSE score at baseline was 15.2 ± 2.9 and the mean Apathy Scale score was 27.7 ± 6.7 . Changes on apathy scores over time were not different between active and sham tDCS ( P = 0.552 for repeated measures ) . Further analyses confirm that changes from baseline did not differ between groups after the sixth session ( active tDCS -1.95 ( 95%CI -3.49 , -0.41 ) ; sham-tDCS -2.05 ( 95%CI -3.68 , -0.42 ) ; P = 0.989 ] . Similarly , tDCS had no effect on secondary outcomes ( P > 0.40 ) . tDCS was well tolerated and not associated with significant adverse effects . CONCLUSION In this adequately powered study for minimal clinical ly significant difference , our findings show that using the parameters we chose for this study , repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD Objective : To estimate rates of progression from mild cognitive impairment ( MCI ) to dementia and of reversion from MCI to being cognitively normal ( CN ) in a population -based cohort . Methods : Participants ( n = 534 , aged 70 years and older ) enrolled in the prospect i ve Mayo Clinic Study of Aging were evaluated at baseline and every 15 months to identify incident MCI or dementia . Results : Over a median follow-up of 5.1 years , 153 of 534 participants ( 28.7 % ) with prevalent or incident MCI progressed to dementia ( 71.3 per 1,000 person-years ) . The cumulative incidence of dementia was 5.4 % at 1 year , 16.1 % at 2 , 23.4 % at 3 , 31.1 % at 4 , and 42.5 % at 5 years . The risk of dementia was elevated in MCI cases ( hazard ratio [ HR ] 23.2 , p < 0.001 ) compared with CN subjects . Thirty-eight percent ( n = 201 ) of MCI participants reverted to CN ( 175.0/1,000 person-years ) , but 65 % subsequently developed MCI or dementia ; the HR was 6.6 ( p < 0.001 ) compared with CN subjects . The risk of reversion was reduced in subjects with an APOE ε4 allele ( HR 0.53 , p < 0.001 ) , higher Clinical Dementia Rating Scale – Sum of Boxes ( HR 0.56 , p < 0.001 ) , and poorer cognitive function ( HR 0.56 , p < 0.001 ) . The risk was also reduced in subjects with amnestic MCI ( HR 0.70 , p = 0.02 ) and multidomain MCI ( HR 0.61 , p = 0.003 ) . Conclusions : MCI cases , including those who revert to CN , have a high risk of progressing to dementia . This suggests that diagnosis of MCI at any time has prognostic value OBJECTIVES Previous studies have shown that anodal transcranial direct current stimulation ( tDCS ) of the left dorsolateral prefrontal cortex ( DLPFC ) led to an improvement of various cognitive functions in patients with Alzheimer dementia , early affected by short-term memory deficits . Since this approach has not been evaluated in the context of vascular dementia , which rather affects the velocity of cognitive responses , we aim ed at improving these functions by applying repetitive sessions of anodal tDCS . METHODS Four 20-minute sessions of 2mA anodal or sham at-home tDCS were applied to the left DLPFC in a single-blinded r and omised study of 21 patients with mild vascular dementia , with parallel-group design . The effect of tDCS on cognitive testing was assessed up to two weeks beyond the stimulation time . RESULTS A similar clinical ly meaningful improvement of various cognitive and behavioral dysfunction characteristics could be observed following either active or sham tDCS , whereas visual recall , and reaction times in the n-back task as well as in the go/no-go test improved only in the active tDCS group . CONCLUSIONS In patients with mild vascular dementia , anodal tDCS of the left DLPFC is able to produce additional effects to cognitive training on visual short-term memory , verbal working memory , and executive control OBJECTIVE To estimate the economic costs of dementia in 2002 using an economic evaluation model for dementia care . METHODS Data were from the Korea National Survey of the Long-Term Care Need ( LTC survey ) ( n = 5058 ) , two prospect i ve 1-year studies [ one clinical trial ( n = 234 ) , one naturalistic community cohort study ( n = 107 ) ] , and two epidemiologic community studies for prevalence of dementia ( n = 1037 + 1481 ) . Daily costs and proportions of different levels of institutional service provided were collected from the LTC survey . Re source use in the community included health care services , social care services , out-of-pocket purchase for self-support , caregiver time and missed work of caregiver . Costs in community were calculated based on re source utilization multiplied by the unit costs for each re source . RESULTS Total annual costs of dementia were estimated to be over 2.4 billion US dollars for 272,000 dementia sufferers . Costs in community represent 96 % of the total annual costs , while costs of informal care and missed work of caregivers were 1.3 billion US dollars , or 55 % of total annual cost . Average annual costs of full time care ( FTC ) and pre-FTC in community LTC were 44 121 US dollars and 13 273 US dollars per person , whereas cost per patient who did not need community LTC was 3,986 US dollars . CONCLUSION Given that the number of dementia sufferers is projected to increase in the near future and that larger part of the costs are subsidized by the government , the economic and social costs of dementia is significant not only for dementia sufferers and their caregivers , but also for society BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . The long pre clinical phase of Alzheimer 's disease provides opportunities for potential disease‐modifying interventions in prodromal stages such as mild cognitive impairment ( MCI ) . Anodal transcranial direct current stimulation ( anodal‐tDCS ) , with its potential to enhance neuroplasticity , may allow improving cognition in MCI In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp . Excitability changes of up to 40 % , revealed by transcranial magnetic stimulation , were accomplished and lasted for several minutes after the end of current stimulation . Excitation could be achieved selectively by anodal stimulation , and inhibition by cathodal stimulation . By varying the current intensity and duration , the strength and duration of the after-effects could be controlled . The effects were probably induced by modification of membrane polarisation . Functional alterations related to post-tetanic potentiation , short-term potentiation and processes similar to postexcitatory central inhibition are the likely c and i date s for the excitability changes after the end of stimulation . Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive , painless , reversible , selective and focal way Transcranial direct current stimulation ( tDCS ) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2 ) has been shown to induce shifts of cortical excitability during and after stimulation . These shifts are polarity-specific with cathodal tDCS result ing in a decrease and anodal stimulation in an increase of cortical excitability . In clinical and cognitive studies , stronger stimulation intensities are used frequently , but their physiological effects on cortical excitability have not yet been explored . Therefore , here we aim ed to explore the effects of 2 mA tDCS on cortical excitability . We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects . Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects , respectively . Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials ( MEPs ) from the right first dorsal interosseous muscle . Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes , and motor thresholds . Intracortical effects of stimulation were obtained by cortical silent period ( CSP ) , short latency intracortical inhibition ( SICI ) and facilitation ( ICF ) , and I wave facilitation . The above-mentioned protocol s were recorded both before and immediately after tDCS in r and omized order . Additionally , single-pulse MEPs , motor thresholds , SICI and ICF were recorded every 30 min up to 2 h after stimulation end , evening of the same day , next morning , next noon and next evening . Anodal as well as cathodal tDCS at 2 mA result ed in a significant increase of MEP amplitudes , whereas 1 mA cathodal tDCS decreased corticospinal excitability . A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed . At 1 mA , cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition . No significant changes were observed in the other protocol s. Sham tDCS did not induce significant MEP alterations . These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation , but might also shift the direction of excitability alterations . This should be taken into account for applications of the stimulation technique using different intensities and duration s in order to achieve stronger or longer lasting after-effects |
13,460 | 30,543,644 | The trend in Sweden is that surgical treatment of PHF is increasing .
Evidence was scarce regarding comparisons of different surgical options for humerus fracture treatment .
The cost of plate fixation of a PHF was at least USD 3900 higher than non-surgical treatment , costs for complications excluded .
There is moderate/low certainty of evidence that surgical treatment of moderately displaced PHF in elderly patients has not been proven to be superior to less costly non-surgical treatment options . | OBJECTIVES The objective of this Health Technology Assessment was to evaluate effectiveness , complications and cost-effectiveness of surgical or non-surgical treatment for proximal , diaphyseal or distal fractures of the humerus in elderly patients .
Secondary objectives were to evaluate the intervention costs per treatment of proximal humerus fractures ( PHF ) and to investigate treatment traditions of PHF in Sweden . | BACKGROUND Previous studies have shown good clinical results in patients with proximal humeral fractures ( PHFs ) treated with locking intramedullary nails or locking plates . Our study compared the clinical and radiographic outcomes in patients with 2- and 3-part surgical neck fractures . METHODS In this prospect i ve , r and omized controlled trial , 72 patients with 2- or 3-part surgical neck PHFs were r and omly assigned to receive fixation with locking intramedullary nails ( nail group ) or locking plates ( plate group ) . The primary outcome was the 12-month Constant-Murley score . The secondary outcomes included the Disabilities of the Arm , Shoulder and H and score , the visual analog scale pain score , the shoulder passive range of motion , the neck-shaft angle , and complication rates . RESULTS There was no significant mean treatment group difference in the Constant-Murley score at 12 months ( 70.3 points for the nail group vs. 71.5 points for the plate group ; P = .750 ) or at individual follow-up assessment s. There were no differences in the 3- , 6- and 12-month Disabilities of the Arm , Shoulder and H and scores , visual analog scale scores , and range of motion , except for the medial rotation at 6 months . The neck-shaft angle was equivalent between the groups at 12 months . There were significant differences over 12 months in total complication rates ( P = .002 ) and reoperation rates ( P = .041 ) . There were no significant differences for the rotator cuff tear rate ( P = .672 ) . CONCLUSION Fixation of PHFs with locking plates or locking intramedullary nails produces similar clinical and radiologic results . Nevertheless , the complication and reoperation rates were higher in the nail group Study Design A prospect i ve cohort study nested in a r and omized controlled trial . Objectives To determine and compare responsiveness and minimal clinical ly important change of the modified Constant score ( CS ) and the Oxford Shoulder Score ( OSS ) . Background The OSS and the CS are commonly used to assess shoulder outcomes . However , few studies have evaluated the measurement properties of the OSS and CS in terms of responsiveness and minimal clinical ly important change . Methods The study included 126 patients who reported having difficulty returning to usual activities 8 to 12 weeks after arthroscopic decompression surgery for subacromial impingement syndrome . The assessment at baseline and at 3 months included the OSS , the CS , and the European Quality of Life-5 Dimensions-3 Level ( EQ-5D-3L ) index . Responsiveness was assessed as follows : by correlation analysis between the change scores of the OSS , CS , and EQ-5D-3L index , and the Patient Global Impression of Change ( PGIC ) scale ; by receiver-operating-characteristic ( ROC ) curve analysis using the PGIC scale as an external anchor ; and by effect-size statistics . Results At 3 months , a follow-up assessment of 112 patients ( 89 % ) was conducted . The change scores of the CS and the OSS were more strongly correlated with the external anchor ( PGIC scale ) than the change score of the EQ-5D-3L index . The areas under the ROC curves exceeded 0.80 for both shoulder scores , with no significant differences between them , and comparable effect-size estimates were observed for the CS and the OSS . Minimal clinical ly important change ROC values were 6 points for the OSS and 11 points for the CS , with upper 95 % cutoff limits of 12 and 22 points , respectively . Conclusion The CS and the OSS were both suitable for assessing improvement after decompression surgery Purpose The aim of this study was to compare the functional outcome , quality of restoration , and complication rate after open reduction and internal fixation ( ORIF ) of displaced or unstable 2- , 3- and 4-part humeral fractures using two different locking plates . Methods The data used in this analysis was prospect ively collected in two large multicentre studies in 15 European Level 1 trauma centres . A total of 318 patients with proximal humeral fractures were treated with ORIF using either the locking proximal humerus plate ( LPHP ) or proximal humeral internal locking system ( PHILOS ) . Outcome measurements included Constant and Neer scores , evaluation of local pain at the fracture site and complications , and radiographic assessment at one year . Results At one year , the mean Constant scores ( relative to the contralateral shoulder ) improved significantly for both groups and were above 80 % for 2- , 3- , and 4-part fractures . A significantly shorter surgical time , less pain at the fracture site , and better functional outcome was achieved by PHILOS-treated patients with 2-part fractures throughout the one-year follow-up month and with 3-part fractures at three months ( p < 0.05 ) . There was no difference between the treatment outcomes for 4-part fractures , and no difference in the complication rates ( p > 0.05 ) . Conclusions PHILOS and LPHP can be considered as useful implants for ORIF of displaced and unstable proximal humeral fractures . There was a slight advantage of the PHILOS system with regard to operative time and functional outcome , especially for the treatment of 2- and 3-part fractures Aims The PROximal Fracture of the Humerus Evaluation by R and omisation ( PROFHER ) r and omised clinical trial compared the operative and non‐operative treatment of adults with a displaced fracture of the proximal humerus involving the surgical neck . The aim of this study was to determine the long‐term treatment effects beyond the two‐year follow‐up . Patients and Methods Of the original 250 trial participants , 176 consented to extended follow‐up and were sent postal question naires at three , four and five years after recruitment to the trial . The Oxford Shoulder Score ( OSS ; the primary outcome ) , EuroQol 5D‐3L ( EQ‐5D‐3L ) , and any recent shoulder operations and fracture data were collected . Statistical and economic analyses , consistent with those of the main trial were applied . Results OSS data were available for 164 , 155 and 149 participants at three , four and five years , respectively . There were no statistically or clinical ly significant differences between operative and non‐operative treatment at each follow‐up point . No participant had secondary shoulder surgery for a new complication . Analyses of EQ‐5D‐3L data showed no significant between‐group differences in quality of life over time . Conclusion These results confirm that the main findings of the PROFHER trial over two years are unchanged at five years OBJECTIVES To compare the outcomes of intramedullary fibular allograft ( IFA ) with locking compression plates ( LCPs ) versus shoulder hemi-arthroplasty ( HA ) in osteoporotic four-part proximal humeral fracture ( PHF ) . METHODS Between January 2010 and December 2012 , totally 60 cases with osteoporotic four-part PHF were enrolled in this study and were r and omly separated into IFA and LCPs group and HA group ( n=30 ) . Additionally , surgery indexes for patients in the two groups , such as Constant-Murley score ( CMS ) , the Disability of Arm , Shoulder and H and ( DASH ) score , individual subject evaluation of the outcomes , plain X-ray , and computer tomography ( CT ) scanning were evaluated and compared . RESULTS CMS , DASH score , activities of daily living ( ADL ) , and range of motion ( ROM ) were statistically higher in the IFA and LCPs group than those in the HA group at the last follow-up , whereas the pain were obviously lower than that in the HA group . Besides , patients in the IFA and LCPs group had higher abduction , external rotation with elbow , strength , and satisfactory rating compared with HA group at the last follow-up . However , one case developed avascular necrosis ( AVN ) , one case encountered screw perforation , and one case experienced varus displacement in the IFA and LCPs group , while there were 2 , 4 , and 2 cases suffered from superficial infection , shoulder stiffness , tuberosity migration in the HA group , respectively . CONCLUSION IFA with LCP have an advantage in functional outcomes than shoulder HA . LEVEL OF EVIDENCE Level II . Prospect i ve cohort study Abstract Background Surgical treatment for displaced proximal humeral fractures is widely used . However , there are very few r and omized controlled studies comparing surgical treatment to conservative treatment , and the evidence is debated . The aim of this study was to describe patients with displaced proximal humeral fractures in a 2-years extension of a r and omized controlled trial , their functional outcome and quality of life . Material s and methods Patients from a single-center r and omized controlled study of fifty patients aged 60 or above with displaced proximal humeral fracture ( AO/OTA group B2 or C2 ) were r and omized to surgical or conservative treatment . Surgery was performed with an angular stable implant . The main outcome was Constant score at 2-year follow-up . Secondary outcomes were an ASES self- assessment form , the 15D quality of life assessment and radiographs at 2 years . Results A marked improvement of shoulder function and health-related quality of life for both surgically and conservatively treated patients occurs between 6 and 12 months . Almost no change was observed between 1 and 2 year . There were no significant differences between the two treatments at 2-year follow-up . Conclusions In this r and omized controlled trial , surgical treatment proved no better results than conservative treatment for patients with displaced proximal humeral fracture at 2-year follow-up Purpose The purpose of this study was to evaluate the clinical benefit of medial support screws for locking plating of proximal humerus fractures . Methods Seventy-two consecutive patients underwent prospect i ve treatment for proximal humerus fractures with locking plates between October 2007 and September 2008 . Sixty-eight patients accomplished a mean 30.8-month follow-up and were r and omized into two groups : 39 patients were treated with only a locking plate and were classified in the –MSS ( medial support screw ) group , and 29 patients were included in the + MSS group , which were fixed with additional medial support screws . Clinical and radiological investigations were performed in both groups . Results The fractures united at an average of 13.6 weeks after final surgery . Comparably better shoulder function recovery was achieved in the + MSS group with regard to the Constant shoulder score ( P = 0.01 ) , with the respective excellent and good rates of 79 % and 62 % . Eleven patients developed various complications . A statistical difference ( P = 0.036 ) was observed regarding the failure rate ( 23.1 % in the −MSS group vs. 3.4 % in the + MSS group ) . The early loss of fixation was related to higher age ( P < 0.001 ) and less initial neck-shaft angle ( NSA ) ( P = 0.011 ) of the patients . However , bone mineral density was not significantly associated with loss of fixation ( P = 0.076 ) . Although no difference was found in all types of the fractures between the + MSS and −MSS groups regarding immediate postoperative NSA , we observed a significantly lower final NSA in the −MSS group and greater secondary angle loss in the subgroup of Neer three-part ( P = 0.033 and 0.015 , respectively ) and four-part fractures ( P = 0.043 and 0.027 ) . Conclusions Anatomical reduction can substantially decrease the risk of postoperative failure in locking plating of proximal humerus fractures . Medial support for proximal humerus fractures seems to have no benefits in Neer two-part fractures . However , the additional medial support screws inserted into the medio-inferior region of the humeral head may help to enhance mechanical stability in complex fractures and allow for better maintenance of reduction Abstract Background Fractures of the distal radius are extremely common injuries in adults . However , the optimal management remains controversial . In general , fractures of the distal radius are treated non-operatively if the bone fragments can be held in anatomical alignment by a plaster cast or orthotic . However , if this is not possible , then operative fixation is required . There are several operative options but the two most common in the UK , are Kirschner-wire fixation ( K-wires ) and volar plate fixation using fixed-angle screws ( locking-plates ) . The primary aim of this trial is to determine if there is a difference in the Patient-Reported Wrist Evaluation one year following K-wire fixation versus locking-plate fixation for adult patients with a dorsally-displaced fracture of the distal radius . Methods / design All adult patients with an acute , dorsally-displaced fracture of the distal radius , requiring operative fixation are potentially eligible to take part in this study . A total of 390 consenting patients will be r and omly allocated to either K-wire fixation or locking-plate fixation . The surgery will be performed in trauma units across the UK using the preferred technique of the treating surgeon . Data regarding wrist function , quality of life , complications and costs will be collected at six weeks and three , six and twelve months following the injury . The primary outcome measure will be wrist function with a parallel economic analysis . Discussion This pragmatic , multi-centre trial is due to deliver results in December 2013.Trial registration Current Controlled Trials IS RCT N31379280 UKCRN portfolio ID Fifty patients with complex distal radial fractures treated by primary external fixation were compared with 50 with similar fractures treated by closed medullary pinning . All the patients had Frykman type-VIII injuries . The two groups were similar in regard to demographic characteristics and the method of treatment was r and omly chosen . All the fractures healed within three months . In the external fixation group 92 % of fractures healed in excellent alignment as did 88 % of the medullary pinning group . Both groups had similar results with respect to eventual function , range of motion , and grip strength . Complications and complaints were fewer and the estimated costs of treatment were significantly less in the medullary pinning group . More patients were satisfied with closed medullary fixation than with external fixation Objectives The objective of this study was to perform a meta- analysis of all r and omised controlled trials ( RCTs ) comparing surgical and non-surgical management of fractures of the proximal humerus , and to determine whether further analyses based on complexity of fracture , or the type of surgical intervention , produced disparate findings on patient outcomes . Methods A systematic review of the literature was performed identifying all RCTs that compared surgical and non-surgical management of fractures of the proximal humerus . Meta- analysis of clinical outcomes was performed where possible . Subgroup analysis based on the type of fracture , and a sensitivity analysis based on the type of surgical intervention , were also performed . Results Seven studies including 528 patients were included . The overall meta- analysis found that there was no difference in clinical outcomes . However , subgroup and sensitivity analyses found improved patient outcomes for more complex fractures managed surgically . Four-part fractures that underwent surgery had improved long-term health utility scores ( mean difference , MD 95 % CI 0.04 to 0.28 ; p = 0.007 ) . They were also less likely to result in osteoarthritis , osteonecrosis and non/malunion ( OR 7.38 , 95 % CI 1.97 to 27.60 ; p = 0.003 ) . Another significant subgroup finding was that secondary surgery was more common for patients that underwent internal fixation compared with conservative management within the studies with predominantly three-part fractures ( OR 0.15 , 95 % CI 0.04 to 0.63 ; p = 0.009 ) . Conclusion This meta- analysis has demonstrated that differences in the type of fracture and surgical treatment result in outcomes that are distinct from those generated from analysis of all types of fracture and surgical treatments grouped together . This has important implication s for clinical decision making and should highlight the need for future trials to adopt more specific inclusion criteria . Cite this article : S. Sabharwal , N. K. Patel , D. Griffiths , T. Athanasiou , C. M. Gupte , P. Reilly . Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus : Findings of a meta- analysis Bone Joint Res 2016;5:470–480 . DOI : 10.1302/2046 - 3758.510.2000638 Objectives The PROximal Fracture of the Humerus : Evaluation by R and omisation ( PROFHER ) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures . The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics , injury characteristics and the nature of the surgical treatment . Methods A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015 . Data gathered for the 110 patients included patient demographics , injury characteristics , mode of surgical fixation , the grade of operating surgeon and the cost of the surgical implants . Results A majority of the patients were female ( 66 % , 73 of 110 ) . The mean patient age was 62 years ( range 18 to 89 ) . A majority of patients met the inclusion criteria for the PROFHER trial ( 75 % , 83 of 110 ) . Plate fixation was the most common mode of surgery ( 68 % , 75 patients ) , followed by intramedullary fixation ( 12 % , 13 patients ) , reverse shoulder arthroplasty ( 10 % , 11 patients ) and hemiarthroplasty ( 7 % , eight patients ) . The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases ( 91 % , 100 patients ) . Implant costs for plate fixation were significantly less than both hemiarthroplasty ( p < 0.05 ) and reverse shoulder arthroplasty ( p < 0.0001 ) . Implant costs for intramedullary fixation were significantly less than plate fixation ( p < 0.01 ) , hemiarthroplasty ( p < 0.0001 ) and reverse shoulder arthroplasty ( p < 0.0001 ) . Conclusions Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may , therefore , have been effectively managed non-operatively . Cite this article : Mr B. J. F. Dean . A review of current surgical practice in the operative treatment of proximal humeral fractures : Does the PROFHER trial demonstrate a need for change ? Bone Joint Res 2016;5:178–184 . DOI : 10.1302/2046 - 3758.55.2000596 BACKGROUND The aim of the study was to report the 2-year outcome after a displaced 3-part fracture of the proximal humerus in elderly patients r and omized to treatment with a locking plate or nonoperative treatment . PATIENTS AND METHODS We included 60 patients , mean age 74 years ( range , 56 - 92 ) , 81 % being women . The main outcome measures were the Constant and Disabilities of the Arm , Shoulder and H and ( DASH ) scores and the health-related quality of life ( HRQoL ) according to the EQ-5D . RESULTS At the final 2-year follow-up , the results for range of motion ( ROM ) , function and HRQoL were all in favor of the locking plate group . The mean flexion in the locking plate group was 120 ° compared to 111 ° in the nonoperative group ( P = .36 ) and the mean abduction was 114 ° compared to 106 ° ( P = .28 ) . The corresponding values for the Constant score were 61 versus 58 ( P = .64 ) , for DASH 26 versus 35 ( P = .19 ) , and the mean EQ-5D ( index ) score was 0.70 compared to 0.59 ( P = .26 ) . In spite of good primary reduction in 86 % of the fractures in the locking plate group , 13 % of the patients had a fracture complication requiring a major reoperation and 17 % had a minor reoperation . CONCLUSION The results of our study indicate an advantage in functional outcome and HRQoL in favor of the locking plate compared to nonoperative treatment in elderly patients with a displaced 3-part fracture of the proximal humerus , but at the cost of additional surgery in 30 % of the patients BACKGROUND This study evaluated the internal and external responsiveness of the EuroQol EQ-5D ( EuroQol Group , Rotterdam , The Netherl and s ) health status component , defined as the instrument 's ability to capture clinical ly important changes in patients with a proximal humeral fracture within the context of a prospect i ve study . MATERIAL S AND METHODS To evaluate the internal responsiveness of the EQ-5D , the observed change and the st and ardized response mean ( SRM ) in relation to the change in the EQ-5D(index ) score were calculated . To calculate external responsiveness , an external criterion ( EC ) was constructed by using the Disabilities of the Arm , Shoulder and H and ( DASH ) score . Receiver operating characteristic ( ROC ) curves and logistic regression analysis were used in the evaluation . RESULTS The mean change score from prefracture status to the 4-month follow-up for the EQ-5D was -20.9 and the corresponding SRM was 0.90 , indicating good internal responsiveness . The clearly improved or clearly deteriorated patients according to the EC ( DASH ) reported change scores of approximately 12 points in the EQ-5D , corresponding to moderately strong SRMs , which , together with the results of the ROC analyses and logistic regression , indicated a good external responsiveness . CONCLUSION The EQ-5D displayed good internal and external responsiveness in patients with proximal humeral fractures and can be recommended for use as a quality of life measure in patients with this particular injury Objectives : To evaluate complications after distal radius fracture surgery . Design : Prospect i ve registry study . Setting : Nationwide registry study . Patients : A total of 36,618 patients who underwent surgery because of a distal radius fracture during the period from January 1 , 2001 to December 31 , 2009 were followed from the date of operation until the occurrence of either reoperation , a new distal radius fracture , death , or December 31 , 2010 , whichever occurred first . Main Outcome Measurement : The occurrence of reoperations after different surgical methods is presented as proportions , incidence rates , and in a Kaplan – Meier survival analysis curve . Types and distributions of complications are presented for pinning , external fixation ( EF ) , and plating , respectively . Results : The incidence of reoperation after fracture surgery using EF , pins , and plating was 100 [ 95 % confidence interval ( CI ) : 93–107 ] , 140 ( 95 % CI : 127–153 ) , and 222 ( 95 % CI : 207–237 ) per 10,000 person years , respectively . After stratified analysis adjusting for age and gender , the differences remained significant when comparing plating with EF ( P = 0.001 ) and pinning ( P = 0.01 ) . Pinning and EF patients displayed an earlier onset of the complications when compared with plated patients . Conclusions : The incidence of reoperation was higher for patients treated with a plate than for patients treated with pins or EF . The timing of the reoperations differed in that pinning and EF patients displayed an earlier onset when compared with plated patients . Level of Evidence : Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence BACKGROUND Proximal humeral fractures account for 5 - 6 % of all fractures in adults . There is considerable variation in whether or not surgery is used in the management of displaced fractures involving the surgical neck . OBJECTIVE To evaluate the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment of the majority of displaced fractures of the proximal humerus involving the surgical neck in adults . DESIGN A pragmatic parallel-group multicentre r and omised controlled trial with an economic evaluation . Follow-up was for 2 years . SETTING Recruitment was undertaken in the orthopaedic departments of 33 acute NHS hospitals in the UK . Patient care pathways included outpatient and community-based rehabilitation . PARTICIPANTS Adults ( aged ≥ 16 years ) presenting within 3 weeks of their injury with a displaced fracture of the proximal humerus involving the surgical neck . INTERVENTIONS The choice of surgical intervention was left to the treating surgeons , who used techniques with which they were experienced . Non-surgical treatment was initial sling immobilisation followed by active rehabilitation . Provision of rehabilitation was comparable in both groups . MAIN OUTCOME MEASURES The primary outcome was the Oxford Shoulder Score ( OSS ) assessed at 6 , 12 and 24 months . Secondary outcomes were the 12-item Short Form health survey , surgical and other shoulder fracture-related complications , secondary surgery to the shoulder or increased/new shoulder-related therapy , medical complications during inpatient stay and mortality . European Quality of Life-5 Dimensions data and treatment costs were also collected . RESULTS The mean age of the 250 trial participants was 66 years and 192 ( 77 % ) were female . Independent assessment using the Neer classification identified 18 one-part fractures , 128 two-part fractures and 104 three- or four-part fractures . OSS data were available for 215 participants at 2 years . We found no statistically or clinical ly significant differences in OSS scores between the two treatment groups ( scale 0 - 48 , with a higher score indicating a better outcome ) over the 2-year period [ difference of 0.75 points in favour of the surgery group , 95 % confidence interval ( CI ) -1.33 to 2.84 ; p = 0.479 ; data from 114 surgery and 117 non-surgery participants ] or at individual time points . We found no statistically significant differences between surgical and non-surgical group participants in SF-12 physical or mental component summary scores ; surgical or shoulder fracture-related complications ( 30 vs. 23 respectively ) ; those undergoing further shoulder-related therapy , either surgery ( 11 vs. 11 respectively ) or other therapy ( seven vs. four respectively ) ; or mortality ( nine vs. five respectively ) . The base-case economic analysis showed that , at 2 years , the cost of surgical intervention was , on average , £ 1780.73 more per patient ( 95 % CI £ 1152.71 to £ 2408.75 ) than the cost of non-surgical intervention . It was also slightly less beneficial in terms of utilities , although this difference was not statistically significant . The net monetary benefit associated with surgery is negative . There was only a 5 % probability of surgery achieving the criterion of costing < £ 20,000 to gain a quality -adjusted life-year , which was confirmed by extensive sensitivity analyses . CONCLUSIONS Current surgical practice does not result in a better outcome for most patients with displaced fractures of the proximal humerus involving the surgical neck and is not cost-effective in the UK setting . Two areas for future work are the setting up of a national data base of these fractures , including the collection of patient-reported outcomes , and research on the best ways of informing patients with these and other upper limb fractures about initial self-care . TRIAL REGISTRATION Current Controlled Trials IS RCT N50850043 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 24 . See the NIHR Journals Library website for further project information Objectives : To evaluate the results of plate osteo synthesis using either polyaxial or nonpolyaxially locked screw – plate systems in proximal humeral fractures in the elderly . Design : Prospect i ve , r and omized . Setting : Level I trauma center . Methods : Fifty-six patients ( older than 60 years ) with isolated , displaced three- and four-part fractures were included . Twenty-five patients ( median age , 75.5 years ) were r and omized to a polyaxial locking screw plate ( Group 1 ) , whereas 31 patients ( median age , 72 years ) were treated with a locking screw plate ( Group 2 ) . Follow-up evaluations were performed 3 , 6 , and 12 months postoperatively using the Simple Shoulder Test , Disabilities of the Arm , Shoulder and H and score , and Constant score as well as radiographs . The results and the complications were compared between both groups . Results : Forty-eight patients were available for follow-up ( Group 1 , 20 of 25 ; Group 2 , 28 of 31 ) . The Simple Shoulder Test , Disabilities of the Arm , Shoulder and H and , and Constant score improved significantly from 3 to 12 months and did not differ between groups . Twelve months after the index procedure , the Simple Shoulder Test score was 8.6 ± 3.2 points in Group 1 and 9.7 ± 1.8 points in Group 2 . The Disabilities of the Arm , Shoulder and H and score was 17.8 ± 16.2 in Group 1 and 15.7 ± 11.8 in Group 2 . The mean Constant score amounted to 73 % ± 17 % in Group 1 and 81 % ± 13 % in Group 2 . There were six complications in Group 1 and eight in Group 2 . Conclusions : Both the functional outcomes and the rate of complications after polyaxial locked plate osteo synthesis of proximal humeral fractures in elderly patients were comparable to those treated with nonpolyaxial implants . Despite the theoretical advantages of polyaxial locked plating in proximal humerus fractures , this study could not show a verifiable clinical advantage of these plates Background Four-part fractures of the proximal humerus account for 3 % of all humeral fractures and are regarded as the most difficult fractures to treat in the elderly . Various authors recommend nonoperative treatment or hemiarthroplasty , but the literature is unclear regarding which provides better quality of life and function . Questions / purpose sWe therefore performed a r and omized controlled trial to compare ( 1 ) function , ( 2 ) strength , and ( 3 ) pain and disability in patients 65 years and older with four-part humeral fractures treated either nonoperatively or with hemiarthroplasty . Methods We r and omly allocated 50 patients to one of the two approaches . There were no differences in patient demographics between the two groups . The Constant-Murley score was the primary outcome measure . Secondary outcome measures were the Simple Shoulder Test , abduction strength test as measured by a myometer , and VAS scores for pain and disability . All patients were assessed at 12 months . Results We found no between-group differences in Constant-Murley and Simple Shoulder Test scores at 3- and 12-months followup . Abduction strength was better at 3 and 12 months in the nonoperatively treated group although the nonoperatively treated patients experienced more pain at 3 months ; this difference could not be detected after 12 months . Conclusions We observed no clear benefits in treating patients 65 years or older with four-part fractures of the proximal humerus with either hemiarthroplasty or nonoperative treatment . Level of Evidence Level I , therapeutic study . See Instructions for Authors for a complete description of levels of evidence OBJECTIVE To investigate the effect of treatment of osteoporotic proximal humeral fractures in elderly patients with a proximal humeral internal locking system ( PHILOS ) and minimally invasive injectable graft ( MIIG ) . METHODS Patients who conformed to the inclusion criteria were r and omly divided into two groups : group A ( 21 cases ) were treated with PHILOS alone and group B ( 29 cases ) were treated with PHILOS augmentation plus minimally invasive injectable graft ( MIIG ) X3 Hivisc . Postoperative follow-up was performed regularly to check for complications , reduction loss and fracture healing by imaging . Shoulder joint function was scored and clinical results evaluated according to the Neer scoring system . RESULTS All patients were followed-up and achieved fracture healing . The complication rate in group A ( six cases ) was greater than in group B ( one case ) , the differences being statistically significant . The reduction loss in group A ( 2.9 ± 0.4 mm ) was greater than in group B ( 1.5 ± 0.3 mm ) , this difference also being statistically significant . According to the Neer system , the excellent and good rate was 76.2 % in group A and 82.8 % in group B. CONCLUSION PHILOS using MIPPO and augmented with MIIG X3 Hivisc produces satisfactory clinical results in aged patients with osteoporotic proximal humeral fractures and the method has advantages such as relatively minor trauma , stable fixation , fewer complications , and better joint function AIMS A pragmatic multicentre r and omised controlled trial ( PROFHER ) was conducted in United Kingdom National Health Service ( NHS ) hospitals to evaluate the clinical effectiveness and cost effectiveness of surgery compared with non-surgical treatment for displaced fractures of the proximal humerus involving the surgical neck in adults . METHODS A cost utility analysis from the NHS perspective was performed . Differences between surgical and non-surgical treatment groups in costs and quality adjusted life years ( QALYs ) at two years were used to derive an estimate of the cost effectiveness of surgery using regression methods . RESULTS Patients r and omised to receive surgical intervention accumulated mean greater costs and marginally lower QALYs than patients r and omised to non-surgery . The surgical intervention cost a mean of £ 1758 more per patient ( 95 % confidence intervals ( CI ) £ 1126 to £ 2389 ) . Total QALYs for the surgical group were smaller than those for non-surgery -0.0101 ( 95 % CI -0.13 to 0.11 ) . The probability of surgery being cost effective was less than 10 % given the current NICE willingness to pay at a threshold of £ 20 000 for an additional QALY . The results were robust to sensitivity analyses . DISCUSSION The results suggest that current surgical treatment is not cost effective for the majority of displaced fractures of the proximal humerus involving the surgical neck in the United Kingdom 's NHS . TAKE HOME MESSAGE The results of this trial do not support the trend of increased surgical treatment for patients with displaced fractures of the proximal humerus involving the surgical neck within the United Kingdom NHS BACKGROUND Intramedullary nailing of displaced proximal humerus fractures is an attractive option in the elderly patient . However , in recent reports , some existing intramedullary nails have shown high rate of complications , so new design s are being developed . The objective of the present study is to report on outcomes and complications when comparing a straight to a curvilinear nail design . METHODS We prospect ively include 54 patients with Neer 's 2- or 3-part proximal humerus fractures . Two were lost to follow-up , 26 were surgically treated with a new straight humeral nail ( MultiLoc , Synthes ) mean age 69 ( range , 47 - 87 years ) , and 26 with a curvilinear nail ( Polarus , Acumed ) mean age 71 ( range , 38 - 89 years ) . At final follow-up ( average 14 months ) , patients underwent a clinical and radiographic evaluation . Clinical outcome was assessed with the adjusted Constant score . RESULTS All but 1 fracture went on to radiographic union . Mean Constant score in the Polarus nail was 72.7 ± 16.0 and 83.3 ± 16.7 in the MultiLoc ( P = .246 ) . Symptoms related with rotator cuff disease were present in 19/26 patients ( 73 % ) and in 9/26 ( 34.6 % ) , respectively ( P = .001 ) . The mean neck-shaft angle at final follow-up was 135 ° in the MultiLoc group and 130 ° in the Polarus group ( P > .05 ) . Reoperation rate was 42 % for Polarus and 11.5 % for MultiLoc . CONCLUSION Straight intramedullary nails had a comparable union rate to an accepted curvilinear design , with a much lower incidence of complications . Rotator cuff pain and dysfunction can be minimized with the use of newer generation straight nails This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Objectives : To assess the treatment preferences of orthopaedic surgeons for displaced three- and four-part proximal humerus fractures . Design : Cross-sectional survey . Setting : Academic and nonacademic institutions across Canada . Patients / Participants : Members of the Canadian Orthopedic Trauma Society and the Joint Orthopedic Initiative for National Trials of the Shoulder . Intervention : Mailed question naire requesting treatment preferences for eight clinical scenarios with differing patient age ( 45 or 68 years ) , patient activity level ( active/healthy or frail/low dem and ) , and fracture type ( Neer III or IV ) . Main Outcome Measurements : Treatment preference for each clinical scenario using a five-level ordinal scale . Results : Thirty-six completed question naires were included in the analysis . Internal fixation , particularly with locking plates , was the preferred treatment for young patients regardless of fracture type or activity level . Treatment preferences for elderly patients demonstrated the least consensus . Hemiarthroplasty , locked plating , and nonoperative management all received high treatment preferences depending on the fracture type and activity level of the patient . Conclusions : This survey quantifies treatment preferences for a wide range of strategies used to manage displaced proximal humerus fractures . The results of this survey suggest that , despite consulting orthopaedic trauma and shoulder experts , a wide range of treatments appear acceptable for displaced fractures in the elderly . Prospect i ve clinical trials are needed to guide effective treatment decisions for these patients Introduction Aim of this study was to evaluate outcomes of operative as compared to conserveative treatment for two-part humerus fractures at the surgical neck . Methods Data from a prospect i ve multi-centre cohort study on four treatment options ( conservative treatment and three implants , i.e. LPHP , PHILOS and PHN ) for proximal humerus fractures were evaluated in this post hoc analysis . All patients with two-part fractures of the surgical neck ( AO types A2 , n = 54 and A3 , n = 110 ) were identified and included for the analysis . All operatively treated patients were gathered and compared to those receiving conservative treatment . Primary outcome parameters were pain , range of motion and absolute and relative Constant scores at 3 , 6 and 12 months following injury and coronal plane alignment at 12 months . Results Operative ( n = 133 ) and non-operative ( n = 31 ) groups were comparable with regard to all parameters assessed including mean age ( 62.9 vs. 65.6 , P = 0.479 ) , gender ( 27 vs. 29 % male , P = 0.826 ) and fracture distribution ( 65 vs. 77 % A3 type , P = 0.207 ) . 26 of the 31 conservatively treated and 103 of the 133 operatively treated patients ( 84 and 77 % , respectively ) were available for final follow-up . There was a continuous improvement for all outcome parameters in both treatment groups ( P < 0.001 ) . Operative treatment result ed in a more effective reduction of pain at 3 months ( 51 vs. 76 % reporting pain at fracture site , P = 0.03 ) and a reduction of coronal plane malalignment . Both range of motion and Constant scores were , however , comparable in both groups at all follow-up visits . Relative and absolute Constant scores were generally excellent at final follow-up ( 74 vs. 74 , P = 0.528 and 89 vs. 91 , P = 0.494 , respectively ) . Conclusions Both non-operative treatment and operative treatment using modern implants ( LPHP , PHILOS and PHN ) can be considered safe and effective treatment options for two-part fractures of the proximal humerus . Operative treatment may result in better range of motion and reduced pain in the early postoperative course of treatment Abstract The optimal surgical treatment of displaced proximal humeral fractures is controversial . New implants providing angular stability have been introduced to maintain the intraoperative reduction . In a multi-institutional study , we prospect ively enrolled and followed 152 patients with unilateral displaced and unstable proximal humeral fractures treated either with an ante grade angular and sliding stable proximal interlocking nail or an angular stable plate . Fractures were classified according to the Neer four-segment classification . Clinical , functional , and radiographic followups were performed 3 , 6 , and 12 months after surgery . Absolute and relative ( to the contralateral shoulder ) Constant-Murley scores were used to assess postoperative shoulder function . Using age , gender , and fracture type , we identified 76 pairs ( 152 patients ) for a matched-pairs analysis . Relative Constant-Murley scores 12 months after treatment with an angular and sliding stable nail and after plate fixation were 81 % and 77 % , respectively . We observed no differences between the two groups . Stabilization of displaced proximal humeral fractures with either an angular stable intramedullary or an extramedullary implant seems suitable with both surgical treatment options . Level of Evidence : Level III , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence OBJECTIVE This study aims to evaluate the costs and health outcome for surgical and conservative treatment of displaced proximal humeral fractures . DESIGN This study is a r and omised controlled trial . PARTICIPANTS This study included 50 patients aged 60 or older admitted to hospital with a severely displaced three- or four-part fracture . INTERVENTIONS The patients were treated surgically with an angular stable interlocking implant ( 25 patients ) or conservative treatment ( 25 patients ) . MAIN OUTCOME MEASURE The outcomes measured included quality -adjusted life years ( QALYs ) and societal costs . RESULTS At 12 months ' follow-up , the mean difference in the number of QALYs was 0.027 ( 95 % confidence interval (CI)=-0.025 , 0.078 ) while the mean difference in total health-care costs was 597 euro in favour of surgery ( 95 % CI=-5291 , 3777 ) . CONCLUSION There was no significant difference in QALYs or costs between surgical and conservative treatment of severe displaced proximal humeral fractures BACKGROUND There is no consensus on what type of arthroplasty is best for the treatment of complex proximal humeral fractures in elderly patients . The purpose of this prospect i ve study was to compare the outcomes of reverse shoulder arthroplasty ( RSA ) and hemiarthroplasty ( HA ) . METHODS Sixty-two patients older than 70 years were r and omized to RSA ( 31 patients ) and HA ( 31 patients ) . One HA patient died at 1 year , and she was excluded . The mean follow-up was 28.5 months ( range , 24 - 49 months ) . RESULTS Compared with HA patients , RSA patients had significantly higher ( P = .001 ) mean University of California-Los Angeles ( 29.1 vs 21.1 ) and Constant ( 56.1 vs 40.0 ) scores , forward elevation ( 120.3 ° vs 79.8 ° ) , and abduction ( 112.9 ° vs 78.7 ° ) but no difference in internal rotation ( 2.7 ° vs 2.6 ° ; P = .91 ) . The Disabilities of the Arm , Shoulder , and H and score was higher in the HA patients ( 17 vs 29 ; P = .001 ) . In the HA group , 56.6 % of tuberosities healed and 30 % resorbed . Patients with failure of tuberosities had significantly worse functional outcomes . There were 2 complications ( intraoperative humeral fracture and superficial infection ) . One patient was manipulated under general anesthesia because of postoperative stiffness . Six patients with HA had proximal migration that required revision to RSA . In the RSA group , 64.5 % of tuberosities healed and 13.2 % resorbed . Functional outcome was irrespective of healing of the tuberosities . Notching was observed in only 1 RSA patient . One patient developed a hematoma and another a deep infection requiring a 2-stage revision to another RSA . CONCLUSION RSA result ed in better pain and function and lower revision rate . Revision from HA to RSA does not appear to improve outcomes Abstract This is a r and omised study to compare two types of osteo synthesis to mobilise wrists after distal fractures of the radius . Inclusion criteria were Older type 2 and 3 fractures . External fixation was managed with Hoffmann II compact non-bridging . Internal fixation was managed with Micronail . Patients were followed up for 12 weeks . The primary outcome was the results of the disabilities of arm , shoulder and h and ( DASH ) question naire . The secondary outcomes were answers to the patient-rated wrist evaluation ( PRWE ) , grip strength , satisfaction , radial length , and volar tilt . Thirty patients were r and omised to have external fixation and 31 to have internal fixation . There were no significant differences in DASH score . Internal fixation gave significantly better grip strength at five ( p = 0.00 ) and 12 weeks ( p = 0.03 ) . The operating time was significantly shorter ( p = 0.00 ) when non-bridging external fixation was used , and there were minor radiological differences . An activity-based costing analysis showed that external fixation cost three times more overall We conducted a prospect i ve , r and omized , controlled trial to compare functional outcomes , complications , and reoperation rates in elderly patients with displaced intra-articular , distal humeral fractures treated with open reduction-internal fixation ( ORIF ) or primary semiconstrained total elbow arthroplasty ( TEA ) . Forty-two patients were r and omized by sealed envelope . Inclusion criteria were age greater than 65 years ; displaced , comminuted , intra-articular fractures of the distal humerus ( Orthopaedic Trauma Association type 13C ) ; and closed or Gustilo grade I open fractures treated within 12 hours of injury . Both ORIF and TEA were performed following a st and ardized protocol . The Mayo Elbow Performance Score ( MEPS ) and Disabilities of the Arm , Shoulder and H and ( DASH ) score were determined at 6 weeks , 3 months , 6 months , 12 months , and 2 years . Complication type , duration , management , and treatment requiring reoperation were recorded . An intention-to-treat analysis and an on-treatment analysis were conducted to address patients r and omized to ORIF but converted to TEA intraoperatively . Twenty-one patients were r and omized to each treatment group . Two died before follow-up and were excluded from the study . Five patients r and omized to ORIF were converted to TEA intraoperatively because of extensive comminution and inability to obtain fixation stable enough to allow early range of motion . This result ed in 15 patients ( 3 men and 12 women ) with a mean age of 77 years in the ORIF group and 25 patients ( 2 men and 23 women ) with a mean age of 78 years in the TEA group . Baseline demographics for mechanism , classification , comorbidities , fracture type , activity level , and ipsilateral injuries were similar between the 2 groups . Operative time averaged 32 minutes less in the TEA group ( P = .001 ) . Patients who underwent TEA had significantly better MEPSs at 3 months ( 83 vs 65 , P = .01 ) , 6 months ( 86 vs 68 , P = .003 ) , 12 months ( 88 vs 72 , P = .007 ) , and 2 years ( 86 vs 73 , P = .015 ) compared with the ORIF group . Patients who underwent TEA had significantly better DASH scores at 6 weeks ( 43 vs 77 , P = .02 ) and 6 months ( 31 vs 50 , P = .01 ) but not at 12 months ( 32 vs 47 , P = .1 ) or 2 years ( 34 vs 38 , P = .6 ) . The mean flexion-extension arc was 107 degrees ( range , 42 degrees -145 degrees ) in the TEA group and 95 degrees ( range , 30 degrees -140 degrees ) in the ORIF group ( P = .19 ) . Reoperation rates for TEA ( 3/25 [ 12 % ] ) and ORIF ( 4/15 [ 27 % ] ) were not statistically different ( P = .2 ) . TEA for the treatment of comminuted intra-articular distal humeral fractures result ed in more predictable and improved 2-year functional outcomes compared with ORIF , based on the MEPS . DASH scores were better in the TEA group in the short term but were not statistically different at 2 years ' follow-up . TEA may result in decreased reoperation rates , considering that 25 % of fractures r and omized to ORIF were not amenable to internal fixation . TEA is a preferred alternative for ORIF in elderly patients with complex distal humeral fractures that are not amenable to stable fixation . Elderly patients have an increased baseline DASH score and appear to accommo date to objective limitations in function with time Background There is a lack of consensus regarding optimal surgical management of displaced and unstable three-part proximal humeral fractures . Questions / purpose sThe objective of this prospect i ve observational study was to compare the clinical and radiologic outcomes of plate versus nail fixation of three-part proximal humeral fractures . Patients and Methods Two hundred eleven patients with unstable three-part proximal humeral fractures were treated with ORIF using plate ( PHILOS [ proximal humeral interlocking system]/LPHP [ locking proximal humerus plate ] ) or nail ( PHN [ proximal humeral nail ] ) osteo synthesis . Outcome measurements included pain , Constant and Murley and Neer scores , and the occurrence of complications at 3 , 6 , and 12 months postsurgery . Regression analysis and the likelihood ratio test were used to evaluate differences between the cohorts . Results Throughout the 1-year followup period the Constant and Murley scores improved significantly for both cohorts ; there was no significant difference between the nail group compared with the plate group . Also , 1-year Neer scores were similar between the two cohorts . Patients in the PHN group perceived significantly less pain compared with patients in the plate fixation group at 3 , 6 and 12 months after surgery . We observed 79 local complications in 60 patients with no significant risk difference between the treatment groups ; 35 intraoperative complications were directly related to the initial surgical procedure . Conclusions The similar 1-year outcomes for nail versus plate fixation of three-part proximal humeral fractures suggest that both techniques may be useful for internal fixation of these fractures . Many complications were related to incorrect surgical technique and therefore can be avoided . Advanced surgical skills and experience are considered to be more critical for successful operative treatment of three-part proximal humeral fractures than the selection of the implant . Level of Evidence Level II , therapeutic study ( prospect i ve comparative study ) . See the Guidelines for Authors for a complete description of levels of evidence BACKGROUND Treatment of complex three and four-part proximal humeral fractures with hemiarthroplasty in elderly patients has yielded mixed clinical results . Reverse shoulder arthroplasty has emerged as a treatment option for comminuted proximal humeral fractures for these patients . The purpose of the study was to perform a prospect i ve evaluation of patient outcomes comparing hemiarthroplasty and reverse shoulder arthroplasty for the treatment of comminuted proximal humeral fractures in elderly patients . METHODS Fifty-three consecutive elderly patients ( average age , 74.4 years ) underwent an arthroplasty for a complex proximal humeral fracture . Indications for arthroplasty were four-part fractures , three-part fractures with severe comminution of the greater tuberosity , and fractures that involved an articular split of the humeral head . Twenty-six patients underwent hemiarthroplasty ( the HA group ) , followed by twenty-seven patients who underwent reverse shoulder arthroplasty ( the RSA group ) . A total of forty-seven patients ( twenty-three in the HA group and twenty-four in the RSA group ) were available for follow-up at a minimum of two years . RESULTS Final average outcome scores were lower in the HA group than in the RSA group ( American Shoulder and Elbow Surgeons [ ASES ] score of 62 versus 77 [ p = 0.0001 ] and Simple Shoulder Test [ SST ] of 5.8 versus 7.4 [ p = 0.0062 ] ) , and patient-reported satisfaction was lower in the HA group than in the RSA group ( 61 % versus 91 % ; p = 0.038 ) . Radiographic healing of the tuberosities occurred in 61 % of the patients in the HA group compared with 83 % of the patients in the RSA group ( p = 0.17 ) . Forward elevation of the arm was higher in the RSA group ( 139 ° ) than in the HA group ( 100 ° ) ( p = 0.0002 ) , but no significant differences were observed for shoulder external rotation or internal rotation . Complication rates in both groups were similar . Three patients ( 13 % ) in the HA group elected revision to reverse shoulder arthroplasty because of failed tuberosity healing and result ant shoulder pseudoparesis . CONCLUSIONS In this series , reverse shoulder arthroplasty result ed in better clinical outcomes and a similar complication rate compared with hemiarthroplasty for the treatment of comminuted proximal humeral fractures in the elderly BACKGROUND Published reports about locked nailing for displaced comminuted proximal humeral fractures are few and the results contradictory . METHODS Locked nailing was used to treat 27 selective patients with displaced three-part proximal humeral fractures . The average age of patients was 54.3 years . The operative indications were persistent severe displacement , intact or minimally displaced lesser tuberosity , tolerance of anesthesia , and adherence to rehabilitation programs . Three patients had associated shoulder dislocation and two had fractures with diaphyseal extension . By transdeltoid approach , the fractures were reduced and then fixed by ante grade nailing with either upward or downward locking screws . The patients were prospect ively followed up for an average of 24 months . RESULTS All fractures achieved eventual union . Three patients with proximal screw loosening required screw removal . On the basis of Neer criteria , excellent or satisfactory results were obtained in 21 patients whose scores averaged 87.5 points . Six patients had unsatisfactory outcomes , with an average of 75.8 points . Two patients with the complication of avascular necrosis still had a satisfactory outcome . Varus deformity of shoulder joints , deformity of the greater tuberosity , collapse of the humeral head , and old age could adversely affect shoulder elevation . However , the anatomic abnormalities might have limited effects on the pain scale , muscle power , and shoulder stability . CONCLUSIONS Locked nailing can be an effective treatment for selected severely displaced three-part proximal humeral fractures . It is particularly useful for fractures with diaphyseal involvement . Familiarity with the fracture deformity and experience with the surgical techniques are critical for successful treatment results BACKGROUND The aim of the study was to report the 2-year outcome after a displaced 4-part fracture of the proximal humerus in elderly patients r and omized to treatment with a hemiarthroplasty ( HA ) or nonoperative treatment . PATIENTS AND METHODS We included 55 patients , mean age 77 ( range , 58 - 92 ) years , 86 % being women . Follow-up examinations were done at 4 , 12 , and 24 months . The main outcome measures were health-related quality of life ( HRQoL ) according to the EQ-5D and the DASH and Constant scores . RESULTS At the final 2-year follow-up the HRQoL was significantly better in the HA group compared to the nonoperative group , EQ-5D ( index ) score 0.81 compared to 0.65 ( P = .02 ) . The results for DASH and pain assessment were both in favor of the HA group , DASH score 30 versus 37 ( P = .25 ) and pain according to VAS 15 versus 25 ( P = .17 ) . There were no significant differences regarding the Constant score or range of motion ( ROM ) . Both groups achieved a mean flexion of approximately 90 - 95 ° and a mean abduction of 85 - 90 ° . The need for additional surgery was low : 3 patients in the HA group and 1 patient in the nonoperative group . CONCLUSION The results of the study demonstrated a significant advantage in quality of life in favor of HA , as compared to nonoperative treatment in elderly patients with a displaced 4-part fracture of the proximal humerus . The main advantage of HA appeared to be less pain while there were no differences in ROM The objective of this study was to determine the effect of different prosthetic systems on the functional and radiographic outcomes after shoulder arthroplasty for fractures . This study comprised 35 patients ( 28 women and 7 men ) with a mean age of 74 years ( range , 56 - 88 years ) who sustained 4-part fractures of the proximal humerus and were r and omly allocated to 2 different groups regarding the type of prosthesis . The 2 systems used differ mainly in the type of fixation of the tuberosities . In group 1 ( EPOCA ) , the fixation was achieved with wire cables through a medial and a lateral hole in the stem , whereas in group 2 ( HAS ) , the fixation was performed by use of transosseous braided sutures . After a follow-up of 1 year , the functional and radiographic outcomes were evaluated . The retrieved data demonstrate that rigid fixation and anatomic positioning of the tuberosities ( group 1 ) increase the rate of bony healing superior to all other factors . There was a statistically significant difference regarding the relative individual Constant score ( P = .001 ) and the mean active range of motion ( flexion , P < .001 ; abduction , P = .001 ; external rotation in adduction , P = .01 ; and external rotation in 90 degrees abduction , P = .001 ) when both groups were compared , showing a better outcome in the EPOCA group for all parameters . Radiologic findings , like heterotopic ossification , glenoid erosion , or subluxation , had no significant influence on the outcome in this study . Accurate placement of the tuberosities and healing at the bone-bone interface of the rotator cuff seem to be the most important factors influencing the outcome in prosthetic care of fractures BACKGROUND The minimal clinical ly important difference ( MCID ) is increasingly used to evaluate treatment effectiveness . The MCID for the Constant score has not been previously reported . MATERIAL S AND METHODS A prospect ively collected cohort of 802 consecutive shoulders with arthroscopically treated partial- or full-thickness rotator cuff tears was analyzed . The Constant score was measured preoperatively and at 3 months and 1 year postoperatively . At follow-up visits , the patients were asked a simple 2-stage question : Is the shoulder better or worse after the operation compared with the preoperative state ? This single 2-level question was used as an indicator of patient satisfaction and as an anchor to calculate the MCID for the Constant score . RESULTS At 1 year , 781 ( 97.4 % ) patients ( 474 men , 307 women ) were available for follow-up . The preoperative Constant score was 53.1 ( SD 17.2 ) in all patients , 56.2 ( SD 17.4 ) in male patients , and 48.2 ( SD 15.6 ) in female patients . Postoperatively at 3 months , the scores were 61.7 ( SD 16.4 ) in all patients , 65.1 ( SD 16.1 ) in male patients , and 56.8 ( SD 15.5 ) in female patients . At 1 year , the scores were 75.9 ( SD 15.2 ) in all patients , 79.0 ( SD 14.9 ) in male patients , and 71.0 ( SD 14.3 ) in female patients . At 3 months postoperatively , 92.2 % of male patients and 87.2 % of female patients were satisfied with the outcome ( P = .027 ) ; at 1 year , the satisfaction was 93.2 % and 89.5 % , respectively ( P = .067 ) . Five different statistical approaches yielded 5 different MCID estimates ( range , 2 - 16 ) . The 3-month mean change estimate of MCID was 10.4 points . CONCLUSION Our study demonstrates an MCID estimate of 10.4 points as the threshold for the Constant score in patients with rotator cuff tear . LEVEL OF EVIDENCE Basic science study , validation of outcomes instruments/classification systems This r and omized controlled trial compares 2 mobilization regimens after shoulder hemiarthroplasty for acute 3- and 4-part fractures . The aim was to establish whether the length of immobilization plays a role in the functional outcome , tuberosity healing , and subsequent range of motion . The same prosthesis and surgical technique were used . We recruited 59 patients into the study ; 31 were r and omized to early ( 2 weeks ) mobilization and 28 to late ( 6 weeks ) mobilization . Greater tuberosity migration was assessed with a series of radiographs , and the functional outcome was assessed with the Constant Shoulder Assessment and Oxford shoulder scores . Of the patients , 49 ( mean age , 70 years ) met the inclusion criteria and were followed up for 12 months . Greater tuberosity migration occurred in 3 cases in the early mobilization group and once in the late mobilization group ( P > .10 ) . There was no significant difference in the Constant Shoulder Assessment and Oxford scores between the 2 groups . Although there was a decreased incidence of tuberosity migration in the group undergoing late mobilization , this was not statistically significant BACKGROUND Significant controversy surrounds optimal treatment of displaced 4-part proximal humeral fractures . Reverse total shoulder arthroplasty ( RTSA ) has recently been proposed as an alternative to hemiarthroplasty ( HA ) and open reduction-internal fixation ( ORIF ) . Several authors have question ed the additional implant cost for RTSA . The purpose of this study was to compare outcomes and cost of RTSA , HA , and ORIF . MATERIAL S AND METHODS We prospect ively evaluated patients who underwent RTSA for displaced 3- and 4-part proximal humeral fractures and then retrospectively developed age- and sex-matched control groups with 3- and 4-part proximal humeral fractures who underwent HA and ORIF . Range of motion including active forward elevation and external rotation and time to achieve active forward elevation > 90 ° were recorded . American Shoulder and Elbow Surgeons ( ASES ) , Short-Form 12-item ( SF-12 ) , and Simple Shoulder Test ( SST ) scores were recorded . In addition , treatment cost was assessed by Medicare data and implant list prices . RESULTS This study enrolled 27 patients ; 9 underwent RTSA , 9 HA , and 9 ORIF . Minimum follow-up was 1 year . No significant differences were seen in SST , ASES , or SF-12 scores . Significantly more patients achieved > 90 ° of active forward elevation after RTSA ( P = .012 ) . RTSA provided significant cost savings to Medicare compared with HA and ORIF ( P = .002 . ) CONCLUSION In this case-control study , RTSA appears to provide superior range of motion earlier and more predictably than HA and ORIF , with significant cost savings to Medicare |
13,461 | 30,621,796 | Conclusions There is considerable heterogeneity in intervention content across patient navigator interventions .
Our results provide a schema from which to develop PN interventions and illustrate how an evidence -based model was used to develop a real-world PN intervention . | Background There is a great deal of variation in the design and delivery of patient navigator ( PN ) programs , making it difficult to design or adopt these interventions in new context s. We ( 1 ) systematic ally review ed the literature to generate a preliminary program theory to describe how patient navigator interventions are design ed and delivered ; and ( 2 ) describe how the result ing program theory was applied in context to inform a prototype for a patient navigator program . | BACKGROUND African Americans suffer disproportionately from diabetes complications , but little research has focused on how to improve diabetic control in this population . There are also few or no data on a combined primary care and community-based intervention approach . METHODS We r and omly assigned 186 urban African Americans with type 2 diabetes ( 76 % female , mean A SD age 59 A 9 years ) to 1 of 4 parallel arms : ( 1 ) usual care only ; ( 2 ) usual care + nurse case manager ( NCM ) ; ( 3 ) usual care + community health worker ( CHW ) ; ( 4 ) usual care + nurse case manager/community health worker team . Using the framework of the Precede-Proceed behavioral model , interventions included patient counseling regarding self-care practice s and physician reminders . RESULTS The 2-year follow-up visit was completed by 149 individuals ( 84 % ) . Compared to the Usual care group , the NCM group and the CHW group had modest declines in HbA(1c ) over 2 years ( 0.3 and 0.3 % , respectively ) , and the combined NCM/CHW group had a greater decline in HbA(1c ) ( 0.8 % . P = 0.137 ) . After adjustment for baseline differences and /or follow-up time , the combined NCM/CHW group showed improvements in triglycerides ( -35.5 mg/dl ; P = 0.041 ) and diastolic blood pressure , compared to the usual care group ( -5.6 mmHg ; P = 0.042 ) . CONCLUSIONS Combined NCM/CHW interventions may improve diabetic control in urban African Americans with type 2 diabetes . Although results were clinical ly important , they did not reach statistical significance . This approach deserves further attention as a means to reduce the excess risk of diabetic complications in African Americans Background : Lack of concordance between medications listed in the medical record and taken by the patient contributes to poor outcomes . We sought to determine whether patients who received health coaching by medical assistants improved their medication concordance and adherence . Methods : This was a nonblinded , r and omized , controlled , pragmatic intervention trial . English- or Spanish-speaking patients , age 18 to 75 years , with poorly controlled type 2 diabetes , hypertension , and /or hyperlipidemia were enrolled from 2 urban safety net clinics and r and omized to receive 12 months of health coaching versus usual care . Results : Outcomes included concordance between medications documented in the medical record and those reported by the patient and adherence based on the patient-reported number of days ( of the last 7 ) on which patient took all prescribed medications . The proportion of medications completely concordant increased in the coached group versus the usual care group ( difference in change , 10 % ; P = .05 ) . The proportion of medications listed in the chart but not taken significantly decreased in the coached group compared with the usual care group ( difference in change , 17 % ; P = .013 ) . The mean number of adherent days increased in the coached but not in the usual care group ( difference in change , 1.08 ; P < .001 ) . Conclusions : Health coaching by medical assistants significantly increases medication concordance and adherence Patient navigation ( PN ) programs are being widely implemented to reduce disparities in cancer care for racial/ethnic minorities and the poor . However , few systematic studies cogently describe the processes of PN . We qualitatively analyzed 21 transcripts of semistructured exit interviews with three navigators about their experiences with patients who completed a r and omized trial of PN . We iteratively discussed codes/categories , reflective remarks , and ways to focus/organize data and developed rules for summarizing data . We followed a three-stage analysis model : reduction , display , and conclusion drawing/verification . We used ATLAS.ti_5.2 for text segmentation , coding , and retrieval . Four categories of factors affecting cancer care outcomes emerged : patients , navigators , navigation processes , and external factors . These categories formed a preliminary conceptual framework describing ways in which PN processes influenced outcomes . Relationships between processes and outcomes were influenced by patient , navigator , and external factors . The process of PN has at its core relationship-building and instrumental assistance . An enhanced underst and ing of the process of PN derived from our analyses will facilitate improvement in navigators ’ training and rational design of new PN programs to reduce disparities in cancer-related care OBJECTIVE To assess the impact of health coaching on patients ' in their primary care provider . METHODS R and omized controlled trial comparing health coaching with usual care . PARTICIPANTS Low-income English or Spanish speaking patients age 18 - 75 with poorly controlled type 2 diabetes , hypertension and /or hyperlipidemia . MAIN OUTCOME MEASURE Patient trust in their primary care provider measured by the 11-item Trust in Physician Scale , converted to a 0 - 100 scale . ANALYSIS Linear mixed modeling . RESULTS A total of 441 patients were r and omized to receive 12 months of health coaching ( n=224 ) vs. usual care ( n=217 ) . At baseline , the two groups were similar to those in the usual care group with respect to demographic characteristics and levels of trust in their provider . After 12 months , the mean trust level had increased more in patients receiving health coaching ( 3.9 vs. 1.5 , p=0.47 ) , this difference remained significant after adjustment for number of visits to primary care providers ( adjusted p=.03 ) . CONCLUSIONS Health coaching appears to increase patients trust in their primary care providers . PRACTICE IMPLICATION S Primary care providers should consider adding health coaches to their team as a way to enhance their relationship with their patients Debates over the degree to which st and ards of evidence and methods from traditional clinical research can or should apply to quality improvement ( QI ) have recurred over the past 10 years.1–4 When , if ever , do we need a r and omised controlled trial ( RCT ) demonstrating benefit to decide that an intervention has worked ? Can we recommend QI interventions for widespread adoption even without supportive RCTs ? On one side of the debate , some have argued that QI and the RCT are like oil and water — never the twain shall mix . Certainly , many have argued , we should not presume that RCTs represent the gold st and ard for evidence in QI . On the face of it , the report by Mate et al 5 supports this oil and water view of RCTs and QI interventions . The authors report their struggles conducting a pragmatic , multisite RCT of a complex intervention to reduce perinatal transmission of HIV in KwaZulu-Natal Province , South Africa . The intervention included socioadaptive strategies,6 , 7 such as engaging local health system leaders , securing a commitment to the aims of the project , and providing participating health centres with the tools to perform data -driven improvement cycles . It also promoted specific best practice s for key steps in the prevention of perinatal transmission of HIV ( eg , increasing the proportion of women receiving early antenatal care that includes HIV counselling and testing , increasing the proportion of mothers with low CD4 counts who receive treatment , and so on ) . The authors initially planned to evaluate this complex intervention using an equally complex study design —a step-wedge , cluster RCT involving 48 clusters of clinics ( for a total of 222 individual clinics ) in three waves of intervention and control sites ; hence , the ‘ step-wedge ’ label . It will come as no surprise to most readers that this double dose of complexity — from the intervention itself and the trial design —overwhelmed OBJECTIVES We tested the effectiveness of a culturally tailored , behavioral theory-based community health worker intervention for improving glycemic control . METHODS We used a r and omized , 6-month delayed control group design among 164 African American and Latino adult participants recruited from 2 health systems in Detroit , Michigan . Our study was guided by the principles of community-based participatory research . Hemoglobin A1c ( HbA1c ) level was the primary outcome measure . Using an empowerment-based approach , community health workers provided participants with diabetes self-management education and regular home visits , and accompanied them to a clinic visit during the 6-month intervention period . RESULTS Participants in the intervention group had a mean HbA1c value of 8.6 % at baseline , which improved to a value of 7.8 % at 6 months , for an adjusted change of -0.8 percentage points ( P < .01 ) . There was no change in mean HbA1c among the control group ( 8.5 % ) . Intervention participants also had significantly greater improvements in self-reported diabetes underst and ing compared with the control group . CONCLUSIONS This study contributes to the growing evidence for the effectiveness of community health workers and their role in multidisciplinary teams engaged in culturally appropriate health care delivery Objectives . Although people with HIV experience significant oral health problems , many consistently identify oral health as an unmet health care need . We conducted a r and omized controlled trial to evaluate the impact of a dental case management intervention on dental care use . Methods . We evaluated the intervention according to self-reported dental care use at 6- , 12- , and 18-month follow-ups . Multivariable logistic models with generalized estimating equations were used to assess the effects of the intervention over time . Results . The odds of having a dental care visit were about twice as high in the intervention group as in the st and ard care group at 6 months ( adjusted odds ratio [ OR ] = 2.52 ; 95 % confidence interval [ CI ] = 1.58 , 4.08 ) and 12 months ( adjusted OR = 1.98 ; 95 % CI = 1.17 , 3.35 ) , but the odds were comparable in the 2 groups by 18 months ( adjusted OR = 1.07 ; 95 % CI = 0.62 , 1.86 ) . Factors significantly associated with having a dental care visit included frequent physician visits and dental care referrals . Conclusions . We demonstrated that a dental case management intervention targeting people with HIV was efficacious but not sustainable over time . Barriers not addressed in the intervention must be considered to sustain its use over time Background : There is limited high- quality evidence about the impact of patient navigation ( PN ) on outcomes for patients with diagnosed cancer . Methods : We pooled data from two sites from the national Patient Navigation Research Program . Patients ( n = 438 ) with newly diagnosed breast ( n = 353 ) or colorectal cancer ( n = 85 ) were r and omized to PN or usual care . Trained lay navigators met with patients r and omized to PN to help them assess treatment barriers and identify re sources to overcome barriers . We used intent-to-treat analysis to assess time to completion of primary treatment , psychologic distress ( impact of events scale ) , and satisfaction ( patient satisfaction with cancer-related care ) within 3 months after initiation of cancer treatment . Results : The sample was predominantly middle-aged ( mean age = 57 ) and female ( 90 % ) ; 44 % were race-ethnic minorities ( 44 % ) , 46 % reported lower education levels , 18 % were uninsured , and 9 % reported a non-English primary language . The r and omized groups were comparable in baseline characteristics . Primary analysis showed no statistically significant group differences in time to completion of primary cancer treatment , satisfaction with cancer-related care , or psychologic distress . Subgroup analysis showed that socially disadvantaged patients ( i.e. , uninsured , low English proficiency , and non-English primary language ) who received PN reported higher satisfaction than those receiving usual care ( all P < 0.05 ) . Navigated patients living alone reported greater distress than those receiving usual care . Conclusions : Although the primary analysis showed no overall benefit , the subgroup analysis suggests that PN may improve satisfaction with care for certain disadvantaged individuals . Impact : PN for cancer patients may not necessarily reduce treatment time nor distress . Cancer Epidemiol Biomarkers Prev ; 21(10 ) ; 1673–81 . © 2012 AACR BACKGROUND AND OBJECTIVES Many patients with ESRD , particularly minorities and women , face barriers in completing the steps required to obtain a transplant . These eight sequential steps are as follows : medical suitability , interest in transplant , referral to a transplant center , first visit to center , transplant workup , successful c and i date , waiting list or identify living donor , and receive transplant . This study sought to determine the effect of navigators on completion of steps . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Cluster r and omized , controlled trial at 23 Ohio hemodialysis facilities . One hundred sixty-seven patients were recruited between January 2009 and August 2009 and were followed for up to 24 months or until study end in February 2011 . Trained kidney transplant recipients met monthly with intervention participants ( n=92 ) , determined their step in the transplant process , and provided tailored information and assistance in completing the step . Control participants ( n=75 ) continued to receive usual care . The primary outcome was the number of transplant process steps completed . RESULTS Starting step did not significantly differ between the two groups . By the end of the trial , intervention participants completed more than twice as many steps as control participants ( 3.5 versus 1.6 steps ; difference , 1.9 steps ; 95 % confidence interval , 1.3 - 2.5 steps ) . The effect of the intervention on step completion was similar across race and sex subgroups . CONCLUSIONS Use of trained transplant recipients as navigators result ed in increased completion of transplant process steps BACKGROUND A r and omized , controlled trial was conducted to evaluate the impact of a directly administered antiretroviral therapy program ( DAART ) and intensive adherence case management ( IACM ) intervention on virologic and immunologic response to highly active antiretroviral therapy ( HAART ) among patients at 3 public human immunodeficiency virus clinics in Los Angeles County , California . METHODS Participants included 250 treatment-naive and treatment-experienced persons for whom no more than 1 prior HAART regimen had failed . Five days per week for 6 months , a community worker delivered 1 HAART dose to DAART participants and observed the participant take it . IACM participants met weekly with a case manager to overcome barriers to HAART adherence . A control group ( the st and ard of care [ SOC ] group ) received the usual care . RESULTS The majority of patients were Latino ( 64 % ) or African American ( 24 % ) ; 57 % were monolingual Spanish speakers . Seventy-five percent of the patients were male , and 64 % reported an annual income of < 10,000 dollars . In an intent-to-treat analysis , no statistical differences were observed in the percentage of patients with an undetectable viral load ( i.e. , < 400 copies/mL ) at 6 months between the DAART group ( 54 % ) , IACM group ( 60 % ) , and SOC group ( 54 % ; P>.05 ) . An on-treatment analysis determined that there were no statistical differences in the percentage of patients with an undetectable viral load at 6 months between the DAART group ( 71 % ) , IACM group ( 80 % ) , and SOC group ( 74 % ; P>.05 ) . Additionally , there were no statistical differences in 6-month changes in the CD4 + cell count or in self-reported adherence to therapy . CONCLUSIONS Among patients with limited prior HAART experience and adherence barriers that had not been assessed before r and omization , no differences were found in virologic or immunologic response for DAART or IACM , compared with SOC , at 6 months . DAART and IACM did not improve short-term outcomes when SOC included other means of adherence support that were not controlled for by the study design OBJECTIVE Both acute and chronic complications of diabetes account for a disproportionate percentage of US health care expenditures . Despite improvements in diabetes care , the incidence of adverse events in children with type 1 diabetes remains high , particularly for youths with poor glycemic control . Cost-effective intervention programs design ed to reduce complications are needed . This study evaluated a low-intensity , nonmedical intervention using a case manager ( called a " Care Ambassador " ) , with and without the supplementation of psychoeducational modules , design ed to monitor and encourage routine diabetes care visits to reduce short-term adverse outcomes and improve glycemic control in youths with type 1 diabetes . METHODS We performed a 2-year prospect i ve , r and omized clinical trial in 299 youths with type 1 diabetes , aged 7 to 16 years , comparing 3 treatment programs ( Care Ambassador [ CA ] , Care Ambassador plus psychoeducational modules [ CA+ ] , and st and ard multidisciplinary diabetes care [ SC ] ) . The study was conducted in a large metropolitan US city from April 1997 through April 2000 . Number of medical visits , frequency of hypoglycemic events , hospital/emergency department ( ED ) utilization , and glycosylated hemoglobin A1c were assessed during follow-up . RESULTS During the 2-year study period , both the CA and CA+ groups had significantly more routine visits ( mean [ st and ard deviation ] : 7.3 [ 2.06 ] and 7.5 [ 2.02 ] , respectively ) compared with the SC group ( 5.4 [ 2.62 ] ) . The CA+ intervention group had significantly reduced rates of short-term adverse outcomes compared with the other 2 groups ; 25 % fewer total hypoglycemic events , 60 % fewer severe hypoglycemic events , and 40 % fewer hospitalizations and ED visits . " High-risk " youths in the CA+ group ( baseline glycosylated hemoglobin A1c > or = 8.7 % ) were 3.4-fold ( 1.57 - 7.41 ) more likely to improve their glycemic control compared with those at high risk in the other 2 groups . CONCLUSIONS For youths with type 1 diabetes , the CA and CA+ interventions increased visit frequency . Youths in the CA+ intervention had reduced rates of hypoglycemia and hospital/ED utilization with estimated annual cost savings of 80 000 dollars to 90 000 dollars . The CA+ intervention compared with the other 2 groups improved glycemic control in " high-risk " youths . Nonmedical case management incorporating psychoeducational modules seems to be a cost-effective approach to improving outcomes in youths with diabetes PURPOSE To determine whether a nurse navigator intervention improves quality of life and patient experience with care for people recently given a diagnosis of breast , colorectal , or lung cancer . PATIENTS AND METHODS Adults with recently diagnosed primary breast , colorectal , or lung cancer ( n = 251 ) received either enhanced usual care ( n = 118 ) or nurse navigator support for 4 months ( n = 133 ) in a two-group cluster r and omized , controlled trial with primary care physicians as the units of r and omization . Patient-reported measures included the Functional Assessment of Cancer Therapy-General ( FACT-G ) Quality of Life scale , three subscales of the Patient Assessment of Chronic Illness Care ( PACIC ) , and selected subscales from a cancer adaptation of the Picker Institute 's patient experience survey . Self-report measures were collected at baseline , 4 months , and 12 months . Automated administrative data were used to assess time to treatment and total health care costs . RESULTS There were no significant differences between groups in FACT-G scores . Nurse navigator patients reported significantly higher scores on the PACIC and reported significantly fewer problems with care , especially psychosocial care , care coordination , and information , as measured by the Picker instrument . Cumulative costs after diagnosis did not differ significantly between groups , but lung cancer costs were $ 6,852 less among nurse navigator patients . CONCLUSION Compared with enhanced usual care , nurse navigator support for patients with cancer early in their course improves patient experience and reduces problems in care , but did not differentially affect quality of life OBJECTIVES We evaluated the effectiveness of a community-based participatory research -grounded intervention among women receiving Temporary Assistance for Needy Families ( TANF ) with chronic health conditions in increasing ( 1 ) health care visits , ( 2 ) Medicaid knowledge and skills , and ( 3 ) health and functional status . METHODS We used a r and omized controlled trial design to assign 432 women to a public health nurse case management plus Medicaid intervention or a wait-control group . We assessed Medicaid outcomes pre- and posttraining ; other outcomes were assessed at 3 , 6 , and 9 months . RESULTS Medicaid knowledge and skills improved ( P < .001 for both ) . Intervention group participants were more likely to have a new mental health visit ( odds ratio [ OR ] = 1.92 ; P = .007 ) , and this likelihood increased in higher-risk subgroups ( OR = 2.03 and 2.83 ; P = .04 and .006 , respectively ) . Depression and functional status improved in the intervention group over time ( P = .016 for both ) . No differences were found in routine or preventive care , or general health . CONCLUSIONS Health outcomes among women receiving TANF can be improved with public health interventions . Additional strategies are needed to further reduce health disparities in this population Objective : The Antiretroviral Treatment Access Study ( ARTAS ) assessed a case management intervention to improve linkage to care for persons recently receiving an HIV diagnosis . Methods : Participants were recently diagnosed HIV-infected persons in Atlanta , Baltimore , Los Angeles and Miami . They were r and omized to either st and ard of care ( SOC ) passive referral or case management ( CM ) for linkage to nearby HIV clinics . The SOC arm received information about HIV and local care re sources ; the CM intervention arm included up to five contacts with a case manager over a 90-day period . The outcome measure was self-reported attendance at an HIV care clinic at least twice over a 12-month period . Results : A higher proportion of the 136 case-managed participants than the 137 SOC participants visited an HIV clinician at least once within 6 months [ 78 versus 60 % ; adjusted relative risk ( RRadj ) , 1.36 ; P = 0.0005 ) and at least twice within 12 months ( 64 versus 49 % ; RRadj , 1.41 ; P = 0.006 ) . Individuals older than 40 years , Hispanic participants , individuals enrolled within 6 months of an HIV-seropositive test result and participants without recent crack cocaine use were all significantly more likely to have made two visits to an HIV care provider . We estimate the cost of such case management to be US$ 600–1200 per client . Conclusion : A brief intervention by a case manager was associated with a significantly higher rate of successful linkage to HIV care . Brief case management is an affordable and effective re source that can be offered to HIV-infected clients soon after their HIV diagnosis Clinicians who are asked to participate in quality improvement programmes in healthcare organizations are often heard to ask for the evidence that they ‘ work ’ . By that , they often mean they want r and omized controlled trials , which show that accreditation , or credentialing , or criterion-based audit , or adverse event monitoring , or continuous quality improvement programmes , or whatever approach is being used cause meaningful and worthwhile improvements in the quality of care [ 1 ] . When they learn that there are relatively few experimental studies of quality improvement interventions [ 2 ] , and those which do exist often show weak or moderate effects at best , this state of affairs is sometimes used to argue that it is not worthwhile investing time and effort in quality improvement . After all , the argument goes , we should not embark on using a new clinical intervention such as a drug or a surgical procedure without solid experimental evidence of its effectiveness , so why should we have a lower threshold for the adoption of organizational interventions like quality improvement programmes ? Surely , they too should be proven to ‘ work ’ before they are adopted or implemented widely ? This point of view needs to be challenged . It is founded on a fundamental misunderst and ing of the place of experimental methods in investigating and underst and ing complex social interventions , which is commonplace particularly among clinicians and biomedical research ers and which can seriously hamper those both research ing OBJECTIVE To determine the effect of a bicultural community health worker ( CHW ) on completion of diabetes education in an inner-city Hispanic patient population and to evaluate the impact of completion of the education program on patient knowledge , self-care behaviors , and glycemic control . RESEARCH DESIGN AND METHODS Patients were r and omized into CHW intervention and non-CHW intervention groups . All patients received individualized , comprehensive diabetes education from a certified diabetes nurse educator after baseline demographic information , diabetes knowledge , diabetes self-care practice s , and glycohemoglobin levels were assessed . Rates of education program completion were determined . Diabetes knowledge , self-care practice s , and glycohemoglobin levels were reassessed at program completion and at a later postprogram follow-up medical appointment and compared to baseline . Logistic regression analysis and the Mantel-Haenszel χ2 statistic were used to determine the effect of the CHW assignment on program completion . Analyses of covariance were performed with end-of-treatment behavior scores , knowledge scores , and glycohemoglobin levels as outcome variables , controlling for baseline values and testing for the effect of CHW assignment . RESULTS Of 64 patients enrolled in the study , 40 ( 63 % ) completed and 24 ( 37 % ) dropped out before completing the diabetes education program . Of the patients having CHW intervention , 80 % completed the education program , compared with 47 % of patients without CHW intervention ( P = 0.01 ) . “ Dropouts ” were younger ( age 47.5 ± 12.5 years [ mean ± SD ] ) compared with patients who completed the program ( 55.9 ± 9.9 years ) ( P = 0.004 ) . Dropout status showed no significant relationship to educational level achieved or literacy level . For the program “ completers , ” knowledge levels and selected self-care practice s significantly improved , and glycohemoglobin levels improved from a baseline level of 11.7 % to 9.9 % at program completion ( P = 0.004 ) and 9.5 % at the postprogram follow-up ( P < 0.001 ) . The effect of the CHW assignment on program completion , controlling for financial status and language spoken , was extremely robust ( P = 0.007 ) . The effect of the CHW on knowledge , self-care behavior , or glycohemoglobin outcome variables was not statistically significant . CONCLUSIONS These findings suggest that intervention with a bicultural CHW improved rates of completion of a diabetes education program in an inner-city Hispanic patient population irrespective of literacy or educational levels attained . Our data further suggests that completion of individualized diabetes educational strategies leads to improved patient knowledge , self-care behaviors , and glycemic control The authors implemented a controlled , r and omized trial that compared 2 interventions : the provision of written re source navigation information ( enhanced usual care [ EUC ] ) versus written information plus patient navigation ( TPN ) aim ed at improving adjuvant treatment adherence and follow‐up among 487 low‐income , predominantly Hispanic women with breast cancer or gynecologic cancer PURPOSE Health coaching by medical assistants could be a financially viable model for providing self-management support in primary care if its effectiveness were demonstrated . We investigated whether in-clinic health coaching by medical assistants improves control of cardiovascular and metabolic risk factors when compared with usual care . METHODS We conducted a 12-month r and omized controlled trial of 441 patients at 2 safety net primary care clinics in San Francisco , California . The primary outcome was a composite measure of being at or below goal at 12 months for at least 1 of 3 uncontrolled conditions at baseline as defined by hemoglobin A1c , systolic blood pressure , and low-density lipoprotein ( LDL ) cholesterol . Secondary outcomes were meeting all 3 goals and meeting individual goals . Data were analyzed using χ2 tests and linear regression models . RESULTS Participants in the coaching arm were more likely to achieve both the primary composite measure of 1 of the clinical goals ( 46.4 % vs 34.3 % , P = .02 ) and the secondary composite measure of reaching all clinical goals ( 34.0 % vs 24.7 % , P = .05 ) . Almost twice as many coached patients achieved the hemoglobin A1c goal ( 48.6 % vs 27.6 % , P = .01 ) . At the larger study site , coached patients were more likely to achieve the LDL cholesterol goal ( 41.8 % vs 25.4 % , P = .04 ) . The proportion of patients meeting the systolic blood pressure goal did not differ significantly . CONCLUSIONS Medical assistants serving as in-clinic health coaches improved control of hemoglobin A1c and LDL levels , but not blood pressure , compared with usual care . Our results highlight the need to underst and the relationship between patients ’ clinical conditions , interventions , and the context ual features of implementation |
13,462 | 32,081,967 | The accumulated evidence indicated that the symptomatic burden of COPD appears greatest in the morning , particularly upon waking , and that these morning symptoms have a substantial impact on patients ’ ability to function normally through the day ; they also worsen quality of life .
The literature also confirmed the importance of pharmacotherapy in the management of daytime COPD symptoms , and in helping normalize daily functioning . | There is no single source of compiled data on symptoms experienced by patients with chronic obstructive pulmonary disease ( COPD ) when awake and active throughout the day .
The aim of this systematic review was to evaluate the prevalence , variability , and burden ( i.e. , bothersomeness and /or intensity ) , and the impact of daytime COPD symptoms on other outcomes .
The review also evaluated the impact of interventions and the measures /tools used to assess daytime COPD symptoms in patients . | Background / Aims Patients with chronic obstructive pulmonary disease ( COPD ) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning . The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation . Methods Data of 133 patients with severe airflow limitation were analyzed in a prospect i ve , non-interventional study . A clinical symptom question naire was completed by patients at baseline . In patients having morning symptoms , defined by at least one or more prominent or aggravating symptom during morning activities , a morning activity question naire was also completed at baseline and following 2 months of COPD treatment . Results The most frequently reported COPD symptom was breathlessness ( 90.8 % ) . Morning symptoms were reported in 76 ( 57 % ) patients ; these had more frequent and severe clinical COPD symptoms . The most frequently reported morning activity was getting out of bed ( 82.9 % ) . The long acting muscarinic antagonist ( odds ratio [ OR ] , 6.971 ; 95 % confidence interval [ CI ] , 1.317 to 11.905 ) and chest tightness ( OR , 0.075 ; 95 % CI , 0.011 to 0.518 ) were identified as significantly related to absence of morning symptoms . There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment . Conclusions Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities . These patients also have more prevalent and severe COPD symptoms . The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD Background The combination of aclidinium bromide , a long-acting anticholinergic , and formoterol fumarate , a long-acting beta2-agonist ( 400/12 μg twice daily ) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease ( COPD ) , and is approved in the European Union as a maintenance treatment . The effect of this combination on symptoms of COPD and exacerbations is less well established . We examined these outcomes in a pre-specified analysis of pooled data from two 24-week , double-blind , parallel-group , active- and placebo-controlled , multicentre , r and omised Phase III studies ( ACLIFORM and AUGMENT ) . Methods Patients ≥40 years with moderate to severe COPD ( post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity < 70 % and FEV1 ≥30 % but < 80 % predicted normal ) were r and omised ( ACLIFORM : 2:2:2:2:1 ; AUGMENT : 1:1:1:1:1 ) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg , aclidinium 400 μg , formoterol 12 μg or placebo via Genuair ™ /Pressair ® . Dyspnoea ( Transition Dyspnoea Index ; TDI ) , daily symptoms ( EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [ E-RS ] question naire ) , night-time and early-morning symptoms , exacerbations ( Healthcare Re source Utilisation [ HCRU ] and EXACT definitions ) and relief-medication use were assessed . Results The pooled intent-to-treat population included 3394 patients . Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 ( all p < 0.05 ) . Over 24 weeks , significant improvements in E-RS total score , overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies ( all p < 0.05 ) . The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo ( p < 0.05 ) but not monotherapies ; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo ( p < 0.01 ) and aclidinium ( p < 0.05 ) . Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo ( all p < 0.05 ) but not the monotherapies . Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium ( p < 0.01 ) . Conclusions Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo , aclidinium and formoterol in patients with moderate to severe COPD . Furthermore , aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo . Trial registration NCT01462942 and NCT01437397 ( Clinical Trials.gov UNLABELLED Indacaterol is a novel , inhaled , long-acting β(2)-agonist providing 24-h bronchodilation with once-daily ( o.d . ) dosing in patients with COPD . In this double-blind , incomplete block crossover study , patients with moderate-to-severe COPD were r and omised to receive three treatment cycles from : indacaterol 300 μg o.d . dosed PM or AM , salmeterol 50 μg twice daily or placebo , each for 14 days . Trough FEV(1 ) was measured 24 h after indacaterol , and 12 h after salmeterol . Ninety-six patients ( mean age : 64 years ; post-bronchodilator FEV(1 ) 57 % predicted , FEV(1)/FVC 55 % ) were r and omised ; 83 completed . After 14 days , the difference vs. placebo in trough FEV(1 ) for PM indacaterol was 200 mL ( p < 0.001 [ primary analysis ] ) and for AM indacaterol was 200 mL ( p < 0.001 ) . Compared with salmeterol , trough FEV(1 ) for PM indacaterol was 110 mL higher ( p < 0.001 ) , and for AM indacaterol was 50 mL higher ( p = NS ) . Over 14 days , vs. placebo , both PM and AM indacaterol improved the % of nights with no awakenings ( by 11.9 and 8.1 points ; p < 0.01 ) ; the % of days with no daytime symptoms ( by 6.7 and 5.5 points ; p < 0.05 ) ; and the % of days able to perform usual activities ( by 6.7 and 7.8 points ; p < 0.05 ) . Indacaterol provided 24-h bronchodilation and improvement in symptoms regardless of whether taken regularly in the morning or evening . CLINICAL TRIAL REGISTRATION Clinical Trials.gov NCT00615030 Abstract Background : This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD . Methods : In this 12-week , double-blind , multicenter trial , patients were r and omized ( 1:1:1 ) to inhaled twice-daily aclidinium 200 μg , aclidinium 400 μg , or placebo . Primary and secondary endpoints were changes from baseline in trough FEV1 and peak FEV1 at Week 12 , respectively . Health status ( St. George 's Respiratory Question naire [ SGRQ ] ) , COPD symptoms ( Transitional Dyspnea Index [ TDI ] , night and early morning symptoms ) , and safety were also assessed . Results : A total of 561 patients ( mean age , 64 ± 9 years ) with a mean baseline FEV1 of 1.36 ± 0.54 L ( 47.2 % of predicted value ) were r and omized . At Week 12 , aclidinium 200 μg and 400 μg showed significant improvements from baseline in mean ( 95 % CI ) trough FEV1 compared with placebo by 86 ( 45 , 127 ) mL and 124 ( 83,164 ) mL , respectively , and in peak FEV1 by 146 ( 101 , 190 ) mL and 192 ( 148 , 236 ) mL , respectively ( p ≤ 0.0001 for all ) . Both aclidinium doses also provided significant improvements in SGRQ , TDI and almost all COPD symptom scores compared with placebo ( p < 0.05 for all ) . Incidences of adverse events ( AEs ) were similar across treatment groups . The incidence of anticholinergic AEs was low and similar across groups ( dry mouth : 0.5%–1.6 % ; constipation : 0%-1.1 % ) . Conclusions : Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 μg and 400 μg was associated with significant improvements in bronchodilation , health status , and COPD symptoms . Both doses were well tolerated and had safety profiles similar to placebo . Trial Registration : This ACCORD I study ( AClidinium in Chronic Obstructive Respiratory Disease I ) was registered on clinical trials.gov ( NCT00891462 ) as “ Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease ( COPD ) ” Background Symptoms , particularly dyspnea , and activity limitation , have an impact on the health status and the ability to function normally in patients with chronic obstructive pulmonary disease ( COPD ) . Methods To develop an electronic patient diary ( eDiary ) , qualitative patient interviews were conducted from 2009 to 2010 to identify relevant symptoms and degree of bother due to symptoms . The eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in the 26-week QVA149 SHINE study . Two morning assessment s ( since awakening and since the last assessment ) and one evening assessment were made each day . Assessment s covered five symptoms ( “ shortness of breath , ” “ phlegm/mucus , ” “ chest tightness , ” “ wheezing , ” and “ coughing ” ) and two impact items ( “ bothered by COPD ” and “ difficulty with activities ” ) and were scored on a 10-point numeric scale . Results Patient compliance with the eDiary was 90.4 % at baseline and 81.3 % at week 26 . Correlations between shortness of breath and impact items were > 0.95 . Regression analysis showed that shortness of breath was a highly significant ( P<0.0001 ) predictor of impact items . Exploratory factor analysis gave a single factor comprising all eDiary items , including both symptoms and impact items . Shortness of breath , the total score ( including five symptoms and two impact items ) , and the five-item symptom score from the eDiary performed well , with good consistency and reliability . The eDiary showed good sensitivity to change , with a 0.6 points reduction in the symptoms scores ( on a 0–10 point scale ) representing a meaningful change . Conclusion The eDiary was found to be valid , reliable , and responsive . The high correlations obtained between “ shortness of breath ” and the ratings of “ bother ” and “ difficulty with activities ” confirmed the relevance of this symptom in patients with COPD . Future studies will be required to explore further psychometric properties and their ability to differentiate between COPD treatments Background A previous Phase IIIb study ( NCT01462929 ) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium , and improvement of symptoms versus placebo . This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study . Methods Symptomatic patients ( defined as those with Evaluating Respiratory Symptoms [ E-RS ™ ] in COPD baseline score ≥10 units ) received aclidinium bromide 400 μg twice daily ( BID ) , tiotropium 18 μg once daily ( QD ) , or placebo , for 6 weeks . Lung function , COPD respiratory symptoms , and incidence of adverse events ( AEs ) were assessed . Results In all , 277 symptomatic patients were included in this post hoc analysis . Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second ( FEV1 ) from baseline to week 6 at all time points over 24 hours versus placebo . In addition , improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 ( aclidinium 157 mL , tiotropium 67 mL ; P<0.001 ) and week 6 ( aclidinium 153 mL , tiotropium 90 mL ; P<0.05 ) . Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 ( aclidinium 136 mL , tiotropium 68 mL ; P<0.05 ) and week 6 ( aclidinium 137 mL , tiotropium 71 mL ; P<0.05 ) . Aclidinium also improved early-morning and nighttime symptom severity , limitation of early-morning activities , and E-RS Total and domain scores versus tiotropium ( except E-RS Chest Symptoms ) and placebo over 6 weeks . Tolerability showed similar incidence of AEs in each arm . Conclusion In this post hoc analysis of symptomatic patients with moderate to severe COPD , aclidinium 400 μg BID provided additional improvements compared with tiotropium 18 μg QD in : 1 ) bronchodilation , particularly during the nighttime , 2 ) daily COPD symptoms ( E-RS ) , 3 ) early-morning and nighttime symptoms , and 4 ) early-morning limitation of activity ABSTRACT Early detection of treatment response is important in the long-term treatment and management of patients with chronic obstructive pulmonary disease ( COPD ) . This analysis evaluated whether early improvement in symptoms , recorded in the first 7 or 14 days via an electronic diary ( eDiary ) compared with baseline , can predict clinical ly meaningful treatment responders at 12 weeks . CRYSTAL was a 12-week , r and omized , open-label study that demonstrated the increased effectiveness of indacaterol/glycopyrronium ( IND/GLY ) or glycopyrronium ( GLY ) , after a direct switch from on-going baseline therapies , in patients with symptomatic COPD and moderate airflow obstruction . The co- primary endpoints were trough forced expiratory volume in 1 second ( FEV1 ) and transition dyspnea index ( TDI ) at Week 12 . Patients ' symptom status was recorded daily in an eDiary . Of 4,389 patients r and omized , 3,936 and 3,855 reported symptoms on Days 7 and 14 , respectively . Patients who reported an early decrease in symptoms on Day 7 or 14 were more likely to achieve the minimal clinical ly important difference of ≥100 mL in trough FEV1 or ≥ 1 point in TDI at Week 12 . Using stepwise multivariate regression models we identified as best predictors of FEV1 responders the decrease in wheeze on Day 7 , and nighttime symptoms and wheeze on Day 14 ; best predictors of TDI responders were decrease in nighttime symptoms and wheeze on Day 7 , and nighttime symptoms , sputum and wheeze on Day 14 . Early symptom improvement at Day 7 or 14 , especially wheeze and nighttime symptoms , may identify patients with clinical ly important improvement in lung function and dyspnea at Week 12 Background : Patients with chronic obstructive pulmonary disease ( COPD ) often experience symptoms and problems with activities early in the morning . This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function , symptoms and activities early in the morning . Methods : Lung function ( peak expiratory flow [ PEF ] and forced expiratory volume in 1 second [ FEV 1 ] ) and symptoms were measured at bedside and activities were measured during the morning using a six-item question naire concerning basic morning routines . In a r and omised , double-blind , multicentre , cross-over study , 442 patients with COPD aged ≥40 years ( pre-bronchodilator FEV1 ≤50 % ; FEV1/vital capacity < 70 % ) received budesonide/formoterol ( 320/9 µg , one inhalation twice daily ) dry powder inhaler ( DPI ) or salmeterol/fluticasone ( 50/500 µg , one inhalation twice daily ) DPI daily , for 1 week each , separated by a 1- to 2-week washout . Lung function ( PEF and FEV1 ) shortly after rising from bed in the morning , symptoms and basic morning activities were assessed by electronic diary ( e-Diary ) recordings . Results : Budesonide/formoterol and salmeterol/fluticasone treatment increased morning PEF 5 minutes post-dose , measured as a mean improvement from baseline over the full study period ( primary endpoint ; adjusted mean change : 15.1 l/min and 14.2 l/min , respectively [ difference 1.0 l/min ; p = 0.603 ] ) . Mean morning FEV1 improved more following budesonide/ formoterol treatment versus salmeterol/fluticasone at 5 minutes ( 0.12 l versus 0.09 l ; p = 0.090 ) and 15 minutes ( 0.14 l versus 0.10 l ; p < 0.05 ) post-dose . Budesonide/formoterol demonstrated a more rapid onset of effect as reflected by increases in e-Diary-recorded PEF and FEV 1 from pre-dose to 5 and 15 minutes post-dose ( all p < 0.001 ) and spirometry at the clinic measured after the first dose ( FEV1 p < 0.001 ; 5 minutes post-dose ) . Improvements in symptom scores within 15 minutes after drug administration were similar for both drugs , but budesonide/formoterol treatment result ed in significantly greater improvements in total morning activities score ( getting washed , dried , dressed , eating breakfast and walking around the home ; 0.22 versus 0.12 respectively , p < 0.05 ) . Both treatments were well tolerated . Conclusions : Short-term treatment with budesonide/formoterol DPI or salmeterol/fluticasone DPI was effective in patients with COPD . Budesonide/formoterol had a more rapid onset of effect compared with salmeterol/fluticasone and result ed in greater improvements in ability to perform morning activities despite the lower inhaled corticosteroid dose Background Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease ( COPD ) . We evaluated the effect of aclidinium bromide 400 μg twice daily ( BID ) on respiratory symptoms , assessed using the Evaluating Respiratory Symptoms in COPD ( E-RS ™ : COPD ) scale ( formerly EXACT-RS ) . Methods Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week , double-blind , r and omized Phase III studies evaluating aclidinium monotherapy ( ATTAIN ) or combination therapy ( AUGMENT COPD I ) in patients with moderate to severe airflow obstruction . Patients were stratified by Global initiative for chronic Obstructive Lung Disease ( GOLD ) Groups A – D. Change from baseline in E-RS scores , proportion of responders ( patients achieving pre-defined improvements in E-RS scores ) , and net benefit ( patients who improved minus patients who worsened ) were analyzed . Results Of 1210 patients , 1167 had data available for GOLD classification . Mean ( st and ard deviation ) age was 63.2 ( 8.6 ) years , 60.7 % were male , and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted . Compared with placebo , aclidinium 400 μg BID significantly improved RS-Total ( 2.38 units vs 0.79 units , p < 0.001 ) and domain scores ( all p < 0.001 ) at Week 24 , and doubled the likelihood of being an RS-Total score responder ( p < 0.05 ) , irrespective of GOLD group . The net benefit for RS-Total ( Overall : 56.9 % vs 19.4 % ; A + C : 65.7 % vs 6.3 % ; B + D : 56.0 % vs 20.8 % , for aclidinium 400 μg BID and placebo respectively ; all p < 0.05 ) and domain scores ( all p < 0.05 ) was significantly greater with aclidinium compared with placebo , in both GOLD Groups A + C and B + D. Conclusions Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients ’ level of symptoms at baseline . Net treatment benefit was similar in patients with low or high levels of symptoms . Trial registration ATTAIN ( Clinical Trials.gov identifier : NCT01001494 ) and AUGMENT COPD I ( Clinical Trials.gov identifier : NCT01437397 ) Abstract Background : Glycopyrronium is a once daily ( o.d . ) long-acting muscarinic antagonist that is approved for maintenance treatment of COPD . This post-hoc pooled analysis of two phase III studies , GLycopyrronium bromide in COPD airWays 1 and 2 ( GLOW1 and GLOW2 ) , evaluated the effects of glycopyrronium compared with placebo and tiotropium over 26–52 weeks in patients with moderate-to-severe COPD . Methods : Patients aged ≥40 years were r and omised to 26 weeks ’ treatment with glycopyrronium 50 μg o.d . or placebo ( GLOW1 ) or 52 weeks ’ treatment with glycopyrronium 50 μg o.d . , placebo , or open-label tiotropium 18 μg o.d . ( GLOW2 ) . The primary efficacy endpoint in both studies was trough forced expiratory volume in one second ( FEV1 ) at Week 12 . Other outcomes included additional spirometry endpoints , moderate or severe exacerbations , dyspnoea , health status , rescue medication use and safety . Serial spirometry over 24 hours was conducted in a subset of patients . Results : Of 1888 subjects r and omised , 98.2 % were analysed ( glycopyrronium 1059 , tiotropium 267 , placebo 528 ) . Least squares mean ( LSM ) trough FEV1 was significantly higher with glycopyrronium versus placebo at Week 12 ( treatment difference ± st and ard error [ SE ] : 103 ± 11.2 mL ; p < 0.001 ) , as well as at Day 1 and Weeks 26 and 52 . More patients achieved ≥100 mL increase in trough FEV1 from baseline with glycopyrronium versus placebo at all assessment s ( p < 0.001 ) . Glycopyrronium significantly improved FEV1 immediately after the first dose on Day 1 versus placebo ( 90 mL at 5 minutes , 144 mL at 15 minutes ; both p < 0.001 ) and versus tiotropium ( 43 mL at 5 minutes , 65 mL at 15 minutes ; both p < 0.001 ) . Glycopyrronium significantly improved other spirometry endpoints and provided clinical ly meaningful 24 hour bronchodilation versus placebo at most timepoints from Day 1 onwards ( p < 0.05 ) . Time to first moderate or severe exacerbation was significantly prolonged with glycopyrronium versus placebo over 26 and 52 weeks ( 36 % and 33 % , respectively ; both p < 0.001 ) . Glycopyrronium provided significantly greater relief of dyspnoea , improved health status and reduced rescue medication use versus placebo . Glycopyrronium was safe and well tolerated . Conclusions : Glycopyrronium 50 μg o.d . provided early bronchodilation after the first dose that was sustained for 24 hours , and reduced the risk of exacerbations compared with placebo , with efficacy at least equivalent to tiotropium . Trial Registration s : NCT01005901 and NCT00929110 Background Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease ( COPD ) that are greater than those derived from either treatment alone . The efficacy and safety of a fixed-dose combination ( FDC ) of aclidinium bromide , a long-acting muscarinic antagonist , and formoterol fumarate , a long-acting β2-agonist , in patients with moderate to severe COPD are presented . Methods In this 24-week double-blind study , 1692 patients with stable COPD were equally r and omized to twice-daily treatment with FDC aclidinium 400μg/formoterol 12μg ( ACL400/FOR12 FDC ) , FDC aclidinium 400μg/formoterol 6μg ( ACL400/FOR6 FDC ) , aclidinium 400μg , formoterol 12μg , or placebo administered by a multidose dry powder inhaler (Genuair ® /Pressair ® )*. Co primary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 ( FDCs versus aclidinium ) and change from baseline to week 24 in morning predose ( trough ) FEV1 ( FDCs versus formoterol ) . Secondary endpoints were change from baseline in St. George ’s Respiratory Question naire ( SGRQ ) total score and improvement in Transition Dyspnea Index ( TDI ) focal score at week 24 . Safety and tolerability were also assessed . Results At study end , improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium ( 108 mL and 87 mL , respectively ; p < 0.0001 ) . Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol ( 45 mL ; p = 0.0102 ) , a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC . Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end ( p < 0.0001 ) , with differences over placebo exceeding the minimal clinical ly important difference of ≥4 points and ≥1 unit , respectively . All treatments were well tolerated , with safety profiles of the FDCs similar to those of the monotherapies . Conclusions Treatment with twice-daily aclidinium 400μg/formoterol 12μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy ; clinical ly significant improvements in dyspnea and health status were evident compared with placebo . Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD .Trial registration Clinical trials.gov NCT01437397.*Registered trademarks of Almirall S.A. , Barcelona , Spain ; for use within the US as Pressair ® and Genuair ® within all other licensed territories BACKGROUND --The acute response to bronchodilators in patients with chronic obstructive pulmonary disease ( COPD ) is modest ; it has , however , been suggested that these patients may benefit from long term treatment . METHODS --To investigate the efficacy of salmeterol in smokers with moderate to severe COPD a double blind , r and omised , crossover comparison was performed between salmeterol ( 50 micrograms twice daily ) and placebo in 63 patients with stable COPD ( mean age 65 years ) . Prior to inclusion , all patients had a forced expiratory volume in one second ( FEV1 ) of < 60 % of predicted and an improvement in FEV1 of < 15 % following 400 micrograms inhaled salbutamol . Patients received four weeks of therapy with each of the treatment regimens . Assessment of efficacy was made with recording of morning and evening peak expiratory flow rates ( PEF ) , respiratory symptoms , and use of rescue salbutamol . FEV1 was measured before and after nebulised salbutamol prior to r and omisation and at the end of each treatment period . RESULTS --Morning PEF values were higher during the salmeterol than during the placebo period , although the mean treatment difference was small ( 12 l/min ( 95 % confidence limits 6 to 17 ) ) . No difference in mean evening PEF values was found . Diurnal variation in PEF , assessed as the difference between the morning PEF and that of the previous evening , was more pronounced during the placebo than during the salmeterol period . The mean spirometric values ( including reversibility in FEV1 ) obtained at the end of the two treatment periods were similar . Compared with placebo , treatment with salmeterol was associated with lower daytime and night time symptom scores and less use of rescue salbutamol both during the day and the night . The patients rated the treatment with salmeterol better than treatment with placebo . CONCLUSIONS --This study shows that , compared with placebo , treatment with salmeterol produces an improvement in respiratory symptoms and morning PEF values in patients with moderate to severe COPD . Treatment with long acting beta agonists may therefore result in an improvement in functional status , even in patients suffering from apparently nonreversible obstructive pulmonary disease Abstract Background : This is the first comparison of two combination therapies , fluticasone propionate/salmeterol and ipratropium bromide/albuterol ( salbutamol ) , for the treatment of patients with COPD . Methods : A r and omized , double-blind , double-dummy , parallel group , multicenter evaluation of fluticasone propionate/salmeterol 250/50 µg twice daily via DISKUS ® and ipratropium bromide/albuterol 36/206 µg four times daily via metered-dose inhaler over 8 weeks was conducted at 41 research sites in the US . Morning pre-dose FEV1 , 6-hour serial spirometry , PEF , dyspnea , night-time awakenings , supplemental albuterol use , and patient diary evaluations of symptoms were evaluated . Results : A total of 365 patients with symptomatic COPD were enrolled . The treatment groups were similar in mean age ( 63.3 and 63.9 years ) , screening pulmonary function ( 44.1 % and 43.2 % of predicted FEV1 ) , race ( 96 % and 95 % White ) , and sex distribution ( 59 % and 60 % male ) . Both fluticasone propionate/salmeterol and ipratropium bromide/albuterol improved lung function , symptoms , and supplemental albuterol use compared with baseline . Fluticasone propionate/salmeterol was more effective than ipratropium bromide/albuterol for improvement in morning pre-dose FEV1 , morning PEF , 6-hour FEV1 area under the curve ( AUC6 ) , Transition Dyspnea Index ® ( TDI ) focal score , daytime symptom score , night-time awakenings , sleep symptoms , and albuterol-free nights ( p ≤ 0.013 ) . Compared with day 1 , at week 8 the FEV1 AUC6 significantly increased with fluticasone propionate/salmeterol and significantly decreased with ipratropium bromide/albuterol ( p ≤ 0.003 ) . The incidence of adverse events was similar between treatment groups , except for a higher incidence of oral c and idiasis with fluticasone propionate/salmeterol . Conclusions : Short-term treatment with the combined inhaled corticosteroid and long-acting β2-adrenoceptor agonist fluticasone propionate/salmeterol result ed in greater control of lung function and symptoms than combined ipratropium bromide/albuterol bronchodilator therapy , in patients with COPD Background Cough and sputum are troublesome symptoms in chronic obstructive pulmonary disease ( COPD ) and are associated with adverse outcomes . The efficacy of aclidinium bromide 400 µg twice daily in patients with stable COPD has been established in two phase III studies ( ACCORD COPD I and ATTAIN ) and a phase IIIb active-comparator study . This analysis evaluated cough-related symptoms across these studies . Method Patients were r and omised to placebo , aclidinium 200 µg or 400 µg twice daily in ACCORD ( 12 weeks ) and ATTAIN ( 24 weeks ) , or to placebo , aclidinium 400 µg twice daily or tiotropium 18 µg once daily ( 6-week active-comparator study ) . Analysed end points included changes from baseline in Evaluating Respiratory Symptoms ( E-RS ; formerly known as EXAcerbations of Chronic pulmonary disease Tool ) , total and cough/sputum scores and frequency/severity of morning and night-time cough and sputum symptoms . Results Data for 1792 patients were evaluated . E-RS cough/sputum domain scores were significantly reduced with aclidinium 400 µg versus placebo in ATTAIN ( −0.7 vs −0.3 , respectively ; p<0.01 ) and the active-comparator study ( −0.6 vs −0.2 , respectively ; p<0.01 ) . In the active-comparator study , significantly greater improvements were observed with aclidinium versus placebo for severity of morning cough ( −0.19 vs −0.02 ; p<0.01 ) and phlegm ( −0.19 vs −0.02 ; p<0.05 ) . In ACCORD , aclidinium reduced night-time cough frequency ( −0.36 vs 0.1 for placebo ; p<0.001 ) and severity ( −0.24 vs −0.1 for placebo ; p<0.05 ) , and frequency of night-time sputum production ( −0.37 vs 0.05 for placebo ; p<0.001 ) . Conclusions Aclidinium 400 µg twice daily improves cough and sputum expectoration versus placebo in stable COPD . Trial registration numbers NCT00891462 ; NCT01001494 ; NCT01462929 STUDY OBJECTIVES To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone . DESIGN A r and omized , double-blind , double-dummy , two-period , crossover clinical trial . SETTING Twenty-four clinics and university medical centers in nine countries . PATIENTS One hundred seventy-two patients with baseline FEV(1 ) < or = 65 % predicted , with FEV(1 ) reversibility to salbutamol not exceeding the normal variability of the measurement , and symptomatic despite regular treatment with ipratropium bromide . INTERVENTIONS Each patient received two treatments in r and om order : either inhaled formoterol dry powder , 12 microg bid , in addition to ipratropium bromide , 40 microg qid for 3 weeks , followed by salbutamol , 200 microg qid , in addition to ipratropium , 40 microg qid for 3 weeks , or vice versa . MEASUREMENTS AND RESULTS Efficacy end points included morning premedication peak expiratory flow ( PEF ) during the last week of treatment ( primary end point ) , the area under the curve ( AUC ) for FEV(1 ) measured for 6 h after morning dose on the last day of treatment , and symptom scores ( from daily diary recordings ) . Morning PEF and the AUC for FEV(1 ) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium ( p = 0.0003 and p < 0.0001 , respectively ) . The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores ( p = 0.0042 ) . The safety profile of the two treatments was comparable . CONCLUSIONS In COPD patients requiring combination bronchodilator treatment , the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol Background Patients with chronic obstructive pulmonary disease ( COPD ) experience respiratory symptoms , which impair quality of life . This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status . Methods Data were pooled from two 24-week , r and omized , placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD ( ACLIFORM [ NCT01462942 ] and AUGMENT [ NCT01437397 ] ) . These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a ) Evaluating Respiratory Symptoms ( E-RS ™ ) score ≥10/<10 and b ) Baseline Dyspnea Index score < 7/≥7 . Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second ( FEV1 ) , Transition Dyspnea Index , E-RS total score , early-morning and nighttime symptom severity , early-morning limitation of activities , and exacerbation rate . Results Data for 3,394 patients were analyzed ( mean age : 63.5 years ; 60.5 % male ) . In both definitions of less and more symptomatic patients , aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo ( P<0.001 ) and both monotherapies ( P<0.05 ) . Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo ( P<0.05 ) and formoterol ( P<0.05 ) ; improvements were greater in more symptomatic patients . Improvements versus aclidinium were also observed in more symptomatic patients ( P<0.05 ) . Aclidinium/formoterol improved dyspnea , early-morning symptom severity , and limitation of activities versus placebo in both less and more symptomatic patients ( P<0.001 ) . In more symptomatic patients , aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies ( P<0.05 ) . The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients . Conclusion Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD , regardless of the definition used . Furthermore , patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1 , dyspnea , and early-morning symptoms Background Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) whose symptoms are insufficiently controlled by bronchodilator monotherapy . GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol ( IND ) and the long-acting muscarinic antagonist glycopyrronium ( GLY ) versus IND alone in patients with moderate-to-severe COPD . Material s and methods In this r and omized , double-blind , parallel group , placebo-controlled , 12-week study , patients were r and omized 1:1 to IND 150 μg and GLY 50 μg daily ( IND + GLY ) or IND 150 μg daily and placebo ( IND + PBO ) ( all delivered via separate Breezhaler ® devices ) . The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second ( FEV1 ) at week 12 . Other end points included trough FEV1 at day 1 , FEV1 area under the curve from 30 minutes to 4 hours ( AUC30min–4h ) , peak FEV1 , inspiratory capacity and trough forced vital capacity ( FVC ) at day 1 and week 12 , and transition dyspnea index ( TDI ) focal score , COPD symptoms , and rescue medication use over 12 weeks . Results A total of 449 patients were r and omized ( IND + GLY , 226 ; IND + PBO , 223 ) ; 94 % completed the study . On day 1 and at week 12 , IND + GLY significantly improved trough FEV1 versus IND + PBO , with treatment differences of 74 mL ( 95 % CI 46–101 mL ) and 64 mL ( 95 % CI 28–99 mL ) , respectively ( both P<0.001 ) . IND + GLY significantly improved postdose peak FEV1 , FEV1 AUC30min–4h , and trough FVC at day 1 and week 12 versus IND + PBO ( all P<0.01 ) . TDI focal score and COPD symptoms ( percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score ) were significantly improved with IND + GLY versus IND + PBO ( P<0.05 ) . The incidence of adverse events was similar for the two treatment groups . Conclusion In patients with moderate-to-severe COPD , once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1 , with significant improvements in patient-centered outcomes Background Symptomatic relief is an important treatment goal for patients with COPD . To date , no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-vali date d according to FDA and EMA guidelines . The EXACT – Respiratory Symptoms ( E-RS ) scale is a patient-reported outcome ( PRO ) measure design ed to address this need . The E-RS utilizes 11 respiratory symptom items from the existing and vali date d 14-item EXACT , which measures symptoms of exacerbation . The E-RS total score quantifies respiratory symptom severity , and 3 domains assess breathlessness , cough and sputum , and chest symptoms . Methods This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables : one 6-month ( N = 235 , US ) and two 3-month ( N = 749 ; N = 597 ; international ) . Subjects completed the E-RS as part of a daily eDiary . Tests of reliability , validity , and responsiveness were conducted in each data set . Results In each study , RS-Total score was internally consistent ( Cronbach α ) ( 0.88 , 0.92 , 0.92 ) and reproducible ( intra-class correlation ) in stable patients ( 2 days apart : 0.91 ; 7 days apart : 0.71 , 0.74 ) . RS-Total scores correlated significantly with the following criterion variables ( Spearman 's rho ; p < 0.01 , all comparisons listed here ) : FEV1 % predicted ( -0.19 , -0.14 , -0.15 ) ; St. George 's Respiratory Question naire ( SGRQ ) ( 0.65 , 0.52 , 0.51 ) ; Breathlessness , Cough , and Sputum Scale ( BCSS ) ( 0.89 , 0.89 ) ; modified Medical Research Council dyspnoea scale ( mMRC ) ( 0.40 ) ; rescue medication use ( 0.43 , 0.42 ) ; Functional Performance Inventory Short-Form ( FPI-SF ) ( 0.43 ) ; 6-minute walk distance ( 6-MWT ) ( -0.30 , -0.14 ) and incremental shuttle walk ( ISWT ) ( -0.18 ) tests . Correlations between these variables and RS-Breathlessness , RS-Cough and Sputum , RS-Chest Symptoms scores supported subscale validity . RS-Total , RS-Breathlessness , and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity ( p < 0.0001 ) . RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs ( p < 0.0001 ) . Sensitivity to changes in health status ( SGRQ ) , symptoms ( BCSS ) , and exercise capacity ( 6MWT , ISWT ) were also shown and responder definitions using criterion- and distribution-based methods are proposed . Conclusions Results suggest the E-RS is a reliable , valid , and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials . Trial registration MPEX : NCT00739648 ; AZ1 : NCT00949975 ; AZ 2 : In between exacerbations , chronic obstructive pulmonary disease ( COPD ) is usually regarded as a stable condition , but there is increasing recognition of variability in this state . This cross-sectional study assessed patients ' perception of symptom variability . Participants were out patients > 45 yrs old with COPD , current or ex-smokers , forced expiratory volume in 1 s ( FEV1 ) < 50 % predicted , FEV1/forced vital capacity < 0.7 and no exacerbation leading to therapeutic intervention in the previous 3 months . Patients ' perceptions of COPD symptoms and their impact on daily life activities were recorded . Alterations in therapy use in response to COPD worsening were also recorded . COPD symptoms were experienced by 2,258 ( 92.5 % ) out of 2,441 patients during the 7 days before interview . Breathlessness was the most common symptom ( 72.5 % ) . Daily and /or weekly symptom variability was reported by 62.7 % of symptomatic patients ; the morning was the worst time of day . Factors associated with perception of variability of breathlessness included younger age , symptom severity and recruitment to the study by general practitioners . The perception of variability was significantly different between European countries or regions . Patient-perceived COPD symptoms vary over the day and the week , and impact on daily activities ; morning being the worst time of day . The majority of patients appear not to adjust treatment when symptoms worsen Background The purpose of this study was to confirm the efficacy and safety of twice-daily glycopyrrolate 15.6 µg , a long-acting muscarinic antagonist , in patients with stable , symptomatic , chronic obstructive pulmonary disease ( COPD ) with moderate-to-severe airflow limitation . Methods The GEM1 study was a 12-week , multicenter , double-blind , parallel-group , placebo-controlled study that r and omized patients with stable , symptomatic COPD with moderate-to-severe airflow limitation to twice-daily glycopyrrolate 15.6 µg or placebo ( 1:1 ) via the Neohaler ® device . The primary objective was to demonstrate superiority of glycopyrrolate versus placebo in terms of forced expiratory volume in 1 second area under the curve between 0 and 12 hours post morning dose at week 12 . Other outcomes included additional spirometric end points , transition dyspnea index , St George ’s Respiratory Question naire , COPD Assessment Test , rescue medication use , and symptoms reported by patients via electronic diary . Safety was also assessed during the study . Results Of the 441 patients r and omized ( glycopyrrolate , n=222 ; placebo , n=219 ) , 96 % of patients completed the planned treatment phase . Glycopyrrolate demonstrated statistically significant ( P<0.001 ) improvements in lung function versus placebo . Glycopyrrolate showed statistically significant improvement in the transition dyspnea index focal score , St George ’s Respiratory Question naire total score , COPD Assessment Test score , rescue medication use , and daily total symptom score versus placebo at week 12 . Safety was comparable between the treatment groups . Conclusion Significant improvement in lung function , dyspnea , COPD symptoms , health status , and rescue medication use suggests that glycopyrrolate is a safe and effective treatment option as maintenance bronchodilator in patients with stable , symptomatic COPD with moderate-to-severe airflow limitation Background Morning symptoms associated with COPD have a negative impact on patients ’ quality of life . Long-acting bronchodilators with rapid onset may relieve patients ’ symptoms . In the Symptoms and Pulmonary function in the moRnING study , we prospect ively compared the rapid onset bronchodilator profile of glycopyrronium ( GLY ) and tiotropium ( TIO ) during the first few hours after dosing in patients with moderate-to-severe COPD . Methods Patients were r and omized ( 1:1 ) to receive either once-daily GLY ( 50 μg ) or TIO ( 18 μg ) and corresponding placebos in a cross-over design for 28 days . The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4 hours ( AUC0 - 4h ) forced expiratory volume in 1 second ( FEV1 ) after the first dose . The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Question naire 3 hours post-inhalation . Results One-hundred and twenty-six patients were r and omized ( male 70.2 % ; mean age 65.7 years ) and 108 patients completed the study . On Day 1 , GLY result ed in significantly higher FEV1 AUC0 - 4h after the first dose versus TIO ( treatment difference [ Δ ] , 0.030 L , 95 % confidence interval 0.004–0.056 , P=0.025 ) . Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO . Post hoc analysis of the FEV1 AUC0 - 4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes ( Δ=0.029 L , P=0.015 ) , 15 minutes ( Δ=0.033 L , P=0.026 ) , and 1 hour ( Δ=0.044 L , P=0.014 ) . Safety results were comparable between both treatments . Conclusion The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration , thus extending the clinical data that support a faster onset of action of GLY versus TIO Abstract Background : This r and omized , double-blind , Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . Methods : Patients received aclidinium 400 μg twice daily ( morning and evening ) , tiotropium 18 μg once daily ( morning ) , or placebo for 6 weeks . The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose ( FEV1 AUC0–24 ) at week 6 . Secondary and additional endpoints included FEV1 AUC12–24 , COPD symptoms ( EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [ E-RS ] total score and additional symptoms question naire ) , and safety . Results : Overall , 414 patients were r and omized and treated ( FEV1 1.63 L [ 55.8 % predicted ] ) . Compared with placebo , FEV1 AUC0–24 and FEV1 AUC12–24 were significantly increased from baseline with aclidinium ( ∆ = 150 mL and 160 mL , respectively ; p < 0.0001 ) and tiotropium ( ∆ = 140 mL and 123 mL , respectively ; p < 0.0001 ) at week 6 . Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium ( p < 0.0001 ) than tiotropium ( p < 0.05 ) versus placebo . Only aclidinium significantly reduced the severity of early-morning cough , wheeze , shortness of breath , and phlegm , and of nighttime symptoms versus placebo ( p < 0.05 ) . Adverse-event ( AE ) incidence ( 28 % ) was similar between treatments . Few anticholinergic AEs ( < 1.5 % ) or serious AEs ( <3 % ) occurred in any group . Conclusions : Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks . Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium . Aclidinium was generally well tolerated Background Aclidinium/formoterol is a twice-daily ( BID ) fixed-dose combination ( FDC ) in development for chronic obstructive pulmonary disease ( COPD ) . The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed . Methods In this 24-week double-blind , parallel-group , active- and placebo-controlled , multicentre Phase III study , patients ( ≥40 years , post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity < 70 % and FEV1 ≥30 % but < 80 % predicted normal ) were r and omised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg ( n = 385 ) or 400/6 μg ( n = 381 ) , aclidinium 400 μg ( n = 385 ) , formoterol 12 μg ( n = 384 ) or placebo ( n = 194 ) BID via Genuair ® /Pressair ® a . Results At Week 24 , aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium ( 125 mL [ 95 % CI : 90 , 160 ; p < 0 · 001 ] and 69 mL [ 95 % CI : 34 , 105 ; p < 0.001 ] , respectively ) and trough FEV1 versus formoterol ( 85 mL [ 95 % CI : 51 , 119 ; p < 0.001 ] and 53 mL [ 95 % CI : 19 , 87 ; p < 0.01 ] , respectively ; co- primary endpoints ) . Additionally , aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index ( TDI ) focal score versus placebo ( 1.29 units [ 95 % CI : 0.73 , 1.86 ; p < 0.001 ] and 1.16 units [ 95 % CI : 0.59 , 1.73 ; p < 0.001 ] , respectively ; secondary endpoint ) . All treatments were well tolerated , with safety profiles of the FDCs similar to those of placebo and monotherapy . Conclusions Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy , and dyspnoea versus placebo , with no increase in safety risk . Aclidinium/formoterol may be an effective treatment for patients with COPD .Trial registration Clinical Trials.gov : NCT01462942 Few studies have investigated the variability of COPD -related symptoms or factors related to symptom variability . This observational , prospect i ve , multicentre study was conducted to describe the number and intensity of morning and night-time respiratory symptoms and their variability over one week using the Night-time and Early Morning Symptoms of COPD Instruments ( NiSCI and EMSCI ) to evaluate stable COPD patients . Logistic regression analyses were performed to investigate factors associated with symptom variability . A total of 2669 patients were evaluated ( mean age , 67.7 years ; 80.9 % men ; mean FEV1 50.6 % ) . Of these , 48 % reported night-time symptoms and 71 % reported morning symptoms . Of the 2293 patients who completed the NiSCI and EMSCI , 90 % showed variability in either symptom number ( 89.6 % ) or symptom intensity ( 15.8 % ) . More severe dyspnoea , more exacerbations during the previous year and the exacerbator or mixed COPD -asthma phenotypes were associated with variability in symptom number or intensity . Anxiety was significantly associated with variability in symptom number and intensity . Most COPD patients showed symptom variability over a weeklong period , especially in terms of symptom number . Several COPD -related factors , mainly factors related to more severe disease and more frequent exacerbations , were associated with increased symptom variability RATIONALE Indacaterol is the first once-daily , long-acting inhaled beta(2)-agonist bronchodilator studied in patients with chronic obstructive pulmonary disease ( COPD ) . OBJECTIVES To demonstrate greater efficacy of indacaterol versus placebo on FEV(1 ) at 24 hours post dose ( trough ) after 12 weeks , to compare efficacy with placebo and tiotropium , and to evaluate safety and tolerability over 26 weeks . MEASUREMENTS Patients with moderate-to-severe COPD were r and omized to double-blind indacaterol 150 or 300 microg or placebo , or open-label tiotropium 18 microg , all once daily , for 26 weeks . The primary efficacy outcome was trough FEV(1 ) at 12 weeks . Additional analyses ( not adjusted for multiplicity ) included transition dyspnea index ( TDI ) , health status ( St George 's Respiratory Question naire [ SGRQ ] ) , and exacerbations . Serum potassium , blood glucose , and QTc interval were measured . RESULTS A total of 1,683 patients ( age , 63.3 yr ; post-bronchodilator FEV(1 ) , 56 % predicted ; FEV(1)/FVC , 0.53 ) were r and omized to the four treatment arms . Trough FEV(1 ) at Week 12 increased versus placebo by 180 ml with both indacaterol doses and by 140 ml with tiotropium ( all P < 0.001 vs. placebo ) . At Week 26 , for indacaterol 150/300 microg , respectively , versus placebo , TDI increased ( 1.00/1.18 , P < 0.001 ) and SGRQ total score decreased ( -3.3/-2.4 , P < 0.01 ) ; corresponding results with tiotropium were 0.87 ( P < 0.001 ) for TDI and ( -1.0 , P = not significant ) for SGRQ total score . The incidence of adverse events , low serum potassium , high blood glucose , and prolonged QTc interval was similar across treatments . CONCLUSIONS Indacaterol was an effective once-daily bronchodilator and was at least as effective as tiotropium in improving clinical outcomes for patients with COPD . Clinical trial registered with clinical trials.gov ( NCT 00463567 ) BACKGROUND The inhaled long-acting muscarinic antagonist aclidinium bromide has been shown to significantly improve lung function parameters and symptom severity in patients with COPD in r and omised placebo- and active-controlled clinical studies . To obtain a comprehensive view of the treatment effects , patient-reported outcomes were investigated in a real-life COPD population in routine clinical practice in Austria . METHODS Multicentre , prospect i ve , non-interventional study in patients with COPD who were newly initiated on treatment with Eklira ® Genuair ® ( aclidinium bromide ; recommended dose 400 μg twice daily ) as first-line or add-on therapy . Patients were either treatment naïve or switched from other COPD medications . Health-related quality of life by means of the COPD Assessment Test ™ ( CAT ) and symptom-related variables were evaluated at the first visit ( baseline ) and after approximately 12 weeks of treatment . Features of the inhaler were assessed by patients and physicians at the follow-up visit . RESULTS A total of 795 COPD patients ( 56 % male ; median age : 64 years ) were enrolled and treated . During the observational period , the proportion of patients with at least moderate nighttime symptoms , early-morning symptoms , and limitations in morning activities decreased from 45.0 % to 21.4 % , from 57.7 % to 26.0 % , and from 49.9 % to 25.3 % , respectively . All improvements from baseline in symptom severity and activity limitation were statistically significant ( p < 0.0001 , all tests ) . The mean ( ±SD ) frequency of nocturnal awakenings decreased from 1.2 ( ±1.4 ) to 0.7 ( ±1.2 ) times per night ( p < 0.0001 ) . Quality of life improved significantly in patients treated with aclidinium bromide over 3 months compared to baseline ( p < 0.0001 ; mean CAT total score : 18.5 ± 7.5 vs. 13.8 ± 7.3 ) . Up to 90 % of the patients and up to 91 % of the physicians assessed individual features of the inhaler as ' very good ' or ' good ' . Aclidinium bromide was well tolerated ; 6.9 % of the patients reported adverse drug reactions , none of which were serious . CONCLUSIONS This non-interventional study indicated beneficial effects of Eklira ® Genuair ® in the treatment of COPD with regard to nighttime and early-morning symptoms , limitation of morning activities , and quality of life under routine conditions . The acceptance of the inhaler device was high , which is a prerequisite to ensure adherence in long-term therapy This report concerns the development and validation of two patient-reported outcomes question naires developed to assess chronic obstructive pulmonary disease ( COPD ) patients ’ ability to perform morning activities and to evaluate their morning symptoms . Based on interviews with COPD patients , the Capacity of Daily Living during the Morning ( CDLM ) question naire and the Global Chest Symptoms Question naire ( GCSQ ) were developed , linguistically vali date d and incorporated into two multicentre , r and omised trials involving a total of 1,100 COPD patients ; those trials were registered at Clinical Trials.gov ( NCT00496470 and NCT00542880 ) . Data from these trials were used to determine the reliability , validity and responsiveness of the question naires and to derive estimates of minimal important differences ( MIDs ) . Both question naires displayed good-to-high reliability ( Cronbach ’s & agr ; 0.75–0.93 ) . Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly ( p<0.001 ) with symptoms , health-related quality of life ( HRQoL ) and use of rescue medication . In both trials , CDLM and GCSQ scores discriminated between patients with different levels of HRQoL , as assessed by the St George 's Respiratory Question naire for COPD patients ( SGRQ-C ) , but not with disease severity , as assessed by the Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) criteria . A significant improvement in CDLM and GCSQ scores occurred in response to treatment . Estimations of MID scores , corresponding to an SGRQ-C MID of 4 , were 0.20 for the CDLM question naire and 0.15 for the GCSQ . Both the CDLM question naire and the GCSQ are easy-to-use , reliable , responsive , self-administered question naires that report on patients ' symptoms and ability to perform morning activities Abstract Background : This survey assessed the impact of symptoms of COPD on patients ’ ability to perform activities throughout the day and the extent to which physicians provided advice including how medications may help maintain quality of life . Methods : The survey had three inclusion criteria – physician ’s diagnosis of COPD , age 30–70 years and presence of at least one of four listed symptoms to a greater extent in the morning . Participants were r and omly selected from a panel who had previously agreed to participate in surveys . The survey was conducted in eight countries and contained 31 questions in the main section on the effects of symptoms of COPD throughout the day on patients ’ ability to perform tasks , how patients adjusted their lives and the extent to which physicians offered advice and support . Results : Routine activities took 10–15 minutes longer and more strenuous activities around 30 minutes longer than before symptoms had become worse in the morning . Half had made changes to their morning routines and just over half confirmed that morning symptoms affected the rest of their day . The majority believed their medications provided sufficient relief of morning symptoms but less than a quarter believed they helped improve their ability to perform tasks . Physicians were unlikely to discuss this aspect of patient care routinely even though there was evidence to suggest that the challenge of performing tasks had a greater impact on patients than the symptoms themselves . Conclusions : Morning symptoms of COPD can severely compromise patients ’ ability to perform tasks throughout the day . Despite this , physicians are unlikely to discuss with patients how their ability to perform tasks might be improved This retrospective analysis of data from two multi-center , r and omized , double-blind , parallel group studies compared the efficacy of fluticasone propionate/salmeterol ( FSC ) 250/50 mcg twice daily with ipratropium bromide/albuterol ( IB/ALB ) 36/206 mcg four times daily in albuterol-reversible ( n=320 [ 44 % ] ) and non-reversible ( n=399 [ 56 % ] ) patients with COPD . In reversible and non-reversible patients , both treatments significantly increased FEV(1)AUC(0 - 6h ) from baseline and the magnitude of improvement was larger in reversible patients . FSC increased FEV(1)AUC(0 - 6h ) by 1.46+/-0.08 and 1.98+/-0.13 l-h at Day 1 and Week 8 , respectively , in reversible patients , compared with 0.71+/-0.06 and 0.94+/-0.10 l-h in non-reversible patients ( p<0.001 ) . With IB/ALB , increases were 1.46+/-0.08 and 1.19+/-0.11 l-h at Day 1 in reversible patients and Week 8 , respectively , and 0.89+/-0.06 and 0.74+/-0.09 l-h ( p < or = 0.041 ) in non-reversible patients . After 8 weeks , in both the reversible and non-reversible population s , the FEV(1 ) AUC(0 - 6h ) significantly increased with FSC treatment ( p < or = 0.002 ) and significantly decreased with IB/ALB ( p < or = 0.010 ) . In both reversibility groups , improvement in Transition Dyspnea Index ( TDI ) scores , overall daytime diary symptom scores and nocturnal symptom measures were significantly greater with FSC treatment compared with IB/ALB ( p < or = 0.044 ) . Reversibility status was not predictive of the magnitude of reduction in symptom scores . We conclude that both reversible and non-reversible patients receive greater clinical benefit with FSC compared with IB/ALB and acute bronchodilator reversibility is not useful for differentiating patients based on symptomatic responses to FSC compared with IB/ALB INTRODUCTION DACCORD is an ongoing , longitudinal , non-interventional study within the German COPD National Prospect i ve Registry . This manuscript describes the baseline characteristics of the first 5924 participants , recruited between November 2012 and November 2013 . METHODS The main inclusion criteria are a physician diagnosis of COPD , age ≥40 years , and initiating or changing COPD maintenance medication . Data collected included : Demographic and disease characteristics ; prescribed medication ; symptoms ; COPD Assessment Test ( CAT ) ; modified Medical Research Council dyspnoea score ( mMRC ) ; exacerbations ; comorbidities ; and forced expiratory volume in 1 s ( FEV1 ) . RESULTS Approximately 60 % of the population are male , with mean age of 65.7 years and FEV1 61.6 % predicted . On entry to the study the majority of patients reported symptoms , most commonly exertional dyspnoea ( 85.9 % ) and cough ( 65.7 % ) . According to GOLD 2010 , 48.6 % of patients were classified as GOLD II . GOLD 2011 classification was influenced by the symptoms criterion : 43.7 and 45.3 % of patients were classified as GOLD B or D using CAT , compared with 26.4 and 34.0 % , respectively , using mMRC . The majority of patients were receiving a LAMA-containing regimen , with 39.4 % overall receiving ICS . A total of 78.3 % of patients reported at least one comorbidity , most commonly cardiovascular . CONCLUSION In conclusion , DACCORD is a large , prospect i ve , non-interventional study that provides an informative and intriguing picture of the typical COPD patient in Germany The efficacy and safety of salmeterol alone was compared with the combination of salmeterol plus ipratropium and with placebo during long-term treatment in patients with stable chronic obstructive pulmonary disease . In addition , the single-dose effect in response to the first dose of treatment was studied over 12 h. The patients ( n=144 ; age 64+/-7 yrs , forced expiratory volume in one second ( FEV1 ) 44+/-11 % pred ) participated in a three-centre double-blind double-placebo parallel group study and were r and omized after a run-in period of 2 weeks to receive either salmeterol 50 microg b.i.d . , salmeterol 5 microg b.i.d . plus ipratropium 40 microg q.i.d . or placebo for a period of 12 weeks . The single-dose study demonstrated that salmeterol produced a significant increase in FEV1 ( peak of 7 % pred ) and specific airway conductance ( sGaw ) ( maximum of 60 % baseline ) for > or = 12 h. The combination of salmeterol plus ipratropium elicited a greater bronchodilator response ( 11 % and 94 % increases respectively ) than salmeterol alone during the first 6 h after inhalation . During treatment there were significant improvements in daytime symptom scores and morning peak expiratory flow in both the salmeterol and the salmeterol plus ipratropium groups ( p<0.001 ) , with an associated decrease in the use of rescue salbutamol . Improvements in FEV1 and sGaw were greater in the salmeterol plus ipratropium group than in the patients receiving only salmeterol . Thirty-five patients had an exacerbation ; 11 ( 23 % ) in the salmeterol group ( versus placebo NS ) , six ( 13 % ) in the salmeterol plus ipratropium group ( versus placebo p<0.01 ) and 18 ( 36 % ) in the placebo group . In conclusion , in patients with severe stable chronic obstructive pulmonary disease , long-term treatment with either salmeterol alone or salmeterol plus ipratropium is safe and effective . There was added benefit from the combination therapy in terms of improvement in airways obstruction , but not for improvement in symptom control or need for rescue salbutamol BACKGROUND QVA149 is an inhaled fixed-dose combination therapy under development for the treatment of chronic obstructive pulmonary disease ( COPD ) . It combines indacaterol ( a longacting β2-agonist ) with glycopyrronium ( a longacting muscarinic antagonist ) as a dual bronchodilator . We aim ed to compare the efficacy , safety , and tolerability of QVA149 versus salmeterol-fluticasone ( SFC ) over 26 weeks in patients with moderate-to-severe COPD . METHODS In this multicentre double-blind , double-dummy , parallel-group study , 523 patients ( age 40 years or older , Global Initiative for Chronic Obstructive Lung Disease [ GOLD ] stages II-III , without exacerbations in the previous year ) were r and omly assigned ( 1:1 ; via automated , interactive response technology and stratified for smoking status ) to once-daily QVA149 110/50 μg or twice-daily SFC 50/500 μg for 26 weeks . Efficacy was assessed in the full analysis set ( r and omised patients who received at least one dose of study drug ) ; safety was assessed in all patients who received at least one dose of study drug . The primary endpoint was to demonstrate the superiority of QVA149 compared with SFC for the st and ardised area under the curve from 0 to 12 h post dose for forced expiratory volume in 1 second ( FEV1 AUC0 - 12h ) after 26 weeks of treatment . This trial was registered at Clinical Trial.gov , NCT01315249 . FINDINGS Between March 25 , 2011 , and March 12 , 2012 , 259 patients were r and omly assigned to receive QVA149 and 264 to receive SFC . At week 26 , FEV1 AUC0 - 12h was significantly higher with QVA149 than with SFC ( treatment difference 0·138 L ; 95 % CI 0·100 - 0·176 ; p<0·0001 ) . Overall incidence of adverse events ( including COPD exacerbations ) was 55·4 % ( 143 of 258 ) for the QVA149 group and 60·2 % ( 159 of 264 ) for the SFC group . Incidence of serious adverse events was similar between treatment groups ( QVA149 , 13 of 258 [ 5·0 % ] ; SFC 14 of 264 [ 5·3 % ] ) ; COPD worsening was the most frequent serious adverse event ( one of 13 [ 0·4 % ] and three of 14 [ 1·1 % ] , respectively ) . INTERPRETATION Once-daily QVA149 provides significant , sustained , and clinical ly meaningful improvements in lung function versus twice-daily SFC , with significant symptomatic benefit . These results indicate the potential of dual bronchodilation as a treatment option for non-exacerbating symptomatic COPD patients . FUNDING Novartis Pharma AG We studied circadian variation in FVC , FEV1 , PEF , TLC , VC , and RV between 9:00 A.M. and 9:00 P.M. and analyzed how this variation affected estimated longitudinal change . Data from 876 adults were obtained in a longitudinal survey of sample s from two Dutch areas . Subjects participated in four surveys held at 3-yr intervals between 1975 and 1985 . FVC , FEV1 , PEF , and VC increased from 9:00 A.M. until noon and decreased afterwards . TLC was constant over the day , whereas RV decreased from 9:00 A.M. to noon . Average variation in FVC , FEV1 and PEF , expressed as percentages of average level , was 4 . 8 % ( 200 ml ) , 2.8 % ( 86 ml ) , and 3.1 % ( 250 ml/s ) , respectively . These results are compatible with circadian changes in airway size . No differences in variability were found between men and women . Significantly larger changes between 9:00 A.M. and noon were found in young adults , smokers , and those with respiratory symptoms than in other subgroups . Adjustment for diurnal variation reduced , albeit slightly , residual st and ard deviations of estimated longitudinal declines . Average diurnal change was large relative to underlying longitudinal change . Its effect on longitudinal change within an individual can therefore be large depending on age , smoking habits , symptomatology , number of visits , time of measurement , and difference in time between measurements . However , when people are measured at r and om times during the day for at least three visits , or when measurements are made after 11:00 A.M. , effects of diurnal variation in pulmonary function on estimated average longitudinal decline are minimal BACKGROUND QVA149 is an inhaled , once-daily fixed-dose dual bronchodilator combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium ( NVA237 ) for the treatment of chronic obstructive pulmonary disease ( COPD ) . We investigated the safety and efficacy of QVA149 over 52 weeks . METHODS This 52-week , multicenter , double-blind , parallel-group , placebo-controlled study r and omized ( 2:1 ) patients with moderate-to-severe COPD to once-daily QVA149 ( 110 μg indacaterol/50 μg glycopyrronium ) or placebo delivered via the Breezhaler device . Primary endpoint was safety and tolerability for treatment-emergent adverse events ( AEs ) . Secondary endpoints included safety based on vital signs , electrocardiograms ( ECGs ) , laboratory evaluations , and pre-dose forced expiratory volume in 1 s ( FEV1 ) . RESULTS Of 339 patients r and omized , QVA149 [ n = 226 ] , placebo [ n = 113 ] ; 76.9 % male , mean age : 62.6 years , post-bronchodilator FEV1 : 57.4 % predicted , 83.5 % completed study . A smaller percentage of patients discontinued in the QVA149 group ( 14.2 % ) compared with placebo ( 21.2 % ) . Overall incidence of AEs was similar in the QVA149 ( 57.8 % ) and placebo ( 56.6 % ) groups , with most AEs being mild to moderate in severity . The numerical differences in some AEs observed could be at least in part explained by differences in baseline patient characteristics . No clinical ly relevant differences were observed between treatment groups for vital signs or ECG parameters . The five deaths reported were unrelated to study medication ( QVA149 , n = 4 [ 1.8 % ] ; placebo , n = 1 [ 0.9 % ] ) . QVA149 demonstrated rapid and clinical ly meaningful bronchodilation sustained over 52 weeks versus placebo . CONCLUSION QVA149 demonstrated a good safety and tolerability profile , providing rapid and sustained bronchodilation over 52 weeks in patients with moderate-to-severe COPD . Clinical Trials.gov identifier : NCT01120717 RATIONALE Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease . Combining these medications may provide additional benefits . OBJECTIVES To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting beta(2)-agonist combination therapy . METHODS In this 12-week , r and omized , double-blind , parallel-group , multicenter study , after a 2-week run-in , 660 subjects ( 75 % male ; mean age , 62 yr ; FEV(1 ) , 1.1 L ; 38 % predicted normal ) , 40 years of age or older , received tiotropium ( 18 microg once daily ) plus either budesonide/formoterol ( 320/9 microg ) ( n = 329 ) or placebo ( n = 331 ) twice daily . MEASUREMENTS AND MAIN RESULTS Clinic predose ( primary outcome ) and postdose FEV(1 ) , predose and postdose forced vital capacity and inspiratory capacity , and health status were measured . Other outcomes included daily measurements taken at home ( pre- and postdose morning FEV(1 ) and peak expiratory flow , morning symptoms and activities , and morning reliever use ) , severe exacerbations , and tolerability . Over the treatment period , budesonide/formoterol plus tiotropium significantly increased predose FEV(1 ) by 6 % ( 65 ml ) and postdose by 11 % ( 123 and 131 ml at 5 and 60 min postdose , respectively ) versus tiotropium alone ( both P < 0.001 ) . Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone . The number of severe exacerbations decreased by 62 % ( rate ratio , 0.38 ; 95 % confidence interval , 0.25 - 0.57 ; P < 0.001 ) . Both treatments were well tolerated . CONCLUSIONS In patients with chronic obstructive pulmonary disease , budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function , health status , morning symptoms and activities , and reduces severe exacerbations . Clinical trial registered with www . clinical trials.gov ( NCT00496470 ) |
13,463 | 22,407,585 | AND IMPLICATION S OF KEY FINDINGS The analysis suggests a moderate effect of electronically generated , individually tailored reminders on clinician behaviour during the clinical encounter . | OBJECTIVE To synthesis e current evidence for the influence on clinical behaviour of patient-specific electronically generated reminders available at the time of the clinical encounter . | OBJECTIVE To study the effect of a computerized medical record and other practice factors on the delivery of preventive health care . DESIGN Prospect i ve , controlled trial . SETTING University general internal medicine teaching clinic . PARTICIPANTS Forty-five internal medicine residents and their 4 supervising attending physicians . INTERVENTION The study group used a computerized ambulatory medical record system that included health care maintenance reminders . The control group used a conventional paper record with a health care maintenance flow sheet . MEASUREMENTS AND MAIN RESULTS The computer reminders significantly increased health care maintenance recommendations made to patients for proctosigmoidoscopy , tetanus vaccination , influenza vaccination , and pneumococcal vaccination , but not for fecal occult blood testing , mammography , Pap smears , or serum thyroxine screening in the elderly . First-year residents were nearly twice as successful as third-year residents in overall health care maintenance . Success scores varied markedly depending on which attending physician was supervising the residents . We found a strong interaction among group assignment , supervising attending , and level of training such that the reminders doubled success scores among first-year residents supervised by two of the attending physicians but had little effect on other subgroups . The time of year and the format of the reminder also had important effects for some of the maneuvers . CONCLUSIONS Although computerized medical records markedly improved the performance of prevention maneuvers by committed physicians , many physicians using computer systems failed to make use of the re source . The reasons for this were complex . Future work in this area should carefully control for personal behaviors and focus upon administrative changes that more effectively implement these potentially powerful tools 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 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 OBJECTIVE Computerized physician order entry with clinical decision support has been shown to improve medication safety in adult in patients , but few data are available regarding its usefulness in the long-term care setting . The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a warning message to the prescriber via a computerized clinical decision support system and assessing the extent to which these alerts would affect prescribers ' actions . DESIGN The study was set within a r and omized controlled trial of computerized clinical decision support conducted in the long-stay units of a large , academically-affiliated long-term care facility . In March 2002 , a computer-based clinical decision support system ( CDSS ) was added to an existing computerized physician order entry ( CPOE ) system . Over a subsequent one-year study period , prescribers ordering drugs for residents on three resident-care units of the facility were presented with alerts ; these alerts were not displayed to prescribers in the four control units . MEASUREMENTS We assessed the frequency of drug orders associated with various categories of alerts across all participating units of the facility . To assess the impact of actually receiving an alert on prescriber behavior during drug ordering , we calculated separately for the intervention and control units the proportion of the alerts , within each category , that were followed by an appropriate action and estimated the relative risk of an appropriate action in the intervention units compared to the control units . RESULTS During the 12 months of the study , there were 445 residents on the participating units of the facility , contributing 3,726 resident-months of observation time . During this period , 47,997 medication orders were entered through the CPOE system-approximately 9 medication orders per resident per month . 9,414 alerts were triggered ( 2.5 alerts per resident-month ) . The alert categories most often triggered were related to risks of central nervous system side-effects such as over-sedation ( 20 % ) . Alerts for risk of drug-associated constipation ( 13 % ) or renal insufficiency/electrolyte imbalance ( 12 % ) were also common . Twelve percent of the alerts were related to orders for warfarin . Overall , prescribers who received alerts were only slightly more likely to take an appropriate action ( relative risk 1.11 , 95 % confidence interval 1.00 , 1.22 ) . Alerts related to orders for warfarin or central nervous system side effects were most likely to engender an appropriate action , such as ordering a recommended laboratory test or canceling an ordered drug . CONCLUSION Long-term care facilities must implement new system-level approaches with the potential to improve medication safety for their residents . The number of medication orders that triggered a warning message in this study suggests that CPOE with a clinical decision support system may represent one such tool . However , the relatively low rate of response to these alerts suggests that further refinements to such systems are required , and that their impact on medication errors and adverse drug events must be carefully assessed OBJECTIVE The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease ( CAD ) care and to assess physician attitudes toward this reminder system . DESIGN We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics . Clinics were r and omized so that physicians received either evidence -based electronic reminders within their patients ' electronic medical record or usual care . There were five reminders for diabetes care and four reminders for CAD care . MEASUREMENTS The primary outcome was receipt of recommended care for diabetes and CAD . We created a summary outcome to assess the odds of increased compliance with overall diabetes care ( based on five measures ) and overall CAD care ( based on four measures ) . We surveyed physicians to assess attitudes toward the reminder system . RESULTS Baseline adherence rates to all quality measures were low . While electronic reminders increased the odds of recommended diabetes care ( odds ratio [ OR ] 1.30 , 95 % confidence interval [ CI ] 1.01 - 1.67 ) and CAD ( OR 1.25 , 95 % CI 1.01 - 1.55 ) , the impact of individual reminders was variable . A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD . The majority of physicians ( 76 % ) thought that reminders improved quality of care . CONCLUSION An integrated electronic reminder system result ed in variable improvement in care for diabetes and CAD . These improvements were often limited and quality gaps persist OBJECTIVE Interruptive alerts within electronic applications can cause " alert fatigue " if they fire too frequently or are clinical ly reasonable only some of the time . We assessed the impact of non-interruptive , real-time medication laboratory alerts on provider lab test ordering . DESIGN We enrolled 22 outpatient practice s into a prospect i ve , r and omized , controlled trial . Clinics either used the existing system or received on-screen recommendations for baseline laboratory tests when prescribing new medications . Since the warnings were non-interruptive , providers did not have to act upon or acknowledge the notification to complete a medication request . MEASUREMENTS Data were collected each time providers performed suggested laboratory testing within 14 days of a new prescription order . Findings were adjusted for patient and provider characteristics as well as patient clustering within clinics . RESULTS Among 12 clinics with 191 providers in the control group and 10 clinics with 175 providers in the intervention group , there were 3673 total events where baseline lab tests would have been advised : 1988 events in the control group and 1685 in the intervention group . In the control group , baseline labs were requested for 771 ( 39 % ) of the medications . In the intervention group , baseline labs were ordered by clinicians in 689 ( 41 % ) of the cases . Overall , no significant association existed between the intervention and the rate of ordering appropriate baseline laboratory tests . CONCLUSION We found that non-interruptive medication laboratory monitoring alerts were not effective in improving receipt of recommended baseline laboratory test monitoring for medications . Further work is necessary to optimize compliance with non-critical recommendations Advance directives name a surrogate decision maker or provide written instructions with the intent of extending patient autonomy with respect to end-of-life decisions [ 1 - 3 ] . Supported on various grounds by the public [ 1 ] , physicians [ 4 ] , ethicists [ 5 ] , and legislators [ 6 ] , advance directives have also been promoted as a way to control the high costs of health care at the end of life [ 7 , 8 ] . Most patients are interested in establishing advance directives , but few actually complete them [ 1 , 9 , 10 ] . In 1990 , the U.S. Congress passed the Patient Self-Determination Act , which requires hospitals to inform admitted patients about their right to record advance directives [ 6 , 11 ] . The Act does not dictate who should initiate these discussion s ( patients , physicians , or an admissions officer , for example ) [ 12 , 13 ] . It is therefore not surprising that the Act has had little effect on the rate of completion of advance directives [ 11 , 13 - 15 ] . Because hospitalized patients are often acutely ill and lose their ability to make decisions [ 3 ] , it may be more appropriate to discuss such issues before hospitalization [ 12 , 16 , 17 ] . Other interventions aim ed at increasing the establishment of advance directives have met with mixed success [ 18 ] . With one exception [ 19 ] , patient education has had little or no effect [ 20 - 24 ] . More effective interventions have trained physicians , social workers , or counselors to discuss advance directives [ 18 , 22 , 25 - 27 ] ; this has led to the conclusion that counseling by a clinician is the best catalyst for the completion of advance directives [ 28 ] . However , little is known about how to educate and motivate clinicians to solicit advance directives [ 28 ] . We [ 29 - 31 ] and others [ 32 ] have previously shown that computer reminders increase physician compliance with practice guidelines . In this study , we tested the hypothesis that reminding primary care physicians to discuss advance directives would stimulate such discussion s and lead to the establishment of more advance directives . Methods Setting and Patients This study was approved by the institutional review board of Indiana University as expedited research with waiver of informed consent from both patients and physicians . It was conducted in the General Medicine Practice [ 31 ] , an academic primary care practice affiliated with an urban public teaching hospital . This practice is staffed by general internal medicine faculty , fellows , and residents . Each resident and fellow attends the General Medicine Practice one half-day per week ; faculty attend one to four half-days per week . Residents always practice with the same attending faculty physicians . All physicians , except for study investigators , were eligible to participate . At the time of this study , the General Medicine Practice comprised four separate practice s with separate waiting areas , clerks , and nurses . Each practice held eight half-day sessions per week . Each session was attended by two faculty members and two or three residents , each of whom provided primary care to assigned panels of patients . Residents were required to briefly discuss each patient with the attending faculty . Fellows served as faculty and were treated as such . Since 1981 , a computerized program has r and omly assigned new physicians to the practice sessions [ 31 ] . New patients have been sequentially assigned to open appointment slots ; this result ed in no important differences in patients or clinical practice among the sessions [ 29 , 33 ] . We included patients who were at risk for acute deterioration ( and therefore might benefit from advance directives ) because of advanced age ( 75 years , the typical threshold for the oldest old ) or because they were 50 years of age or older and had one of the following chronic conditions : cardiac ischemia , heart failure , chronic lung disease , cancer other than nonmelanomatous skin cancer , cerebrovascular disease , renal insufficiency , or cirrhosis . We chose 50 years of age as a cut-off to yield sufficient numbers of patients . A computer program identified eligible patients among those with scheduled appointments at the General Medicine Practice by using problem lists and test results stored in the Regenstrief Medical Record System [ 34 ] . Eligible patients who kept appointments at the General Medicine Practice were approached by research assistants in the waiting room . The research assistants , who were blinded at all times to the patients ' study groups , explained the study to the patients , invited them to participate , and interviewed those who agreed to participate ; patients from nursing homes and prisons and patients who were deaf or did not speak English were excluded . The assistants then administered the Pfeiffer Mental Status Question naire [ 35 ] ; patients whose scores indicated cognitive dysfunction were excluded . The remaining patients provided sociodemographic information and stated whether they had previously discussed or completed advance directives ; patients who had completed advance directives were excluded . Patients also stated their preferences with regard to six treatments in the event of a terminal illness [ 36 ] . Advance Directives Before the study , we created two separate forms for instruction directives and proxy directives ; these forms became the official advance directive documents of the hospital and its outpatient services . The instruction directive allowed patients to indicate whether , in the event of terminal illness and mental incapacity , they wanted or did not want eight types of care : cardiopulmonary resuscitation , mechanical ventilation , surgery , invasive procedures , nutrition and hydration , transfusion of blood or blood products , antibiotics , or noninvasive diagnostic tests . The primary care physician had to sign each completed instruction directive form to indicate that he or she was aware of its contents . The proxy directive design ated both primary and secondary health care representatives . We placed both advance directive forms in a drawer of the desk of each physician in the General Medicine Practice . We also placed the forms in a bin near the door of the staff room along with other forms and requisitions and business reply envelopes for patients who wanted to complete the forms at home . Research assistants entered the data from completed forms into the Regenstrief Medical Record System , where the forms were available for viewing through computer terminals and workstations in all inpatient and outpatient venues [ 34 ] . Before the study , the three physician-investigators presented the basic concepts of advance directives at gr and rounds . They also had face-to-face meetings with each physician in the General Medicine Practice and explained how to complete and process the forms . We encouraged physicians to discuss advance directives with their elderly and debilitated patients and posted flyers in each practice staffing room suggesting that physicians discuss advance directives with patients who had the target study conditions . Study Methods The intent of the r and omization scheme was to expose physicians to the same type of reminder or reminders , or no reminders , during all of their scheduled primary care visits with enrolled patients . At the time of this study , 32 weekly half-day sessions took place on the four General Medicine Practice practice s. Two sessions attended by study investigators were excluded . We r and omly assigned all of the physicians who worked in a particular half-day session to the same reminder category . At the time of r and omization , 16 physicians ( all of whom were faculty members ) practice d in more than 1 session per week ( 14 practice d in 2 sessions and 2 practice d in 3 sessions ) . Therefore , we r and omly assigned the sessions in a stepped manner by first allocating the 16 physicians and all of their associated sessions to four categories : control ( no reminders ) , computer-generated reminders for instruction directives , computer-generated reminders for proxy directives , and computer-generated reminders for both types of directives . We then r and omly assigned the remaining 8 sessions and their physicians to the four categories ( Table 1 ) . Each practice contained sessions in all four categories , which were equally distributed between mornings and afternoons . Table 1 . Results of R and omization All physicians routinely received computer-generated reminders for patients with scheduled visits . They were reminded to give preventive care , note abnormal test results , and avoid drug interactions [ 29 , 34 ] . These reminders appeared at the bottom of computer-generated printed encounter forms [ 34 ] ( Figure 1 ) . Physicians routinely review ed the encounter forms and the practice chart immediately before visiting the patient . As recommended by Litzelman and coworkers [ 37 ] , the advance directive reminders were followed by a choice list ( discussed today , next visit , not applicable , patient too ill , patient refuses to discuss , I disagree with advance directives ) . Instruction directives were called advance directives , and proxies were called health care representatives ( Figure 1 ) . Figure 1 . General Medicine Practice encounter form showing reminders for both types of advance directive . After patients were enrolled , research assistants attempted to interview them in the waiting room after each scheduled appointment to assess whether they had discussed advance directives with their physicians that day . Patients who answered yes were defined as having had an advance directive discussion . During the first scheduled General Medicine Practice visit in the 5-month period between 11 and 16 months after enrollment , a close-out interview was attempted . If no scheduled visit had occurred by 15 months after enrollment , the close-out interview was attempted by telephone . Form completion was defined as having occurred if either completed form was received between study enrollment and 30 days after the final interview ( this made it possible to receive by mail forms that were completed after the close-out OBJECTIVE To review all r and omized clinical trials addressing the efficacy of clinical information systems and to determine the clinical setting s , types of interventions , and effects studied . DATA SOURCES Extensive and systematic MEDLINE search es were conducted using a combination of medical subject headings ( MeSH ) and textword terms to collect trial reports . Manual search es of books and monographs as well as informal contacts were also used . STUDY SELECTION The eligibility criteria were ( 1 ) r and omized controlled clinical trial , ( 2 ) computerized information intervention in the study group , and ( 3 ) effect measured on the process or outcome of care . DATA EXTRACTION Two research assistants independently abstract ed from the selected reports the following structured information : trial sites , computerized interventions , effect variables , and outcomes . Three investigators evaluated the combined list of trial features for setting , intervention , and effect . The statistical analysis included an evaluation of agreement in developing classifications and an analysis of the ratio of positive trial outcomes . DATA SYNTHESIS Most information services were tested in outpatient care ( 82 % ) , particularly in primary care ( 66 % ) . The information intervention targeted the provider in 64 % of the trials . The effect was primarily measured for the process of care ( 76 % ) . Provider prompt/reminder , computer-assisted treatment planner , interactive patient education/therapy , and patient prompt/reminder were significantly successful interventions ( sign test , P < .05 ) . CONCLUSIONS R and omized clinical trials confirm that four generic information interventions are active ingredients of computer systems and can make a significant difference in family medicine ( physician and patient reminders , treatment planner , and patient education ) . To manage care and improve quality , primary care computer systems should incorporate these effective information services 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 Computers are steadily being incorporated in clinical practice . We conducted a nonr and omised , controlled , prospect i ve trial of electronic messages design ed to enhance adherence to clinical practice guidelines . We studied 126 physicians and nurse practitioners who used electronic medical records when caring for 349 patients with HIV infection in a primary care practice . We analysed the response times of clinicians to the situations that triggered alerts and reminders , the number of ambulatory visits , and hospitalisation . The median response times to 303 alerts in the intervention group and 388 alerts in the control group were 11 and 52 days ( p < 0.0001 ) , respectively . The median response time to 432 reminders in the intervention group was 114 days and that for 360 reminders in the control group was over 500 days ( p < 0.0001 ) . There was no effect on visits to the primary care practice . There was , however , a significant increase in the rate of visits outside the primary care practice ( p = 0.02 ) , which is explained by the increased frequency of visits to ophthalmologists . There were no differences in admission rates ( p = 0.47 ) , in admissions for pneumocystosis ( p = 0.09 ) , in visits to the emergency ward ( p = 0.24 ) , or in survival ( p = 0.19 ) . We conclude that the electronic medical record was effective in helping clinicians adhere to practice guidelines 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 The majority of general practitioners in the Netherl and s have replaced traditional paper-based patient records with computer-based records ; physicians enter patient data themselves in the computer during patient encounters ( 1 ) . The use of electronic patient records creates new opportunities to influence physician behavior through implementation of decision support systems ( 2 - 7 ) . In recent years , research ers have documented various computer-based decision support systems that have influenced physician behavior ( 8 - 17 ) . Other investigators , however , have reported that computer-based decision support has not affected patient care ( 18 ) . To resolve the issue , investigators have compared the results of studies that were conducted in different setting s , used different methods , and involved different population s ( 19 ) . Studies comparing different methods of providing computer-based decision support in r and omized trials are not available . In the Netherl and s , 3 % to 4 % of patient encounters with general practitioners in primary care result in the ordering of blood tests ( 20 ) . However , ordering of blood tests is not always appropriate ( 21 - 29 ) . Research ers argue that excessive ordering of tests causes physicians to pursue evaluation of false-positive results , which in turn leads to additional unnecessary diagnostic examinations ( 30 - 35 ) . Two methods have proven effective in reducing the number of tests ordered by Dutch general practitioners . The first method is based on restricting the number of tests that are listed on an order form . Zaat and colleagues ( 36 , 37 ) developed a restricted paper order form that replaced the existing form . The second method involves introduction of indication-oriented order forms that are based on clinical practice guidelines ( 38 - 40 ) . We hypothesized that an indication-oriented order form based on guidelines , which would provide an optimally restricted list of tests that are relevant for a specific indication , would be more effective in decreasing the number of tests ordered compared with an order form that provides an initially limited list of tests . We therefore conducted a r and omized trial to compare the effect of two versions of BloodLink , a computer-based clinical decision support system , on blood test ordering among Dutch general practitioners . Methods Participants In August and September 1995 , all 64 practice s ( 94 general practitioners ) in the region of Delft , the Netherl and s , were invited to participate in the study . Only practice s that had replaced their paper-based patient records with electronic records and were using the computer during patient encounters were eligible . A total of 46 practice s ( 62 general practitioners ) agreed to participate . R and omization To avoid contamination , we performed r and om allocation at the level of the practice ( 41 , 42 ) . The practice s were first stratified by type : solo practice s or group practice s ( two or more general practitioners in the same practice ) . Each practice was subsequently assigned by simple r and om allocation to use BloodLink-Restricted or BloodLink- Guideline for the full study period . A research er who was not involved in the study and was blinded to the identity of the practice s performed the r and omization by using a r and om-numbers table . After r and omization , 22 practice s involving 30 general practitioners were assigned to use BloodLink-Restricted and 24 practice s involving 32 general practitioners were assigned to use BloodLink- Guideline . Intervention We developed two versions of BloodLink , a computer-based decision support system . BloodLink-Restricted initially displays a reduced list of tests , whereas BloodLink- Guideline is based on the guidelines of the Dutch College of General Practitioners . Both versions of BloodLink are integrated with the computer-based patient record ( 43 ) . The option to use BloodLink was added to the screen that the general practitioner uses when entering data in the electronic patient record during patient encounters . The general practitioner can activate BloodLink to order blood tests as an alternative to using paper order forms . Because the total number of tests that can be ordered is too large to display on a computer screen , a set of tests is presented for selection . If the physician requires additional tests that are not currently displayed , he or she can type the first few letters of the names of the required tests , and the system will present all possible matches ( including those corresponding to possible typing errors of the general practitioner ) for selection . The number of tests that the general practitioners had at their disposal was the same both before and during the intervention ( 52 clinical chemistry tests and 46 microbiological tests ) . Options for specific instructions to the laboratory ( for example , urgent processing or fasting values ) are available . Once the physician has made his or her selection s , BloodLink prints a patient-specific test order form and instructions for the laboratory and up date s the patient record with the tests that have been ordered . The only difference between the two versions of BloodLink is the method used to present the initial set of tests to the general practitioner . BloodLink-Restricted is based on the idea of a restricted order form . It offers the general practitioner an initial set of 15 tests that have been shown to cover most of the clinical situations seen in primary care ( 36 ) . BloodLink-Restricted can be viewed as a general electronic order form that presents only 15 tests on the screen , together with a field labeled other tests that allows the physician to request any other blood test ( 43 ) . The 15 tests are alanine aminotransferase , aspartate aminotransferase , total bilirubin , cholesterol , creatinine , erythrocyte sedimentation rate , free thyroxine , -glutamyltransferase , glucose ( and fasting glucose ) , glycosylated hemoglobin , hemoglobin , mean corpuscular volume , PaulBunnell , potassium , and thyroid-stimulating hormone . At any time , the physician can customize tests for individual patients by adding or deleting tests . BloodLink- Guideline is based on the guidelines of the Dutch College of General Practitioners . By January 1996 , the Dutch College of General Practitioners had published 54 guidelines . Some guidelines focus on symptoms that are frequently seen in the primary care setting , such as acute diarrhea , acute sore throat , low back pain , alcohol abuse , fever in children , and sleeping disorders . Other guidelines focus on common diseases in primary care , such as diabetes , asthma , depression , dementia , and eczema . Finally , a set of guidelines covers preventive medicine . We review ed the most recent version of each guideline , available in January 1996 , and noted whether it contained a reference to a blood test ( 44 ) . We determined the clinical situation in which the test should be performed ( indication ) and the tests that should be performed in that situation ( advised tests ) . When general practitioners activate the system , BloodLink- Guideline first provides an overview of the available guidelines . The names of these guidelines are familiar to Dutch general practitioners . The general practitioner selects the appropriate guideline . A guideline may describe several different indications for requesting blood tests ; for example , the guideline for blood tests and liver disease mentions 10 different indications . After the indication has been identified , the system proposes the relevant tests . The general practitioner then decides whether to adhere to the protocol . At any time , the physician can customize tests for individual patients by adding or removing tests from the proposed list . Although new guidelines are published at regular intervals , the currently available guidelines cover only a limited set of indications for blood tests ( 44 ) . In the absence of national guidelines , local or regional guidelines may be used . The version of BloodLink- Guideline used during the clinical trial in the Delft region included three regional guidelines for anemia , AIDS , and clotting disorders , in addition to all national guidelines . Even with these additional guidelines , BloodLink- Guideline does not cover all possible indications for blood tests in primary care . To deal with these situations , the general practitioner can select the heading other indication and order any test . Protocol Before the study , the general practitioners were using two paper order forms : one for clinical chemistry and one for microbiology . After BloodLink was installed , one of the authors gave a brief orientation presentation to the participating practitioners . During a 3-month phase-in period , the general practitioners were allowed to use BloodLink in their practice s to become acquainted with the system . After this period , the general practitioners were asked whether they were willing to participate in the trial . The study period was March 1996 through February 1997 . Physicians always had the choice to use either the BloodLink software or the paper forms to order clinical chemistry and microbiology tests ; thus , paper order forms were still available during the entire intervention period . When the general practitioner ordered blood tests during a patient encounter , only one order form was generated regardless of whether the general practitioner used paper forms or BloodLink . The electronic patient record monitored use of BloodLink by the practitioners . To include the requests for blood tests that were made by using traditional paper forms , we retrieved from the regional laboratory all requests for blood tests . Outcomes We counted the number of order forms that the laboratory received from the general practitioners and the number of tests on each form . The main outcome measure was the average number of tests per order form ( including paper forms ) per practice ( summary variable ) . We defined the most frequently ordered tests as the tests that accounted for 80 % of the total number of tests ordered . For these tests , we In a r and omized trial three ways of increasing rates of cervical screening were compared for women attending a family medicine center . Working from computerized medical records , 1,587 women aged 18 to 35 years who were overdue for a screening test were included in the study . In a control group , no formal method was used to encourage patients to attend for screening , and 13.7 percent obtained a test within the trial year . In one intervention group the physician was issued a message identifying those women visiting the center for a routine appointment who were due for screening ; 16.1 percent were screened . Sending a letter to patients in a second group yielded a 25.9 percent compliance rate . In a third group the practice nurse called patients on the telephone to advise them to obtain the test , and 20.0 percent complied . Reminders issued to the physician provide a low-cost , opportunistic approach to reach women who happen to visit the practice , but this approach should be supplemented by telephoning or sending a letter to those women who do not attend regularly Despite its demonstrated efficacy in reducing breast carcinoma mortality , screening mammography remains underutilized and its promotion in the primary care setting provides an important opportunity for intervention 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 OBJECTIVES Prescribing alerts generated by computerized drug decision support ( CDDS ) may prevent drug-related morbidity . However , the vast majority of alerts are ignored because of clinical ir relevance . The ability to customize commercial alert systems should improve physician acceptance because the physician can select the circumstances and types of drug alerts that are viewed . We tested the effectiveness of two approaches to medication alert customization to reduce prevalence of prescribing problems : on-physician-dem and versus computer-triggered decision support . Physicians in each study condition were able to preset levels that triggered alerts . DESIGN This was a cluster trial with 28 primary care physicians r and omized to either automated or on-dem and CDDS in the MOXXI drug management system for 3,449 of their patients seen over the next 6 months . MEASUREMENTS The CDDS generated alerts for prescribing problems that could be customized by severity level . Prescribing problems included dosing errors , drug-drug , age , allergy , and disease interactions . Physicians r and omized to on-dem and activated the drug review when they considered it clinical ly relevant , whereas physicians r and omized to computer-triggered decision support viewed all alerts for electronic prescriptions in accordance with the severity level they selected for both prevalent and incident problems . Data from administrative cl aims and MOXXI were used to measure the difference in the prevalence of prescribing problems at the end of follow-up . RESULTS During follow-up , 50 % of the physicians receiving computer-triggered alerts modified the alert threshold ( n = 7 ) , and 21 % of the physicians in the alert-on-dem and group modified the alert level ( n = 3 ) . In the on-dem and group 4,445 prescribing problems were identified , 41 ( 0.9 % ) were seen by requested drug review , and in 31 problems ( 75.6 % ) the prescription was revised . In comparison , 668 ( 10.3 % ) of the 6,505 prescribing problems in the computer-triggered group were seen , and 81 ( 12.1 % ) were revised . The majority of alerts were ignored because the benefit was judged greater than the risk , the interaction was known , or the interaction was considered clinical ly not important ( computer-triggered : 75.8 % of 585 ignored alerts ; on-dem and : 90 % of 10 ignored alerts ) . At the end of follow-up , there was a significant reduction in therapeutic duplication problems in the computer-triggered group ( odds ratio 0.55 ; p = 0.02 ) but no difference in the overall prevalence of prescribing problems . CONCLUSION Customization of computer-triggered alert systems is more useful in detecting and resolving prescribing problems than on-dem and review , but neither approach was effective in reducing prescribing problems . New strategies are needed to maximize the use of drug decision support systems to reduce drug-related morbidity 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 OBJECTIVE To assess the effect of three computerized reminder systems on compliance with tetanus vaccination . DESIGN Prospect i ve r and omized controlled trial . SETTING Ottawa Civic Hospital Family Medicine Centre . PARTICIPANTS Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were r and omly assigned , by family , to a control group , a physician reminder group , a telephone reminder group or a letter reminder group . The remaining 2480 patients were not included in the r and omized portion of the study but were monitored . Results are presented for the 5242 r and omized patients and the 2369 nonr and omized patients for whom there was no up-to- date record of tetanus vaccination at the start of the trial . INTERVENTIONS For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient 's tetanus vaccination status and to recommend vaccination ; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose . MAIN OUTCOME MEASURE Proportion of patients who received tetanus toxoid during the study year or who had a cl aim of vaccination in the previous 10 years . MAIN RESULTS The rate of recorded tetanus vaccination in the r and omized control group was 3.2 % . The difference between that rate and those for the three reminder groups was 19.6 % in the physician reminder group ( 95 % confidence interval [ CI ] 17.1 % to 22.2 % , p less than 0.00001 ) , 20.8 % in the telephone reminder group ( 95 % CI 18.3 % to 23.5 % , p less than 0.00001 ) and 27.4 % in the letter reminder group ( 95 % CI 24.8 % to 30.2 % , p less than 0.00001 ) ) . The letter reminders were more effective than either the telephone reminders ( p = 0.00013 ) or the physician reminders ( p less than 0.00001 ) in improving compliance . The cost to the practice per additional vaccination recorded was 43 for the physician reminders , $ 5.43 for the telephone reminders and $ 6.05 for the letter reminders . CONCLUSIONS Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage . More intensive interventions would be required to approach that goal . However , such interventions do not appear to be justified given the rarity of tetanus 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 BACKGROUND Overuse of blood products is common , but prior efforts to improve transfusion decisions have met with limited success . STUDY DESIGN AND METHODS This study examines transfusion practice s before and after a conventional educational intervention followed by a r and omized controlled trial of a decision support ( DS ) intervention with computerized physician order entry ( CPOE ) for red blood cell , platelet , and fresh-frozen plasma orders . The study was conducted in an academic medical center between April 2003 and June 2004 . Orders originating from units not using CPOE with DS ( e.g. , the emergency department ) were excluded . Junior housestaff were r and omly assigned into a control group and an intervention group who received DS for transfusion orders . Transfusion orders were initially classified according to guideline rules as DS-agree or DS-disagree . Chart review s assessed inappropriateness for all DS-disagree orders and a sample of DS-agree orders . The total of inappropriate transfusion orders included chart review confirmed DS-disagree orders and DS-agree orders reclassified as inappropriate . RESULTS The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and r and omly assigned junior housestaff were 72.6 percent ( 2154/2967 ) and 71.9 percent ( 1259/1752 ) and improved after conventional education to 63.8 percent ( 1699/2663 ; p < 0.0001 ) and 63.3 percent ( 1263/1996 ; p < 0.0001 ) , respectively . The percentage of inappropriate orders in the DS intervention group continued to improve ( 59.6 % , 804/1350 ; p < 0.0001 ) . Physicians accepted 14 percent ( 133/939 ) of new DS-recommended orders , especially recommendations to increase transfusion doses ( 73 % ) . CONCLUSIONS Education and computerized DS both decreased the percentage of inappropriate transfusions , although the residual amount of inappropriate transfusions remained high STUDY OBJECTIVE To determine the effect of displaying previous results of diagnostic tests on the ordering of selected outpatient tests . DESIGN Sixteen-week controlled trial with a 13-week pre-intervention and 8-week post-intervention observation periods . Patients were r and omly assigned to intervention or control groups so that each physician was his or her own control . Only scheduled visits were included . R and omization occurred before the pre-intervention observation period . SETTING Academic primary care general medicine clinic affiliated with an urban general hospital . SUBJECTS Pre-intervention period : 111 physicians ( 97 internal medicine residents , 14 faculty internists ) , 4683 patients , 5942 scheduled visits . INTERVENTION period : same 111 physicians , 5946 patients , 8148 visits . Post-intervention period : 76 physicians ( 62 residents , 14 faculty ) , 2571 patients , 2858 scheduled visits . INTERVENTION With an order for one of eight selected diagnostic tests through microcomputer workstations , a window was opened on the screen and previous test results were displayed along with the time interval between the first and last result . Tests were ordered for control patients into the same workstations without previous results displayed . MEASUREMENTS AND MAIN RESULTS Previous results of one or more study tests were available for display for 96 % of scheduled patients . Significantly lower results ( p less than 0.05 by paired t-test ) for the selected tests were found for intervention patient visits than for control visits : charges per visit ( mean + /- SE ) for intervention patients $ 12.17 + /- 0.62 , compared with $ 13.99 + /- 0.77 for controls , a 13.0 % difference ; tests per visit were 0.51 + /- 0.03 , compared with 0.56 + /- 0.03 , an 8.5 % difference . The number of study tests ordered decreased significantly for intervention patients ( 16.8 % ) and for controls ( 10.9 % ) . During the post-intervention period , ordering of study tests increased for both groups , but the increase from the intervention period was not significant . CONCLUSIONS Presenting physicians with previous test results reduced the ordering of those tests . The actual effect may have been greater than 13 % , because there were reductions in study tests ordered for both intervention and control patients during the intervention period when compared with the pre-intervention period , and both tended to rise after the intervention , or display , was turned off BACKGROUND Primary care data bases contain cardiovascular disease risk factor data , but practical tools are required to improve identification of at-risk patients . AIM To test the effects of a system of electronic reminders ( the ' e-Nudge ' ) on cardiovascular events and the adequacy of data for cardiovascular risk estimation . DESIGN OF STUDY R and omised controlled trial . SETTING Nineteen general practice s in the West Midl and s , UK . METHOD The e-Nudge identifies four groups of patients aged over 50 years on the basis of estimated cardiovascular risk and adequacy of risk factor data in general practice computers . Screen messages highlight individuals at raised risk and prompt users to complete risk profiles where necessary . The proportion of the study population in the four groups was measured , as well as the rate of cardiovascular events in each arm after 2 years . RESULTS Over 38 000 patients ' electronic records were r and omised . The intervention led to an increase in the proportion of patients with sufficient data who were identifiably at risk , with a difference of 1.94 % compared to the control group ( 95 % confidence interval [ CI ] = 1.38 to 2.50 , P<0.001 ) . A corresponding reduction occurred in the proportion potentially at risk but requiring further data for a risk estimation ( difference = -3.68 % , 95 % CI = -4.53 to -2.84 , P<0.001 ) . No significant difference was observed in the incidence of cardiovascular events ( rate ratio = 0.96 , 95 % CI = 0.85 to 1.10 , P = 0.59 ) . CONCLUSION Automated electronic reminders using routinely collected primary care data can improve the adequacy of cardiovascular risk factor information during everyday practice and increase the visibility of the at-risk population A computerized medical decision-making system was used to monitor signs and predisposing factors of digoxin intoxication in patients receiving digoxin . This process automatically review ed the patient 's data base nightly for drug interactions , laboratory data and electrocardiographic findings with known association with digoxin intoxication . These decisions were formated into a " digoxin alert report " and sent to line printers in the nursing division to be placed on the individual patients ' charts . To assess the effect of these reports on patient management , a r and omized double-blind study was undertaken . Patients were assigned to an alert or nonalert group . Alert reports were withheld from charts of patients in the nonalert group . A medical record review was subsequently carried out , wherein the physician 's orders were search ed to identify actions taken with possible relation to the digoxin alerts . The computer monitored 396 patients over a 3 month period . Of these , 211 ( 53 % ) were r and omized to the alert group and 185 ( 47 % ) to the nonalert group . Seventy-two percent of patients received at least one alert . The most frequently occurring alerts included : hypoxemia , hypokalemia , concurrent use of a beta-adrenergic blocking agent , renal insufficiency and ventricular arrhythmia . Results from the record review demonstrated a 22 % increase in physician actions for the alert group . Specifically , patients in the alert group were 2.7 times more likely to have a serum digoxin determination ordered and 2.8 times more likely to have digoxin withheld on the day of a digoxin alert than were patients in the nonalert group Objective : To improve compliance with computer-generated reminders to perform fecal occult blood testing ( FOBT ) , mammography , and cervical Papanicolaou ( Pap ) testing . Design : Six-month prospect i ve , r and omized , controlled trial . Setting : Academic primary care general internal medicine practice .Subjects : Thirty-one general internal medicine faculty , 145 residents , and 5,407 patients with scheduled visits who were eligible for any of the three cancer screening protocol s . Intervention : Primary care teams of internal medicine residents and faculty received either routine computer reminders ( control ) or the same reminders to which they were required to circle one of four responses : 1 ) “ done/order today , ” 2 ) “ not applicable to this patient , ” 3 ) “ patient refused , ” or 4 ) “ next visit . ” Results : Intervention physicians complied more frequently than control physicians with all reminders combined ( 46 % vs 38 % , respectively , p=0.002 ) and separately with reminders for FOBT ( 61 % vs 49 % , p=0.0007 ) and mammography ( 54 % vs 47 % , p=0.036 ) but not cervical Pap testing ( 21 % vs 18 % , p=0.2 ) . Intervention residents responded significantly more often than control residents to all reminders together and separately to reminders for FOBT and mammography but not Pap testing . There was no significant difference between intervention and control faculty , but the compliance rate for control faculty was significantly higher than the rate for control residents for all reminders together and separately for FOBT but not mammography or Pap testing . The intervention ’s effect was greatest for patients ≥70 years old , with significant results for all tests , together and singly , for residents but not faculty . Intervention physicians felt that the reminders were not applicable 21 % of the time ( due to inadequate data in patients ’ electronic medical records ) and stated that their patients refused 10 % of the time . Conclusions : Requiring physicians to respond to computer-generated reminders improved their compliance with preventive care protocol s , especially for elderly patients for whom control physicians ’ compliance was the lowest . However , 100 % compliance with cancer screening reminders will be unattainable due to incomplete data and patient refusal OBJECTIVE With the advent of hospital payment by diagnosis-related group ( DRG ) , length of stay ( LOS ) has become a major issue in hospital efforts to control costs . Because the Columbia-Presbyterian Medical Center ( CPMC ) has had above-average LOSs for many DRGs , the authors tested the hypothesis that a computer-generated informational message directed to physicians would shorten LOS . DESIGN R and omized clinical trial with the patient as the unit of r and omization . SETTING AND STUDY POPULATION From June 1991 to April 1993 , at CPMC in New York , 7,109 patient admissions were r and omly assigned to an intervention ( informational message ) group and 6,990 to a control ( no message ) group . INTERVENTION A message giving the average LOS for the patient 's admission or provisional DRG , as assigned by hospital utilization review , and the current LOS , in days , was included in the main menu for review of test results in the hospital 's clinical information system , available at all nursing stations in the hospital . MAIN OUTCOME MEASURE Hospital LOS . RESULTS The median LOS for study patients was 7 days . After adjustment for covariates including age , sex , payor , patient care unit , and time trends , the mean LOS in the intervention group was 3.2 % shorter than that in the control group ( p = 0.022 ) . CONCLUSION Computer-generated patient-specific LOS information directed to physicians was associated with a reduction in hospital LOS Abstract BACKGROUND : In New Zeal and , more than 5 % of people aged 50 years and older have undiagnosed diabetes ; most of them attend family practitioners ( FPs ) at least once a year . OBJECTIVES : To test the effectiveness of patients or computers as reminders to screen for diabetes in patients attending FPs . DESIGN : A r and omized-controlled trial compared screening rates in 4 intervention arms : patient reminders , computer reminders , both reminders , and usual care . The trial lasted 2 months . The patient reminder was a diabetes risk self- assessment sheet filled in by patients and given to the FP during the consultation . The computer reminder was an icon that flashed only for patients considered eligible for screening . PARTICIPANTS : One hundred and seven FPs . MEASUREMENTS : The primary outcome was whether each eligible patient , who attended during the trial , was or was not tested for blood glucose . Analysis was by intention to treat and allowed for clustering by FP . RESULTS : Patient reminders ( odds ratio [ OR ] 1.72 , 95 % confidence interval [ CI ] 1.21 , 2.43 ) , computer reminders ( OR 2.55 , 1.68 , 3.88 ) , and both reminders ( OR 1.69 , 1.11 , 2.59 ) were all effective compared with usual care . Computer reminders were more effective than patient reminders ( OR 1.49 , 1.07 , 2.07 ) . Patients were more likely to be screened if they visited the FP repeatedly , if patients were non-European , if they were “ regular ” patients of the practice , and if their FP had a higher screening rate prior to the study . CONCLUSIONS : Patient and computer reminders were effective methods to increase screening for diabetes . However , the effects were not additive 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 PURPOSE To determine the impact of giving physicians computerized reminders about apparently redundant clinical laboratory tests . SUBJECTS AND METHODS We performed a prospect i ve r and omized controlled trial that included all in patients at a large teaching hospital during a 15-week period . The intervention consisted of computerized reminders at the time a test was ordered that appeared to be redundant . Main outcome measures were the proportions of clinical laboratory orders that were canceled and the proportion of the tests that were actually performed . RESULTS During the study period , there were 939 apparently redundant laboratory tests among the 77,609 study tests that were ordered among the intervention ( n = 5,700 patients ) and control ( n = 5,886 patients ) groups . In the intervention group , 69 % ( 300 of 437 ) of tests were canceled in response to reminders . Of 137 overrides , 41 % appeared to be justified based on chart review . In the control group , 51 % of ordered redundant tests were performed , whereas in the intervention group only 27 % of ordered redundant tests were performed ( P < 0.001 ) . However , the estimated annual savings in laboratory charges was only $ 35,000 . This occurred because only 44 % of redundant tests performed had computer orders , because only half the computer orders were screened for redundancy , and because almost one-third of the reminders were overridden . CONCLUSIONS Reminders about orders for apparently redundant laboratory tests were effective when delivered . However , the overall effect was limited because many tests were performed without corresponding computer orders , and many orders were not screened for redundancy BACKGROUND Prophylaxis against deep-vein thrombosis in hospitalized patients remains underused . We hypothesized that the use of a computer-alert program to encourage prophylaxis might reduce the frequency of deep-vein thrombosis among high-risk hospitalized patients . METHODS We developed a computer program linked to the patient data base to identify consecutive hospitalized patients at risk for deep-vein thrombosis in the absence of prophylaxis . The program used medical-record numbers to r and omly assign 1255 eligible patients to an intervention group , in which the responsible physician was alerted to a patient 's risk of deep-vein thrombosis , and 1251 patients to a control group , in which no alert was issued . The physician was required to acknowledge the alert and could then withhold or order prophylaxis , including graduated compression stockings , pneumatic compression boots , unfractionated heparin , low-molecular-weight heparin , or warfarin . The primary end point was clinical ly diagnosed , objective ly confirmed deep-vein thrombosis or pulmonary embolism at 90 days . RESULTS More patients in the intervention group than in the control group received mechanical prophylaxis ( 10.0 percent vs. 1.5 percent , P<0.001 ) or pharmacologic prophylaxis ( 23.6 percent vs. 13.0 percent , P<0.001 ) . The primary end point occurred in 61 patients ( 4.9 percent ) in the intervention group , as compared with 103 ( 8.2 percent ) in the control group ; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent ( 95 percent confidence interval , 92.5 to 95.4 percent ) and 90.6 percent ( 95 percent confidence interval , 88.7 to 92.2 percent ) , respectively ( P<0.001 ) . The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent ( hazard ratio , 0.59 ; 95 percent confidence interval , 0.43 to 0.81 ; P=0.001 ) . CONCLUSIONS The institution of a computer-alert program increased physicians ' use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk 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 Despite its effectiveness as a method of controlling cervical carcinoma , the use of Pap smear testing remains incomplete , and its promotion in the primary care setting provides an important opportunity for intervention 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 PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease BACKGROUND Preventive care is an important role for general practitioners , yet opportunities for prevention are often missed . METHOD We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice . All patients who attended were r and omised by the terminal digit of their record number . RESULTS The control uptake of opportunistic prevention was low ; ranging from 1.5 % ( tetanus immunisation ) to 27 % ( influenza immunisation ) . The reminders increased this by significant but small amounts for four out of 12 activities ( immunisation for tetanus and pneumococcus and recording of allergies and weight ) , insignificant increases for four ( mumps , measles and rubella immunisation , recording of smoking , and taking of cervical smears and of blood pressure ) , and insignificantly decreased influenza immunisation , and screening for diabetes and hyperlipidaemia . DISCUSSION Opportunistic electronic reminders have the potential to increase preventive care in general practice Less than 20 percent of elderly and other high-risk persons targeted for annual influenza vaccination are immunized each year . In most busy practice setting s , it is difficult for primary care physicians to identify every patient in need of preventive health interventions . The purpose of this study was to assess the effect of microcomputer-generated reminders on influenza vaccination rates in a university-based family practice center . The practice uses an interactive encounter form system from which up date d clinical information is routinely entered into a cumulative data base . During a 2-month period , 686 patients were identified in the data base as eligible to receive influenza vaccine according to accepted criteria . Practice physicians ( n = 32 ) were stratified by level of training and r and omized to one of three groups , thereby receiving printed reminders on the encounter forms of all , none , or half of their eligible patients . Patients of physicians who always received reminders were more likely to receive influenza vaccine during the study period than patients of the never-reminded physicians ( 51 percent versus 30 percent , P < 0.001 ) . Patients whose physicians received reminders for only half their patients had an intermediate likelihood of receiving a vaccination if a reminder was printed ( 38 percent ) but were less likely than the patients of never-reminded physicians to receive the vaccine if no reminder was printed ( 20 percent , P < 0.001 ) . This study suggests that physicians learn to depend on reminders for preventive health activities and that reminders are most effective when they are provided at every patient encounter 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 In a r and omized , controlled trial ( N = 8,298 ) the authors compared three ways of encouraging patients in a large family practice to obtain a blood pressure check . Working from computerized medical records at a teaching familymedicine center , the study included patients aged 18 years and over who had not had a blood pressure measurement during the previous year . In a normalcare control group , 21.1 % of those due for a blood pressure reading obtained one during the trial year . In one intervention group , a computer-generated message reminded the doctor to check the blood pressure of patients who happened to visit the center for an appointment ; 30.7 % of patients allocated to this group were checked . In the second group , the nurse contacted patients by telephone and encouraged 24.1 % of those who were due for a check to obtain one . Sending a letter to patients in the third group yielded a 35.7 % compliance rate . Considering the costs of the three interventions , the physician reminder was the most cost effective , followed by the letter reminder . Although statistically significant , the impact of the reminders was modest . A better approach might involve a combination of routine reminders to the physician , followed by letters to noncompliant patients 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 |
13,464 | 25,748,047 | In summary , our study suggests that WT1 may be a potential marker to predict DFS/RFS/PFS in solid tumor patients . | Though proposed as a promising target antigen for cancer immunotherapy , the prognostic value of Wilms ' tumor 1 ( WT1 ) in solid tumors remains inconclusive .
Here , we report a systematic review and meta- analysis of the association between WT1 expression and prognosis in solid tumors . | Introduction Calretinin and Wilms ’ tumor gene ( WT1 ) are mesothelial markers routinely used to confirm the diagnosis of malignant pleural mesothelioma ( MPM ) . We investigated the prognostic value of calretinin and WT1 expression in predicting survival in a series of patients diagnosed with MPM in our institution . Material s and methods Fifty-two patients diagnosed of MPM were retrospectively review ed . Calretinin and WT1 were stained for IHC analysis in formalin-fixed , paraffin-embedded sections and positivity was considered for tumors with > 1 % of tumor cells stained . Survival data were calculated by the Kaplan – Meier method and Cox regression was used to evaluate the prognostic value of the variables . Results Calretinin IHC expression was positive in 83.7 % of patients and WT1 in 78.1 % . A significant association of calretinin and WT1 expression with epithelial histology was detected ( p = 0.030 and p = 0.010 ) . We found a significant increase in OS in patients with epithelial subtype , PS1 and neutrophil – lymphocyte ratio ( NLR ) ≤5 ( p < 0.05 ) . In the IHC markers analysis , we found a significant increase in OS for patients with WT1 positive expression ( 16.4 vs. 2.3 m , p = 0.013 ) , but not differences for calretinin expression ( 16.6 vs. 5.0 months , p = 0.37 ) . In the multivariate analysis , epithelial histology and WT1 remained as significant prognostic factors for survival ( p = 0.004 and p = 0.010 , respectively ) . Conclusion In our series of 52 MPM patients , epithelial histology , PS , NLR and WT1 expression are significant prognostic factors for survival . We concluded that WT1 , but not calretinin , is a useful prognostic factor in MPM . The role of WT1 assessment is worth of prospect i ve validation in future studies on MPM Purpose : We performed a phase I trial to investigate the safety , clinical responses , and Wilms ' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells ( DC ) pulsed with a mixture of three types of WT1 peptides , including both MHC class I and II – restricted epitopes , in combination with chemotherapy . Experimental Design : Ten stage IV patients with pancreatic ductal adenocarcinoma ( PDA ) and 1 patient with intrahepatic cholangiocarcinoma ( ICC ) who were HLA-positive for A*02:01 , A*02:06 , A*24:02 , DRB1 * 04:05 , DRB1 * 08:03 , DRB1 * 15:01 , DRB1 * 15:02 , DPB1 * 05:01 , or DPB1 * 09:01 were enrolled . The patients received one course of gemcitabine followed by biweekly intradermal vaccinations with mature DCs pulsed with MHC class I ( DC/WT1-I ; 2 PDA and 1 ICC ) , II ( DC/WT1-II ; 1 PDA ) , or I/II – restricted WT1 peptides ( DC/WT1-I/II ; 7 PDA ) , and gemcitabine . Results : The combination therapy was well tolerated . WT1-specific IFNγ-producing CD4 + T cells were significantly increased following treatment with DC/WT1-I/II . WT1 peptide-specific delayed-type hypersensitivity ( DTH ) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/II and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II . The WT1-specific DTH-positive patients showed significantly improved overall survival ( OS ) and progression-free survival ( PFS ) compared with the negative control patients . In particular , all 3 patients with PDA with strong DTH reactions had a median OS of 717 days . Conclusions : The activation of WT1-specific immune responses by DC/WT1-I/II combined with chemotherapy may be associated with disease stability in advanced pancreatic cancer . Clin Cancer Res ; 20(16 ) ; 4228–39 . © 2014 AACR |
13,465 | 23,843,630 | Qualitative analysis revealed that greater general parenting stress was associated with greater parental responsibility for treatment management and was unrelated to illness duration and severity across illness population s. Greater parenting stress was associated with poorer psychological adjustment in caregivers and children with chronic illness . | OBJECTIVE To critically review , analyze , and synthesize the literature on parenting stress among caregivers of children with asthma , cancer , cystic fibrosis , diabetes , epilepsy , juvenile rheumatoid arthritis , and /or sickle cell disease . | CONTEXT Rates of obesity and other childhood chronic conditions have increased over recent decades . Patterns of how conditions change over time have not been widely examined . OBJECTIVE To evaluate change in prevalence of obesity and other chronic conditions in US children , including incidence , remission , and prevalence . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study using the National Longitudinal Survey of Youth-Child Cohort ( 1988 - 2006 ) of 3 nationally representative cohorts of children . Children were aged 2 through 8 years at the beginning of each study period , and cohorts were followed up for 6 years , from 1988 to 1994 ( cohort 1 , n = 2337 ) , 1994 to 2000 ( cohort 2 , n = 1759 ) , and 2000 to 2006 ( n = 905 ) . MAIN OUTCOME MEASURES Parent report of a child having a health condition that limited activities or schooling or required medicine , special equipment , or specialized health services and that lasted at least 12 months . Obesity was defined as a body mass index at or above the 95th percentile for age . Chronic conditions were grouped into 4 categories : obesity , asthma , other physical conditions , and behavior/learning problems . RESULTS The end- study prevalence of any chronic health condition was 12.8 % ( 95 % confidence interval [ CI ] , 11.2%-14.5 % ) for cohort 1 in 1994 , 25.1 % ( 95 % CI , 22.7%-27.6 % ) for cohort 2 in 2000 , and 26.6 % ( 95 % CI , 23.5%-29.9 % ) for cohort 3 in 2006 . There was substantial turnover in chronic conditions : 7.4 % ( 95 % CI , 6.5%-8.3 % ) of participants in all cohorts had a chronic condition at the beginning of the study that persisted to the end , 9.3 % ( 95 % CI , 8.3%-10.3 % ) reported conditions at the beginning that resolved within 6 years , and 13.4 % ( 95 % CI , 12.3%-14.6 % ) had new conditions that arose during the 6-year study period . The prevalence of having a chronic condition during any part of the 6-year study period was highest for cohort 3 ( 51.5 % ; 95 % CI , 47.3%-55.0 % ) , and there were higher rates among male ( adjusted odds ratio [ AOR ] , 1.24 ; 95 % CI , 1.07 - 1.42 ) , Hispanic ( AOR , 1.36 ; 95 % CI , 1.11 - 1.67 ) , and black ( AOR , 1.60 ; 95 % CI , 1.35 - 1.90 ) youth . CONCLUSIONS Prevalence of chronic conditions among children and youth increased from 1988 to 2006 . However , presence of these conditions was dynamic over each 6-year cohort OBJECTIVE To report initial feasibility and outcome from a pilot study of a new three-session intervention for caregivers of children newly diagnosed with cancer , Surviving Cancer Competently Intervention Program-Newly Diagnosed ( SCCIP-ND ) . METHOD Nineteen families ( 38 caregivers ) were r and omly assigned to SCCIP-ND or treatment as usual subsequent to learning of their child 's illness . The study design included pre- and 2-month postintervention assessment s , with state anxiety and posttraumatic stress symptoms as outcomes . Feasibility was based on therapist feedback and supervision , program evaluations , and data from study -tracking procedures . RESULTS SCCIP-ND appears to be an acceptable intervention that can be used successfully with caregivers over the first few months after diagnosis . Recruitment and retention data document feasibility but also highlight challenges . Preliminary outcome data show changes in the desired direction [ e.g. , reduced anxiety and parental posttraumatic stress symptoms ( PTSS ) ] . CONCLUSIONS The pilot data are supportive of the value and challenges of developing evidence -based family interventions in pediatric psychology Low-income African American children have disproportionately higher asthma morbidity and mortality . Education alone may not address barriers to asthma management due to psychosocial stress . This study evaluated the efficacy of a home-based family intervention integrating asthma education and strategies to address stress using a community-based participatory research model . Children age 8 to 13 with poorly controlled asthma and their caregivers were recruited from an urban hospital and an asthma camp . Caregivers with elevated scores on a stress measure were enrolled . Forty-three families were r and omized to the 4- to 6-session Home Based Family Intervention ( HBFI ) or the single session of Enhanced Treatment as Usual ( ETAU ) . All families received an asthma action plan and dust mite covers ; children performed spirometry and demonstrated MDI/spacer technique at each home visit . The HBFI addressed family-selected goals targeting asthma management and stressors . Asthma management , morbidity , family functioning , and caregiver stress were assessed at baseline , postintervention , and 6 months after the intervention . ED visits and hospitalizations were ascertained by medical record review for a year after intervention completion . Only one child ( 5 % ) in HBFI had an asthma-related hospitalization compared to 7 patients ( 35 % ) in ETAU in the year following intervention . Participants in both groups demonstrated improved asthma management and family functioning , and reduced ED visits , symptom days , missed school days , and caregiver stress , but there were no differential treatment effects . The results suggest that a home-based intervention addressing medical and psychosocial needs may prevent hospitalizations for children with poorly controlled asthma and caregivers under stress OBJECTIVE To compare glycemic control , body mass index ( BMI ) , neurocognitive function , and parenting stress for preschool-aged diabetic children r and omized to treatment either with continuous subcutaneous insulin infusion ( CSII ) or with intensive insulin injection therapy ( IIT ) . METHODS Children < 5 yr of age diagnosed with type 1 diabetes mellitus for at least 12 months were r and omized to either CSII ( n = 21 ) or IIT ( n = 21 ) for 6 months . After 6 months , the IIT group began CSII therapy and the CSII group continued on pumps . Hemoglobin A1c ( HbA1c ) and BMI percent were collected at baseline , 3 , 6 , 9 , and 12 months . Neurocognitive assessment s ( Developmental Test of Visual-Motor Integration and Stanford-Binet Intelligence Scale : Fourth Edition ) were administered to children , and parenting and child behavior assessment s ( Parenting Stress Index and Child Behavior Checklist ) were completed by parents and at baseline , 6 , and 12 months . RESULTS Thirty-five children completed the study . Mean HbA1c decreased significantly over the study period ( 8.9 % + /- 0.6 vs. 8.5 % + /- 0.7 , p = 0.006 ) . Initiation of CSII result ed in an HbA1c decrease of 0.4 % after 3 months ( p = 0.002 ) ; however , in the CSII first group , the HbA1c at 12 months was not significantly different from study start ( 8.8 % + /- 0.6 vs. 8.5 % + /- 0.6 ; p = 0.4 ) . There were no significant changes in BMI % , neurocognitive , parenting , and child behavior measures between groups . CONCLUSION Initiation of CSII vs. continuing IIT does not significantly influence HbA1c , BMI , neurocognitive , or parenting stress parameters in a research study setting Risk- and -resistance models identify factors that predict psychosocial adjustment to pediatric chronic illness , including sickle cell disease ( SCD ) , but have not been applied to underst and health outcomes . The study objectives were to examine prospect ively the relationship of coping and family functioning with health outcomes for adolescents with SCD , accounting for sociodemographic and psychosocial risk . Forty-one adolescents and their families ( 41 primary caregivers , 9 second caregivers , and 15 healthy siblings ) completed paper- and -pencil measures of coping and family functioning at a baseline assessment ( time 1 ) . At both time 1 and time 2 ( 1 y later ) , disease severity , SCD complications , healthcare utilization , and average hemoglobin level were derived from medical file review s. Time 1 disease-related parenting stress predicted time 2 health outcomes ; however , there were no significant associations for coping . Families concordant in reporting lower family functioning had teens with increased disease severity and greater healthcare utilization . Examination of moderation of disease-related parenting stress by a risk index showed main effects for risk and for disease-related parenting stress for time 2 disease severity and time 2 healthcare utilization . Interaction effects were not significant . Efforts to explore specific mechanisms by which adaptive family functioning contributes to health outcomes for adolescents with SCD should continue , with particular attention to addressing the potential role of multiple sociodemographic and psychosocial risk variables The ketogenic diet is increasingly used for the management of difficult-to-control seizures in children . Here , we describe the first prospect i ve study of the effects of the diet on development , behavior , and parenting stress . Participants were 65 children ( 36 males , 29 females ) with intractable seizures , ages 18 months to 14 years 6 months , enrolled in a prospect i ve study at the Johns Hopkins Hospital , Baltimore , MD , USA , to study the diet 's efficacy . Children were assessed before diet initiation and at 1-year follow-up . At follow-up , 52 % ( 34 of 65 ) children remained on the diet . Mean seizure frequency decreased from 25 per day before diet initiation to less than two per day 1 year later . At follow-up , mean developmental quotient showed statistically significant improvement ( p<0.05 ) , with significant behavioral improvements in attention and social functioning . Parental stress was essentially unchanged . No baseline factor examined predicted diet adherence , and the primary reason for diet discontinuation was insufficient seizure control . These preliminary results support prior anecdotal reports of the beneficial effects of the diet on cognition and behavior BACKGROUND Hypoglycemia in preschool children limits the effectiveness of insulin therapy . Continuous subcutaneous insulin infusion ( CSII ) is not widely used in this group . OBJECTIVES This study was design ed ( 1 ) to test the hypothesis that compared with twice-daily insulin injection , CSII decreases the SD of the mean daily blood glucose ( BG ) and improves glycemic control and ( 2 ) to evaluate the effect of CSII on parental anxiety using the Parental Stress Index ( PSI ) scale . METHODS Ten subjects < 6 years of age and receiving insulin injections were recruited . Each underwent two 72-h CGMS ( Medtronic Minimed , Northridge , CA ) monitoring periods and then was started on CSII and re-monitored 3 and 6 months later . We assessed the effects of CSII on the mean BG and SD of BG values , A1c , PSI scores , and number , distribution , and duration of hypoglycemic episodes . RESULTS Pooled pre- and post-CSII data were compared . There was a 22 % decrease in the BG variability ( mean + /- SD 93 + /- 19 mg/dL vs. 72 + /- 5 mg/dL ; P = 0.02 ) and a 13 % decrease in A1c ( 8.6 + /- 0.8 % vs. 7.5 + /- 0.7 % ; P = 0.01 ) . There was a decrease in the 24-h median number and duration of hypoglycemic episodes [ 1.16 vs. 0 episodes/24 h ( P = 0.01 ) and 1.19 vs. 0.05 h/24 h ( P = 0.01 ) , respectively ] , as well as the median number and duration of nighttime episodes [ 0.83 vs. 0 episode/night ( P = 0.008 ) and 0.98 vs. 0 h/night ( P = 0.008 ) , respectively ] . We found no statistically significant change in the PSI score . CONCLUSIONS CSII in preschool children is feasible and safe . Pump therapy reduced the glycemic excursions and decreased hypoglycemia duration and frequency In a prospect i ve study of 137 children ( 47 with cystic fibrosis , 48 with congenital heart disease , 42 with no chronic illness ) , four domains were examined as predictors of parent-reported behavioral problems , particularly internalizing problems , at 4 years of age : child health , child temperament , parent-child relationships , and family environment . Family environment , as measured by the Parenting Stress Index at 1 , 2 , and 3 years , was the most powerful predictor . This suggests that this index is useful as an early screen for children at risk for behavioral problems and that a reduction of parenting stress is an appropriate target of preventive interventions . J Dev Behav Pediatr 18:304 - 313 , 1997 |
13,466 | 23,922,167 | Currently there is no research evidence to suggest that any type of hydrocolloid wound dressing is more effective in healing diabetic foot ulcers than other types of dressing or a topical cream containing plant extracts . | BACKGROUND Foot ulcers in people with diabetes are a prevalent and serious global health issue .
Wound dressings are regarded as important components of ulcer treatment , with clinicians and patients having many different types to choose from including hydrocolloid dressings .
There is a range of different hydrocolloids available including fibrous-hydrocolloid and hydrocolloid ( matrix ) dressings .
A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use .
OBJECTIVES To compare the effects of hydrocolloid wound dressings with no dressing or alternative dressings on the healing of foot ulcers in people with diabetes . | Honey dressing has been used to promote wound healing for years but scanty scientific studies did not provide enough evidence s to justify it benefits in the treatment of diabetic foot ulcers . We conducted a prospect i ve study to compare the effect of honey dressing for Wagner 's grade -II diabetic foot ulcers with controlled dressing group ( povidone iodine followed by normal saline ) . Surgical debridement and appropriate antibiotics were prescribed in all patients . There were 30 patients age between 31 to 65-years-old ( mean of 52.1 years ) . The mean healing time in the st and ard dressing group was 15.4 days ( range 9 - 36 days ) compared to 14.4 days ( range 7 - 26 days ) in the honey group ( p < 0.005 ) . In conclusion , ulcer healing was not significantly different in both study groups . Honey dressing is a safe alternative dressing for Wagner grade -II diabetic foot ulcers : In recent years , skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements . This review details the pioneering work of numerous investigators that led to the following precursors of tissue-engineered skin replacement : cultured autologous keratinocyte grafts , cultured allogeneic keratinocyte grafts , autologous/allogeneic composites , acellular collagen matrices , and cellular matrices . It also discusses the rationale for the development of the newer products and describes the technical advances leading to the development of Apligraf , a tissue-engineered human skin product OBJECTIVE To compare the efficacy and tolerability of a new ionic silver alginate matrix ( Askina Calgitrol Ag ) with that of a st and ard silver-free alginate dressing ( Algosteril ) . METHOD Patients with locally infected chronic wounds ( pressure ulcers , venous or mixed aetiology leg ulcers , diabetic foot ulcers ) or acute wounds were eligible for this prospect i ve , open-label , controlled and r and omised trial . Patients were r and omised to receive one of the two dressings for a two-week period . Criteria of efficacy were based on the evolution , from day 1 to day 15 , of local signs of infection using a clinical score ranging from 0 to 18 , and the evolution of the bacteriological status for each wound . The latter was determined by ( blind ) bacteriological examinations of results obtained from two biopsies performed at days 1 and 15 . A three-point scale ( deterioration , unchanged , improvement ) was also used . Acceptability , usefulness and tolerance were also assessed . RESULTS Forty-two patients ( 20 women and 22 men , 68.9 + /- 18.8 and 66.5 + /- 15.7 years old respectively ) were r and omly assigned to receive either Askina Calgitrol Ag ( n=20 ) or Algosteril ( n=22 ) . Most had chronic wounds such as pressure ulcers ( 57 % ) or venous or mixed aetiology leg ulcers and diabetic foot ulcers ( 29 % ) ; few had acute wounds ( 14 % ) . Clinical scores of infection were comparable in both groups at inclusion , 8.9 + /- 2.4 and 8.6 + /- 3.2 in the Askina Calgitrol Ag group and the Algosteril group respectively ( not significant ) , but decreased significantly in both groups at day 15 , 3.8 + /- 2.9 in the Askina Calgitrol Ag group ( p=0.001 ) and 3.8 + /- 3.4 in the Algosteril group ( p=0.007 ) . There was no significant difference between the two groups at day 15 . Although there was also no significant difference in bacteriological status between the treatment groups , a trend in favour of Askina Calgitrol Ag was found for the relative risk of improvement , especially in patients who were not treated with antibiotics either at the beginning of the study or during it . No differences between groups were observed regarding local tolerance , acceptability and usefulness of the dressings . CONCLUSION The regression of local signs of infection , local tolerance , acceptability and usefulness were similar for the two dressings . However , Askina Calgitrol Ag improved the bacteriological status of the wounds . Further trials are required to show that it has a positive impact on the healing process Summary The EURODIAB IDDM Complications Study involved the examination of 3250 r and omly selected insulin-dependent diabetic patients , from 31 centres in 16 European countries . Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs , vibration perception threshold , tests of autonomic function and the prevalence of impotence . The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences . Significant correlations were observed between the presence of diabetic peripheral neuropathy with age ( p < 0.05 ) , duration of diabetes ( p < 0.001 ) , quality of metabolic control ( p < 0.001 ) , height ( p < 0.01 ) , the presence of background or proliferative diabetic retinopathy ( p < 0.01 ) , cigarette smoking ( p < 0.001 ) , high-density lipoprotein cholesterol ( p < 0.001 ) and the presence of cardiovascular disease ( p < 0.05 ) , thus confirming previous associations . New associations have been identified from this study – namely with elevated diastolic blood pressure ( p < 0.05 ) , the presence of severe ketoacidosis ( p < 0.001 ) , an increase in the levels of fasting triglyceride ( p < 0.001 ) , and the presence of microalbuminuria ( p < 0.01 ) . All the data were adjusted for age , duration of diabetes and HbA1c . Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction , there was no overall association of alcohol consumption and neuropathy . The reported problems of impotence were extremely variable between centres , suggesting many cultural and attitudinal differences in the collection of such information in different European countries . In conclusion , this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy . [ Diabetologia ( 1996 ) 39 : 1377–1384 OBJECTIVE : A r and omized controlled trial to evaluate the effectiveness of a polyhexamethylene biguanide ( PHMB ) foam dressing compared with a similar non-antimicrobial foam for the treatment of superficial bacterial burden , wound-associated pain , and reduction in wound size . SETTING AND PARTICIPANTS : This study was conducted in 2 wound healing clinics-a university hospital-based clinic and a community-based clinic . Forty-five chronic wound subjects , stratified to either foot or leg ulcers , were followed for 5 weeks . METHODS : A multicenter , prospect i ve , double-blind , pilot , r and omized controlled clinical trial with 3 study visits ( Weeks 0 , 2 , 4 ) documented pain and local wound characteristics using NERDS and STONEES clinical criteria to determine superficial bacterial damage or deep/surrounding infection . RESULTS : The use of PHMB foam dressing was a significant predictor of reduced wound superficial bacterial burden ( P = .016 ) at week 4 as compared with the foam alone . Pain reduction was also statistically significant at week 2 ( P = .0006 ) and at week 4 ( P = .02 ) in favor of the PHMB foam dressings . Polymicrobial organisms were recovered at week 4 in 5.3 % in the PHMB foam dressing group versus 33 % in the control group ( P = .04 ) . Subjects r and omized to the PHMB foam dressing had a 35 % median reduction in wound size by week 4 , compared with 28 % in the control group . CONCLUSIONS : PHMB foam dressing successfully reduced chronic wound pain and bacterial burden OBJECTIVES To determine the comparative effectiveness and cost-effectiveness of three dressing products , N-A , Inadine and Aquacel , for patients with diabetic foot ulcers , as well as the feasibility and consequences of less frequent dressing changes by health-care professionals . DESIGN A multicentre , prospect i ve , observer-blinded , parallel group , r and omised controlled trial , with three arms . SETTING Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK . PARTICIPANTS Patients over age 18 with type 1 or type 2 diabetes with a chronic ( present for at least 6 weeks ) full-thickness foot ulcer ( on or below the malleoli ) not penetrating to tendon , periosteum or bone , and with a cross-sectional area between 25 and 2500 mm(2 ) . INTERVENTIONS Participants were r and omised 1:1:1 to treatment with one of N-A ( a non-adherent , knitted , viscose filament gauze ) , Inadine ( an iodine-impregnated dressing ) , both traditional dressings , or Aquacel , a newer product . MAIN OUTCOME MEASURES The primary outcome measure was the number of ulcers healed in each group at week 24 . Secondary measures included time to healing , new ulcerations , major and minor amputations , and episodes of secondary infection . RESULTS A total of 317 patients were r and omised . After 88 withdrawals , 229 remained evaluable . A greater proportion of smaller ( 25 - 100 mm(2 ) ulcers healed within the specified time ( 48.3 % versus 37.3 % ; p = 0.048 ) . There was , however , no difference between the three dressings in terms of percentage healed by 24 weeks , or in the mean time to healing , whether analysed on the basis of intention to treat ( Inadine 44.4 % , N-A 38.7 % , Aquacel 44.7 % ; not significant ) or per protocol ( Inadine 55.2 % , N-A 59.4 % , Aquacel 63.0 % ; not significant ) . There was no difference in the quality of healing , as reflected in the incidence of recurrence within 12 weeks . Likewise , there was no difference in the incidence of adverse events , although a greater proportion of those r and omised to the non-adherent dressings were withdrawn from the study ( 34.9 % versus 29.1 % Aquacel and 19.4 % Inadine ; p = 0.038 ) . The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings ( mean cost per patient : N-A 14.85 pounds , Inadine 17.48 pounds , Aquacel 43.60 pounds ) . The higher cost of Aquacel was not offset by the fewer dressings required . There was no difference in measures of either generic or condition-specific measures of quality of life . However , there was a significant difference in the change in pain associated with dressing changes between the first and second visits , with least pain reported by those receiving non-adherent dressings ( p = 0.012 ) . There was no difference in the costs of professional time , and this may relate to the number of dressing changes undertaken by non-professionals . Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer , although this ranged from 22 % to 82 % between the different centres . CONCLUSIONS As there was no difference in effectiveness , there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service , thus generating potentially substantial savings . The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs . TRIAL REGISTRATION Current Controlled Trials IS RCT N78366977 Nonhealing diabetic foot ulcers are a common cause of amputation . Emerging cellular therapies such as platelet-rich plasma gel provide ulcer management options to avoid loss of limb . The purpose of this prospect i ve , r and omized , controlled , blinded , multicenter clinical study was to evaluate the safety and efficacy of autologous platelet-rich plasma gel for the treatment of nonhealing diabetic foot ulcers . One hundred , twenty-nine ( 129 ) patients were screened ; 72 completed a 7-day screening period and met the study inclusion criteria . Patients were r and omized into two groups - the st and ard care with platelet-rich plasma gel or control ( saline gel ) dressing group - and evaluated biweekly for 12 weeks or until healing . Healing was confirmed 1 week following closure and monitored for another 11 weeks . An independent audit led to the exclusion of 32 patients from the final per- protocol analysis because of protocol violations and failure to complete treatment . In this group , 13 out of 19 ( 68.4 % ) of the platelet-rich plasma gel and nine out of 21 ( 42.9 % ) of the control wounds healed . After adjusting for wound size outliers ( n = 5 ) , significantly more platelet-rich plasma gel ( 13 out of 16 , 81.3 % ) than control gel ( eight out of 19 , 42.1 % ) treated wounds healed ( P = 0.036 , Fisher 's exact test ) . Kaplan-Meier time-to-healing also was significantly different between groups ( log-rank , P = 0.0177 ) . No treatment-related serious adverse events were reported and bovine thrombin used in the preparation of PRP did not cause Factor V inhibition . When used with good st and ards of care , the majority of nonhealing diabetic foot ulcers treated with autologous platelet-rich plasma gel can be expected to heal A prospect i ve , multicenter , r and omized , controlled 12-week study was undertaken to evaluate the effectiveness of a human fibroblast-derived dermis for treating foot ulcers in the diabetic patient . This report summarizes the findings from one center . Following a 2-week screening period , patients were r and omized to either human fibroblast-derived dermis ( HFDD ) ( Dermagraft ) plus saline-moistened gauze or to the control group ( CT ) of saline-moistened gauze alone . Effectiveness end points were : 1 ) wound closure by week 12 , 2 ) time to wound closure , and 3 ) percent wound closure by week 12 . Safety was assessed by review of adverse events and laboratory findings . Patients r and omized to HFDD received an application at day 0 and up to seven additional treatments . All patients in each group received shoes with custom-molded inserts and were seen weekly . The study population was comprised of 28 patients ( 14 HFDD/14 CT ) with chronic ulcers ( > 6 weeks ' duration at time of screening ) . By week 12 , significantly more chronic ulcers healed in the HFDD group than in the CT group ( 71.4 % versus 14.3 % , p = .003 ) . Healed HFDD patients achieved wound closure significantly faster than CT patients ( p = .004 ) . Patients treated with HFDD showed a statistically significant higher percent of wound closure by week 12 than did CT patients ( p = .002 ) . The percent of patients who experienced an infection involving their study wound was less in the HFDD group than in the CT group . It was concluded that HFDD is a safe and effective treatment for chronic foot ulcers in diabetic patients Background There are many barriers to patient participation in r and omised controlled trials of cancer treatments . To increase participation in trials , strategies need to be identified to overcome these barriers . Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in r and omised controlled trials ( RCTs ) of cancer treatments . Methods A systematic review was conducted . Published and unpublished studies in any language were search ed for in fifteen electronic data bases , including MEDLINE , EMBASE , CINAHL and PsycINFO , from inception to the end of 2004 . Studies of any interventions to improve cancer patient participation in RCTs , which reported the change in recruitment rates , were eligible for inclusion . RCTs and non-r and omised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included . Data were extracted by one review er into structured summary tables and checked for accuracy by a second review er . Each included study was assessed against a checklist for method ological quality by one review er and checked by a second review er . A narrative synthesis was conducted . Results Eight studies were identified that met the inclusion criteria : three RCTs , two non-r and omised controlled trials and three observational studies . Six of the studies had an intervention that had some relevance to the UK . There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs , though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer . Although there was no evidence of an effect in any of the studies , the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work . Conclusion There is not a strong evidence -base for interventions that increase cancer patient participation in r and omised trials . Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials Background Diabetes is becoming one of the most common chronic diseases , and ulcers are its most serious complication . Beginning with neuropathy , the subsequent foot wounds frequently lead to lower extremity amputation , even in the absence of critical limb ischemia . In recent years , some research ers have studied external shock wave therapy ( ESWT ) as a new approach to soft tissue wound healing . The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers . Methods We design ed a r and omized , prospect i ve , controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies . One group was treated with st and ard care and shock wave therapy . The other group was treated with only st and ard care . The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization . Results After 20 weeks of treatment , 53.33 % of the ESWT-treated patients had complete wound closure compared with 33.33 % of the control patients , and the healing times were 60.8 and 82.2 days , respectively ( p < 0.001 ) . Significant differences in the index of the re-epithelization were observed between the two groups , with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group ( p < 0.001 ) . Conclusion Therefore , ESWT may be a useful adjunct in the management of diabetic foot ulceration . Trial registration Current Controlled Trials IS RCT Wound closure using topical negative pressure ( TNP ) has been reported to be effective , but equipment costs can be prohibitive in re source -challenged countries . Because nonhealing wounds are exceedingly common in developing countries such as India , the ability to optimize wound care with limited re sources is very important . To investigate the feasibility and efficacy of providing TNP in an Indian medical referral center , a r and omized controlled trial comparing a locally constructed TNP device ( treatment ) to wet-to-dry gauze dressings ( control ) was conducted . Eligible study participants ( N = 48 ) were recruited from the inpatient wards . Wound etiologies included diabetic foot ulcers ( 15 ) , pressure ulcers ( 11 ) , cellulitis/fasciitis ( 11 ) , and " other " ( 11 ) . Following enrollment , wound size was assessed using computer-aided measurements of digital photographs and block-r and omized to the study arms using a concealed allocation table . Wounds in both treatment groups were débrided before dressing application and patients were followed until wound closure or being lost to follow-up for an average of 26.3 days ( + /- 18.5 ) in the control and 33.1 days ( + /- 37.3 ) in the treatment group . No statistically significant differences in time to closure between the two treatment groups were observed except in a subset analysis of pressure ulcers ( mean 10 + /- 7.11 days for treatment and 27 + /- 10.6 days in control group , P = 0.05 ) . Direct costs to close a pressure ulcer also were lower in the TNP than in the control group . A review of the literature suggests the outcomes obtained using a locally constructed TNP device are similar to those obtained using commercially available devices . As a result of this study , a dedicated tissue viability team has been established to identify wounds suitable for TNP , oversee treatment , monitor the need for surgical débridement , and employ wound healing principles and technology appropriately . These results suggest that inexpensive material s can be utilized for TNP wound closure in a developing country Diabetic foot wounds present a great challenge to wound care practitioners . The objective of this pilot study was to determine whether vacuum-assisted closure ( V.A.C. ) therapy would afford quicker wound resolution as compared to saline-moistened gauze in the treatment of postoperative diabetic foot wounds . Ten patients were r and omized into either the experimental V.A.C. group or control saline gauze group . Included in the study were diabetic patients 18 to 75 years of age who had a nonhealing foot ulceration . Excluded were those patients with venous disease , coagulopathy , or those who had active infections not resolved by initial surgical debridement . All foot ulcers were surgically debrided prior to initiation of V.A.C. or gauze treatment . In the experimental group , V.A.C. dressings were applied in accordance with manufacturer 's protocol for chronic wounds and changed every 48 hours . In the control group , saline gauze dressings were applied at the time of surgical debridement and changed twice a day thereafter . Measurements and photos were obtained to document wound progress . Main outcome measures included : 1 ) time to satisfactory healing ( calculated from date of initial debridement to date of definitive closure , and 2 ) change in wound surface area ( calculated from initial wound tracing to final tracing ) . Satisfactory healing in the V.A.C. group was achieved in 22.8 ( + /- 17.4 ) days , compared to 42.8 ( + /- 32.5 ) days in the control group . Surface area changes of 28.4 % ( + /- 24.3 ) average decrease in wound size in the V.A.C. group , compared to a 9.5 % ( + /- 16.9 ) average increase in the control group during measurement period OBJECTIVE To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospect i ve multicenter trial of diabetic patients with foot ulceration . RESEARCH DESIGN AND METHODS We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospect i ve , r and omized controlled trial . RESULTS Wound area measurements at baseline and after 4 weeks were performed in 203 patients . The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53 % . Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58 % , whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9 % ( P < 0.01 ) . The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers ( 1.5 versus 0.8 cm2 , P < 0.02 ) . The percent change in wound area at 4 weeks in those who healed was 82 % ( 95 % CI 70 - 94 ) , whereas in those who failed to heal , the percent change in wound area was 25 % ( 15 - 35 ; P < 0.001 ) . CONCLUSIONS The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks . This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to st and ard care and may need additional treatment OBJECTIVE To evaluate the utility of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers . RESEARCH DESIGN AND METHODS Nineteen subjects with either insulin- dependent diabetes mellitus ( IDDM ) or non-insulin-dependent diabetes mellitus ( NIDDM ) and foot ulcers were r and omly assigned to the polymeric dressing or conventional wet-to-dry saline dressings . Subjects had foot ulcer site measurements performed every 3 weeks . The subjects using conventional therapy were allowed to cross over to polymeric dressing after 2 months . RESULTS At the end of 2 months , in the patients using the polymeric dressing , ulcer size was reduced to 35 ± 16 % of baseline . The patients on conventional therapy had an ulcer size of 105 ± 28 % of baseline ( P < 0.03 , polymeric vs. conventional ) . Patients initially treated with wet-to-dry saline were crossed over into the polymeric membrane treatment and demonstrated a decrease to 35 ± 11 % of baseline size ( P < 0.02 ) after an additional 2 months . CONCLUSIONS The semipermeable polymeric membrane dressing is a useful therapeutic option for treating uncomplicated chronic diabetic foot ulcers Effects of a topical cream containing P. amboinicus ( Lour . ) Spreng . ( Lamiaceae ) and C. asiatica ( L. ) Urban ( Umbelliferae ) were evaluated and compared to effects of hydrocolloid fiber wound dressing for diabetic foot ulcers . A single-center , r and omized , controlled , open-label study was conducted . Twenty-four type 1 or type 2 diabetes patients aged 20 years or older with Wagner grade 3 foot ulcers postsurgical debridement were enrolled between October 2008 and December 2009 . Twelve r and omly assigned patients were treated with WH-1 cream containing P. amboinicus and C. asiatica twice daily for two weeks . Another 12 patients were treated with hydrocolloid fiber dressings changed at 7 days or when clinical ly indicated . Wound condition and safety were assessed at days 7 and 14 and results were compared between groups . No statistically significant differences were seen in percent changes in wound size at 7- and 14-day assessment s of WH-1 cream and hydrocolloid dressing groups . A slightly higher proportion of patients in the WH-1 cream group ( 10 of 12 ; 90.9 % ) showed Wagner grade improvement compared to the hydrocolloid fiber dressing group but without statistical significance . For treating diabetic foot ulcers , P. amboinicus and C. asiatica cream is a safe alternative to hydrocolloid fiber dressing without significant difference in effectiveness OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) . St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care OBJECTIVE To evaluate the clinical efficacy and safety of HYAFF 11-based autologous dermal and epidermal grafts in the management of diabetic foot ulcers . RESEARCH DESIGN AND METHODS A total of 79 patients with diabetic dorsal ( n = 37 ) or plantar ( n = 42 ) ulcers were r and omized to either the control group with nonadherent paraffin gauze ( n = 36 ) or the treatment group with autologous tissue-engineered grafts ( n = 43 ) . Weekly assessment , aggressive debridement , wound infection control , and adequate pressure relief ( fiberglass off-loading cast for plantar ulcers ) were provided in both groups . Complete wound healing was assessed within 11 weeks . Safety was monitored by adverse events . RESULTS Complete ulcer healing was achieved in 65.3 % of the treatment group and 49.6 % of the control group ( P = 0.191 ) . The Kaplan-Meier mean time to closure was 57 and 77 days , respectively , for the treatment versus control groups . Plantar foot ulcer healing was 55 % and 50 % in the treatment and control groups , respectively . Dorsal foot ulcer healing was significantly different , with 67 % in the treatment group and 31 % in the control group ( P = 0.049 ) . The mean healing time in the dorsal treatment group was 63 days , and the odds ratio for dorsal ulcer healing compared with the control group was 4.44 ( P = 0.037 ) . Adverse events were equally distributed between the two groups , and none were related to the treatments . CONCLUSIONS The autologous tissue-engineered treatment exhibited improved healing in dorsal ulcers when compared with the current st and ard dressing . For plantar ulcers , the off-loading cast was presumably paramount and masked or nullified the effects of the autologous wound treatment . This treatment , however , may be useful in patients for whom the total off-loading cast is not recommended and only a less effective off-loading device can be applied OBJECTIVE To compare the wound healing rate and incidence of infection in wounds treated with either a bioactive dressing ( containing hydrophilic mucopolysaccharide , chitosan ) or conservative treatment ( gauze ) . METHOD Eighty-five patients with diabetic foot ulcers , pressure ulcers or leg ulcers were r and omised to receive either the bioactive study dressing ( n=33 patients , 45 wounds ) or the control dressing ( n=52 patients , 53 wounds ) for 21 days . Wound size , stage where appropriate and the presence of infection were recorded at each dressing change . Thirty-one of these 85 patients dropped out of the study during the three-month post-treatment follow-up , when wound size and grade were assessed on a monthly basis . Data were therefore analysed on 54 patients , of whom 32 ( 34 wounds ) were in the treatment group and 22 ( 26 wounds ) in the control group . RESULTS In the control group , four pressure ulcers healed , but the remaining wounds all deteriorated and became infected , requiring antibiotics . In contrast , in the treatment group 29/34 wounds healed completely , and none became infected ; the remaining five wounds healed during the follow-up period . The difference between the two groups in the number of wounds that healed was statistically significant ( p<0.001 ) , as was that for the number of healed pressure ulcers p<0.05 . CONCLUSION Use of a moist bioactive wound dressing significantly increased the healing rate when compared with the traditional dressings used in the participating hospitals . This will in turn bring significant cost savings OBJECTIVE To assess the effect of a tissue-engineered human dermis ( Dermagraft ) in healing diabetic foot ulcers . RESEARCH DESIGN AND METHODS This controlled prospect i ve multicenter r and omized single-blinded pilot study evaluated healing over a 12-week period in 50 patients with diabetic foot ulcers . These patients were r and omized into four groups ( three different dosage regimens of Dermagraft and one control group ) . All patients received identical care except for the use of Dermagraft tissue . Ulcer healing was assessed by percentage of wounds achieving complete or 50 % closure , time to complete or 50 % closure , and volume and area measurements . RESULTS Ulcers treated with the highest dosage of Dermagraft , one piece applied weekly for 8 weeks ( group A ) , healed significantly more often than those treated with conventional wound closure methods ; 50 % ( 6 of 12 ) of the Dermagraft-treated and 8 % ( 1 of 13 ) of the control ulcers healed completely ( P = 0.03 ) . The percentage of wounds achieving 50 % closure was also significantly higher ( 75 vs. 23 % ; P = 0.018 ) , and the time to complete or 50 % closure was faster ( P = 0.056 ) . The group A regimen was more effective than other treatment regimens . All three were better than the control , however , and a dose-response was observed . There were no safety concerns . After a mean of 14 months of follow-up ( range 11 - 22 months ) , there were no recurrences in the Dermagraft-healed ulcers . CONCLUSIONS Dermagraft was associated with more complete and rapid healing in diabetic foot ulcers . The recurrence data may indicate an improved quality of wound healing Chronic wounds of the lower extremity are a therapeutic dilemma . In India , chronic wounds are caused by factors other than impaired circulation and diabetes , which account for most of this clinical problem in Western societies . A study of 2 topical agents , placental extract and phenytoin powder , is presented in this paper . One hundred fifty patients were r and omly assigned to these treatments or to saline dressings ( control ) . It was observed that patients receiving active topical treatments responded better than those in the control group . The importance of this finding should be viewed with the perspective that these topical treatments are inexpensive and easily available in India . The study also piloted measurements of angiogenic responses in 1 group , and the findings encourage further exploration with the technique and topical agent OBJECTIVE To compare an ibuprofen-releasing foam dressing ( Biatain Ibu , ColoplastA/S ) with local best practice in the treatment of painful exuding wounds . METHOD In this large-scale r and omised comparative study , 853 patients were r and omised to either ibuprofen-releasing foam ( test ) dressing ( n=467 ) or local best practice ( n=386 ) . Primary endpoint was wound pain relief from day 1 - 7 , assessed by the patients twice daily using a five-point verbal rating scale . Secondary endpoints were reduction in pain intensity from day 0 - 7 ( assessed using an 11-point numeric box scale ) , quality of life ( assessed using the WHO-5 well-being index and effect on health-related activities of daily living ) and the incidence of adverse events . RESULTS After seven days significantly more patients in the experimental group experienced relief from temporary and persistent pain and a reduction in pain intensity , when compared with patients in the local best practice group ( p<0.0001 ) . They also experienced a greater improvement in quality of life . The number of adverse events in both groups was low . CONCLUSION The test dressing provided an appropriate wound healing environment , relieved temporary and persistent wound pain , and decreased pain intensity . It was also associated with an improvement in quality of life An open r and omized controlled study was carried out of 44 diabetic patients with necrotic foot ulcers treated with adhesive zinc oxide tape ( MeZinc ) or with an adhesive occlusive hydrocolloid dressing ( DuoDerm ) . Fourteen of the 21 patients treated with MeZinc had their necrotic ulcers improved by at least 50 % compared to six out of 21 with the hydrocolloid dressing ( P < 0·025 ) . Fifteen patients showed an increase in the area of necrosis during the course of the 5‐week study and of these , 10 had been treated with the hydrocolloid dressing AIM This paper is a report of a study to compare a medical grade honey with conventional treatments on the healing rates of wounds healing by secondary intention . BACKGROUND There is an increasing body of evidence to support the use of honey to treat wounds , but there is a lack of robust r and omized trials on which clinicians can base their clinical judgement . METHOD A sample of 105 patients were involved in a single centre , open-label r and omized controlled trial in which patients received either a conventional wound dressing or honey . Data were collected between September 2004 and May 2007 . RESULTS The median time to healing in the honey group was 100 days compared with 140 days in the control group . The healing rate at 12 weeks was equal to 46.2 % in the honey group compared with 34.0 % in the conventional group , and the difference in the healing rates ( 95 % confidence interval , CI ) at 12 weeks between the two groups was 12.2 % ( -13.6 % , 37.9 % ) . The unadjusted hazard ratio ( 95 % CI ) from a Cox regression was equal to 1.30 ( 0.77 , 2.19 ) , P = 0.321 . When the treatment effect was adjusted for confounding factors ( sex , wound type , age and wound area at start of treatment ) , the hazard ratio increased to 1.51 but was again not statistically significant . CONCLUSION Wound area at start of treatment and sex are both highly statistically significant predictors of time to healing . These results support the proposition that there are clinical benefits from using honey in wound care , but further research is needed AIMS Diabetic foot ulcers ( DFUs ) are at risk of infection and impaired healing , placing patients at risk of lower extremity amputation . DFU care requires debridement and dressings . A prospect i ve , multicentre study compared clinical efficacy and safety of AQUACEL Hydrofiber dressings containing ionic silver ( AQAg ) with those of Algosteril calcium alginate ( CA ) dressings in managing out- patients with Type 1 or 2 diabetes mellitus and non-ischaemic Wagner Grade 1 or 2 DFUs . METHODS Patients stratified by antibiotic use on enrolment were r and omly assigned to similar protocol s including off-loading , AQAg ( n = 67 ) or CA ( n = 67 ) primary dressings and secondary foam dressings for 8 weeks or until healing . Clinical efficacy measures were healing outcomes and primarily healing speed . Adverse events were recorded . RESULTS AQAg and CA groups were comparable at baseline . All ulcer healing outcomes improved in both groups . The mean time to healing was 53 days for AQAg ulcers and 58 days for CA ulcers ( P = 0.34 ) . AQAg-treated ulcers reduced in depth nearly twice as much as CA-treated ulcers ( 0.25 cm vs. 0.13 cm ; P = 0.04 ) . There was more overall ulcer improvement and less deterioration in AQAg subjects ( P = 0.058 ) , particularly in the subset initially using antibiotics ( P = 0.02 ) . Safety profiles of both groups were similar . CONCLUSION When added to st and ard care with appropriate off-loading , AQAg silver dressings were associated with favourable clinical outcomes compared with CA dressings , specifically in ulcer depth reduction and in infected ulcers requiring antibiotic treatment . This study reports the first significant clinical effects of a primary wound dressing containing silver on DFU healing This study compared the treatment of total contact casting ( TCC ) with traditional dressing treatment ( TDT ) in the management of diabetic plantar ulcers . Forty patients with diabetes mellitus and a plantar ulcer but with nogross infection , osteomyelitis , or gangrene were r and omly assigned to the TCC group ( n = 21 ) or TDT group ( n = 19 ) . Age , sex , ratio of insulin-dependent diabetes mellitus to non-insulin-dependent diabetes mellitus , duration of diabetes mellitus , vascular status , size and duration of ulcer , and sensation were not significantly different between groups ( P > .05 ) . In the experimental group , TCC was applied on the initial visit , and subjects were instructed to limit ambulation to ∼33 % of their usual activity . Subjects in the control group were prescribed dressing changes and accommodative footwear and were instructed to avoid bearing weight on the involved extremity . Ulcers were considered healed if they showed complete skin closure with no drainage . Ulcers were considered not healed if they showed no decrease in size by 6 wk or if infection developed that required hospitalization . In the TCC group , 19 of 21 ulcers healed in 42 ± 29 days ; in the TDT group , 6 of 19 ulcers healed in 65 ± 29 days . Significantly more ulcers healed ( χ2 = 12.4 , P < .05 ) and fewer infections developed ( χ2 = 4.1 , P < .05 ) in the TCC group . We conclude TCC is a successful method of treating diabetic plantar ulcers but requires careful application , close follow-up , and patient compliance with scheduled appointments to minimize complications HYPOTHESIS Promogran , a wound dressing consisting of collagen and oxidized regenerated cellulose , is more effective that st and ard care in treating chronic diabetic plantar ulcers . DESIGN R and omized , prospect i ve , controlled multicenter trial . SETTING University teaching hospitals and primary care centers . PATIENTS A total of 276 patients from 11 centers were enrolled in the study . The mean age of the patients was 58.3 years ( range , 23 - 85 years ) . All patients had at least 1 diabetic foot ulcer . INTERVENTIONS Patients were r and omized to receive Promogran ( n = 138 ) or moistened gauze ( control group ; n = 138 ) and a secondary dressing . Dressings were changed when clinical ly required . The maximum follow-up for each patient was 12 weeks . MAIN OUTCOME MEASURE Complete healing of the study ulcer ( wound ) . RESULTS After 12 weeks of treatment , 51 ( 37.0 % ) Promogran-treated patients had complete wound closure compared with 39 ( 28.3 % ) control patients s , but this difference was not statistically significant ( P = .12 ) . The difference in healing between treatment groups achieved borderline significance in the subgroup of patients with wounds of less than 6 months ' duration . In patients with ulcers of less than 6 months ' duration , 43 ( 45 % ) of 95 Promogran-treated patients healed compared with 29 ( 33 % ) of 89 controls ( P = .056 ) . In the group with wounds of at least 6 months ' duration , similar numbers of patients healed in the control ( 10/49 [ 20 % ] ) and the Promogran ( 8/43 [ 19 % ] ; P = .83 ) groups . No differences were seen in the safety measurements between groups . Patients and investigators expressed a strong preference for Promogran compared with moistened gauze . CONCLUSIONS Promogran was comparable to moistened gauze in promoting wound healing in diabetic foot ulcers . It showed an additional efficacy for ulcers of less than 6 months ' duration that was of marginal statistical significance . Furthermore , Promogran had a safety profile that was similar to that of moistened gauze , with greater user satisfaction . Therefore , Promogran may be a useful adjunct in the management of diabetic foot ulceration , especially in ulcers of less than 6 months ' duration BACKGROUND It is hypothesized that moisture regulation specific to the area of contact results in local wound conditions more amenable to healing , which would result in faster and more frequent wound closure . TheraGauze is a new polymer-impregnated dressing design ed to regulate moisture to a varying degree over the entire surface of a wound . METHODS This prospect i ve , r and omized , multicenter study examined outcomes from treatment of diabetic foot ulcers with TheraGauze and TheraGauze in conjunction with becaplermin . We also compared these outcomes with historical data from the literature that used saline-moistened gauze and becaplermin . RESULTS The rates of wound closure with TheraGauze and TheraGauze + becaplermin were 0.37 and 0.41 cm(2)/week , respectively ( P = .34 ) . The difference between these values was not statistically significant . We also observed high closure rates at 12 weeks ( 46.2 % in both groups ) and 20 weeks ( 61.5 % with TheraGauze alone and 69.2 % with TheraGauze + becaplermin ) . These data were also compared with historical data for closure rates ( 0.18 cm(2)/week ) and percentage of wounds closed using saline-moistened gauze alone and becaplermin with saline-moistened gauze ( 0.24 cm(2)/week ) from a variety of studies . CONCLUSIONS Wounds in which moisture content was regulated with TheraGauze showed more rapid change in wound area and a higher percentage of wounds achieving closure at 12 and 20 weeks regardless of whether becaplermin was used Bone marrow (BM)-derived mesenchymal stem cells ( MSCs ) represent a promising population for supporting new concepts in cellular therapy . This study was undertaken to assess the efficacy and feasibility of autologous BM-derived MSCs in the treatment of chronic nonhealing ulcers ( diabetic foot ulcers and Buerger disease ) of the lower extremities . A total of 24 patients with nonhealing ulcers of the lower limb were enrolled and r and omized into implant and control groups . In the implant group , the patients received autologous cultured BM-derived MSCs along with st and ard wound dressing ; the control group received only the st and ard wound dressing regimen , followed up for at least a 12-week period . Wound size , pain-free walking distance , and biochemical parameters were measured before therapy and at every 2-week interval following intervention . The implant group had significant improvement in pain-free walking distance and reduction in ulcer size as compared to those in the control group . In the implant group for Buerger disease , the ulcer area decreased from 5.04 + /- 0.70 cm(2 ) to 1.48 + /- 0.56 cm(2 ) ( p < 0.001 ) , whereas the pain-free walking distance increased from 38.33 + /- 17.68 m to 284.44 + /- 212.12 m ( p < 0.001 ) . In the diabetic foot ulcer group , the ulcer size decreased from 7.26 + /- 1.41 cm(2 ) to 2 + /- 0.98 cm(2 ) ( p < 0.001 ) at 12 weeks . Mononuclear cells were cultured for a minimum of five passages and characterized by cell-surface markers showing CD90 + , CD105 + , and CD34(- ) . There was no significant alteration in the biochemical parameters observed during the follow-up period , indicating normal liver and renal function following intervention . Biopsy microsection of implanted tissues showed development of dermal cells ( mainly fibroblasts ) , including mature and immature inflammatory cells . The study indicates that autologous implantation of BM-derived MSCs in nonhealing ulcers accelerates the healing process and improves clinical parameters significantly p < 0.01 ) and the median time to complete wound closure ( 7 vs. 15 weeks , p= 0.0021 , rank-sum test ) . There was no difference in the wound closure rate of meshed and unmeshed graft at 4 , 8 , 12 , or 24 weeks ( p > 0.05 ) . Three indolent localized wound infections in the tissue-engineered skin graft group were the only complication . Tissue-engineered skin grafting can be used safely in previously ischemic wounds after lower extremity revascularization . Treatment with this graft promotes healing more rapidly and in more patients than st and ard moist dressings . It obviates the risk , inconvenience , and expense of donor skin harvesting , anesthesia , and hospitalization associated with autologous skin grafting . This graft may represent an advance in the treatment of previously ischemic lower extremity foot wounds AIM In addition to contemporary compression therapy , one of the therapeutic approaches is the use of a topical wound care agent . The goal of this pilot registry study is to evaluate the efficacy and safety of a uniquely design ed ointment containing multivalent silver oxide ( Ag4O4 ) in the healing of difficult diabetic or venous ulcerations . METHODS Patients who had ulcers result ing from chronic venous insufficiency or diabetes participated in this open-label , r and omized registry study . All patients were evaluated by measuring both the area of the ulceration and microcirculatory parameters . 148 patients were included in the study and categorized into two main groups : venous ulcers and diabetic ulcers . Each main group was then r and omized into two sub-groups : topical treatment with silver oxide ointment and the control group ( st and ard cleaning and compression management methods , without silver ointment ) . All patients were treated with accepted cleaning and compression management . RESULTS . In subjects with venous ulcers : After 4 weeks , the silver treatment was more effective than the control group treatment : Skin PO2 was increased 2.1 times more than the control group ( 17.4 % to 8.2 % ) and skin flux ( RF ) was improved 1.6 times more than the control group ( -38.7 % to -24.2 % ) . The total surface area of the ulcer was significantly reduced in the silver treatment group by 1.9 times the control group ( -88.7 % to -46.9 % ) . In addition , in the silver treatment group we observed complete closure of the ulceration in 42 % of subjects compared to 22 % in the control group ( P=<0.05 ) . In subjects with diabetic ulcers : after 4 weeks , the silver treatment was more effective than the control group treatment : Skin PO2 increased 2.6 times more than the control group ( 23.3 % to 9.1 % ) and skin flux ( RF ) was significantly improved 4.3 times more than the control group(-26.7 % to -6.2 % ) . The total surface area of the ulcer was significantly reduced in the silver treatment group by 3.7 times the control group ( -89.0 % to -23.9 % ) . In addition , in the silver treatment group we observed complete closure of the ulceration in 39 % of subjects compared to 16 % in the control group ( P</=0.05 ) . CONCLUSION This pilot study provides observational data on the efficacy of local treatment of ulcers with a multivalent silver oxide containing ointment . The silver ointment improved microcirculation and the healing rate of all 78 patients that were treated with multivalent silver ointment and closed twice as many ulcers in 4 weeks compared to the control groups ( 40.7 % silver treatment compared to 19.4 % for the control ) . This study demonstrates the feasibility of this type of treatment and provides evidence of efficacy to plan larger r and omized controlled studies . The large number of patients that were helped in this study demonstrates the efficacy of multivalent silver oxide topical ointment and its important role in ulcer therapy The presence of an ulcer beneath callus on the diabetic foot has been a well-documented and common clinical finding . We have conducted a prospect i ve study to examine whether callus can be used to predict plantar intrinsic neuropathic diabetic foot ulcer formation . Sixty-three diabetic patients ( 43 male , 25 Type 1 ) , median age 62 years ( IQ range 52 , 67 ) , median diabetes duration 17 years ( IQ range 8,25 ) participated in the study . All had neuropathy and peak plantar foot pressures ( measured using a dynamic optical pedobarograph ) > or = 10 kg cm-2 . Calluses and previous ulcers were documented and classified . All ulcers occurring prior to and during the study were recorded , re-examination was 15.4 ( range 10 - 22 ) months from baseline . Seven ulcers ( 6 patients ) occurred during the study . Pressures were higher in the ulcer than non-ulcer sub-group ( p = 0.04 ) with a relative risk of developing an ulcer of 4.7 for an area of elevated plantar pressure . This compares with a relative risk of 11.0 for an ulcer developing under an area of callus , and a relative risk of 56.8 for an ulcer developing on a site of previous ulceration . This study confirms that a history of previous ulceration is the highest risk factor for ulceration and demonstrates , for the first time , that the presence of plantar callus is highly predictive of subsequent ulceration . Careful history taking and examination of the foot to detect the presence of callus require no special training or equipment and callus should be recognized as a ' high risk ' factor for foot ulceration AIMS The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of diabetic foot ulcers , but knowledge of its effects on wound healing is sparse . The objective of this study was to evaluate the effects of felted foam on wound healing in diabetic foot ulcers compared with a st and ard method of plantar pressure relief . MATERIAL S AND METHODS A total of 54 Type 1 or Type 2 diabetic patients with neuropathic diabetic foot ulcers were evaluated in this prospect i ve r and omized controlled study . Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing . The patients were consecutively enrolled in the study ; 24 patients were r and omized to the felted foam therapy , and 30 patients were r and omized to conventional therapy . RESULTS In the felted foam group , the initial average wound area was 102.3 + /- 45.3 mm2 ( mean + /- sd ) , and 5.4 + /- 3.1 mm2 after 10 weeks with an average healing time of 75 days [ 95 % confidence interval ( CI ) 67 - 84 ] . In the conventional therapy group , the initial average wound area was 112.5 + /- 50.8 mm2 , and 10.6 + /- 4.2 mm2 after 10 weeks with an average healing time of 85 days ( 95 % CI 79 - 92 ) ( P = 0.03 ) . The mean wound radius decreased by 0.48 mm ( 95 % CI 0.42 - 0.56 ) per week in the felted foam group and by 0.39 mm ( 95 % CI 0.35 - 0.42 ) per week in the conventional group ( P = 0.005 ) . CONCLUSIONS The felted foam technique appears to be at least as effective as conventional plantar ulcer treatment . It may be a useful alternative in treating neuropathic foot ulceration , especially in patients who are not able to avoid weight-bearing reliably Efficacy and safety of a collagen-alginate topical wound dressing ( FIBRACOL Collagen-Alginate Wound Dressing ) in the treatment of diabetic foot ulcers was compared with that of regular gauze moistened with normal saline . Seventy-five patients with foot ulcers were assigned r and omly in a 2:1 ratio to the collagen-alginate test dressing or the gauze dressing . At the end of the study , the mean percent reduction of the wound area was 80.6 % + /- 6 % in the collagen-alginate dressing group and 61.1 % + /- 26 % in the gauze dressing group ( p = .4692 ) . Thirty-nine ( 78 % ) patients treated with the collagen-alginate dressing achieved > or = 75 % wound area reduction , compared with 15 ( 60 % ) of gauze-treated patients . Complete healing was achieved in 24 ( 48 % ) of the collagen-alginate dressing group and 9 ( 36 % ) of the gauze dressing group . Wound size , when averaged over the 8-week period and with the duration of the ulcer taken into account , was reduced significantly in the collagen-alginate dressing group , as compared with the gauze dressing group ( df = 1 , p = .0049 ) . It is concluded that the collagen-alginate test dressing is as or more effective and safe as the currently used treatment Diabetic foot ulcers with exposure of tendon , muscle , or bone imply a high probability for deep infections and amputations . Delayed healing times are often described . The aim of this study was to compare the clinical effect and economic cost of cadexomer iodine with st and ard treatment in diabetic feet with cavity ulcers . Patients with deep , exudative foot ulcers were included in a 12-week open , r and omised , comparative study . When ulcers stopped exudating , vaseline gauze was used in both groups until the end of the study . Costs were estimated for dressing material , staff and transportation . Clinical ly relevant improvement was seen in 12 patients treated with cadexomer iodine and in 13 patients treated with st and ard treatment . The average weekly cost was SEK 903 and SEK 1,421 , respectively , of which the major part was costs for staff and transportation related to frequency of dressing changes . Treatment with cadexomer iodine ointment ( Iodosorb ) showed no clinical difference compared to topical treatment consisting of gentamicin solution , streptodornase/streptokinase , or dry saline gauze but was associated with considerably lower weekly treatment costs 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 This 12-week , prospect i ve , r and omised , controlled multi-centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix ( AM ) ( study group ) and st and ard of care ( control group ) therapies . Eighty-six patients were r and omised into study ( 47 patients ) and control ( 39 patients ) groups . No significant differences in demographics or pre-treatment ulcer data were calculated . Complete healing and mean healing time were 69.6 % and 5.7 weeks , respectively , for the study group and 46.2 % and 6.8 weeks , respectively , for the control group . The proportion of healed ulcers between the groups was statistically significant ( P = 0.0289 ) , with odds of healing in the study group 2.7 times higher than in the control group . Kaplan-Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate ( P = 0.015 ) for the control group ( 53.9 % ) compared with the study group ( 30.4 % ) . After adjusting for ulcer size at presentation , which was a statistically significant covariate ( P = 0.0194 ) , a statistically significant difference in non healing rate between groups was calculated ( P = 0.0233 ) , with odds of healing 2.0 times higher in the study versus control group . This study supports the use of single-application AM therapy as an effective treatment of diabetic , neuropathic ulcers Optimal treatment for large diabetic foot wounds is ill defined . The purpose of this study was to compare the rate of wound healing with the Vacuum Assisted Closure device ™ ( VAC ) to conventional moist dressings in the treatment of large diabetic foot wounds . Diabetics with significant soft tissue defects of the foot were considered for enrollment . Patients were r and omized to receive either moist gauze dressings or VAC treatments for 2 weeks , after which they were treated with the alternative dressing for an additional 2 weeks . Wounds were photographed weekly and wound dimensions calculated in a blinded fashion with spatial analysis software . Percent change in wound dimensions were calculated and compared for each weekly assessment and over 2 weeks of therapy with each dressing type . Ten patients were enrolled in the trial , but two were lost to follow-up and two were withdrawn . Complete data were available for analysis on seven wounds in six patients . Average length , width , and depth of the wounds at initiation of the trial was 7.7 , 3.5 , and 3.1 cm , respectively . Only the wound depth was significantly decreased over the weeks of the trial to 1.2 cm ( p < 0.05 ) . VAC dressings decreased the wound volume and depth significantly more than moist gauze dressings ( 59 % vs. 0 % and 49 % vs. 8 % , respectively ) . VAC dressings were associated with a decrease in all wound dimensions while wound length and width increased with moist dressings . In summary , over the first several weeks of therapy , VAC dressings decreased wound depth and volume more effectively than moist gauze dressings . Negative-pressure wound treatment may accelerate closure of large foot wounds in the diabetic patient BACKGROUND The study aim ed at comparing the efficacy and tolerance of an alginate wound dressing with a vaseline gauze dressing in the treatment of diabetic foot lesions . METHODS This open-label r and omized multicenter controlled study was design ed to assess the effect of an up to 6-week treatment with either calcium alginate or vaseline gauze dressings . Lesions were either acute or chronic , under cleansing , and with a surface area of 1 - 50 cm(2 ) ; osteomyelitis and severe hypovascularization were non- inclusion criteria . Dressings were changed every day then , once granulation had occurred , every 2 to 3 days . Primary outcome was the proportion of patients with granulation tissue over 75 % of the wound area and having a 40 % decrease in wound surface area ; secondary outcomes were pain on dressing changes , the number of dressing changes , and adverse events . RESULTS Seventy-seven patients were enrolled . Due to the premature cessation of treatment in 13 patients , it was decided to reduce the period of the efficacy analysis to 4 weeks ( without revising the criteria of efficacy ) . The success rate was of 42.8 % in the calcium alginate group and of 28.5 % in the vaseline gauze group ( not significant difference ) . A subsequent analysis of granulation tissue surfaces covering the wounds at week 4 ( all surfaces taken together ) showed a superiority of calcium alginate ( p=0.04 ) . Pain on dressing change was lower in the calcium alginate group ( p=0.047 ) and the total number of dressing changes tended also to be lower ( p=0.07 ) . Adverse events , which occurred 4 times in the calcium alginate group and 6 times in the other , were judged independent of the treatments . CONCLUSIONS As compared with vaseline gauze , calcium alginate appears to be more appropriate for topical treatment of diabetic foot lesions in terms of both healing and tolerance This investigation was conducted to determine if a correlation exists between wound healing outcomes and serial debridement in chronic venous leg ulcers ( VLUs ) and diabetic foot ulcers ( DFUs ) . We retrospectively analyzed the results from two controlled , prospect i ve , r and omized pivotal trials of topical wound treatments on 366 VLUs and 310 DFUs over 12 weeks . Weekly wound surface area changes following debridement and 12-week wound closure rates between centers and patients were evaluated . VLUs had a significantly higher median wound surface area reduction following clinical visits with surgical debridement as compared with clinical visits with no surgical debridement ( 34 % , p=0.019 ) . Centers where patients were debrided more frequently were associated with higher rates of wound closure in both clinical studies ( p=0.007 VLU , p=0.015 DFU ) . Debridement frequency per patient was not statistically correlated to higher rates of wound closure ; however , there was some minor evidence of a positive benefit of serial debridement in DFUs ( odds ratio-2.35 , p=0.069 ) . Our results suggest that frequent debridement of DFUs and VLUs may increase wound healing rates and rates of closure , though there is not enough evidence to definitively conclude a significant effect . Future clinical research in wound care should focus on the relationship between serial surgical wound debridement and improved wound healing outcomes as demonstrated in this study The purpose of this study was to determine the recurrence rate of diabetic neurotrophic foot ulcers that had healed in a treatment protocol using topically applied growth factors released from platelets . Thirty-six patients with diabetic neurotrophic foot ulcers were entered into a r and omized prospect i ve double-blind 20-week trial of topically applied platelet growth factors or buffered saline dressings . Ulcers had been present for 15.5 months ( mean , range 2 to 60 months ) . Sixteen patients ( 44 % ) healed and were followed up for as many as 30 months to determine the rate of ulcer recurrence . Eleven patients ( 68.8 % ) had ulcers that recurred , including 10 treated with platelet growth factors and one treated with buffered saline solution . These ulcers had been present for 20 months ( range 5 to 60 months ) before healing . Average time to ulcer recurrence was 2.2 months ( range 0.25 to 7 months ) . Five ulcers ( 31.2 % ) remained healed , including four treated with platelet growth factors and one treated with buffered saline solution . These healed , nonrecurring ulcers had been present for 5 months ( range 2 to 6 months ) before healing . Average follow up was 25 months ( range 24 to 30 months ) . Ulcers were more likely to recur if they had been present longer before healing . If patients were not compliant in wearing footwear to protect the healed ulcer , the ulcers were prone to early recurrence . These data indicate that ulcers healed by using growth factors in the form of a platelet growth factors did not have more durable skin over the ulcer and were prone to early ulcer recurrence This is the interim analysis of a prospect i ve , r and omized , controlled study comparing diabetic foot ulcer healing in patients being treated with either noncontact normothermic wound therapy ( Warm-UP ; Augustine Medical Inc. Eden Prairie , MN ) applied for 1 hour 3 times daily until healing or 12 weeks , or st and ard care ( saline-moistened gauze applied once a day ) . Surgical debridement and adequate foot off-loading was provided to both groups . Evaluations were performed weekly and consisted of acetate tracings , wound assessment , and serial photography . Twenty patients have completed the trial and both treatment groups were distributed evenly ( N = 10 ) . Ulcers treated with noncontact normothermic wound therapy had a greater mean percent wound closure than control-treated ulcers at each evaluation point ( weeks 1 - 12 ) . After 12 weeks , 70 % of the wounds treated with noncontact normothermic wound therapy were healed compared with 40 % for the control group . In this subset of patients there have been no adverse events associated with noncontact normothermic wound therapy The concept of moist wound healing is not fully implemented in daily practice in Germany . Thus , the objective of this investigation was to evaluate the use of Tielle hydropolymer dressings in chronic exuding wounds in primary care . A total of 6,993 patients with pressure sores ( 26.6 % ) , venous leg ulcers ( 59.8 % ) , diabetic foot disease ( 9.5 % ) and other wounds ( 5.1 % ) were enrolled into three multicentre , open-label , single-arm , prospect i ve phase-IV studies for an observational period of either 4 or 12 weeks . Within the 4 (12)-week study using Tielle , 43.3 % ( 59.1 % ) of the wounds healed and 51.6 % ( 36.9 % ) improved . Wound area was reduced by 78.2 % ( 85.1 % ) . Medium or strong levels of exu date s were reduced from 57.4 % to 6.7 % ( 4.0 % ) . Cosmetic results were excellent or good in 96.3 % . Compared with patients ' previous treatment , efficacy and tolerability were assessed as better or much better in 92.5 % and 70.4 % , respectively . 97.1 % of the patients remained free of adverse events . The frequency of dressing changes was reduced from 5 to 3 per week ( -43 % ) . Tielle provides an effective and safe dressing in the management of chronic exuding wounds in primary care improving patient 's comfort . Due to longer wearing times , Tielle may also be cost saving AIMS To test the safety and effectiveness of carboxyl-methyl-cellulose dressing ( Aquacel ; ConvaTec , UK ) in the management of deep diabetic foot ulcers , a group of consecutive out- patients attending the foot clinic of the Department of Metabolic Diseases was studied . METHODS Patients were selected according to the following inclusion criteria : a foot ulcer deeper than 1 cm for > 3 weeks , good peripheral blood supply ( palpable peripheral pulses or ABPI > 0.9 ) . Exclusion criteria were as follows : active infection , as evident from clinical signs ( purulent discharge , redness , swelling , tenderness ) and confirmed by culture exams , plasma creatinine > 2 mg/dl , recent episodes of ketoacidosis , malignancies , and any therapy or pathology which might interfere with the healing process . Twenty patients were enrolled in the study and having obtained their informed consent , their lesions were surgically debrided with the complete elimination of all necrotic tissue and debris up to the bleeding healthy tissue ; then ulcers were staged and measured , and patients were r and omly assigned to two different treatment groups . Patients in group A were dressed with saline-moistened gauze , while patients in group B were dressed with Aquacel according to the manufacturer 's instructions . All patients in both groups received special post-operative shoes ( Podiabetes ; Zeno Buratto , Treviso , Italy ) and crutches until complete re-epithelialization . Ulcers were all left to heal by secondary intent . After 8 weeks patients were blindly evaluated for : the rate of reduction of lesional volume ( RLV ) , rate of granulation tissue ( GT ) , number of infective complications ( IC ) . Intralesional ( ILTC ) and perilesional ( PLTC ) temperatures were also recorded with a thermocouple surface digital thermometer , and the difference between the two values ( Delta TC ) was calculated . Healing time ( HT , days ) , was then compared between the two groups . Data were compared by analysis of variance ( ANOVA ) , linear regression , Kaplan-Meier survival analysis and Fisher 's exact test . RESULTS HT was significantly shorter in Group B than in Group A ( P < 0.001 ) . RLV was significantly ( P < 0.01 ) higher in Group B patients compared with Group A , as well as GT ( P < 0.05 ) . IC were in 1/10 Group B and in 3/10 Group A ( P = 0.582 ) . In addition , both ILTC and Delta TC were higher in Group B compared with Group A ones ( P < 0.01 ) . CONCLUSIONS Carboxyl-methyl-cellulose dressings were shown to be safe , effective and well tolerated in the management of non-ischaemic , non-infected deep diabetic foot ulcers OBJECTIVE To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers . RESEARCH DESIGN AND METHODS Thirteen patients entered a r and omized , double-blind trial of topically applied CT-102 APST vs. placebo ( normal saline ) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers . CT-102 APST ( Curative Technologies , Setauket , NY ) was prepared from homologous platelets and contained multiple growth factors including PDGF , PDAF , EGF , PF-4 , TGF-β , aFGF , and bFGF . Inclusion criteria for subjects included diabetes , ulcer of > 8 wk duration , peri-wound transcutaneous oxygen tension > 30 mmHg , platelet count > 100,000/mm3 , and no wound infection . Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume , < 100 cm2 in area , and involved subcutaneous tissue . RESULTS In the CT-102 group , 5 of 7 ulcers were healed ( 100 % epithelialized ) by 15 wk , but only 1 of 6 ulcers was healed by 20 wk with placebo ( P < 0.05 ) . Average percent reduction in ulcer area at 20 wk was 94 % for CT-102 vs. 73 % for placebo . Daily reduction in ulcer volume was 73.8 ± 42.4 mm3/day ( mean ± SE ) for CT-102 vs. 21.8 ± 8.1 mm3/day for placebo ( P < 0.05 ) . Daily reduction in ulcer area was 6.2 ± 1.8 mm2/day for CT-102 vs. 1.8 ± 0.4 mm2/day for placebo ( P < 0.05 ) . CONCLUSIONS CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials This study compared the efficacy and safety of Apligraf ( Organogenesis , Inc. , Canton , MA ) in combination with st and ard therapy versus st and ard therapy alone in the treatment of neuropathic diabetic foot ulcers . Efficacy was assessed by time to complete wound healing ( by 12 weeks ) and incidence of complete wound closure ( at 12 weeks ) . This was an international multi-center , r and omized , controlled study . Patients were eligible for entry into the study if the following criteria were met : type 1 or type 2 diabetes mellitus , age 18 to 80 years , adequate glycemic control , and the presence of a full-thickness neuropathic ulcer for at least 2 weeks prior to the initial screening visit . Following the 2-week screening period , the 2 treatment groups received st and ard ulcer care consistent with international treatment guidelines that comprised sharp debridement , saline-moistened dressings , and a non — weight bearing regimen . There were 106 subjects screened for enrollment , 82 r and omized to the treatment groups , and 72 treated ( 33 Apligraf subjects and 39 st and ard therapy subjects ) before the study was terminated . Kaplan — Meier curves indicated a trend for shorter time to complete wound healing in the Apligraf group compared with the st and ard therapy group ( p = .059 ; log-rank test ) . The median time to healing was 84 days in the Apligraf group , whereas no median time to healing could be determined for the st and ard therapy group because < 50 % of the st and ard therapy subjects healed . By 12 weeks , 51.5 % ( 17/33 ) Apligraf subjects had achieved complete wound closure compared with 26.3 % ( 10/38 ) of st and ard therapy subjects ( p = .049 ; Fisher 's exact test ) . Even though the study was halted prematurely , this study suggested that the use of Apligraf result ed in a higher incidence of wound closure by 12 weeks |
13,467 | 21,849,010 | The interventions which showed significant improvement in outcomes were primarily multifaceted and complex , with proactive care management and involvement of mental health specialists .
The most commonly used elements of multifaceted interventions included patient educational strategies , telephone follow-up to monitor patients ' progress , as well as providing medication support and feedback to primary care providers .
Overall , educational interventions alone were ineffective in improving antidepressant medication adherence .
In conclusion , improving adherence to antidepressants requires a complex behavioural change and there is some evidence to support behavioural and multifaceted interventions as the most effective in improving antidepressant medication adherence and depression outcomes . | Non-adherence to antidepressant medications is a significant barrier to the successful treatment of depression in clinical practice .
This review aims to systematic ally assess the effectiveness of interventions for improving antidepressant medication adherence among patients with unipolar depression , and to evaluate the effect of these interventions on depression clinical outcomes . | Among a sample of 119 distressed high-utilizers of primary care , 45 % of patients evaluated by a psychiatrist as needing antidepressant treatment had been treated in the year before the examination . However , only 11 % of the patients needing antidepressants had received adequate dosage and duration of pharmacotherapy . In the year following the intervention , study patients whose physicians were advised regarding treatment during a psychiatric consultation were more likely to receive antidepressant medications ( 52.7 % ) relative to a r and omized control group ( 36.1 % ) . However , the intervention did not significantly increase the provision of adequate antidepressant therapy ( 37.1 % vs 27.9 % ) . Among study patients using antidepressants , patient characteristics did not differentiate patients who received adequate dosage and duration of antidepressant medications from those who did not . Analysis of data on the duration of antidepressant therapy for all health maintenance organization enrollees initiating use of antidepressants showed that only 20 % of patients who had been given prescriptions for first-generation antidepressants ( amitriptyline , imipramine , or doxepin ) filled four or more prescriptions in the following six months , compared to 34 % of patients who had prescriptions for newer antidepressants ( nortriptyline , desipramine , trazodone and fluoxetine ) . Experimental research evaluating whether these newer medications ( with more favorable side effect profiles ) improve adherence , and thereby patient outcome , is needed Background Evidence -based practice s design ed for large urban clinics are not necessarily portable into smaller isolated clinics . Implementing practice -based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists . Objective The purpose of the Telemedicine Enhanced Antidepressant Management ( TEAM ) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists . Design Matched sites were r and omized to the intervention or usual care . Participants Small VA Community-based outpatient clinics with no on-site psychiatrists , but access to telepsychiatrists . In 2003–2004 , 395 primary care patients with PHQ9 depression severity scores ≥12 were enrolled , and followed for 12 months . Patients with serious mental illness and current substance dependence were excluded . Measures Medication adherence , treatment response , remission , health status , health-related quality of life , and treatment satisfaction . Results The sample comprised mostly elderly , white , males with substantial physical and behavioral health comorbidity . At baseline , subjects had moderate depression severity ( Hopkins Symptom Checklist , SCL-20 = 1.8 ) , 3.7 prior depression episodes , and 67 % had received prior depression treatment . Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 ( odds ratio [ OR ] = 2.1 , p = .04 ) and 12 months ( OR = 2.7 , p = .01 ) . Intervention patients were more likely to respond by 6 months ( OR = 2.0 , p = .02 ) , and remit by 12 months ( OR = 2.4 , p = .02 ) . Intervention patients reported larger gains in mental health status and health-related quality of life , and reported higher satisfaction . Conclusions Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies The object of the study was to evaluate outcomes of a r and omized clinical trial ( RCT ) of a pharmacist intervention for depressed patients in primary care ( PC ) . We report antidepressant ( AD ) use and depression severity outcomes at 6-months . The RCT was conducted between 1998 and 2000 in 9 eastern Massachusetts PC practice s. We studied 533 patients with major depression and /or dysthymia as determined by a screening test done at the time of a routine PC office visit . The majority of participants had recurrent depressive episodes ( 63.5 % with > /=4 lifetime episodes ) , and 49.5 % were taking AD medications at enrollment . Consultation in person and by telephone was performed by a clinical pharmacist who assisted the primary care practitioner ( PCP ) and patient in medication choice , dose , and regimen , in accordance with AHCPR depression guidelines . Six-month AD use rates for intervention patients exceeded controls ( 57.5 % vs. 46.2 % , P = .03 ) . Furthermore , the intervention was effective in improving AD use rates for patients not on ADs at enrollment ( 32.3 % vs. 10.9 % , P = .001 ) . The pharmacist intervention proved equally effective in subgroups traditionally considered difficult to treat : those with chronic depression and dysthymia . Patients taking ADs had better modified Beck Depression Inventory ( mBDI ) outcomes than patients not taking ADs , ( -6.3 points change , vs. -2.8 , P = .01 ) but the outcome differences between intervention and control patients were not statistically significant ( 17.7 BDI points vs. 19.4 BDI points , P = .16 ) . Pharmacists significantly improved rates of AD use in PC patients , especially for those not on ADs at enrollment , but outcome differences were too small to be statistically significant . Difficult-to-treat subgroups may benefit from pharmacists ' care Background : Depression is undertreated in primary care setting s. Little research investigates the impact of patient involvement in decisions on guideline -concordant treatment and depression outcomes . Objective : The objective of this study was to determine whether patient involvement in decision-making is associated with guideline -concordant care and improvement in depression symptoms . Design : Prospect i ve cohort study . Setting : Multisite , nationwide r and omized clinical trial of quality improvement strategies for depression in primary care . Subjects : Primary care patients with current symptoms and probable depressive disorder . Measurements : Patients rated their involvement in decision-making ( IDM ) about their care on a 5-point scale from poor to excellent 6 months after entry into the study . Depressive symptoms were measured every 6 months for 2 years using a modified version of theCenter for Epidemiologic Studies –Depression ( CES-D ) scale . We examined probabilities ( Pr ) of receipt of guideline -concordant care and resolution of depression across IDM groups using multivariate logistic regression models controlling for patient and provider factors . Results : For each 1-point increase in IDM ratings , the probability of patients ’ report of receiving guideline -concordant care increased 4 % to 5 % ( adjusted Pr 0.31 vs. 0.50 for the lowest and highest IDM ratings , respectively , P < 0.001 ) . Similarly , for each 1-point increase in IDM ratings , the probability of depression resolution increased 2 % to 3 % ( adjusted Pr 0.10 vs. 0.19 for the lowest and highest IDM ratings respectively , P = 0.004 ) . Conclusions : Depressed patients with higher ratings of involvement in medical decisions have a higher probability of receiving guideline -concordant care and improving their symptoms over an 18-month period . Interventions to increase patient involvement in decision-making may be an important means of improving care for and outcomes of depression OBJECTIVE This study evaluated the effectiveness of a structured telephone-based care management program for patients in a prepaid health plan receiving new antidepressant prescriptions from psychiatrists . METHODS Potential participants were identified with computerized medical records and contacted by telephone . Eligible and consenting participants were r and omly assigned to continued usual care ( N=104 ) or to a three-session telephone care management program ( N=103 ) . Care management contacts included assessment of depressive symptoms , medication adherence , and medication side effects with structured feedback to treating psychiatrists . Effectiveness was assessed three and six months after r and omization by blinded telephone assessment s ( depression scale on the Hopkins Symptom Checklist [ SCL ] and patient-rated global improvement ) . Computerized records were used to assess medication adherence and frequency of in-person follow-up visits . RESULTS Compared with usual care , the care management intervention had no significant effect on the mean score of the SCL depression scale at six months , on the probability of 50 percent improvement in depressive symptoms ( 41 percent for care management and 37 percent for usual care ) , or on the probability of patient-rated improvement ( 57 percent for care management and 52 percent for usual care ) . Patients assigned to care management made significantly more medication management visits over six months ( 2.4 visits compared with 2.0 visits ; p=.035 ) , but there were no significant differences in rates of adequate medication treatment . CONCLUSIONS This study found that a low-intensity telephone care management program did not appear to significantly improve clinical outcomes for patients starting antidepressant treatment . Compared with findings from earlier primary care studies , this study found that patients receiving care from a psychiatrist received more intensive treatment , although many still experienced poor outcomes Context Most successful disease management interventions for depression care have required intensive involvement of care managers or mental health specialists . Contribution The authors r and omly assigned 41 primary care physicians from 5 clinics to receive either depression decision support or usual care . Depression decision support was provided by a team that included a psychiatrist and a nurse care manager and involved an initial telephone contact , patient education , monthly record review , and sending a progress report to primary care physicians every 3 months . Depression severity improved equally in both groups over 12 months , despite evidence that intervention clinicians delivered more depression-related services . Implication s Decision support improved processes of depression care but not outcomes . The Editors Depression is a common problem worldwide . According to projections from the World Health Organization ( WHO ) , depression will be the second leading cause of disability in the developed world by 2020 ( 1 ) . One in 10 primary care patients meets criteria for major depression ( 2 ) , yet underrecognition and undertreatment are common ( 3 , 4 ) . Untreated depression is associated with increased deaths , adverse medical outcomes , deficits in function and well-being , and increased use of health services ( 3 , 59 ) . Multifaceted , collaborative interventions have been shown to improve depression-related outcomes in primary care ( 1022 ) . These interventions include decision support for clinicians , self-management support for patients , clinical information systems modifications , and care management . Care management typically consists of patient education and activation , symptom and treatment adherence monitoring , and self-management reinforcement ( 23 ) . Most collaborative depression interventions have relied on intensive involvement of care managers and specialists , usually shifting responsibility and workload toward mental health or research teams . Clinical systems may not be capable of sustaining this level of intensity . We therefore developed a multifaceted depression decision support intervention , which was design ed to optimize primary care clinicians ' abilities to treat depression without adding substantial new re sources . We aim ed to determine the effect of depression decision support on clinical outcomes and processes of care among patients with depression in a Veterans Affairs ( VA ) primary care setting . Methods Design Overview Our clinician-level , cluster r and omized , controlled trial studied depression decision support versus usual care . We r and omly assigned clinicians to either group and nested patients within clinician group assignment . We recruited participants between July 2002 and October 2003 from 5 primary care clinics of a VA medical center and followed patients for 12 months . The local institutional review board approved the study , and all patients and clinicians gave written informed consent . Setting Approximately 25000 veterans were treated during the study period in the 5 primary care clinics ( 3 urban and 2 rural clinics ) . Mental health clinicians are available on site in all clinics to provide consultation and brief treatment . A separate , more traditional mental health clinic serves approximately 8000 patients with chronic mental illnesses . Participants Full- and part-time staff physicians , fellows , physician assistants , and nurse practitioners were eligible to participate , and 41 ( 95 % ) of 43 eligible clinicians agreed to participate . To decrease variability in baseline depression-related knowledge and skills , we invited all clinicians to participate in the MacArthur Foundation depression education program ( 2427 ) before r and omization . In two 4-hour sessions , the program addresses communication skills and knowledge related to recognizing and managing depression . All patients of participating clinicians were eligible for the study . Research assistants review ed medical records of patients with upcoming primary care appointments ( within 4 to 6 weeks ) . They excluded patients who had received treatment from mental health specialists within the previous 6 months ; who had received a diagnosis of psychotic disorder , dementia , or bipolar disorder ; or who were considered to be terminally ill . They mailed study introduction letters to nonexcluded patients . The letters informed the patients that the research team would call them within 2 weeks unless they declined screening by notifying the study office . Telephone screening measures included the Patient Health Question naire ( PHQ-9 ) ( 28 ) and the Short Blessed Test screening for dementia ( 29 ) . We invited patients with PHQ-9 scores of 10 to 25 ( moderate to severe depression ) ( 30 ) to attend in-person enrollment interviews . We referred patients with PHQ-9 scores greater than 25 ( very severe depression ) or active dangerous ideation for urgent care , and we excluded them from participation . Enrollment interviews were scheduled within 2 weeks of primary care visits and usually took place the same day . The primary inclusion criterion was a repeated PHQ-9 score of 10 to 25 or a Hopkins Symptom Checklist-20 ( SCL-20 ) ( 31 ) score of 1.0 or greater at the enrollment interview . Of the 5434 patients who were mailed study introduction letters , 3500 ( 64 % ) were reached by telephone and were offered screening ( Figure 1 ) , and 3103 ( 89 % ) of those patients completed telephone screening . Of these patients , 560 ( 18 % ) had PHQ-9 scores between 10 and 25 and were eligible for in-person enrollment interviews . Of the 402 patients who completed the enrollment interviews , 375 had repeated PHQ-9 scores between 10 and 25 or SCL-20 scores of 1.0 or greater and were enrolled in the study . Figure 1 . Study flow chart . PHQ-9 = Patient Health Question naire . R and omization After clinicians participated in the MacArthur Foundation depression education program , we r and omly assigned clinicians to receive depression decision support or to usual care . Patients were nested within clinician assignment group . A stratified technique used a r and om-number generator to produce equivalent distributions across clinician type ( physician vs. physician 's assistant or nurse practitioner ) and clinic site . Clinicians in one clinic with substantial variation in caseload size were ranked by caseload and underwent block r and omization . Intervention The depression decision support team consisted of 1 psychiatrist who was assigned up to 4 hours per week and 1 nurse care manager who was assigned up to 8 hours per week . Within 1 to 2 weeks after enrollment , the depression decision support care manager attempted to call each intervention patient to provide education , explore barriers , emphasize adherence to treatment , and encourage communication with clinicians about depression ( Table 1 ) . Supplemental educational material s were mailed to all intervention patients . During the telephone call , patients were invited to attend a 2-hour group depression education program led by the care manager or a depression education class offered by the mental health team in 1 of the urban clinics . Aside from this single early telephone contact , only rare additional contact between the depression decision support care manager and patients was expected . Table 1 . Summary of Depression Decision Support Intervention and Usual Care Components The depression decision support team met weekly and review ed PHQ-9 scores ( collected by the research team at baseline and at 1 , 3 , 6 , 9 , and 12 months ) and medication and appointment data from the medical records . The team review ed each intervention patient record at least monthly . Using a data base , the depression decision support care manager compiled symptom severity and adherence data , posttraumatic stress disorder and alcohol screening results ( obtained from routine clinic screening ) , and treatment recommendations into a treatment progress report . The report was mailed to each intervention clinician for all of their enrolled patients quarterly . If primary care clinicians did not respond to initial PHQ-9 scores greater than 15 or when patients ' depression did not adequately improve ( PHQ-9 score>10 at 3 months or PHQ-9 score>5 at 6 , 9 , or 12 months ) , the depression decision support team review ed records again and then contacted clinicians or their nurses to discuss treatment strategies or to offer consultation . When the depression decision support team and primary care clinician agreed that psychiatric consultation might be helpful , the psychiatrist arranged a visit . When ongoing mental health specialty care was indicated , the depression decision support team facilitated a referral . Usual Care Clinicians received notifications when their patients enrolled in the study and were provided baseline PHQ-9 scores ( Table 1 ) . Usual care clinicians had access to all initial and follow-up PHQ-9 scores ( available in the medical record ) , but usual care clinicians did not receive notifications , reminders , or recommendations about scores from the depression decision support team . Usual care clinicians and their patients also had access to mental health services , including on-site mental health teams . Outcomes and Measurements Blinded research assistants collected baseline patient data in person and PHQ-9 scores ( at 1 , 3 , 6 , 9 , and 12 months ) and outcome data ( at 6 and 12 months ) by telephone . When patients could not be reached by telephone , research assistants mailed question naires to them . Baseline measures included demographic information , Medical Outcomes Study 36-item Short Form for Veterans ( SF-36V ) scores for health-related quality of life ( 32 ) , SCL-20 score for depression severity ( 31 ) , Alcohol Use Disorders Identification Test score ( 33 , 34 ) , PHQ scores for anxiety and panic disorders ( 35 ) , Posttraumatic Stress Disorder Checklist score ( 36 ) , Medical Outcomes Study pain effects score ( 37 ) , and the dysthymia stem from the WHO Composite International Diagnostic Interview ( 38 ) . The PHQ-9 from the enrollment interview was used to CONTEXT Few depressed older adults receive effective treatment in primary care setting s. OBJECTIVE To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) collaborative care management program for late-life depression . DESIGN R and omized controlled trial with recruitment from July 1999 to August 2001 . SETTING Eighteen primary care clinics from 8 health care organizations in 5 states . PARTICIPANTS A total of 1801 patients aged 60 years or older with major depression ( 17 % ) , dysthymic disorder ( 30 % ) , or both ( 53 % ) . INTERVENTION Patients were r and omly assigned to the IMPACT intervention ( n = 906 ) or to usual care ( n = 895 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education , care management , and support of antidepressant management by the patient 's primary care physician or a brief psychotherapy for depression , Problem Solving Treatment in Primary Care . MAIN OUTCOME MEASURES Assessment s at baseline and at 3 , 6 , and 12 months for depression , depression treatments , satisfaction with care , functional impairment , and quality of life . RESULTS At 12 months , 45 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline compared with 19 % of usual care participants ( odds ratio [ OR ] , 3.45 ; 95 % confidence interval [ CI ] , 2.71 - 4.38 ; P<.001 ) . Intervention patients also experienced greater rates of depression treatment ( OR , 2.98 ; 95 % CI , 2.34 - 3.79 ; P<.001 ) , more satisfaction with depression care ( OR , 3.38 ; 95 % CI , 2.66 - 4.30 ; P<.001 ) , lower depression severity ( range , 0 - 4 ; between-group difference , -0.4 ; 95 % CI , -0.46 to -0.33 ; P<.001 ) , less functional impairment ( range , 0 - 10 ; between-group difference , -0.91 ; 95 % CI , -1.19 to -0.64 ; P<.001 ) , and greater quality of life ( range , 0 - 10 ; between-group difference , 0.56 ; 95 % CI , 0.32 - 0.79 ; P<.001 ) than participants assigned to the usual care group . CONCLUSION The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practice Non-adherence to antidepressant drug treatment is common . In a recent study in depressed primary care patients , we reported a strong relationship between adherence and response after 6 months . With the use of a naturalistic design , the patients in that study were prospect ively followed for 2 years . The purpose of the present study was to investigate the patients ' long-term outcome and , in particular , to examine the impact of patients ' treatment adherence on response , remission and relapse . Of the 1031 patients in the intent-to-treat ( ITT ) sample , 835 completed the study . After 2 years , the overall remission rate defined as a Montgomery – Åsberg Depression Rating Scale score of nine or less was 68 % in the ITT sample analysed with the last observation carried forward ( LOCF ) technique , and 75 % in observed cases . In total , 34 % of the responders experienced at least one relapse . Response rates ( LOCF ) were significantly higher in adherent compared to non-adherent patients at week 24 [ 95 % confidence interval (CI)=21.4–32.1 ] , year 1 ( 95 % CI=12.3–22.2 ) and year 2 ( 95 % CI=9.2–19.0 ) . Remission rates ( LOCF ) were also significantly higher in the group of adherent patients at week 24 ( 95 % CI=9.6–21.5 ) , year 1 ( 95 % CI=10.0–21.5 ) and year 2 ( 95 % CI=11.0–22.0 ) . No relationship between adherence and relapse rate was observed , although the mean time from response to first sign of relapse was significantly longer in the adherent patients ( 95 % CI=9–97 days ) . In conclusion , this 2-year follow-up study showed superior long-term recovery in patients who were adherent to antidepressant medication compared to non-adherent patients BACKGROUND Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects , many patients treated with antidepressant medications by primary care physicians have persistent symptoms . METHODS A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were r and omized to a collaborative care intervention ( n = 114 ) or usual care ( n = 114 ) by the primary care physician . Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment . Follow-up assessment s were completed at 1 , 3 , and 6 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls . Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months . CONCLUSIONS A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants , satisfaction with care , and depressive outcomes compared with usual care OBJECTIVE To examine the contribution of medication adherence to 12-month depression scores in the context of other psychosocial and clinical predictors of depression in a sample of older adults treated for depression . METHODS Secondary analysis of a prospect i ve cohort study involving 241 older patients undergoing depression treatment using a st and ardized algorithm . Depression was measured at baseline and 12-months post-baseline . Baseline predictor variables included antidepressant adherence , barriers to antidepressant adherence , four domains of social support , basic and instrumental activities of daily living ( BADLs and IADLs ) , and clinical factors including past history of depression and medical comorbidities . RESULTS Nearly 28 % of patients reported being nonadherent with their antidepressant medication . In bivariate analyses , greater antidepressant medication nonadherence , more medication barriers , poorer subjective social support , less non-family interaction , greater BADL and IADL limitations , poor self-rated health , higher baseline depression scores , and not having diabetes were related to higher 12-month depression scores . In multivariable analyses , greater medication nonadherence , not having diabetes , poorer subjective social support , greater BADL limitations , and higher baseline depression scores were related to higher 12-month depression scores . CONCLUSION Interventions should be directed toward improving antidepressant adherence and modifiable psychosocial variables OBJECTIVE Non-compliance presents a constant challenge to effective therapy . Many studies only investigate early treatment discontinuation and not other measures like adherence to treatment regimen . We compared adherence in depressed patients using either a selective serotonin reuptake inhibitor ( fluoxetine ) or a tricyclic antidepressant ( amitriptyline ) , and examined its clinical relevance through adverse events , drop-out rates , and outcome . Adherence was measured electronically with the MEMS ( Medication Event Monitoring System ) . DESIGN Nine-week double blind , r and omized controlled trial . SETTING Ambulatory psychiatric care . PATIENTS R and om sample of 66 depressed ( DSM-III-R criteria ) patients . INTERVENTION Fluoxetine 20 mg or amitriptyline 150 mg . MAIN OUTCOME MEASURES Time course of adherence and its relation to severe adverse events , drop-outs and outcome . RESULTS Non-adherence to the treatment regimen occurred frequently in both treatment groups : 31 % of patients had at least one 3-day drug holiday , and 34 % of patients had at least one episode of three pills in a 24-h period . Over-consumption occurred more frequently during the early phases of treatment while under-consumption occurred more frequently during the later phases . Patients on amitriptyline ( P=0.03 ) and patients with a higher pill intake ( P=0.01 ) experienced more severe adverse events . Patients on amitriptyline ( P=0.009 ) and patients with a lower adherence to the treatment regimen ( P=0.004 ) discontinued from treatment more frequently . The final Hamilton score was significantly predicted by a longer duration of treatment and by a better adherence , but only in amitriptyline users . CONCLUSIONS Non-adherence to the treatment regimen has important clinical consequences . Pharmacodynamics and human behavior predict risk for severe adverse events and drop-outs . Moreover , in amitriptyline users but not in fluoxetine users , better adherence predicts a better outcome OBJECTIVE To compare the effectiveness of a multifaceted intervention in patients with depression in primary care with the effectiveness of " usual care " by the primary care physician . DESIGN A r and omized controlled trial among primary care patients with major depression or minor depression . PATIENTS Over a 12-month period a total of 217 primary care patients who were recognized as depressed by their primary care physicians and were willing to take antidepressant medication were r and omized , with 91 patients meeting criteria for major depression and 126 for minor depression . INTERVENTIONS Intervention patients received increased intensity and frequency of visits over the first 4 to 6 weeks of treatment ( visits 1 and 3 with a primary care physician , visits 2 and 4 with a psychiatrist ) and continued surveillance of adherence to medication regimens during the continuation and maintenance phases of treatment . Patient education in these visits was supplemented by videotaped and written material s. MAIN OUTCOME MEASURES Primary outcome measures included short-term ( 30-day ) and long-term ( 90-day ) use of antidepressant medication at guideline dosage levels , satisfaction with overall care for depression and antidepressant medication , and reduction in depressive symptoms . RESULTS In patients with major depression , the intervention group had greater adherence than the usual care controls to adequate dosage of antidepressant medication for 90 days or more ( 75.5 % vs 50.0 % ; P < .01 ) , were more likely to rate the quality of the care they received for depression as good to excellent ( 93.0 % vs 75.0 % ; P < .03 ) , and were more likely to rate antidepressant medications as helping somewhat to helping a great deal ( 88.1 % vs 63.3 % ; P < .01 ) . Seventy-four percent of intervention patients with major depression showed 50 % or more improvement on the Symptom Checklist-90 Depressive Symptom Scale compared with 43.8 % of controls ( P < .01 ) , and the intervention patients also demonstrated a significantly greater decrease in depression severity over time compared with controls ( P < .004 ) . In patients with minor depression , the intervention group had significantly greater adherence than controls to adequate dosage of antidepressant medication for 90 days or more ( 79.7 % vs 40.3 % ; P < .001 ) and more often rated antidepressant medication as helping somewhat to helping a great deal ( 81.8 % vs 61.4 % ; P < .02 ) . However , no significant differences were found between the intervention and control groups in the percentage of patients who were satisfied with the care they received for depression ( 94.4 % vs 89.3 % ) , in the percentage who experienced a 50 % or more decrease in depressive symptoms , or in the decrease of depressive symptoms over time . CONCLUSION A multifaceted intervention consisting of collaborative management by the primary care physician and a consulting psychiatrist , intensive patient education , and surveillance of continued refills of antidepressant medication improved adherence to antidepressant regimens in patients with major and with minor depression . It improved satisfaction with care and result ed in more favorable depressive outcomes in patients with major , but not minor , depression CONTEXT Care of patients with depression in managed primary care setting s often fails to meet guideline st and ards , but the long-term impact of quality improvement ( QI ) programs for depression care in such setting s is unknown . OBJECTIVE To determine if QI programs in managed care practice s for depressed primary care patients improve quality of care , health outcomes , and employment . DESIGN R and omized controlled trial initiated from June 1996 to March 1997 . SETTING Forty-six primary care clinics in 6 US managed care organizations . PARTICIPANTS Of 27332 consecutively screened patients , 1356 with current depressive symptoms and either 12-month , lifetime , or no depressive disorder were enrolled . INTERVENTIONS Matched clinics were r and omized to usual care ( mailing of practice guidelines ) or to 1 of 2 QI programs that involved institutional commitment to QI , training local experts and nurse specialists to provide clinician and patient education , identification of a pool of potentially depressed patients , and either nurses for medication follow-up or access to trained psychotherapists . MAIN OUTCOME MEASURES Process of care ( use of antidepressant medication , mental health specialty counseling visits , medical visits for mental health problems , any medical visits ) , health outcomes ( probable depression and health-related quality of life [ HRQOL ] ) , and employment at baseline and at 6- and 12-month follow-up . RESULTS Patients in QI ( n = 913 ) and control ( n = 443 ) clinics did not differ significantly at baseline in service use , HRQOL , or employment after nonresponse weighting . At 6 months , 50.9 % of QI patients and 39.7 % of controls had counseling or used antidepressant medication at an appropriate dosage ( P<.001 ) , with a similar pattern at 12 months ( 59.2 % vs 50.1 % ; P = .006 ) . There were no differences in probability of having any medical visit at any point ( each P > or = .21 ) . At 6 months , 47.5 % of QI patients and 36.6 % of controls had a medical visit for mental health problems ( P = .001 ) , and QI patients were more likely to see a mental health specialist at 6 months ( 39.8 % vs 27.2 % ; P<.001 ) and at 12 months ( 29.1 % vs 22.7 % ; P = .03 ) . At 6 months , 39.9 % of QI patients and 49.9 % of controls still met criteria for probable depressive disorder ( P = .001 ) , with a similar pattern at 12 months ( 41.6 % vs 51.2 % ; P = .005 ) . Initially employed QI patients were more likely to be working at 12 months relative to controls ( P = .05 ) . CONCLUSIONS When these managed primary care practice s implemented QI programs that improve opportunities for depression treatment without m and ating it , quality of care , mental health outcomes , and retention of employment of depressed patients improved over a year , while medical visits did not increase overall AIMS To assess the advantages and disadvantages of four methods for study ing compliance with antidepressants : self-report scores , tablet counts , a microprocessor ( MEMS ) container system and the assay of nordothiepin and dothiepin concentrations in plasma . METHODS The techniques were used in 88 patients commencing tricyclic antidepressants in the setting of UK general practice . RESULTS The MEMS system proved to be the most informative technique allowing identification of the precise time of container opening , the demonstration of ' drug holidays ' and early cessation of therapy . Self-report scores ( Morisky ) proved a useful screening technique with a sensitivity of 72.2 % and specificity of 74.1 % for > or = 80 % compliance . Although tablet counts were possible in 84 patients ( 95 . 5 % ) they were unreliable in 19 ( 21.6 % ) . Blood concentration assays proved the least acceptable method to patients and were possible in only 53 ( 60.2 % ) . A ratio of nordothiepin : dothiepin > or = 1.1 cl aim ed , by others , to identify noncompliance was only reliable when concentrations were low . CONCLUSIONS Both the MEMS system and self-report scores proved useful methods for identifying noncompliant patients in the setting of UK general practice . Although compliance was higher than reported in previous studies with 70 patients ( 79.5 % ) completing 6 weeks treatment , general practitioners tended to prescribe subtherapeutic doses OBJECTIVE To test the impact of a novel psychosocial intervention to improve antidepressant adherence and depression outcomes among older adults prescribed pharmacotherapy by their primary care physician ( PCP ) . DESIGN A r and omized controlled pilot study was conducted to examine the usefulness of the Treatment Initiation and Participation ( TIP ) program as an intervention to improve antidepressant adherence and depression outcomes . SETTING The study was conducted at two primary care clinics in New York city : one clinic served geriatric adults and the second clinic served a diverse group of mixed aged adults . PARTICIPANTS The sample consisted of adults aged 60 years and older with major depression who were recommended antidepressant therapy by their PCPs . INTERVENTION All participants were prescribed antidepressant therapy and r and omly assigned to either the intervention ( TIP ) or the treatment as usual ( TAU ) group . The TIP intervention identifies and targets psychological barriers to depression care , especially stigma , as well as fears and misconceptions of depression and its treatment . TIP participants are encouraged to develop a treatment goal and create an adherence strategy . MEASUREMENT Study participants were assessed at entry , 6 , 12 , and 24 weeks later . Adherence was measured based on self-report with chart verification . Depression severity was measured using the Hamilton Depression Rating Scale . RESULTS Participants in TIP were significantly more adherent to their antidepressant pharmacotherapy at all assessment time points and had a significantly greater decrease in depressive symptoms than older adults who received TAU . CONCLUSION The results provide support for the usefulness of TIP as a brief intervention to improve adherence to depression medication treatment provided in primary care setting To measure the effects of a collaborative care model that emphasized the role of clinical pharmacists in providing drug therapy management and treatment follow-up to patients with depression , we conducted a r and omized controlled trial at a staff model health maintenance organization . We compared the outcomes of subjects treated in this collaborative care model ( 75 patients , intervention group ) with subjects receiving usual care ( 50 patients , control group ) . After 6 months , the intervention group demonstrated a significantly higher drug adherence rate than that of the control group ( 67 % vs 48 % , odds ratio 2.17 , 95 % confidence interval 1.04 - 4.51 , p=0.038 ) . Patient satisfaction was significantly greater among members r and omly assigned to pharmacists ' services than among controls , and provider satisfaction surveys revealed high approval rates as well . Changes in re source utilization were favorable for the intervention group , but differences from the control group did not achieve statistical significance . Clinical improvement was noted in both groups , but the difference was not significant . Clinical pharmacists had a favorable effect on multiple aspects of patient care . Future studies of this model in other health care setting s appear warranted The objective of this article is to provide a detailed description of interactions between patients with depression and pharmacists . Analysis was conducted on patients from the intervention arm ( n=268 ) of an r and omized controlled trial that evaluated the impact of a clinical pharmacist on the outcomes for depressed primary care patients from nine metropolitan Boston practice s. The main outcome measure was the amount of intervention time spent with patients , physicians , and other activities . Details of the behavioral intervention and a categorization of the activities are offered . Pharmacists reported 978 encounters with 268 patients in 6 months . Eighty percent of patient encounters occurred by telephone . Initial encounters took 45 min if in person and 13.3 min if by telephone . Subsequent encounters followed a similar pattern . Follow-up visits occurred 2.3 times per patient . Physician contact took considerably less time . In total , the pharmacist intervention took 70.3 min per patient over 6 months ; 42.2 % of encounters involved an activity related to non-antidepressant medication and 85 % of encounters involved general support . Other activities ( education , advocating antidepressants , and motivating adherence ) occurred in at least 50 % of encounters . Pharmacists repeated intervention activities in the same category approximately two to three times . Interventions to improve the care of depression in primary care patients must anticipate encountering intense needs for information , personal support , and help negotiating the healthcare system . Research that identifies relationships between the components ( active ingredients ) of an intervention and the outcomes of care will benefit future intervention strategies and contribute to improved and efficient care PURPOSE The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated . METHODS Patients diagnosed with a new episode of depression and started on anti-depressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) for one year . EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education , the initiation and adjustment of antidepressant dosages , the monitoring of patient adherence to the regimen , the management of adverse reactions , and the prevention of relapse . The patients in the UC group served as controls . Outcomes were measured by the Hopkins Symptom Checklist , Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for major depression , health-related quality of life , medication adherence , patient satisfaction , and use of depression-related health care services . An intent-to-treat analysis was used . RESULTS Seventy-four patients were r and omized to EC or UC . At baseline , the EC group included more patients diagnosed with major depression than did the UC group ( p = 0.04 ) . All analyses were adjusted for this difference . In both groups , mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year . There were no statistically significant differences between treatment groups in depression symptoms , quality of life , medication adherence , provider visits , or patient satisfaction . CONCLUSION Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting result ed in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year BACKGROUND Depression is a major individual and public-health burden throughout the world and is managed mainly in primary care . The most effective strategy to reduce this burden has been believed to be education of primary -care practitioners . We tested this assumption by assessing the effectiveness of an educational programme based on a clinical - practice guideline in improving the recognition and outcome of primary -care depression . METHODS We carried out a r and omised controlled trial in a representative sample of 60 primary -care practice s ( 26 % of the total ) in an English health district . Education was delivered to practice teams and quality tested by feedback from participants and expert raters . The primary endpoints were recognition of depression , defined by the hospital anxiety and depression ( HAD ) scale , and clinical improvement . Analysis was by intention to treat . FINDINGS The education was well received by participants , 80 % of whom thought it would change their management of patients with depression . 21409 patients were screened , of whom 4192 were classified as depressed by the HAD scale . The sensitivity of physicians to depressive symptoms was 39 % in the intervention group and 36 % in the control group after education ( odds ratio 1.2 [ 95 % CI 0.88 - 1.61 ] ) . The outcome of depressed patients as a whole at 6 weeks or 6 months after the assessment did not significantly improve . INTERPRETATION Although well received , this in- practice programme , which was design ed to convey the current consensus on best practice for the care of depression , did not deliver improvements in recognition of or recovery from depression This study was design ed to investigate the impact of a time-phased patient education program ( RHYTHMS ) on medication compliance and treatment outcomes of primary care patients diagnosed with major depression and started on antidepressant pharmacotherapy . Two hundred forty-six depressed patients , diagnosed and treated at one of three outpatient clinics affiliated with the Kaiser-Permanente Northwest Region ( KPNW ) healthcare system , were r and omly assigned to either receive or not receive ( usual care ) the educational material s by mail . Depression severity and functional impairment affecting patients ' quality of life were assessed at baseline and 4 , 12 , and 30 weeks later . Self-reported impressions of improvement and patient satisfaction with treatment were also assessed at follow-up . Clinical assessment data were obtained using an interactive voice response ( IVR ) system . Study subjects were compensated $ 5 , $ 10 , $ 15 , and $ 25 for completing each assessment ( Baseline to Week 30 , respectively ) . Upon study completion , prescription fill data of the subjects were extracted from the KPNW Pharmacy System for analysis of medication compliance . Most of the study subjects ( 63.5 % ) responded to the pharmacotherapy treatment by study end-point . Few statistically significant differences in either treatment outcomes or duration of medication compliance were found between the treatment groups , and significant differences found were of fairly small magnitude . Patients not receiving the educational material s initially exhibited a more positive response to treatment ( Week 4 ) , but this difference did not persist at later follow-ups and was associated with significantly higher relapse rates . A strong time-dose relationship was evident between the duration of the initial treatment episode and treatment outcomes at follow-up , but r and omized treatment assignment did not influence the duration of initial medication compliance . Educational programs design ed to encourage depressed patients to obtain adequate pharmacotherapy likely provide medical benefits . Such benefits appear to be relatively subtle and method ological differences between studies contribute to inconsistent conclusions concerning observed benefits . The intent of providing time-phased educational material s to patients is to maximize the relevance of such information by synchronizing it with typical recovery processes and issues . This study suggests that additional efforts at engaging patients earlier after the initiation of treatment might be of most benefit The goals of this study were to examine how physician communication style impacts client beliefs and medication taking behavior during treatment for depression . The study uses a communication framework and prospect i ve design to examine physician communication and client beliefs as treatment is initiated and again 2 months later . Two telephone interviews were conducted with 100 clients enrolled from 23 community pharmacies . Clients report that physician communication styles vary . In follow-up , 25 % of the clients were not satisfied with their medication and 82 % reported missing doses or stopping treatment earlier than recommended . Path analysis showed that physician initial communication style positively influences client knowledge and initial beliefs about the medication . Clients with more positive beliefs about the treatment are more likely to see the physician in follow-up and are more satisfied with treatment after attempting medication use . Physician follow-up communication style and client satisfaction are both predictive of better medication adherence OBJECTIVES The authors examine whether physician education has enduring effects on treatment of depression . METHODS Depressed primary care patients initiating antidepressant treatment from primary care clinics of a staff-model health maintenance organization were studied . Quasi-experimental and before- and -after comparisons of physician practice s , supplemented with patient surveys , were used to compare the process of care and depression outcomes . Intervention consisted of extensive physician education that spanned a 12-month period . This included case-by-case consultations , didactics , academic detailing ( eg , clearly stating the educational and behavioral objectives to individual physicians ) , and role-play of optimal treatment . Main outcome measures were divided into two groups . Quasi-experimental sample s included : ( 1 ) antidepressant medication selection and ( 2 ) adequacy ( dosage and duration ) of pharmacotherapy . Survey sample s included : ( 3 ) intensity of follow-up ; ( 4 ) physician delivered educational messages regarding depression treatment ; ( 5 ) patient satisfaction ; and ( 6 ) depression outcomes . RESULTS No lasting educational effect was observed consistently in any of the outcomes measured . CONCLUSIONS There was no enduring improvement in the treatment of depression for primary care patients . Depression treatment guidelines were achieved contemporaneously , however , for intervention patients enrolled in a multifaceted program of collaborative care during the training period . These results suggest that continuing programs of reorganized service delivery to support the role of a primary care physician ( eg , on-site mental health personnel , close monitoring of patient progress and adherence ) , in addition to physician training , are essential for the success of guideline implementation BACKGROUND High utilizers of nonpsychiatric health care services have disproportionally high rates of undiagnosed or undertreated depression . OBJECTIVE To determine the impact of offering a systematic primary care-based depression treatment program to depressed " high utilizers " not in active treatment . DESIGN R and omized clinical trial . SETTING One hundred sixty-three primary care practice s in 3 health maintenance organizations located in different geographic regions of the United States . PATIENTS A group of 1465 health maintenance organization members were identified as depressed high utilizers using a 2-stage telephone screening process . Eligibility criteria were met by 410 patients and 407 agreed to enroll : 218 in the depression management program ( DMP ) practice s and 189 in the usual care ( UC ) group . INTERVENTION The DMP included patient education material s , physician education programs , telephone-based treatment coordination , and antidepressant pharmacotherapy initiated and managed by patients ' primary care physicians . MAIN OUTCOME MEASURES Depression severity was measured using the Hamilton Depression Rating Scale ( Ham-D ) and functional status using the Medical Outcomes Study 20-item short form ( SF-20 ) subscales . Outpatient visit and hospitalization rates were measured using the health plan 's encounter data . RESULTS Based on an intent-to-treat analysis , at least 3 antidepressant prescriptions were filled in the first 6 months by 151 ( 69.3 % ) of 218 of DMP patients vs 35 ( 18.5 % ) of 189 in UC ( P < .001 ) . Improvements in Ham-D scores were significantly greater in the intervention group at 6 weeks ( P = .04 ) , 3 months ( P = .02 ) , 6 months ( P < .001 ) , and 12 months ( P < .001 ) . At 12 months , DMP intervention patients were more improved than UC patients on the mental health , social functioning , and general health perceptions scales of the SF-20 ( P < .05 for all ) . CONCLUSION In depressed high utilizers not already in active treatment , a systematic primary care-based treatment program can substantially increase adequate antidepressant treatment , decrease depression severity , and improve general health status compared with usual care Abstract OBJECTIVE : To determine whether redefining primary care team roles would improve outcomes for patients beginning a new treatment episode for major depression . DESIGN : Following stratification , 6 of 12 practice s were r and omly assigned to the intervention condition . Intervention effectiveness was evaluated by patient reports of 6-month change in 100-point depression symptom and functional status scales . SETTING : Twelve community primary care practice s across the country employing no onsite mental health professional . PATIENTS : Using two-stage screening , practice s enrolled 479 depressed adult patients ( 73.4 % of those eligible ) ; 90.2 % completed six-month follow-up . INTERVENTION : Two primary care physicians , one nurse , and one administrative staff member in each intervention practice received brief training to improve the detection and management of major depression . MAIN RESULTS : In patients beginning a new treatment episode , the intervention improved depression symptoms by 8.2 points ( 95 % confidence interval [ CI ] , 0.2 to 16.1 ; P=.04 ) . Within this group , the intervention improved depression symptoms by 16.2 points ( 95 % CI , 4.5 to 27.9 ; P=.007 ) , physical role functioning by 14.1 points ( 95 % CI , 1.1 to 29.2 ; P=.07 ) , and satisfaction with care ( P=.02 ) for patients who reported antidepressant medication was an acceptable treatment at baseline . Patients already in treatment at enrollment did not benefit from the intervention . CONCLUSIONS : In practice s without onsite mental health professionals , brief interventions training primary care teams to assume redefined roles can significantly improve depression outcomes in patients beginning a new treatment episode . Such interventions should target patients who report that antidepressant medication is an acceptable treatment for their condition . More research is needed to determine how primary care teams can best sustain these redefined roles over time CONTEXT Both antidepressant medication and structured psychotherapy have been proven efficacious , but less than one third of people with depressive disorders receive effective levels of either treatment . OBJECTIVE To compare usual primary care for depression with 2 intervention programs : telephone care management and telephone care management plus telephone psychotherapy . DESIGN Three-group r and omized controlled trial with allocation concealment and blinded outcome assessment conducted between November 2000 and May 2002 . SETTING AND PARTICIPANTS A total of 600 patients beginning antidepressant treatment for depression were systematic ally sample d from 7 group-model primary care clinics ; patients already receiving psychotherapy were excluded . INTERVENTIONS Usual primary care ; usual care plus a telephone care management program including at least 3 outreach calls , feedback to the treating physician , and care coordination ; usual care plus care management integrated with a structured 8-session cognitive-behavioral psychotherapy program delivered by telephone . MAIN OUTCOME MEASURES Blinded telephone interviews at 6 weeks , 3 months , and 6 months assessed depression severity ( Hopkins Symptom Checklist Depression Scale and the Patient Health Question naire ) , patient-rated improvement , and satisfaction with treatment . Computerized administrative data examined use of antidepressant medication and outpatient visits . RESULTS Treatment participation rates were 97 % for telephone care management and 93 % for telephone care management plus psychotherapy . Compared with usual care , the telephone psychotherapy intervention led to lower mean Hopkins Symptom Checklist Depression Scale depression scores ( P = .02 ) , a higher proportion of patients reporting that depression was " much improved " ( 80 % vs 55 % , P<.001 ) , and a higher proportion of patients " very satisfied " with depression treatment ( 59 % vs 29 % , P<.001 ) . The telephone care management program had smaller effects on patient-rated improvement ( 66 % vs 55 % , P = .04 ) and satisfaction ( 47 % vs 29 % , P = .001 ) ; effects on mean depression scores were not statistically significant . CONCLUSIONS For primary care patients beginning antidepressant treatment , a telephone program integrating care management and structured cognitive-behavioral psychotherapy can significantly improve satisfaction and clinical outcomes . These findings suggest a new public health model of psychotherapy for depression including active outreach and vigorous efforts to improve access to and motivation for treatment Medication non-adherence is a major obstacle in the treatment of affective disorders . The primary objective of this study was to evaluate two different interventions to improve adherence to antidepressant drugs . Secondary objectives included response to treatment , relation between adherence and response , patient satisfaction and tolerability . A r and omized controlled design was used to assess the effect of a patient educational compliance enhancing programme ( CP ) and therapeutic drug monitoring in 1031 major depressed patients treated with sertraline for 24 weeks and managed by their general practitioner . Adherence was measured by question ing , measurable serum levels of sertraline and desmethylsertraline , appointments kept and a composite index including all three methods . Treatment adherence was found in 37–70 % of patients , depending on the method used . Neither of the interventions result ed in a significant increase in adherence rate . However , significantly more patients in the CP group had responded at week 24 compared to patients in the control group . Overall , significantly more adherent patients responded to treatment compared to non-adherent patients , regardless of method used to determine adherence . This large study demonstrates that treatment response increases when using an educational compliance programme and that a strong relationship between treatment adherence and response exists OBJECTIVE To investigate whether an intervention by Dutch community pharmacists improves the drug attitude of depressive patients , who are prescribed a nontricyclic antidepressant by their general practitioner ( GP ) . METHOD A r and omized controlled trial with a 3-month follow-up was conducted among consecutive general practice patients who go to 19 pharmacists for antidepressants . The trial consisted of a control group ( n=79 ) that received usual care and an intervention group ( n=69 ) that received three drug coaching contacts at the pharmacy and a 25-min take-home video on the background of depression and the effects of medication . OUTCOME MEASURE Drug attitude ( DAI ) . RESULTS At the baseline measurement there were no significant differences between the intervention and control group on any demographic and health status variables or on clinical symptoms . At the 3-month follow-up intervention patients had a better drug attitude ( P=0.03 ) than their controls and evaluated the coaching of their pharmacist as more positive . They also felt the video to be useful . It had changed their ideas about medication . CONCLUSIONS Coaching by community pharmacists is an effective way to improve drug attitude of depressive primary care patients and it is acceptable to them BACKGROUND Despite high rates of relapse and recurrence , few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment . We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care . METHODS Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were r and omized to a relapse prevention program ( n = 194 ) or usual primary care ( n = 192 ) . Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aim ed at enhancing adherence to antidepressant medication , recognition of prodromal symptoms , monitoring of symptoms , and development of a written relapse prevention plan . Follow-up assessment s were completed at 3 , 6 , 9 , and 12 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls . Intervention patients had significantly fewer depressive symptoms , but not fewer episodes of relapse/recurrence over the 12-month follow-up period . CONCLUSIONS A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes OBJECTIVE To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration . DESIGN A r and omized , controlled , unblinded , mixed experimental design . SETTING Eight Wisconsin community pharmacies within a large managed care organization . PATIENTS A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies . INTERVENTIONS Patients were r and omized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring ( PGEM ) or usual pharmacist 's care . Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies . MAIN OUTCOME MEASURES Patient 's frequency of feedback with the pharmacist , antidepressant knowledge , antidepressant beliefs , antidepressant adherence at 3 and 6 months , improvement in depression symptoms , and orientation toward treatment progress . RESULTS Of the 60 patients who completed the study , 28 received PGEM and 32 received usual pharmacist 's care . Results showed that PGEM had a significant and positive effect on patient feedback , knowledge , medication beliefs , and perceptions of progress . There were no significant group differences in patient adherence or symptoms at 3 months ; however , PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months ( P < or = .05 ) . CONCLUSION Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists . Longer-term studies with larger sample s are needed to assess the generalizability of findings . Future research also needs to explore additional ways to improve clinical outcomes Adherence to drug therapy is a limitation in treatment success for major depressive disorder ( MDD ) . The influence of RHYTHMS , an information and ongoing interactive program design ed by Pfizer Pharmaceuticals , to address patient adherence to sertraline therapy was evaluated in a primary care setting using a r and omized , double-blind , parallel group controlled trial over 29 weeks . Remission was the primary outcome evaluated . At study completion , no statistically significance between group differences was noted for remission rates , treatment adherence or mean Hamilton Depression Rating Scale ( HDRS ) score . However , the RHYTHMS group reported significantly greater satisfaction with knowledge received about depression and its treatment and demonstrated significantly greater satisfaction with treatment received . We conclude that the application of RHYTHMS in a primary care setting has a substantial role in improving satisfaction with sertraline treatment by patients with MDD |
13,468 | 22,515,274 | Our results support the fact that the G allele of A118 G polymorphism of OPRM1 moderates the effect of naltrexone in patients with alcohol dependence .
This genetic marker may therefore identify a subgroup of individuals more likely to respond to this treatment | Previous studies have suggested that the effect of naltrexone in patients with alcohol dependence may be moderated by genetic factors .
In particular , the possession of the G allele of the A118 G polymorphism of the µ-opioid receptor gene ( OPRM1 ) has been associated with a better response to naltrexone , although controversial results have been reported .
The aim of this paper is to combine previous findings by means of a systematic review and a meta- analysis . | This study compared the effects of nefazodone , a serotonergic antidepressant , with the opioid antagonist naltrexone , and an inactive placebo in 183 alcohol-dependent subjects receiving weekly relapse prevention psychotherapy . Following a single-blind , placebo lead-in period , subjects were r and omly assigned to receive study medication , which they took under double-blind conditions for 11 weeks . Naltrexone treatment was associated with significantly more adverse neuropsychiatric and gastrointestinal effects , poorer compliance , and a greater rate of treatment attrition . There were no reliable between-group differences in drinking behavior . These results indicate that nefazodone is not efficacious for treatment of alcohol dependence . Furthermore , the clinical utility of naltrexone seems to be limited by its adverse effects , a finding that has important implication s for efforts to develop medications to treat alcohol dependence AIMS To determine the clinical ly ascertained variables that are related to satisfactory response to naltrexone ( NTX ) treatment of alcohol dependence after detoxification . METHODS The use of intake and outcome variables were measured in a r and omized 3-month open-controlled trial comparing the effects of naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on the maintenance of abstinence in the final 28 days ( n = 336 , all male ) . RESULTS Predictors of a positive response to NTX treatment were family history of alcoholism ( P = 0.010 ) , early age at onset of drinking problems ( P = 0.014 ) and comorbid use of other drugs of abuse ( P < 0.001 ) . Among the subjects not treated with NTX , the greater the number of predictor variables , the lower the final 28 days abstinence rates ( P = 0.00003 ) , but this was not the case in patients treated with NTX ( P = 0.844 ) . CONCLUSIONS Patients with these features , suggesting biological vulnerability overall have poorer outcomes , but this can be reduced with NTX treatment . The type of alcoholism should be considered before deciding on the pharmacological strategy BACKGROUND Naltrexone ( NTX ) has proven to be effective with alcoholics in treatment , with most controlled clinical trials showing beneficial effects on heavy drinking rates . However , little is known about the behavioral mechanisms underlying the effects of NTX on drinking , or about patient characteristics that may moderate NTX 's effects on drinking . In this study , ecological momentary assessment ( EMA ) techniques were used to investigate some of the putative mechanisms of naltrexone 's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems . Polymorphisms in the D4 dopamine receptor ( DRD4 ) gene and the mu-opiate receptor ( OPRM1 ) gene , family history of alcohol problems , age of onset of alcoholism and gender were explored as potential moderators of NTX 's effects . METHODS After a 1-week placebo lead-in period , heavy drinkers ( n = 180 ) , 63 % of whom were alcohol-dependent , were r and omized to 3 weeks of daily naltrexone ( 50 mg ) or placebo . Throughout the study , participants used EMA on palm-pilot computers to enter , in real time , drink data , urge levels , and subjective effects of alcohol consumption . RESULTS Naltrexone reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals ; NTX decreased urge levels in participants with younger age of alcoholism onset ; NTX increased time between drinks in participants who had more relatives with alcohol problems ; and NTX reduced the stimulating effects of alcohol in women . OPRM1 status did not moderate any of NTX 's effects . CONCLUSIONS These results confirm earlier findings of NTX 's effects on drinking and related subjective effects , and extend them by describing individual difference variables that moderate these effects in the natural environment , using data collected in real time CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 BACKGROUND Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed . The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural setting s. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene ( OPRM1 ) predicted response to naltrexone , as had been reported in Caucasians . METHODS R and omized , controlled trial enrolling 101 Alaskans with alcohol dependence , including 68 American Indians/Alaska Natives . Participants received 16 weeks of either ( 1 ) placebo ( placebo naltrexone + placebo sertraline ) , ( 2 ) naltrexone monotherapy ( 50 mg naltrexone + sertraline placebo ) and ( 3 ) naltrexone + sertraline ( 100 mg ) plus nine sessions of medical management and supportive advice . Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence . RESULTS Naltrexone monotherapy demonstrated significantly higher total abstinence ( 35 % ) compared with placebo ( 12 % , p = 0027 ) and longer , but not statistically different , Time to First Heavy Drinking Day ( p = 0.093 ) . On secondary measures , naltrexone compared with placebo demonstrated significant improvements in percent days abstinent ( p = 0.024 ) and drinking-related consequences ( p = 0.02 ) . Combined sertraline and naltrexone did not differ from naltrexone alone . The pattern of findings was generally similar for the American Indian/Alaska Native sub sample . Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele . There was a small number of Asp40 carriers , precluding statistical testing of the effect of this allele on response . CONCLUSIONS Naltrexone can be used effectively to treat alcoholism in remote and rural communities , with evidence of benefit for American Indians and Alaska Natives . New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism Given the evidence from retrospective studies indicating that alcohol-dependent patients with homozygous or heterozygous A118 G variant of the & mgr;-opioid receptor , OPRM1 , gene have significantly better outcomes when treated with naltrexone ; this study examined this prospect ively in 100 alcohol-dependent participants prescribed naltrexone for 12 weeks and offered six sessions of cognitive-behavioral therapy or intervention . Comparisons were made among OPRM1 genotypic groups on several outcome measures . Naltrexone treatment produced significant decreases in self-reported and objective indicators of alcohol use and craving from baseline ( P<0.0001 and 0.017 , respectively ) , particularly during the first 2 months of treatment , with 68 % completing the study . However , there was no evidence of a significant association between OPRM1 A118 G genotype and treatment success on any of the outcome measures . Therefore , while naltrexone was an effective treatment for alcohol dependence , the OPRM1 A118 G genotype was not a predictor of success Naltrexone has repeatedly been shown to reduce drinking in alcohol-dependent patients . Previous clinical research suggests that naltrexone may be more effective at reducing drinking among patients with high levels of alcohol craving at the beginning of treatment . In addition , laboratory studies suggest that naltrexone may be more efficacious among patients with a high familial loading of alcohol problems . We explored both of these possibilities in the context of the first 12-week phase of a double blind , placebo-controlled naltrexone trial . A total of 121 patients were r and omized to receive 100 mg/day naltrexone and 62 patients were r and omized to receive placebo . Both naltrexone and placebo were given in conjunction with a psychosocial intervention design ed to be integrated with the use of pharmacotherapy . This intervention was administered by nurse practitioners . Overall , patients r and omized to naltrexone reported drinking five or more drinks on fewer days than did placebo controls ( p = .04 ) . Interactions were observed between medication group assignment and both craving level prior to r and omization ( p = .02 ) and family loading of alcohol problems ( p = .05 ) . In both cases , the interaction was in the predicted direction . These data suggest that patients with high levels of alcohol craving or a strong family history of alcoholism are more likely to benefit from naltrexone treatment Acamprosate and naltrexone are effective medications in the treatment of alcoholism . However , effect sizes are modest . Pharmacogenomics may improve patient‐treatment‐matching and effect sizes . It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system , whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system . Alcohol‐dependent subjects were r and omly assigned to either acamprosate or naltrexone . Subjects participated in a cue‐exposure experiment at the day before and at the last day of medication . Reductions in cue‐induced craving and physiological cue reactivity were measured . Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid , dopamine , glutamate and GABA‐receptors . Significant matching effects were found for polymorphisms at the DRD2 , GABRA6 and GABRB2 gene . In addition , a trend was found for the OPRM1 polymorphism . This provides evidence for the matching potential of genotypes . It is expected that more effective treatments can be offered when genetic information is used in patient‐treatment‐matching CONTEXT Clinical trials have suggested a modest effect of naltrexone as a pharmacotherapy for alcoholism , and a recent study has suggested that the effects may be moderated by variations in the mu-opioid receptor gene ( OPRM1 ) . However , the mechanism by which naltrexone may be differentially effective as a function of the OPRM1 genotype is unclear . OBJECTIVES ( 1 ) To replicate and exp and on the association between the A118 G single nucleotide polymorphism(SNP ) of the OPRM1 gene and alcohol sensitivity , ( 2 ) to examine the effects of naltrexone on alcohol sensitivity , and ( 3 ) to test the A118 G SNP of the OPRM1 gene as a moderator of the effects of naltrexone on alcohol sensitivity . DESIGN A within-subject , double-blind , placebo-controlled laboratory trial of naltrexone . SETTING Participants were recruited from the community . PARTICIPANTS Non-treatment-seeking heavy drinkers were enrolled in the study . Prospect i ve genotyping was conducted to over sample for the genetic variant of interest . Intervention After taking naltrexone ( 50 mg ) or placebo , participants completed an intravenous alcohol challenge session in which they were assessed at baseline and at each of the 3 target breath alcohol concentrations : 0.02 , 0.04 , and 0.06 mg/L. MAIN OUTCOME MEASURES The Biphasic Alcohol Effects Scale , the Alcohol Urge Question naire , the Profile of Mood States , and the Alcohol Rating Scale were administered . RESULTS Individuals with at least 1 copy of the G allele reported lower alcohol craving and higher alcohol-induced " high " across rising breath alcohol concentrations . Naltrexone was found to blunt alcohol 's effects on stimulation , positive mood , craving , and enjoyment . The effects of naltrexone on blunting alcohol-induced high were stronger among individuals with the G allele . CONCLUSION This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy Polymorphisms of the mu-opioid receptor ( OPRM1 ) and dopamine D4 receptor ( DRD4 ) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions . This study examined these associations in the natural environment using ecological momentary assessment . Participants were non-treatment-seeking heavy drinkers ( n = 112 , 52 % female , 61 % alcohol dependent ) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment . Data were culled from 5 consecutive days of drinking reports prior to medication r and omization . Analyses revealed that , after drinking , carriers of the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and lower levels negative mood , as compared to homozygotes for the Asn40 variant . Carriers of the long allele ( i.e. , > or=7 t and em repeats ) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele . Effects of OPRM1 and DRD4 variable-number-of-t and em-repeats genotypes appear to be alcohol dose-dependent . Specifically , carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated blood alcohol concentration ( eBAC ) , and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose , as compared to carriers of the major allele for each gene . Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode . This study extends findings on subjective intoxication , urge to drink , and their genetic bases from controlled laboratory to naturalistic setting BACKGROUND Recent studies examining the moderating effects of polymorphic variation in opioid receptor genes have yielded conflicting results . We examined opioid receptor gene polymorphisms as moderators of the therapeutic effects of the opioid antagonist nalmefene . METHODS Participants ( n = 272 ) were subjects who consented to the pharmacogenetic analysis of a multi-site , r and omized , placebo-controlled trial of targeted nalmefene for the reduction of heavy drinking . We genotyped two single nucleotide polymorphisms ( SNPs ) in OPRM1 ( including A118 G , a commonly studied SNP that encodes an Asn40Asp amino acid substitution ) , two SNPs in OPRD1 , and one SNP in OPRK1 , which encode the mu- , delta- , and kappa-opioid receptors , respectively . Regression analysis served to examine the moderating effects of these SNPs on medication response . RESULTS As previously described by Karhuvaara et al. ( 2007 ) , nalmefene significantly reduced the number of heavy drinking and very heavy drinking days per week , compared with placebo . There were no main or moderating effects of the genotypes examined on these outcomes . CONCLUSIONS Our finding that the therapeutic effects of targeted nalmefene were not moderated by polymorphic variation in opioid receptor genes is consistent with two recent reports showing that variation in opioid receptor genes does not moderate the response to naltrexone . However , these findings contrast with those from two other studies , in which the Asn40Asp polymorphism in OPRM1 moderated the naltrexone treatment response . Additional research is needed to clarify the role of variation in opioid receptor genes on the response to opioid antagonist treatment of alcoholism BACKGROUND Naltrexone ( NTX ) reduces drinking and craving in alcoholic individuals in treatment and also in heavy drinkers . Polymorphisms in the D4 dopamine receptor ( DRD4 ) gene and mu-opiate receptor gene ( OPRM1 ) may moderate NTX 's effects on craving . This study examined these c and i date genes as moderators of the effects of NTX on cue-elicited urge to drink in non-treatment-seeking heavy drinkers . METHOD Data from the subset of 93 participants who consented for genetic testing in a larger study of medication effects were used to examine pharmacogenetic hypotheses . The non-treatment-seeking male and female heavy drinkers ( 62 % alcohol dependent ) were genotyped for the variable number of t and em repeats polymorphism in the DRD4 gene [ L=7 or more ( n=34 ) , S = less than 7 ( n=56 ) ] and Asn40Asp single-nucleotide polymorphism in the OPRM1 gene [ 29 aspartate ( Asp ) carriers and 59 asparagine ( Asn ) homozygotes ] . Ten days after r and omization to NTX ( 50 mg ) or placebo , participants completed an alcohol cue reactivity assessment . RESULTS Any medication effects were all accounted for by interaction with genotype . Naltrexone increased urge for alcohol in Asp carriers across alcohol and neutral beverage cue trials and had no effect on homozygous Asn carriers . Asp40 carriers on either medication had greater decreases ( from resting baseline ) in mean arterial blood pressure across all beverage cue trials compared with Asn carriers . For DRD4 , no differential medication effects by DRD4 polymorphism were found . Alcohol dependence diagnosis did not moderate the effects of gene and medication on cue-elicited measures . DISCUSSION The differential responses to NTX due to variation in the OPRM1 gene may help explain conflicting results in clinical trials and suggest directions for patient-treatment matching This study examined the association between two specific polymorphisms of the gene encoding the mu-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo . A total of 82 patients ( 71 of European descent ) who were r and omized to naltrexone and 59 who were r and omized to placebo ( all of European descent ) in one of three r and omized , placebo-controlled clinical trials of naltrexone were genotyped at the A(+118)G ( Asn40Asp ) and C(+17)T ( Ala6Val ) SNPs in the gene encoding the mu-opioid receptor ( OPRM1 ) . The association between genotype and drinking outcomes was measured over 12 weeks of treatment . In subjects of European descent , individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse ( p=0.044 ) and a longer time to return to heavy drinking ( p=0.040 ) than those homozygous for the Asn40 allele . There were no differences in overall abstinence rates ( p=0.611 ) , nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo . These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a mu-receptor antagonist . If replicated , these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone BACKGROUND Pre clinical studies have implicated GABAergic neurosteroids in behavioral responses to alcohol . Naltrexone is thought to blunt the reinforcing effects of alcohol , and a few studies have found that the effects of naltrexone are moderated by the Asn40Asp polymorphisms of the OPRM1 gene . The present study seeks to integrate these lines of research by testing ( i ) the moderating role of the functional Asn40Asp polymorphism of the OPRM1 gene on naltrexone-induced alternations in GABAergic neurosteroid levels , namely (3alpha,5alpha)-3-hydroxypregnan-20-one ( allopregnanolone , ALLO ) ; and ( ii ) the combined effects of naltrexone or genotype with alcohol administration on neurosteroid levels in a sample of at-risk drinkers . METHODS Participants were 32 ( 9 females ) nontreatment-seeking heavy drinkers who completed a placebo-controlled laboratory study of naltrexone ( 50 mg/d for 3 days ) and provided complete sets of serum sample s for ALLO assays before and after alcohol administration under both naltrexone and placebo conditions . RESULTS Naltrexone treatment raised ALLO levels among carriers of the Asp40 allele , but not homozygotes for the Asn40 allele . The Asn40Asp polymorphism did not moderate effects of naltrexone on cortisol levels . Ethanol infusion modestly reduced ALLO levels in all subjects , independent of genotype or naltrexone exposure . CONCLUSIONS Naltrexone increased ALLO levels among individuals with the Asn40Asp allele suggesting a potential neurosteroid contribution to the neuropharmacological effects of naltrexone among Asp40 carriers |
13,469 | 18,843,671 | Active management is associated with small reductions in the CS rate , but it is highly prescriptive and interventional .
It is possible that some components of the active management package are more effective than others . | BACKGROUND Approximately 15 % of women have caesarean sections ( CS ) and while the rate varies , the number is increasing in many countries .
This is of concern because higher CS rates do not confer additional health gain but may adversely affect maternal health and have implication s for future pregnancies .
Active management of labour has been proposed as a means of reducing CS rates .
This refers to a package of care including strict diagnosis of labour , routine amniotomy , oxytocin for slow progress and one to one support in labour .
OBJECTIVES To determine whether active management of labour reduces CS rates in low-risk women and improves satisfaction . | The authors have carried out a r and om study on 75 cases in order to evaluate objective ly the therapeutic methods usually employed in cases of dystocia in starting labour . These studies have shown the superiority of Syntocinon using an infusion together with epidural analgesia . This attitude goes against the methods of treatment usually used in France . The authors explain the reasons for their choice in the light of factors that they have observed using other therapeutic methods Objective To compare labour outcomes using aggressive or expectant management protocol OBJECTIVE To determine whether cervical dilatation at the time of placement of patient-requested epidural affects cesarean rates or lengths of labors in actively managed parturients . METHODS The charts of 255 women r and omized to active management of labor ( n = 125 ) or control protocol s ( n = 130 ) were review ed and stratified to early epidural placement ( up to 4 cm cervical dilatation ) versus late placement ( more than 4 cm ) . RESULTS Women with early epidural placement had shorter labors than those with late placement ( 11.6 + /- 4.6 versus 13.2 + /- 5.6 hours ; P = .02 ) . Active management reduced the length of labor compared with controls regardless of epidural timing , with a reduction of 1.4 hours in early epidural placement ( 10.9 + /- 4.7 versus 12.3 + /- 4.3 hours ; P = .04 ) and 3.6 hours in those with later placement ( 11.0 + /- 3.6 versus 14.6 + /- 6.2 hours ; P = .004 ) . Cesarean rates did not vary significantly ( early 14.5 % versus late 7.9 % ; P = .21 ) . Early epidural placement did not lengthen the second stage of labor or increase operative vaginal delivery rates . CONCLUSION Early epidural placement did not affect lengths of labor or cesarean rates and was actually associated with shorter labor compared with late epidural placement . Women managed actively in labor , regardless of timing of epidural placement , had shorter labors than controls BACKGROUND Active management of labor reduces the length of labor and rate of prolonged labor , but its effect on satisfaction with care , within a r and omized controlled trial , has not previously been reported . The study objectives were to establish if a policy of active management of labor affected any aspect of maternal satisfaction , and to determine the independent explanatory variables for satisfaction with labor care in a low-risk nulliparous obstetric population . METHODS Nulliparous women at National Women 's Hospital in Auckl and , New Zeal and , in spontaneous labor at term with singleton pregnancy , cephalic presentation , and without fetal distress were r and omized after the onset of labor to active management ( n = 320 ) or routine care ( n = 331 ) . Active management included early amniotomy , two-hourly vaginal assessment s , and early use of high dose oxytocin for slow progress in labor . Routine care was not prespecified . Maternal satisfaction with labor care was assessed by postal question naire at 6 weeks postpartum . Sensitivity analyses were performed , and logistic regression models were developed to determine independent explanatory variables for satisfaction . RESULTS Of the 651 women r and omized in the trial , 482 ( 74 % ) returned the question naires . Satisfaction with labor care was high ( 77 % ) and did not significantly differ by treatment group . This finding was stable when sensitivity analysis was performed . The first logistic regression model found independent associations between satisfaction and adequate pain relief , one-to-one midwifery care , adequate information and explanations by staff , accurate expectation of length of labor , not having a postpartum hemorrhage , and fewer than three vaginal examinations during labor . The second model found fewer than three vaginal examinations and one-to-one midwifery care as significant explanatory variables for satisfaction with labor care . CONCLUSIONS Active management did not adversely affect women 's satisfaction with labor and delivery care in this trial . Future studies should concentrate on measurement of potential predictors before and during labor The objective of our study was prospect ively compare the effect in the rate of cesarean section of active labor management and of traditional labor management in primiparas with physiological term pregnancy . From september 1 , 1993 to may 31 , 1994 , 145 primiparas with physiological term pregnancy were r and omly assigned to one group of active labor management ( study group , n = 75 ) and to one group of traditional labor management ( control group , n = 70 ) . Cesarean section rate was 9.3 % in the study group and 20 % in the control group ( p < 0.05 ) . There was no increase in fetal morbidity or mortality . Active labor management can reduce cesarean section rate in primiparas with physiological term pregnancy OBJECTIVE To compare the costs of a protocol of active management of labor with those of traditional labor management . DESIGN Cost analysis of a r and omized controlled trial . METHODS From August 1992 to April 1996 , we r and omly allocated 405 women whose infants were delivered at the University of New Mexico Health Sciences Center , Albuquerque , to an active management of labor protocol that had substantially reduced the duration of labor or a control protocol . We calculated the average cost for each delivery , using both actual costs and charges . RESULTS The average cost for women assigned to the active management protocol was $ 2,480.79 compared with an average cost of $ 2,528.61 for women in the control group ( P = 0.55 ) . For women whose infant was delivered by cesarean section , the average cost was $ 4,771.54 for active management of labor and $ 4,468.89 for the control protocol ( P = 0.16 ) . Spontaneous vaginal deliveries cost an average of $ 27.00 more for actively managed patients compared with the cost for the control protocol . CONCLUSIONS The reduced duration of labor by active management did not translate into significant cost savings . Overall , an average cost saving of only $ 47.91 , or 2 % , was achieved for labors that were actively managed . This reduction in cost was due to a decrease in the rate of cesarean sections in women whose labor was actively managed and not to a decreased duration of labor Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery . Design Prospect i ve cohort study within the 2005 WHO global survey on maternal and perinatal health . Setting 410 health facilities in 24 areas in eight r and omly selected Latin American countries ; 123 were r and omly selected and 120 participated and provided data Participants 106 546 deliveries reported during the three month study period , with data available for 97 095 ( 91 % coverage ) . Main outcome measures Maternal , fetal , and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery , adjusted for clinical , demographic , pregnancy , and institutional characteristics . Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.5 ) for intrapartum caesarean and 2.3 ( 1.7 to 3.1 ) for elective caesarean ) . The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries . With cephalic presentation , there was a trend towards a reduced odds ratio for fetal death with elective caesarean , after adjustment for possible confounding variables and gestational age ( 0.7 , 0.4 to 1.0 ) . With breech presentation , caesarean delivery had a large protective effect for fetal death . With cephalic presentation , however , independent of possible confounding variables and gestational age , intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care ( 2.1 ( 1.8 to 2.6 ) and 1.9 ( 1.6 to 2.3 ) , respectively ) and the risk of neonatal mortality up to hospital discharge ( 1.7 ( 1.3 to 2.2 ) and 1.9 ( 1.5 to 2.6 ) , respectively ) , which remained higher even after exclusion of all caesarean deliveries for fetal distress . Such increased risk was not seen for breech presentation . Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery , but rupturing of membranes may be protective . Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations The aim of this r and omised trial was to determine the effect of the policy of active management of labour in all its components on the rate of caesarean section in a Nigerian district hospital setting . Two hundred and twenty-one nulliparous women fulfilling selected inclusion criteria were r and omised to receive active management of labour , and 227 control women received routine labour management . Labour was significantly shortened by over 2 hours with active management of labour , and caesarean section reduced ( 9 % vs. 16 % , RR 0.57 , 95 % CI 0.34 - 0.95 ) . There were no significant differences in maternal infectious morbidity , uterine hyperstimulation syndromes , ruptured uterus or neonatal Apgar scores between the two groups . We conclude that active management of labour shortens primigravid labour and reduces caesarean risk OBJECTIVE Much of fever during term labor may not be infectious but rather a consequence of the use of epidural analgesia . Therefore , we investigated the association of elevated maternal intrapartum temperature with neonatal outcome when the infant does not develop an infection . METHODS We studied 1218 nulliparous women with singleton , term pregnancies in a vertex presentation and spontaneous labor . Women were excluded if their temperature was > 99.5 degrees F at admission for delivery , if they were diabetic or had an active genital herpes infection or if their infant developed a neonatal infection , had a congenital infection , or had a major malformation . Maximum intrapartum temperature was categorized as : < /=100.4 degrees F ( afebrile ) , 100.5 degrees F to 101 degrees F , and > 101 degrees F. RESULTS During labor , 123 women ( 10.1 % ) developed a fever > 100.4 degrees F ; 62 ( 5.1 % ) women had a maximum temperature of 100.5 degrees F to 101 degrees F and 61 ( 5.0 % ) women had a maximum temperature > 101 degrees F. Of febrile women , 97.6 % had received epidural analgesia for pain relief . Infants of women developing a fever > 100.4 degrees F were more likely to have a 1-minute Apgar score < 7 ( 22.8 % for > 100.4 degrees F vs 8.0 % for afebrile ) and to be hypotonic after delivery ( 4.8 % for > 100.4 degrees F vs.5 % for afebrile ) . Compared with infants of afebrile women , infants whose mothers ' maximum temperature was > 101 degrees F were more likely to require bag and mask resuscitation ( 11.5 % vs 3.0 % ) and to be given oxygen therapy in the nursery ( 8.2 % vs 1.3 % ) . We also found a higher rate of neonatal seizure with fever ( 3.3 % vs.2 % ) , but the number of infants with seizure was small ( n = 4 ) . All associations remained essentially the same after controlling for confounding in logistic regression analyses . CONCLUSIONS Intrapartum maternal fever , particularly if > 101 degrees F , was associated with a number of apparently transient adverse effects in the newborn . Larger studies are needed to investigate the association of intrapartum fever with neonatal seizures and to determine whether any lasting injury to the fetus may occur BACKGROUND Over the past two decades , the rate of cesarean section in the United States has risen from 5 percent to 25 percent of deliveries , primarily because of the increased frequency of dystocia ( arrest of labor ) . One strategy that has been proposed for increasing the rate of vaginal delivery is a program of active management of labor that encourages early amniotomy , early diagnosis of slow progress in labor , and the use of higher than usual doses of oxytocin ; the efficacy and safety of this approach are uncertain , however . METHODS We conducted a r and omized trial in which nulliparous women in spontaneous labor at term were r and omly assigned to either active management of labor or traditional management . With active management , amniotomy was performed within one hour of the diagnosis of labor , and when the rate of cervical dilation was less than 1 cm per hour , oxytocin was infused at an initial rate of 6 mU per minute . The dose was increased by 6 mU per minute every 15 minutes ( to a maximum of 36 mU per minute ) until there were seven contractions every 15 minutes . RESULTS For the women assigned to active management ( n = 351 ) , the cesarean-section rate was 10.5 percent , as compared with 14.1 percent for those assigned to traditional management ( n = 354 , P = 0.18 ) . The 26 percent reduction in the cesarean-section rate was due primarily to a decrease in dystocia . After we controlled for potential confounding variables , the reduction in the rate of delivery by cesarean section was statistically significant ( odds ratio for women given active as compared with traditional management , 0.57 ; 95 percent confidence interval , 0.36 to 0.95 ) . With active management , the average length of labor was shortened by 1.66 hours , principally because of earlier amniotomy and earlier use of oxytocin . There was no increase in maternal or neonatal morbidity , and there were significantly fewer infectious complications in the mothers . CONCLUSIONS The program we studied for the active management of labor reduces the incidence of dystocia and increases the rate of vaginal delivery without increasing maternal or neonatal morbidity OBJECTIVE To determine the effect of an active management of a labor program on the rate of cesarean section and labor outcomes in low-risk nulliparous pregnancies in a setting with limited re sources . MATERIAL AND METHOD Nine hundred and seventy-five low risk nulliparous pregnant women were r and omized to receive either active management of a labor program ( n = 325 ) or conventional management ( n = 650 ) . The rate of cesarean section and labor outcomes were compared between the two groups using Chi-square and t-tests . RESULTS The subjects in the active management program had significantly shortened first stage of labor and total duration of labor compared with the conventional group ( 538.0 + /- 242.9 min vs 589.4 + /- 263.8 min , p < 0.05 , 539.3 + /- 261.4 min vs 610.3 + /- 264.4 min , p < 0.001 , respectively ) . There was no statistical difference found in the rate of cesarean section and other labor outcomes . CONCLUSION The active management program shortened the first stage and duration of labor in low-risk nulliparous pregnant women BACKGROUND Active management of labor is a multifaceted program that , as implemented at the National Maternity Hospital in Dublin , is associated with a lower rate of cesarean delivery than the rate usually found in the United States . We conducted a r and omized trial to evaluate the efficacy of this approach in lowering the rate of cesarean section among women delivering their first babies . METHODS We r and omly assigned 1934 nulliparous women at low risk of complications of pregnancy , before 30 weeks ' gestation , to active management of labor or to a usual-care group . The components of active management were customized childbirth classes ; strict criteria for the diagnosis of labor ; st and ardized management of labor , including early amniotomy and treatment with high-dose oxytocin ; and one-to-one nursing . A low-risk subgroup was defined as including women with full-term , uncomplicated pregnancies who spontaneously went into labor ( the protocol -eligible subgroup ) . Women meeting these criteria who had been r and omly assigned to the active-management group were admitted to a separate unit where their labor was managed by trained , certified nurse-midwives . RESULTS There was no difference between groups in the rate of cesarean section either among all women ( active management , 19.5 percent ; usual care , 19.4 percent ) or in the protocol -eligible subgroup ( active management , 10.9 percent ; usual care , 11.5 percent ) . In the protocol -eligible subgroup , the median duration of labor was shortened by 2.7 hours by active management ( from 8.9 to 6.2 hours ) , and the rate of maternal fever was lower ( 7 percent vs. 11 percent , P = 0.007 ) . The percentage of women in whom labor lasted longer than 12 hours was three times higher in the usual-care group than in the active-management group ( 26 percent vs. 9 percent , P < 0.001 ) . CONCLUSIONS Active management of labor did not reduce the rate of cesarean section in nulliparous women but was associated with a somewhat shorter duration of labor and less maternal fever OBJECTIVE Our goal was to evaluate whether active management of labor lowers cesarean section rates , shortens the length of labor , and overcomes any negative effects of epidural analgesia on nulliparous labor . STUDY DESIGN We r and omly assigned 405 low-risk term nulliparous patients to either an active management of labor ( n = 200 ) or our usual care control protocol ( n = 205 ) . Patients who were undergoing active management of labor were diagnosed as being in labor on the basis of having painful palpable contractions accompanied by 80 % cervical effacement , underwent early amniotomy , and were treated with high-dose oxytocin for failure to progress adequately in labor . RESULTS The cesarean section rate in the active management of labor group was lower than that of controls but not significantly so ( active management , 7.5 % ; controls , 11.7 % ; p = 0.36 ) . The length of labor in the active management group was shortened by 1.7 hours ( from 11.4 to 9.7 hours , p = 0.001 ) . Fifty-five percent of patients received epidural analgesics ; a reduction in length of labor persisted despite the use of epidural analgesics ( active management 11.2 hours vs control 13.3 hours , p = 0.001 ) . A significantly greater proportion of active management patients were delivered by 12 hours compared with controls ( 75 % vs 58 % , p = 0.01 ) ; this difference also persisted despite the use of epidural analgesics ( 66 % vs 51 % , p = 0.03 ) . CONCLUSIONS Patients undergoing active management had shortened labors and were more likely to be delivered within 12 hours , differences that persisted despite the use of epidural analgesics . There was a trend toward a reduced rate of cesarean section OBJECTIVE Our purpose was to compare maternal and fetal factors that influence the route of delivery with active management of labor and a traditional labor management protocol . STUDY DESIGN Data were collected prospect ively on 346 consecutive patients receiving active management of labor and 354 patients who were managed traditionally . Within each group demographic and labor characteristics of patients undergoing cesarean section were compared with those of patients having vaginal deliveries by means of the Student t test , chi 2 analysis , and stepwise logistic regression . RESULTS With both active management of labor and traditional labor management success in achieving vaginal delivery was related to the station of the fetal vertex at admission , the need for oxytocin augmentation of labor , the uterine response to oxytocin , the use of epidural anesthesia , and the development of chorioamnionitis . By means of multiple logistic regression analysis maternal age , height , payor status , and birth weight were also identified as risk factors for cesarean section with traditional labor management but not with active management of labor . CONCLUSIONS Differences were identified in risk factors for cesarean section between active management and traditional labor management . Active management of labor may diminish or eliminate some patient characteristics as risk factors for cesarean birth The aggressive management of early labor has been suggested as a means to lower the cesarean section rate for dystocia . The aim of our study was to prospect ively evaluate a protocol of early intervention in primigravid women with infrequent uterine contractions during early labor in relation to the course of labor , the cesarean section rate , and the perinatal morbidity . In our population the active management of labor did not alter the mode of delivery or the perinatal outcome . Furthermore , the course and duration of labor were not significantly different between the management and control groups Active management of labour has been developed to the extent that an assurance is given to every woman who attends this hospital that her first baby will be born within 12 hours . This assurance could lead to a welcome change in present attitudes because the mere prospect of prolonged labour is often a cause of serious concern during a first pregnancy . Labour of strictly limited duration makes it possible to provide every woman with a personal nurse , and it places the problem of pain in a new setting . The results of a prospect i ve study of 1,000 consecutive primigravidae are presented , and the guidelines to a st and ard policy of management are denned . Difficulty in meeting the commitment to early delivery arose almost exclusively in cases in which the diagnosis of labour was in doubt ; only seven women were retained in the delivery unit for 12 hours |
13,470 | 30,022,832 | The results also indicated EPO does not increase the risk of a venous thromboembolism event .
Conclusion Preoperative administration of EPO was shown to generally increase Hb levels during the whole perioperative period ; however , the extent of the positive effects varies with time points .
Additionally , EPO minimizes the need for transfusion significantly in patients undergoing hip or knee surgery without increasing the chance of developing thrombotic complications .
Therefore , EPO offers an alternative blood management strategy in total hip arthroplasty and total knee arthroplasty | Purpose The debate is still ongoing on the effectiveness and safety of erythropoietin ( EPO ) treatment in orthopedic surgeries .
Specifically , previous studies have not compared the dynamic change of hemoglobin ( Hb ) levels between different transfusion methods .
Besides , complications or side effects of this alternative have not been quantitatively analyzed .
We conducted a meta- analysis and systemic review to evaluate the efficacy of EPO on Hb levels observed during the whole perioperative period as well as the volume of allogeneic blood transfusion ( ABT ) , the risk of venous thromboembolism , and application frequency of ABT in hip and knee surgery . | Forty patients who were scheduled for a total hip arthroplasty were enrolled in a prospect i ve study and were r and omly divided into two groups . Group 1 received recombinant human erythropoietin ( 300 U/kg twice a week ) , and group 2 received placebo . The medication was started 2 weeks before the operation , and only one dose of medication was given after the operation . Autologous blood was administered at the same time as the medication until the hemoglobin level sank to 10 g/dl . Forty-eight and 49 units of autologous blood were collected in group 1 and group 2 , respectively . Intraoperative homologous blood was transfused only to patients in group 2 . Seven and 13 units of allogenic blood were transfused into group 1 and group 2 patients during the postoperative period , respectively . There were no any significant differences between the groups in terms of early postoperative hemoglobin level and amount of autologous blood collected . However , the increase of the reticulocyte count in patients who received erythropoietin was significantly higher than in the group 2 patients . The study showed that short-term and low-dose erythropoietin usage strongly stimulates the bone marrow . Erythropoietin administration and preoperative autologous blood donation diminished the total units of allogenic blood required during the intraoperative or postoperative pe-riod . Autologous blood administration without concurrent erythropoietin did not stimulate the bone marrow adequately This prospect i ve r and omized trial compared preoperative autologous blood donation ( PAD ) with epoetin alfa in patients undergoing primary total knee reconstruction . Fifty adult patients with pretreatment hemoglobin level of 100 to 130 g/L were r and omized to either epoetin alfa 40,000 U at preoperative days 14 and 7 or to a st and ard PAD protocol . Patient characteristics and operative blood loss were similar between groups . Baseline hematological parameters for epoetin alfa vs PAD were not significantly different ; however , by the day of surgery the epoetin alfa group had significantly higher hemoglobin ( 130 vs 114 g/L ; P < .001 ) , hematocrit ( 0.408 vs 0.352 ; P < .001 ) , and reticulocyte count ( 3.4 vs 2.1 x 10(9 ) cells per liter ; P < .001 ) . These differences remained significant for 1 to 2 days postoperatively . There was no significant difference in the incidence of allogeneic transfusions between groups ( 28 % for epoetin alfa vs 8 % for PAD ; P = .1383 ) . Both treatments were generally well tolerated . Epoetin alfa appears to be a safe alternative to PAD in patients who are at risk for transfusion in the perioperative period following total knee arthroplasty Abstract Recombinant human erythropoietin ( rHuEPO ) is effective in allowing autologous blood donation in patients unable to donate because of anemia . As adverse effects of rHuEPO might include activation of coagulation and possibly fibrinolysis , we investigated these possibilities in the context of autologous blood donation preceding hip surgery . Thirty-seven patients who donated 800 ml of autologous blood for elective hip surgery were r and omly assigned to either a group of 20 receiving preoperative treatment with rHuEPO ( erythropoietin β ) , 6000 U i.v . twice weekly for 3 weeks , or an untreated control group of 17 . A significant increase in platelet count was associated with autologous blood donation and intraoperative blood loss with or without rHuEPO . Coagulation and fibrinolysis were increased significantly by intraoperative blood loss in both groups , but not by rHuEPO . Coagulation and fibrinolysis were not activated by rHuEPO for elective hip surgery In a prospect i ve r and omized study we investigated the potential of subcutaneous recombinant human erythropoietin ( rhEpo ) as adjuvant treatment for autologous blood transfusions ( 3 units ) in elective surgery . Four and 2 weeks before surgery , 49 patients received 6 x 10,000 U of rhEpo . delta Hb values ( days -28 and 0 ) of the rhEpo group were compared to delta Hb values of 52 controls ( no rhEpo ) . Reticulocytes were measured at days -21 , -14 , -7 and 0 . Peri- and postoperative supplementary homologous blood requirements were compared in the two r and omized groups . delta Hb of rhEpo group was 0.96 g/dl ( mean value ) and 2.38 for controls . Reticulocyte count increased earlier and to higher levels in rhEpo-treated patients . Except in 1 case , Epo was well tolerated . These results indicate that autologous predonation ( 3 x 400 ml ) does not create anemia if adjuvant Epo treatment is given . However , homologous blood requirements were not significantly different , which is probably due to the fact that 96 of the 101 treated patients underwent elective orthopedic surgery requiring limited blood replacement . Significant benefit of the Epo regimen can be expected in elective cardiovascular and hepatic surgery where larger amounts of blood ( 5 - 6 units ) are needed BACKGROUND The increasing incidence of osteoporotic hip fracture ( HF ) has raised the requirements of red blood cell ( RBC ) transfusions , whereas this scarce re source may cause morbidity and mortality . STUDY DESIGN AND METHODS This study was a multicenter , r and omized , double-blind , clinical trial that aim ed to assess efficacy of ferric carboxymaltose ( FCM ) with or without erythropoietin ( EPO ) in reducing RBC transfusion in the perioperative period of HF . Participants ( patients > 65 years admitted with HF and hemoglobin [ Hb ] levels of 90 - 120 g/L ) were r and omly assigned to receive a preoperative single dose of 1 g of FCM ( short intravenous [ IV ] infusion over 15 min ) , plus 40,000 IU of subcutaneous EPO ( EPOFE arm ) ; versus 1 g of IV FCM plus subcutaneous placebo ( FE arm ) ; and versus IV and subcutaneous placebo ( placebo arm ) . Primary endpoint was the percentage of patients who received RBC transfusion , and secondary endpoints were the number of RBC transfusions per patient , survival , hemoglobinemia , and health-related quality of life ( HRQoL ; by means of Short Form 36 Version 2 question naire ) . RESULTS A total of 306 patients ( 85 % women , mean age 83 ± 6.5 years ) were included . A total of 52 , 51.5 , and 54 % of patients required RBC transfusion in the EPOFE , FE , and placebo arms , respectively , with no significant differences in the number of RBC transfusions per patient , survival , HRQoL , and adverse events among treatment groups . A significant increase in Hb levels was achieved at discharge ( 102 g/L vs. 97 g/L ) and 60 days after discharge ( 125 g/L vs. 119 g/L ) in the EPOFE arm with respect to placebo arm ; in addition , a higher rate of patients recovered from anemia in the EPOFE arm with respect to the placebo arm ( 52 % vs. 39 % ) , 60 days after discharge . CONCLUSION Preoperative treatment with FCM alone or in combination with EPO improved recovery from postoperative anemia , but did not reduce the needs of RBC transfusion in patients with HF Total hip joint arthroplasty is frequently associated with transfusion of allogeneic blood ( 1 , 2 ) . Although serologic screening has reduced the risk for viral infection to a low level ( 3 , 4 ) , the public is highly concerned about this potential complication of transfusion ( 5 ) . Therefore , further refinement of strategies to avoid exposure to allogeneic blood is needed . The most commonly used preventive strategy is autologous blood donation ( 6 ) . Blood is collected from the patient before surgery and is reinfused if transfusion is necessary . In the past decade , this maneuver , which reduces exposure to pathogens and red cell alloimmunization , has become a st and ard of care in orthopedic surgery ( 7 , 8) . However , autologous blood donation has several disadvantages . First , donation and banking of autologous blood are inconvenient to patients ( 9 , 10 ) . Second , phlebotomy increases the prevalence of postoperative anemia and transfusion ( either autologous or allogeneic ) ( 11 ) . Third , use of autologous blood is not without risk ( 12 , 13 ) . Bacterial contamination of predonated blood ( 14 ) and major transfusion reactions ( due to administrative error ) ( 15 ) are rare but may be life-threatening . Finally and most important , many patients are not eligible for predonation because of concomitant medical conditions ( 16 ) . Erythropoietin , a glycoprotein produced by the kidney , stimulates production of red blood cells from the bone marrow ( 17 ) . Administration of recombinant human erythropoietin ( epoetin alfa ) reduces the risk for allogeneic blood transfusion in patients undergoing total hip joint arthroplasty ( 18 , 19 ) . Factors that influence the response to epoetin alfa include the dose and timing of treatment ( 20 ) , coadministration of iron ( 21 , 22 ) , and baseline hemoglobin concentration ( 23 ) . Although several different preoperative regimens have been described , the regimen approved by the U.S. Food and Drug Administration consists of four subcutaneous injections of epoetin alfa , 600 U/kg of body weight , administered before surgery ( weeks 3 , 2 , and 1 and the day of surgery ) ( 24 ) . Thus , a person weighing 70 kg would require a total dose of 168 000 U. On the basis of subgroup analysis from a previous study ( 18 ) , we hypothesized that a high dose of oral iron used in conjunction with a more prolonged epoetin alfa dosing schedule might produce a better hematologic response than that obtained with the st and ard regimen . We therefore evaluated the efficacy of two different epoetin alfa dose regimens . Methods Patients The study was a double-blind , r and omized , parallel-group , multicenter clinical trial comparing the efficacy of epoetin alfa ( Eprex , Janssen-Ortho Inc. , Toronto , Ontario , Canada ) with placebo in adult patients undergoing total hip joint arthroplasty . The trial was conducted at 13 teaching and 4 community hospitals in Canada from May 1996 to April 1999 . The protocol was approved by the institutional review board of each participating center . Eligible patients had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood . At centers where an autologous blood donation program was available , blood predonation was discussed with patients ; those who participated in the study were either ineligible for predonation because of medical contraindication or declined this option . Persons with rheumatoid arthritis , recent gastrointestinal or intracranial bleeding , iron deficiency , seizures , blood dyscrasias , or uncontrolled hypertension ( diastolic blood pressure>100 mm Hg ) were excluded from the study . Patients who required revision arthroplasty or those in whom red cell salvage devices were considered essential were not enrolled . All patients gave written informed consent . Baseline and R and omization Procedures Participants were screened for eligibility 7 weeks before surgery . A history and physical examination were performed , and a complete blood count , iron studies , and blood chemistry were obtained ; patients then began oral iron therapy . Six weeks before surgery , eligible patients were r and omly assigned to one of three treatment groups . R and omization was performed according to a computer-generated schedule using a block size of 13 and an allocation ratio of 3:5:5 to the high-dose epoetin group , low-dose epoetin group , or placebo group , respectively . Treatment Regimens Patients began daily oral iron therapy at least 42 days before surgery and continued therapy until the day of hospital discharge . Three capsules per day were recommended . In patients who were intolerant of iron , the number of capsules was reduced to the point of tolerability . The iron preparation prescribed was Niferex-150 ( Schwarz Pharma , Mequon , Wisconsin ) . This polysaccharideiron complex was selected because of its good tolerability and high bioavailability of elemental iron ( 150 mg per capsule ) ( 25 ) . Patients received four weekly subcutaneous injections of placebo , high-dose epoetin alfa ( 40 000 U ) , or low-dose epoetin alfa ( 20 000 U ) starting 4 weeks before surgery . The total possible dose was 160 000 U in the high-dose group and 80 000 U in the low-dose group . The study drug was withheld if the hemoglobin concentration was 150 g/L or more , systolic blood pressure was 200 mm Hg or more , or the diastolic blood pressure was 105 mm Hg or more . During the trial , the study coordinator at the data coordinating center , who was aware of the patient 's hemoglobin concentration , authorized administration of study drug before each visit . This person had no contact with patients and did not assess outcomes . Follow-up Schedule Patients were evaluated 28 , 21 , 14 , and 7 days before surgery . At these visits , vital signs and adverse events were recorded by the visiting nurse . Patients , surgeons , and nurses were unaware of treatment assignments and laboratory results . Hemoglobin concentration on the day of surgery was available to the surgeon and other health care personnel , but the reticulocyte count and the previous hemoglobin concentration were not . Blood loss was quantified by weighing sponges and measuring suction volume intraoperatively and subtracting the volume of the irrigation fluid . Patients were seen 1 , 3 , and 5 days after surgery ; blood work was performed at these times . On the fifth day after surgery , patients underwent duplex ultrasonography ( 26 , 27 ) to evaluate both legs for the presence of deep venous thrombosis . Transfusion Policy Transfusion of allogeneic blood was performed according to the usual practice of attending surgeons and anesthesiologists . We did not establish criteria for transfusion ; however , the usual policy in Canada is not to perform transfusion in asymptomatic patients on the basis of a specific hemoglobin threshold . No patient donated or received autologous blood . Outcome Measures The primary outcome measure was occurrence of allogeneic blood transfusion . Secondary outcomes were changes in reticulocyte count and hemoglobin concentration . Adverse events were determined according to World Health Organization criteria ( 28 ) . The proportion of patients who experienced thromboembolic disease ( proximal or distal deep venous thrombosis and pulmonary embolus ) and serious adverse events was compared among the treatment groups . Statistical Analysis Before the start of the study , retrospective chart review was performed to estimate the transfusion rate in patients undergoing hip arthroplasty ( n = 471 ) who had characteristics similar to those of our patients . In those patients , the rate of allogeneic transfusion was 39 % ( 95 % CI , 34 % to 43 % ) . The reduction in the transfusion rate considered clinical ly important was 20 % . On the basis of pharmacokinetic data , the higher dose of epoetin alfa was judged likely to be more efficacious ( 29 ) than the lower dose . Therefore , we estimated that the transfusion rate would decrease from 40 % to 15 % in the high-dose group and from 40 % to 20 % in the low-dose group . In accordance with these assumptions , we used an asymmetric r and omization schedule that allocated a greater number of patients to the low-dose epoetin alfa and placebo groups ( 5 patients for every 3 that were allocated to the high-dose epoetin alfa group ) . This maneuver ensured adequate statistical power ( 80 % ) to compare the transfusion rate in the high-dose and low-dose groups with that in the placebo group . Since an allowance of 5 % was made for unevaluable patients , 83 patients per group were required in the low-dose and placebo groups and 50 patients were needed in the high-dose group . Accordingly , the total sample size requirement was 216 patients . All statistical analyses of efficacy measures were performed on an intention-to-treat basis , which was prospect ively defined to include patients who had received at least one dose of study medication and subsequently underwent surgery within 1 week of the scheduled date . Separate chi-square tests were done to compare the proportion of patients who required transfusion in the placebo group with that among patients assigned to the low-dose epoetin alfa group or the high-dose epoetin alfa group . Bonferroni correction was used as a conservative method of adjusting for multiple comparisons ( 30 ) . Accordingly , an error of 0.025 was considered to indicate statistical significance . Continuous outcome measures were compared by using analysis of variance . Logistic regression analyses were performed to explore the relationship between occurrence of transfusion and age , sex , weight , body mass index , predicted blood volume , baseline reticulocyte count , preoperative reticulocyte count , change in reticulocyte count , baseline hemoglobin concentration , preoperative hemoglobin concentration , change in hemoglobin concentration , baseline serum ferritin level , preoperative serum ferritin level , baseline serum iron level , preoperative serum iron level , number of days receiving iron therapy before surgery , baseline erythropoietin level , and treatment with epoetin alfa . Variables significant at the 0.10 level were examined further in a A multicenter , r and omized , open-label , parallel-group study was conducted to compare the safety and efficacy of perioperative recombinant human erythropoietin ( Epoetin alfa ) with the safety and efficacy of preoperative autologous donation ( PAD ) in total joint arthroplasty . A total of 490 patients scheduled for total joint ( i.e. , hip or knee ) surgery and having hemoglobin ( Hb ) levels > or = 11 to < or = 13 g/dL were r and omized to receive weekly doses of subcutaneous Epoetin alfa on preoperative Days -21 , -14 , and -7 , and on the day of surgery , or to participate in a PAD program . The mean baseline Hb level in both groups was 12.3+/-0.6 g/dL , increasing to 13.8 g/dL in the Epoetin alfa-treated group and decreasing to 11.1 g/dL in the PAD group before or on the day of surgery . In the PAD group , 156/219 ( 71.2 % ) patients were transfused with autologous blood , and 42/219 ( 19.2 % ) patients were transfused with allogeneic blood . A smaller proportion , 27/209 ( 12.9 % ) patients , in the Epoetin alfa-treated group were transfused with allogeneic blood ( P = .078 compared with the PAD group ) . Moreover , patients in the PAD group received a total of 325 units of blood ( 79 allogeneic units and 246 autologous units ) compared with patients in the Epoetin alfa group who received a total of 54 units of blood . The mean postoperative Hb level was 11.0 g/dL in the Epoetin alfa-treated group and 9.2 g/dL in the PAD group . Compared with the PAD arm , mean Hb levels measured preoperatively , postoperatively on Day 1 , and at discharge visits were significantly greater in the Epoetin alfa-treated arm ( P < .0001 ) This prospect i ve r and omised clinical trial evaluated the effect of alternatives for allogeneic blood transfusions after total hip replacement and total knee replacement in patients with pre-operative haemoglobin levels between 10.0 g/dl and 13.0 g/dl . A total of 100 patients were r and omly allocated to the Eprex ( pre-operative injections of epoetin ) or Bellovac groups ( post-operative retransfusion of shed blood ) . Allogeneic blood transfusions were administered according to hospital policy . In the Eprex group , 4 % of the patients ( two patients ) received at least one allogeneic blood transfusion . In the Bellovac group , where a mean 216 ml ( 0 to 700 ) shed blood was retransfused , 28 % ( 14 patients ) required the allogeneic transfusion ( p = 0.002 ) . When comparing Eprex with Bellovac in total hip replacement , the percentages were 7 % ( two of 30 patients ) and 30 % ( nine of 30 patients ) ( p = 0.047 ) respectively , whereas in total knee replacement , the percentages were 0 % ( 0 of 20 patients ) and 25 % ( five of 20 patients ) respectively ( p = 0.042 ) . Pre-operative epoetin injections are more effective but more costly in reducing the need for allogeneic blood transfusions in mildly anaemic patients than post-operative retransfusion of autologous blood BACKGROUND Preoperative anemia has been associated with increased risk of allogeneic blood transfusion and postoperative morbidity and mortality . The prevalence of preoperative anemia and its association with postoperative outcomes has not previously been reported in relation to fast-track elective total hip arthroplasty ( THA ) and total knee arthroplasty ( TKA ) . We aim ed to evaluate the prevalence of preoperative anemia in elective fast-track THA and TKA and its association with risk of perioperative transfusion , prolonged length of hospital stay ( LOS ) , and postoperative readmission . STUDY DESIGN AND METHODS This was a prospect i ve observational data base study with data obtained from six high-volume Danish fast-track surgical centers . Preoperative hemoglobin and patient demographics were collected prospect ively using question naires while outcome and transfusion data were collected using national data bases and patient charts . Adjusted risk estimates for transfusion , prolonged LOS , and all-cause readmission according to preoperative anemia status were obtained by multivariate logistic regression . RESULTS A total of 5.165 THA or TKA procedures were included with a mean patient age of 67 ± 11 years and a median LOS of 2 ( interquartile range , 2 - 3 ) days . A total of 662 patients ( 12.8 % ) had preoperative anemia according to World Health Organization classification . Preoperative anemia was associated with increased risk of receiving transfusion during admission ( odds ratio [ OR ] , 4.7 ; 95 % confidence interval [ CI ] , 3.8 - 5.8 ) , increased risk of readmission within 90 days from surgery ( OR , 1.4 ; 95 % CI , 1.1 - 1.9 ) , and increased risk of LOS of more than 5 days ( OR , 2.5 ; 95 % CI , 1.9 - 3.4 ) after adjustment for preoperative patient-related risk factors . CONCLUSION Preoperative anemia in elective fast-track THA and TKA is independently associated with transfusion and increased postoperative morbidity , supporting the need for preoperative evaluation and treatment Background The primary objective of this study was to assess the number of erythropoietin ( EPO ) injections required to reach a hematocrit ( Ht ) of 40 % in moderately anemic patients . The secondary objective was to compare this strategy with autologous blood donation ( ABD ) in elective orthopedic surgery in terms of red blood cell ( RBC ) production . Study design and methods 93 patients with a baseline Ht between 30 and 39 % were r and omized into two groups the day of the preoperative assessment . In the EPO group , patients received 40,000 UI/week sc until they reached a maximal Ht of 40 % . In the ABD group , a RBC pack was collected every week as long as the Ht was above 33 % . Results Two EPO injections were necessary to reach a 40 % Ht in 63 % of the patients . It was possible to collect two RBC packs in 45 % of the patients in the ABD group . Volume of RBC production was significantly higher in the EPO group : 268 ± 142 mL vs 141 ± 129 ( P = 0.0001 ) . In the EPO group , Ht was significantly higher on days one and three after surgery and at discharge . The energy score was better in the EPO group . In the ABD group , 12.6 % patients vs 6.5 % in the EPO group received allogeneic transfusion ( ns ) . Conclusion Only two EPO injections were sufficient to reach a Ht of 40 % in the majority of patients . Therefore , to improve cost/effectiveness , the number of EPO injections should be related to baseline Ht instead of the four injections recommended in the product monograph . RésuméObjectifÉvaluer le nombre d’injections d’érythropoïétine ( EPO ) nécessaires pour atteindre un hématocrite ( Ht ) de 40 % chez des patients modérément anémiques . Aussi , comparer cette stratégie avec le don de sang autologue ( DSA ) en chirurgie orthopédique réglée en termes de production de globules rouges (GR).MéthodeDes patients ( n = 93 ) présentant un Ht de base de 30 à 39 % ont été répartis en deux groupes le jour de l’évaluation préopératoire . Ceux du groupe EPO ont reçu 40,000 UI/semaine sc jusqu’à ce qu’ils présentent un Ht maximal de 40 % . Dans le groupe DSA , un culot globulaire a été prélevé chaque semaine tant que l’Ht était au-dessus de 33%.RésultatsIl a fallu deux injections d’EPO pour atteindre un Ht de 40 % chez 63 % des patients . Il a été possible de prélever deux culots chez 45 % des patients du groupe DSA . Le volume de production de GR a été significativement plus élevé chez ceux du groupe EPO : 268 ± 142mL vs 141 ± 129 ( P = 0,0001 ) . Dans le groupe EPO , l’Ht a été significativement plus élevé aux jours un et trois après l’opération et au moment du congé . Le score d’asthénie était moins prononcé dans le groupe EPO . Une transfusion allogénique a été faite chez 12,6 % des patients du groupe DSA vs 6,5 % du groupe EPO ( ns ) . Conclusion Il a suffi de deux injections d’EPO seulement pour atteindre un Ht de 40 % chez la majorité des patients . Donc , pour améliorer l’efficacité des coûts , il faudrait relier le nombre d’injection d’EPO à l’Ht de base plutôt que de faire les quatre injections recomm and ées dans la monographie du produit Background and objective : Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications , such as postoperative infection due to immune suppression and thus hospitalization time . This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate . Methods : In an open r and omized controlled multicentre trial in patients undergoing orthopaedic surgery , the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries . Haemoglobin ( Hb ) values , transfusions , time to ambulation , time to discharge , infections and safety were evaluated in patients with preoperative Hb concentrations 10‐13 g dL−1 ( on‐treatment population : epoetin n = 460 ; control n = 235 ) , from study entry until 4‐6 weeks after surgery . Outcome was also compared in patients with and without transfusion . Results : Epoetin‐treated patients had higher Hb values from the day of surgery until discharge ( P < 0.001 ) and lower transfusion rates ( 12 % vs. 46 % ; P < 0.001 ) . Epoetin treatment delivered no significant effect on postoperative recovery ( time to ambulation , time to discharge and infection rate ) . However , the time to ambulation ( 3.8 ± 4.0 vs. 3.1 ± 2.2 days ; P < 0.001 ) and the time to discharge ( 12.9 ± 6.4 vs. 10.2 ± 5.0 days ; P < 0.001 ) was longer in the transfused than in the non‐transfused patients . Side‐effects in both groups were comparable . Conclusions : Epoetin alfa increases perioperative Hb concentration in mild‐to‐moderately anaemic patients and thus reduces transfusion requirements . Patients receiving blood transfusions require a longer hospitalization than non‐transfused patients IMPORTANCE There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury . OBJECTIVE To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds ( 7 and 10 g/dL ) on neurological recovery after traumatic brain injury . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 200 patients ( erythropoietin , n = 102 ; placebo , n = 98 ) with closed head injury who were unable to follow comm and s and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012 . The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20 % and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications . Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks ( n = 74 ) and then the 24- and 48-hour doses were stopped for the remainder of the patients ( n = 126 ) . There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS Intravenous erythropoietin ( 500 IU/kg per dose ) or saline . Transfusion threshold maintained with packed red blood cells . MAIN OUTCOMES AND MEASURES Glasgow Outcome Scale score dichotomized as favorable ( good recovery and moderate disability ) or unfavorable ( severe disability , vegetative , or dead ) at 6 months postinjury . RESULTS There was no interaction between erythropoietin and hemoglobin transfusion threshold . Compared with placebo ( favorable outcome rate : 34/89 [ 38.2 % ; 95 % CI , 28.1 % to 49.1 % ] ) , both erythropoietin groups were futile ( first dosing regimen : 17/35 [ 48.6 % ; 95 % CI , 31.4 % to 66.0 % ] , P = .13 ; second dosing regimen : 17/57 [ 29.8 % ; 95 % CI , 18.4 % to 43.4 % ] , P < .001 ) . Favorable outcome rates were 37/87 ( 42.5 % ) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 ( 33.0 % ) for 10 g/dL ( 95 % CI for the difference , -0.06 to 0.25 , P = .28 ) . There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL ( 22/101 [ 21.8 % ] vs 8/99 [ 8.1 % ] for the threshold of 7 g/dL , odds ratio , 0.32 [ 95 % CI , 0.12 to 0.79 ] , P = .009 ) . CONCLUSIONS AND RELEVANCE In patients with closed head injury , neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL result ed in improved neurological outcome at 6 months . The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events . These findings do not support either approach in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00313716 In patients scheduled to undergo major orthopedic surgery , predonation of autologous blood ( AB ) has emerged as a means of avoiding subsequent exposure to allogeneic blood . However , patients with a baseline hematocrit ( Hct ) less than 40 % may not be able to donate sufficient AB to fully meet their requirements . In female patients with a baseline Hct < or = 39 % , epoetin alfa ( 300 to 600 IU/kg twice weekly for 3 weeks ) significantly increased the amount of AB donated prior to elective orthopedic surgery and significantly reduced allogeneic blood requirements in comparison with placebo . Iron availability was a critical factor in determining the response to epoetin alfa . In these patients , parenteral supplementation with iron saccharate significantly increased the amount of AB donated and the volume of red blood cells ( RBCs ) collected in comparison with oral iron alone . Parenteral iron supplementation , therefore , ensures that sufficient iron is available to meet the dem and s of epoetin alfa-accelerated erythropoiesis in patients enrolled in an AB donation program Purpose Our aim was to evaluate the effectiveness of two different dosing regimens of human recombinant erythropoietin ( rHu-EPO ) for preoperative autologous blood collection in patients undergoing total hip arthroplasty ( THA ) . Methods Prospect i ve r and omised trials in which erythropoietin 15,000 IU was administered intravenously twice a week or 30,000 IU once a week ( total 90,000 IU ) combined with ferrous II sulphate ( Ferro-Gradumet 2 ) orally and compared with Ferro-Gradumet 2 alone . Results Although different dosing regimens of rHu-EPO administration during preoperative autologous blood donation have similar effects on the collection of two units of autologous blood , preoperative haemoglobin level and perioperative allogenic blood transfusion , a once weekly dose regimen of rHu-EPO was more convenient ( although not statistically significantly ) for patients . Conclusion We recommend the more practical and comfortable but yet highly effective therapeutic regimen with a single weekly intravenous administration of rHu-EPO for patients scheduled for THA BACKGROUND Previous reports have suggested that the use of recombinant human erythropoietin is effective for decreasing the need for perioperative allogeneic blood transfusion . The purpose of this study was to evaluate the efficacy of erythropoietin in combination with , and compared with , preoperative autologous donation for reducing allogeneic blood requirements for total joint arthroplasty . METHODS Two hundred and forty patients undergoing primary and revision total hip or knee arthroplasty were enrolled into three groups with different treatment regimens : ( 1 ) erythropoietin and preoperative autologous donation ( Group 1 ) , ( 2 ) erythropoietin alone ( Group 2 ) , and ( 3 ) preoperative autologous donation alone ( Group 3 ) . Patients were evaluated with regard to requirements for allogeneic transfusion , change from the baseline to the lowest postoperative hemoglobin value , postoperative complications , and adverse reactions . RESULTS The rate of allogeneic transfusion was 11 % in Group 1 ( erythropoietin and preoperative autologous donation ) compared with 28 % in Group 2 ( erythropoietin alone ) and 33 % in Group 3 ( preoperative autologous donation alone ) . Within Group 1 , patients who had a unilateral primary arthroplasty had an allogeneic transfusion rate of 4 % and those who had a bilateral or revision arthroplasty had an allogeneic transfusion rate of 17 % . In Groups 2 and 3 , the allogeneic transfusion rates were 14 % and 15 % , respectively , for the patients who had a unilateral primary arthroplasty and 35 % and 47 % , respectively , for those who had a bilateral or revision arthroplasty . CONCLUSIONS Preoperative use of erythropoietin in conjunction with preoperative autologous donation reduces the need for allogeneic blood transfusion associated with total joint arthroplasty more effectively than does either erythropoietin or preoperative autologous donation alone INTRODUCTION Thromboembolic events ( TEE ) are serious complications after total hip ( THA ) and knee arthroplasty ( TKA ) , with reported in-hospital incidences of about 0.5 - 1 % for venous thromboembolic events ( VTE ) and 0.2 % for myocardial infa rct ions ( MI ) and stroke . However , little data exist on in-hospital TEE when using a st and ardized fast-track protocol with early mobilization . MATERIAL S AND METHODS A large detailed cohort study in primary unilateral THA and TKAs on " early " ( in-hospital or after discharge but within 1week of surgery ) and 30-days TEEs , including prospect i ve recording of patient characteristics , complete follow-up through the Danish National Patient Register , and detailed evaluation on disposing factors and consequences of " early " TEEs through review of medical records . RESULTS In 13,775 procedures with a median LOS of 2days , 43 ( 0.32 % ; 95 % CI : 0.23 - 0.42 ) " early " and 90 ( 0.65 % ; 95 % CI : 0.53 - 0.80 ) 30-day TEEs were recorded . " Early " TEEs consisted of 9 ( 0.07 % ; 95 % CI : 0.04 - 0.13 ) MI , 10 ( 0.08 % 95 % CI : 0.04 - 0.13 ) strokes , 13 ( 0.09 % ; 95 % CI : 0.05 - 0.16 ) pulmonary embolisms and 11 ( 0.08 % ; 95 % CI : 0.04 - 0.15 ) deep venous thromboses . Most TEEs were in patients with irreversible dispositions ( e.g. previous TEE , high age and cardiac disease ) , but 5 of 9 MIs were associated with postoperative anemia . All in-hospital VTE ( n : 16 ) occurred while patients received recommended thromboprophylaxis . CONCLUSIONS Incidence of " early " TEEs after fast-track THA and THA is low , but MIs may be further reduced by improving perioperative treatment of anemia . Further research is needed regarding interventions for prevention of " early " TEE in disposed patients BACKGROUND Preoperative treatment with rHuEPO ( epoetin alfa : EPREX , Janssen-Cilag ; or PROCRIT , Ortho Biotech ) in conjunction with iron supplementation increases the erythropoietic response in elective orthopedic surgery patients , but it is not known whether the magnitude of this response is dependent on the route of iron administration . STUDY DESIGN AND METHODS Non-iron-deficient patients undergoing elective orthopedic surgery ( N = 110 ) with baseline Hb > or = 10 to < or = 13 g per dL were r and omly assigned to receive either epoetin alfa ( 600 IU/kg ) plus IV iron ( n = 29 ) or oral iron ( n = 29 ) or placebo plus IV iron ( n = 25 ) or oral iron ( n = 27 ) in this 14-day study . RBC production , Hb , Hct , reticulocytes , iron status , and adverse events were monitored throughout the study . RESULTS Epoetin alfa treatment plus either oral or IV iron supplementation significantly increased total RBC production , Hb , Hct , and reticulocytes over the values seen with the respective placebo treatments ( p = 0.0001 ) . There were no differences between the epoetin alfa treatment groups . Placebo treatment plus oral or IV iron supplementation was not associated with increases in hematologic values . There were no differences in the incidence of adverse events among the treatment groups . CONCLUSION There was a comparable erythropoietic response to epoetin alfa , irrespective of the route of iron administration . The route of iron administration , therefore , does not modulate the erythropoietic response to epoetin alfa in patients who are not iron deficient . Safety and convenience benefits may be gained by adopting oral iron supplementation in this patient subset Background : Controversy exists about the advantages of predeposit of autologous blood ( PDAB ) , and whether more comfortable blood conservation regimens may yield comparable results . To test the hypothesis that preoperative treatment with recombinant human erythropoietin ( rHuEPO ) with or without acute concomitant normovolaemic haemodilution ( ANHD ) is as effective as PDAB in reducing allogeneic blood transfusions , we conducted a prospect i ve r and omised study in women undergoing primary hip replacement This study evaluated whether patients receiving a two-dose regime of epoetin alfa received less allogeneic blood than patients donating autologous blood before primary hip arthroplasty . Consenting patients with a hemoglobin level between 12 and 15 g/dL were r and omly assigned to a two-dose administration of epoetin alfa ( 19 patients ) or autologous donation ( 21 patients ) . Sixteen percent of the patients in the epoetin alfa group and 52 % of the patients in the autologous donation group received transfusions , with a mean volume of 90 cc per patient in the epoetin alfa group and 340 cc in the autologous donation group . Hemoglobin was similar at screening ; however , the epoetin alfa group achieved a higher hemoglobin ( 14.6 g/dL ) than the autologous donation group ( 12.6 g/dL ) before surgery . Hemoglobin remained significantly higher in the epoetin alfa group for 3 days after surgery . Administration of two doses of epoetin alfa provided patients with effective and safe reduction of allogeneic blood transfusions and decreased the necessity and difficulty of autologous donation before total hip arthroplasty Background : Patient blood management combines the use of several transfusion alternatives . Integrated use of erythropoietin , cell saver , and /or postoperative drain reinfusion devices on allogeneic erythrocyte use was evaluated using a restrictive transfusion threshold . Methods : In a factorial design , adult elective hip- and knee-surgery patients with hemoglobin levels 10 to 13 g/dl ( n = 683 ) were r and omized for erythropoietin or not , and subsequently for autologous reinfusion by cell saver or postoperative drain reinfusion devices or for no blood salvage device . Primary outcomes were mean allogeneic intra- and postoperative erythrocyte use and proportion of transfused patients ( transfusion rate ) . Secondary outcome was cost-effectiveness . Results : With erythropoietin ( n = 339 ) , mean erythrocyte use was 0.50 units (U)/patient and transfusion rate 16 % while without ( n = 344 ) , these were 0.71 U/patient and 26 % , respectively . Consequently , erythropoietin result ed in a nonsignificant 29 % mean erythrocyte reduction ( ratio , 0.71 ; 95 % CI , 0.42 to 1.13 ) and 50 % reduction of transfused patients ( odds ratio , 0.5 ; 95 % CI , 0.35 to 0.75 ) . Erythropoietin increased costs by & OV0556;785 per patient ( 95 % CI , 262 to 1,309 ) , that is , & OV0556;7,300 per avoided transfusion ( 95 % CI , 1,900 to 24,000 ) . With autologous reinfusion , mean erythrocyte use was 0.65 U/patient and transfusion rate was 19 % with erythropoietin ( n = 214 ) and 0.76 U/patient and 29 % without ( n = 206 ) . Compared with controls , autologous blood reinfusion did not result in erythrocyte reduction and increased costs by & OV0556;537 per patient ( 95 % CI , 45 to 1,030 ) . Conclusions : In hip- and knee-replacement patients ( hemoglobin level , 10 to 13 g/dl ) , even with a restrictive transfusion trigger , erythropoietin significantly avoids transfusion , however , at unacceptably high costs . Autologous blood salvage devices were not effective BACKGROUND Previous clinical trials have shown that the use of recombinant human erythropoietin ( EPO ) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation . However , the role of EPO therapy in nonanemic patients remains undefined . To identify this role , a r and omized , controlled , multicenter dose-escalation trial was conducted in patients whose initial hematocrit was > 39 percent ( 0.39 ) . STUDY DESIGN AND METHODS EPO ( 150 , 300 , or 600 units/kg ) or placebo was administered intravenously at each of six phlebotomy visits over a 3-week study period . Sixteen ( 14 % ) of 116 patients were unable to complete the treatment protocol because of adverse events ( n = 11 ) or for personal reasons ( n = 5 ) ; 2 patients ( 1 EPO and 1 placebo ) experienced serious adverse events . RESULTS In 91 evaluable patients , additional red cell production during the study period was 440 + /- 176 , 621 + /- 215 , 644 + /- 196 , and 856 + /- 206 mL ( mean + /- SD ) , respectively , for patients receiving placebo and EPO at 150 , 300 , and 600 units/kg ( p < 0.05 for all EPO groups compared to placebo ) . However , the percentages of patients in each group who received allogeneic blood did not differ : 2 ( 9 % ) of 23 placebo patients and 6 ( 9 % ) of 68 EPO patients . CONCLUSION It is concluded that , while EPO therapy increased preoperative red cell production , no clinical benefit could be demonstrated in autologous blood donors who were not anemic at first blood donation Background : Recombinant human erythropoietin in combination with preoperative autologous blood donation is an established regime for avoiding allogenic blood transfusions . The aim of the study was to determine endogenous erythropoietin production and haemoglobin recovery after preoperative autologous blood donation and surgery , with or without recombinant human erythropoietin treatment This r and omized trial assessed the effect of recombinant human erythropoietin ( EPO ) vs preoperative autologous donation ( PAD ) on postoperative vigor and h and grip strength in patients undergoing primary total joint arthroplasty . Adults with baseline hemoglobin level of 11 to 14 g/dL received EPO ( 600 IU/kg once weekly for 4 doses , n = 130 ) or PAD ( n = 121 ) before primary , unilateral hip or knee arthroplasty . Mean changes in vigor score and h and grip strength from baseline were not significantly different between treatment groups . Multivariate analyses found a significant treatment effect favoring EPO over PAD for vigor , but not for h and grip strength . Patients in the EPO group had higher hemoglobin levels and required fewer transfusions . Both treatments were well tolerated . Additional study is needed to eluci date the influence of blood management strategies on postoperative vigor BACKGROUND This r and omized controlled study was undertaken to determine the effect of recombinant human erythropoietin ( rHuEPO ) on erythropoiesis , autologous blood collection , and allogeneic transfusion risk in elective surgery patients with low baseline hematocrits . STUDY DESIGN AND METHODS Patients ( n = 204 ) with low baseline hematocrits ( < or = 39 % ) , scheduled for orthopedic surgery within 25 to 35 days , were seen every 3 to 4 days for 21 days . At each visit , 450 mL of blood was collected if the hematocrit was > or = 33 percent , and rHuEPO ( 600 U/kg ) or placebo was administered intravenously . RESULTS One hundred seventy-three patients were evaluable . The number of autologous units collected from the rHuEPO and control groups , respectively , was 4.5 + /- 1.0 and 3.0 + /- 1.1 ( p < 0.001 ) , and marrow production of red cells increased by 668 + /- 222 and 353 + /- 155 mL over and above baseline production ( p < 0.05 ) . Allogeneic blood transfusion was required by 31 percent of control and 20 percent of rHuEPO patients ( p = 0.09 ) . Excluding 8 patients who received > 6 units , 29 percent of control and 14 percent of rHuEPO patients required allogeneic blood ( p = 0.015 ) . Logistic regression modeling determined that the risk of allogeneic transfusion was reduced by rHuEPO ( p = 0.025 ) . CONCLUSION The use of rHuEPO stimulates erythropoiesis , permits the storage of more autologous blood , and reduces allogeneic transfusion risk in patients with low hematocrits who are undergoing elective orthopedic surgery . Additional studies are necessary to determine the optimal schedules of rHuEPO administration and autologous blood collection as well as the cost-effectiveness of this strategy BACKGROUND The authors examined the impact of parenteral iron and recombinant human erythropoietin-β ( rHuEPO-β ) administered in the bilateral total knee replacement arthroplasty ( TKRA ) , on postoperative anemia and transfusion requirements in iron-deficient patients . STUDY DESIGN AND METHODS A total of 108 iron-deficient patients were r and omly assigned to two groups : Group C ( control ) or Group IE ( 200 mg of iron sucrose intravenously over 1 hr and 3000 IU of rHuEPO-β subcutaneously during the operation and during the postoperative period if the hemoglobin [ Hb ] level was 70 - 80 g/L ) . One or 2 units of blood were transfused to patients in both groups according to postoperative Hb level ( between 60 and 70 g/L or betweeen 50 and 60 g/L , respectively ) . Perioperative laboratory and clinical outcomes ( Hb , iron variables , postoperative bleeding amount , and number of units of RBCs transfused and incidences ) were documented . RESULTS Although preoperative Hb and the amount of postoperative bleeding were comparable in the two groups , Hb levels at 1 , 2 , and 3 days and at 2 and 6 weeks postoperation were significantly higher in Group IE . Furthermore , the transfusion rate was significantly lower in Group IE ( 20.4 % vs. 53.7 % , p=0.011 ) and the mean number of red blood cell units transfused was markedly lower in Group IE ( 0.2±0.5 vs. 0.8±0.8 , p=0.005 ) . Postoperative iron , ferritin , and transferrin saturation levels were significantly higher in Group IE . CONCLUSIONS Treatment with parenteral iron and low-dose rHuEPO-β in bilateral TKRA effectively attenuated anemia and decreased transfusion requirements in iron-deficient patients This r and omized , multicentre , parallel-group study assessed the efficacy of epoetin beta in reducing the transfusion frequency in patients ineligible for autologous blood donation prior to surgery . The patients ( n = 194 ) received either epoetin beta ( 125 or 250 IU/kg , once weekly ) or no therapy for 3–4 weeks before surgery . The pre-operation haemoglobin levels were markedly increased in the epoetin beta groups ( 125 IU/kg : + 1.1 g/dl ; 250 IU/kg : + 1.6 g/dl ) , but not in the control group . The transfusion frequency was significantly reduced in both epoetin groups as compared with the control group ( p = 0.046 ) . Epoetin beta was well tolerated , and no serious adverse events were observed . Low-dose administration of epoetin beta before elective surgery reduces the transfusion frequencies in patients not eligible for autologous blood donation We have prospect ively evaluated the efficacy of an individualized pre-operative blood saving protocol in elective total hip arthroplasty ( THA ) or total knee arthroplasty ( TKA ) . The primary aim was to obtain a pre-operative haemoglobin ( Hb ) level of > or = 14 g dL(-1 ) . A reduction in requirements for allogeneic transfusion was considered the second aim . Several strategies are available for increasing pre-operative Hb levels and reducing red blood cell ( RBC ) transfusions following THA or TKA , but the success of these programmes depends on selecting the most appropriate treatment for each patient . Three hundred and five patients with an indication of elective THA or TKA were individually assigned to the following strategies according to Hb and ferritin levels and medical conditions : ( a ) no pre-operative intervention , ( b ) oral iron therapy , ( c ) intravenous ( i.v . ) iron therapy , ( d ) recombinant human erythropoietin alpha with i.v . iron and ( e ) pre-operative autologous donation ( PAD ) plus oral iron . Eighty-two percent of the patients reached a pre-operative Hb level of > or = 14 g dL(-1 ) compared with 62 % of patients with Hb levels of > or = 14 g dL(-1 ) at the baseline visit . Treatment with PAD showed a significant reduction in the pre-operative Hb levels . The rate of RBC transfusion was 18.8 % compared with 31.5 % of matched historic group ( P < 0.001 ) . In conclusion , all patients scheduled to undergo THA or TKA should be c and i date s for an individualized pre-operative blood salvage programme |
13,471 | 19,588,335 | Adverse events occurred more frequently with combination therapy than placebo , but were generally described as mild to moderate in severity and rarely led to withdrawal .
Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg ; oxycodone is two to three times stronger than codeine .
Efficacy increases when combined with paracetamol .
Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated , comparable to commonly used non-steroidal anti-inflammatory drugs , with the benefit of longer duration of action | BACKGROUND Oxycodone is a strong opioid agonist used to treat severe pain .
It is commonly combined with milder analgesics such as paracetamol .
This review up date s a previous review that concluded , based on limited data , that all doses of oxycodone exceeding 5 mg , with or without paracetamol , provided analgesia in postoperative pain , but with increased incidence of adverse events compared with placebo .
Additional new studies provide more reliable estimates of efficacy and harm .
OBJECTIVES To assess efficacy , duration of action , and associated adverse events of single dose oral oxycodone , with or without paracetamol , in acute postoperative pain in adults . | Purpose : To test the hypothesis that an experienced surgeon is associated with less postoperative nausea and vomiting ( PONV ) BACKGROUND Combination therapy has been widely used for the clinical management of acute pain . By combining 2 drugs with different mechanisms of action , such therapy provides additive analgesic effects while reducing the risk for adverse effects . OBJECTIVE This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo in a dental pain model . METHODS This was a multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group , single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars . Patients were r and omly assigned to receive oxycodone 5 mg/ibuprofen 400 mg , oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , or placebo . The primary outcome measures were total pain relief through 6 hours after dosing ( TOTPAR6 ) , sum of pain intensity differences through 6 hours ( SPID6 ) , and adverse events . Secondary efficacy measures included SPID3 and TOTPAR3 , peak pain relief , peak pain intensity difference , time to onset of pain relief , time to use of rescue medication , proportion of patients reporting pain half gone , and the patient 's global evaluation . RESULTS Two hundred forty-nine patients ( 43.5 % male ; 87.5 % white ; mean age , 19.1 years ; mean body weight , 153.6 pounds ) were r and omized to treatment as follows : 62 to oxycodone 5 mg/ibuprofen 400 mg , 61 to oxycodone 5 mg/acetaminophen 325 mg , 63 to hydrocodone 7.5 mg/acetaminophen 500 mg , and 63 to placebo . Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo ( mean [ SD ] TOTPAR6 , 14.98 [ 5.37 ] , 9.53 [ 6.77 ] , 8.36 [ 6.68 ] , and 5.05 [ 6.49 ] , respectively ; P < 0.001 , oxycodone 5 mg/ibuprofen 400 mg vs all other treatments ) . SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments ( mean : 7.78 [ 4.11 ] , 3.58 [ 4.64 ] , 3.32 [ 4.73 ] , and 0.69 [ 4.85 ] ; P < 0.001 ) . Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points ( P < 0.001 , all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [ P = 0.006 ] ) , with the exception of the time to onset of analgesia . The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg ( 6.5 % and 3.2 % , respectively ) and placebo ( 3.2 % and 1.6 % ) . Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg ( P = 0.011 and P = 0.009 , respectively ) but not with hydrocodone 7.5 mg/acetaminophen 500 mg . CONCLUSIONS In this study in patients with moderate to severe pain after surgery to remove impacted third molars , oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested , and was associated with fewer adverse events In this double-blind , parallel-group study , we compared 3 oxymorphone immediate-release ( IR ) doses with placebo for efficacy and with oxycodone IR and placebo for safety in patients with acute moderate-to-severe postsurgical pain . During the single-dose phase ( n = 300 ) , patients received oxymorphone IR 10 , 20 , or 30 mg ; oxycodone IR 10 mg ; or placebo . All oxymorphone IR doses were superior for providing pain relief for 8 h ( P < 0.05 ) , with a significant analgesic dose response ( P < 0.001 ) . Significant pain intensity differences occurred by 45 min ( 20- and 30-mg doses ; P < 0.05 ) . Discontinuations for lack of efficacy totaled 42 % among placebo-treated patients and 27 % among those treated with oxymorphone IR . Patients requiring rescue medication after 3 h were allowed to receive additional study drug every 4 to 6 h as needed for the multiple-dose phase ( n = 164 ) . All oxymorphone groups maintained analgesia for 48 h. The median dosing interval was > 9.5 h for oxymorphone IR 30 mg and ≥7 h for the other groups . Opioid-related adverse events , similar among groups , were generally mild or moderate . Oxymorphone IR 10 , 20 , or 30 mg provided significant dose-related pain relief compared with placebo , and this relief was maintained over several days with a safety profile comparable to that of oxycodone IR The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug , flurbiprofen , and a long-acting local anesthetic , etidocaine , was evaluated for the suppression of acute postoperative pain . Subjects having two impacted third molars removed at two appointments received either the experimental combination or st and ard treatment in a r and omized , crossover design . The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery , 1.5 % etidocaine with 1:200,000 epinephrine five minutes before surgery , and 100 mg flurbiprofen three hours after surgery . St and ard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery , 2 % lidocaine with 1:100,000 epinephrine five minutes before surgery , and a second dose of the oxycodone-acetaminophen combination three hours after surgery . Pain intensity was rated hourly from one to seven hours after surgery , using a variety of ordinal and analog scales . The flurbiprofen-etidocaine combination result ed in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients . This study shows that pretreatment with a nonsteroidal anti-inflammatory drug , flurbiprofen , in combination with a long-acting local analgesic , etidocaine , suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability STUDY OBJECTIVE To determine whether the addition of morphine to the axillary block local anesthetic solution provides improved or prolonged postoperative analgesia . DESIGN Prospect i ve , r and omized , double-blind clinical trial with 24-hour follow-up . SETTING Ambulatory unit of a large academic referral center . PATIENTS Consecutive healthy volunteers scheduled for elective upper extremity surgery . INTERVENTIONS Patients in the treatment group ( AX ) were given intravenous ( IV ) saline and had morphine 0.1 mg/kg added to their axillary block solution . Control subjects ( CT ) received morphine 0.1 mg/kg IV and had saline added to their axillary block solution . All axillary blocks were performed using 0.55 ml/kg of 1.5 % lidocaine with epinephrine 1:200,000 . MEASUREMENTS AND MAIN RESULTS During the first 24 hours after surgery , visual analog scale ( VAS ) scores , supplementary analgesic ( oxycodone 5 mg with acetaminophen 500 mg ) use , and complications were recorded . Both groups had similar VAS scores throughout the study . In the 24-hour postoperative study period , AX patients required approximately half as many doses ( median , 2 doses ; range , 0 to 7 doses of supplemental analgesic as CT patients ( median , 4 doses ; range , 0 to 12 doses ) . There were no major complications in either group . CONCLUSIONS The addition of morphine 0.1 mg/kg to the local anesthetic axillary block solution provided improved postoperative analgesia without an increased frequency of side effects or major complications Fifty – four orthopaedic patients were given either indomethacin ( 25–50 mg bolus plus infusion , 5–7.5 mg h‐1 ) or only lactated Ringer solution intravenously over 20 h in a r and omized and double – blind fashion . The study was started at the casualty department as soon as possible after the decision to operate was made . The patients were given a spinal block with bupivacaine , and the evaluation included postoperative analgesia and IVY bleeding times . Indomethacin plasma concentrations were measured and found to be at a therapeutic level throughout the study . The oxycodone dose ( mean s.d . ) during the postoperative observation was lower in the indomethacin group ( 17.4 13.7 mg ) than in the control group ( 25.6 15.6 mg ) ( P = 0.05 ) . Fewer patients in the indomethacin group needed oxycodone more than once during the follow – up period ( P < 0.001 ) . The mean IVY bleeding time was prolonged in the indomethacin group after 20 h of infusion ( P < 0.05 ) . No abnormal bleeding was observed immediately postoperatively . However , at the end of the infusion there were more patients who bled through their b and ages and casts in the indomethacin group ( 4/28 vs. 1/26 ) 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 Sixty patients who were scheduled to have an elective total hip or knee arthroplasty were r and omly assigned to one of three groups of twenty patients each before operation with spinal anesthesia . A double-blind technique was used throughout the study . The patients in Group I ( control group ) received hyperbaric 1 per cent tetracaine with epinephrine as the subarachnoid spinal anesthetic ; the patients in Group II ( morphine group ) , hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Duramorph ( morphine sulphate ) , 0.5 milligram ; and those in Group III ( Dilaudid group ) , hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Dilaudid ( hydromorphone hydrochloride ) , 0.002 milligram per kilogram of body weight . During the first twenty-four hours after the operation , the patients in Group II and Group III had significantly less pain compared with those in Group I. This was shown by the use of a visual linear-analog pain scale ( p less than 0.05 ) , the patients ' ratings of the quality of relief of pain ( p less than 0.02 ) , and comparative measurements of the pain-altering medications that were used ( p less than 0.05 ) . The patients in Group II and Group III did not have any more complications or side effects than those in Group I. There was no significant difference in the quality and duration of analgesia between Group II and Group III BACKGROUND . Various medications may be used before , during , or after hair transplantation surgery ( HTS ) with the aims of maximizing patient comfort , reducing unwanted side effects , and improving the results of HTS . OBJECTIVE . The objectives of this study were to determine the current practice pattern and rationale for drug prescribing by a group of leading hair transplant surgeons and to review the literature for the evidence upon which these prescribing patterns were based . METHODS . A postal question naire was sent to 16 hair transplant surgeons from the United States and Canada , and the answers were analyzed . The relevant evidence ‐based literature concerning HTS was review ed by medline search . RESULTS . Question naires suitable for analysis were received from 14 of the surgeons . There were many differences in the pattern of prescribing drugs for the HTS procedure . There was general agreement about the use of local anesthetics but no consensus about the withholding of agents that might increase bleeding ; the use of pre‐ and postoperative analgesics ; the use of topical and systemic antibiotics ; the use of corticosteroids ; or minoxidil . R and omized controlled studies relating to these issues for HTS were not identified in the literature . conclusion . A lack of consensus exists about the drugs used in HTS based on a lack of evidence ‐based medicine Lysine acetylsalicylate ( LAS ) is a soluble salt of acetylsalicylic acid and can be given parenterally . LAS 12.5 mg kg-1 and 25 mg kg-1 were compared with oxycodone 0.15 mg kg-1 in the treatment of pain after operation in 60 patients undergoing varicose vein surgery . Both treatments almost completely relieved moderate to severe pain for the 3-h observation period . The time until the peak of action was longer after LAS ( 60 - 90 min ) than after oxycodone ( 30 - 60 min ) . No significant differences were found between the smaller and larger doses of LAS , suggesting a plateau effect . Further clinical experiments with LAS using i.v . mode of administration and other pain models are warranted Eighty patients undergoing upper abdominal surgery were r and omly allocated to four groups according to the postoperative pain treatment . All patients had a st and ardized balanced anaesthesia and for postoperative analgesia either intramuscular oxycodone and /or metamizol ( IM ) , intercostal block with 0.5 % bupivacaine ( IC ) , epidurally 4 mg morphine ( EM ) or i.v . infusion of fentanyl 0.54—0.99 μg min‐1 + on‐dem and boluses of 7.2–13.5 μg ( ODAG ) were given . The pain intensity 2 h postoperatively was similar in all groups , mean score ranging from 3.2–4.3 on a scale from 0–10 . At 24 h also , when additional intramuscular analgesics had been administered if needed , the mean pain scores did not vary much ; 2.4 in the ODAC group to 3.4 in the IC group . The time until the first request for additional analgesia was longer in the EM group than in the IM group ( 7.5 h vs. 3.5 h ) . There were no differences between the groups in chest X‐ray , peak expiratory flow or respiratory rate postoperatively , but in the capillary blood‐gas analyses there was a greater number of slightly elevated Pco2 values ( 6.0–7.3 kPa ) in the ODAC group than in the others . The amount of fentanyl infused in 24 h to the ODAC patients varied considerably , 814–2233 μg , as did the number of on‐dem and boluses , 3–155 . At 24 h , an efficacy rating “ good ” was distributed as follows : IM 9/20 , IC 11/20 , EM 11/20 and ODAC 13/20 . In the whole patient material 92.5 % rated their condition as “ good ” or “ fair ” Background : For patients with chronic pain , treatment with oral analgesics is considered most convenient and feasible . Sometimes , however , the oral route can not be used because of difficulties with swallowing , nausea , vomiting and gastrointestinal obstruction . To investigate the applicability of the nasal route for the administration of oxycodone , we studied the intravenous and intranasal pharmacokinetics of oxycodone in healthy volunteers BACKGROUND St and ard therapy ( ST ) for postoperative pain after knee and hip replacement at the Hamilton Health Sciences Henderson Hospital consists of epidural analgesia or patient-controlled analgesia for the first 48 hours , followed by oral or parenteral analgesics , or both , on an as-needed basis . We compared the efficacy and safety of scheduled controlled-release ( CR ) oxycodone hydrochloride ( OxyContin ; Purdue Pharma , Pickering , Ont . ) and ST for postoperative pain 48 hours after primary knee and hip replacement . METHODS In 2 separate 3-week studies of similar design , pain intensity , pain relief , length of hospital stay , analgesic use and side effects of CR oxycodone ( n = 70 ) and ST ( n = 101 ) were evaluated . In the CR oxycodone trial , a dose de-escalation protocol was used . RESULTS At the time of discharge from hospital , patients in the CR oxycodone group recorded lower mean ( and st and ard deviation ) pain intensity scores than the ST group ( 20.2 [ 17.9 ] v. 27.7 [ 21.5 ] mm on a 100-mm visual analogue scale ; p = 0.021 ) . Length of hospital stay was 5.5 and 6.4 days for the CR oxycodone and ST groups respectively ( p < 0.001 ) . CR oxycodone patients used less opioid ( morphine equivalent ) while in hospital than ST patients ( p < 0.001 ) , and the average number of daily administrations of analgesics in hospital was 2.1 and 3.5 for CR oxycodone and ST patients respectively ( p < 0.001 ) . ST patients reported more nausea and vomiting , pruritus and fever than the CR oxycodone patients , but less somnolence , constipation , dizziness , confusion and tachycardia . CONCLUSIONS CR oxycodone every 12 hours is as effective as ST in treating postoperative pain but length of hospital stay was shorter and analgesic administration in the hospital was used less frequently , providing potential hospital cost savings and reduced use of health care re sources Effective postoperative analgesia with minimal side effects remains an important goal in enabling increasingly complex surgical procedures to be performed on an outpatient basis . In this study , we examined the efficacy of postoperative analgesia in 90 patients undergoing anterior cruciate ligament reconstruction using a patellar tendon autograft , with a 24-hour hospital stay . Patients were r and omized to receive either intramuscular ketorolac supplemented by oral oxycodone , or intravenous morphine via patient-controlled analgesia ( PCA ) device , for postoperative analgesia . Patients were monitored for 2 hours in the recovery room , then every 4 hours until discharge , for the presence of complications of nausea , vomiting , urinary retention , pruritus , and dizziness . Pain was assessed using a visual analog scale ( VAS ) on the morning of postoperative day one . All patients were discharged by 24 hours after surgery . Ten ( 20 % ) of the patients receiving ketorolac/oxycodone versus 31 ( 79 % ) of those receiving PCA morphine experienced postoperative complications ( P < .05 ) . Postoperative nausea , vomiting , and urinary retention were each significantly more common in the PCA morphine group ( P < .05 ) . The incidence of pruritus and dizziness was low overall . There was no significant difference between groups in the severity of postoperative pain as assessed using a VAS . We conclude that ketorolac/oxycodone may provide comparable analgesia with fewer undesirable side effects than PCA morphine in patients undergoing anterior cruciate ligament reconstruction . Patients receiving ketorolac/oxymorphone may have a better quality recovery and more rapid discharge Intravenous morphine and oxycodone were given double blind in doses of 0.05 mg/kg after major abdominal surgery to 39 patients . The dosing interval was 5 min , until the patient did not want any further analgesics . Less oxycodone was needed than morphine , both to achieve the “ first state of pain relief ” ( 13.2 mg vs. 24.9 mg ) and during the whole 2‐h study period ( 21.8 mg vs. 34.2 mg ) . The “ first state of pain relief ” was achieved faster ( 28 min vs. 46 min ) and lasted longer ( 39 min vs. 27 min ) with oxycodone than morphine . Morphine caused more sedation and a greater decrease in the mean arterial blood pressure than oxycodone . In other respects the two opioids were comparable 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 STUDY OBJECTIVES To compare the peripheral analgesic effect of oxycodone , an opioid agonist , to the effect of bupivacaine infiltration and parenteral oxycodone administration in conjunction with shoulder surgery . DESIGN Prospect i ve , r and omized , double-blind study . SETTING University teaching hospital . PATIENTS 42 ASA physical status I and II patients scheduled for shoulder surgery with general anesthesia . INTERVENTIONS Patients were r and omized to three study groups : at the end of the surgery patients received either 10 ml of 0.5 % bupivacaine ( group BIB ) or 5 mg of oxycodone in 10 ml of saline ( group OIB ) in the subacromial bursa ; or 5 mg of oxycodone intramuscularly ( group OIM ) . Postoperative analgesia was provided by patient-controlled analgesia ( PCA ) . MEASUREMENTS AND MAIN RESULTS The fentanyl requirements were recorded for the 24-hour postoperative period and the total perioperative period . Postoperative pain was assessed by visual analog scale for pain ( VASP ) . Plasma oxycodone concentrations were measured in groups OIB and OIM . The total perioperative fentanyl consumption was significantly lower in groups BIB ( 0.97 + /- 0.09 mg ) and OIB ( 1.23 + /- 0.12 mg ) than in group OIM ( 1.61 + /- 0.12 mg ) ( p = 0.01 and 0.048 , respectively ) . Groups BIB and OIB were similar ( p = 0.34 ) . The absorption of oxycodone was significantly lower after subacromial than after intramuscular administration . CONCLUSION Intrabursal oxycodone and intrabursal bupivacaine reduced perioperative analgesic requirements similarly . Intrabursal oxycodone may offer an effective , simple , and safe method for postoperative analgesia after shoulder surgery Intravenous lysine acetylsalicylate ( LAS ) and oxycodone were compared under double-blind conditions for analgesia after upper abdominal surgery in sixty patients anaesthetized by N2O -- O2 - -halothane -- relaxant technique . Either 125 mg/10 kg or 250 mg/10 kg LAS or 0.4 mg/10 kg or 0.8 mg/10 kg oxycodone was r and omly administered when the patients complained of moderate or severe postoperative pain . When 30 min had elapsed following the injection of the test drug , oxycodone was given in 4 mg increments on dem and until adequate pain relief was achieved . At 15 min postdrug , the lower dose of LAS offered significantly less pain relief than all other test drugs . At 30 min , the effect of the higher dose of LAS reached almost the analgesic level of the higher dose of oxycodone but only the latter provided significantly ( P less than 0.05 ) better analgesia than the low dose of LAS . About 50 % less additional narcotic supplementation was dem and ed following higher doses of both drugs when compared to lower ones . LAS 250 mg/10 kg ( c. 1.8 g/70 kg ) was found approximately equipotent to oxycodone 0.8 mg/10 kg ( c. 6 mg/70 kg ) . However , LAS had a slower onset of action . Sweating seemed to occur more frequently after LAS than oxycodone , but significant changes in respiratory rate or sedation following LAS-oxycodone combinations when compared to oxycodone alone were not noted . The results show that for analgesia after upper abdominal surgery , 1.8 g of LAS may be substituted for about 6 mg of oxycodone 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 efficacy of mild analgesics after 160 various superficial operations was studied by comparing intravenous lysine‐acetylsalicylate ( LAS ) 1.8 g , Litalginr̀ 4 ml ( metamizole = dipyrone 2.0 g+pitophenone 8.0 mg ) or paracetamol 0.5 g to oxycodone 4 mg . At 15 min postdrug , oxycodone 4 mg had the best peak effect but this significant ( p<0.05 ) difference to mild analgesics disappeared at 30 min , and thereafter all test analgesics showed an equally low effect . Two‐thirds of the patients anaesthetized without peroperative analgesics needed pain relief when recovering from superficial surgery . The need for pain relief was lowest after varicose vein operations , 40 % of the patients as compared to about 70 % after other types of superficial surgery . In 42 % of the patients requiring pain relief , the test analgesics alone gave sufficient pain relief . The rest needed an additional 5 mg of oxycodone , on average , to be comfortable . The combined use of mild analgesics and oxycodone for adequate pain relief did not seem to reduce the postdrug sedation as compared to oxycodone alone . The results indicate that in traditional clinical dosages LAS , dipyrone or paracetamol can substitute about 5 mgoxycodone but offer sufficient analgesia only in about 40 % of the patients recovering from superficial surgery BACKGROUND The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase , or COX , -2-specific inhibitor , valdecoxib , with oxycodone/ acetaminophen in patients who have undergone oral surgery . METHODS In total , 205 eligible subjects in Study A and 201 in Study B were r and omized to receive a single oral dose of valdecoxib ( 20 or 40 milligrams ) , a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo . Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted . Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia . RESULTS In both studies , subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and ( among those who received valdecoxib 40 mg ) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen . Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen . Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo . CONCLUSIONS Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen , and it has a superior duration of analgesic effect in patients after oral surgery . Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen . CLINICAL IMPLICATION S The current st and ard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products . The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials SUMMARY Objective : To compare the efficacy of a single dose of rofecoxib 50 mg with a single dose of oxycodone/acetaminophen 10/650 mg over 6 h as well as with a multidose regimen of oxycodone/acetaminophen 10/650 mg followed by oxycodone/acetaminophen 5/325 mg over 24 h. Research design and methods : In this double-blind , r and omized , two-phase study , patients with moderate to severe pain after surgical extraction of ≥ 2 third molars , including one m and ibular impaction , were treated with rofecoxib 50 mg , oxycodone/acetaminophen 10/650 mg ( single-dose phase ) followed by 5/325 mg every 6 h as needed ( multidose phase ) , or placebo . Patients rated their pain relief and intensity at 18 time points over 24 h. Efficacy was measured over 6 and 24 h by total pain relief ( TOPAR ) , sum of pain intensity difference ( SPID ) , and patient global assessment of response to therapy ( PGART ) . Primary endpoint for the single dose comparison was TOPAR over 6 h ; SPID was the key 24-h endpoint . Onset of analgesic effect , peak analgesic effect , and duration of analgesic effect were also evaluated . Adverse experiences were recorded . Results : 271 patients were r and omized to treatment with rofecoxib ( n = 121 ) , oxycodone/acetaminophen ( n = 120 ) , or placebo ( n = 30 ) . For the single dose comparison , rofecoxib-treated patients achieved pain relief at least as effective as oxycodone/acetaminophen-treated patients as assessed by TOPAR6 ( 12.9 vs 11.3 , 95 % CI on difference = [ –0.1 , 3.2 ] , p = 0.059 ) . Patients also rated a single dose of rofecoxib as at least as effective as multidose oxycodone/acetaminophen over 24 h on SPID24 ( 21.9 vs 18.1 , 95 % CI on difference = [ –1.0 , 8.8 ] , p = 0.122 ) . Patients treated with oxycodone/acetaminophen had a shorter time to onset of analgesia than patients treated with rofecoxib ( 24 vs 35 min , p < 0.05 ) . Patients in the active treatment groups achieved similar peak effects during the single-dose phase . Individuals treated with rofecoxib demonstrated a longer duration of analgesic effect than those treated with a single dose of oxycodone/acetaminophen . Patients on active treatment demonstrated better efficacy than patients on placebo on these prespecified endpoints ( p < 0.001 for both comparisons ) . Fewer rofecoxib than oxycodone/acetaminophen patients experienced adverse events ( 47.9 vs 75.8 % , p < 0.001 ) , including nausea ( 19.0 vs 42.5 % , p < 0.001 ) , vomiting ( 9.9 vs 24.2 % , p < 0.01 ) , and dizziness ( 7.4 vs 31.7 % , p < 0.001 ) . Conclusion : Patients treated with a single dose of rofecoxib 50 mg achieved an overall analgesic effect at least as effective as patients treated with a single-dose of oxycodone/acetaminophen 10/650 mg over 6 h and multidose oxycodone/acetaminophen over 24 h , with fewer adverse experiences of nausea ( p < 0.001 ) , vomiting ( p < 0.01 ) , and dizziness ( p < 0.001 ) The effect of intrapleural bupivacaine in the treatment of post – thoracotomy pain was evaluated . Bupivacaine , 0.5 % 20 ml , with adrenaline ( 5 μg/ml ) was given through an indwelling intrapleural catheter , at 4–h intervals four times daily for 2 days . No pleural suction was applied during and 10 min after each injection . A control group received intramuscular oxycodone on request . A visual analogue scale ( VAS ) , a pain question naire ( PQ ) and registration of the need for supplementary analgesics were used for the assessment of postoperative analgesia . Blood – gas analyses showed elevated Pacoz values in both groups on the day of operation and on the first postoperative day , without differences between the groups . Plasma concentrations of bupivacaine did not reach toxic values , and no symptoms of central nervous toxicity or any other untoward reactions were found during the study period . Clinical ly , there was some pain relief after the intrapleural bupivacaine . The VAS and PQ scores 30 min after bupivacaine instillations diminished to an extent similar to that after oxycodone treatment . The need for analgesics during the day of operation was less in the bupivacaine group than in the control group ( P < 0.001 ) . The number of oxycodone supplementation doses during 48 h postoperatively was , however , not smaller in the bupivacaine group than in the control group Ninety-six women undergoing laparoscopic tubal ligation were r and omized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine , 60 micrograms/kg of oxycodone , or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design . The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared . In the group receiving diclofenac , 83 % of the patients required analgesic supplementation with morphine . This contrasted ( P less than 0.01 ) with 33 % of the patients receiving either oxycodone or the higher dose of dexmedetomidine . After the first dose of oxycodone was injected , the visual analogue scale for pain ( 0%-100 % ) was reduced from 58 % to 33 % , whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine . Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17 % . More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone ( P less than 0.001 ) . Both doses of dexmedetomidine decreased heart rate when compared with diclofenac ( P less than 0.001 ) . In the group given 0.4 microgram/kg of dexmedetomidine , 33 % of the patients required atropine for bradycardia . The authors conclude that after laparoscopic tubal ligation , intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia & 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 BACKGROUND Patients are typically switched from parenteral opioids to oral opioids during the 24 to 48 hours after surgery . In June 2006 , an oral immediate-release ( IR ) tablet formulation of oxymorphone was approved for the treatment of acute moderate to severe pain . Single doses of oxymorphone IR have been reported to provide significant pain relief after orthopedic surgery . OBJECTIVE This study assessed the efficacy and tolerability of multiple fixed doses of oxymorphone IR in the treatment of acute postoperative pain after abdominal surgery . METHODS This was a multicenter , r and omized , double-blind , active- and placebo-controlled , parallel-group study in men and women aged > or=18 years undergoing abdominal surgery that required a > or=3-cm incision . Patients who discontinued short-acting parenteral opioids and developed moderate or severe pain ( 4-point categorical scale [ none , mild , moderate , or severe ] and pain intensity > or=50 mm on a 100-mm visual analog scale [ from 0 = no pain to 100 = worst pain imaginable ] ) within 30 hours after abdominal surgery were r and omized to receive oxymorphone IR 10 or 20 mg , oxycodone IR 15 mg , or placebo every 4 to 6 hours after the previous dose . The study included 2 efficacy assessment s : a single-dose evaluation for up to 6 hours after the dose , and a multipledose evaluation for up to 48 hours after the first dose . Pain was assessed at 15-minute intervals during the hour after the first dose , hourly thereafter for the next 5 hours , and before each subsequent dose . The primary efficacy end point was the median time to study discontinuation for all causes . Assessment of tolerability was based on the proportion of study discontinuations due to treatment-emergent adverse events ( AEs ) . RESULTS Three hundred thirty-one patients were included in the study . Demographic characteristics were similar across all groups : 98.8 % ( 327 ) of patients were women , and 80.1 % ( 265 ) of the abdominal surgeries were hysterectomies . The mean ( SD ) age of the study population was 42.6 ( 9.3 ) years . The median time to study discontinuation for all causes was significantly longer for all active treatments compared with placebo ( oxymorphone IR 10 mg , 17.9 hours ; oxymorphone IR 20 mg , 20.3 hours ; oxycodone IR 15 mg , 24.1 hours ; placebo , 4.8 hours ; P < 0.006 ) . Oxymorphone IR 20 mg was significantly more effective than placebo over the 6-hour single-dose evaluation ( P < 0.05 ) . With multiple dosing , all active-treatment groups had significantly lower least squares mean current and average pain intensities compared with placebo ( P < 0.004 and P < 0.005 , respectively ) . The least squares means of the average pain intensity were significantly lower among patients treated with oxymorphone IR 10 mg , oxymorphone IR 20 mg , or oxycodone IR 15 mg compared with those who received placebo ( 39.7 , 35.2 , 39.8 , and 50.1 , respectively ; P < 0.005 ) . Discontinuations due to treatment-emergent AEs did not differ significantly between groups : 8.5 % ( 7/82 ) , 17.3 % ( 14/81 ) , 13.3 % ( 11/83 ) , and 12.9 % ( 11/85 ) in the oxymorphone IR 10-mg , oxymorphone IR 20-mg , oxycodone IR 15-mg , and placebo groups , respectively . The proportions of patients reporting at least 1 treatment-emergent AE were 46.3 % ( 38/82 ) , 51.9 % ( 42/81 ) , and 54.2 % ( 45/83 ) in the oxymorphone IR 10-mg , oxymorphone IR 20-mg , and oxycodone IR 15-mg groups , respectively , compared with 34.1 % ( 29/85 ) in the placebo group ( P = NS ) . The fixed-dose design was a study limitation , as it did not allow titration to effect and thus did not mirror clinical practice . CONCLUSION In this predominantly female population undergoing abdominal surgery , oxymorphone IR given every 4 to 6 hours for up to 48 hours provided efficacious and tolerable analgesia for moderate to severe pain Thirteen analgesic drugs , four of them at two dose levels , four analgesics in combination with antagonist or neuroleptic agents , and saline have been evaluated simultaneously in the relief of postoperative pain . The method of assessment was design ed to favour drugs which provided freedom from pain with minimum depression of consciousness . Only levorphanol 2 mg proved significantly superior to pethidine 100 mg , which was used as the st and ard reference drug . Oxycodone 10 mg , pentazocine 20 mg , and the morphine 10 mg and cyclizine 50 mg combination were the most successful of the remaining drugs . None of the drug combinations was significantly better than the analgesic drug given alone Purpose To compare the efficacy of the nonsteroidal antiinflammatory drugs ( NSAID ) , ketorolac and diclofenac in prevention of pain after maxillofacial surgery . Methods Sixty ASA I– II patients ( 30 in each group ) received r and omly , and double blindly either ketorolac 0.4 mg · kg− 1 or diclofenac 1.0 mg · kg− 1 iv after general anaesthesia induction , before surgical incision . In the ketorolac group , the same dose was repeated iv three times at six hour intervals . The diclofenac group patients received diclofenac 1.0 mg μ kg− 1 after 12 hr iv . Rescue analgesic medication consisting of oxycodone 0.03 mg · kg− 1 iv , was administered by a patient controlled analgesia apparatus . Results Two patients in the ketorolac and three patients in the diclofenac group did not need oxycodone during the study period . On average , 12 and 11 doses of oxycodone were needed in the ketorolac and the diclofenac groups , respectively ( NS ) . Sideeffects were similar in both groups . All patients except one were satisfied with the pain therapy . Conclusion Parenteral ketorolac ( 0.4 mg · kg− 1 four times in 24 hr ) and diclofenac ( 1 mg · kg− 1 twice in 24 hr ) were similar , but insufficient alone , for analgesia after maxillofacial surgery . RésuméObjectifComparer l’efficacité des antiinflammatoires non stéroïdiens kétotolac et diclofénac pour la prévention de la douleur en chirurgie maxillofaciale . MéthodeSoixante patients ASA I et II ( 30 dans chaque groupe ) , r and omisés et en double aveugle , ont reçu soit kétorolac 0,4 mg · kg− 1 soit diclofénac 1,0 mg · kg− 1 après l’induction de l’anesthésie et avant l’incision . Dans le groupe kétorolac , la même dose intraveineuse a été répétée trois fois avec un intervalle de six heures . Le groupe diclofénac a reçu le diclofénac 1,0 mg · kg− 1 iv après 12 h. L’oxycodone 0,03 mg · kg− 1 iv administré à l’aide d’un système autocontrôlé servait d’analgésique de sauvetage . RésultatDeux patients du groupe kétorolac et trois patients du groupe diclofénac n’ont pas eu besoin d’oxycodone pendant l’étude . En moyenne , 12 et 11 doses d’oxycodone ont été nécessaires respectivement dans le groupe kétorolac et dans le groupe diclofénac ( NS ) . Les effets secondaires ont été les mêmes dans les deux groupes . Tous les patients excepté un ont été satisfaits de leur analgésie . Conclusion Le kétorolac ( 0,4 mg · kg− 1 quatre fois en 24 h ) et le diclofénac ( 1 mg · kg− 1 deux fois en 24 h ) ont eu le même effet , mais à eux seuls ont été insuffisants pour procurer l’analgésie après une chirurgie maxillofaciale In a double‐blind crossover study , morphine and oxycodone hydrochloride were administered to 20 patients who were experiencing severe cancer pain . The peroral doses were determined on the basis of patient‐controlled intravenous titration . The assumed oral bioavailability ratios were 44 % ( group 1 , first 10 patients ) and 33 % ( group 2 , last 10 patients ) for morphine and 66 % ( group 1 ) and 50 % ( group 2 ) for oxycodone hydrochloride , respectively . However , the patients were able to readjust their oral dosings . Equal analgesia was achieved with both drugs , but the intravenous dose of oxycodone hydrochloride needed was 30 % higher than that of morphine . The median calculated oral/intravenous ratios giving comparable analgesia were 0.31 for morphine and 0.70 for oxycodone hydrochloride . Morphine caused more nausea than oxycodone hydrochloride and hallucinations occurred only during morphine treatment . Otherwise , there were no major differences in the side effects between these two opioids Although both acetaminophen and oxycodone are commonly used analgesics , they were not available as a combination until recently . Since oxycodone is not available as a single entity , there is no archival or even anectodal information on the efficacy and safety of this combination . The purpose of this study was to evaluate the relative efficacy of various doses of the combination that could be used in dental situations . The single-dose efficacy and safety of acetaminophen 500 mg . , oxycodone 5 mg . , acetaminophen 500 mg . + oxycodone 5 mg . , acetaminophen 1,000 mg . + oxycodone 5 mg . , acetaminophen 1,000 mg . + oxycodone 10 mg . , and placebo were compared in out patients who experienced moderate to severe pain after surgical removal of inpacted third molars . Analgesic data were analyzed by analysis of variance and Duncan 's multiple range test . All active treatments were superior to placebo , with the high-ratio combination being the most efficacious . This treatment also had the highest incidence of limiting side effects . A positive dose-effect relationship was evident for both acetaminophen 500 mg . and 1,000 mg . and for oxycodone 5 mg . and 10 mg In a series of three studies involving dental out patients undergoing removal of impacted third molars , preoperative and postoperative administration of flurbiprofen ( Ansaid , Upjohn ) led to superior pain relief when compared with acetaminophen alone or in combination with oxycodone . Patient preference and global evaluations clearly favored flurbiprofen . Side effects were mild and generally more common in patients receiving the opiate/mild analgesic combination . In two additional studies , flurbiprofen and etidocaine , a long-acting local anesthetic , also result ed in significantly less postoperative pain than a combination of acetaminophen/oxycodone and lidocaine ; 67 percent of patients in the flurbiprofen plus etidocaine group reported no or only slight pain during the entire observation period . The greater analgesic efficacy of flurbiprofen appears to represent a genuine therapeutic advantage , since it is not achieved at the expense of greater side effects While pharmacokinetic/pharmacodynamic relationships for opioids have not been consistently demonstrable or sufficiently predictive , there remain compelling reasons to pursue such relationships . Among the reasons for pursuing pharmacokinetic/ pharmacodynamic relationships is the prospect of predicting the time‐action characteristics of new therapeutics on the basis of early studies in normals using pharmacodynamic surrogates for analgesia . The realization of such a model could improve the efficiency of development of analgesics The objective of this double-masked , parallel-group , multicenter , inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery . In the 8-hour , single-dose phase , 238 patients received single oral doses of bromfenac ( 50 or 100 mg ) , acetaminophen 650 mg/oxycodone 10 mg , ibuprofen 400 mg , or placebo . In the multiple-dose phase , 204 patients received bromfenac , acetaminophen/oxycodone , or ibuprofen for up to 5 days . In the single-dose phase , both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone , but the responses to bromfenac were longer lasting . Bromfenac produced significantly better overall ( 8-hour ) analgesic summed scores than acetaminophen/oxycodone . Ibuprofen was less efficacious than the other analgesics . The remedication rate was lower in both bromfenac groups than in the other treatment groups . The acetaminophen/oxycodone group reported more somnolence and vomiting . Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination , with a longer duration of action . Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study Summary Twenty-one patients who had undergone total hip replacement were r and omly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine i m ( I ) and 20 mg ( II ) or 60 mg of extradural pethidine ( III ) in a double-blind design .The degree of analgesia , the adverse effects , and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale ( VAS ) . Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine . Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry ( GCMS ) . Hypoalgesia to pin prick test was evaluated . Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose . A significant difference in pain score compared with the i m group was found after the higher extradural dose only between 0.5 and 1 h (p<0.05).The area under the curve ( AUC ) of pain score versus time ( 0–18 h ) was not significantly different between groups . The recorded adverse effects were minor in all three groups . The terminal half-lives and plasma clearances of pethidine , and the time to peak concentration were not different between the groups . Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect . The present study shows that extradural pethidine produces shortlived analgesia , in contrast to the long-lasting effect of morphine found in other studies Background : Morphine has been the st and ard opioid in patient‐controlled analgesia ( PCA ) . Oxycodone , the analgesic potency of which in i.v . administration has been suggested to be slightly greater than that of morphine , has not yet been studied for its efficacy in PCA OBJECTIVE The objective was to determine whether , when compared with traditional dietary advancement , early oral intake following major gynecologic surgery leads to a reduction in the length of hospitalization . METHODS Patients undergoing major abdominal gynecologic surgery were invited to participate in this study . After informed consent was obtained , they were r and omized to one of two groups . The control group ( group 1 ) was treated traditionally . Oral intake was initiated only after documentation of bowel function , which was defined by two of the following three criteria : ( 1 ) bowel sounds ; ( 2 ) flatus or bowel movement ; and ( 3 ) subjective hunger . Those assigned to the study group ( group 2 ) were given a clear liquid diet on postoperative day 1 . Once 500 cc was tolerated , a regular diet was given . Patients were evaluated on a daily basis for bowel sounds , flatus , bowel movement , hunger , nausea , vomiting , and need for nasogastric tube decompression . The groups were compared with regard to length of hospital stay , length of postoperative ileus , and incidence of adverse effects including nausea , vomiting , and postoperative complications . Statistical analyses were performed with the Student t and chi 2 tests . RESULTS The demographic characteristics of the control ( N = 47 ) and study groups ( N = 49 ) were similar , with no significant differences in underlying medical conditions , prior abdominal surgery , or diagnosis of a malignancy . The groups did not vary statistically in the number of subjects who required postoperative antiemetics or postoperative biscodyl suppository . There was a statistically significant reduction in the length of hospitalization for those patients on the early feeding regimen . The average length of stay for group 1 was 4.02 days + /- 0.30 ( SEM ) , while that for group 2 was 3.12 days + /- 0.16 ( P = 0.008 ) . While there was a significantly higher incidence of emesis in the study population , this was not associated with any untoward outcome , and this group actually tolerated a solid diet nearly one full day earlier ( 2.72 days + /- 0.14 vs 1.88 days + /- 0.14 , P < 0.0001 ) . CONCLUSIONS Early postoperative oral intake results in a decreased length of hospitalization and is well tolerated when compared with traditional dietary management in patients undergoing abdominal surgery on a university gynecologic oncology service This r and omized , controlled trial compared the analgesic efficacy and safety of the new oxycodone 10-mg/acetaminophen 325-mg formulation ( Percocet ) for the treatment of acute pain following oral surgery with double the dose of oxycodone alone ( controlled-release [ CR ] oxycodone 20 mg [ OxyContin ] ) . A total of 150 male and female patients with > or = 2 full or partial bone-impacted m and ibular molars , at least moderate persistent pain , and moderate trauma received a single dose of combination agent , CR oxycodone , or placebo following oral surgery and rated pain intensity and pain relief over the next 6 hours . The intent-to-treat population comprised 141 patients ( 55 on combination agent , 56 on oxycodone , and 30 on placebo ) . Combination agent and CR oxycodone were significantly superior to placebo for all efficacy measures . Combination agent was statistically superior to CR oxycodone in four of five outcome measures of pain intensity and pain relief ( PPID , PPAR , SPID , and SPRID ) . It also provided a faster onset and 24 % reduction in the number of patients reporting treatment-related adverse events compared with twice the dose of opioid alone . This new formulation offers the combination of two analgesic drugs with complementary mechanisms of action , which results in enhanced analgesia , an " opioid-sparing " effect , and an improved side effect and safety profile Sixty patients undergoing gynaecological laparotomies under isoflurane anaesthesia received 0.4 mg of buprenorphine sublingually or 0.12 mg/kg of oxycodone intramuscularly in r and om order for preanaesthetic medication . Patients premedicated with buprenorphine were given buprenorphine before , during and after anaesthesia and patients premedicated with oxycodone received fentanyl before and during anaesthesia and oxycodone after anaesthesia . Buprenorphine premedication produced less drowsiness and sedation and alleviated patients ' apprehension significantly ( P<0.05 ) less than oxycodone . Systolic and diastolic blood pressure and heart rate were significantly ( P<0.05 to P<0.01 ) higher after intubation in the buprenorphine group when compared with the oxycodone plus fentanyl group . After anaesthesia , spontaneous respiration started rapidly ; the return of consciousness and immediate recovery occurred at the same rate in both groups . In the recovery room moderate to severe pain was more common ( P<0.05 ) in the oxycodone plus fentanyl group than in the buprenorphine group . The respiratory rate in the recovery room was lower among patients given buprenorphine , and two patients given buprenorphine developed severe respiratory depression . In the ward ( 2 to 24 h after operation ) sublingual buprenorphine provided pain relief as good as intramuscularly administered oxycodone . No differences were noted in the incidence or severity of emetic symptoms between the groups . It is concluded that buprenorphine can provide good postoperative pain relief for gynaecological laparotomies performed under light isoflurane anaesthesia , but patients need to be monitored carefully after operation because of the possibility of respiratory depression Intravenous lidocaine , a nonspecific Na-channel blocker , was used to assess the dental impaction model for evaluation of neuropathic pain drugs . Sixty patients , experiencing moderate or severe pain after removal of > or = 2 third molars , were r and omized ( 2:2:1:1 ) to lidocaine ( 4 mg/kg ; maximal dose 300 mg ) , oxycodone/acetaminophen ( 10/650 mg ) , placebo , and active placebo ( diphenhydramine , 50 mg ) . Lidocaine provided a modest degree of pain relief . Predefined endpoints of total pain relief and sum of pain intensity at 2 , 4 , and 6 hours showed numerically , not statistically significantly , greater pain relief versus placebo . A significantly greater effect over placebo was observed in peak effect and at shorter time points ( 30 minutes and 1 hour ) , consistent with the pharmacokinetic profile ( plasma concentration of approximately 2 mug/mL ) . Oxycodone/acetaminophen provided significantly greater analgesia versus placebo , validating study conduct , and significantly greater pain relief was observed versus lidocaine , which is consistent with a smaller portion of dental extraction pain being of neuropathic origin Our objective in this study was to compare the analgesic effects of etoricoxib and oxycodone/acetaminophen in a postoperative dental pain model . Patients experiencing moderate to severe pain after extraction of two or more third molars were r and omized to single doses of etoricoxib 120 mg ( n = 100 ) , oxycodone/acetaminophen 10/650 mg ( n = 100 ) , or placebo ( n = 25 ) . The primary end-point was total pain relief over 6 h. Other end-points included patient global assessment of response to therapy ; onset , peak , and duration of effect ; and rescue opioid analgesic use . Active treatments were statistically significantly superior to placebo for all efficacy measures . Total pain relief over 6 h for etoricoxib was significantly more than for oxycodone/acetaminophen ( P < 0.001 ) . Patient global assessment of response to therapy at 6 and 24 h was superior for etoricoxib . Both drugs achieved rapid onset , although the time was faster for oxycodone/acetaminophen by 5 min . The peak effect was similar for both drugs . Compared with oxycodone/acetaminophen patients , etoricoxib patients experienced a longer analgesic duration , had a smaller percentage requiring rescue opioids during 6 and 24 h , and required less rescue analgesia during 6 and 24 h. Oxycodone/acetaminophen treatment result ed in more frequent adverse events ( AEs ) , drug-related AEs , nausea , and vomiting compared with etoricoxib treatment . In conclusion , etoricoxib 120 mg provided superior overall efficacy compared with oxycodone/acetaminophen 10/650 mg and was associated with significantly fewer AEs Sixty patients scheduled for colonic surgery were r and omly allocated to four groups according to postoperative pain medication : I. Control group , the patients received oxycodone intramuscularly ( 0.15 mg kg1 ) on request . II . Epidural bupivacaine ( 0.25 % ) continuously administered by infusion pump , 66 ml h‐1 , for 48 h. III . Epidural morphine , 2–6 mg , at the end of operation and repeated on the first and second postoperative mornings . IV . Epidural morphine , 2–6 mg per die , administered for 48 h continuously by infusion pump . All patients received a balanced anaesthesia with enflurane , fentanyl and vecuronium . Postoperatively , intramuscular oxycodone was given on request . There were no significant differences between the groups in changes in peak flow , spirometry and blood‐gas analyses postoperatively . Pain intensity ( visual analogue scale ) was lower in Groups II and III at 3 h and in Group IV at 24 h compared to the control Group I. All the epidurally treated groups needed less additional analgesics than the control Group I. Postoperatively bowel movements occurred on the second day in Group II ( bupivacaine ) as compared to the fourth day in all other groups ( P < 0.05 ) PURPOSE Use of oxycodone for chronic cancer pain has been hampered by its short elimination half-life . This study was design ed to compare the efficacy and safety of controlled-release formulations of oxycodone and morphine for cancer pain . PATIENTS AND METHODS Thirty-two adult patients with cancer pain and a > or = 3-day history of stable analgesia with oral opioids provided written informed consent and were r and omized to controlled-release oxycodone or controlled-release morphine for 7 days . To blind the study using available tablet strengths , the dose ratio of oxycodone to morphine was set at 1:1.5 . On day 8 , patients were crossed over to the alternate drug for 7 days . Pain intensity was assessed using a visual analog scale ( VAS 0 to 100 mm ) and a categorical scale ( CAT 0 to 4 ) . Side effects were assessed using a checklist ( four-point categorical severity ) and a nondirected question naire . Patients and investigators made blinded global ratings of efficacy and treatment preference . RESULTS Twenty-three patients completed the study ( 10 men , 13 women ) . The VAS and CAT scores were ( mean+/-SD ) 23+/-21 and 1.2+/-0.8 on controlled-release oxycodone , and 24+/-20 ( P=.43 ) and 1.3+/-0.7 ( P=.36 ) on controlled-release morphine . No period or carryover effect was detected . There were no significant differences in adverse effects ( P=.40 ) or ratings of efficacy and preference . The median oxycodone/morphine dose ratio was 1.5 and the maximum was 2.3 . CONCLUSION Controlled-release oxycodone is as safe and effective as controlled-release morphine in the treatment of cancer pain BACKGROUND The sensation of pain arises from both central and peripheral sites , and inflammation may be one of its underlying causes . Combination therapy with analgesic agents having multimodal mechanisms of action and complementary pharmacokinetic properties enhances pain relief by addressing the different pathways of pain while limiting individual drug doses and , therefore , the potential for adverse effects caused by any single agent . Oxycodone and ibuprofen each have been used effectively as monotherapy and in other combinations for the treatment of acute pain ; a fixed combination of these analgesics may improve pain relief in the setting of abdominal or pelvic surgery , where trauma and any result ant inflammation may be present at the same time . OBJECTIVE This study evaluated and compared the analgesic efficacy and tolerability of a single-dose combination tablet containing oxycodone 5 mg/ibuprofen 400 mg with either agent alone and with placebo in women who had undergone abdominal or pelvic surgery . METHODS In this multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group trial , women experiencing moderate to severe pain between 14 and 48 hours after surgery were r and omized per protocol to receive a single dose of study medication in a 3:3:1:1 ratio ( combination oxycodone/ibuprofen , ibuprofen , oxycodone , and placebo , in that order ) . Over a 6-hour study period , patients recorded their assessment s of pain intensity ( 100-mm visual analog scale and 4-point scale ) , relief from starting pain , and overall evaluation of study drug based on prespecified definitions and rating scales . Based on these data , the following primary efficacy end points were determined : total pain relief 6 hours after dosing ( TOTPAR6 ) and sum of pain intensity differences 6 hours after dosing ( SPID6 ) . Other end points included the time to onset of pain relief , time to use of rescue medication , and patient 's global rating of analgesic effectiveness . Tolerability was evaluated on the basis of observed and patient-reported adverse events and findings on physical examination . RESULTS Four hundred fifty-six women participated in the study . They were primarily white and had a mean age of 41.6 years and a mean body weight of 171.5 pounds . Combination treatment was associated with significantly better TOTPAR6 and SPID6 scores compared with ibuprofen alone ( P < 0.02 and P < 0.015 , respectively ) , oxycodone alone ( P < 0.009 and P < 0.001 ) , or placebo ( both , P < 0.001 ) . Fewer patients receiving combination treatment required rescue medication , and the time to use of rescue medication was significantly longer in the combination-treatment group compared with the other groups ( P < 0.05 ) . Patients ' global ratings of analgesic efficacy were significantly higher in the combination-treatment group compared with all other groups ( P < 0.044 vs ibuprofen alone ; P < 0.001 vs oxycodone alone and placebo ) . The onset of pain relief occurred within 15 minutes of dosing with all 4 regimens . Nausea was the most frequently reported treatment-emergent adverse event in all 4 groups . The incidence of treatment-emergent adverse events was highest with placebo ( 55.0 % ) , followed by oxycodone alone ( 44.2 % ) , ibuprofen alone ( 42.3 % ) , and combination treatment ( 40.8 % ) . CONCLUSIONS In this population of women who had undergone abdominal or pelvic surgery , the combination of oxycodone 5 mg/ibuprofen 400 mg was significantly more effective than either agent alone or placebo in the treatment of moderate to severe postoperative pain We have studied the effect of tropisetron , a 5-HT3-receptor antagonist , on postoperative nausea , vomiting and pain in 54 patients , aged 50 - 83 yr , after major hip or knee surgery . The patients were given subarachnoid injection of plain 0.5 % bupivacaine , mixed with preservative-free morphine 0.3 mg , for surgical and postoperative analgesia . In a double-blind fashion , either tropisetron 5 mg ( 1 mg ml-1 ) or saline 5 ml was injected i.v . 30 min after spinal administration of bupivacaine and morphine . The number of patients needing i.m . oxycodone for pain relief , the total number of oxycodone doses or the mean time to the first i.m . oxycodone administration did not differ significantly between the two groups . The number of patients who became nauseated or vomited during the observation period did not differ significantly between groups . Seventeen patients had nausea and 11 vomited in the tropisetron group , compared with 20 and 13 , respectively , in the control group during the first 24 Interscalene brachial plexus block was performed on 40 patients for prophylactic pain relief after shoulder surgery . A dose of 1.25 mg/kg of 0.5 % , bupivacaine was injected for the block ( Group 1 ) and continued with an infusion of 0.25 % , bupivacaine 0.25 mg/kg/h ( Group 2 ) . If the postoperative analgesia was insufficient , the patients received i.m . oxycodone 0.15 mg/kg . In Group 1 , one patient managed without oxycodone supplementation during the 24‐h observation period compared with eight patients in Group 2 [ P < 0.01 ) . The rest of the patients received 3.8 ± 1.6 doses ( Group 1 ) and 2.5 ± 1.2 doses ( Group 2 ) of oxycodone ( P < 0.05 ) . At 30 min , the mean bupivacaine plasma concentration was 1.0 pg/ml in Group 1 and 0.9 pg/ ml in Group 2 . The mean plasma level of bupivacaine increased from 0.7 μg/ml after 180 min to 1.1 μg/ml ( P < 0.01 ) after 24 h of infusion , providing some evidence of accumulation during infusion . The dizziness and confusion experienced by three patients could be associated with the local anaesthetic , as they obtained relief after the infusion was stopped & 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 Intravenous indomethacin infusion ( 75 mg/10 h ) for relief of pain after ankle surgery was compared with placebo in a double-blind study . Ninety-seven patients were operated on for a malleolar fracture or ruptured ligament of the ankle under single-dose spinal anesthesia . In the indomethacin group , 14 out of 49 patients were free from pain , 4/47 in the control group . Severe pain was experienced by 24/49 in the indomethacin group and by 41/47 in the control group . Supplementary intramuscular oxycodone was needed for 24 patients in the indomethacin group and for 41 control patients . In 1 patient , i.v . indomethacin administration caused serious arterial hypotension necessitating discontinuation of the medication . Intravenous indomethacin reduced the need of opiate for alleviation of postoperative pain , but the possibility of hypersensitivity reaction calls for particular attention The efficacy and safety of grade d doses ( 10 , 20 , and 30 mg ) of controlled-release ( CR ) oxycodone was compared with that of immediate-release ( IR ) oxycodone ( 15 mg ) , immediate-release oxycodone 10 mg in combination with acetaminophen 650 mg ( APAP ) , and placebo in a single-dose , double-blind , r and omized , parallel-group study . The participants , 182 in patients experiencing moderate to severe pain after abdominal or gynecologic surgery , provided hourly ratings of pain intensity and relief for 12 hours after administration . All active treatments were significantly superior to placebo for many hourly measurements and for the sum of pain intensity differences ( SPID ) and total pain relief ( TOTPAR ) . A dose response was found among the three levels of CR oxycodone for pain relief and peak pain intensity difference ( PID ) , with the 20- and 30-mg doses being significantly better than the 10-mg dose . For all active treatments , peak PID and peak pain relief occurred approximately 2 to 4 hours after administration . The median time to onset of relief was 32 minutes for oxycodone plus APAP , 41 minutes for IR oxycodone , and 46 minutes for CR oxycodone 30 mg . Duration of pain relief showed that the 10- , 20- , and 30-mg doses of CR oxycodone had duration s of action of 10 to 12 hours compared with IR oxycodone and oxycodone plus APAP ( both approximately 7 hours ) . Typical adverse events , particularly somnolence , occurred in all active treatment groups . Treatment with CR oxycodone was safe and effective in this study , and its characteristics will be beneficial in the treatment of pain This r and omized study examined the effect of transcutaneous electrical nerve stimulation ( TENS ) and indomethacin on postoperative opiate requirement in 60 patients after cholecystectomy . An open intravenous bolus of 25 mg of indomethacin followed by an infusion of 5 mg in 1 h , alone or combined with either low or high frequency TENS , was administered during the study period of 16 h. An intravenous bolus of either 5 mg of oxycodone or 0.15 mg of buprenorphine was administered double blindly for postoperative pain relief . The number of doses of buprenorphine given ( 3 , 9 ) differed ( P = 0.01 ) from the number of doses of oxycodone given ( 5 , 4 ) . Neither indomethacin nor TENS reduced the postoperative opiate requirement The 297 cases observed and recorded were selected at r and om from the surgical cases performed in this hospital and included abdominoperineal resections for carcinoma of the rectum , prostatectomies , appendicectomies , hysterectomies and colporrhaphies , gastrectomies and cholecystectomies , mastectomies , thyroidectomies , sixty-two orthopedic procedures and twelve Cmarian sections . The ages of the patients varied from children to octogenarians in all stages of physical fitness . No special effort was made to select any special type or age group or any particular surgical procedure Approximately equianalgesic oral doses of codeine , an oxycodone compound resembling Percodan , and pentazocine were compared for adverse effects in a double-blind , r and omized study of four doses of each drug given over two days to 247 postsurgical patients with pain . Placebo and parenteral morphine were also treated as negative and positive controls , respectively . Approximately 50 patients each received one of the five drugs . Codeine , pentazocine , and morphine had the same incidence of adverse effects ( 22 to 28 per cent ) . One capsule of oxycodone compound was the analgesic equivalent of 12.5 mg morphine with an adverse effect incidence of 4 per cent ( placebo 8 per cent ) . Smoking made no difference in analgesic effect or adverse effects . Analgesics given in the evening intervening between the two days may have affected the analgesic performance of placebo The effects of a prostagl and in synthesis inhibitor ( diclofenac , Voltaren ® ) and an opiate ( oxycodone , Oxa‐nest ® ) on postoperative pain were compared . Included in the study were 85 c and i date s for various operations . Patients requesting an analgesic were given either 75 mg of diclofenac or 10 mg of oxycodone as an intramuscular injection . The onset of analgesic effect occurred within 13 ± 4 min with oxycodone and within 16 ± 8 min with diclofenac . The analgesic effect of diclofenac was slightly weaker than that of oxycodone ( on a pain scale of 1–4 , 1.6/2.1 after 0.5 h and 1.5/1.8 after 1 h ) . The patients again asked for an analgesic after an average of 4.6 h in the oxycodone group and after an average of 6.1 h in the diclofenac group . The average number of injections required until the first postoperative morning was 2.5 in the oxycodone group and 1.8 in the diclofenac group . Side‐effects : 21 patients in the oxycodone group reported a total of 39 side‐effects and eight patients in the diclofenac group a total of 10 side‐effects . Diclofenac is an alternative to opiates in the management of postoperative pain . It is especially useful in patients in whom opiates cause side‐effects 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 The analgesic dose‐effect relationship of nefopam was compared in a double‐blind r and omised trial with that of oxycodone in immediate postoperative pain . Nefopam 15 mg or oxycodone 4 mg was given every 10 min i.v . ( maximum six times ) to patients in pain after upper abdominal surgery until their wound pain ( scored 0–3 ) disappeared . The mean pain intensity ( PI ) , initially 2.2 in both groups , decreased by approximately the same extent for up to two doses in both groups ( to 1.5 after nefopam 30 mg and to 1.1 after oxycodone 8 mg ) . Thereafter PI was significantly less in the oxycodone group and diminished almost linearily to 0.1 after the sixth dose ( 24 mg ) . In the nefopam group , the PI score fell to 1.1 after the fourth dose ( 60 mg ) . This seemed to be the “ ceiling ” effect since additional doses up to 90 mg did not result in greater pain relief . In the oxycodone group , only two patients ( 12 % ) needed maximal dosage ( 6 times 4 mg ) , one of them requiring 32 mg of oxycodone . In the nefopam group , 12 patients ( 75 % ) needed further pain relief after the maximal dosage ( 6 times 15 mg ) . In these patients , oxycodone ( maximally 16 mg ) gave satisfactory analgesia . Drowsiness and a decrease in the respiratory rate were the principal side‐effects of oxycodone , whereas tachycardia , restlessness , sweating and nausea were more frequent after nefopam OBJECTIVE The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain . BACKGROUND Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen . METHODS This r and omized , double-blind , parallel-group , single-dose , active-comparator , placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo . Analgesia was assessed over 8 hours . RESULTS Mean pain relief ( PR ) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups ( n = 61 and 59 , respectively ) at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , 4 , and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5 , 6 , and 8 hours ( P < or = 0.05 ) . Mean pain intensity difference ( PID ) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , and 4 hours and significantly greater for hydrocodone with ibuprofen at 5 , 6 , 7 , and 8 hours ( P < or = 0.05 ) . Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals ( P < 0.05 ) . The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- , 0- to 4- , 0- to 6- , and 0- to 8-hour intervals . The median estimated time to onset of analgesia , mean peak PR score , median time to remedication , and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen . Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo ( n = 60 ) . The number of patients experiencing adverse events was similar for each of the 3 groups ( 11 [ 18.0 % ] , hydrocodone with ibuprofen ; 7 [ 11.9 % ] , oxycodone with acetaminophen ; and 6 [ 10.0 % ] , placebo ) . CONCLUSIONS In this study , a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain . Both treatments were superior to placebo . The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy OBJECTIVE This study compared the efficacy and safety of a single dose of oxycodone 5 mg/ibuprofen 400 mg versus its individual components and placebo in a third-molar extraction model . METHODS In this multicenter , double-blind , double-dummy , parallel-group investigation , subjects with moderate to severe pain within 5 hours after extraction of > or = 2 ipsilateral bony impacted third molars were r and omized to single doses of oxycodone 5 mg/ibuprofen 400 mg , ibuprofen 400 mg , oxycodone 5 mg , or placebo . Primary efficacy variables were the sum of pain intensity difference over 6 hours ( SP1D6 ) and total pain relief through 6 hours ( TOTPAR6 ) . The pharmacokinetics of oxycodone and ibuprofen , alone and in combination , were also determined in a subset of patients . RESULTS A total of 498 subjects were r and omized to treatment ( 187 to oxycodone 5 mg/ibuprofen 400 mg , 186 to ibuprofen 400 mg , 63 to oxycodone 5 mg , and 62 to placebo ) . Baseline demographics were generally similar among treatment groups , despite differences in sex ( P = 0.041 ) and race ( P = 0.023 ) . Combination therapy was associated with greater analgesia than ibuprofen alone , oxycodone alone , or placebo ( mean [ SE ] TOTPAR6 : 13.3 [ 0.52 ] , 12.2 [ 0.52 ] , 4.3 [ 0.82 ] , and 4.2 [ 0.83 ] , respectively [ P < 0.001 vs oxycodone or placebo , P = 0.012 vs ibuprofen ] ; mean [ SE ] SP1D6 : 6.54 [ 0.42 ] , 5.41 [ 0.44 ] , 0.14 [ 0.60 ] , and 0.32 [ 0.59 ] , respectively [ P < 0.001 vs oxycodone or placebo , P = 0.002 vs ibuprofen ] ) . Combination therapy was well tolerated . Pharmacokinetic results implied no interaction between oxycodone and ibuprofen . CONCLUSIONS In this study , a single dose of oxycodone 5 mg/ibuprofen 400 mg was fast-acting , effective , and well tolerated in subjects with moderate to severe pain after dental surgery . Oxycodone 5 mg alone did not provide an efficacy benefit over placebo in this study Etude comparative portant sur 168 malades . L'indomethacine se montre plus efficace que BACKGROUND Opiates , acetaminophen , nonselective nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and cyclooxygenase-2-selective inhibitors such as rofecoxib are used in the treatment of acute pain because of their anti-inflammatory and /or analgesic properties . Rofecoxib has demonstrated an improved gastrointestinal safety profile compared with nonselective NSAIDs . OBJECTIVE The aim of this study was to compare the analgesic efficacy and tolerability profile of rofecoxib 50 mg with those of the central ly acting , nonsalicylate , opiate/nonopiate analgesic combination oxycodone/acetominophen 5/325 in patients with pain after dental surgery . METHODS In this r and omized , double-blind , placebo- and active comparator-controlled study , patients experiencing moderate to severe postoperative pain after extraction of > or = 2 third molars ( including > or = 1 m and ibular impaction ) received a single oral dose of rofecoxib 50 mg , oxycodone/acetaminophen 5/325 mg , or placebo . End points included total pain relief over 6 hours ( TOPAR6 , the primary end point ) and 4 hours ( TOPAR4 ) , patient 's global assessment of treatment at 6 hours ( GLOBAL6 ) and 24 hours ( GLOBAL24 ) , summed pain intensity difference over 6 hours ( SPID6 ) , onset of analgesic effect ( time to perceptible/meaningful pain relief , using a 2-stopwatch method ) , peak pain relief ( PEAKPR ) , peak pain intensity difference ( PEAKPID ) , and duration of analgesic effect ( time to use of rescue analgesia ) . RESULTS Two hundred twelve patients ( 63 % female , 37 % male ; 76 % white , 24 % other ; mean [ SD ] age , 20.9 [ 4.4 ] years ; age range , 16 - 41 years ) were enrolled in the study and received a single oral dose of rofecoxib 50 mg ( n = 90 ) , oxycodone/acetaminophen 5/325 mg ( n = 91 ) , or placebo ( n = 31 ) . The analgesic effect of rofecoxib was significantly greater than that of oxycodone/acetaminophen at P < 0.001 for TOPAR6 , TOPAR4 , GLOBAL6 , GLOBAL24 , and SPID6 ; at P < 0.010 for PEAKPR and PEAKPID ; and at P < 0.001 for median time to use of rescue analgesia . Significantly fewer patients in the rofecoxib group ( 72.2 % ) took rescue analgesia within 24 hours postdose compared with the oxycodone/acetaminophen group ( 94.5 % ; P < 0.001 ) and the placebo group ( 96.8 % ; P < 0.02 ) . Both active treatments were similar with respect to onset of analgesic effect . Both were generally well tolerated ; the overall incidence of adverse experiences in the rofecoxib , oxycodone/acetaminophen , and placebo groups was 51.1 % , 64.8 % , and 48.4 % , respectively . Rofecoxib was associated with a significantly lower incidence of nausea ( 18.9 % vs 39.6 % ; P < 0.001 ) and vomiting ( 6.7 % vs 23.1 % ; P < 0.001 ) compared with oxycodone/acetaminophen . CONCLUSIONS In study patients with moderate to severe pain after dental surgery , rofecoxib 50 mg had a greater analgesic effect than oxycodone/acetaminophen 5/325 mg and was associated with less nausea and vomiting Major knee surgery is associated with moderate or severe post-operative pain . Intrathecal morphine and continuous femoral 3-in-1 block were compared prospect ively in 40 patients for pain after major knee surgery under spinal anaesthesia , with 4 mL isobaric 0.5 % bupivacaine . In a r and om order , 20 patients received preservative free morphine 0.3 mg mixed with spinal bupivacaine . In 20 patients , following spinal anaesthesia with only bupivacaine , femoral 3-in-1 block was performed post-operatively with 0.5 % bupivacaine 2 mg kg-1 . The block was continued via a catheter with 0.25 % bupivacaine 0.1 mL h-1 kg-1 until the next morning ( 24 h after induction of spinal anaesthesia ) . Intramuscular oxycodone was given as a rescue analgesic in all patients . Two patients from the femoral group were excluded due to technical failure . Three patients in the morphine group and one patient in the femoral group did not need any additional oxycodone . In the morphine group on average 2.8 ( range 0 - 7 ) and in the femoral group 3.2 ( 0 - 5 ) additional doses of oxycodone were needed during the 24 h observation period . The mean pain scores were significantly lower in the morphine group at 9 and 12 h into the 24-h trial . Itching was seen only in the morphine group ( 40 % of the patients ) . Other side effects were similar in the two groups . All patients were satisfied with their pain therapy . Both intrathecal morphine and femoral 3-in-1 block alone were insufficient for the treatment of severe pain after major knee surgery Background and Objectives . Peripherally administered opioids , e.g. , intra‐articular morphine , exert their analgesic action on local opioid receptors . The present study investigated the safety and efficacy of intrabursal oxycodone and bupivacaine in comparison with bupivacaine infiltration and interscalene brachial plexus block in conjunction with shoulder surgery . Methods . A prospect i ve , r and omized study was conducted in 45 patients ( 15 per group ) undergoing elective shoulder surgery during general anesthesia . At the end of the surgery , patients received either 10 mL 0.5 % bupivacaine ( group B ) or 5 mg oxycodone and 10 mL 0.5 % bupivacaine ( group OB ) in the subacromial bursa ; interscalene plexus blocks were performed preoperative ( group IPB ) . Postoperative analgesia was provided by patient‐controlled analgesia , and the amount of intravenous fentanyl used during the total perioperative period was recorded . Postoperative pain was assessed by a visual analog scale . Results . The total fentanyl consumption was lower in groups OB and IPB than in group B , and the difference reached statistical significance for both groups ( P = .045 and P = .006 , respectively ) . However , the groups OB and IPB did not differ in respect to their fentanyl requirements ( P = 1.000 ) . Visual analog scores for pain were lowest in group IBP during the first 6 postoperative hours . The incidence of adverse effects was similar in all groups ; serious adverse effects did not occur . Conclusions . According to the present study , intrabursal oxycodone and bupivacaine offer an acceptable and efficient method for postoperative analgesia after shoulder surgery Ketoprofen ( Orudis ) is a nonsteroidal anti‐inflammatory drug that is currently approved in the United States for the management of mild to moderate pain . The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain . This r and omized , double‐blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen , the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride , 650 mg acetaminophen , or placebo in 240 patients with severe postoperative pain after cesarean section . Analgesia for the first dose was assessed over an 8‐hour period . Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose ( 325 mg acetaminophen plus 5 mg oxycodone ) were also assessed for up to 7 days . The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures . A dose response was observed between the two doses of ketoprofen , with the 100 mg dose providing significantly greater analgesia over the lower dose . Ketoprofen , 100 mg , was at least as effective as the combination and its effects lasted longer , with the exception of hour 1 when the combination was superior . Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups . Significantly more patients who took repeated doses of the combination ( 84 % ) than those who took either dose of ketoprofen ( 70 % ) had adverse effects . Ketoprofen at both dose levels was shown to be effective , long‐lasting , and well tolerated , and it should be considered as a viable option for the management of moderate to severe postoperative pain The pharmacokinetics of oxycodone have been determined after single-dose administration by the intravenous ( 4.6–7.3 mg ) , oral ( tablets , 9.1 mg and syrup , 9.1 mg ) , and rectal ( 30 mg ) routes , in 48 patients undergoing minor surgery . There were no significant differences in the mean elimination half-lives between the intravenous ( 5.45 ± 1.43 h ) , oral tablets ( 5.65 ± 1.13 h ) , oral syrup ( 4.80 ± 1.13 h ) , and rectal suppository ( 5.40 ± 1.19 h ) formulations of oxycodone . After intravenous administration , the mean plasma clearance of oxycodone was 25.5 ± 10.1 L/h and the mean volume of distribution at steady state was 2.5 ± 0.8 L/kg . The mean normalized area under the curve ( AUC/D ) obtained after intravenous dosing ( 48.2 ± 30.2 μg · h/L/mg ) was more than twice the AUC/D values obtained after the administration of oxycodone tablets ( 19.8 ± 3.5 μg · h/L/mg ) , oxycodone syrup ( 17.5 ± 5.3 μg · h/L/mg ) , and rectal suppository ( 20.3 ± 5.1 μg · h/L/mg ) , indicating that the amount of oxycodone reaching the systemic circulation after the extravascular routes of administration was < 50 % of that obtained after intravenous dosing . The mean absorption lag times after oxycodone tablets ( 0.52 ± 0.33 h ) , oxycodone syrup ( 0.48 ± 0.40 h ) , and rectal suppository ( 0.76 ± 0.47 h ) were consistent with the onset of pharmacological effects reported by the patients |
13,472 | 23,450,585 | Data from studies of warmth and energy efficiency interventions suggested that improvements in general health , respiratory health , and mental health are possible .
Studies which targeted those with inadequate warmth and existing chronic respiratory disease were most likely to report health improvement .
Impacts following housing-led neighbourhood renewal were less clear ; these interventions targeted areas rather than individual households in most need .
There were few reports of adverse health impacts following housing improvement .
Warmth improvements were associated with increased usable space , increased privacy , and improved social relationships ; absences from work or school due to illness were also reduced .
Housing investment which improves thermal comfort in the home can lead to health improvements , especially where the improvements are targeted at those with inadequate warmth and those with chronic respiratory disease .
The health impacts of programmes which deliver improvements across areas and do not target according to levels of individual need were less clear , but reported impacts at an area level may conceal health improvements for those with the greatest potential to benefit .
Best available evidence indicates that housing which is an appropriate size for the householders and is affordable to heat is linked to improved health and may promote improved social relationships within and beyond the household .
In addition , there is some suggestion that provision of adequate , affordable warmth may reduce absences from school or work . | BACKGROUND The well established links between poor housing and poor health indicate that housing improvement may be an important mechanism through which public investment can lead to health improvement .
Intervention studies which have assessed the health impacts of housing improvements are an important data re source to test assumptions about the potential for health improvement .
Evaluations may not detect long term health impacts due to limited follow-up periods .
Impacts on socio-economic determinants of health may be a valuable proxy indication of the potential for longer term health impacts .
OBJECTIVES To assess the health and social impacts on residents following improvements to the physical fabric of housing . | BACKGROUND There has been little rigorous economic analysis of the relationship between asthma and improved housing . AIM To evaluate the cost-effectiveness of installing ventilation systems , and central heating if necessary , in homes of children with ' moderate ' or ' severe ' asthma . DESIGN AND SETTING An incremental cost-effectiveness analysis alongside a pragmatic r and omised controlled trial of a tailored package of housing modifications design ed to improve ventilation and household heating in homes within Wrexham County Borough , Wales , UK . METHOD A total of 177 children aged between 5 and 14 years , identified from general practice registers , were studied . Parents reported on the quality of life of their children over a 12-month period . General practice s reported on health-service re sources used by those children , and their asthma-related prescriptions , over the same period . RESULTS The tailored package shifted 17 % of children in the intervention group from ' severe ' to ' moderate ' asthma , compared with a 3 % shift in the control group . The mean cost of these modifications was £ 1718 per child treated or £ 12300 per child shifted from ' severe ' to ' moderate ' . Healthcare costs over 12 months following r and omisation did not differ significantly between intervention and control groups . Bootstrapping gave an incremental cost-effectiveness ratio ( ICER ) of £ 234 per point improvement on the 100-point PedsQL ™ asthma-specific scale , with 95 % confidence interval ( CI ) = £ 140 to £ 590 . The ICER fell to £ 165 ( 95 % CI = £ 84 to £ 424 ) for children with ' severe ' asthma . CONCLUSION This novel and pragmatic trial , with integrated economic evaluation , reported that tailored improvement of the housing of children with moderate to severe asthma is likely to be a cost-effective use of public re sources . This is a rare example of evidence for collaboration between local government and the NHS Background Improvements in health are an important expected outcome of many housing infrastructure programs . The authors aim ed to determine if improvement in the notoriously poor housing infrastructure in Australian Indigenous communities results in reduction in common childhood illness and to identify important mediating factors in this relationship . Methods The authors conducted a prospect i ve cohort study of 418 children aged 7 years or younger in 10 Australian Indigenous communities , which benefited most substantially from government-funded housing programs over 2004–2005 . Data on functional and hygienic state of houses , reports of common childhood illness and on socio-economic conditions were collected through inspection of household infrastructure and interviews with children 's carers and householders . Results After adjustment for a range of potential confounding variables , the analysis showed no consistent reduction in carers ' reporting of common childhood illnesses in association with improvements in household infrastructure , either for specific illnesses or for these illnesses in general . While there was strong association between improvement in household infrastructure and improvement of hygienic condition of the house , there were only marginal improvements in crowding . Conclusions High levels of household crowding and poor social , economic and environmental conditions in many Australian Indigenous communities appear to place major constraints on the potential for building programs to impact on the occurrence of common childhood illness . These findings reinforce the need for building programs to be supported by a range of social , behavioural and community-wide environmental interventions in order for the potential health gains of improved housing to be more fully realised BACKGROUND Few robust studies have tested whether enhancing housing also improves health . AIM To evaluate the effectiveness of installing ventilation systems , and central heating where necessary , in the homes of children with moderate or severe asthma . DESIGN AND SETTING Pragmatic r and omised controlled trial ( RCT ) in homes within Wrexham County Borough , Wales , UK . METHOD A pragmatic RCT was carried out , of a tailored package of housing improvements providing adequate ventilation and temperature , following inspection by a housing officer . One hundred and ninety-two children with asthma aged 5 to 14 years , identified from general practice registers , were r and omised to receive this package , either immediately or a year after recruitment . At baseline , and after 4 and 12 months , parents reported their child 's asthma-specific and generic quality of life , and days off school . RESULTS The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months . At 12 months , this showed an adjusted mean difference between groups of 7.1 points ( 95 % confidence interval [ CI ] = 2.8 to 11.4 , P= 0.001 ) : a moderate st and ardised effect size of 0.42 . The generic quality -of-life scale showed reported physical problems were significantly reduced at 4 months , but not quite at 12 months , when the mean difference was 4.5 ( 95 % CI = -0.2 to 9.1 , P= 0.061 ) . The improvement in psychosocial quality of life at 12 months was not significant , with a mean difference of 2.2 ( 95 % CI = -1.9 to 6.4 , P= 0.292 ) . Parent-reported school attendance improved , but not significantly . CONCLUSION This novel and pragmatic trial , with integrated economic evaluation , found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems . Collaborative housing initiatives have potential to improve health Background : It is not clear whether associations between respiratory symptoms and indoor mould are causal . A r and omised controlled trial was conducted to see whether asthma improves when indoor mould is removed . Methods : Houses of patients with asthma were r and omly allocated into two groups . In one group , indoor mould was removed , fungicide was applied and a fan was installed in the loft . In the control group , intervention was delayed for 12 months . Question naires were administered and peak expiratory flow rate was measured at baseline , 6 months and 12 months . Results : Eighty-one houses were allocated to the intervention group and 83 to the control group ; 95 participants in 68 intervention houses and 87 in 63 control houses supplied follow-up information . Peak expiratory flow rate variability declined in both groups , with no significant differences between them . At 6 months , significantly more of the intervention group showed a net improvement in wheeze affecting activities ( difference between groups 25 % , 95 % CI 3 % to 47 % ; p = 0.028 ) , perceived improvement of breathing ( 52 % , 95 % CI 30 % to 74 % ; p<0.0001 ) and perceived reduction in medication ( 59 % , 95 % CI 35 % to 81 % ; p<0.0001 ) . By 12 months the intervention group showed significantly greater reductions than the controls in preventer and reliever use , and more improvement in rhinitis ( 24 % , 95 % CI 9 % to 39 % ; p = 0.001 ) and rhinoconjunctivitis ( 20 % , 95 % CI 5 % to 36 % ; p = 0.009 ) . Conclusions : Although there was no objective evidence of benefit , symptoms of asthma and rhinitis improved and medication use declined following removal of indoor mould . It is unlikely that this was entirely a placebo effect In a field study carried out in three rural communities in Paraguay in a zone endemic for Chagas disease , we implemented three different vector control interventions --spraying , housing improvement , and a combination of spraying plus housing improvement -- which effectively reduced the triatomine infestation . The reduction of triatomine infestation was 100 % ( 47/47 ) in the combined intervention community , whereas in the community where housing improvement was carried out it was 96.4 % ( 53/55 ) . In the community where fumigation alone was used , the impact was 97.6 % ( 40/41 ) in terms of domiciliary infestation . In all the houses where an intervention was made , an 18-month follow-up showed reinfestation rates of less than 10 % . A serological survey of the population in the pre- and post-intervention periods revealed a shift in positive cases towards older age groups , but no significant differences were observed . The rate of seroconversion was 1.3 % ( three new cases ) in the community with housing improvement only , but none of these cases could have result ed from vector transmission . The most cost-effective intervention was insecticide spraying , which during a 21-month follow-up period had a high impact on triatomine infestation and cost US$ 29 per house as opposed to US$ 700 per house for housing improvement An outst and ing feature of marginalized Roma communities is their severely subst and ard living conditions , which contribute to their worse health status compared to the majority . However , health consequences of international and local-level housing initiatives in most cases fail to be assessed prospect ively or evaluated after implementation . This paper summarizes the result of a retrospective health impact assessment of a Roma housing project in Hungary in comparison with the outcome evaluation of the same project . Positive impacts on education , in- and outdoor conditions were noted , but negative impacts on social networks , housing expenses and maintenance , neighbourhood satisfaction and no sustained change in health status or employment were identified . Recommendations are made to improve efficiency and sustainability of housing development initiatives among disadvantaged population Background New Zeal and homes are underheated by international st and ards , with average indoor temperatures below the WHO recommended minimum of 18 ° C . Research has highlighted the connection between low indoor temperatures and adverse health outcomes , including social functioning and psychological well-being . Both health effects and social effects can impact on school absence rates . The aim of this study was to determine whether more effective home heating affects school absence for children with asthma . Methods A single-blinded r and omised controlled trial of heating intervention in 409 households containing an asthmatic child aged 6–12 years , where the previous heating was an open fire , plug-in electric heater or unflued gas heater . The intervention was the installation of a more effective heater of at least 6 kW before the winter of 2006 in half the houses . Demographic and health information was collected both before and after the intervention . Each child 's school was contacted directly and term-by-term absence information for that child obtained for 2006 and previous years where available . Results Complete absence data were obtained for 269 out of 409 children . Compared with the control group , children in households receiving the intervention experienced on average 21 % ( p=0.02 ) fewer days of absence after allowing for the effects of other factors . Conclusion More effective , non-indoor polluting heating reduces school absence for asthmatic children RATIONALE Particulate air pollution is associated with cardiovascular morbidity . One hypothesized mechanism involves oxidative stress , systemic inflammation , and endothelial dysfunction . OBJECTIVES To assess an intervention 's impact on particle exposures and endothelial function among healthy adults in a woodsmoke-impacted community . We also investigated the underlying role of oxidative stress and inflammation in relation to exposure reductions . METHODS Portable air filters were used in a r and omized crossover intervention study of 45 healthy adults exposed to consecutive 7-day periods of filtered and nonfiltered air . MEASUREMENTS AND MAIN RESULTS Reactive hyperemia index was measured as an indicator of endothelial function via peripheral artery tonometry , and markers of inflammation ( C-reactive protein , interleukin-6 , and b and cells ) and lipid peroxidation ( malondialdehyde and 8-iso-prostagl and in F(2α ) ) were quantified . Air filters reduced indoor fine particle concentrations by 60 % . Filtration was associated with a 9.4 % ( 95 % confidence interval , 0.9 - 18 % ) increase in reactive hyperemia index and a 32.6 % ( 4.4 - 60.9 % ) decrease in C-reactive protein . Decreases in particulate matter and the woodsmoke tracer levoglucosan were associated with reduced b and cell counts . There was limited evidence of more pronounced effects on endothelial function and level of systemic inflammation among males , overweight participants , younger participants , and residents of wood-burning homes . No associations were noted for oxidative stress markers . CONCLUSIONS Air filtration was associated with improved endothelial function and decreased concentrations of inflammatory biomarkers but not markers of oxidative stress . Our results support the hypothesis that systemic inflammation and impaired endothelial function , both predictors of cardiovascular morbidity , can be favorably influenced by reducing indoor particle concentrations UNLABELLED Inuit infants have high rates of reported hospitalization for respiratory infection , associated with overcrowding and reduced ventilation . We performed a r and omized , double-blind , placebo controlled trial to determine whether home heat recovery ventilators ( HRV ) would improve ventilation and reduce the risk of respiratory illnesses in young Inuit children . Inuit children under 6 years of age living in several communities in Nunavut , Canada were r and omized to receive an active or placebo HRV . We monitored respiratory symptoms , health center encounters , and indoor air quality for 6 months . HRVs were placed in 68 homes , and 51 houses could be analyzed . Subjects had a mean age of 26.8 months . Active HRVs brought indoor carbon dioxide concentrations to within recommended concentrations . Relative humidity was also reduced . Use of HRV , compared with placebo , was associated with a progressive fall in the odds ratio for reported wheeze of 12.3 % per week ( 95%CI 1.9 - 21.6 % , P = 0.022 ) . Rates of reported rhinitis were significantly lower in the HRV group than the placebo group in month 1 ( odds ratio 0.20 , 95%CI 0.058 - 0.69 , P = 0.011 ) and in month 4 ( odds ratio 0.24 , 95%CI 0.054 - 0.90 , P = 0.035 ) . There were no significant reductions in the number of health center encounters , and there were no hospitalizations . Use of HRVs was associated with in improvement in air quality and reductions in reported respiratory symptoms in Inuit children . PRACTICAL IMPLICATION S Reduced ventilation is common in the houses of Inuit children in a rct ic Canada , and is associated with an increased risk of respiratory infection . Installation of HRV brings indoor carbon dioxide concentration , as a marker of adequate ventilation , to within recommended concentrations , although relative humidity is also reduced . Installation of HRV is associated with improvements in indoor air quality , and a reduced risk of wheezing and rhinitis not associated with cold air exposure in young Inuit children . Further research is required to explore traditional Inuit cultural attitudes about air movement in dwellings Background : Housing is an important environmental influence on population health , and there is growing evidence of health effects from indoor environment characteristics such as low indoor temperatures . However , there is relatively little research , and thus little firm guidance , on the cost-effectiveness of public policies to retrospectively improve the st and ards of houses . The purpose of this study was to value the health , energy and environmental benefits of retrofitting insulation , through assessing a number of forms of possible benefit : a reduced number of visits to GPs , hospitalisations , days off school , days off work , energy savings and CO2 savings . Methods : All these metrics are used in a cluster r and omised trial — the “ Housing , Insulation and Health Study ” —of retrofitting insulation in 1350 houses , in which at least one person had symptoms of respiratory disease , in predominantly low-income communities in New Zeal and . Results : Valuing the health gains , and energy and CO2 emissions savings , suggests that total benefits in “ present value ” ( discounted ) terms are one and a half to two times the magnitude of the cost of retrofitting insulation . Conclusion : This study points to the need to consider as wide a range of benefits as possible , including health and environmental benefits , when assessing the value for money of an intervention to improve housing quality . From an environmental , energy and health perspective , the value for money of improving housing quality by retrofitting insulation is compelling A r and omised trial of 178 patients in Aberdeen , UK with a previous hospital admission for chronic obstructive pulmonary disease ( COPD ) was carried out in order to determine whether improving home energy efficiency improves health-related quality of life in COPD patients . 118 patients were r and omised and 60 agreed to monitoring only . Energy efficiency upgrading was carried out in 42 % of homes r and omised to intervention . Independent energy efficiency action was taken by 15 % of control participants and 18 % in the monitoring group . The main outcome measures were respiratory and general health status , home energy efficiency and hospital admissions . Intention-to-treat analysis found no difference in outcomes between the two groups . In 45 patients , who had energy efficiency action independent of original r and omisation , there were significant improvements in respiratory symptom scores ( adjusted mean 9.0 , 95 % CI 2.5–15.5 ) , decreases in estimated annual fuel costs ( -£65.3 , 95 % CI -£31.9– -£98.7 ) and improved home energy efficiency rating ( 1.1 , 95 % CI 0–1.4 ) . COPD patients are unlikely to take up home energy efficiency upgrading , if offered . Secondary “ pragmatic ” analysis suggests that those who do take action may achieve clinical ly significant improvement in respiratory health , which is not associated with an increase in indoor warmth A three-year study ( 1999 - 2001 ) was initiated in the UK to assess the effect of improving housing conditions in 3 - 4 bedroom , single-family unit , social rented sector houses on the health of the occupants . The houses were r and omised into two groups . Phase I houses received extensive upgrading including wet central heating , on dem and ventilation , double-glazed doors , cavity wall and roof/loft insulation . An identical intervention for Phase II houses was delayed for one year . As part of this r and omised waiting list study , discrete measurements were made of indoor environmental variables in each house , to assess the short-term effects of improving housing conditions on the indoor environment . Variables representative of indoor environmental conditions were measured in the living room , bedroom and outdoors in each of the three years of the study . In 2000 , there was a significant difference between the changes from 1999 to 2000 between Phase I ( up grade d ) and II ( not then up grade d ) houses for bedroom temperatures ( p=0.002 ) . Changes in wall surface dampness and wall dampness in Phase I houses were also significantly different to the change in Phase II houses in 2000 ( p=0.001 ) , but by 2001 the Phase I houses had reverted to the same dampness levels they had before upgrading . The housing up grade s increased bedroom temperatures in all houses . Other indoor environmental variables were not affected This paper describes the purpose and methods of a single-blinded , clustered and r and omised trial of the health impacts of insulating existing houses . The key research question was whether this intervention increased the indoor temperature and lowered the relative humidity , energy consumption and mould growth in the houses , as well as improved the health and well-being of the occupants and thereby lowered their utilisation of health care . Households in which at least one person had symptoms of respiratory disease were recruited from seven predominantly low-income communities in New Zeal and . These households were then r and omised within communities to receive retrofitted insulation either during or after the study . Measures at baseline ( 2001 ) and follow-up ( 2002 ) included subjective measures of health , comfort and well-being and objective measures of house condition , temperature , relative humidity , mould ( speciation and mass ) , endotoxin , beta glucans , house dust mite allergens , general practitioner and hospital visits , and energy or fuel usage . All measurements referred to the three coldest winter months , June , July and August . From the 1352 households that were initially recruited , baseline information was obtained from 1310 households and 4413 people . At follow-up , 3312 people and 1110 households remained , an 84 % household retention rate and a 75 % individual retention rate . Final outcome results will be reported in a subsequent paper . The study showed that large trials of complex environmental interventions can be conducted in a robust manner with high participation rates . Critical success factors are effective community involvement and an intervention that is valued by the participants This study aim ed to explore the role of dwelling conditions and neighbourhood characteristics in explaining the frequently observed association between housing tenure and health . A postal question naire , focusing on a number of specific aspects of the home and the area , was sent to a r and om sample of adults in the west of Scotl and ( achieved sample size 2867 , response rate 50 % ) . The health measures were limiting long-st and ing illness , self-assessed health , recent symptoms , and anxiety and depression . Having controlled for age , sex , and marital status , housing tenure explained , respectively , 2.7 % , 5.4 % , 3.9 % , 2.4 % and 5.4 % of the variance in these variables . These percentages were reduced by between 93 % ( for anxiety ) and 73 % ( for self-assessed health ) when housing problems , housing fixtures , overcrowding , dwelling type , access to garden , area type and area amenities were introduced into the model . This suggests that features of the dwelling and its surroundings help to explain observed associations between tenure and health in the UK , and that housing and area problems may be particularly important . Housing improvements and urban regeneration may help to reduce the health gap between housing tenures , and more generally to reduce inequalities in health Objective To determine whether insulating existing houses increases indoor temperatures and improves occupants ' health and wellbeing . Design Community based , cluster , single blinded r and omised study . Setting Seven low income communities in New Zeal and . Participants 1350 households containing 4407 participants . Intervention Installation of a st and ard retrofit insulation package . Main outcome measures Indoor temperature and relative humidity , energy consumption , self reported health , wheezing , days off school and work , visits to general practitioners , and admissions to hospital . Results Insulation was associated with a small increase in bedroom temperatures during the winter ( 0.5 � C ) and decreased relative humidity ( −2.3 % ) , despite energy consumption in insulated houses being 81 % of that in uninsulated houses . Bedroom temperatures were below 10 � C for 1.7 fewer hours each day in insulated homes than in uninsulated ones . These changes were associated with reduced odds in the insulated homes of fair or poor self rated health ( adjusted odds ratio 0.50 , 95 % confidence interval 0.38 to 0.68 ) , self reports of wheezing in the past three months ( 0.57 , 0.47 to 0.70 ) , self reports of children taking a day off school ( 0.49 , 0.31 to 0.80 ) , and self reports of adults taking a day off work ( 0.62 , 0.46 to 0.83 ) . Visits to general practitioners were less often reported by occupants of insulated homes ( 0.73 , 0.62 to 0.87 ) . Hospital admissions for respiratory conditions were also reduced ( 0.53 , 0.22 to 1.29 ) , but this reduction was not statistically significant ( P=0.16 ) . Conclusion Insulating existing houses led to a significantly warmer , drier indoor environment and result ed in improved self rated health , self reported wheezing , days off school and work , and visits to general practitioners as well as a trend for fewer hospital admissions for respiratory conditions STUDY OBJECTIVE To examine whether changes in environmental housing quality influence the wellbeing of movers taking into account other dimensions of housing quality and sociodemographic factors . DESIGN Cross sectional telephone survey . Associations between changes in satisfaction with 40 housing quality indicators ( including environmental quality ) and an improvement in self rated health ( based on a st and ardised question ) were analysed by multiple logistic regression adjusting for sociodemographic variables . Objective measures of wellbeing or environmental quality were not available . SETTING North western region of Switzerl and including the city of Basel . PARTICIPANTS R and om sample of 3870 subjects aged 18–70 who had moved in 1997 , participation rate 55.7 % . RESULTS A gain in self rated health was most strongly predicted by an improved satisfaction with indicators related to the environmental housing quality measured as “ location of building ” ( adjusted odds ratio ( OR ) = 1.58 , 95 % confidence intervals ( CI ) = 1.28 , 1.96 ) and “ perceived air quality ” ( OR=1.58 , 95 % CI=1.24 , 2.01 ) and to the apartment itself , namely “ suitability ” ( OR=1.77 , 95 % CI=1.41 , 2.23 ) , “ relationship with neighbours ” ( OR=1.46 , 95 % CI=1.19 , 1.80 ) and “ noise from neighbours ” ( OR=1.32 , 95 % CI=1.07 , 1.64 ) . The destination of moving and the main reason to move modified some of the associations with environmental indicators . CONCLUSION An improvement in perceived environmental housing quality was conducive to an increase in wellbeing of movers when other dimensions of housing quality and potential confounders were taken into account Objective To assess whether non-polluting , more effective home heating ( heat pump , wood pellet burner , flued gas ) has a positive effect on the health of children with asthma . Design R and omised controlled trial . Setting Households in five communities in New Zeal and . Participants 409 children aged 6 - 12 years with doctor diagnosed asthma . Interventions Installation of a non-polluting , more effective home heater before winter . The control group received a replacement heater at the end of the trial . Main outcome measures The primary outcome was change in lung function ( peak expiratory flow rate and forced expiratory volume in one second , FEV1 ) . Secondary outcomes were child reported respiratory tract symptoms and daily use of preventer and reliever drugs . At the end of winter 2005 ( baseline ) and winter 2006 ( follow-up ) parents reported their child ’s general health , use of health services , overall respiratory health , and housing conditions . Nitrogen dioxide levels were measured monthly for four months and temperatures in the living room and child ’s bedroom were recorded hourly . Results Improvements in lung function were not significant ( difference in mean FEV1 130.7 ml , 95 % confidence interval −20.3 to 281.7 ) . Compared with children in the control group , however , children in the intervention group had 1.80 fewer days off school ( 95 % confidence interval 0.11 to 3.13 ) , 0.40 fewer visits to a doctor for asthma ( 0.11 to 0.62 ) , and 0.25 fewer visits to a pharmacist for asthma ( 0.09 to 0.32 ) . Children in the intervention group also had fewer reports of poor health ( adjusted odds ratio 0.48 , 95 % confidence interval 0.31 to 0.74 ) , less sleep disturbed by wheezing ( 0.55 , 0.35 to 0.85 ) , less dry cough at night ( 0.52 , 0.32 to 0.83 ) , and reduced scores for lower respiratory tract symptoms ( 0.77 , 0.73 to 0.81 ) than children in the control group . The intervention was associated with a mean temperature rise in the living room of 1.10 ° C ( 95 % confidence interval 0.54 ° C to 1.64 ° C ) and in the child ’s bedroom of 0.57 ° C ( 0.05 ° C to 1.08 ° C ) . Lower levels of nitrogen dioxide were measured in the living rooms of the intervention households than in those of the control households ( geometric mean 8.5 μg/m3 v 15.7 μg/m3 , P<0.001 ) . A similar effect was found in the children ’s bedrooms ( 7.3 μg/m3 v 10.9 μg/m3 , P<0.001 ) . Conclusion Installing non-polluting , more effective heating in the homes of children with asthma did not significantly improve lung function but did significantly reduce symptoms of asthma , days off school , healthcare utilisation , and visits to a pharmacist . Trial registration Clinical Trials NCT00489762 Study objective : To evaluate self-reported changes in housing quality and health associated with housing-led area regeneration . Design : A prospect i ve study over 1 year using structured interviews with 50 households who moved to new housing and with 50 matched controls who did not move . Setting and participants : Residents of two social rented housing schemes in the West of Scotl and . Results : Small but not statistically significant increases in levels of “ excellent ” or “ good ” self-reported health status were found in both groups . Both intervention and control groups experienced reductions in problems related to warmth , but no significant change in how they felt about their house . Conclusions : It is feasible to conduct prospect i ve controlled studies to evaluate the health effects of housing improvement using matched control groups . The absence of marked improvement in health after moving to new housing might be due to the small sample size or to the limited potential to improve health through this intervention alone Objective : To assess the effect of a publicly funded domestic heating programme on self-reported health . Design , setting and participants : A prospect i ve controlled study of 1281 households in Scotl and receiving new central heating under a publicly funded initiative , and 1084 comparison households not receiving new heating . The main outcome measures were self-reported diagnosis of asthma , bronchitis , eczema , nasal allergy , heart disease , circulatory problems or high blood pressure ; number of primary care encounters and hospital contacts in the past year ; and SF-36 Health Survey scores . Results : Usable data were obtained from 61.4 % of 3849 respondents originally recruited . Heating recipients reported higher scores on the SF-36 Physical Functioning scale ( difference 2.51 ; 95 % CI 0.67 to 4.37 ) and General Health scale ( difference 2.57 ; 95 % CI 0.90 to 4.34 ) . They were less likely to report having received a first diagnosis of heart disease ( OR 0.69 ; 95 % CI 0.52 to 0.91 ) or high blood pressure ( OR 0.77 ; 95 % CI 0.61 to 0.97 ) , but the groups did not differ significantly in use of primary care or hospital services . Conclusions : Provision of central heating was associated with significant positive effects on general health and physical functioning ; however , effect sizes were small . Evidence of a reduced risk of first diagnosis with heart disease or high blood pressure must be interpreted with caution , due to the self-reported nature of the outcomes , the limited time period and the failure to detect any difference in health service use The nutritional impact of a water and sanitation intervention in a rural community of Bangladesh , comprising the provision of h and pumps , construction of latrines and hygiene education was assessed . During 3 years , the quarterly anthropometric measures of about 200 children aged 12 - 35 months from the intervention community were compared with those of a similar number of children from a control area . The interventions reduced the incidence of diarrhoea by 25 per cent among the children less than 5 years of age . There was no significant difference in nutritional status , however , between the two groups of children . Moreover , within the intervention area , indicators of water and latrine use were not significantly related to the children 's nutritional status . This suggests that either the obtained reduction of diarrhoea was not large enough to have an impact on nutritional status or that diarrhoea is not an important cause of malnutrition in this community An integrated water supply , sanitation and hygiene ( WSH ) education intervention project was run by the International Centre for Diarrhoeal Disease Research , Bangladesh , over the period 1983 - 87 . In the intervention area the project provided h and pumps , pit latrines , and hygiene education to about 800 households . The control population did not receive any interventions , but had access to the usual government and private WSH facilities . After 1987 no external support was provided to maintain these provisions . A cross-sectional follow-up survey , which was carried out in 1992 , involved about 500 r and omly selected households from the intervention and control areas . In 1992 about 82 % of the pumps were still in good functional condition and of these , 94 % had been functioning well in 1987 . Fewer latrines were functional in 1992 ( 64 % ) than at the end of 1987 ( 93 % ) . In the former intervention area about 84 % of the adults were using sanitary latrines in 1992 compared with only 7 % in the control area . Knowledge related to disease transmission , however , was poor and similar in both areas . People cl aim ed that they used the WSH facilities to improve the quality of their lives . The prevalence of diarrhoeal diseases in the 1992 survey among the control population was about twice that among those in the intervention area STUDY OBJECTIVE --The aim was to test the hypothesis that provision of household amenities such as domestic hot water systems and bathrooms changed hygiene which thereby triggered the epidemic of appendicitis in Anglesey after the second world war . DESIGN --The study was a cross sectional survey with histories of housing and appendicectomy obtained from Anglesey residents by postal question naire . The main outcome measure was reported appendicectomy . SETTING --Four general practice s in Anglesey . SUBJECTS--2531 men and women born during 1923 - 62 and r and omly selected from age-sex registers . Overall response rate was 73.7 % . MAIN RESULTS --Subjects born into households with amenities -- piped water , hot water systems , and bathrooms had , if anything , a reduced risk of appendicectomy . However , those who subsequently moved to houses that lacked amenities were at significantly higher risk than people born into houses without amenities who later acquired them . CONCLUSIONS --Provision of household amenities was not the important trigger to the epidemic of appendicitis which occurred in Anglesey after the second world war . Rather , the trigger may have been reduction in domestic crowding caused by the falling birth rate . Findings among those who moved house support other evidence that after infancy household amenities protect against appendicitis and contributed to the fall in appendicitis rates in Anglesey after 1965 In a short term qualitative study exploring the impact that improvements to housing might have upon the health of household members , respondents perceived significant benefits of housing improvements for physical and mental health , and for both children and adults . There is a need for prospect i ve research which monitors health and wellbeing before , during , and after housing improvement and which uses independent measures of health Objective : To assess the short term health effects of improving housing . Design : R and omised to waiting list . Setting : 119 council owned houses in south Devon , UK . Participants : About 480 residents of these houses . Intervention : Upgrading houses ( including central heating , ventilation , rewiring , insulation , and re-roofing ) in two phases a year apart . Main outcome measures : All residents completed an annual health question naire : SF36 and GHQ12 ( adults ) . Residents reporting respiratory illness or arthritis were interviewed using condition-specific question naires , the former also completing peak flow and symptom diaries ( children ) or spirometry ( adults ) . Data on health service use and time lost from school were collected . Results : Interventions improved energy efficiency . For those living in intervention houses , non-asthma-related chest problems ( Mann – Whitney test , p = 0.005 ) and the combined asthma symptom score for adults ( Mann – Whitney test , z = 2.7 , p = 0.007 ) diminished significantly compared with control houses . No difference between intervention and control houses was seen for SF36 or GHQ12 . Conclusions : Rigorous study design s for the evaluation of complex public health and community based interventions are possible . Quantitatively measured health benefits are small , but as health benefits were measured over a short time scale , there may have been insufficient time for measurable improvements in general and disease-specific health to become apparent Objective To establish whether rehousing people to new dwellings had impacts upon residents ’ mental health and psychosocial benefits derived from the home . Methods A prospect i ve controlled study across Scotl and involving 723 householders ( 334 intervention ; 389 control ) . Interviews were carried out just prior to the move , and 2 years thereafter . Results Changes in self-reported psychosocial benefits were greater than changes in mental health . Respondents in family households appeared to have gained the most and those in older person households the least . For those in families , the most consistent effects flowed from improvements in space , privacy and change of location ; for those in adult-only households , improvements in crime and safety mattered most . Gains in psychosocial benefits were associated with improved mental health ( SF-36 ) scores . Conclusions Rehousing has substantial impacts on residential conditions and on psychosocial benefits , and lesser ( possibly indirect ) impacts upon mental health . Housing is a complex intervention applied to a heterogeneous group for a range of reasons . Hence its impacts result from different aspects of residential change for particular types of household BACKGROUND The relationship between exposure to house dust mite ( HDM ) allergens and prevalence of sensitization to these allergens in patients with asthma has been confirmed in many studies . Mite population growth is regulated by humidity . Reducing humidity and removing allergen by efficient vacuuming should control mite allergen and reduce symptoms . OBJECTIVE We sought to investigate the effect of mechanical ventilation and high-efficiency vacuuming on HDM numbers and Der p 1 concentrations in the homes of mite-sensitive asthmatic subjects and to evaluate the effect of any reductions on symptoms . METHODS The homes of 40 HDM-sensitive asthmatic subjects were r and omized to receive ( 1 ) mechanical ventilation and a high-efficiency vacuum cleaner ( HEVC ) ; ( 2 ) mechanical ventilation alone ; ( 3 ) an HEVC alone ; and ( 4 ) no intervention . Homes and patients were monitored for 12 months . Change in absolute humidity , mite numbers , Der p 1 concentrations , lung function , bronchial hyperresponsiveness , and symptom scores were analyzed . RESULTS Homes with mechanical ventilation achieved significantly lower humidity levels than those without ( P < .001 ) , with an associated reduction of mite numbers ( P < .05 ) and Der p 1 concentrations ( P < .001 ¿ in nanograms per gram , P = .006 ¿ in milligrams per square meter ) in bedroom carpets and some other mite sources in the ventilated areas of the homes . The addition of a vacuum cleaner enhanced this effect . There was a trend for an improvement in histamine PC(20 ) ( P = .085 ) in the patients whose homes were ventilated . CONCLUSION The use of a mechanical ventilation system in suitable homes result ed in some reduction in numbers of HDM and Der p 1 concentrations . The addition of an HEVC slightly enhanced the effect but not sufficiently to see an improvement in symptoms BACKGROUND A r and omized study of the effect on people 's health of improving their housing is underway in Torbay . The link between poor health , particularly respiratory health , and poor housing conditions has been recognized for a long time , but there have been few intervention studies to demonstrate that improving housing can improve health . In 1994 , South and West Devon Health Authority set up a community development project in a deprived area of Torbay , in response to the concerns of local primary health-care workers . A community development worker helped local residents survey their homes for dampness and record their respiratory symptoms . The survey reported high levels of condensation/dampness and respiratory illness and the Council agreed to direct the majority of their housing improvement funds to the estate over the next 3 years . The Health Authority , University of Plymouth and Torbay Council were successful in obtaining funding to evaluate the housing improvements from the NHS R & D programme . PARTICIPANTS AND METHODS Of 119 houses eligible for the study , 50 were chosen at r and om and improved in the first year . The rest were improved the following year . Question naires screening for health problems were sent to all 580 residents and baseline surveys of the indoor environment were also carried out . More detailed health surveys were completed by community nurses visiting residents in their homes . All adults were asked to complete SF-36 and GHQ 12 question naires , as well as disease-specific question naires if appropriate . PROGRESS All houses in the study have now been improved , including insulation , double-glazing , re-roofing , heating , ventilation and electrical rewiring . Follow-up surveys are underway Lack of empirical evidence that living in damp houses has detrimental effects on health may partly be due to inadequate research . A preliminary study was therefore carried out of a r and om sample of council owned residences in a deprived area of Edinburgh , a respondent from consenting households being interviewed to obtain a profile of the physical and mental health of all adults and children . In addition , information was gathered about other factors that might be important , particularly smoking and selective bias in the allocation of tenants to houses . Independent measures of dampness were made by environmental health officers . No conclusive effects of damp on the health of adults were identified . Nevertheless , children living in damp houses , especially where fungal mould was present , had higher rates of respiratory symptoms , which were unrelated to smoking in the household , and higher rates of symptoms of infection and stress . Housing should remain an important public health issue , and the effects of damp warrant further investigation BACKGROUND Housing conditions are recognised as an important determinant of health . In the UK , interventions to improve domestic heating are in place with the expectation that they will improve health . As a component of evaluating such policies , this study assesses whether specific health outcomes are significantly associated with the extent and duration of domestic heating use , either directly or via a possible mediating effect of internal environmental conditions . METHODS Baseline data from a prospect i ve controlled study evaluating the health effects of a publicly-funded programme of heating improvements in Scotl and were used to assess associations among heating use , internal conditions , and three specific health outcomes . RESULTS There were significant associations ( P < 0.01 ) between measures of heating use and the presence of environmental problems in the home , such as mould and condensation . The presence of such problems was , in turn , found to be significantly predictive of two health outcomes derived from the SF-36 ( P < 0.01 ) and of adult wheezing ( P < 0.05 ) . The direction of significant associations was highly consistent : greater levels of heating were associated with reduced likelihood of environmental problems , and the presence of environmental problems was linked to poorer health status . Heating use was not directly associated with the health outcomes considered . CONCLUSIONS The study findings are consistent with a conceptual model in which health may be influenced by usage patterns of domestic heating , via the mediating effect of poor internal environmental conditions . Since these findings are based on cross-sectional data , interpretation must be carried out cautiously . However , if confirmed by planned future work they have important implication s for policy initiatives relating to domestic heating and fuel poverty |
13,473 | 27,657,801 | The strongest predictors of nocebo effects were a higher perceived dose of exposure , explicit suggestions that the exposure triggers arousal or symptoms , observing people experiencing symptoms from the exposure , and higher expectations of symptoms .
CONCLUSIONS To reduce nocebo induced symptoms associated with medication or other interventions clinicians could reduce expectations of symptoms , limit suggestions of symptoms , correct unrealistic dose perceptions , and reduce exposure to people experiencing side effects . | OBJECTIVES Medication side effects are common , often leading to reduced quality of life , nonadherence , and financial costs for health services .
Many side effects are the result of a psychologically mediated " nocebo effect . "
This review identifies the risk factors involved in the development of nocebo effects . | Summary Nonspecific placebo factors such as patients ' perceptions of a treatment and expectations toward effect seem to be central to the clinical efficacy of acupuncture analgesia . ABSTRACT It is well known that acupuncture has pain‐relieving effects , but the contribution of specific and especially nonspecific factors to acupuncture analgesia is less clear . One hundred one patients who developed pain of ≥3 on a visual analog scale ( VAS , 0 to 10 ) after third molar surgery were r and omized to receive active acupuncture , placebo acupuncture , or no treatment for 30 min with acupuncture needles with potential for double‐blinding . Patients ' perception of the treatment ( active or placebo ) and expected pain levels ( VAS ) were assessed before and halfway through the treatment . Looking at actual treatment allocation , there was no specific effect of active acupuncture ( P = .240 ) , but there was a large and significant nonspecific effect of placebo acupuncture ( P < .001 ) , which increased over time . Interestingly , however , looking at perceived treatment allocation , there was a significant effect of acupuncture ( P < .001 ) , indicating that patients who believed they received active acupuncture had significantly lower pain levels than those who believed they received placebo acupuncture . Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings after both active and placebo acupuncture ( up to 69.8 % ) . This is the first study to show that under optimized blinding conditions , nonspecific factors such as patients ' perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self‐reinforcing effects in acupuncture treatment . To obtain an effect of acupuncture in clinical practice , it may therefore be important to incorporate and optimize these factors OBJECTIVE This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect . It also investigated whether medication br and ing ( br and or generic labeling ) moderated social modeling effects . METHOD Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications ( actually placebos ) on preexamination anxiety . After taking the medication , participants were r and omized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication . Differences in symptom reporting , blood pressure , heart rate , and anxiety were assessed between the social modeling of side effects and no modeling groups . RESULTS Seeing a female confederate report side effects reduced the placebo effect in systolic ( p = .009 ) and diastolic blood pressure ( p = .033 ) . Seeing a female confederate report side effects also increased both total reported symptoms ( mean [ SE ] 7.35 [ .54 ] vs. 5.16 [ 0.53 ] p = .005 ) and symptoms attributed to the medication ( 5.27 [ 0.60 ] vs. 3.04 [ 0.59 ] p = .01 ) , although the effect on symptoms was only seen in female participants . Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group . Social modeling did not affect heart rate or anxiety . Medication br and ing did not influence placebo or nocebo outcomes . CONCLUSIONS The social modeling of symptoms can substantially reduce or eliminate the placebo effect . Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females Background : Expectancy and modeling have been cited as factors in mass psychogenic illness ( MPI ) , which reportedly affects more women than men . Purpose : The purpose of the study is to assess the effects of expectancy and modeling in a controlled laboratory analogue of MPI . Methods : Students were r and omly assigned to inhale or not inhale an inert placebo described as a suspected environmental toxin that had been linked to four symptoms typical of reported instances of MPI . Half of the students observed a female confederate inhale the substance and subsequently display the specified symptoms . Results : Students who inhaled the placebo reported greater increases in symptoms , and the increase was significantly greater for the specified symptoms than for other symptoms . Observation of the confederate displaying symptoms increased specified symptoms significantly among women but not among men . Changes in reported symptoms were significantly associated with changes in unobtrusively observed behavior . Conclusions : Symptoms typical of clinical reports of MPI can be induced by manipulating response expectancies , and the effects are specific rather than generalized . Among women , this effect is enhanced by observing another participant ( who in this study is also female ) display symptoms . This suggests that the preponderance of women showing symptoms in outbreaks of MPI may be due to gender-linked differences in the effects of modeling on psychogenic symptoms OBJECTIVES : Multiple chemical sensitivity is a poorly understood syndrome in which various symptoms are triggered by chemically unrelated , but often odorous substances , at doses below those known to be harmful . This study focuses on the process of pavlovian acquisition and extinction of somatic symptoms triggered by odours . METHODS : Diluted ammonia and butyric acid were odorous conditioned stimuli ( CS ) . The unconditioned stimulus ( US ) was 7.4 % CO2 enriched air . One odour ( CS+ ) was presented together with the US for 2 minutes ( CS+ trial ) , and the other odour ( CS- ) was presented with air ( CS-trial ) . Three CS+ and three CS-exposures were run in a semi-r and omised order ; this as the acquisition ( conditioning ) phase . To test the effect of the conditioning , each subject then had one CS+ only -- that is , CS+ without CO2 - - and one CS- test exposure . Next , half the subjects ( n = 32 ) received five additional CS+ only exposures ( extinction group ) , while the other half received five exposures to breathing air ( wait group ) . Finally , all subjects got one CS+ only test exposure to test the effect of the extinction . Ventilatory responses were measured during and somatic symptoms after each exposure . RESULTS : More symptoms were reported upon exposure to CS+ only than to CS-odours , regardless of the odour type . Altered respiratory rate was only found when ammonia was CS+ . Five extinction trials were sufficient to reduce the level of acquired symptoms . CONCLUSION : Subjects can acquire somatic symptoms and altered respiratory behaviour in response to harmless , but odorous chemical substances , if these odours have been associated with a physiological challenge that originally had caused these symptoms . The conditioned symptoms can subsequently be reduced in an extinction procedure . The study further supports the plausibility of a pavlovian conditioning hypothesis to explain the pathogenesis of MCS Abstract Medical treatment is usually accompanied by a warning about potential side effects . While constituting an important component of informed consent , these warnings may themselves contribute to side effects via the placebo effect . We tested this possibility using a 2 × 2 between-subjects design . Under the guise of a trial of a new hypnotic , 91 undergraduates experiencing difficulty sleeping were allocated to receive a warning about a target side effect ( either increase or decrease in appetite , counterbalanced ) or no warning and then to receive placebo treatment or no treatment for one week . Placebo treatment led to significantly better sleep on almost all self-reported outcomes , suggesting a placebo effect for reported sleep difficulty . Actigraphy recordings were unaffected by treatment . There was a clear effect of the warning in that placebo treated participants who were warned about side effects were much more likely to report the target side effect than those not warned about side effects . Implication s for clinical practice are discussed The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance . The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure . We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions . Six hundred patients , seen in three different centres ( Genoa , Naples and Verona ) with a history of reactions to drugs , underwent a blind oral challenge with the administration of an indifferent substance and active drugs . The administration of an inert substance provoked untoward reactions in 54 patients ( 27 % ) in Verona , 60 ( 30 % ) in Naples and 48 ( 24 % ) in Genoa . The overall occurrence of nocebo effect was 27 % . The majority of reactions were subjective symptoms ( itching , malaise , headache etc ) , perceived as troublesome by all subjects . The occurrence was significantly higher in women than in men . Our data , collected in a large population , confirm that the nocebo effect occurs frequently in clinical practice . In managing adverse drug reactions through oral challenge the nocebo effect is m and atory to recognize false positive responses Objective Generic medications are associated with reduced perceived effectiveness , increased perceived adverse effects , and increased rates of nonadherence compared with br and -name medications . This study examined the effect of an apparent medication formulation change on subjective and objective measures of medication effectiveness and medication side effects . Methods Sixty-two university students participated in a study purportedly testing the effectiveness of fast-acting & bgr;-blocker medications in reducing preexamination anxiety . All tablets were placebos . In session 1 , all participants received a yellow tablet ( “ Betaprol ” ) . In session 2 , participants were r and omly allocated to receive Betaprol ( no change condition ) or a white tablet labeled either as “ Novaprol ” ( br and ed change condition ) or “ Generic ” ( generic change condition ) . Blood pressure and state anxiety were measured before and after tablet ingestion . Side effects attributed to medication were assessed . Results The no change group showed significantly greater decreases in systolic blood pressure ( mean [ M ] [ st and ard deviation ] = −7.72 mm Hg , st and ard error [ SE ] = 1.45 ) than the br and ed change ( M = −2.75 mm Hg , SE = 1.44 , p = .02 ) and generic change ( M = −3.26 mm Hg , SE = 1.45 , p = .03 ) groups . The no-change group showed significantly greater decreases in state anxiety ( M = −1.53 , SE = 0.33 ) than the br and ed change ( M = −0.50 , SE = 0.33 , p = .03 ) and generic change ( M = −0.52 , SE = 0.33 , p = .04 ) groups . Significantly more side effects were attributed to the medication in the generic change ( M = 1.83 , SE = 0.23 ) ( but not the br and ed change ) condition when compared with the no change condition ( M = 0.87 , SE = 0.31 , p = .03 ) . Conclusions Medication formulation change , particularly to generic medication , seems to be associated with reduced subjective and objective measures of medication effectiveness and increased side effects Caffeine consumption , a ubiquitous cultural phenomenon with significant health implication s may be governed by some of the same principles which affect other drug use [ 1 ] . We hypothesized that pharmacological and expectancy effects may be two of those principles . A balanced placebo design was used with 100 male undergraduates to separate caffeine 's active drug effects from the expectancy of having consumed caffeine on mood , performance , and physiological measures . The manipulation of expectancies was highly effective on subjects ' judgments of caffeine dosage , regardless of actual caffeine content . As predicted , expectancy set and caffeine content appeared equally powerful , and worked additively , to affect subjects ' ratings of how much the coffee influenced their mood and performance . Main effects on systolic and diastolic blood pressure , pulse rate , and a fatigue measure were found for caffeine vs. no caffeine groups only . Additional increases in diastolic blood pressure for smokers were noted within the caffeine-receiving conditions . Results are discussed with heuristic and health implication Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract . Rationale : To test the classical conditioning and expectancy theories of placebo effects . Objective : Two experiments investigated whether administration of caffeine-associated stimuli elicited conditioned arousal , and whether information that a drink contained or did not contain caffeine modulated arousal . Method : Experiment 1 ( n=21 ) used a 2 Caffeine ( 0 and 2 mg/kg ) × 2 Solution ( Coffee , Juice ) × 2 Information ( Told caffeine , Told not-caffeine ) within-subjects design . Experiment 2 ( n=48 ) used a 2 Solution ( Coffee , Orange juice ) × 3 Information ( Told caffeine , Told not-caffeine , No information ) between-subjects design . Indexes of arousal were skin conductance responses and levels , startle eyeblink reflexes , cardiovascular measures , and the Bond and Lader 1974 mood scale . Results : Caffeine-associated stimuli increased alertness , contentedness and skin conductance levels , and information that the drink contained caffeine decreased calmness in Experiment 1 . However , unexpected information about the caffeine content of the drink , and the order of the conditions , could have masked some effects of the experimental manipulations . Experiment 2 followed up this hypothesis . The results showed a conditioned increase in startle eyeblink reflexes , and that caffeine-associated stimuli together with information that the drink contained caffeine increased contentedness . Conclusions : Caffeine-associated stimuli increased arousal , and information about the content of the drink modulated arousal in the direction indicated by the information . Thus , both the classical conditioning and expectancy theories of placebo effects received support , and placebo effects were strongest when both conditioned responses and expectancy-based responses acted in the same direction & NA ; A nocebo response on pressure pain was induced by social observational learning but not by verbal suggestion . The nocebo response correlated with pain catastrophizing , especially the subscale “ Helplessness ” . & NA ; Nocebo effects can be acquired by verbal suggestion , but it is unknown whether they can be induced through observational learning and whether they are influenced by factors known to influence pain perception , such as pain anxiety or pain catastrophizing . Eighty‐five female students ( aged 22.5 ± 4.4 years ) were r and omly assigned to one of three conditions . Participants in the control condition ( CC ) received information that an ointment had no effect on pain perception . Participants in the verbal suggestion condition ( VSC ) received information that it increased pain sensitivity . Participants in the social observational learning condition ( OLC ) watched a video in which a model displayed more pain when ointment was applied . Subsequently , all participants received three pressure pain stimuli ( 60 seconds ) on each h and . On one h and , the ointment was applied prior to the stimulation . Numerical pain ratings were collected at 20‐second intervals during pain stimulation . The participants filled in question naires regarding pain‐related attitudes ( Pain Anxiety Symptoms Scale , Pain Catastrophizing Scale , and Somatosensory Amplification Scale ) . Participants in the OLC showed higher pain ratings with than without ointment . Pain ratings within the CC and the VSC were at the same level with and without ointment . In the VSC , the pain ratings were higher than in the CC with and without ointment . The nocebo response correlated with pain catastrophizing but not with pain anxiety or somatosensory amplification . A nocebo response to pressure pain was induced by observational learning but not by verbal suggestion . This finding highlights the importance of investigating the influence of observational learning on nocebo hyperalgesia In 459 migraine attacks , information provided to patients ( from negative to neutral to positive ) modified placebo and medication outcomes in a progressive fashion . Placebo and Medication Effects in Episodic Migraine Placebo and medication effects are intimately related in clinical practice and drug development . In new work , Kam-Hansen et al. investigated how information — ranging from “ negative ” to “ neutral ” to “ positive”—provided to patients , who received either active drug or placebo , modified their headache pain as measured by patient-reported pain scores . In a r and omized order over six consecutive attacks , 66 patients with episodic migraine received either placebo or Maxalt ( 10-mg rizatriptan ) under three information conditions ( told placebo , told Maxalt or placebo , told Maxalt ) . Each participant also reported on an initial no-treatment attack , yielding a total of 459 documented migraine attacks . Maxalt was superior to placebo for pain relief . Increasing information from negative to neutral to positive progressively enhanced the effects of both placebo and Maxalt . The efficacy of open-label placebo was superior to that of no treatment . Relative to no treatment , the placebo , under each information condition , accounted for more than 50 % of the drug effect . The benefits of placebo persisted even when the placebo was honestly described . Whether treatment involves medication or placebo , the information provided to patients and the ritual of pill taking are important components of medical care . Information provided to patients is thought to influence placebo and drug effects . In a prospect i ve , within-subjects , repeated- measures study of 66 subjects with episodic migraine , we investigated how variations in medication labeling modified placebo and drug effects . An initial attack with no treatment served as a control . In six subsequent migraine attacks , each participant received either placebo or Maxalt ( 10-mg rizatriptan ) administered under three information conditions ranging from negative to neutral to positive ( told placebo , told Maxalt or placebo , told Maxalt ) ( N = 459 documented attacks ) . Treatment order was r and omized . Maxalt was superior to placebo for pain relief . When participants were given placebo labeled as ( i ) placebo , ( ii ) Maxalt or placebo , and ( iii ) Maxalt , the placebo effect increased progressively . Maxalt had a similar progressive boost when labeled with these three labels . The efficacies of Maxalt labeled as placebo and placebo labeled as Maxalt were similar . The efficacy of open-label placebo was superior to that of no treatment . Relative to no treatment , the placebo , under each information condition , accounted for more than 50 % of the drug effect . Increasing “ positive ” information incrementally boosted the efficacy of both placebo and medication during migraine attacks . The benefits of placebo persisted even if placebo was honestly described . Whether treatment involves medication or placebo , the information provided to patients and the ritual of pill taking are important components of care Abstract Objective To investigate whether a sham device ( a vali date d sham acupuncture needle ) has a greater placebo effect than an inert pill in patients with persistent arm pain . Design A single blind r and omised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls . Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study . Setting Academic medical centre . Participants 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale . Interventions Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks . Main outcome measures Arm pain measured on a 10 point pain scale . Secondary outcomes were symptoms measured by the Levine symptom severity scale , function measured by Pransky 's upper extremity function scale , and grip strength . Results Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups , but changes were not different between the groups ( −0.14 , 95 % confidence interval −0.52 to 0.25 , P = 0.49 ) . Changes in severity scores for arm symptoms and grip strength were similar between groups , but arm function improved more in the placebo pill group ( 2.0 , 0.06 to 3.92 , P = 0.04 ) . Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group ( −0.33 ( −0.40 to −0.26 ) v −0.15 ( −0.21 to −0.09 ) , P = 0.0001 ) and on the symptom severity scale ( −0.07 ( −0.09 to −0.05 ) v −0.05 ( −0.06 to −0.03 ) , P = 0.02 ) . Differences were not significant , however , on the function scale or for grip strength . Reported adverse effects were different in the two groups . Conclusions The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in . Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals Objective Somatic symptoms that occur in response to odors can be acquired in a pavlovian conditioning paradigm . The present study investigated 1 ) whether learned symptoms can generalize to new odors , 2 ) whether the generalization gradient is linked to the affective or irritant quality of the new odors , and 3 ) whether the delay between acquisition and testing modulates generalization . Methods Conditional odor stimuli ( CS ) were ( diluted ) ammonia and niaouli . One odor was mixed with 7.4 % CO2-enriched air ( unconditional stimulus ) during 2-minute breathing trials ( CS+ trial ) , and the other odor was presented with air ( CS− trial ) . Three CS+ and three CS− trials were conducted in a semir and omized order ( acquisition phase ) . The test phase involved one CS+-only ( CS+ without CO2 ) and one CS− test trial , followed by three trials using new odors ( butyric acid , acetic acid , and citric aroma ) . Half of the subjects ( N = 28 ) were tested immediately , and the other half were tested after 1 week . Ventilatory responses were measured during and somatic symptoms were measured after each trial . Results Participants had more symptoms in response to CS+-only exposures , but only when ammonia was used as the CS+ . Also , generalization occurred : More symptoms were reported in response to butyric and acetic acid than to citric aroma and only in participants who had been conditioned . Both the selective conditioning and the generalization effect were mediated by negative affectivity of the participants . The delay between the acquisition and test phases had no effect . Conclusions Symptoms that occur in response to odorous substances can be learned and generalize to new substances , especially in persons with high negative affectivity . The findings further support the plausibility of a pavlovian perspective of multiple chemical sensitivity Objective : To find evidence of classically conditioned placebo effects in a placebo‐controlled crossover drug study . Specifically , we tested a prediction of the conditioning model that the placebo response will be greater after drug exposure than before Background Placebo effects have been reported in type I allergic reactions . However the neuropsychological mechanisms steering placebo responses in allergies are largely unknown . The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions . Methods 62 patients with house dust mite allergy were r and omly allocated to either a conditioned ( n = 25 ) , sham-conditioned ( n = 25 ) or natural history ( n = 12 ) group . During the learning phase ( acquisition ) , patients in the conditioned group received the H1-receptor antagonist desloratadine ( 5 mg ) ( unconditioned stimulus/US ) together with a novel tasting gustatory stimulus ( conditioned stimulus/CS ) . Patients in the sham-conditioned control group received the CS together with a placebo pill . After a wash out time of 9 days patients in the conditioned and sham-conditioned group received placebo pills together with the CS during evocation . Allergic responses documented by wheal size after skin prick test and symptom scores after nasal provocation were analyzed at baseline , after last desloratadine treatment and after the 1st and 5th CS re-exposure . Results Both conditioned and sham-conditioned patients showed significantly decreased wheal sizes after the 1st CS-evocation and significantly decreased symptom scores after the 1st as well as after the 5th evocation compared to the natural history control group . Conclusions These results indicate that placebo responses in type I allergy are not primarily mediated by learning processes , but seemed to be induced by cognitive factors such as patients ’ expectation , with these effects not restricted to a single evocation OBJECTIVE Prior investigations have failed to find reliable personality differences in placebo responding . The present study tests the hypothesis that personality and situational variables interact to determine placebo responding . METHODS Optimists and pessimists were r and omly assigned to one of three conditions . In the first condition , the participants were told that they were to ingest a pill that would make them feel unpleasant ( deceptive-expectation group ) . In the second condition , the participants were told that they were to ingest a pill that would make them feel either unpleasant or was an inactive substance ( conditional-expectation group ) . Finally , a third group was told they were to ingest a pill that was inactive ( control group ) . RESULTS Pessimists were more likely than optimists to follow a negative-placebo expectation when given a deceptive expectation , but not when given a conditional expectation . CONCLUSION The personality variable optimism-pessimism relates to placebo responding when individuals are given a deceptive but not a conditional expectation . This suggests that personality and situational variables interact to determine placebo responding We studied the effect of suggestion and different instructions in a balanced placebo design . One hundred and fifty-nine subjects were r and omized into a 2 * 4 factorial design . All subjects except a control group received a caffeine placebo . Subjects were r and omized to a condition which was identical to an earlier study , or received an information about scientifically proven effects of caffeine ( factor 1 ) . The second factor varied instructions : subjects were either made to expect coffee , no coffee or were in a double blind condition and were told either coffee or placebo would be applied . Dependent measures were blood pressure , heart rate , well-being and a cognitive task . There was one main effect of the instruction factor ( P=0.03 ) on diastolic blood pressure , with the group ' told caffeine ' reporting significantly smaller decrease in diastolic blood pressure than controls and subjects in the double blind condition . There were no other main effects on both the instruction or suggestion factor , and no interactions . Contrary to the literature , instruction effects were very small . This was apparently due to the fact that placebo-caffeine in the dose used in this study --one cup of strong ' coffee'--did not produce expectancy effects strong enough to affect the parameters measured . It is concluded that the placebo-caffeine research paradigm is not suitable for research ing instruction effects in Germany , and that reported effects should be reproduced with tighter controls Effects of inhaled essential oils ( EOs ) can not be explained by pharmacological mechanisms alone . The study aim ed to investigate the effects of pleasantness of and expectancies evoked by EOs . A double-blind experiment with a within-subject design was carried out with the participation of 33 volunteering adults ( 15.2 % male ; mean age 37.7 ± 10.90 years ) . Participants were exposed to three EOs ( rosemary , lavender , and eucalyptus ) for three minutes in a quasi-r and om order , expectations were simply assessed prior to exposure . Subjective ( perceived ) changes in alertness , heart rate ( HR ) , and blood pressure ( BP ) , and objective changes in HR , BP , and indices of heart rate variability were recorded . Significant group-level differences in changes in alertness and no differences for the cardiovascular variables were found . Participants ' expectations predicted changes in alertness in the case of rosemary and lavender oils but had no impact on cardiovascular variables . EOs ' pleasantness had no effect on any assessed variable . Perceived changes in BP and HR were not related to the respective objective changes but were connected to perceived changes in alertness . Expectancies play an important role in the subjective effects of inhaled EOs . Perceived subjective changes are used to estimate changes in non-conscious ( e.g. , visceral ) states OBJECTIVE Administration of the muscle relaxant carisoprodol and placebo was crossed with information that was agonistic or antagonistic to the effect of carisoprodol . It was investigated whether information alone induced physiological and psychological responses , and whether information modified the response to the drug . METHODS Half of the subjects received capsules containing 525 mg carisoprodol together with information that the drug acted in a specific way ( Groups Relaxant/C , Stimulant/C , and No Information/C ) . The other half of the subjects received lactose ( Groups Relaxant/L , Stimulant/L , and No Information/L ) . Dependent variables were blink reflexes and skin conductance responses , subjective measures of tension and sleepiness , and serum carisoprodol and meprobamate concentrations . Recordings were made between 15 and 130 minutes after administration of the capsules . RESULTS The Stimulant/L group reported more tension compared with the other two groups , and carisoprodol increased tension even more in the Stimulant/C group . The Relaxant/C group displayed higher levels of carisoprodol serum concentration compared with the other groups that received carisoprodol . CONCLUSIONS Reported tension was modulated in the direction suggested by the stimulant information . The effect of carisoprodol on tension was also modulated by stimulant information . Increased carisoprodol absorption in the group that received relaxant information could be a mechanism in the placebo response & NA ; The efficacy of repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex for neuropathic pain relief is founded on double‐blind studies versus placebo . In these studies , however , the analgesic effect of active interventions remained modest compared with the placebo effect . This observation led us to re‐evaluate the intrinsic placebo action on pain relief according to the relative timing of active and sham rTMS interventions . In a r and omized controlled study including 45 patients , we compared the analgesic effect of sham rTMS that either preceded or followed an active rTMS , which could be itself either successful or unsuccessful . Placebo analgesia differed significantly when the sham rTMS session followed a successful or an unsuccessful active rTMS . Placebo sessions induced significant analgesia when they followed a successful rTMS ( mean pain decrease of 11 % ) , whereas they tended to worsen pain when following an unsuccessful rTMS ( pain increase of 6 % ) . Only when the sham intervention was applied before any active rTMS were placebo scores unchanged from the baseline . These results probably reflect an unconscious conditioned learning . The timing of placebo relative to active interventions should be taken into account in rTMS studies for pain relief , and possibly in other conditions too . The fact that placebo effects could be enhanced by a previous rTMS with an analgesic effect as low as 10 % suggests that a 30 % pain decrease threshold in therapeutic trials may be too severe because smaller analgesic effects may have a clinical significance too . Sham rTMS induces significant analgesia only when preceded by a successful active stimulation . Such a placebo modulation is probably related to an unconscious conditioned learning OBJECTIVE Medically unsubstantiated ' intolerances ' to foods , chemicals and environmental toxins are common and are frequently discussed in the media . Idiopathic environmental intolerance attributed to electromagnetic fields ( IEI-EMF ) is one such condition and is characterized by symptoms that are attributed to exposure to electromagnetic fields ( EMF ) . In this experiment , we tested whether media reports promote the development of this condition . METHODS Participants ( N=147 ) were r and omly assigned to watch a television report about the adverse health effects of WiFi ( n=76 ) or a control film ( n=71 ) . After watching their film , participants received a sham exposure to a WiFi signal ( 15 min ) . The principal outcome measure was symptom reports following the sham exposure . Secondary outcomes included worries about the health effects of EMF , attributing symptoms to the sham exposure and increases in perceived sensitivity to EMF . RESULTS 82 ( 54 % ) of the 147 participants reported symptoms which they attributed to the sham exposure . The experimental film increased : EMF related worries ( β=0.19 ; P=.019 ) ; post sham exposure symptoms among participants with high pre-existing anxiety ( β=0.22 ; P=.008 ) ; the likelihood of symptoms being attributed to the sham exposure among people with high anxiety ( β=.31 ; P=.001 ) ; and the likelihood of people who attributed their symptoms to the sham exposure believing themselves to be sensitive to EMF ( β=0.16 ; P=.049 ) . CONCLUSION Media reports about the adverse effects of supposedly hazardous substances can increase the likelihood of experiencing symptoms following sham exposure and developing an apparent sensitivity to it . Greater engagement between journalists and scientists is required to counter these negative effects In a laboratory study we examined the hypothesis that placebo expectations enhance the initial identification of placebo-relevant sensations over placebo-irrelevant sensations . Participants ( N = 102 ) were r and omly assigned to one of three expectation groups . In the first group , participants ingested a placebo capsule and were told it was caffeine ( deceptive expectation ) . In a second group , participants ingested a placebo capsule and were told it may be caffeine or it may be a placebo ( double-blind expectation ) . Participants in the third group were given no expectation . All participants then tallied the placebo-relevant and placebo-irrelevant sensations they experienced during a 7-min period . Participants in the deceptive expectation group identified more placebo-relevant sensations than placebo-irrelevant sensations . No-expectation participants identified more placebo-irrelevant sensations than placebo-relevant sensations . Participants given the double-blind expectation identified an equal amount of placebo-relevant and irrelevant sensations . The amount of both placebo-relevant and placebo-irrelevant sensations detected mediated the relationship between the expectation manipulation and subsequent symptom reports . These data support the position that expectations cause placebo responding , in part , by altering how one identifies bodily sensations This study examined the role of expectancy in the placebo effect of a sham dietary supplement for weight loss in 114 obese adults with metabolic syndrome . All participants received lifestyle education and were r and omized to 1 of 3 conditions : ( 1 ) a daily placebo capsule and told that they were taking an active weight loss supplement , ( 2 ) daily placebo and told they had a 50 % r and om chance of receiving either the active or placebo , or ( 3 ) no capsules . At 12 weeks , weight loss and metabolic outcomes were similar among the 3 groups . Participants in both groups that took capsules showed decreased weight loss self-efficacy and increased expectations of benefit from dietary supplements . Participants not taking capsules showed the opposite . Adverse events were more frequently reported in groups taking capsules than those who were not . These findings suggest that supplements without weight loss effects may have nocebo effects through diminished self-efficacy Abstract Objective : Although placebo controls are a st and ard measure in clinical trials the mechanisms underlying placebo effects are still not fully understood . We hypothesised that information about the likelihood of receiving placebo might influence the perception of adverse effects in volunteers participating in a clinical trial . Methods : Healthy subjects received either nifedipine 20 mg or placebo in an adaptive two-stage crossover study . Sixty subjects were r and omised to a group given either correct ( 50 % chance ) or misleading ( 100 % chance ) information about the likelihood of receiving the active drug . A sum of the severity scores from visual analogue scales over all individual adverse effects was defined as the primary endpoint . Results : The analysis revealed no difference in the primary endpoint between the two groups . This lack of difference may in part be attributable to a conditioning effect as on the first study day higher symptom scores were reported by the participants than on the second study day . Furthermore , the day effect seemed to arise mainly when the first day treatment was the placebo . For the placebo the day effect was clearly significant ( p = 0.012 ) , with higher scores on the first day . A further explorative finding in patients given placebo was a tendency for higher scores in the group with the misleading information ( p = 0.08 ) . Nothing of that sort was found in the analysis for active treatment . The day effect collapsed and the factor information did not show any tendency of being a potential influence . Conclusions : In the present study we did not find a statistically significant effect of misleading information on reported adverse events . The large treatment and day effects observed made it difficult to detect a potential small information effect . However , this study excluded a strong and relevant effect of information on the frequency and severity of reported adverse events Subjects were given varying doses of a placebo , consisting of decaffeinated coffee , with double-blind or deceptive instructions . Deceptive administration simulated clinical situations in that subjects were led to believe that they were receiving an active drug . In contrast , subjects in double-blind conditions were aware that they might receive a placebo . Double-blind and deceptive administration of the placebo produced different , and in some instances , opposite effects on pulse rate , systolic blood pressure , and subjective mood . Deceptive administration produced an increase in pulse rate , whereas double-blind administration did not . A theoretically predicted curvilinear effect on systolic blood pressure , alertness , tension , and certainty of having consumed caffeine was confirmed with deceptive administration , but not with double-blind administration . Double-blind administration produced curves in the opposite direction on each of these variables . The effects of the placebo on motor performance varied as a function of subject 's beliefs about the effects of caffeine . These data challenge the validity of double-blind experimental design s and suggest that this common method of drug assessment may lead to spurious conclusions BACKGROUND A number of people are reporting an environmental sensitivity to sub-audible windfarm sound ( infrasound ) , characterised by the experience of recurrent non-specific symptoms . A causal link between exposure and symptoms is not indicated by empirical evidence . Research indicates symptoms may be explained by the nocebo response , whereby health concerns and negative expectations , created from social discourse and media reports , trigger symptom reporting . OBJECTIVE The experimental aim was to test whether providing a nocebo explanation for symptoms , to individuals reporting symptomatic experiences during infrasound exposure , would ameliorate symptoms during further exposure . METHOD Sixty-six volunteers were r and omly assigned to nocebo explanation or biological explanation groups . Participants were concurrently exposed to infrasound and audible windfarm sound , while reporting on current symptoms and mood , during two exposure sessions . Preceding session one , participants watched a presentation integrating media warnings about purported health risks posed by windfarm infrasound . Before session two , nocebo explanation participants viewed material outlining how nocebo responding could explain symptom reporting . Instead biological explanation participants watched material presenting pathophysiological theories for symptoms . RESULTS During session one , participants reported increased symptoms and mood deterioration from baseline assessment . During session two symptom reporting and mood deterioration was maintained by biological explanation participants , while mood and symptoms reported by nocebo explanation participants returned to baseline levels . CONCLUSION Results indicate that providing an explanation of the nocebo response , followed by exposure to infrasound , has the potential to operate as an intervention to reduce symptomatic experiences in people reporting symptoms attributed to windfarm generated infrasound OBJECTIVE To study the adverse side-effects to medication and define their principle characteristics . DESIGN A descriptive , crossover , observation study with no r and om distribution . SETTING The population cared for at a Health Centre in Toledo . PATIENTS Those over 15 years old during a 6-month period . MEASUREMENTS AND MAIN RESULTS 64 adverse side-effects were detected , classified as follows : definite , 10.9 % ; probable , 68.7 % ; possible , 20.3 % . The rate of adverse side-effects was 2.67 per thous and prescriptions and 2.22 per thous and consultations . Distribution by gender was 62.5 % women and 37.5 % men . The 35 - 45 age group was the one with most adverse side-effects . The most affected systems were the digestive apparatus ( 46.50 % ) , followed by the nervous system ( 27.50 % ) and the skin ( 16.22 % ) . The most commonly involved pharmacological groups were : analgesics and non-steroid anti-inflammatories ( 34.37 % ) and drugs for the cardiovascular system ( 26.56 % ) . 98.43 % were trivial and none serious . Evolution was : 59.37 % recovered on stopping the drug and 23.43 % with the help of treatment . CONCLUSIONS The number of suspected adverse side-effects in the Centre is high , but they were trivial . It was confirmed that adverse side-effects suppose a frequent medical problem in Primary Care . It is important to make health professionals aware so that , when prescribing , they bear in mind the drug risk/benefit relationship . The identification and communication of adverse side-effects , especially of medicines newly on the market , is also important OBJECTIVE A prior investigation found that individuals low in optimism are more likely to follow a negative placebo ( nocebo ) expectation . The present study tested the hypothesis that individuals high in optimism are more likely to follow a positive placebo expectation . METHODS Individuals ( N=56 ) varying in their level of optimism were r and omly assigned to one of three conditions . In the first condition , participants were given the expectation that a placebo sleep treatment would improve their sleep quality ( placebo expectation condition ) . In the second condition , participants engaged in the same sleep treatment activity but were not given the positive placebo expectation ( treatment control condition ) . Finally , a third group did not receive the positive placebo expectation and also did not engage in the placebo sleep treatment ( no-placebo control condition ) . RESULTS Optimism was positively associated with better sleep quality in the placebo expectation condition ( r=.48 , P<.05 ) . Optimism scores were not associated with better sleep quality in either the treatment control condition ( r=-.17 , P=.46 ) or the no-placebo control condition ( r=-.24 , P=.35 ) . CONCLUSION Dispositional optimism relates to placebo responding . This relationship , however , is not manifested in a simple increase or decrease in all types of placebo responding . Rather , it appears that , as optimism increases , response to the positive placebo expectation increases , whereas response to nocebo expectation decreases . It is recommended that future research on personality and placebo effects consider the interaction between situational and dispositional variables Two experiments ( N=56 ) investigated the relationship between subjects ’ expectancies concerning the effect of caffeine on a motor skill , and the type of placebo response . Male subjects were assigned to four groups . Three groups expected to receive caffeine but received a placebo . Prior to the placebo , two of the groups received information about the effect of caffeine on a motor skill task which led one group E(+ ) to expect enhanced performance , and the other E(− ) to expect impairment . The third placebo group received no information E ( ? ) . A control group E(0 ) received no beverage , so neither caffeine nor any effect on performance was expected . The expected type of effect predicted the type of placebo response displayed . Group E(+ ) displayed greater improvement under placebo than did group E(0 ) , and group E(− ) performed more poorly than those in group E(0 ) . No placebo response was observed in group E ( ? ) . Placebo effects on mood were correlated with subjects ’ predictions about the effect of caffeine on mood . The role of expectancies in response to placebos and psychoactive drugs is discussed OBJECTIVE Placebo effects on pain and other subjective parameters are well-established , but the evidence for placebo effects on autonomic functions is scarce . Our r and omized-controlled trial aim ed to investigate autonomic responses after a suggestive placebo intervention intended to increase or decrease blood pressure ( BP ) . METHODS 92 healthy subjects inhaled a placebo spray with the prior suggestion that it contained an effective drug to either increase or decrease BP , or the information that a placebo was administered ( controls ) . BP , heart rate , stroke volume , peripheral resistance , heart rate variability and skin conductance level were monitored 30min before and after placebo administration . The expected and the subjectively perceived drug effect were measured by means of visual analog scales . RESULTS We found no statistically significant differences between the groups with respect to BP , heart rate , stroke volume , total peripheral resistance and heart rate variability responses to the verbal suggestions . Skin conductance response was more pronounced in the BP decrease group compared with controls ( p=0.04 ) , but this finding might be due to chance , given the multiple tests . Within the total study sample , BP , total peripheral resistance , low frequency power of heart rate variability and skin conductance were significantly higher after the placebo spray independent of the associated suggestions . Subjects in the BP increase and BP decrease condition had higher ratings of the expected and the subjectively perceived drug effect compared with controls ( all p<0.05 ) . CONCLUSION We found no evidence that specific verbal suggestions during placebo interventions affect BP in healthy subjects The present study examined reports of placebo and nocebo symptoms in a college sample . The study was presented under the guise of a clinical trial to evaluate the effectiveness of an over-the-counter herbal supplement intended to enhance cognitive performance . Participants were informed they would be receiving either an herbal supplement or a placebo , and each was provided with a mock list of possible beneficial and adverse effects of the “ supplement . ” In fact , all participants received placebo . Symptoms were endorsed by a significant majority of participants following placebo ingestion . More important , results indicated that the few participants who believed they received an herbal supplement endorsed ( via self-report ) significantly more symptoms than those who believed they received a placebo . Neither anxiety nor social desirability was significantly related to symptom reporting . Results suggest that beliefs concerning treatment received may subsequently affect the degree of placebo response in a no-treatment group . Implication s for clinical trials and future research are discussed With odors as conditioned stimuli ( CSs ) and CO2-enriched air as the unconditioned stimulus , participants learned to exhibit respiratory responses and somatic complaints on presentation of only the odor CS+ . Studied was whether complaints during CS+-only trials were inferred from the conditioned somatic responses or were based on activated memory of the complaints during acquisition . Participants ( N = 56 ) were either attentionally directed away or not from the complaints during acquisition , and the effects on somatic complaints during test were studied . Respiratory responses , heart rate , and somatic complaints were measured . No physiological conditioning effects were found . However , more complaints were reported to the CS+ than to the CS- odor , but only when the CS+ was foul smelling . This effect was modulated by the attention manipulation , showing that the learned complaints during the test phase were based on memory of the acquisition complaints and not on physiological responses during the test A significant response to placebo in r and omized controlled trials of treatments for cancer‐related fatigue ( CRF ) had been reported . A retrospective study was conducted to determine the frequency and predictors of response to placebo effect and nocebo effects in patients with CRF treated in those trials |
13,474 | 27,658,148 | There was no difference in bias between clinical or laboratory operators in two devices .
Conclusions : This is the first meta- analysis to directly compare performance of POC HbA1c devices .
Use of a device with a mean negative bias compared to a laboratory method may lead to higher levels of glycemia and a lower risk of hypoglycaemia . | Abstract Background : Point-of-care ( POC ) devices could be used to measure hemoglobin A1c ( HbA1c ) in the doctors ’ office , allowing immediate feedback of results to patients .
Reports have raised concerns about the analytical performance of some of these devices .
We carried out a systematic review and meta- analysis using a novel approach to compare the accuracy and precision of POC HbA1c devices . | In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old . Such investigations are often analysed inappropriately , notably by using correlation coefficients . The use of correlation is misleading . An alternative approach , based on graphical techniques and simple calculations , is described , together with the relation between this analysis and the assessment of repeatability The recommended method for assessing long-term blood glucose control in diabetic patients is the measurement of glycated haemoglobin ( Hb ) . The Ames DCA 2000 system for assaying glycated Hb uses an immunoassay with a monoclonal antibody specific for an aminoacid sequence within the HblAc molecule . This study compared the performance of the DCA 2000 system for HblAc measurement with that of high-performance liquid chromatography ( HPLC ) . A total of 1.016 insulin-dependent and non-insulin-dependent diabetic patients from 5 outpatient clinics took part . The correlation coefficients between DCA 2000 and HPLC data ranged between 0.94 and 0.98 , depending on site . The mean variations and 95 % confidence intervals for the differences between the results for each sample were : site A 0.172 ( -1.186 to 1.53 ) , site B -0.275 ( -1.317 to 0.767 ) , site C -0.146 ( -0.868 to 0.576 ) , site D -0.088 ( -0.864 to 0.688 ) , and site E -0.251 ( -1.099 to 0.597 ) . The sensitivity of the DCA 2000 assay ranged between 80 and 94 % , and the specificity between 88 and 100 % , depending on site . For pooled results , the correlation coefficient assayed by the two methods was 0.95 . The mean variation was -0.116 and the 95 % confidence interval -1.23 to 0.998 . The sensitivity of DCA 2000 was 91 % , and the specificity 94 % . DCA tended to underestimate HbAlc slightly as compared to HPLC . This study confirms the reliability of DCA 2000 for measuring glycated Hb . The system is easy to use and provides valuable information for the care of the diabetic patients BACKGROUND Glycosylated hemoglobin evaluation is very important for assessing the control of diabetes . Since the use of point-of-care ( POC ) devices for monitoring HbA1c is increasing , it is important to determine how these devices compare in relation to instrumentation used in the central laboratory ( CL ) . METHODS Eighty-eight r and omly selected sample s previously analyzed using the Bio-Rad Variant ™ II Hemoglobin Testing System were run on three POC Analyzers ( Siemens DCA Vantage ™ Analyzer , Axis-Shield Afinion ™ AS100 Analyzer , and Bio-Rad In2it ™ Analyzer ) . RESULTS All POC instruments showed good correlation to the CL method ( R(2)>0.95 for all methods ) . HbA1c levels obtained using Variant II ( mean=7.9 ; 95 % CI=7.5 - 8.3 % ) and In2it ( mean=7.9 ; 95 % C.I.=7.5 - 8.2 % ) instruments were found to have no statistical mean difference ( p=0.21 ) , while the values obtained using DCA Vantage ( mean=7.2 % C.I.=6.9 - 7.5 % ) and Afinion ( mean=7.3 % C.I.=7.0 - 7.6 % ) instruments were different ( p<0.001 ) from those of the CL method . The Afinion and DCA Vantage instruments increasingly underestimated the HbA1c compared to the CL as the HbA1c values increased . These differences were even more striking when the estimated average glucose is calculated . CONCLUSIONS Despite significant variation of results among the POC instruments evaluated relative to the CL method and pending resolution of HbA1c st and ardization issues , we conclude that all of the POC instruments can be used for HbA1c determination if clinicians are given instrument specific reference ranges Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) OBJECTIVE Accurate and reliable HbA1c results can be obtained at the time of the office visit by using benchtop analyzers . We tested the hypothesis that immediately available HbA1c results could improve glycemic control by changing physician or patient behavior or both . RESEARCH DESIGN AND METHODS A r and omized controlled trial was conducted in 201 type 1 and insulin-treated type 2 diabetic patients attending an academic diabetes center . HbA1c levels , changes in insulin therapy , and use of health care re sources were assessed during a 12-month follow-up period . RESULTS HbA1c levels decreased significantly at 6 and 12 months in the immediate assay group ( -0.57 + /- 1.44 and -0.40 + /- 1.65 % , respectively ; P < 0.01 ) but did not change in the control group ( -0.11 + /- 0.79 and -0.19 + /- 1.16 % , respectively ; NS ) . The changes were similar for both type 1 and type 2 diabetic patients . There were no differences in the rates of hypoglycemic events or use of health care re sources . CONCLUSIONS In the setting of a controlled r and omized trial , the immediate feedback of HbA1c results at the time of patient encounters result ed in a significant improvement of glycemic control at 6-month follow-up and persisted for the 12-month study . The introduction of this assay was positively received by both patients and physicians Background : Glycohemoglobin A1c ( HbAlc ) is a universally accepted tool for glycemic control . Portable HbAlc devices for use in physicians ' offices are desirable because they provide immediate results that physicians can share with their patients . This has been shown to enhance self-management in patients with diabetes . We undertook this study to evaluate the accuracy and precision of a recently introduced device , the AlcNow ® InView ™ capillary monitor . Method : Previously tested EDTA-preserved whole blood sample s from our laboratory pool were preselected based on the results of HbAlc to cover a range from 4 to 13 % . HbAlc was then measured using an AlcNow InView capillary monitor . Blinded aliquots of these sample s were then sent to a National Glycohemoglobin St and ardization Program (NGSP)-certified reference laboratory for comparison . One sample with a laboratory HbAlc result of 9.2 % was measured with the InView device nine successive times to assess the device precision . The consistency between the measurement of HbAlc measured by the reference laboratory and the AlcNow InView device was analyzed via linear regression . Results : Thirty-five sample s were tested . The correlation between HbAlc measured by the InView device and the reference laboratory , as well as our own laboratory , was 0.96 . The coefficient of variation was 2.7l ° % . Conclusions : Results of this study confirm the accuracy and precision of the InView capillary HbAlc monitor . However , the feasibility , reproducibility , and cost-effectiveness of this promising device in the real-life setting s of physicians ' offices must be verified by prospect i ve clinical studies Background : The measurement of haemoglobin A1c(HbA1c ) by high-performance liquid chromatography ( HPLC ) is generally deemed unsuitable for point of care testing ( POCT ) due to its complexity and extended turnaround times ( TAT ) . The aim of this project was to evaluate two new HPLC instruments , the Bio-Rad D10 and the Primus PDQ , as POCT instruments compared with Bayer 's DCA2000 HbA1c immunoassay analyser in our paediatric diabetes clinic . Methods : A total of 228 sample s were analysed , of which 160 analyses were performed in our paediatric diabetes clinic . HbA1c results were compared by the Passing-Bablok agreement test , the Bl and -Altman difference analysis , within- and between-run imprecision , and TAT . Results : : The agreement test and difference analysis showed a correlation of r 2=0.96 and a mean HbA1c difference of < 0.1 % between the three analysers . The PDQ and the D10 achieved the within-run target coefficient of variation ( CV ) of < 2 % at an HbA1c of 7.5 % . Between-run imprecision at an HbA1c of 10.8 % produced CV of 3.5 % , 2.4 % and 1.6 % for the D10 , DCA2000 and PDQ , respectively . TAT studies confirmed that the PDQ was substantially faster than the DCA2000 and D10 . Conclusions : The PDQ had the shortest TAT , afforded r and om access and exhibited acceptable imprecision , and hence is the preferred instrument for our POCT environment Rapid in clinic measurement of glycated hemoglogin ( HbA1c ) allows to determine the level of metabolic control within a few minutes on capillary blood . We have evaluated the new DCA Vantage ( Siemens ) based on an immunological technique , replacing the DCA 2000 + ( Siemens ) . The study included 120 unselected young type 1 diabetic patients , with different degrees of metabolic control . The DCA Vantage was compared with the HPLC system ( Menarini HA 8160 ) whose deviation from the DCCT was < 0.1 % across the clinical range . The mean underestimation of the DCA Vantage was -0.40 % . The agreement limits ( + /- 1.96 SD ) were between 0.14 % and -0.93 % ; this means + /- 0.53 % around -0.40 % . In conclusion , the DCA Vantage underestimates HbA1c levels ; however it met the acceptance criteria of having a coefficient of variation < 3 % OBJECTIVE Failure to meet goals for glycemic control in primary care setting s may be due in part to lack of information critical to guide intensification of therapy . Our objective is to determine whether rapid-turnaround A1c availability would improve intensification of diabetes therapy and reduce A1c levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS In this prospect i ve controlled trial , A1c was determined on capillary glucose sample s and made available to providers , either during ( " rapid " ) or after ( " routine " ) the patient visit . Frequency of intensification of pharmacological diabetes therapy in inadequately controlled patients and A1c levels were assessed at baseline and after follow-up . RESULTS We recruited 597 subjects . Patients were 79 % female and 96 % African American , with average age of 61 years , duration of diabetes 10 years , BMI 33 kg/m(2 ) , and A1c 8.5 % . The rapid and routine groups had similar clinical demographics . Rapid A1c availability result ed in more frequent intensification of therapy when A1c was > /=7.0 % at the baseline visit ( 51 vs. 32 % of patients , P = 0.01 ) , particularly when A1c was > 8.0 % and /or r and om glucose was in the 8.4 - 14.4 mmol/l range ( 151 - 250 mg/dl ) . In 275 patients with two follow-up visits , A1c fell significantly in the rapid group ( from 8.4 to 8.1 % , P = 0.04 ) but not in the routine group ( from 8.1 to 8.0 % , P = 0.31 ) . CONCLUSIONS Availability of rapid A1c measurements increased the frequency of intensification of therapy and lowered A1c levels in patients with type 2 diabetes in an urban neighborhood health center BACKGROUND In 2003 , a new General Medical Services ( GMS ) contract was agreed between UK general practitioners and the Department of Health . The three diabetes codes DM5-DM7 require glycated haemoglobin ( HbA(1c ) ) testing and comprise 30 points in total , with 27 points being related to target glycaemic control . We compared two routinely used Diabetes Control and Complications Trial (DCCT)-aligned HbA(1c ) methods to determine if different HbA(1c ) methods could lead to postcode treatment to target across the UK . METHODS A total of 164 specimens were r and omly selected from diabetic patients attending the Diabetes Centre at the Ipswich Hospital . Sample s were analysed on both a DCA 2000 + Analyser and a Variant II analyser . RESULTS Despite a mean difference of only 6.5 % between the two methods , 32 ( 19.5 % ) and 63 ( 38.4 % ) patient sample s had an HbA(1c ) < or = 7.4 % with the Variant II analyser and DCA 2000 + Analyser , respectively . Thus , the two methods differed according to the DM6 GMS target by 31 patients , or 18.9 % of the total number of patients in this study . The difference between the two methods was statistically significant with P < 10(-09 ) ( McNemar 's test ) . CONCLUSIONS DCCT-alignment has improved the transferability of HbA(1c ) values ; however , it is not perfect . It is important that the limitations of current DCCT-aligned HbA(1c ) methods are understood by health-care professionals and policy makers , as these may have important financial and clinical implication In order to evaluate a novel technique for measuring haemoglobin A1c using a cassette-based immunoassay method we have undertaken a laboratory evaluation using 48 patient sample s and a separate within-clinic prospect i ve study of 59 diabetic patients . Individuals were recruited from general ( 48 patients ) , paediatric ( 19 patients ) , obstetric ( 24 patients ) , and general practice ( 15 patients ) diabetic clinics . Agreement was evaluated between HbA1c results obtained using the new method ( AMES DCA 2000 ) and an established laboratory assay ( DIAMAT HPLC system ) . The mean differences between the two results ( AMES DCA 2000-DIAMAT ) ( 95 % confidence intervals ) were : laboratory -0.69 % ( -1.42 to 0.04 % ) ; paediatric clinic -0.93 % ( -1.93 to 0.07 % ) ; obstetric clinic -0.29 % ( -1.09 to 0.51 % ) , and general practice clinic -0.77 % ( -1.3 to -0.24 % ) . For the AMES DCA 2000 , the coefficient of variation for HbA1c of 5.2 % was 1.6 % and for HbA1c of 13 % , 2.4 % . This instrument was used without difficulty by four different operators . Intra-assay coefficient of variation for each operator was < 3.4 % . In 9/18 patients where a specific assessment of clinical utility was made , knowledge of the HbA1c result at the time of consultation lead to a change in treatment . Methodology of this type may be used successfully within a diabetic clinic setting in both primary care and hospital environments OBJECTIVES The objectives were to evaluate the correlation between r and om glucose and hemoglobin A1c ( HbA1c ) in emergency department ( ED ) patients without known diabetes and to determine the ability of diabetes screening in the ED to predict outpatient diabetes . METHODS This was a cross-sectional study at an urban academic ED . The authors enrolled consecutive adult patients without known diabetes during eight 24-hour periods . Point-of-care ( POC ) r and om capillary glucose and HbA1c levels were tested , as well as laboratory HbA1c in a subset of patients . Participants with HbA1c > or = 6.1 % were scheduled for oral glucose tolerance test ( OGTT ) . RESULTS The 265 enrolled patients were 47 % female and 80 % white , with a median age of 42 years . Median glucose and HbA1c levels were 93 mg/dL ( interquartile range [ IQR ] = 82 - 108 ) and 5.8 % ( IQR = 5.5 - 6.2 ) , respectively . The correlation between POC and laboratory HbA1c was r = 0.96 , with mean difference 0.33 % ( 95 % confidence interval [ CI ] = 0.27 % to 0.39 % ) . Glucose threshold > or = 120 mg/dL had 89 % specificity and 26 % sensitivity for predicting the 76 ( 29 % ) patients with abnormal HbA1c ; > or = 140 mg/dL had 98 % specificity and 14 % sensitivity . The correlation between r and om glucose and HbA1c was moderate ( r = 0.60 ) and was affected by age , gender , pr and ial status , corticosteroid use , and current injury . Only 38 % of participants with abnormal HbA1c returned for OGTTs ; 38 % had diabetes , 34 % had impaired fasting glucose/impaired glucose tolerance , and 28 % had normal glucose tolerance . CONCLUSIONS ED patients have a high prevalence of undiagnosed diabetes . Although screening with POC r and om glucose and HbA1c is promising , improvement in follow-up with confirmatory testing and initiation of treatment is needed before opportunistic ED screening can be recommended |
13,475 | 25,070,788 | For the prevention of LBP , there was moderate quality evidence to suggest back education and promotion programs are not effective in reducing LBP prevalence in children and adolescents . | Purpose To identify and evaluate the effectiveness of conservative treatment approaches used in children and adolescents to manage and prevent low back pain ( LBP ) . | Background Many authors have reported about the high prevalence rates of self-reported back pain in children . Nevertheless , little is known about the diagnosis of back disorders - regardless of whether the diagnosis is associated with back pain or not . Therefore , the aim of this study was to analyse the prevalence rates and costs of diagnosis of back disorders in childhood and youth . Methods We conducted a secondary data analysis of a large , population based German data set ( 2,300,980 insurants of statutory health insurance funds ) which allowed for identification of prevalence rates of diagnoses of back disorders in children ( age group 0 - 14 years ) and youths ( age group 15 - 24 years ) using three digit ICD-10 codes for dorsopathies ( M40 - M54 : kyphosis and lordosis ; scoliosis ; spinal osteochondrosis ; other deforming dorsopathies ; ankylosing spondylitis ; other inflammatory spondylopathies ; spondylosis ; other spondylopathies ; spondylopathies in diseases classified elsewhere ; cervical disc disorders ; other intervertebral disc disorders ; other dorsopathies , not elsewhere classified ; dorsalgia ) . Direct treatment costs were calculated based on the real incurred costs for cases with a singular diagnosis of a back disorder . Wherever possible , the results of the r and om sample were extrapolated to all insurants of statutory health insurance funds ( i. e. , about 90 % of the German population ) . Results We found prevalence rates for the diagnosis of back disorders to range between 0.01 - 12.5 % . " Scoliosis " ( M41 ) and " dorsalgia " ( M54 ) were the most frequent diagnoses in both age groups . Based on these results , it was calculated that in 2002 alone , approximately 1.4 million children/youths in Germany were diagnosed with " dorsalgia " ( M54 ) , and that the direct costs for back disorders in childhood and youth accounted for at least 100 million Euros . Conclusions Instead of focusing on the individual , and self-reported disorder or disability , this analysis allowed for the detailed evaluation of medical experts ' opinion on back disorders in childhood and youth and for a more objective or public health oriented insight in the topic of diagnosis of back pain and other back disorders . However , due to the method ological limitations by using ICD-10 coding , st and ardized r and om validity checks of population based data sets should be m and atory Within the scope of primary prevention regarding back functioning in children , research on the stability of intervention effects is indispensable . Along this line , the transition from childhood to adolescence is an important phase to evaluate the potential stability of intervention effects because of the typically mechanical and psychological dem and s related to adolescence . The main aim of the current study was to investigate the effects of a back education program at 2-year follow-up , in youngsters aged 13–14 years , on back posture knowledge , fear-avoidance beliefs and self-reported pain . An additional purpose was to evaluate which aspects of postural behavior were integrated in youngsters ’ lifestyles . At 2-year follow-up , the study sample included 94 secondary schoolchildren in the intervention group ( mean age 13.3 ± 0.8 years ) and 101 controls ( mean age 13.2 ± 0.7 years ) . The back posture program that had been implemented for two school years consisted of back education and the stimulation of postural dynamism in the class through support and environmental changes . A question naire was completed comparable to the pretest , posttest and follow-up evaluations . The current study demonstrated at 2-year follow-up stability of the improved general ( F = 1.590 , ns ) and specific ( F = 0.049 , ns ) back posture knowledge in children who had received early back posture education . Back posture education did not result in increased fear-avoidance beliefs ( F = 1.163 , ns ) or mounting back and /or neck pain reports ( F = 0.001 , ns ) . Based on self-reports for postural behavior , youngsters who had received the back posture program in the elementary school curriculum integrated crucial sitting and lifting principles conform to biomechanical favorable postural behavior . The steady intervention effects 2-year post-intervention demonstrated that intensive back posture education through the elementary school curriculum is effective till adolescence . Future research on the impact of early school-based back posture promotion in relation to the integration of back posture principles according to a biomechanical favorable lifestyle and back pain prevalence later in life is essential We tested the effects of implementing ergonomically design ed school furniture on measures of comfort , sitting posture and symptoms . Three classes of fourth grade rs ( 10 years old ) were r and omly assigned either to a control group using traditional furniture or to an experimental group which received the ergonomically design ed furniture . In both groups question naires were completed and sitting behaviour was observed twice before and after the intervention as well as at a five-month follow-up period . Although the experimental groups rated their furniture as being significantly more comfortable , differences in actual sitting behaviour were small . The experimental class experienced a reduction in musculoskeletal symptoms relative to the control group after implementing the ergonomically design ed furniture . Since pupils did not automatically sit ' properly ' in the ergonomic furniture , these results demonstrate the need for proper instructions and adjustment . Increased comfort and decreased symptoms may be used to motivate pupils to sit correctly . Our results suggest that furniture design is one aspect of a multidimensional problem Purpose Population based studies have demonstrated that children and adolescents often complain of low back pain . A group-r and omized controlled trial was carried out to investigate the effects of a postural education program on school backpack habits related to low back pain in children aged 10–12 year . Methods The study sample included 137 children aged 10.7 years ( SD = 0.672 ) . Six classes from two primary schools were r and omly allocated into experimental group ( EG ) ( N = 63 ) or control group ( CG ) ( N = 74 ) . The EG received a postural education program over 6 weeks consisting of six sessions , while the CG followed the usual school curriculum . A question naire was fulfilled by the participants at pre-test , post-test , and 3 months after the intervention finished . The outcomes collected were : ( 1 ) try to load the minimum weight possible , ( 2 ) carry school backpack on two shoulders , ( 3 ) belief that school backpack weight does not affect to the back , and ( 4 ) the use of locker or something similar at school . A sum score was computed from the four items . Results Single healthy items mostly improved after the intervention and remained improved after 3-month follow-up in EG , while no substantial changes were observed in the CG . Healthy backpack use habits score was significantly increased at post-test compared to baseline in the EG ( P < 0.000 ) , and remained significantly increased after 3-month , compared to baseline ( P = 0.001 ) . No significant changes were observed in the CG ( P > 0.2 ) . Conclusions The present study findings confirm that children are able to learn healthy backpack habits which might prevent future low back pain Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists PURPOSE The effect of education on proper wearing of a backpack was studied to determine whether or not a middle school population would improve posture during load carriage by maintaining a more natural posture and to determine if schoolchildren would comply with proper backpack wearing . METHOD 17 middle school children with a mean age of 12.7 years were r and omized into control and intervention groups . Participants were videotaped in four conditions from an anterior view and from a lateral view . Members of both groups participated in Sessions A and C , which consisted of videotaping of the four conditions . Intervention members additionally participated in Session B , consisting of education on how to wear a backpack properly . All participants were interviewed concerning their participation and its effect on how they wore their backpack . Video footage was analyzed to calculate the change in skeletal angles as a result of different methods of load carriage . Interview data was coded and analyzed . RESULTS No quantitative significance was found between control and intervention groups in regards to education on proper backpack wearing improving posture . Interviews revealed that intervention group members benefited from the education on proper wearing of a backpack . 87.5 % of the intervention group members proceeded to continue wearing the backpack properly after the education intervention . CONCLUSIONS Education regarding proper wearing of a backpack may impact the middle school aged child by improving quality of life as noted through decrease in reports of musculoskeletal pain by participants 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 No previous r and omised controlled trials had been undertaken investigating the effect of school seating on back pain in 14 to 16 year olds . This study was design ed to test the effect of the use of a high-density foam wedge on normal school seating on the intensity of back pain . DESIGN R and omised controlled trial . SETTING Suffolk , a predominantly rural county in eastern Engl and . PARTICIPANTS One hundred and eighty-five students with back pain were recruited from 12 schools . R and omisation was stratified by school . The control and intervention groups included 92 and 83 students , respectively . INTERVENTION Following a 1-week baseline observation period , each student in the intervention group was given a wedge to use on their school chairs . OUTCOME MEASURE The primary outcome measure was pain intensity ( numerical rating scale , 0 to 10 ) recorded in pain diaries over 4 weeks . R and om effects models were used to analyse the pain intensity data . RESULTS Ninety-seven students ( 46 control group , 51 intervention group ) completed the trial . For the intervention group , pain intensity was reduced significantly over the 3 weeks of wedge use . The average reduction in pain intensity was estimated to be 0.709 points ( 95 % confidence interval 0.341 to 1.077 ) , representing a 58 % reduction in back pain for those in the intervention group . CONCLUSION Use of a wedge reduced the intensity of back pain significantly , especially in the evenings . The results suggest that further research into the longer-term effect of seating on pain intensity in adolescents should be considered QUESTION Does an eight-week exercise program reduce the intensity and prevalence of low back pain in 12 - 13 year old children ? Does it decrease the childhood physical risk factors for low back pain and promote a sense of well-being ? DESIGN R and omised trial with concealed allocation and assessor blinding . PARTICIPANTS Seventy-two 12 - 13 year old children , who had complained of low back pain in the past three months . INTERVENTION The experimental group completed eight exercise classes of 40 - 45 minutes duration over eight weeks conducted by a physiotherapist , whilst the control group received no intervention . OUTCOME MEASURES The primary outcome was pain intensity measured on a 10-cm visual analogue scale . Secondary outcomes included 3-month prevalence of pain , childhood physical risk factors for low back pain , and sense of well-being . Measures were taken at baseline ( Month 0 ) , post-intervention ( Month 3 ) , and three months later ( Month 6 ) . RESULTS Pain intensity over the past month had decreased by 2.2 cm ( 95 % CI 1.0 to 3.5 ) more for the experimental group than the control group at Month 3 and was still 2.0 cm ( 95 % CI 0.5 to 3.5 ) less than the control group at Month 6 . The absolute risk reduction for 3-month prevalence in low back pain in the experimental group was 24 % ( 95 % CI 4 to 41 ) compared with the control group at Month 3 , and 40 % ( 95 % CI 18 to 57 ) at Month 6 . There were also statistically-significant between-group differences in neural mobility . CONCLUSION Exercise is effective in reducing the intensity and prevalence of low back pain in children . TRIAL REGISTRATION Clinical trials NCT00786864 This study evaluated the efficacy of an exercise programme as an intervention for recurrent non-specific low-back pain ( NLSBP ) in adolescents . A r and omized controlled trial was conducted with an experimental group ( n = 27 , age 14.6 years ) who participated in an 8-week exercise programme and a matched control group ( n = 27 , age 14.6 years ) who continued normal daily activities . All participants suffered from recurrent NSLBP . Pre and post intervention measures of NSLBP status ( pain severity and consequences ) and daily inactivity ( time spent sitting , PC time , TV time ) were reported in one week diaries . Two-way mixed ANOVA ( independent variables : pre/post and experimental/control ) was conducted for each dependent variable , significance was set at P < 0.05 . Significant interaction effects were identified for the severity of pain , number of occasions missing sport due to NSLBP and amount of sport participated in . In each case the experimental group benefited from the exercise programme . In contrast , no significant interaction effects were observed for physical inactivity , both groups spent a similar amount of time sitting , watching TV and using a PC pre- and post- intervention . It was concluded that an exercise programme acted as an effective short-term treatment strategy for NSLBP in adolescents . Further evaluation is required to assess the long-term effectiveness The purpose of this study was to evaluate the efficacy of a specific 8-week exercise rehabilitation program as an intervention to treat recurrent nonspecific low back pain in adolescents . A r and omized controlled trial involving 54 adolescents ( 14.6 + /- 0.6 years ) who suffered from recurrent nonspecific low back pain participated in either the exercise rehabilitation program or a control condition . Pre- and postintervention measures of low back pain status and biological risk indicators were taken . Two-way mixed ANOVA was conducted and significance was set at p < .01 . Significant improvement was noted in the exercise rehabilitation group for perceived severity of pain ( effect size 1.47 ) and number of occasions missing physical activity ( effect size 0.99 ) . Significant improvement in the exercise rehabilitation group for sit- and -reach performance , hip range of motion , lumbar sagittal mobility ( modified Schöber ) , and number of sit-ups in 60 s were also identified . In conclusion , the specific exercise program appeared to provide positive benefits for adolescents suffering from recurrent nonspecific low back pain . Further evaluation is required to evaluate the effectiveness of the exercise rehabilitation program in relation to other interventions and to assess the long-term effectiveness Study Design . A r and omized controlled trial was performed . Objectives . To evaluate how 2 different treatment options affect perception of health , pain , and physical functioning over time among children and adolescents with low back pain ( LBP ) . Summary of Background Data . LBP among children and adolescents has increased . The literature shows that children with LBP also suffer from this condition as adults . Thus , it is important to prevent and treat LBP in children and adolescents . Methods . Forty-five children and adolescents were consecutively r and omized into one of 2 treatment groups and were studied for 12 weeks . Group 1 was given individualized physical therapy and exercise and a st and ardized self-training program and back education . Group 2 was given self-training program and back education but no individualized therapy . The children and adolescents were tested before and after the treatment period . Child Health Question naire Child Form 87 , Rol and & Morris Disability Question naire , Painometer , Back Saver Sit and Reach , and test of trunk muscle endurance were used to evaluate the interventions . Results . Both groups improved statistically significant in most parameters over time . On comparison between the groups the physical function measured by Rol and & Morris Disability Question naire and the duration of pain measured by Painometer improved statistically significant in Group 1 . Conclusion . An individual assessment by a knowledgeable physiotherapist and an active treatment model improve how children and adolescents experience their back problems with respect to health and physical function , pain , strength , and mobility , regardless of whether treatment consists of a home exercise program with follow-up or home exercise combined with exercise and treatment supervised by a physiotherapist |
13,476 | 23,029,285 | / SIGNIFICANCE This meta- analysis confirms that artemisinin derivatives used in combination with praziquantel have the potential to increase the cure rates in schistosomiasis treatment , but not artesunate alone .
It is also confirmed that repeated doses of artemisinin derivatives play a prophylactic role , significantly reducing the incidence of Schistosoma japonicum infections compared with placebo | BACKGROUND Chemotherapy based on repeated doses of praziquantel is still the most effective control strategy against Schistosomiasis , however artemisinin derivatives emerged as a family of compounds with schistomicide activity .
The aim of the present work is to compare the efficacy of artemisinin-based therapies in the treatment and prophylaxis of human schistosomiasis . | OBJECTIVE To evaluate the safety and efficacy of combining artemether ( AM ) and praziquantel ( PZQ ) in different regimens for treating acute schistosomiasis japonica . METHODS We undertook a r and omized , double-blind , placebo-controlled trial within four specialized schistosomiasis hospitals in the Dongting Lake region , Hunan province , China , between May 2003 and December 2005 . Study participants were r and omized into one of four treatment regimes : group A received 60 mg/kg PZQ + 6 mg/kg AM ; group B received 60 mg/kg PZQ + AM placebo ; group C received 120 mg/kg PZQ + 6 mg/kg AM ; and group D received 120 mg/kg PZQ + AM placebo . All participants were followed up over a 45-day period . The primary endpoint of the trial was human infection status ( determined by positive stool examination ) . Secondary endpoints involved clinical observations and blood biochemistry , including monitoring haemoglobin and alanine aminotransferase levels over time . FINDINGS Treatment efficacies of the four different treatment regimens were 98.0 % , 96.4 % , 97.7 % and 95.7 % for group A , B , C , and D respectively ( P > 0.05 ) . The group B had a greater treatment efficacy ( 96.4 % ) than the group D ( 95.7 % ) ( P > 0.05 ) . Group A treatment was better for clearance of fever ( P < 0.05 ) and result ed in a shorter hospitalization time ( P < 0.05 ) . CONCLUSION This is the first report of a r and omized , double-blind , placebo-controlled trial for evaluating combined chemotherapy with AM and two different dosages ( 60 mg/kg and 120 mg/kg ) of PZQ in the treatment of acute schistosomiasis japonica in China . The combination of AM and PZQ chemotherapy did not improve treatment efficacy compared with PZQ alone . PZQ given as a dosage of 60 mg/kg ( 1 day , 3 x 20 mg/kg doses at 4 - 5 hour intervals ) may be as effective as a dosage of 120 mg/kg ( 6 days , 20 mg/kg for each day split into 3 doses at 4 - 5 hour intervals ) Background This study was conducted to determine the efficacy of the antimalarial artemisinin-based combination therapy ( ACT ) artesunate + sulfamethoxypyrazine/pyrimethamine ( As+SMP ) , administered in doses used for malaria , to treat Schistosoma haematobium in school aged children . Methodology /Principal Findings The study was conducted in Djalakorodji , a peri-urban area of Bamako , Mali , using a double blind setup in which As+SMP was compared with praziquantel ( PZQ ) . Urine sample s were examined for Schistosoma haematobium on days −1 , 0 , 28 and 29 . Detection of haematuria , and haematological and biochemical exams were conducted on day 0 and day 28 . Clinical exams were performed on days 0 , 1 , 2 , and 28 . A total of 800 children were included in the trial . The cure rate obtained without viability testing was 43.9 % in the As+SMP group versus 53 % in the PZQ group ( Chi2 = 6.44 , p = 0.011 ) . Egg reduction rates were 95.6 % with PZQ in comparison with 92.8 % with As+SMP , p = 0.096 . The proportion of participants who experienced adverse events related to the medication was 0.5 % ( 2/400 ) in As+SMP treated children compared to 2.3 % ( 9/399 ) in the PZQ group ( p = 0.033 ) . Abdominal pain and vomiting were the most frequent adverse events in both treatment arms . All adverse events were categorized as mild . Conclusions / Significance The study demonstrates that PZQ was more effective than As+SMP for treating Schistosoma haematobium . However , the safety and tolerability profile of As+SMP was similar to that seen with PZQ . Our findings suggest that further investigations seem justifiable to determine the dose/efficacy/safety pattern of As+SMP in the treatment of Schistosoma infections . Trial Registration Clinical Trials.gov BACKGROUND Schistosomiasis is an important parasitic disease in Kenya . Decreasing susceptibility of schistosomes to praziquantel , the major drug used to reduce disease morbidity , has made assessment of new antischistosomal drugs a priority . We aim ed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis . METHODS In this open-label r and omised trial in Rarieda district of western Kenya , we enrolled school children ( aged 6 - 15 years ) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample . Computer-generated block r and omisation was used to assign children ( 1:1 ) to receive artesunate ( 100 mg ) with sulfalene ( also known as sulfamethoxypyrazine ; 250 mg ) plus pyrimethamine ( 12.5 mg ) as one dose every 24 h for 3 days or one dose of praziquantel ( 40 mg/kg per day ) . The primary efficacy endpoint was the number of participants cured 28 days after treatment . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01054651 . RESULTS Between October and December , 2009 , 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine ( n=106 ) or praziquantel ( n=106 ) . 69 patients ( 65 % ) were cured in the praziquantel treatment group compared with 15 ( 14 % ) in the artesunate with sulfalene plus pyrimethamine treatment group ( p<0.0001 ) . Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel ( 22 % [ n=23 ] vs 49 % [ n=52 ] , p<0.0001 ) , and no drug-related serious adverse events occurred . INTERPRETATION The st and ard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya . Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear Artemether is an efficacious antimalarial drug that also displays antischistosomal properties . Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum , S. mansoni and S. haematobium , and thus prevents morbidity . These findings have been confirmed in clinical trials for the former two parasites ; administered orally once every 2 - 3 weeks , artemether significantly reduced the incidence and intensity of patent infections . Here , we present the first r and omized , double-blind , placebo-controlled trial of artemether against S. haematobium , done in a highly endemic area of Côte d'Ivoire . Urine specimens from 440 schoolchildren were examined over 4 consecutive days , followed by two systematic praziquantel treatments 4 weeks apart . S. haematobium-negative children were r and omized to receive 6 mg/kg artemether ( N = 161 ) or placebo ( N = 161 ) . Medication was administered orally for a total of six doses once every 4 weeks . Adverse events were assessed 72 hours after medication , and perceived illness episodes were monitored throughout the study period . Incidence and intensity of S. haematobium infections , and microhematuria and macrohematuria were assessed 3 weeks after the final dosing . We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine ( SP ) . Oral artemether was well tolerated . The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients ( 49 % versus 65 % , protective efficacy : 0.25 , 95 % CI : 0.08 - 0.38 , P = 0.007 ) . The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients ( 3.4 versus 7.4 eggs/10 mL urine , P < 0.001 ) . Heavy S. haematobium infections , microhematuria and macrohematuria , and the incidence of malaria parasitemia were all significantly lower in artemether recipients . In conclusion , previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium , although the protective efficacy was considerably lower . These findings enlarge the scope and potential of artemether and further contribute to discussion s of its role as an additional tool for integrated schistosomiasis control Recently , artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections . Therefore , a double-blind , r and omized , placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon . The 300 infected schoolchildren included in the study were r and omized to receive artesunate plus placebo ( n=90 ) , praziquantel plus placebo ( n=90 ) , artesunate and praziquantel ( n=90 ) , or only placebo ( n=30 ) . End points were efficacy , assessed as cure on day 56 , and tolerability . All treatment regimens were well tolerated . The praziquantel plus placebo-treated group attained a cure rate of 73 % , artesunate plus placebo a rate of 27 % , the combination of artesunate and praziquantel a rate of 81 % , and placebo alone a rate of 20 % . In summary , earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections OBJECTIVE To study the preventive effect of oral artemether ( Art ) against schistosomal infection in the field . METHODS In Minglang District of Yiyang City , Hunan Province , there is an islet with embankment type endemic area in the southern Dongting Lake region . From August to October 1994 the residents who frequently contacted the infested water were selected for study and allocated to the Art group and the control group . About one month before the preventive Art administration , all the residents understudied were examined by stool hatching technique , and then treated orally with praziquantel at a single dose of 40 mg/kg in stool egg-negative residents and 50 mg/kg in stool egg-positive ones . In the Art group , the first dose of 6 mg/kg was given at the end of August , followed by 3 repeated doses every 15 days . Placebo ( starch ) was given to the control group at the same time as in the Art group . The preventive efficacy was evaluated by stool examination 25 - 32 days after the last medication . RESULTS In the Art group , 20 out of 365 studied residents became stool positive with an infection rate of 5.5 % , while in the control group , 51 out of 376 studied residents were stool positive with an infection rate of 13.6 % . The egg count per gram of feces ( EPG ) determined by the Kato-Katz method was 122 + /- 79 in the Art group and 681 + /- 909 in the control group . Meanwhile , two cases of acute schistosomiasis were found in the control group , but none was observed in the Art group . No apparent adverse side effect was seen during the treatment with Art . CONCLUSION Oral Art exhibited apparent preventive effect on the residents who contacted the infested water in schistosomiasis endemic area OBJECTIVE To study the preventive effect of artemether ( Art ) in protecting the people from schistosome infection during flood fighting in schistosomiasis endemic area of Poyang Lake , Jiangxi Province . METHODS From mid July to mid August in 1996 , the water level in Poyang Lake rose due to torrential rains and 2 embankments , Zhedi and Jiangtongdi , which appeared in dangerous situation and were selected as the pilot spots . After those who went to fight against flood arrived at the pilots their sera were collected within 48 hours and were examined with indirect hemagglutination test ( IHA ) , enzyme-linked immunosorbent assay ( ELISA ) and McAb-ELISA . Individuals with negative outcome in the 3 tests were then selected as the study subjects and were allocated r and omly to the Art or the control group . The first dose of Art given to the individuals contacted with the infested water within 11 - 15 days was 6 mg/kg . If the individual continually contacted the infested water , the same dose of Art was given once every 15 days . After the individuals withdrew from the pilot , one more dose of Art was administered 7 - 15 days later . Placebo ( starch ) was given to individuals in the control group at the same period as in artemether group . Stool examinations were made in both groups 40 - 50 days after the last medication for evaluation of the preventive effect of artemether . Double blind method was used in the administration of both artemether and placebo . RESULTS In Zhedi pilot , the individuals fought against flood for about 1 month . In Art group , 99 individuals receiving 3 doses of the drug completed the stool examination with egg-positive rate of 4 % and no acute schistosomiasis was seen . In the control group , among 110 people who completed the observation , 44 were egg-positive with an infection rate of 40 % , and 29 were identified as having acute schistosomiasis . In Jiangtondi , the studied individuals contacted the infested water for only about 4 hours . But in the control group 4 out of 102 individuals were egg-positive , while none of the 103 individuals in Art group receiving 2 doses of the drug showed schistosome infection . No apparent side effect was seen in the people treated with artemether . CONCLUSION After oral Art was given to the people fighting against flood in schistosomiasis endemic area of Poyang Lake , it was shown that the oral Art has a promising effect on controlling acute schistosomiasis and reducing the infection rate AIM To assess the preventive effect of oral artesunate against S. japonicum infection . METHODS Residents in two pilots in the schistosomiasis endemic regions , 562 cases in Yanghe pilot , Wangjiang County and 218 cases in Shashan pilot , Guichi City , Anhui Province , were selected for this study . The residents were divided into two groups . Group I received artesunate 6 mg/kg once every 2 weeks for 4 times 2 wk after contacting with infested water from July to September in 1997 . Group II received the same dosage of placebo at the corresponding times . Four weeks after the last administration , stool examination using hatching method and Kato 's method was conducted to evaluate the effect . RESULTS In Yanghe pilot , 2 cases were hatching positive in the artesunate-treated group with an infection rate of 0.7 % ( 2/273 ) , while 11 cases were stool positive in placebo group with an infection rate of 3.8 % ( 11/289 ) and a mean EPG of 26.40 + /- 1.49 . In Shashan pilot , all cases in artesunate-treated group were stool negative , while 7 cases were stool positive in the placebo group with an infection rate of 6.3 % ( 7/111 ) , and a mean EPG of 14.23 + /- 2.14 . The protection rate of artesunate was 80.9 % and 100 % , respectively , in the two pilots . CONCLUSION Artesunate can protect the residents from S. japonicum infection effectively To further strengthen the evidence -base of artemether for the control of schistosomiasis japonica , a r and omised controlled trial was carried out in the Poyang Lake region , a highly endemic area in southern China . A total of 783 individuals , aged 6 - 60 years , were enrolled . They were first given a single oral dose of praziquantel ( 50 mg/kg ) . Then , they were r and omly assigned oral artemether ( 6 mg/kg ) or placebo , administered once every 2 weeks for 9 - 11 doses , covering the entire transmission season for Schistosoma japonicum in 2004 . Stool examination 1 month after the final dosing revealed eggs of S. japonicum in 3/373 ( 0.8 % ) of the artemether recipients and 56/361 ( 15.0 % ) in placebo recipients ( chi2=53.69 , P<0.001 ) . Compared to the baseline , the geometric mean intensity of S. japonicum infection had decreased by 96.1 % in the artemether group , and increased by 50.8 % in the placebo group . No acute cases of schistosomiasis japonica were observed in the artemether group , whereas three such cases were reported from the placebo group . Compliance with regard to multi-doses of artemether and placebo was 84.9 , and 77.9 % , respectively . This study confirms that repeated oral artemether produces no drug-related adverse effects , significantly reduces incidence and intensity of patent S. japonicum infection and results in high compliance . Hence it can be used as an additional tool for the control of schistosomiasis japonica in the lake regions of China OBJECTIVE To examine the prophylactic effect of artesunate on schistosomiasis japonica by killing schistosomula . METHODS Mice , rabbits and dogs after infection with cercariae of schistosoma japonicum ( S. japonicum ) were treated with artesunate on the 7th day at a dose of 300 mg/kg , 20 - 40 mg/kg and 30 mg/kg respectively once a week for 4 - 6 weeks . A double-blind test was used . A total of 864 persons in highly endemic areas for schistosomiasis were administered either artesunate at a dose of 6 mg/kg once a week for 8 weeks or identical placebo with the same dose-schedule during transmission season for S. japonicum . Four weeks after the last dosing , fecal examinations for S. japonicum eggs and miracidia were carried out to evaluate the prophylactic effect . RESULTS Worm reduction rates in mice , rabbits and dogs were 77.50 - 90.66 % , 99.53 % and 97.10 % respectively . All of the 467 residents in 2 trials were free from eggs or miracidia upon stool examinations whereas in the control groups with placebo , 15 out of 218 ( 6.9 % ) and 26 out of 179 ( 14.5 % ) were stool eggs and /or miracidia positive in the first and second trial , respectively . Side effects were mild . No significant changes in routine blood and urine tests , electrocardiogram , hepatic and renal functions were observed after artesunate administration . CONCLUSIONS Animal experiments and field trials have demonstrated good efficacy of artesunate on killing schistosomula with little side effects . Thus , the drug is suggested to be used on the population in endemic areas for prevention of schistosomiasis Praziquantel is the current mainstay for morbidity control of schistosomiasis . Artemisinin and its derivatives , widely used for the treatment of malaria , also display antischistosomal properties . The present study is an effort to assess the therapeutic efficacy of artesunate , an artemisinin derivative , in Schistosoma haematobium infections in a human population . The efficacy of artesunate and praziquantel were comparatively studied in primary schoolchildren from two villages , Lampsar ( n=180 ) and Makhana ( n=108 ) , located along the Lampsar river in the delta of the Senegal River Basin in Northern Senegal ( West Africa ) . In each village , half of the infected children were treated with a single oral dose of 40 mg/kg praziquantel and half with artesunate following the recommended malaria monotherapy regimen . For both drugs , cure and egg count reduction rates were , without apparent explanation , higher in Makhana than in Lampsar . In both villages , high and nearly comparable egg count reduction rates were obtained with both drugs at each follow-up after treatment ( 5 , 12 and 24 weeks ) in the heavy infected group of children ( > 50 eggs/10 ml of urine ) . No major adverse effects were observed . The results demonstrate that artesunate is effective against S. haematobium , but the results obtained with praziquantel were consistently better BACKGROUND Chemotherapy with praziquantel is the current strategy of choice to control schistosomiasis . However , in view of concern about praziquantel tolerance or resistance , new drugs are needed . Artemether , a derivative of the antimalarial drug artemisinin , kills immature schistosomes of Schistosoma japonicum , and reduces the incidence of infection in field trials . Laboratory studies have also showed activity by this drug against S. mansoni . We report a r and omised double-blind placebo-controlled clinical trial of artemether to prevent S. mansoni infection . METHODS The trial was done in an area of western Côte d'Ivoire endemic for S. mansoni . 354 schoolchildren were enrolled . Stool specimens were screened over four consecutive days , followed by two mass treatments with praziquantel 4 weeks apart . All S. mansoni negative children were r and omly assigned to placebo ( n=151 ) or artemether 6 mg/kg ( n=138 ) orally six times once every 3 weeks . Adverse events were assessed 24 h after treatment . Perceived illness episodes were recorded once a week by interviewing the children with a st and ardised question naire . 3 weeks after the final medication S. mansoni infections were assessed by screening stool sample s. Blood sample s were examined for Plasmodium falciparum before the first and after the last artemether treatment . FINDINGS Oral artemether showed no adverse reactions . The group that received artemether had a significantly lower incidence of S. mansoni infection ( 31/128 versus 68/140 , relative risk : 0.50 [ 95 % CI 0.35 - 0.71 ] , p=0.00006 ) . The geometric mean egg output among positive children in the artemether group was significantly lower than in placebo recipients ( 19 vs 32 eggs/g stool , p=0.017 ) . There was also a significant reduction in the prevalence of P. falciparum . INTERPRETATION Oral artemether is safe and shows a prophylatic effect against S. mansoni . The use of artemether may be recommended in appropriated situations as an additional tool for more effective schistosomiasis control measures . However the application needs to be carefully assessed especially in view of the concern that it could select for resistant plasmodia The combined effects of praziquantel and artesunate in the treatment of urinary schistosomiasis were assessed among 312 r and omly selected schoolchildren aged 4 - 20 years in Adim community , Nigeria . In the preliminary screening , infection was confirmed in 327 ( 38.5 % ) of the 850 subjects screened . Infected subjects who reported for treatment were then divided into six treatment groups of 52 subjects each ; 44 subjects in each group completed their treatment regimens and su bmi tted their urine for post-treatment assessment . Praziquantel and artesunate were administered orally at 40 mg/kg and 4 mg/kg body weight , respectively . Adverse effects due to drug reactions were assessed 72 h after medication and all perceived episodes of illness were treated . Morbidity indicators were assessed 56 days after the final dose of the drug regimens . All treatment regimens were well tolerated . The cure rates were 72.7 % in the praziquantel plus placebo-treated group and 70.5 % in the artesunate plus placebo group , while the artesunate plus praziquantel group had the highest cure rate ( 88.6 % ) . Haematuria and proteinuria were extensively reduced after treatment with the three drug regimens . This study confirmed that the treatment of urinary schistosomiasis with the combination of praziquantel and artesunate is safe and more effective than treatment with either drug alone A group of 110 individuals with Schistosoma mansoni infection was investigated . Patients were allocated to one of three treatment groups and given artesunate or praziquantel alone or both in combination . Combined artesunate-praziquantel significantly increased the number of individuals cured at 5 weeks post-treatment , but at 12 weeks was only better than artesunate alone and at 24 weeks there was no statistically significant difference between the three groups . Egg count reduction rate was similar to the rate obtained with praziquantel used alone |
13,477 | 24,116,973 | The main findings were improved communication , reduced adverse events , better adherence to st and ard operating procedures , and reduced morbidity and mortality .
None of the included studies reported decreased patient safety or quality after introducing safety checklists .
CONCLUSION Safety checklists appear to be effective tools for improving patient safety in various clinical setting s by strengthening compliance with guidelines , improving human factors , reducing the incidence of adverse events , and decreasing mortality and morbidity .
None of the included studies reported negative effects on safety | BACKGROUND Safety checklists have become an established safety tool in medicine .
Despite studies showing decreased mortality and complications , the effects and feasibility of checklists have been question ed .
This systematic review summarises the medical literature aim ing to show the effects of safety checklists with a number of outcomes . | BACKGROUND We aim ed to improve the quality and safety of h and over of patients from surgery to intensive care using the analogy of a Formula 1 pit stop and expertise from aviation . METHODS A prospect i ve intervention study measured the change in performance before and after the implementation of a new h and over protocol that was developed through detailed discussion s with a Formula 1 racing team and aviation training captains . Fifty ( 23 before and 27 after ) postsurgery patient h and overs were observed . Technical errors and information omissions were measured using checklists , and teamwork was scored using a Likert scale . Duration of the h and over was also measured . RESULTS The mean number of technical errors was reduced from 5.42 ( 95 % CI + /-1.24 ) to 3.15 ( 95 % CI + /-0.71 ) , the mean number of information h and over omissions was reduced from 2.09 ( 95 % CI + /-1.14 ) to 1.07 ( 95 % CI + /-0.55 ) , and duration of h and over was reduced from 10.8 min ( 95 % CI + /-1.6 ) to 9.4 min ( 95 % CI + /-1.29 ) . Nine out of twenty-three ( 39 % ) precondition patients had more than one error in both technical and information h and over prior to the new protocol , compared with three out of twnety-seven ( 11.5 % ) with the new h and over . Regression analysis showed that the number of technical errors were significantly reduced with the new h and over ( t = -3.63 , P < 0.001 ) , and an interaction suggested that teamwork ( t = 3.04 , P = 0.004 ) had a different effect with the new h and over protocol . CONCLUSIONS The introduction of the new h and over protocol lead to improvements in all aspects of the h and over . Expertise from other industries can be extrapolated to improve patient safety , and in particular , areas of medicine involving the h and over of patients or information Objective To assess the frequency and nature of adverse events to patients in selected hospitals in developing or transitional economies . Design Retrospective medical record review of hospital admissions during 2005 in eight countries . Setting Ministries of Health of Egypt , Jordan , Kenya , Morocco , Tunisia , Sudan , South Africa and Yemen ; the World Health Organisation ( WHO ) Eastern Mediterranean and African Regions ( EMRO and AFRO ) , and WHO Patient Safety . Participants Convenience sample of 26 hospitals from which 15 548 patient records were r and omly sample d. Main outcome measures Two stage screening . Initial screening based on 18 explicit criteria . Records that screened positive were then review ed by a senior physician for determination of adverse event , its preventability , and the result ing disability . Results Of the 15 548 records review ed , 8.2 % showed at least one adverse event , with a range of 2.5 % to 18.4 % per country . Of these events , 83 % were judged to be preventable , while about 30 % were associated with death of the patient . About 34 % adverse events were from therapeutic errors in relatively non-complex clinical situations . Inadequate training and supervision of clinical staff or the failure to follow policies or protocol s contributed to most events . Conclusions Unsafe patient care represents a serious and considerable danger to patients in the hospitals that were studied , and hence should be a high priority public health problem . Many other developing and transitional economies will probably share similar rates of harm and similar contributory factors . The convenience sampling of hospitals might limit the interpretation of results , but the identified adverse event rates show an estimate that should stimulate and facilitate the urgent institution of appropriate remedial action and also to trigger more research . Prevention of these adverse events will be complex and involves improving basic clinical processes and does not simply depend on the provision of more re sources BACKGROUND Surgery has become an integral part of global health care , with an estimated 234 million operations performed yearly . Surgical complications are common and often preventable . We hypothesized that a program to implement a 19-item surgical safety checklist design ed to improve team communication and consistency of care would reduce complications and deaths associated with surgery . METHODS Between October 2007 and September 2008 , eight hospitals in eight cities ( Toronto , Canada ; New Delhi , India ; Amman , Jordan ; Auckl and , New Zeal and ; Manila , Philippines ; Ifakara , Tanzania ; London , Engl and ; and Seattle , WA ) representing a variety of economic circumstances and diverse population s of patients participated in the World Health Organization 's Safe Surgery Saves Lives program . We prospect ively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery . We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist . The primary end point was the rate of complications , including death , during hospitalization within the first 30 days after the operation . RESULTS The rate of death was 1.5 % before the checklist was introduced and declined to 0.8 % afterward ( P=0.003 ) . Inpatient complications occurred in 11.0 % of patients at baseline and in 7.0 % after introduction of the checklist ( P<0.001 ) . CONCLUSIONS Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals Objective Implementation of a surgical checklist depends on many organisational factors and on socio-cultural patterns . The objective of this study was to identify barriers to effective implementation of a surgical checklist and to develop a best use strategy . Setting 18 cancer centres in France . Design The authors first assessed use compliance and completeness rates of the surgical checklist on a r and om sample of 80 surgical procedures performed under general or loco-regional anaesthesia in each of the 18 centres . They then developed a typology of the organisational and cultural barriers to effective checklist implementation and defined each barrier 's contents using data from collective and semi-structured individual interviews of key staff , the results of an email question naire sent to the 18 centres , and direct observations over 20 h in two centres . Results The study consisted of 1440 surgical procedures , 1299 checklists , and 28 578 items . The mean compliance rate was 90.2 % ( 0 , 100 ) . The mean completion rate was 61 % ( 0 , 84 ) . 11 barriers to effective checklist implementation were identified . Their incidence varied widely across centres . The main barriers were duplication of items within existing checklists ( 16/18 centres ) , poor communication between surgeon and anaesthetist ( 10/18 ) , time spent completing the checklist for no perceived benefit , and lack of underst and ing and timing of item checks ( 9/18 ) , ambiguity ( 8/18 ) , unaccounted risks ( 7/18 ) and a time-honoured hierarchy ( 6/18 ) . Conclusions Several of the barriers to the successful implementation of the surgical checklist depended on organisational and cultural factors within each centre . The authors propose a strategy for change for checklist design , use and assessment , which could be used to construct a feedback loop for local team organisation and national initiatives Objective : To assess whether implementation of a 19-item World Health Organization ( WHO ) Surgical Safety Checklist in urgent surgical cases would improve compliance with basic st and ards of care and reduce rates of deaths and complications . Background : Use of the WHO Surgical Safety Checklist has been shown to be associated with significant reductions in complications and deaths . Before evaluation of this safety tool , concern was raised about whether its use would be practical or beneficial during urgent surgical procedures . Methods : We prospect ively collected clinical process and outcome data for 1750 consecutively enrolled patients 16 years of age or older undergoing urgent noncardiac surgery before and after introduction of the WHO Surgical Safety Checklist in 8 diverse hospitals around the world ; 842 underwent urgent surgery — defined as an operation required within 24 hours of assessment to be beneficial — before introduction of the checklist and 908 after introduction of the checklist . The primary end point was the rate of complications , including death , during hospitalization up to 30 days following surgery . Results : The complication rate was 18.4 % ( n = 151 ) at baseline and 11.7 % ( n = 102 ) after the checklist was introduced ( P = 0.0001 ) . Death rates dropped from 3.7 % to 1.4 % following checklist introduction ( P = 0.0067 ) . Adherence to 6 measured safety steps improved from 18.6 % to 50.7 % ( P < 0.0001 ) . Conclusions : Implementation of the checklist was associated with a greater than one-third reduction in complications among adult patients undergoing urgent noncardiac surgery in a diverse group of hospitals . Use of the WHO Surgical Safety Checklist in urgent operations is feasible and should be considered Background Positive changes in safety culture have been hypothesized to be one of the mechanisms behind the reduction in mortality and morbidity after the introduction of the World Health Organization 's Surgical Safety Checklist ( SSC ) . We aim ed to study the checklist effects on safety culture perceptions in operating theatre personnel using a prospect i ve controlled intervention design at a single Norwegian university hospital . Methods We conducted a study with pre- and post-intervention surveys using the intervention and control groups . The primary outcome was the effects of the Norwegian version of the SSC on safety culture perceptions . Safety culture was measured using the vali date d Norwegian version of the Hospital Survey on Patient Safety Culture . Descriptive characteristics of operating theatre personnel and checklist compliance data were also recorded . A mixed linear regression model was used to assess changes in safety culture . Results The response rate was 61 % ( 349/575 ) at baseline and 51 % ( 292/569 ) post-intervention . Checklist compliance ranged from 77 % to 85 % . We found significant positive changes in the checklist intervention group for the culture factors ‘ frequency of events reported ’ and ‘ adequate staffing ’ with regression coefficients at −0.25 [ 95 % confidence interval ( CI ) , −0.47 to −0.07 ] and 0.21 ( 95 % CI , 0.07–0.35 ) , respectively . Overall , the intervention group reported significantly more positive culture scores — including at baseline . Conclusions Implementation of the SSC had rather limited impact on the safety culture within this hospital BACKGROUND Preventable deaths due to errors in trauma patients with otherwise survivable injuries account for up to 10 % of fatalities in Level I trauma centers , 50 % of these errors occur in the intensive care unit ( ICU ) . The root cause of 67 % of the Joint Commission sentinel events is communication errors . The objective is ( 1 ) to study how critical information de grade s and how it is lost over 24 hours and ( 2 ) to determine whether a structured checklist for ICU h and offs prevents information loss . METHODS Prospect i ve cohort study of trauma and surgical ICU teams observed with and without use of the checklist . An observational period ( control group ) was followed by a didactic session on the science and use of a checklist ( study group ) , which was used for patient management and h and offs . Information was tracked for a 24-hour period and all h and offs . Comparisons use chi or Fisher 's exact test and a p value < 0.05 was defined as significant . RESULTS Three hundred and thirty-two patient ICU days were observed ( 119 control , 213 study ) and 689 patient care items ( 303 control , 386 study ) were followed . Seventy-five ( 10.9 % ) items were lost over 24 hours ; 61 of 303 ( 20.1 % ) without checklist and 14 of 386 ( 3.6 % ) with checklist ( p < 0.0001 ) . Critical laboratory values and test results were the most frequent lost items ( 36.1 % control vs. 4.5 % study p < 0.0001 ) . Six of 75 ( 8.1 % ) items were correctly ordered but not carried out by ICU nursing staff -- all caught and corrected with checklist use . CONCLUSION Critical information is de grade d over 24 hours in the ICU . A structured checklist significantly reduces patient errors due to lost information and communication lapses between trauma ICU team members at h and offs of care OBJECTIVES Perioperative h and offs are a particularly high-risk period given patients ' postprocedural physiology , their physical transport through the hospital , and the triad transfer of personnel , information , and technology . The authors piloted a new perioperative h and off process to guide patient transfers from the cardiac operating room ( OR ) to the cardiac surgical intensive care unit ( CSICU ) . The aim of the study was to evaluate the impact of a st and ardized h and off process on patient care and provider satisfaction . DESIGN A prospect i ve , unblinded intervention study . SETTING A CSICU in a teaching hospital . PARTICIPANTS Two hundred thirty-eight health care practitioners during the transfer of care of 60 patients . INTERVENTIONS The implementation of a st and ardized h and off protocol and checklist . MEASUREMENTS AND MAIN RESULTS After the protocol 's implementation , the presence of all h and off core team members at the bedside increased from 0 % at baseline to 68 % after intervention . The percentage of missed information in the surgery report decreased from 26 % to 16 % ( p = 0.03 ) , but the percentage of missed information in the anesthesia report showed no significant change ( 19 % to 17 % , p > 0.05 ) . H and off satisfaction scores among intensive care unit ( ICU ) nurses increased from 61 % to 81 % . On average , the duration of h and off increased by 1 minute . CONCLUSIONS A st and ardized h and off protocol that guides the transfer of care from the OR team to the CSICU team can reduce the risk of missed information and improve satisfaction among perioperative providers Checklists have been shown to improve patient outcomes . Checklist use is seen in the pre-operative to post-operative phases of the patient pathway . An adhesive checklist was developed for ward rounds due to the positive impact it could have on improving patient safety . Over an eight day period data were collected from five consultant-led teams that were r and omly selected from the surgical department and divided into sticker groups and control groups . Across the board percentage adherence to the Good Surgical Practice Guidelines ( GSPG ) was markedly higher in the sticker study group , 1186 ( 91 % ) in comparison with the control group 718 ( 55 % ) . There was significant improvement of documentation across all areas measured . An adhesive checklist for ward round note taking is a simple and cost-effective way to improve documentation , communication , h and -over , and patient safety . Successfully implemented in a tertiary level centre in Dublin , Irel and it is easily transferable to other surgical departments globally PURPOSE Healthcare includes important processes such as checking to reduce errors . Checking is a prescribed part of many patient care activities with many checks being performed during one hospital admission . Some may be st and ard but unwritten practice s , whereas others are laid down in official guidance . Errors in the bedside checking procedure are the commonest cause of mis-transfusion , so more thorough checking could prevent adverse events . This paper aims to explore and enhance underst and ing regarding healthcare checking procedures . In doing so it seeks to identify a further research agenda . DESIGN / METHODOLOGY /APPROACH The computerised data bases CINAHL , PsycLIT , EMBASE , PubMed , PsycINFO and MEDLINE were search ed using specific indexing terms and free text including " bedside , peri-operative safety , theatre checking and checklists " . Only English publications were included . FINDINGS Like any human activity , checking is part of personality and behaviour . There are several psychological factors relevant to patient safety , including : memory , prospect i ve memory , automaticity and responsibility . All are relevant to healthcare . RESEARCH LIMITATIONS / IMPLICATION S B and olier criteria have not explicitly been used within this review but have been met . It would be beneficial for future review s to explicitly state how B and olier criteria are met . This would possibly enhance the publications ' scientific quality . PRACTICAL IMPLICATION S There is much to learn regarding interacting factors that influence healthcare checking procedures and ultimately checking performance . The authors recommend that relationships between checking and personality should be explored . Furthermore , exploring how healthcare " mindfulness " might be promoted and what reminder/checking strategies healthcare staff already use in their day-to-day work routines should be examined . ORIGINALITY/VALUE Several psychological factors involved in checking and its relevance to healthcare and patient safety are identified . Additionally , recommendations for further research are indicated BACKGROUND We have previously demonstrated that the use of a daily " Quality Rounds Checklist " ( QRC ) can increase compliance with evidence -based prophylactic measures and decrease complications in a busy trauma intensive care unit ( ICU ) over a 3-month period . This study was design ed to determine the sustainability of QRC use over 1 year and examine the relationship between compliance and outcome improvement . METHODS A prospect i ve before-after design was used to examine the effectiveness of the QRC tool in documenting compliance with 16 prophylactic measures for ventilator-associated pneumonia ( VAP ) , deep venous thrombosis , pulmonary embolism , catheter-related bloodstream infection , and other ICU complications . The QRC was implemented on a daily basis for a 1-year period by the ICU fellow on duty . Monthly compliance rates were assessed by a multidisciplinary team for development of strategies for real-time improvement . Compliance and outcomes were captured over 1 year of QRC use . RESULTS QRC use was associated with a sustained improvement of VAP bundle and other compliance measures over a year of use . After multivariable analysis adjusting for age ( > 55 ) , injury mechanism , Glasgow Coma Scale score ( ≤ 8) , and Injury Severity Score ( > 20 ) , the rate of VAP was significantly lower after QRC use , with an adjusted mean difference of -6.65 ( per 1,000 device days ; 95 % confidence interval , -9.27 to -4.04 ; p = 0.008 ) . During the year of QRC use , 3 % of patients developed a VAP if all four daily bundle measures were met for the duration of ICU stay versus 14 % in those with partial compliance ( p = 0.04 ) . The overall VAP rate with full compliance was 5.29 versus 9.23 ( per 1,000 device days ) with partial compliance . Compared with the previous year , a 24 % decrease in the number of pneumonias was recorded for the year of QRC use , representing an estimated cost savings of approximately $ 400,000 . CONCLUSION The use of a QRC facilitates sustainable improvement in compliance rates for clinical ly significant prophylactic measures in a busy Level I trauma ICU . The daily use of the QRC , requiring just a few minutes per patient to complete , equates to cost-effective improvement in patient outcomes OBJECTIVE To assess whether structured team briefings improve operating room communication . DESIGN , SETTING , AND PARTICIPANTS This 13-month prospect i ve study used a preintervention/postintervention design . All staff and trainees in the division of general surgery at a Canadian academic tertiary care hospital were invited to participate . Participants included 11 general surgeons , 24 surgical trainees , 41 operating room nurses , 28 anesthesiologists , and 24 anesthesia trainees . INTERVENTION Surgeons , nurses , and anesthesiologists gathered before 302 patient procedures for a short team briefing structured by a checklist . Main Outcome Measure The primary outcome measure was the number of communication failures ( late , inaccurate , unresolved , or exclusive communication ) per procedure . Communication failures and their consequences were documented by 1 of 4 trained observers using a vali date d observational scale . Secondary outcomes were the number of checklist briefings that demonstrated " utility " ( an effect on the knowledge or actions of the team ) and participants ' perceptions of the briefing experience . RESULTS One hundred seventy-two procedures were observed ( 86 preintervention , 86 postintervention ) . The mean ( SD ) number of communication failures per procedure declined from 3.95 ( 3.20 ) before the intervention to 1.31 ( 1.53 ) after the intervention ( P < .001 ) . Thirty-four percent of briefings demonstrated utility , including identification of problems , resolution of critical knowledge gaps , decision-making , and follow-up actions . CONCLUSIONS Interprofessional checklist briefings reduced the number of communication failures and promoted proactive and collaborative team communication CONTEXT Large clinical trials are the criterion st and ard for making treatment decisions , and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions . OBJECTIVES To determine the rate of full publication of large r and omized trials presented at annual meetings of the American Society of Clinical Oncology ( ASCO ) , quantify bias against publishing nonsignificant results , and identify factors associated with time to publication . DESIGN Survey of 510 abstract s from large ( sample size , > or = 200 ) , phase 3 , r and omized controlled trials presented at ASCO meetings between 1989 and 1998 . Trial results were classified as significant ( P < or = .05 for the primary outcome measure ) or nonsignificant ( P>.05 or not reported ) , and the type of presentation and sponsorship were identified . Subsequent full publication was identified using a search of MEDLINE and EMBASE , completed November 1 , 2001 ; the search was up date d in November 2002 , using the Cochrane Register of Controlled Trials . Authors were contacted if the search es did not find evidence of publication . MAIN OUTCOME MEASURES Publication rate at 5 years ; time from presentation to full publication . RESULTS Of 510 r and omized trials , 26 % were not published in full within 5 years after presentation at the meeting . Eighty-one percent of the studies with significant results had been published by this time compared with 68 % of the studies with nonsignificant results ( P<.001 ) . Studies with oral or plenary presentation were published sooner than those not presented ( P = .002 ) , and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified ( P = .02 ) . These factors remained significant in a multivariable model . The most frequent reason cited by authors for not publishing was lack of time , funds , or other re sources . CONCLUSIONS A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation . Bias against publishing nonsignificant results is a problem even for large r and omized trials . Nonpublication breaks the contract that investigators make with trial participants , funding agencies , and ethics boards OBJECTIVE To assess the impact of the implementation of a daily goals sheet upon nursing perception of communication in an academic , tertiary care paediatric intensive care unit ( PICU ) . DESIGN Prospect i ve , longitudinal , before- and -after intervention surveys . SETTING University affiliated 12-bed PICU . SUBJECTS Bedside nurses . INTERVENTIONS A question naire was administered to PICU nurses addressing their perception of communication . Following this question naire , the use of a daily goals sheet was instituted . A second question naire was administered one year later . Mann-Whitney Rank Sum Test was used to compare differences of the grade d outcome variables . MEASUREMENTS AND MAIN RESULTS The primary outcome was the perception of communication taken from a nursing perspective . Eighty-five percent of nurses felt the daily goals sheet led to improved communication between physicians and nurses in the PICU . All questions related to communication demonstrated a positive influence of the goals sheet , with the perception of the PICU staff working as a team reaching statistical significance ( p=0.05 ) . The perception of the care of one surgical service being attending physician directed also significantly improved after the institution of the goals sheet ( p=0.04 ) . CONCLUSION The institution of a daily goals sheet led to an improvement in nursing perception of communication . Future studies are required to determine if this change in process has a demonstrable effect on health care outcomes of critically ill children , or whether this tool can have the same beneficial effects in other academic and non-academic PICUs BACKGROUND Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses . Most surgical safety interventions have focused on the operating room . Since more than half of all surgical errors occur outside the operating room , it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway . METHODS We examined the effects on patient outcomes of a comprehensive , multidisciplinary surgical safety checklist , including items such as medication , marking of the operative side , and use of postoperative instructions . The checklist was implemented in six hospitals with high st and ards of care . All complications occurring during admission were documented prospect ively . We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist , while accounting for potential confounders . Similar data were collected from a control group of five hospitals . RESULTS In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation , the total number of complications per 100 patients decreased from 27.3 ( 95 % confidence interval [ CI ] , 25.9 to 28.7 ) to 16.7 ( 95 % CI , 15.6 to 17.9 ) , for an absolute risk reduction of 10.6 ( 95 % CI , 8.7 to 12.4 ) . The proportion of patients with one or more complications decreased from 15.4 % to 10.6 % ( P<0.001 ) . In-hospital mortality decreased from 1.5 % ( 95 % CI , 1.2 to 2.0 ) to 0.8 % ( 95 % CI , 0.6 to 1.1 ) , for an absolute risk reduction of 0.7 percentage points ( 95 % CI , 0.2 to 1.2 ) . Outcomes did not change in the control hospitals . CONCLUSIONS Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high st and ard of care . ( Netherl and s Trial Register number , NTR1943 . ) BACKGROUND Clear communication is imperative if teams in any industry expect to make improvements . An estimated 85 % of errors across industries result from communication failures . PURPOSE The purpose of this study was to evaluate and improve the effectiveness of communication during patient care rounds in the intensive care unit ( ICU ) using a daily goals form . DESIGN We conducted a prospect i ve cohort study in collaboration with the Volunteer Hospital Association ( VHA ) , Institute for Healthcare Improvement ( IHI ) , and Johns Hopkins Hospital 's ( JHH ) 16-bed surgical oncology ICU . All patients admitted to the ICU were eligible . Main outcome variables were ICU length of stay ( LOS ) and percent of ICU residents and nurses who understood the goals of care for patients in the ICU . Baseline measurements were compared with measurements of underst and ing after implementation of a daily goals form . RESULTS At baseline , less than 10 % of residents and nurses understood the goals of care for the day . After implementing the daily goals form , greater than 95 % of nurses and residents understood the goals of care for the day . After implementation of the daily goals form , ICU LOS decreased from a mean of 2.2 days to 1.1 days . CONCLUSION Implementing the daily goals form result ed in a significant improvement in the percent of residents and nurses who understood the goals of care for the day and a reduction in ICU LOS . The use of the daily goals form has broad applicability in acute care medicine BACKGROUND Using the World Health Organisation ( WHO ) surgical checklist has been shown to improve the safety of patients undergoing surgery . Its effect on the compliance to venous thromboembolism ( VTE ) guidelines has not been established before . Our objective was to assess if using the WHO checklist improved compliance to VTE prophylaxis guidelines . METHODS Compliance to NICE VTE guidelines were prospect ively assessed in all general surgery patients over two separate audit periods , before and after 6 months of the routine use of the WHO checklist . Correct completion of the checklist was verified . RESULTS 370 patients ( 173 [ 47 % ] male , 197 [ 53 % ] female , mean age 61.6 yrs ) . Non compliance to NICE VTE guidelines was reduced form 16/233 ( 6.9 % ) to 3/137 ( 2.1 % ) after introduction of the checklist ( p = 0.046 Fisher exact test ) . Non compliance was reduced in both emergency and elective procedures . CONCLUSIONS Establishment of the WHO checklist for routine use in all general surgery patients may significantly improve VTE guideline compliance of all general surgery patients Procedural checklists may be useful for increasing the reliability of safety-critical processes because of their potential capacity to improve teamwork , situation awareness , and error catching . To test the hypothesized utility and adaptability of checklists to surgical teams , we performed a r and omized controlled trial of procedural checklists to determine their capacity to increase the frequency of safety-critical behaviors during 47 laparoscopic cholecystectomies . Ten attending surgeons at an academic tertiary care center were r and omized into two equal groups - half of these surgeons received basic team training and used a preprocedural checklist whereas the other half performed st and ard laparoscopic cholecystectomies . All procedures were videotaped and scored by trained review ers for the presence of safety-critical behaviors . There were no differences detected in patient outcomes , case times , or technical proficiency between groups . Cases performed by surgeons in the intervention ( checklist ) group were significantly more likely to involve positive safety-related team behaviors such as case presentations , explicit discussion s of roles and responsibilities , contingency planning , equipment checks , and postcase debriefings . Overall , situational awareness did not significantly differ between the intervention and control groups . Participants in the intervention ( checklist ) group consistently rated their cases as involving less satisfactory subjective levels of comfort , team efficiency , and communication compared with those performed by surgeons in the control group . Surgical procedural safety checklists have the capacity to increase the frequency of positive team behaviors in the operating room during laparoscopic surgery . Adapting to the use of a procedural checklist may be initially uncomfortable for participants |
13,478 | 31,413,628 | As a whole , the results showed clearly superior efficacy of CIM in improving HRQOL .
For different domains of HRQOL , different CIM interventions may play different roles .
In conclusion , CIM may improve the HRQOL of cancer patients . | Complementary and integrative medicine ( CIM ) has been used for improving health-related quality of life ( HRQOL ) in patients with cancer .
The objective of this review is to evaluate the effects of CIMs on the HRQOL of cancer patients . | IMPORTANCE Although many patients with end-stage cancer are offered chemotherapy to improve quality of life ( QOL ) , the association between chemotherapy and QOL amid progressive metastatic disease has not been well-studied . American Society for Clinical Oncology guidelines recommend palliative chemotherapy only for solid tumor patients with good performance status . OBJECTIVE To evaluate the association between chemotherapy use and QOL near death ( QOD ) as a function of patients ' performance status . DESIGN , SETTING , AND PARTICIPANTS A multi-institutional , longitudinal cohort study of patients with end-stage cancer recruited between September 2002 and February 2008 . Chemotherapy use ( n = 158 [ 50.6 % ] ) and Eastern Cooperative Oncology Group ( ECOG ) performance status were assessed at baseline ( median = 3.8 months before death ) and patients with progressive metastatic cancer ( N = 312 ) following at least 1 chemotherapy regimen were followed prospect ively until death at 6 outpatient oncology clinics in the United States . MAIN OUTCOMES AND MEASURES Patient QOD was determined using vali date d caregiver ratings of patients ' physical and mental distress in their final week . RESULTS Chemotherapy use was not associated with patient survival controlling for clinical setting and patients ' performance status . Among patients with good ( ECOG score = 1 ) baseline performance status , chemotherapy use compared with nonuse was associated with worse QOD ( odds ratio [ OR ] , 0.35 ; 95 % CI , 0.17 - 0.75 ; P = .01 ) . Baseline chemotherapy use was not associated with QOD among patients with moderate ( ECOG score = 2 ) baseline performance status ( OR , 1.06 ; 95 % CI , 0.51 - 2.21 ; P = .87 ) or poor ( ECOG score = 3 ) baseline performance status ( OR , 1.34 ; 95 % CI , 0.46 - 3.89 ; P = .59 ) . CONCLUSIONS AND RELEVANCE Although palliative chemotherapy is used to improve QOL for patients with end-stage cancer , its use did not improve QOD for patients with moderate or poor performance status and worsened QOD for patients with good performance status . The QOD in patients with end-stage cancer is not improved , and can be harmed , by chemotherapy use near death , even in patients with good performance status A self-control , r and omized , and open-label clinical trial was performed to test the effects of the unicellular green algae Chlorella and hot water extract supplementation on quality of life ( QOL ) in patients with breast cancer . Forty-five female patients with breast cancer who were living at home and not hospitalized were r and omly assigned to 3 groups receiving vitamin mix tablet ( control ) , Chlorella granules ( test food-1 ) , or Chlorella extract drink ( test food-2 ) daily for one month . The Functional Assessment of Cancer Therapy-Breast ( FACT-B ) , the Izumo scale for abdominal symptom-specific QOL , and a narrative-form question naire were used to determine outcomes . Data of thirty-six subjects were included for final analysis . FACT-B scores at presupplementation found no significant group differences in all subscales . Scores on the breast cancer subscale in the Chlorella granule group significantly increased during the supplementation period ( P = 0.042 ) . Fifty percent of the Chlorella extract group reported positive effects by the test food such as reduction of fatigue and improvements of dry skin ( P < 0.01 versus control group ) . The findings suggested the beneficial effects of Chlorella on breast cancer-related QOL and of Chlorella extract on vitality status in breast cancer patients . These findings need to be confirmed in a larger study Ginger supplementation could be an effective adjuvant treatment for chemotherapy-induced nausea ( CIN ) . The aim of this clinical trial was to address significant method ological limitations in previous trials . Patients ( N = 51 ) were r and omly allocated to receive either 1.2 g of st and ardised ginger extract or placebo per day , in addition to st and ard anti-emetic therapy , during the first three cycles of chemotherapy . The primary outcome was CIN-related quality of life ( QoL ) measured with the Functional Living Index- Emesis ( FLIE ) question naire . Secondary outcomes included acute and delayed nausea , vomiting , and retching as well as cancer-related fatigue , nutritional status , and CIN and vomiting-specific prognostic factors . Over three consecutive chemotherapy cycles , nausea was more prevalent than vomiting ( 47 % vs. 12 % ) . In chemotherapy Cycle 1 , intervention participants reported significantly better QoL related to CIN ( p = 0.029 ) , chemotherapy-induced nausea and vomiting (CINV)-related QoL ( p = 0.043 ) , global QoL ( p = 0.015 ) and less fatigue ( p = 0.006 ) than placebo participants . There were no significant results in Cycle 2 . In Cycle 3 , global QoL ( p = 0.040 ) and fatigue ( p = 0.013 ) were significantly better in the intervention group compared to placebo . This trial suggests adjuvant ginger supplementation is associated with better chemotherapy-induced nausea-related quality of life and less cancer-related fatigue , with no difference in adverse effects compared to placebo Purpose Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors . Mechanisms underlying symptoms may include inflammation . It is hypothesized that n − 3 polyunsaturated fatty acids ( PUFAs ) have anti-inflammatory properties and may reduce symptoms . Methods We conducted a r and omized , double-blind , placebo-controlled study comparing 4.3 g/day n − 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs . Primary endpoints were adherence and tolerability ; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form ( BPI-SF ) and Functional Assessment of Cancer Treatment-Endocrine Symptoms ( FACT-ES ) at 0 , 12 , and 24 weeks . Results Forty-four women were r and omized , of which 35 completed the study . Adherence was ≥ 88 % based on these 35 patients with pill counts as well as change in red blood cell ( RBC ) n − 3 PUFAs . Common toxicities included grade 1 flatulence ( 55 % of both groups ) and belching ( 45 % of n − 3 group ) . Mean pain severity scores ( BPI-SF ) did not change significantly by time or treatment arm . Quality of life , based on FACT-ES scores , significantly decreased within placebo ( p = 0.04 ) , but not the n − 3 group ( p = 0.58 ) , with a trend toward between-group differences ( p = 0.06 ) at 12 weeks , but no significant differences at 24 weeks . RBC n − 3 levels were strongly positively correlated with FACT-ES at 12 weeks , but attenuated at 24 weeks . Conclusion High-dose n − 3 PUFA supplementation is feasible and well tolerated when administered with AIs . Additional studies are needed to evaluate efficacy in prevention of joint symptoms PURPOSE A r and omized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue , erectile dysfunction , urinary incontinence , and overall quality of life ( QOL ) in prostate cancer ( PCa ) patients undergoing external beam radiation therapy ( RT ) . METHODS AND MATERIAL S The participants were r and omized to yoga and no-yoga cohorts ( 1:1 ) . Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT . Comparisons of st and ardized assessment s were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction , urinary incontinence , and QOL before , during , and after RT . RESULTS From October 2014 to January 2016 , 68 eligible PCa patients underwent informed consent and agreed to participate in the study . Of the 68 patients , 18 withdrew early , mostly because of treatment schedule-related time constraints , result ing in 22 and 28 patients in the yoga and no-yoga groups , respectively . Throughout treatment , those in the yoga arm reported less fatigue than those in the control arm , with global fatigue , effect of fatigue , and severity of fatigue subscales showing statistically significant interactions ( P<.0001 ) . The sexual health scores ( International Index of Erectile Function Question naire ) also displayed a statistically significant interaction ( P=.0333 ) . The International Prostate Symptom Score revealed a statistically significant effect of time ( P<.0001 ) but no significant effect of treatment ( P=.1022 ) . The QOL measures had mixed results , with yoga having a significant time by treatment effect on the emotional , physical , and social scores but not on functional scores . CONCLUSIONS A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients OBJECTIVE Although chemotherapy-induced cognitive impairment is common among breast cancer patients , evidence for effective interventions addressing cognitive deficits is limited . This r and omized controlled trial examined the feasibility and preliminary efficacy of a Tibetan Sound Meditation ( TSM ) program to improve cognitive function and quality of life in breast cancer patients . METHODS Forty-seven breast cancer patients ( mean age 56.3 years ) , who were staged I-III at diagnosis , 6 - 60 months post-chemotherapy , and reported cognitive impairment at study entry were recruited . Participants were r and omized to either two weekly TSM sessions for 6 weeks or a wait list control group . Neuropsychological assessment s were completed at baseline and 1 month post-treatment . Self-report measures of cognitive function ( Functional Assessment of Cancer Therapy (FACT)-Cog ) , quality of life ( SF-36 ) , depressive symptoms ( Center for Epidemiologic Studies Depression Scale ) , sleep disturbance ( Pittsburgh Sleep Quality Index ) , fatigue ( Brief Fatigue Inventory ) , and spirituality ( FACT-Sp ) were completed at baseline , the end of treatment , and 1 month later . RESULTS Relative to the control group , women in the TSM group performed better on the verbal memory test ( Rey Auditory Verbal Learning Test trial 1 ) ( p = 0.06 ) and the short-term memory and processing speed task ( Digit Symbol ) ( p = 0.09 ) and reported improved cognitive function ( p = 0.06 ) , cognitive abilities ( p = 0.08 ) , mental health ( p = 0.04 ) , and spirituality ( p = 0.05 ) at the end of treatment but not 1 month later . CONCLUSIONS This r and omized controlled trial revealed that TSM program appears to be a feasible and acceptable intervention and may be associated with short-term improvements in objective and subjective cognitive function as well as mental health and spirituality in breast cancer patients Purpose This study was to evaluate the efficacy of a complementary Chinese treatment modality Guolin-Qigong ( GLQG ) for patients with breast cancer on the body-mind health . Methods A r and omized controlled clinical trial was conducted among 158 women with breast cancer . Subjects were r and omized to receive GLQG ( test group ) versus a physical stretching program ( control group ) following conventional treatment for breast cancer . GLQG and stretching interventions were performed twice a week over 24 weeks . The primary outcome was the change in quality of life ( QoL ) . Secondary outcome measures included anxiety , depression , and clinical indicators . All participants were assessed at four time-points , at the beginning of the study ( T1 ) , after 12 weeks of the intervention ( T2 ) , immediately after 24-week intervention ( T3 ) , and at 48-week follow-up visit ( T4 ) . Results Improvements in QoL were evident in both groups but the test group fared better than the control group at the 12th week ( P < 0.01 ) and particularly in emotional well-being ( P < 0.01 ) and breast cancer-specific well-being ( P < 0.001 ) . The test group showed an improvement in anxiety levels ( P < 0.01 ) , whereas the control group showed improvements in depression ( P < 0.05 ) but there was no significant difference between groups ( P > 0.05 ) . Both groups showed improvements in immunological function and the test group fared better than the control in TNF-α levels ( P < 0.05 ) . The results in subjects who practice d more than 4 times and 6 h per week were similar to that of all subjects ; however , the improvement in anxiety in the GLQG group was more obvious . There are positive correlations between QoL and anxiety and depression . Conclusions Both GLQG and physical stretching are beneficial during recovery following breast cancer . GLQC was more effective in terms of Qol improvements than physical stretching . Both programs brought improvements in anxiety or depression but had were comparable . GLQC group had a greater effect on immunological function than physical exercise BACKGROUND Bojungikki-tang ( Bu-Zhong-Yi-Qi-Tang in Chinese or Hochu-ekki-to in Japanese ) is a widely used herbal prescription in traditional medicine in China , Japan , and Korea . The aim of this study was to investigate the effectiveness of Bojungikki-tang for cancer-related fatigue . METHODS A total of 40 patients with cancer-related fatigue were r and omized into an experimental or a waiting list control group . Patients in the experimental group were treated with Bojungikki-tang ( TJ-41 ) and patients in the waiting list group remained without any intervention for 2 weeks . RESULTS The experimental group showed statistically significant improvements in fatigue level assessed by the Visual Analogue Scale of Global Fatigue ( VAS-F ) measuring the severity of fatigue ( experimental vs control : -1.1 ± 2.1 vs 0.1 ± 0.9 , P < .05 ) and results of Functional Assessment of Cancer Therapy-General ( FACT-G ) , Functional Assessment of Cancer Therapy-Fatigue ( FACT-F ) , and Trial Outcome Index-Fatigue ( TOI-F ) also showed significant improvements ( FACT-G , 3.7 ± 9.9 vs -2.4 ± 9.5 , P < .05 ; FACT-F , F , 8.0 ± 13.6 vs -2.2 ± 14.1 , P < .05 ; TOI-F , 6.5 ± 9.2 vs -0.5 ± 10.9 , P < .05 ) . CONCLUSIONS The results of this study indicate that Bojungikki-tang may have beneficial effects on cancer-related fatigue and quality of lives in cancer patients . More rigorous trials are needed to confirm the efficacy of Bojungikki-tang Importance Fatigue is a common and debilitating late-term effect of breast cancer that is associated with poor sleep and decreased quality of life , yet therapies remain limited . Acupressure has reduced fatigue in previous small studies , but rigorous clinical trials are needed . Objectives To investigate if 6 weeks of 2 types of self-administered acupressure improved fatigue , sleep , and quality of life vs usual care in breast cancer survivors and to determine if changes were sustained during a 4-week washout period . Design , Setting , and Participants Phase 3 r and omized , single-blind , clinical trial conducted from March 1 , 2011 , through October 31 , 2014 . Women were recruited from the Michigan Tumor Registry . Interventions R and omization ( 1:1:1 ) to 6 weeks of daily self-administered relaxing acupressure , stimulating acupressure , or usual care . Main Outcomes and Measures The primary outcome was change in the Brief Fatigue Inventory score from baseline to weeks 6 and 10 . Secondary analyses were sleep ( Pittsburgh Sleep Quality Index ) and quality of life ( Long-Term Quality of Life Instrument ) . Results A total of 424 survivors of stages 0 to III breast cancer who had completed cancer treatments at least 12 months previously were screened , and 288 were r and omized , with 270 receiving relaxing acupressure ( n = 94 ) , stimulating acupressure ( n = 90 ) , or usual care ( n = 86 ) . One woman withdrew owing to bruising at the acupoints . At week 6 , the percentages of participants who achieved normal fatigue levels ( Brief Fatigue Inventory score < 4 ) were 66.2 % ( 49 of 74 ) in relaxing acupressure , 60.9 % ( 42 of 70 ) in stimulating acupressure , and 31.3 % ( 26 of 84 ) in usual care . At week 10 , a total of 56.3 % ( 40 of 71 ) in relaxing acupressure , 60.9 % ( 42 of 69 ) in stimulating acupressure , and 30.1 % ( 25 of 83 ) in usual care continued to have normal fatigue . At neither time point were the 2 acupressure groups significantly different . Relaxing acupressure , but not stimulating acupressure , showed significant improvements in sleep quality compared with usual care at week 6 , but not at week 10 . Only relaxing acupressure significantly improved quality of life vs usual care at weeks 6 and 10 . Conclusions and Relevance Both acupressure arms significantly reduced persistent fatigue compared with usual care , but only relaxing acupressure had significant effects on sleep quality and quality of life . Relaxing acupressure offers a possible low-cost option for managing symptoms . Trial Registration clinical trials.gov Identifier : NCT01281904 Background : A breast cancer diagnosis can entail numerous physical and psychosocial challenges . Yoga practice ( YP ) may contribute to improved well-being for these patients . Primary Study Objective : Investigate feasibility and impact of YP on quality of life ( QoL ) , mood , fatigue , and perceived stress immediately after breast cancer diagnosis . Methods : Thirty women were r and omly assigned to a yoga group ( YG ) or control group ( CG ) immediately after cancer diagnosis . Setting : Pilot study conducted at an academic medical center breast clinic . Participant(s ) : Females ( N = 30 ) who received a biopsy-proven breast cancer diagnosis without metastatic disease . Intervention ( YG ) : One individual YP session at baseline , then 2 individual and 8 weekly group sessions followed by weekly gentle yoga at home ( DVD ) . Question naires and saliva sample s ( ie , cortisol ) completed at baseline and 12 weeks postdiagnosis . Results : Both groups reported significant improvements in QoL postintervention but with no significant difference between groups . Emotional well-being , mood-related tension-anxiety , depression-dejection , and confusion-bewilderment scores improved for both groups , and cortisol and cortisone levels decreased . Lumpectomies were prevalent with YG ( 67 % ) and CG ( 47 % ) . YP was rated as “ very effective , ” providing relaxation ( 85 % ) , stress relief ( 69 % ) , and reduced muscle tension/general feeling of wellness ( each 62 % ) . Conclusion : Feasibility of YP immediately after breast cancer diagnosis was good . Improvement in emotional well-being , anxiety , depression , and levels of confusion was found in both groups . To our knowledge , this is the first study examining the impact of YP immediately after breast cancer diagnosis . Further research in this area is warranted Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract The aim of this study was to evaluate the effectiveness of an additional , individualized , multi-component complementary medicine treatment offered to breast cancer patients at the Merano Hospital ( South Tyrol ) on health-related quality of life compared to patients receiving usual care only . A r and omized pragmatic trial with two parallel arms was performed . Women with confirmed diagnoses of breast cancer were r and omized ( stratified by usual care treatment ) to receive individualized complementary medicine ( CM group ) or usual care alone ( usual care group ) . Both groups were allowed to use conventional treatment for breast cancer . Primary endpoint was the breast cancer-related quality of life FACT-B score at 6 months . For statistical analysis , we used analysis of covariance ( with factors treatment , stratum , and baseline FACT-B score ) and imputed missing FACT-B scores at 6 months with regression-based multiple imputation . A total of 275 patients were r and omized between April 2011 and March 2012 to the CM group ( n = 136 , 56.3 ± 10.9 years of age ) or the usual care group ( n = 139 , 56.0 ± 11.0 ) . After 6 months from r and omization , adjusted means for health-related quality of life were higher in the CM group ( FACT-B score 107.9 ; 95 % CI 104.1–111.7 ) compared to the usual care group ( 102.2 ; 98.5–105.9 ) with an adjusted FACT-B score difference between groups of 5.7 ( 2.6–8.7 , p < 0.001 ) . Thus , an additional individualized and complex complementary medicine intervention improved quality of life of breast cancer patients compared to usual care alone . Further studies evaluating specific effects of treatment components should follow to optimize the treatment of breast cancer patients Objective To determine the feasibility and acceptability of acupuncture in managing fatigue and well-being in breast cancer survivors . Methods A r and omised controlled trial compared acupuncture was with sham acupuncture and wait list controls was performed in Sydney , Australia . A total of 30 women with fatigue following breast cancer treatment participated in the trial . Women received six sessions of acupuncture over 8 weeks . Outcomes related to an assessment of interest to participate in the trial and identification of appropriate recruitment strategies , appropriateness of eligibility criteria and compliance with treatment attendance . Clinical outcomes assessed fatigue and well-being . In-depth interviews were undertaken with seven women , who described their experience of acupuncture . Results Our study demonstrated feasibility with appropriate trial entry criteria , good acceptability and treatment compliance with the study interventions , and with the completion of outcome forms . There was a significant reduction in fatigue for women receiving acupuncture compared with control after 2 weeks mean difference ( MD ) 5.3 , 95 % CI 4.5 to 6.2 , p=0.05 , and a significant improvement in well-being at 6 weeks for acupuncture compared with the sham and wait list control , MD 2.7 , 95 % CI 2.1 to 3.2 , p=0.006 . Women described their experience of acupuncture positively , and interview data may also offer explanations for the improved outcomes of well-being , with women reporting an improvement in sleep , mood and relaxation . Conclusions Fatigue is a common symptom experienced by people recovering from treatment , and an appropriately powered trial to evaluate the effect of acupuncture is needed . Clinical Trial Registration Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au ACTRN12610000720011 OBJECTIVES Despite increased use of integrative medicine in cancer therapy , little data exist on its efficacy . This prospect i ve , r and omized , pilot trial sought to evaluate the feasibility of combined modality integrative medicine ( CM-IM ) in women with ovarian cancer ( OvCA ) and evaluate its effects on quality of life ( QoL ) , chemotherapy toxicity and immunologic profiles . METHODS Women with newly diagnosed OvCA requiring chemotherapy were offered enrollment . Those r and omized to the experimental arm received hypnosis , therapeutic massage and healing touch with each cycle of chemotherapy . The control arm received chemotherapy without CM-IM . All patients completed QoL question naires prior to cycles 1 , 3 and 6 , and 6-months after chemotherapy . Immunologic profiles were measured . Statistical analysis was based on intent-to-treat . Student 's t-test and Fischer 's exact-test were used to determine differences . RESULTS Forty-three women enrolled . All women r and omized to CM-IM were successfully treated . There were no statistical differences between the groups in age , stage , grade , histologic cell type , CA125 levels , or surgical cytoreductive status . There was no difference in overall QoL measurements . Re-hospitalization rates , treatment delays , anti-emetic use , and infection rates were similar . Immunologic profiles revealed no difference between arms for WBC or salivary IgA levels . Women receiving CM-IM had consistently higher levels of CD4 , CD8 and NK cells , although this did not reach statistical significance . CONCLUSIONS Prospect i ve clinical evaluation of integrative medicine for women with gynecologic malignancy is feasible . This first , pilot study of CM-IM in gynecologic oncology demonstrated no improvement in QoL or chemotherapy toxicity . Integrative medicine-associated improvements in immunologic profiles warrant further investigation Background Cancer-related fatigue ( CRF ) is a prominent clinical problem . There are calls for multi-modal interventions . Methods We assessed the feasibility of delivering patient education integrated with acupuncture for relief of CRF in a pilot r and omized controlled trial ( RCT ) with breast cancer survivors using usual care as control . Social cognitive and integrative medicine theories guided integration of patient education with acupuncture into a coherent treatment protocol . The intervention consisted of two parts . First , patients were taught to improve self-care by optimizing exercise routines , improving nutrition , implementing some additional evidence -based cognitive behavioral techniques such as stress management in four weekly 50-minute sessions . Second , patients received eight weekly 50-minute acupuncture sessions . The pre-specified primary outcome , CRF , was assessed with the Brief Fatigue Inventory ( BFI ) . Secondary outcomes included three dimensions of cognitive impairment assessed with the FACT-COGv2 . Results Due to difficulties in recruitment , we tried several methods that led to the development of a tailored recruitment strategy : we enlisted oncologists into the core research team and recruited patients completing treatment from oncology waiting rooms . Compared to usual care control , the intervention was associated with a 2.38-point decline in fatigue as measured by the BFI ( 90 % Confidence Interval from 0.586 to 5.014 ; p < 0.10 ) . Outcomes associated with cognitive dysfunction were not statistically significant . Conclusions Patient education integrated with acupuncture had a very promising effect that warrants conducting a larger RCT to confirm findings . An effective recruitment strategy will be essential for the successful execution of a larger-scale trial . Trial registration Introduction There is an increasing number of new oncology drugs being studied , approved and put into clinical practice based on improvement in progression-free survival , when no overall survival benefits exist . In oncology , the association between progression-free survival and health-related quality of life is currently unknown , despite its importance for patients with cancer , and the unverified assumption that longer progression-free survival indicates improved health-related quality of life . Thus far , only 1 study has investigated this association , providing insufficient evidence and inconclusive results . The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology . Methods and analysis Using the OVID platform in MEDLINE , Embase and Cochrane data bases , we will conduct a systematic review of r and omised controlled human trials addressing oncology issues published starting in 2000 . A team of review ers will , in pairs , independently screen and abstract data using st and ardised , pilot-tested forms . We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life , along with total related error estimates , and a 95 % CI around incremental area . To describe the progression-free survival to health-related quality of life association , we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival . To estimate the association , we will use a weighted simple regression approach , comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR , in the absence of overall survival benefit . Discussion Identifying direction and magnitude of association between progression-free survival and health-related quality of life is critically important in interpreting results of oncology trials . Systematic evidence produced from our study will contribute to improvement of patient care and practice of evidence -based medicine in oncology BACKGROUND Qigong is highly favoured among Asian breast cancer survivors for enhancing health . This study examined the hypothesis that quality of life ( QoL ) in the Qigong group is better than the placebo ( aerobic ) or usual care group . MATERIAL S AND METHODS A total of 197 participants were r and omly assigned to either the 8-week Kuala Lumpur Qigong Trial or control groups in 2010 - 2011 . Measurement taken at baseline and post- intervention included QoL , distress and fatigue . Analysis of covariance ( ANCOVA ) and Kruskal Wallis were used to examine for differences between groups in the measurements . RESULTS There were 95 consenting participants in this 8week trial . The adherence rates were 63 % for Qigong and 65 % for the placebo group . The Qigong group showed significant marginal improvement in Quality of life scores compared to placebo ( mean difference=7.3 unit ; p=0.036 ) , compared to usual care ( mean difference=6.7 unit ; p=0.048 ) on Functional Assessment Cancer Therapy-Breast measure . There were no significant changes between the placebo and usual care groups in fatigue or distress at post intervention ( 8-week ) . CONCLUSIONS Cancer survivors who participated in the Qigong intervention showed slightly better QOL . Follow up studies are greatly needed to evaluate which subgroups may best benefit from Qigong . With a steep rise of cancer survivors , there is an urgent need to explore and engage more cultural means of physical activity to fight side effects of treatment and for cancer control in developing countries Purpose To obtain estimates of time to recruit the study sample , retention , facility-based class attendance and home practice for a study of yoga in breast cancer survivors , and its efficacy on fatigue , quality of life ( QOL ) , and weight change . Methods Sixty-three post-treatment stages 0–III borderline overweight and obese ( body mass index ≥24 kg/m2 ) breast cancer survivors were r and omly assigned to a 6-month , facility- and home-based viniyoga intervention ( n = 32 ) or a waitlist control group ( n = 31 ) . The yoga goal was five practice s per week . Primary outcome measures were changes in QOL , fatigue , and weight from baseline to 6 months . Secondary outcomes included changes in waist and hip circumference . Results It took 12 months to complete recruitment . Participants attended a mean of 19.6 classes and practice d at home a mean of 55.8 times during the 6-month period . At follow-up , 90 % of participants completed question naires and 87 % completed anthropometric measurements . QOL and fatigue improved to a greater extent among women in the yoga group relative to women in the control group , although no differences were statistically significant . Waist circumference decreased 3.1 cm ( 95 % CI , −5.7 and −0.4 ) more among women in the yoga compared with the control group , with no difference in weight change . Conclusions This study provides important information regarding recruitment , retention , and practice levels achieved during a 6-month , intensive yoga intervention in overweight and obese breast cancer survivors . Yoga may help decrease waist circumference and improve quality of life ; future studies are needed to confirm these results Objective To observe the efficacy of Chinese medicine comprehensive therapeutic project in treating the middle/late stage primary hepatic carcinoma ( PHC ) . Methods With prospect i ve r and omized controlled design , 97 patients with PHC were assigned to the test group ( 49 cases ) treated with Chinese medicine comprehensive therapy using Oleum fructus bruceas intervention combining oral intake of Ganji Decoction ( 肝积方 ) and external application of Ailitong ( 癌理通 ) , and the control group ( 48 cases ) treated with chemotherapeutic agents combining iodized oil chemo-embolization and analgesics . The immediate and long-term efficacy , adverse reaction , pain-relieving initial time ( PRIT ) and pain-relieving sustained time ( PRST ) of the treatment , as well as the change in relieving patients ’ quality of life ( QOL ) were observed . Results The difference between the two groups in illness control rate was statistically insignificant ( P>0.05 ) , but the adverse reaction occurence rate in the test group was lesser than that in the control group ( P<0.05 ) . PRIT was insignificantly different in the two groups ( P>0.05 ) , but the PRST was significantly superior in the test group than that in the control group ( 10.37±2.18 h vs 7.78±1.95 h , P<0.01 ) . After treatment , the increased Karnofsky scores in the test group indicated that the patients ’ somatic activity , symptoms and QOL were improved significantly , which were significantly superior to those in the control group ( P<0.05 ) . The survival rate in the two groups was similar at the 3rd month after treatment , but the test group did show superiority in terms of half- and 1-year survival rate ( 65.9 % vs 42.5 % and 38.6 % vs 18.1 % , respectively , P<0.05 ) . The median survival time in the test group was 8.9 months and that in the control group was 5.3 months . Conclusion Chinese medicine comprehensive therapy is an effective treatment for the middle/late stage patients of PHC , and it could extend the PRST , improve the patients ’ QOL and long-term survival with less adverse reaction PURPOSE / OBJECTIVES To determine kefir 's effect on the prevention of gastrointestinal complaints and quality of life ( QOL ) in patients being treated for colorectal cancer . DESIGN R and omized , controlled , prospect i ve , interventional study . SETTING Istanbul University Oncology Institute in Turkey . SAMPLE 40 patients , 20 of whom were r and omized to the experimental ( kefir ) arm and 20 who were r and omized to the control arm . METHODS Informed consent to participate in the study was obtained . Before treatment began , demographics , illness-related characteristics , complaints , and QOL of participants were evaluated . During treatment , side effects were evaluated one week after every cycle of therapy . QOL was evaluated after the third and sixth cycles of treatment . MAIN RESEARCH VARIABLES The effect of kefir on the prevention of gastrointestinal complaints and QOL in patients being treated for colorectal cancer . FINDINGS Following chemotherapy , the experimental ( kefir ) group had more treatment-related gastrointestinal complaints but a decrease in sleep disturbance . No difference was found between the two groups for QOL . CONCLUSIONS Kefir does not prevent or decrease gastrointestinal complaints in patients undergoing chemotherapy for colorectal cancer . Kefir did decrease sleep disturbances in the experimental group . IMPLICATION S FOR NURSING Many patients use complementary and alternative medicine during cancer therapy . This study may provide information about the effectiveness of kefir in patients with cancer The aim of this prospect i ve , r and omized , controlled trial was to investigate the impact of yoga on newly diagnosed patients with early breast cancer in the immediate postoperative phase . 93 women newly diagnosed with early breast cancer were r and omized into an intervention group ( IG ) and a control group ( waiting group , WG ) . The IG started yoga immediately after the operation . The WG started yoga 5 weeks after surgery . Both groups attended yoga classes twice weekly for 5 weeks . Quality of life ( QoL ) was evaluated using the EORTC QLQ-C30 and EORTC QLQ-BR23 question naires before the intervention , immediately after the operation and after 3 months . After 3 months the patients were asked whether yoga improved their physical activity and whether they wished to continue with yoga . The overall QoL ( p = 0.002 ) and the functional status ( p = 0.005 ) increased significantly in the IG , while physical symptoms decreased over time in both groups . 86 % of patients in the IG and only 59 % of patients in the WG ( p = 0.04 ) confirmed a positive change in their physical activity through yoga . More women in the IG intended to continue with yoga ( p = 0.03 ) . Early initiation of yoga as a supportive treatment in cancer had a positive impact on QoL. Teaching yoga allowed patients to practice yoga by themselves , enhanced the patients ' QoL and was found to improve physical activity Purpose Cancer patients often experience diminished cognitive function ( CF ) and quality of life ( QOL ) due to the side effects of treatment and the disease symptoms . This study evaluates the effects of medical Qigong ( MQ ; combination of gentle exercise and meditation ) on CF , QOL , and inflammation in cancer patients . Methods Eighty-one cancer patients recruited between October 2007 and May 2008 were r and omly assigned to two groups : a control group ( n = 44 ) who received the usual health care and an intervention group ( n = 37 ) who participated in a 10-week MQ program . Self-reported CF was measured by the European Organization for Research and Treatment of Cancer ( EORTC-CF ) and the Functional Assessment of Cancer Therapy — Cognitive ( FACT-Cog ) . The Functional Assessment of Cancer Therapy — General ( FACT-G ) was used to measure QOL . C-reactive protein ( CRP ) was assessed as a biomarker of inflammation . Results The MQ group self-reported significantly improved CF ( mean difference ( MD ) = 7.78 , t51 = −2.532 , p = 0.014 ) in the EORTC-CF and all the FACT-Cog subscales [ perceived cognitive impairment ( MD = 4.70 , t43 = −2.254 , p = 0.029 ) , impact of perceived cognitive impairment on QOL ( MD = 1.64 , t45 = −2.377 , p = 0.024 ) , and perceived cognitive abilities ( MD = 3.61 , t45 = −2.229 , p = 0.031 ) ] compared to controls . The MQ group also reported significantly improved QOL ( MD = 12.66 , t45 = −5.715 , p < 0.001 ) and had reduced CRP levels ( MD = −0.72 , t45 = 2.092 , p = 0.042 ) compared to controls . Conclusions Results suggest that MQ benefits cancer patients ’ self-reported CF , QOL , and inflammation . A larger r and omized controlled trial including an objective assessment of CF is planned Objectives : Evidence for complementary therapies as important strategies to relieve cancer treatment-associated symptoms is increasing . Mostly , these complementary therapies start at the end of adjuvant treatments , result ing in a long delay until the well-being of patients is addressed . Further , long distances between the rehabilitation center and the patients ' residence hinder patients ' compliance . Methods : The multimodal outpatient LOTUS Care Cure Project ( LCCP ) was tested in a r and omized controlled trial including patients of various cancer entities and stages while on adjuvant chemotherapy and /or radiotherapy or outpatient aftercare . The intervention group received the LCCP additionally to the conventional treatment ( LCCP group , n = 50 ) . The control group ( CG ) was split into 2 groups , with ( CG1 , n = 33 ) and without ( CG2 , n = 17 ) weekly talks . The primary endpoint was quality of life ( QoL ) after 3 months . Results : In the LCCP group , QoL significantly improved after 3 months compared to CG2 ( p = 0.022 ) but not compared to CG1 . Other parameters showing a significant improvement were cognitive ( p < 0.05 , vs. CG1 and CG2 ) and social function ( p < 0.05 , vs. CG2 ) . Conclusions : This pilot study describes a multimodal outpatient complementary therapy program conducted in parallel with conventional therapies and its potential to significantly improve QoL and reduce treatment-associated side effects . To substantiate these data , multicenter trials are needed Purpose Many cancer patients experience persistent fatigue after the completion of chemotherapy . A previous single-arm study provided evidence for an effect of acupuncture in this population . We conducted a r and omized controlled trial to determine whether acupuncture reduces post-chemotherapy chronic fatigue more effectively than sham acupuncture . Methods Cancer patients reporting significant fatigue persisting for at least 2 months following the completion of chemotherapy were r and omized to receive once weekly true or sham acupuncture for 6 weeks . Fatigue was evaluated before and after treatment using the Brief Fatigue Inventory ( BFI , the primary endpoint ) . Secondary endpoints included the Hospital Anxiety and Depression Scale ( HADS ) and Functional Assessment of Cancer Treatment-General ( FACT-G ) scores . Results One hundred one patients were r and omized with 74 ( 34 true acupuncture ; 40 sham control ) evaluated for the primary endpoint . BFI scores fell by about one point between baseline and follow-up in both groups with no statistically significant difference between groups . HADS and FACT-G scores also improved in both groups , but there was no significant difference between groups . Patients in the sham acupuncture group crossed over to receive true acupuncture in week 7 . No long-term reduction of fatigue scores was observed at the 6-month evaluation . Conclusions True acupuncture as provided in this study did not reduce post-chemotherapy chronic fatigue more than did sham acupuncture . The study is limited by the number of patients lost to follow-up . We also can not exclude the possibility that a more intensive treatment regimen may be more effective BACKGROUND Coenzyme Q10 ( CoQ10 ) is a common antioxidant supplement with known cardioprotective effects and potential anticancer benefits . OBJECTIVES We performed a r and omized , double-blind , placebo-controlled study of oral CoQ10 in female breast cancer patients with the primary objective of determining CoQ10 's effects on self-reported fatigue , depression , and quality of life ( QOL ) . Methods Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were r and omized to oral supplements of 300 mg CoQ10 or placebo , each combined with 300 IU vitamin E , divided into 3 daily doses . Treatment was continued for 24 weeks . Blood tests , QOL measures , and levels of plasma CoQ10 and vitamin E were obtained at baseline and at 8 , 16 , and 24 weeks . Mixed-effects models were used to assess treatment differences in outcomes over time . RESULTS Between September 2004 and March 2009 , 236 women were enrolled . Treatment arms were well balanced with respect to age ( range , 28 - 85 years ) , pathologic stage ( stage 0 , 91 % ; stage 1 , 8 % ; stage II , 1 % ) , ethnicity ( white , 87 % ; black , 11 % ; Hispanic , 2 % ) , and planned therapy . Baseline CoQ10 levels in the CoQ10 and placebo arms were 0.70 and 0.73 microg/mL , respectively ; the 24-week CoQ10 levels were 1.83 and 0.79 microg/mL , respectively . There were no significant differences between the CoQ10 and placebo arms at 24 weeks for scores on the Profile of Mood States-Fatigue question naire ( least squares means , 7.08 vs 8.24 , P = .257 ) , the Functional Assessment of Chronic Illness Therapy-Fatigue tool ( 37.6 vs 37.6 , P = .965 ) , the Functional Assessment of Cancer Therapy-Breast Cancer instrument ( 111.9 vs 110.4 , P = .577 ) , or the Center for Epidemiologic Studies -Depression scale ( 11.6 vs 12.3 , P = .632 ) . CONCLUSIONS Supplementation with conventional doses of CoQ10 led to sustained increases in plasma CoQ10 levels but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment Radiotherapy may lead to side effects that undermine patients ' quality of life ( QOL ) . Although mind‐body practice s like qigong appear to improve QOL in cancer survivors , little is known about their benefits for patients who are receiving radiotherapy . Thus , in the current r and omized controlled trial , the authors examined the efficacy of a qigong intervention on QOL in women with breast cancer during and after treatment This study examined the effects of yoga on quality of life ( QOL ) and psychosocial outcomes in women with breast cancer undergoing radiotherapy . Sixty-one women were r and omly assigned to either a yoga or a wait-list group . Yoga classes were taught biweekly during the 6 weeks of radiotherapy . Participants completed measures of QOL , fatigue , benefit finding ( finding meaning in the cancer experience ) , intrusive thoughts , sleep disturbances , depressive symptoms , and anxiety before radiotherapy and then again 1 week , 1 month , and 3 months after the end of radiotherapy . General linear model analyses revealed that compared to the control group , the yoga group reported significantly better general health perception ( p = .005 ) and physical functioning scores ( p = .04 ) 1 week postradiotherapy ; higher levels of intrusive thoughts 1 month postradiotherapy ( p = .01 ) ; and greater benefit finding 3 months postradiotherapy ( p = .01 ) . There were no other group differences in other QOL subscales for fatigue , depression , or sleep scores . Exploratory analyses indicated that intrusive thoughts 1 month after radiotherapy were significantly positively correlated with benefit finding 3 months after radiotherapy ( r = .36 , p = .011 ) . Our results indicated that the yoga program was associated with statistically and clinical ly significant improvements in aspects of QOL PURPOSE To conduct a pragmatic r and omised controlled trial ( RCT ) to evaluate the effects of reflexology on quality of life ( QofL ) in women with early breast cancer . PATIENTS AND METHODS One hundred and eighty-three women were r and omised 6 weeks post-breast surgery to self-initiated support ( SIS ) ( comparator intervention ) , SIS plus reflexology , or SIS plus scalp massage ( control for physical and social contact ) . Reflexology and massage comprised eight sessions at weekly intervals . The primary end-point was 18 weeks post surgery ; the primary outcome measure was the Trial Outcome Index ( TOI ) of the Functional Assessment of Cancer Therapy ( FACT-B ) - breast cancer version . The secondary end-point was 24 weeks post surgery . Secondary outcome measures were the Hospital Anxiety and Depression Scale ( HADS ) and the Mood Rating Scale ( MRS ) . RESULTS At primary end-point , massage , but not reflexology , was significantly better than SIS on the TOI . Reflexology and massage were both better than SIS for MRS relaxation . Massage was better than reflexology and SIS for MRS easygoingness . At secondary end-point , reflexology , but not massage , was better than SIS on the TOI and MRS relaxation . There were no significant differences between reflexology or massage . There were no significant between group differences in HADS anxiety and depression . Self-reported use of out of study complementary therapies indicated that this was unlikely to have a significant effect on findings . CONCLUSIONS When compared to SIS , reflexology and massage have statistically significant , and , for reflexology , clinical ly worthwhile , effects on QofL following surgery for early breast carcinoma OBJECTIVE The purpose of the study was to assess the efficacy and safety of using Chinese herbal medicine ( CHM ) as maintenance therapy considering the survival of advanced non-small-cell lung cancer ( NSCLC ) patients after first-line conventional platinum-based chemotherapy . DESIGN An open-label , r and omized , controlled trial . SETTING Four hospitals in China . INTERVENTIONS AND MAIN OUTCOME MEASURES A total of 106 patients were eligible and r and omly divided into two groups from four hospitals in China . Both groups received the best supporting care ( BSC ) . Additionally , patients in the trial group were given CHM every day until the disease became aggravated or the patients resigned . The study took both progression-free survival ( PFS ) and quality of life ( QOL ) as the primary outcomes to comprehensively evaluate the effect of the treatment . QOL was measured by the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) 4.0 question naire . Side effects and safety were evaluated at the same time . RESULTS Of the 106 patients , 99 completed the study . After treatment and follow-up for PFS , there were no significant differences in the median PFS time and the 6-month PFS probability between the two groups . However , the 3-month PFS probability in the trial group was significantly higher than that in the control group ( FAS , PPS : P<0.01 ) . For QOL , there were significant differences between the two groups in the following : physical well-being , emotional well-being , functional well-being , lung cancer symptom domain and total score of the FACT-L4.0 ( FAS , PPS : P<0.05 ) . There was no significant difference in the social well-being domain . No serious adverse side effects to the treatment were observed . CONCLUSIONS CHM is well tolerated and may improve the QOL of advanced NSCLC patients . CHM is worth study ing in future investigations PURPOSE This study examines the impact of yoga , including physical poses , breathing , and meditation exercises , on quality of life ( QOL ) , fatigue , distressed mood , and spiritual well-being among a multiethnic sample of breast cancer patients . PATIENTS AND METHODS One hundred twenty-eight patients ( 42 % African American , 31 % Hispanic ) recruited from an urban cancer center were r and omly assigned ( 2:1 ratio ) to a 12-week yoga intervention ( n = 84 ) or a 12-week waitlist control group ( n = 44 ) . Changes in QOL ( eg , Functional Assessment of Cancer Therapy ) from before r and om assignment ( T1 ) to the 3-month follow-up ( T3 ) were examined ; predictors of adherence were also assessed . Nearly half of all patients were receiving medical treatment . RESULTS Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates ( P < .0001 ) . Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL ( P < .008 ) , emotional well-being ( P < .015 ) , social well-being ( P < .004 ) , spiritual well-being ( P < .009 ) , and distressed mood ( P < .031 ) . Sixty-nine percent of intervention participants attended classes ( mean number of classes attended by active class participants = 7.00 + /- 3.80 ) , with lower adherence associated with increased fatigue ( P < .001 ) , radiotherapy ( P < .0001 ) , younger age ( P < .008 ) , and no antiestrogen therapy ( P < .02 ) . CONCLUSION Despite limited adherence , this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors . Among patients not receiving chemotherapy , yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL Background . Chronic fatigue is one of the most restricting symptoms following primary breast cancer treatment , but clinical studies on symptom management are rare . The objective was to evaluate the impact of a multimodal mind – body program ( MMMT ) , including moderate physical activity as compared with a walking intervention alone , on chronic fatigue symptoms of women with stage I to IIIA breast cancer . Patients and Methods . Sixty-four women ( mean age = 56.7 years ) suffering from chronic fatigue after active tumor treatment were r and omly assigned to either an experimental or a control ( n = 32 each ) intervention ( 10 weeks ) . Fatigue , quality of life ( QoL ) , functional well-being , anxiety , and depression were measured with st and ard question naires at baseline , after 10 weeks , and after 3 months . Results . Compared with baseline , both groups had reduced fatigue scores after treatment without any significant difference between groups ( posttreatment , Δ = −0.3 , confidence interval = −1.6 to 1.0 , P = .678 ; follow-up , Δ = −0.4 , confidence interval = −1.8 to 0.9 , P = .510 ) . All patients also improved regarding QoL and general functional well-being . Conclusion . Since both interventions reduced fatigue symptoms and enhanced QoL to a similar extent , we observed no verifiable add-on effect of the MMMT regarding fatigue symptoms . Considering the higher costs with additional expenditure related to MMMT , home-based walking intervention is recommended Carnitine deficiency is prevalent in population s with chronic illness , including cancer . In a recent open-label study , L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients . To further evaluate this finding , adult patients with advanced cancer , carnitine deficiency ( free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females , or acyl/free carnitine ratio of more than 0.4 ) , moderate to severe fatigue , and a Karnofsky Performance Status ( KPS ) score of 50 or more , were r and omly assigned to receive either L-carnitine ( 0.5 g/day for two days , followed by 1g/day for two days , and then 2g/day for 10 days ) or placebo . This double-blind phase was followed by an open-label phase , during which all patients received L-carnitine supplementation for two weeks . Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) , the Linear Analog Scale Assessment s ( LASA ) , the Mini-Mental State Exam ( MMSE ) , and the KPS . Twenty-nine patients ( 12 placebo , 17 L-carnitine ) were included in the intent-to-treat ( ITT ) analysis . From baseline to the end of the double-blind phase , serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 ( P=0.004 ) , and from 22.9+/-19.4 to 45.3+/-17.2 ( P=0.004 ) , respectively , in the L-carnitine-treated group , and from 28.2+/-10.2 to 36.2+/-8.7 ( P = ns ) , and from 22.6+/-7.9 to 28.7+/-8.6 ( P = ns ) in the placebo group , respectively . The planned ITT analysis revealed no significant improvement in any of the study 's endpoints , and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated . However , an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale ( P<0.03 ) , and significantly improved FACT-An functional well-being subscale ( P<0.03 ) , and KPS ( P<0.003 ) , in the group that started with L-carnitine during the double-blind phase . These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients . However , L-carnitine supplementation does increase L-carnitine serum levels , and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a sub population of cancer patients BACKGROUND & AIM Nutritional status frequently deteriorates during chemotherapy in cancer . This is associated with a poor outcome . Since creatine supplementation has shown promising results in various diseases , we investigated the effects of creatine on nutritional status in patients with colorectal cancer undergoing chemotherapy . METHODS Thirty patients with colorectal cancer undergoing chemotherapy were r and omised to receive either creatine ( n=16 ) or placebo ( n=15 ) for 8 weeks . Body composition was determined with bioelectrical impedance analysis ; muscle function by h and grip , hip flexion and knee extension strength and quality of life ( QoL ) was assessed by the QLQ30 question naire . RESULTS Neither muscle function , body cell mass ( BCM ) nor QoL improved , but phase angle , a marker of BCM and cell integrity , increased significantly in the intervention patients ( 5.3+/-0.3 degrees to 5.4+/-0.2 degrees , P=0.030 ) . Evaluating patients with different chemotherapy regimens , however , only intervention patients undergoing less aggressive chemotherapy were shown to benefit , increasing phase angle ( 5.11+/-0.22 degrees to 5.51+/-0.30 degrees , P=0.043 ) as well as BCM ( 27.22+/-2.85 to 29.60+/-3.54 kg , P=0.043 ) . CONCLUSION Creatine failed to improve muscle mass or function and QoL in colorectal cancer patients but improved bioimpedance parameters that are predictive of poor outcome . Creatine might therefore be useful in patients with milder chemotherapy in order to maintain or increase BCM whereas patients undergoing aggressive chemotherapy however are not likely to benefit Background Non-communicable diseases ( NCDs , e.g. cardiovascular disease ) are responsible for high rates of morbidity and the majority of premature deaths worldwide . It is necessary to develop preventative interventions that can reduce the associated risk factors of NCDs . Research ers have found that the biomarker adrenomedullin ( ADM ) becomes elevated years before the onset of NCDs and might play an important role in their development . ADM has also been linked to psychological problems such as stress , anxiety , and depression , which are known risk factors of NCDs . In this r and omized controlled trial , we examined whether participating in a five-week yoga intervention reduces ADM and increases psychological health in middle-aged adults who self-report as moderately to highly stressed , but who otherwise exhibit no physical complaints . Methods One hundred and five adults ( 78 % women ; mean age = 53.5 , SD = 6.7 ) were r and omly assigned to ( 1 ) a five-week Yin yoga intervention , ( 2 ) a five-week intervention combining Yin yoga with psychoeducation and mindfulness practice ( called the YOMI program ) , or ( 3 ) a control group who did not practice yoga or mindfulness for five weeks . Results Compared to the control group , we observed significantly greater pre-post reductions in plasma ADM levels ( p < .001 ) , anxiety ( p ≤ .002 ) , and sleep problems ( p ≤ .003 ) in both intervention groups . Furthermore , the YOMI group exclusively showed significantly greater pre-post reductions in stress ( p = .012 ) and depression ( p = .021 ) compared to the control group . Significant correlations ( p < .05 ) were found between pre-post reductions in ADM and anxiety symptoms ( p = .02 ) and depression ( p = .04 ) in the entire sample . Conclusion The five-week Yin yoga-based interventions appeared to reduce both the physiological and psychological risk factors known to be associated with NCDs . The study suggests that incorporating Yin yoga could be an easy and low-cost method of limiting the negative health effects associated with high stress . Trial registration Clinical Trials.gov BACKGROUND Traditional Chinese medicine ( TCM ) is considered an important complementary therapy with beneficial effects for cancer patients . Elderly patients with non-small-cell lung cancer ( NSCLC ) are a complex patient group with increasing co-morbidity and shrinking physiological reserve , and may derive substantial benefit from the supportive aspects of TCM . Research ers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer . This project was design ed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC . METHODS AND DESIGN This is a double-blind controlled , multi-center , and prospect i ve study with r and omly selected participants from elderly NSCLC patients in China . Seventy-six patients who meet the inclusion criteria will be allocated into two groups , which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles . Progression-free survival ( PFS ) is the primary end point , and the secondary end points are overall survival , objective response rate , time-to-progression , and quality of life ( EORTC QLQ-LC43 , and TCM syndrome score ) . Meanwhile , other end points such as toxicity , side effects and safety of the treatments will be assessed . DISCUSSION Results from this study may provide evidence on the effectiveness , and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC . TRIAL REGISTRATION Clinical Trials.gov . ( Identifier : NCT01780181 ) CONTEXT Breast cancer survivors ( BCS ) face adverse physical and psychological symptoms , often co-occurring . Biologic and psychological factors may link symptoms within clusters , distinguishable by prevalence and /or severity . Few studies have examined the effects of behavioral interventions or treatment of symptom clusters . OBJECTIVES The aim of this study was to identify symptom clusters among post-treatment BCS and determine symptom cluster improvement following the Mindfulness-Based Stress Reduction for Breast Cancer ( MBSR(BC ) ) program . METHODS Three hundred twenty-two Stage 0-III post-treatment BCS were r and omly assigned to either a six-week MBSR(BC ) program or usual care . Psychological ( depression , anxiety , stress , and fear of recurrence ) , physical ( fatigue , pain , sleep , and drowsiness ) , and cognitive symptoms and quality of life were assessed at baseline , six , and 12 weeks , along with demographic and clinical history data at baseline . A three-step analytic process included the error-accounting models of factor analysis and structural equation modeling . RESULTS Four symptom clusters emerged at baseline : pain , psychological , fatigue , and cognitive . From baseline to six weeks , the model demonstrated evidence of MBSR(BC ) effectiveness in both the psychological ( anxiety , depression , perceived stress and QOL , emotional well-being ) ( P = 0.007 ) and fatigue ( fatigue , sleep , and drowsiness ) ( P < 0.001 ) clusters . Results between six and 12 weeks showed sustained effects , but further improvement was not observed . CONCLUSION Our results provide clinical effectiveness evidence that MBSR(BC ) works to improve symptom clusters , particularly for psychological and fatigue symptom clusters , with the greatest improvement occurring during the six-week program with sustained effects for several weeks after MBSR(BC ) training . TRIAL REGISTRATION Name and URL of Registry : Clinical Trials.gov . Registration number : NCT01177124 |
13,479 | 31,522,330 | A power analysis showed that few HIV studies have sufficient power to address male/female differences in NCI but studies with adequate power find evidence of greater NCI in WLWH , particularly in the domains of memory , speed of information processing , and motor function .
Sex is an important determinant of NCI in HIV , and may relate to male/female differences in cognitive reserve , comorbidities ( mental health and substance use disorders ) , and biological factors ( e.g. , inflammation , hormonal , genetic ) | Sex differences in cognitive function are well documented yet few studies had adequate numbers of women and men living with HIV ( WLWH ; MLWH ) to identify sex differences in neurocognitive impairment ( NCI ) and the factors contributing to NCI .
Here , we review evidence that WLWH may be at greater risk for NCI . | BACKGROUND It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other . While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B ( HIV-1B ) infection on both immune and neuroendocrine systems , the consequence of HIV-1 clade C infection ( with structural differences from HIV-1B virus ) on these systems is not clearly understood . METHODS We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids , including cortisol and DHEAS and their relationship with declining CD4 + cell counts in neurologically asymptomatic HIV-C infected individuals ( N=84 ) in order to underst and the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity . RESULTS We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls ( HIV-1C+ , 9.83+/-0.39 vs controls , 8.04+/-0.45 ; p<0.01 ) , there was a significant decrease in DHEAS in HIV-1C+ individuals , compared to that in HIV-negative controls ( 81.02+/-4.9 vs 185.1+/-12.03 , p<0.001 ) , and consequently a significant increase in cortisol : DHEAS ratio in HIV-1 clade C infected persons ( 0.19+/-0.002 vs control 0.058+/-0.006 ; p<0.001 ) . Moreover , in HIV-1C infected individuals , there was a strong positive correlation between DHEAS and CD4 cells ( r=0.2 ; p<0.05 ) , and a strong negative correlation between cortisol , as well as cortisol : DHEAS ratio and CD4 cells ( r=-0.25 ; p<0.01 ; and r=-0.31 ; p<0.001 , respectively ) . CONCLUSIONS These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection , and that the evaluation of increase in plasma cortisol , a decrease in DHEAS , and an increase in cortisol : DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection . Furthermore , these findings may indicate the dysregulation of 3beta-hydroxysteroid dehydrogenase ( 3beta-HSD ) activity , the enzyme involved in the bio synthesis of cortisol and DHEA through the pregnenolone-progesterone pathway , and that it may offer an opportunity for drug discovery targeting re-regulation of 3beta-HSD activity for potential therapeutic application in HIV-1C infection Background : Women progress to death at the same rate as men despite lower plasma HIV RNA ( viral load ) . We investigated sex-specific differences in immune activation and inflammation as a potential explanation . Methods : Inflammatory and immune activation markers [ interferon & ggr ; , tumor necrosis factor ( TNF ) & agr ; , IL-6 , IL-18 , IFN-&ggr ;– induced protein 10 , C-reactive protein ( CRP ) , lipopolysaccharide , and sCD14 ] were measured at weeks 0 , 24 , and 48 after combination antiretroviral therapy ( cART ) in a r and om subcohort ( n = 215 ) who achieved virologic suppression in ACTG A5175 ( Prospect i ve Evaluation of Antiretrovirals in Re source -Limited Setting s ) . Association between sex and changes in markers post-cART was examined using r and om effects models . Average marker differences and 95 % confidence intervals were estimated using multivariable models . Results : At baseline , women had lower median log10 viral load ( 4.93 vs 5.18 copies per milliliter , P = 0.01 ) , CRP ( 2.32 vs 4.62 mg/L , P = 0.01 ) , detectable lipopolysaccharide ( 39 % vs 55 % , P = 0.04 ) , and sCD14 ( 1.9 vs 2.3 µg/mL , P = 0.06 ) vs men . By week 48 , women had higher interferon & ggr ; ( 22.4 vs 14.9 pg/mL , P = 0.05 ) , TNF-&agr ; ( 11.5 vs 9.5 pg/mL , P = 0.02 ) , and CD4 ( 373 vs 323 cells per cubic millimeter , P = 0.02 ) . In multivariate analysis , women had greater increases in CD4 and TNF-&agr ; but less of a decrease in CRP and sCD14 compared with men . Conclusions : With cART-induced viral suppression , women have less reduction in key markers of inflammation and immune activation compared with men . Future studies should investigate the impact of these sex-specific differences on morbidity and mortality Objective : Psychological risk factors ( PRFs ) are associated with impaired learning and memory in HIV-infected ( HIV+ ) women . We determined the dynamic nature of the effects of PRFs and HIV serostatus on learning and memory over time . Design : Multicenter , prospect i ve cohort study . Methods : Every 2 years between 2009 and 2013 ( three times ) , 646 HIV+ and 300 demographically similar HIV-uninfected ( HIV− ) women from the Women 's Interagency HIV Study completed neuropsychological testing and question naires measuring PRFs [ perceived stress , posttraumatic stress disorder ( PTSD ) symptoms , depressive symptoms ] . Using mixed-effects regressions , we examined separate and interactive associations between HIV-serostatus and PRFs on performance over time . Results : HIV+ and HIV− women had similar rates of PRFs . Fluency was the only domain in which performance over time depended on the combined influence of HIV-serostatus and stress or PTSD ( P < 0.05 ) , not depression . In HIV , higher stress and PTSD were associated with a greater cognitive decline in performance ( P < 0.05 ) vs. lower stress and PTSD . Irrespective of time , performance on learning and memory depended on the combined influence of HIV-serostatus and stress or PTSD ( P ⩽ 0.05 ) . In the context of HIV , stress and PTSD were negatively associated with performance . Effects were pronounced on learning among HIV+ women without effective treatment or viral suppression . Regardless of time or HIV-serostatus , all PRFs were associated with lower speed , global neuropsychological , and executive function . Conclusion : More than depression , perceived stress and PTSD symptoms are treatment targets to potentially improve fluency , learning , and memory in women living with HIV particularly when HIV treatment is not optimal Objective : Inflammatory biomarkers associated with cardiovascular disease are elevated in HIV-infected persons . These biomarkers improve with antiretroviral therapy ( ART ) but do not normalize to values observed in HIV-uninfected adults . Little is known regarding biomarkers of inflammation in HIV-infected Peruvians , in whom an increased burden of infectious diseases may exacerbate inflammation , and women , in whom sex difference may alter inflammation compared with men . Methods : Peruvians initiating first-line ART were enrolled in a prospect i ve observational study . Individuals with suppression of HIV RNA plasma loads to less than 30 copies/ml when determined quarterly over 24 months of ART , had biomarkers of inflammation and cellular activation measured pre-ART and at 24-months of ART , and evaluated for associations with sex and clinical parameters . Results : Pre-ART high-sensitivity C-reactive protein ( hsCRP ) values of men were in the high-risk cardiovascular disease category ( > 3.0 mg/l ) more frequently compared with women ( P = 0.02 ) ; most women 's values were in the low/average-risk categories . At 24 months of suppressive ART , hsCRP concentrations decreased in men ( P = 0.03 ) , but tended to increase in women , such that the proportion with high-risk hsCRP did not differ by sex . Pre-ART , soluble CD163 concentrations were higher in women compared with men ( P = 0.02 ) , and remained higher after 24 months of suppressive ART ( P = 0.02 ) . All other inflammatory biomarkers ( P < 0.03 ) decreased across sexes . Biomarker concentrations were not associated with BMI or coinfections . Conclusion : Elevated inflammatory biomarkers persisted despite 24 months of suppressive ART in a subset of Peruvians , and to a greater extent in women compared with men . These findings suggest that lifestyle or pharmacologic interventions may be required to optimize the health of HIV-infected Peruvians , particularly women Background Levels of high-sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , and D-dimer predict mortality in HIV patients on antiretroviral therapy ( ART ) with relatively preserved CD4 + T cell counts . We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART . Methods Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP , IL-6 and D-dimer . Using a nested case-control study design , the biomarkers were measured for 187 deaths and two controls matched on age , sex , clinical site , follow-up time and CD4 + cell counts . Odds ratios were estimated using conditional logistic regression . In addition , for a r and om sample of 100 patients , biomarkers were measured at baseline and 6 months following r and omization to determine whether ART altered their levels . Results Median baseline biomarkers levels for cases and controls , respectively , were 11.25 vs. 3.6 mg/L for hsCRP , 1.41 vs. 0.98 mg/L for D-dimer , and 9.02 vs. 4.20 pg/mL for IL-6 ( all p<0.0001 ) . Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 ( 95 % CI : 1.9–6.7 ) for hsCRP , 2.6 ( 95%CI 1.4–4.9 ) for D-dimer , and 3.8 ( 95 % CI : 1.8–7.8 ) for IL-6 . These associations were stronger for deaths that occurred more proximal to the biomarker measurements . Levels of D-dimer and IL-6 , but not hsCRP , were significantly lower at month 6 after commencing ART compared to baseline ( p<0.0001 ) . Conclusions Among patients with advanced HIV disease , elevated pre-ART levels of hsCRP , IL-6 and D-dimer are strongly associated with early mortality after commencing ART . Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART . Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted . Trial Registration Parent Study : Clinical Trials.gov Background In the Strategies for Management of Anti-Retroviral Therapy trial , all-cause mortality was higher for participants r and omized to intermittent , CD4-guided antiretroviral treatment ( ART ) ( drug conservation [ DC ] ) than continuous ART ( viral suppression [ VS ] ) . We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways , thrombosis , and fibrinolysis . Methods and Findings Stored sample s were used to measure six biomarkers : high sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , amyloid A , amyloid P , D-dimer , and prothrombin fragment 1 + 2 . Two studies were conducted : ( 1 ) a nested case – control study for study ing biomarker associations with mortality , and ( 2 ) a study to compare DC and VS participants for biomarker changes . For ( 1 ) , markers were determined at study entry and before death ( latest level ) for 85 deaths and for two controls ( n = 170 ) matched on country , age , sex , and date of r and omization . Odds ratios ( ORs ) were estimated with logistic regression . For each biomarker , each of the three upper quartiles was compared to the lowest quartile . For ( 2 ) , the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following r and omization . Higher levels of hsCRP , IL-6 , and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality . Unadjusted ORs ( highest versus lowest quartile ) were 2.0 ( 95 % confidence interval [ CI ] , 1.0–4.1 ; p = 0.05 ) , 8.3 ( 95 % CI , 3.3–20.8 ; p < 0.0001 ) , and 12.4 ( 95 % CI , 4.2–37.0 ; p < 0.0001 ) , respectively . Associations were significant after adjustment , when the DC and VS groups were analyzed separately , and when latest levels were assessed . IL-6 and D-dimer increased at 1 mo by 30 % and 16 % in the DC group and by 0 % and 5 % in the VS group ( p < 0.0001 for treatment difference for both biomarkers ) ; increases in the DC group were related to HIV-RNA levels at 1 mo ( p < 0.0001 ) . In an exp and ed case – control analysis ( four controls per case ) , the OR ( DC/VS ) for mortality was reduced from 1.8 ( 95 % CI , 1.1–3.1 ; p = 0.02 ) to 1.5 ( 95 % CI , 0.8–2.8 ) and 1.4 ( 95 % CI , 0.8–2.5 ) after adjustment for latest levels of IL-6 and D-dimer , respectively . Conclusions IL-6 and D-dimer were strongly related to all-cause mortality . Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels . Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation . Trial Registration : Clinical Trials.gov ( NCT00027352 ) OBJECTIVE : To determine the association between patient literacy and hospitalization . DESIGN : Prospect i ve cohort study . SETTING : Urban public hospital . PATIENTS : A total of 979 emergency department patients who participated in the Literacy in Health Care study and had completed an intake interview and literacy testing with the Test of Functional Health Literacy in Adults were eligible for this study . Of these , 958 ( 97.8 % ) had an electronic medical record available for 1994 and 1995 . MEASUREMENTS AND MAIN RESULTS : Hospital admissions to Grady Memorial Hospital during 1994 and 1995 were determined by the hospital information system . We used multivariate logistic regression to determine the independent association between inadequate functional health literacy and hospital admission . Patients with inadequate literacy were twice as likely as patients with adequate literacy to be hospitalized during 1994 and 1995 ( 31.5 % vs 14.9 % , p<.001 ) . After adjusting for age , gender , race , self-reported health , socioeconomic status , and health insurance , patients with inadequate literacy were more likely to be hospitalized than patients with adequate literacy ( adjusted odds ratio [ OR ] 1.69 ; 95 % confidence interval [ CI ] 1.13 , 2.53 ) . The association between inadequate literacy and hospital admission was strongest among patients who had been hospitalized in the year before study entry ( OR 3.15 ; 95 % CI 1.45 , 6.85 ) . CONCLUSIONS : In this study population , patients with inadequate functional health literacy had an increased risk of hospital admission The progression of HIV infection is accompanied by severe immunodepression and cachexia , particularly during advanced stages . The immune depression is due largely to a dramatic drop in the number of CD4 cells . The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue . We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men . The results of five retrospective and prospect i ve studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls . Serum cortisol was elevated at all stages of infection ( + 20 to + 50 % , p < .05 to p < .001 ) particularly in AIDS patients ( stage IV C ) . In contrast , the serum DHEA concentrations were closely correlated with the stage of HIV-infection , being higher in the early stages ( stages II and III or > 500 CD4 ) than in advanced stages ( IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls ( + 40 to 100 % , p < .01 to p < .001 ) . There was a negative linear correlation between the CD4 cell counts and cortisol ( r = -0.4 , p < .02 ) and a positive linear correlation with DHEA ( r = + 0.36 , p < .01 ) . There was no significant correlation between delta body weight and serum cortisol . In contrast , there was a negative correlation between serum DHEA and delta body weight ( % ) ( r = -0.69 , p < .0001 ) and a positive correlation with the cortisol/DHEA ratio ( r = + 0.61 , p < .0001 ) . There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection . This raises the question of whether there is a cause- and -effect relationship between clinical progression and circulating steroid concentrations . Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies BACKGROUND It is unclear whether there are differences between men and women with human immunodeficiency virus type 1 ( HIV-1 ) infection in the plasma level of viral RNA ( the viral load ) . In men , the initial viral load after seroconversion predicts the likelihood of progression to the acquired immunodeficiency syndrome ( AIDS ) , but the relation between the two has not been assessed in women . Currently , the guidelines for initiating antiretroviral therapy are applied uniformly to women and men . METHODS From 1988 through 1998 , the viral load and the CD4 + lymphocyte count were measured approximately every six months in 156 male and 46 female injection-drug users who were followed prospect ively after HIV-1 seroconversion . RESULTS The median initial viral load was 50,766 copies of HIV-1 RNA per milliliter in the men but only 15,103 copies per milliliter in the women ( P<0.001 ) . The median initial CD4 + count did not differ significantly according to sex ( 659 and 672 cells per cubic millimeter , respectively ) . HIV-1 infection progressed to AIDS in 29 men and 15 women , and the risk of progression did not differ significantly according to sex . For each increase of 1 log in the viral load ( on a base 10 scale ) , the hazard ratio for progression to AIDS was 1.55 ( 95 percent confidence interval , 0.97 to 2.47 ) among the men and 1.43 ( 95 percent confidence interval , 0.76 to 2.69 ) among the women . The median initial viral load was 77,822 HIV-1 RNA copies per milliliter in the men in whom AIDS developed and 40,634 copies per milliliter in the men in whom it did not ; the corresponding values in the women were 17,149 and 12,043 copies per milliliter . Given the recommendation that treatment should be initiated when the viral load reaches 20,000 copies per milliliter , 74 percent of the men but only 37 percent of the women in our study would have been eligible for therapy at the first visit after seroconversion ( P<0.001 ) . CONCLUSIONS Although the initial level of HIV-1 RNA was lower in women than in men , the rates of progression to AIDS were similar . Treatment guidelines that are based on the viral load , rather than the CD4 + lymphocyte count , will lead to differences in eligibility for antiretroviral treatment according to sex We prospect ively studied adrenal function in 51 human immunodeficiency virus-positive male patients , including heterosexuals , homosexuals , and iv drug users , classified according to 1987 CDC criteria as belonging to stages II/III or IVC . Basal serum concentrations of cortisol ( F ) , progesterone ( P4 ) and 17 alpha-hydroxyprogesterone ( 17 alpha-OHP4 ) were determined during the two stages . In stage IVC patients , the circadian rhythms of ACTH and F were assessed , and ovine CRH ( oCRH ) and immediate cosyntropin-stimulating tests were evaluated . Serum concentrations of hormones were analyzed in relationship to the absolute CD4 cell count in all subjects . The mean serum F concentration in stage IVC patients , the mean P4 concentration in stage II/III and IVC patients , and the mean 17 alpha-OHP4 level in stage II/III patients were significantly increased compared to control values ( P < 0.0001 , P < 0.0001 , and P < 0.002 , respectively ) . The mean serum F concentration in stage IVC patients was significantly increased compared to that in stage II/III patients ( P < 0.004 ) , and the mean serum 17 alpha-OHP4 concentration in stage II/III patients was significantly increased compared to that in stage IVC patients ( P < 0.02 ) . In the 22 stage IVC patients , the circadian rhythms of ACTH and F were normal in all but 7 for ACTH and 5 for F , whereas oCRH test results indicated that 14 of them had reduced or blunted responses . By contrast , cosyntropin stimulation results were normal . CD4 cell counts were significantly negatively correlated with the serum F concentration ( P < 0.02 ) . In conclusion , during human immunodeficiency virus infection , the serum F concentration was negatively correlated with CD4 cell counts . Cosyntropin test results were normal , but 63 % of the stage IVC men had abnormal responses to oCRH Objective : Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid nongenomic and slow genomic mechanisms . Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD but impairs these abilities in healthy individuals . We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men . Methods : In a double-blind placebo-controlled crossover study , we examined the time-dependent effects of a single low dose of hydrocortisone [ 10 mg ; low-dose hydrocortisone ( LDH ) ] on cognition in 45 HIV-infected men . Participants were r and omized to receive either LDH or placebo and one month later , were given the opposite treatment . At each intervention session , cognition was assessed 30 minutes ( assessing nongenomic effects ) and 4 hours ( assessing genomic effects ) after pill administration . Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session . Results : Compared with placebo , LDH doubled salivary cortisol levels . Cortisol returned to baseline 4 hours postadministration . At the 30-minute assessment , LDH enhanced verbal learning compared with placebo . Greater increases in cortisol were associated with greater enhancements in verbal learning . LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point . Conclusions : The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men . The nonenduring nature of this enhancement may limit its clinical utility but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning This study tested whether estimated premorbid intelligence moderates worsening neurobehavioral dysfunction in HIV infection . 155 homosexual men ( 54 controls , 49 HIV+ asymptomatic , 24 HIV+ symptomatic , 28 AIDS ) with stable disease status were tested on measures of executive function at baseline and 12-month follow-up . Premorbid intelligence was estimated on the basis of a demographically-based regression equation ( Hamsher , 1984 ) , and participants were classified as average or above-average intelligence . Regardless of disease status , participants with above-average IQ showed no declines on measures of executive function across time . In contrast , among those with average IQ , symptomatic groups showed declines , whereas the asymptomatic group did not . The findings support the hypothesis that estimated premorbid intelligence mediates declines in neuropsychological function in patients with stable HIV status . These findings are consistent with theoretical models of cognitive reserve capacity Numerous reports have assessed the neuropsychological functioning of medically asymptomatic HIV-1 infected men . However , to date there have been no published studies of the neuropsychological functioning of asymptomatic HIV-1 infected women , even though women represent the fastest-growing demographic group of HIV-1 infected individuals . In this investigation , 31 women ( 17 asymptomatic HIV-1 seropositive , 14 seronegative ) were administered a battery of neurocognitive and neuropsychiatric instruments . Participants in both groups were matched for age , education , months since injection drug use , and substance use . Group comparisons revealed no significant differences in any of the neurocognitive or neuropsychiatric measures . The results of this preliminary study suggest that clinical ly significant differences in neurobehavioral function are unlikely in medically asymptomatic HIV-1 infected women compared to seronegative controls . However , additional studies are needed with larger sample sizes and with careful attention to possible confounding or masking variables We evaluated neurocognitive function in 149 HIV-seropositive and 82 seronegative women enrolled in the Women 's Interagency HIV Study ( WIHS ) , a large multi-center study of disease progression in women living with HIV/AIDS . We evaluated the prevalence of abnormal neuropsychological ( NP ) test findings in HIV-seropositive and seronegative women and factors associated with increased risk of abnormal NP test performance . Risk of NP impairment was no higher for HIV positive women receiving antiretroviral therapy at testing than for HIV-negative women ( OR = 1.00 ) . However , the risk of abnormal NP performance increased significantly for seropositive women not receiving antiretroviral therapy ( OR = 2.43 ) . Further , treatment status was a significant predictor of NP impairment in a multivariate analysis that included viral load ( OR = 1.48 ) and CD4 count ( OR = 1.08 ) which were not significant . The multivariate analyses controlled for substance use , age , education , head injury , ethnicity , estimated IQ , and psychological distress . This study emphasizes the critical association of antiretroviral therapy with the risk of neurocognitive impairment in women living with HIV/AIDS Endocrine function was prospect ively evaluated in 98 patients ( 73 men and 25 women ) infected by HIV in various stages of illness : Centers for Disease Control groups II ( 19 ) , III ( 20 ) , IVA and IVC2 ( 27 ) , IVC1 and IVD ( 32 ) . Testing included baseline and post-stimulation evaluation of gonadal , thyroidal , and adrenal axes . Although adrenal function was within normal values in most cases , with no differences between patient groups , nine out of 98 patients had either a low baseline or post-stimulation serum cortisol , cytomegalovirus adrenalitis being suspected in two cases . Mineralocorticoid response was normal in all individuals . The main abnormalities were sick euthyroid syndrome with low tri-idothyronine and /or thyroxine in 16 % of patients and hypotestosteronemia in 29 % of men with AIDS . These abnormalities , related to a functional deficiency of the hypothalamic-pituitary axis , were highly correlated with the degree of illness , i.e. weight loss and low CD4 + cell count . It was concluded that endocrine dysfunction in HIV-infected patients is rarely of clinical significance , that it is related more to cachexia and advanced disease than to HIV or opportunistic infections , and that it could serve as a prognostic marker Despite the use of laboratory markers in estimating HIV prognosis , significant variation in the natural history of HIV-1 infection remains unexplained . Recent studies suggest psychosocial risk factors have important prognostic significance in HIV disease . The objective of the present study was to examine the prognostic influence of age , general intellectual functioning , and emotional distress across the spectrum of HIV disease progression . The study sample was drawn from the Multicenter AIDS Cohort Study ( MACS ) , a 13-year , prospect i ve study of HIV-seropositive men recruited from four study centers across the country . The participants were 1,231 HIV-seropositive MACS participants , followed from baseline ( median 8/15/87 ) to the end of the observation period ( 12/15/98 ) . HIV disease progression was evaluated with respect to three outcome measures : ( 1 ) number of years from baseline testing to the first AIDS defining illness ( progression to AIDS ) , ( 2 ) years from baseline to HIV-dementia ( progression to dementia ) , and ( 3 ) years from baseline to death ( survival ) . The influence of psychosocial risk factors on outcome measures was evaluated using survival analyses . General intellectual functioning , age , and somatic symptoms of depression , were found to be significant predictors of HIV disease progression and survival . Older age at baseline was associated with a more rapid progression to dementia and death . Lower Shipley IQ estimates were associated with a more rapid disease progression ( AIDS and dementia ) and shortened survival . Somatic symptoms of depression were associated with shortened survival . In addition , age , IQ , and somatic symptoms of depression , had an additive effect with an increase in the number of risk factors associated with accelerated disease progression and shortened time to death . These findings remained consistent , despite controlling for baseline CD4 and HIV medication use . Psychosocial cofactors are important in underst and ing HIV disease progression . Methods for estimating HIV prognosis may become more reliable if psychosocial factors are considered . Future research will clarify if psychosocial risk factors reflect central nervous system integrity , brain reserve capacity or mediate morbidity and mortality through social economic status , access to health care and other social correlates Background : Women may be more vulnerable to HIV-related cognitive dysfunction compared with men because of sociodemographic , lifestyle , mental health , and biological factors . However , studies to date have yielded inconsistent findings on the existence , magnitude , and pattern of sex differences . We examined these issues using longitudinal data from 2 large , prospect i ve , multisite , observational studies of US women and men with and without HIV . Setting : The Women 's Interagency HIV Study ( WIHS ) and Multicenter AIDS Cohort Study ( MACS ) . Methods : HIV-infected ( HIV+ ) and uninfected ( HIV− ) participants in the Women 's Interagency HIV Study and Multicenter AIDS Cohort Study completed tests of psychomotor speed , executive function , and fine motor skills . Groups were matched on HIV status , sex , age , education , and black race . Generalized linear mixed models were used to examine group differences on continuous and categorical demographically corrected T-scores . Results were adjusted for other confounding factors . Results : The sample ( n = 1420 ) included 710 women ( 429 HIV+ ) and 710 men ( 429 HIV+ ) ( 67 % non-Hispanic black ; 53 % high school or less ) . For continuous T-scores , sex by HIV serostatus interactions were observed on the Trail Making Test parts A & B , Grooved Pegboard , and Symbol Digit Modalities Test . For these tests , HIV+ women scored lower than HIV+ men , with no sex differences in HIV− individuals . In analyses of categorical scores , particularly the Trail Making Test part A and Grooved Pegboard nondominant , HIV+ women also had a higher odds of impairment compared with HIV+ men . Sex differences were constant over time . Conclusions : Although sex differences are generally understudied , HIV+ women vs men show cognitive disadvantages . Elucidating the mechanisms underlying these differences is critical for tailoring cognitive interventions Objective : Low-dose hydrocortisone ( LDH ) enhances aspects of learning and memory in select population s including patients with posttraumatic stress disorder and HIV-infected men . HIV-infected women show impairments in learning and memory , but the cognitive effects of LDH in HIV-infected women are unknown . Design : Double-blind , placebo-controlled , cross-over study examining the time-dependent effects of a single low-dose administration of hydrocortisone ( 10 mg oral ) on cognition in 36 HIV-infected women . Participants were first r and omized to LDH or placebo and then received the opposite treatment one month later . Methods : Cognitive performance was assessed 30 min and 4 h after pill administration to assess , respectively , nongenomic and genomic effects . Self-reported stress/anxiety and salivary cortisol were assessed throughout sessions . Results : LDH significantly increased salivary cortisol levels versus placebo ; levels returned to baseline 4-h postadministration . At the 30-min assessment , LDH enhanced verbal learning and delayed memory , working memory , behavioral inhibition , and visuospatial abilities . At the 4-h assessment , LDH enhanced verbal learning and delayed memory compared with placebo . LDH-induced cognitive benefits related to reductions in cytokines and to a lesser extent to increases in cortisol . Conclusion : The extended benefits from 30 min to 4 h of a single administration of LDH on learning and delayed memory suggest that targeting the hypothalamic – pituitary – adrenal axis may have potential clinical utility in HIV-infected women . These findings contrast with our findings in HIV-infected men who showed improved learning only at the 30-min assessment . Larger , longer term studies are underway to verify possible cognitive enhancing effects of LDH and the clinical significance of these effects in HIV Plasma human immunodeficiency virus type 1 ( HIV-1 ) RNA levels in women are lower early in untreated HIV-1 infection compared with those in men , but women have higher T-cell activation and faster disease progression when adjusted for viral load . It is not known whether these sex differences persist during effective antiretroviral therapy ( ART ) , or whether they would be relevant for the evaluation and implementation of HIV-1 cure strategies . We prospect ively enrolled a cohort of reproductive-aged women and matched men on suppressive ART and measured markers of HIV-1 persistence , residual virus activity , and immune activation . The frequency of CD4 + T cells harboring HIV-1 DNA was comparable between the sexes , but there was higher cell-associated HIV-1 RNA , higher plasma HIV-1 ( single copy assay ) , and higher T-cell activation and PD-1 expression in men compared with women . These sex-related differences in immune phenotype and HIV-1 persistence on ART have significant implication s for the design and measurement of curative interventions |
13,480 | 31,833,410 | Psychophysical studies showed that individuals with BN , in general , had greater preference for sweetness than healthy controls , and those with AN had a greater aversion for fat than controls .
In neuroimaging studies , findings suggested that predictable administration of sweet-taste stimuli was associated with reduced activation in taste-reward regions of the brain among individuals with AN ( e.g. , insula , ventral , and dorsal striatum ) but increased activation in BN and BED .
Discussion : To our knowledge , this systematic review is the first to synthesize literature on taste differences in AN , BN , and BED . | Background : Eating disorders are a significant cause of morbidity and mortality .
The etiology and maintenance of eating-disorder symptoms are not well understood .
Evidence suggests that there may be gustatory alterations in patients with eating disorders .
Objective : This article systematic ally review s research assessing gustatory differences in patients with anorexia nervosa ( AN ) , bulimia nervosa ( BN ) , and binge eating disorder ( BED ) . | The possible differences in processing gustatory stimuli in anorexic patients compared to healthy control subjects was investigated by electrophysiological methods . The electroencephalogram ( EEG ) was recorded in out patients treated with anorexia nervosa ( AN ) and age-matched controls after exposure to sweet ( milk chocolate ) and bitter ( black tea ) taste stimuli . Power spectrum analysis was performed on EEG epochs recorded in the above conditions . Compared to controls a significantly higher percent of theta , and lower percent of alpha1 b and power was found in anorexic patients , irrespective of the kind of taste effects and hemispheric side . The pattern of activation caused by sweet and bitter stimuli was found to be different in these two groups , possibly indicating altered gustatory processing mechanisms in AN We evaluated the changes in taste responsiveness of anorexia nervosa ( AN ) patients during behavior therapy . Taste responsiveness of AN patients was lower at admission when compared to controls but it improved significantly over the course of treatment ( p < 0.01 ) . Taste responsiveness improved prior to increase in body weight . No significant correlation was noted between weight gain and improvement in taste responsiveness . The period required to reach a food intake of 1600 Kcal/day and the duration of hospitalization were highly correlated ( r = 0.72 , p < 0.05 ) . Those who reached 1600 Kcal/day earlier showed more rapid improvements in taste responsiveness . These results suggest that decreased taste responsiveness in AN patients can rapidly improve and such early improvement may result in better progression of treatment Restrictive eating disorders ( ED ) are increasing and represent a serious risk to the health of adolescent females . Restrictive ED in youth are often treated through aggressive short-term refeeding . Although evidence supports that this intervention is the " gold st and ard " for improving ED outcomes in youth , little research has specifically probed appetite and meal-related responses to this type of intensive , short-term refeeding in newly diagnosed individuals . Information about appetite and meal-related dysfunction could provide valuable insights regarding treatment-interfering features of ED in both acute inpatient and longer-term outpatient treatment . The purpose of this study was to evaluate the hunger , fullness , olfactory , and gustatory responses of adolescents with newly-diagnosed restrictive ED and to probe how and when these responses are altered by refeeding . Using a quasi-experimental ecologically valid methodology , this study described and compared profiles of hunger , fullness , olfactory , and gustatory responses in adolescent females ( n = 15 ) with newly diagnosed restrictive ED at hospital admission ( i.e. , severe malnutrition ) and after medical refeeding , in comparison to healthy controls ( n = 15 ) . Results showed that newly diagnosed ( i.e. , malnourished ) adolescents with ED showed significantly different meal-related experiences than controls . Refeeding improved some of these differences , but not all . Following refeeding , females with ED continued to show lower hunger , greater fullness , and lower pleasantness of smell ratings compared to controls . Unpleasantness of taste ratings maladaptively increased , such that females who were re-fed reported more aversive scents than pre-treatment . Profiles of meal-related responses were also identified and compared between groups . The applicability of these findings are discussed within the context of critical periods of change during refeeding treatment and potentially promising intervention targets that might enhance treatment outcomes for adolescents with newly onset , restrictive ED Taste responses to sucrose and fat-containing stimuli were examined in a population of young women with eating disorders . Anorectic-restrictor and anorectic-bulimic patients were compared with normal-weight bulimic patients and with normal-weight control subjects . Sensory estimates of sweetness and fat content of 20 different mixtures of milk , cream , and sugar did not differ among subject groups . In contrast , relative preferences for sugar vs fat as determined by the Response Surface Method differed between patients with eating disorders and control subjects . Normal-weight bulimic patients preferred sweeter stimuli than did control subjects . Anorectic-restrictor and anorectic-bulimic patients liked sweet but disliked high-fat stimuli and showed elevated optimal sugar : fat ( S : F ) ratios . This pattern of response did not change following weight regain . The stability of preference profiles suggests that taste responsiveness may be independent of diagnostic categories , bulimic behaviors , or acute changes in body weight To test the hypothesis that endogenous opiate peptides selectively influence hedonic response to sweet and high-fat foods , the opiate antagonist naloxone , opiate agonist butorphanol , and a saline placebo were administered by intravenous infusion to 16 obese and 25 normal-weight women . Twenty of the women ( 10 obese , 10 lean ) fulfilled DSM-III-R diagnostic criteria for bulimia nervosa , as determined by psychiatric interview . During drug infusion the women tasted and rated 20 sweetened dairy products and were presented with eight snack foods of varying sugar and fat content . Naloxone suppressed hedonic responses in all subject groups and suppressed the consumption of sweet and high-fat foods in binge eaters , but not in nonbingers . Food intakes of obese women were not affected by naloxone . Butorphanol had no effect on either hedonic response or on food consumption in any group . Although opiate blockade is not a viable strategy for weight reduction in the treatment of obesity , it may be useful in the clinical management of the binge-eating disorder The aim of this study was to identify cortical areas important for optimal cognitive aging . 74 participants ( 20 - 88 years ) went through neuropsychological tests and two MR sessions . The sample was split into two age groups . In each , every participant was classified as " high " or " average " on fluid ability tests and on neuropsychological tests related to executive function . The groups were compared with regard to thickness on a point-by-point basis across the entire cortical mantle . The old high fluid performers had thicker cortex than the average performers in large areas of cortex , while there was minimal difference between the groups of high vs. average executive function . Furthermore , the old group with high fluid function had thicker cortex than the young participants in the posterior cingulate and adjacent areas . Further analyses showed that the latter was a result of a complex aging pattern , differing between the two performance groups , with decades of cortical thickening and subsequent thinning Binge eating is often preceded by reports of negative affect , but the mechanism by which affect may lead to binge eating is unclear . This study evaluated the effect of negative affect on neural response to anticipation and receipt of palatable food in women with bulimia nervosa ( BN ) versus healthy controls . We also evaluated connectivity between the amygdala and reward-related brain regions . Females with and without BN ( n=26 ) underwent functional magnetic resonance imaging ( fMRI ) during receipt and anticipated receipt of chocolate milkshake and a tasteless solution . We measured negative affect just prior to the scan . Women with BN showed a positive correlation between negative affect and activity in the putamen , cau date , and pallidum during anticipated receipt of milkshake ( versus tasteless solution ) . There were no significant relations between negative affect and receipt of milkshake . Connectivity analyses revealed a greater relation of amygdala activity to activation in the left putamen and insula during anticipated receipt of milkshake in the bulimia group relative to the control group . The opposite pattern was found for the taste of milkshake ; the control group showed a greater relation of amygdala activity to activation in the left putamen and insula in response to milkshake receipt than the bulimia group . Results show that as negative affect increases , so does responsivity of reward regions to anticipated intake of palatable food , implying that negative affect may increase the reward value of food for individuals with bulimia nervosa or that negative affect has become a conditioned cue due to a history of binge eating in a negative mood Preferences and cravings for sweet high-fat foods observed among obese and bulimic patients may involve the endogenous opioid peptide system . The opioid antagonist naloxone , opioid agonist butorphanol , and saline placebo were administered by intravenous infusion to 14 female binge eaters and 12 normal-weight controls . Eight of the binge eaters were obese . During infusion , the subjects tasted 20 sugar/fat mixtures and were allowed to select and consume snack foods of varying sugar and fat content . Naloxone reduced taste preferences relative to baseline in both binge eaters and controls . Total caloric intake from snacks was significantly reduced by naloxone in binge eaters but not in controls . This reduction was most pronounced for sweet high-fat foods such as cookies or chocolate . No consistent effects on taste preferences or food intakes were observed with butorphanol . Endogenous opioid peptides may be involved in mediating taste responses and preferences for palatable foods , notably those rich in sugar and fat OBJECTIVE Most previous studies of the prevalence , incidence , and outcome of anorexia nervosa have been limited to cases detected through the health care system , which may bias our underst and ing of the disorder 's incidence and natural course . The authors sought to describe the onset and outcomes of anorexia nervosa in the general population . METHOD Lifetime prevalences , incidence rates , and 5-year recovery rates of anorexia nervosa were calculated on the basis of data from 2,881 women from the 1975 - 1979 birth cohorts of Finnish twins . Women who screened positive for eating disorder symptoms ( N=292 ) , their screen-negative female co-twins ( N=134 ) , and 210 r and omly selected screen-negative women were assessed for lifetime eating disorders by telephone by experienced clinicians . To assess outcomes after clinical recovery and to detect residua of illness , women who had recovered were compared with their unaffected co-twins and healthy unrelated women on multiple outcome measures . RESULTS The lifetime prevalence of DSM-IV anorexia nervosa was 2.2 % , and half of the cases had not been detected in the health care system . The incidence of anorexia nervosa in women between 15 and 19 years of age was 270 per 100,000 person-years . The 5-year clinical recovery rate was 66.8 % . Outcomes did not differ between detected and undetected cases . After clinical recovery , the residua of illness steadily receded . By 5 years after clinical recovery , most prob and s had reached complete or nearly complete psychological recovery and closely resembled their unaffected co-twins and healthy women in weight and most psychological and social measures . CONCLUSIONS The authors found a substantially higher lifetime prevalence and incidence of anorexia nervosa than reported in previous studies , most of which were based on treated cases . Most women recovered clinical ly within 5 years , and thereafter usually progressed toward full recovery Previous research has shown that patients with bulimia nervosa ( B ) , anorexia nervosa , restricting type , or restrictive-anorectic ( RA ) , and anorexia nervosa , binge eating , purging type , or anorectic-bulimic ( AB ) exhibit a reduced hedonic response to sucrose compared with control subjects . We hypothesized that this response could be linked to an excessive fear of weight gain rather than a decreased ability to experience pleasure . We therefore compared the hedonic responses to sucrose solutions in B , RA and AB women ( n=20/group ) in two different conditions : sucrose solution swallowed vs. sucrose solution spit . Under double-blind conditions and according to a Latin square design , patients received sucrose in solution ( 0 , 5 , 10 , 20 , and 40 % ) and rated each concentration for pleasantness on a nine-point scale . The two test conditions were r and omly administered . The threshold concentration of sweet taste perception was also assessed , and the subjects filled out Chapman 's Social and Physical Anhedonia Scale . The hedonic response to sucrose adjusted for the sweet taste perception threshold was significantly lower in the ' swallow ' than in the ' spit ' condition . There was a significant effect of sucrose concentrations as well as a significant condition by concentration interaction . When ' fear to swallow ' sucrose solution responses were included as a covariate , the significant difference between the conditions of ' swallow ' or ' spit ' disappeared , but there was a significant concentration by condition by fear to swallow interaction and an almost significant covariate effect . When ' Drive for Thinness ' on the Eating Disorder Inventory was included as a covariate , similar results were obtained . Social Anhedonia but not Physical Anhedonia correlated positively with ' Drive for Thinness ' and ' fear of swallowing sucrose solutions ' , and correlated inversely with maximal hedonic response to the ' swallow ' condition . ' We conclude that the hedonic responses to sucrose in patients with eating disorders are decreased when solutions are swallowed . This may reflect excessive fear of gaining weight rather than decreased ability to experience pleasure ' The overall aim of the present study was to investigate a new method for the screening of taste function in a clinical context . Instead of dripping liquids onto the tongue , thin edible wavers were used . One-hundred healthy subjects participated in the study ( 41 male , 59 female ; mean age : 52 years ; age range : 20 - 89 years ) . Supra-threshold taste stimuli were presented as flavoured wavers made from flour and water . Sequential testing was performed regionally on the anterior one-third of the tongue and as whole mouth testing . When comparing ratings for the 5 different wavers separately for regional and whole mouth testing , differences between qualities only emerged for regional testing . Women were found to have less difficulty in taste identification which was most pronounced for regional testing . No effects of the subjects ' age were observed . In conclusion , the wavers were found to be easy to use ; they have a shelf-life of 2 to 3 years and can be carried in the pocket . The results indicate that the wavers may be suited for the screening of gustatory function , especially in a clinical setting Although it is possible that binge eating in humans is due to increased responsiveness of orosensory excitatory controls of eating , there is no direct evidence for this because food ingested during a test meal stimulates both orosensory excitatory and postingestive inhibitory controls . To overcome this problem , we adapted the modified sham feeding technique ( MSF ) to measure the orosensory excitatory control of intake of a series of sweetened solutions . Previously published data showed the feasibility of a " sip- and -spit " procedure in nine healthy control women using solutions flavored with cherry Kool Aid and sweetened with sucrose ( 0 - 20 % ) . The current study extended this technique to measure the intake of artificially sweetened solutions in women with bulimia nervosa ( BN ) and in women with no history of eating disorders . Ten healthy women and 11 women with BN were r and omly presented with cherry Kool Aid solutions sweetened with five concentrations of aspartame ( 0 , 0.01 , 0.03 , 0.08 and 0.28 % ) in a closed opaque container fitted with a straw . They were instructed to sip as much as they wanted of the solution during 1-minute trials and to spit the fluid out into another opaque container . Across all subjects , presence of sweetener increased intake ( p<0.001 ) . Women with BN sipped 40.5 - 53.1 % more of all solutions than controls ( p=0.03 for total intake across all solutions ) . Self-report ratings of liking , wanting and sweetness of solutions did not differ between groups . These results support the feasibility of a MSF procedure using artificially sweetened solutions , and the hypothesis that the orosensory stimulation of MSF provokes larger intake in women with BN than controls Recent studies suggest that some patients with bulimia nervosa may experience elevated pleasantness responses to sweet taste . This study explored possible associations between symptoms patterns and pleasantness ratings for sucrose solutions in bulimic patients . Subjects included 15 women meeting DSM III-R criteria for narrowly defined bulimia nervosa ( no history of other eating disorder ) ; five patients with current bulimia nervosa and a past history of anorexia nervosa ; and 20 healthy age-matched female controls . Subjects ate a st and ardized breakfast prior to the morning study visit . Sucrose-water solutions ( 0 % to 40 % sucrose ) were rated for sweetness intensity and pleasantness . Patients with narrowly defined bulimia nervosa showed significantly higher pleasantness ratings for 40 % sucrose solutions than controls and patients with a history of anorexia nervosa . Pleasantness ratings were not significantly correlated with frequency of binge eating or purging behaviors . These results extend previous evidence for altered sweet taste pleasantness responses in bulimia nervosa , and for differences in eating-related behaviors between patients with narrowly defined bulimia nervosa vs. those with past anorexia nervosa BACKGROUND The majority of studies on taste and smell in eating disorders have revealed several alterations of olfactory or gustatory functions . Aim of this prospect i ve study was to employ detailed olfactory and gustatory testing in female subjects of three homogenous groups - anorexia nervosa , bulimia nervosa and healthy controls - and to look at the effects of treatment on these measures . METHODS Sixteen hospitalized female patients with anorexia ( restricting type , mean age [M]=24.5 years ) , 24 female patients with bulimia ( purging type , M=24.3 years ) as well as 23 healthy controls ( M=24.5 years ) received olfactory ( " Sniffin ' Sticks " ) and gustatory testing ( " Taste Strips " ) . Group differences in olfactory and gustatory sensitivity , body mass index ( BMI ) , the Beck depression inventory , the eating attitudes test ( EAT ) , and the influence of therapy on gustatory and olfactory function were investigated . RESULTS ( 1 ) Group differences were present for odor discrimination and overall olfactory function with anorexic patients having the lowest scores . ( 2 ) Regarding taste function , controls scored higher than patients with anorexia . ( 3 ) At admission small but significant correlations were found between overall olfactory function and body weight ( r(63)=0.35 ) , BMI ( r(63 ) = 0.37 ) , and EAT score ( r(63 ) = -0.27 ) . Similarly , ( 4 ) the taste test score correlated significantly with body weight ( r(63)= 0.48 ) , and BMI ( r(63 ) = 0.45 ) . Finally , ( 5 ) at discharge overall olfactory and gustatory function were significantly higher compared to admission in anorexic patients . CONCLUSIONS As compared to healthy controls and bulimic patients our results show lowered olfactory and gustatory sensitivities in anorexic patients that improved with increasing BMI and decreasing eating pathology in the course of treatment BACKGROUND In anorexia nervosa ( AN ) , taste and smell are believed to be anhedonic , hunger and pain are muted , and body-image distortion obscures wasting , which together facilitate self-starvation . However , the emphasis on these deficits may be biased because other sensory systems have been sparsely investigated . OBJECTIVES Objectives of the study were to clarify whether these dysfunctions are specific or part of a pattern of sensory-perceptual deficits in AN patients and to test the gustatory senses dissociated from ingestion to clarify whether any deficit is sensory or affective . DESIGN In 15 adolescent , first-episode , hospitalized , restrictive AN patients and 15 matched healthy controls who responded to gustatory stimuli ( intensity and hedonics of 5 basic tastes and tastes and odors of foods and nonfoods ) , size estimation ( manual and oral judgment of size and shape , kinesthesia , and body size and esthetics ) , cold pain , and auditory and visual processing were compared . RESULTS AN patients did not differ on most tests , were better at odor recognition , were less successful in central auditory processing and oral assessment of size and shape , and may have been more sensitive to cold . Body-image dissatisfaction in AN patients was not related to dysfunctional size estimation . CONCLUSIONS There is no systematic sensory-perceptual deficit in AN patients , and specifically , not in gustatory function . The few differences shown might be due to fear of food-related stimuli or comorbidity |
13,481 | 27,327,448 | There was no difference in fracture incidence in the two groups .
Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck .
There was no difference in fracture incidence .
Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels | Mineral and bone disorders that precede kidney transplantation are exacerbated in the post-transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens .
Bone mineral density ( BMD ) decreases following transplantation , leading to increased fracture risk .
The effect of bisphosphonates on fracture is unknown .
The aim of this study was to up date estimates of change in BMD and fracture rates in bisphosphonate-treated kidney transplant recipients through meta- analysis . | Severe osteoporosis frequently is observed after organ transplantation . In kidney transplantation , it adds to pre-existing renal bone disease and strategies to prevent osteoporosis are not established . Eighty kidney recipients were included in a r and omized controlled prospect i ve intervention trial . Treated patients ( n = 40 ) received an injection of ib and ronate , a bisphosphonate , immediately before and at 3 , 6 , and 9 mo after transplantation . The primary outcome measured was the change in bone mineral density . Secondary measures included graft outcome , spinal deformities , fracture rate , body height , and hormonal and metabolic data . Loss of spongy and cortical bone after transplantation was prevented by ib and ronate . Changes of bone mineral density ( ib and ronate versus controls ) were as follows : lumbar spine , -0.9 + /- 6.1 % versus -6.5 + /- 5.4 % ( P < 0.0001 ) ; femoral neck , + 0.5 + /- 5.2 % versus -7.7 + /- 6.5 % ( P < 0.0001 ) ; and midfemoral shaft , + 2.7 + /- 12.2 % versus -4.0 + /- 10.9 % ( P = 0.024 ) . Fewer spinal deformities developed with ib and ronate ( 7 patients with 7 deformities versus 12 patients with 23 deformities ; P = 0.047 ) . Loss of body height was 0.5 + /- 1.0 cm versus 1.1 + /- 1.0 cm in control subjects ( P = 0.040 ) . Two bone fractures occurred in each group . There were fewer acute rejection episodes with ib and ronate ( 11 versus 22 ; P = 0.009 ) . Graft function after 1 yr was comparable . Bone loss , spinal deformation , and loss of body height during the first year after kidney transplantation are prevented by injection of ib and ronate at intervals of 3 mo . The smaller number of rejection episodes of the ib and ronate-treated group should be confirmed and its mechanism should be explored in additional studies BACKGROUND Osteopenia is a major complication of renal transplantation . Immunosuppressive regimens including cyclosporine , which permit the use of lower doses of glucocorticoids , may reduce glucocorticoid-induced osteopenia . METHODS We prospect ively studied the magnitude , distribution , and mechanism of bone loss in 20 adults who received renal allografts from living related donors , who had good renal function , and who were treated with azathioprine , cyclosporine , and low doses of prednisone . We measured serum biochemical markers of bone metabolism , determined the bone mineral density of the second , third , and fourth lumbar vertebrae and the shaft of the radius , and analyzed the histomorphometric features of iliac bone at the time of transplantation and six months later . Measurements of vertebral mineral density were repeated 18 months after transplantation in 17 of the patients . RESULTS After transplantation , the mean serum concentrations of parathyroid hormone , phosphorus , and alkaline phosphatase decreased and the serum calcitriol concentration increased . The mean ( + /- SD ) bone mineral density of the vertebrae had decreased 6.8 + /- 5.6 percent 6 months after transplantation ( P less than 0.05 ) and 8.8 + /- 7.0 percent 18 months after transplantation . In contrast , the bone mineral density of the radius had increased six months after transplantation ( P less than 0.05 ) . The histomorphometric studies showed that the rate of bone formation decreased from 50.5 + /- 44.8 to 23.1 + /- 13.8 microns3 per square micrometer per year ( P less than 0.05 ) , and the formation period lengthened from 70 + /- 42 to 146 + /- 144 days ( P less than 0.05 ) . Consequently , the amount of bone replaced during a remodeling cycle diminished . CONCLUSIONS Osteopenia associated with renal transplantation remains a problem in the cyclosporine era . The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids BACKGROUND Previous studies have shown that alendronate can increase bone mineral density ( BMD ) and prevent radiographically defined ( morphometric ) vertebral fractures . The Fracture Intervention Trial aim ed to investigate the effect of alendronate on the risk of morphometric as well as clinical ly evident fractures in postmenopausal women with low bone mass . METHODS Women aged 55 - 81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture . Results for women with at least one vertebral fracture at baseline are reported here . 2027 women were r and omly assigned placebo ( 1005 ) or alendronate ( 1022 ) and followed up for 36 months . The dose of alendronate ( initially 5 mg daily ) was increased ( to 10 mg daily ) at 24 months , with maintenance of the double blind . Lateral spine radiography was done at baseline and at 24 and 36 months . New vertebral fractures , the primary endpoint , were defined by morphometry as a decrease of 20 % ( and at least 4 mm ) in at least one vertebral height between the baseline and latest follow-up radiograph . Non-spine clinical fractures were confirmed by radiographic reports . New symptomatic vertebral fractures were based on self-report and confirmed by radiography . FINDINGS Follow-up radiographs were obtained for 1946 women ( 98 % of surviving participants ) . 78 ( 8.0 % ) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 ( 15.0 % ) in the placebo group ( relative risk 0.53 [ 95 % Cl 0.41 - 0.68 ] ) . For clinical ly apparent vertebral fractures , the corresponding numbers were 23 ( 2.3 % ) alendronate and 50 ( 5.0 % ) placebo ( relative hazard 0.45 [ 0.27 - 0.72 ] ) . The risk of any clinical fracture , the main secondary endpoint , was lower in the alendronate than in the placebo group ( 139 [ 13.6 % ] vs 183 [ 18.2 % ] ; relative hazard 0.72 [ 0.58 - 0.90 ] ) . The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 ( 0.23 - 0.99 ) and 0.52 ( 0.31 - 0.87 ) . There was no significant difference between the groups in numbers of adverse experiences , including upper-gastrointestinal disorders . INTERPRETATION We conclude that among women with low bone mass and existing vertebral fractures , alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures , as well as other clinical fractures Background . This prospect i ve study was design ed to investigate the long-term evolution of bone mineral density ( BMD ) in kidney transplant recipients . Methods . In 86 patients with functioning grafts , 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression , laboratory parameters and BMD measurements in lumbar spine ( L2–L4 ) and femoral neck ( FN ) were performed by DEXA in the first month after transplantation ( baseline ) and yearly thereafter up to the fourth year . Results . BMD did not change at 12 months in lumbar spine nor in the FN . Detailed analysis identified three patterns of BMD in lumbar spine at 12 months : BMD remained stable in 27 patients ( 31.4 % ) , decreased > 2 % in 31 ( 36.0 % ) and increased > 2 % in 28 ( 32.6 % ) . Patients with no change or gain presented a parallel increase of BMD in FN ( P<0.001 in both groups ) . On multivariate analysis , the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months ( OR 1.402 ; 95 % CI 1.038–1.893 ; P=0.028 ) , calcitriol levels at 12 months ( OR 0.936 ; 95 % CI 0.892–0.982 ; P=0.007 ) and lumbar BMD at baseline ( OR 1.006 ; 95 % CI 1.002–1.010 ; P=0.002 ) . Late treatment with calcium supplements and calcitriol did not improve osteopenia . Conclusions . One third of patients had bone loss mainly during the first year of follow-up . Bone loss was associated to higher baseline BMD , high steroid dose , and lower calcitriol levels at 1 year . Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia . More than 50 % of patients were osteopenic 4 years after transplantation CONTEXT Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures , but its effects on fracture risk have not been studied for women without vertebral fractures . OBJECTIVE To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density ( BMD ) but no vertebral fractures . DESIGN R and omized , blinded , placebo-controlled trial . SETTING Eleven community-based clinical research centers . SUBJECTS Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less ( Hologic Inc , Waltham , Mass ) but no vertebral fracture ; 4432 were r and omized to alendronate or placebo and 4272 ( 96 % ) completed outcome measurements at the final visit ( an average of 4.2 years later ) . INTERVENTION All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol . Subjects were r and omly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial . MAIN OUTCOME MEASURES Clinical fractures confirmed by x-ray reports , new vertebral deformities detected by morphometric measurements on radiographs , and BMD measured by dual x-ray absorptiometry . RESULTS Alendronate increased BMD at all sites studied ( P<.001 ) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group , but not significantly so ( 14 % reduction ; relative hazard [ RH ] , 0.86 ; 95 % confidence interval [ CI ] , 0.73 - 1.01 ) . Alendronate reduced clinical fractures by 36 % in women with baseline osteoporosis at the femoral neck ( > 2.5 SDs below the normal young adult mean ; RH , 0.64 ; 95 % CI , 0.50 - 0.82 ; treatment-control difference , 6.5 % ; number needed to treat [ NNT ] , 15 ) , but there was no significant reduction among those with higher BMD ( RH , 1.08 ; 95 % CI , 0.87 - 1.35 ) . Alendronate decreased the risk of radiographic vertebral fractures by 44 % overall ( relative risk , 0.56 ; 95 % CI , 0.39 - 0.80 ; treatment-control difference , 1.7 % ; NNT , 60 ) . Alendronate did not increase the risk of gastrointestinal or other adverse effects . CONCLUSIONS In women with low BMD but without vertebral fractures , 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity . Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD The clinical profile of ib and ronate as add‐on to calcitriol and calcium was studied in this double‐blind , placebo‐controlled trial of 129 renal transplant recipients with early stable renal function ( ≤ 28 days posttransplantation , GFR ≥ 30 mL/min ) . Patients were r and omized to receive i.v . ib and ronate 3 mg or i.v . placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d . At baseline , 10 weeks and 12 months bone mineral density ( BMD ) and biochemical markers of bone turnover were measured . The primary endpoint , relative change in BMD for the lumbar spine from baseline to 12 months was not different , + 1.5 % for ib and ronate versus + 0.5 % for placebo ( p = 0.28 ) . Ib and ronate demonstrated a significant improvement of BMD in total femur , + 1.3 % versus −0.5 % ( p = 0.01 ) and in the ultradistal radius , + 0.6 % versus −1.9 % ( p = 0.039 ) . Bone formation markers were reduced by ib and ronate , whereas the bone resorption marker , NTX , was reduced in both groups . Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile , virtually maintaining BMD without any loss over 12 months after renal transplantation , whereas adding ib and ronate significantly improved BMD in total femur and ultradistal radius , and also suppressed biomarkers of bone turnover . Ib and ronate was also well tolerated CONTEXT Risedronate , a potent bisphosphonate , has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but , to our knowledge , it has not been evaluated in the treatment of established postmenopausal osteoporosis . OBJECTIVE To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998 . INTERVENTIONS Subjects were r and omly assigned to receive oral treatment for 3 years with risedronate ( 2.5 or 5 mg/d ) or placebo . All subjects received calcium , 1000 mg/d . Vitamin D ( cholecalciferol , up to 500 IU/d ) was provided if baseline levels of 25-hydroxyvitamin D were low . MAIN OUTCOME MEASURES Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessment s of radiographs ; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry . RESULTS The 2.5 mg/d of risedronate arm was discontinued after 1 year ; in the placebo and 5 mg/d of risedronate arms , 450 and 489 subjects , respectively , completed all 3 years of the trial . Treatment with 5 mg/d of risedronate , compared with placebo , decreased the cumulative incidence of new vertebral fractures by 41 % ( 95 % confidence interval [ CI ] , 18%-58 % ) over 3 years ( 11.3 % vs 16.3 % ; P= .003 ) . A fracture reduction of 65 % ( 95 % CI , 38%-81 % ) was observed after the first year ( 2.4 % vs 6.4 % ; P<.001 ) . The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39 % ( 95 % CI , 6%-61 % ) ( 5.2 % vs 8.4 % ; P = .02 ) . Bone mineral density increased significantly compared with placebo at the lumbar spine ( 5.4 % vs 1.1 % ) , femoral neck ( 1.6 % vs -1.2 % ) , femoral trochanter ( 3.3 % vs -0.7 % ) , and midshaft of the radius ( 0.2 % vs -1.4 % ) . Bone formed during risedronate treatment was histologically normal . The overall safety profile of risedronate , including gastrointestinal safety , was similar to that of placebo . CONCLUSIONS These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation . Risedronate is a commonly used third-generation amino-bisphosphonate , but little is known about its effects on the bone health of renal transplant recipients . We r and omly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months . We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment . Treatment with risedronate did not affect bone mineral density ( BMD ) in the overall cohort . In subgroup analyses , it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants . Risedronate did associate with increased osteoid volume and trabecular thickness in male participants , however . There was no evidence for the development of adynamic bone disease . In summary , further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients BACKGROUND Very rapid bone loss , osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion . Glucocorticoids , cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions . Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented , or at least attenuated , by pamidronate and other bisphosphonates . METHOD We prospect ively studied 26 male patients undergoing renal transplantation , and r and omized them to receive either placebo or intravenous pamidronate ( 0.5 mg/kg ) at the time of transplantation and again one month later . All patients received immunosuppression comprising prednisolone , cyclosporine and azathioprine . The bone mineral density ( BMD ) of the second , third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry ( DXA ) . RESULTS Twelve months after transplantation , the mean ( + /- SEM ) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4 % ( P < 0.05 ) . In contrast , patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae . At the femoral neck , placebo-treated patients showed a reduction of BMD of 9 % ( P < 0.005 ) , whereas there was no significant change in the pamidronate treated group . The two study groups had similar patient profiles , serum parathyroid hormone ( PTH ) and aluminium concentrations . After transplantation , comparable falls in the serum creatinine and PTH concentration were found in the two groups . Apart from transient hypocalcemia in two patients , no significant adverse effects of pamidronate were noted . CONCLUSION This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later . The regimen was simple to administer , well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients BACKGROUND We aim ed to investigate different treatment drugs for the prevention of post-transplant bone loss . METHODS Sixty adult male recent renal transplant recipients were enrolled into the study . Patients were r and omized into 4 groups : group I received daily alfacalcidol 0.5 microg PO ; group II received oral alendronate 5 mg/day ; group III received intranasal salmon calcitonin 200 IU every other day ; and group IV was considered a control group . Every patient was supplemented with daily 500 mg oral calcium carbonate . Parameters of bone metabolism were measured before and at 12 months after starting treatment . Bone mineral density ( BMD ) was measured by ( DEXA ) at lumber spine , femoral neck , and forearm before and after treatment period . RESULTS BMD was increased at lumber spine by 2.1 % , 0.8 % , 1.7 % , by 1.8 % , 0.6 % , 1.6 % at femoral neck , and by 3.2 % , 1.9 % , 2.6 % at forearm in groups I , II , and III , respectively , while it decreased by 3.2 % , 3.8 % , and 1.8 % at the same sites , respectively , in control group ( P= < 0.05 ) . iPTH level decreased significantly in group I , while the decrease was insignificant in other groups ( P= 0.003 ) . All other parameters were not statistically significant between treatment groups . Apart from transient hypocalcaemia in 3 patients in group II , and 2 patients in group III , no other significant adverse effects were noted . CONCLUSION This study proves that early bone loss that occurs during the first 12 months after renal transplantation could be prevented by alfacalcidol , calcitonin , or alendronate . Among the treatment groups , alfacalcidol significantly improved the hyperparathyroidism . All treatment drugs are safe and tolerable BACKGROUND Bisphosphonates can prevent bone mineral density loss after renal transplantation , but their effect on trabecular mineralization and bone morphology , two key factors of bone stability , remains unknown . METHODS In a 6-month , r and omized , placebo-controlled study , 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment . At transplantation and after 6 months , mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies . Bone mineral density ( BMD ) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry , and serum biochemical markers of bone metabolism were determined monthly . RESULTS Trabecular calcium content increased significantly in the zoledronic acid group , but remained unchanged in the placebo group . BMD at femoral neck showed no change in the zoledronic acid group , but decreased in the placebo group . BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group . High-turnover bone disease resolved similarly in both groups , as evidence d by a significant decrease of eroded bone surface , osteoclast and osteoblast surface . Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study . Kidney transplant function was stable after zoledronic acid therapy . CONCLUSIONS Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation . The beneficial effect of bisphosphonate therapy is further evidence d by an increase of lumbar spine BMD , and stabilization of femur BMD BACKGROUND Osteopenia and osteoporosis are frequent complications after kidney transplantation . Data for the treatment of low bone mass after kidney transplantation are not available . METHODS To test the efficacy of antiresorptive treatment , 46 patients with osteopenia or osteoporosis after kidney transplantation ( bone mineral density < or = 1.5 SD below normal ) were r and omly assigned to three groups cyclically treated as follows : group 1 with daily oral clodronate ( 800 mg ) and group 2 with daily intranasal calcitonin ( 200 IU ) for 2 weeks every 3 months . These two groups were compared with a control group ( group 3 ) . Every patient was supplemented with 500 mg of calcium per day . Bone mineral density ( BMD ) was measured by dual energy x-ray absorptiometry ( DEXA ) at the lumbar spine and femoral neck before and after the 12-month treatment period . RESULTS BMD at the lumbar spine was increased by 4.6 % in the clodronate group ( n=15 , P=0.005 ) , by 3.2 % in the calcitonin group ( n=16 , P=0.034 ) , and by 1.8 % in the control group ( n=15 , P=0.265 ) . However , the differences in BMD changes among the groups were not statistically significant . During therapy , serum calcium decreased slightly in all groups by 4.6 % ; however , parathyroid hormone values increased significantly in the treatment groups by 116 % . Therapy was well tolerated without impact on graft function . CONCLUSIONS Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation . This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism Abstract : This r and omized , double-masked , placebo-controlled trial evaluated the safety , tolerability and effects on bone mineral density ( BMD ) of alendronate in a large , multinational population of postmenopausal women with low bone mass . At 153 centers in 34 countries , 1908 otherwise healthy , postmenopausal women with lumbar spine BMD 2 st and ard deviations or more below the premenopausal adult mean were r and omly assigned to receive oral alendronate 10 mg ( n = 950 ) or placebo ( n = 958 ) once daily for 1 year . All patients received 500 mg elemental calcium daily . Baseline characteristics of patients in the two treatment groups were similar . At 12 months , mean increases in BMD were significantly ( p≤0.001 ) greater in the alendronate than the placebo group by 4.9 % ( 95 % confidence interval 4.6 % to 5.2 % ) at the lumbar spine , 2.4 % ( 2.0 % to 2.8 % ) at the femoral neck , 3.6 % ( 3.2 % to 4.1 % ) at the trochanter and 3.0 % ( 2.6 % to 3.4 % ) for the total hip . The incidence of nonvertebral fractures was significantly lower in the alendronate than the placebo group ( 19 vs 37 patients with fractures ) , representing a 47 % risk reduction for nonvertebral fracture for alendronate-treated patients ( 95 % confidence interval 10 % to 70 % ; p= 0.021 ) . Incidences of adverse events , including upper gastrointestinal adverse events , were similar in the two groups . Therefore , for postmenopausal women with low bone mass , alendronate is well tolerated and produces significant , progressive increases in BMD at the lumbar spine and hip in addition to significant reduction in the risk of nonvertebral fracture Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures . These are related to underlying renal osteodystrophy , hypophosphatemia , and immunosuppressive treatment regimen . Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation , it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease . A r and omized , prospect i ve , controlled , clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants . Treatment subjects ( PAM ) received pamidronate with vitamin D and calcium at baseline and at months 1 , 2 , 3 , and 6 . Control ( CON ) subjects received vitamin D and calcium only . During months 6 to 12 , the subjects were observed without pamidronate treatment . Biochemical parameters of bone turnover were obtained monthly and , bone mineral density ( BMD ) was obtained at baseline and months 6 and 12 . Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation . PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry . CON had decreased vertebral BMD at 6 and 12 mo ( 4.8 + /- 0.08 and 6.1 + /- 0.09 % , respectively ) . Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo . Bone histology revealed low turnover bone disease in 50 % of the patients at baseline . At 6 mo , all of PAM had adynamic bone disease , whereas 50 % of CON continued to have or developed decreased bone turnover . Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment . Pamidronate treatment was associated with development of adynamic bone histology . Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study Summary This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients . Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation . Introduction The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant ( RT ) population . Methods In this 12-month , r and omized , double-blind , multicenter trial , 39 kidney recipients with diagnosed osteopenia received two doses of 30 mg of disodium pamidronate ( n = 24 ) or placebo ( n = 15 ) , at surgery and 3 months post-RT . All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry ( DXA ) and X-rays were performed at RT , 6 and 12 months post-RT . Biochemical and hormonal determinations were performed before and after treatment . Results Pamidronate significantly reduced spinal bone loss , but no significant benefit was found for the incidence of fractures . Elevated baseline intact parathyroid hormone ( iPTH ) and bone remodeling markers returned to normal levels 3 months post-RT . However , normal procollagen type I N propeptide ( PINP ) concentrations were only maintained in the pamidronate group . After RT , a comparable graft function was observed in both groups according to creatinine values , 25-hydroxyvitamin-D ( 25-OH-D ) levels were improved , and serum calcium levels normalized after a transient fall during the first 3 months . Conclusion A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT INTRODUCTION Steroid-induced osteoporosis is a major problem after organ transplantation . There is considerable evidence that bisphosphonates are effective in decreasing osteoporosis . AIM This prospect i ve study was carried out to see the effects of bisphosphonates on bone mineral density ( BMD ) after successful renal transplantation . MATERIAL AND METHODS Fifty consecutive patients of successful renal transplantation were r and omized into two groups . Group A ( n = 27 ) received 35 mg/wk of Alendronate for 6 months after transplantation . Group B ( n = 23 ) did not receive Alendronate and served as a control . Both groups underwent a pretransplant baseline dual-energy X-ray absorptiometry ( DEXA ) scan of their hips and lumber spines . Both groups received oral calcium and vitamin D supplement . Both groups were matched for the regimen and dose of immunosuppressive drugs . BMD was measured at 3 months and 6 months after transplantation . RESULTS Both groups showed a decline in BMD in early months posttransplantation . However , the 6-month DEXA scans showed a significant rise in BMD in group A as compared to group B. CONCLUSION Bisphosphonates appear to have a beneficial effect on steroid-induced bone loss Background . Reduced bone mineral density ( BMD ) is common in long-term renal transplant recipients and results in a high incidence of fractures . The optimal therapy for these patients is not known . Methods . Baseline BMD determinations were obtained in 211 long-term adult renal transplant recipients . One hundred and seventeen patients with a reduced BMD ( T score ≤ −1 ) were r and omly assigned to treatment with alendronate and calcium ( n=60 ) versus calcitriol and calcium ( n=57 ) . Of these , 46 and 51 patients , respectively , completed 1 year of treatment . Forty-nine patients who were not eligible or did not consent to the trial were followed prospect ively . Results . Reduced baseline BMD ( T score ≤ −1 ) was present in 159 ( 78.7 % ) of patients at the lumbar spine or femur . There was no significant loss of BMD in the prospect ively followed patients during 2.7 years . The average lumbar BMD increased from 0.984±0.149 to 1.025±0.143 g/cm2 ( P < 0.001 ) with alendronate and from 1.014±0.15 to 1.034±0.146 g/cm2 ( P = 0.002 ) with calcitriol . BMD at the femur increased from 0.809±0.092 to 0.836±0.107 g/cm2 ( P < 0.001 ) with alendronate and from 0.830±0.144 to 0.857±0.125 g/cm2 ( P = 0.023 ) with calcitriol . Conclusions . One year of treatment with alendronate or calcitriol , both with calcium supplementation , result ed in significant increases in BMD at the lumbar spine and femur , with a trend toward alendronate being more effective at the spine ( P = 0.082 ) . Further studies are needed to determine whether BMDs continue to increase after 1 year and whether there is any additional benefit to combining vitamin D and alendronate . Larger studies are needed to determine whether treatment decreases fracture rates INTRODUCTION Renal transplant recipients ( RTRs ) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy , hypophosphatemia , and immunosuppression . This process occurs more frequently in the first year after renal transplantation ( RTX ) , result ing in eventual bone loss and fractures . The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX . PATIENTS AND METHODS We prospect ively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years , mean body mass index of 23.6±3.73 , and mean dialysis duration of 25.73±17.67 months . We matched them based on age and sex : the alendronate-treated group received vitamin D ( Vit D ) during the study plus 30 mg alendronate weekly from 1 month after RTX . The control group only received Vit D. We measured serum calcium , phosphate , alkaline phosphatase , blood urea , creatinine , and intact parathyroid hormone ( iPTH ) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine , femur , and radius pretransplant baseline versus 3 and 6 months after RTX . RESULTS At 6 month after RTX , the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 ( P<.01 ) , while it decreased in the control group from 0.897±0.17 to 0.817±0.16 ( P<.001 ) . There was also a significant increase in radius BMD ( P<.001 ) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD ( P<.001 ) in the control group at 6 months . Upon multivariate analysis , there was a significant correlation between alendronate and spine BMD ( r=.45 , P<.001 ) but no linear regression between age , sex , BMI , dialysis duration of or iPTH with femoral , spine , or radius BMD changes at month 6 . CONCLUSION Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX |
13,482 | 28,895,658 | There is no high- quality evidence to inform the comparative effectiveness of LRP or RARP compared to ORP for oncological outcomes .
Urinary and sexual quality of life-related outcomes appear similar .
Overall and serious postoperative complication rates appear similar .
The difference in postoperative pain may be minimal .
Men undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood transfusions . | BACKGROUND Prostate cancer is commonly diagnosed in men worldwide .
Surgery , in the form of radical prostatectomy , is one of the main forms of treatment for men with localised prostate cancer .
Prostatectomy has traditionally been performed as open surgery , typically via a retropubic approach .
The advent of laparoscopic approaches , including robotic-assisted , provides a minimally invasive alternative to open radical prostatectomy ( ORP ) .
OBJECTIVES To assess the effects of laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy compared to open radical prostatectomy in men with localised prostate cancer . | BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) OBJECTIVE To establish a score threshold that constitutes a clinical ly relevant change for each domain of the Exp and ed Prostate Cancer Index Composite ( EPIC ) Short Form ( EPIC-26 ) . Although its use in clinical practice and clinical trials has increased worldwide , the clinical interpretation of this 26-item disease-specific patient-reported quality of life question naire for men with localized prostate cancer would be facilitated by characterization of score thresholds for clinical ly relevant change ( the minimally important differences [ MIDs ] ) . METHODS We used distribution- and anchor-based approaches to establish the MID range for each EPIC-26 domain ( urinary , sexual , bowel , and vitality/hormonal ) based on a prospect i ve multi-institutional cohort of 1201 men treated for prostate cancer between 2003 and 2006 and followed up for 3 years after treatment . For the anchor-based approach , we compared within-subject and between-subject score changes for each domain to an external " anchor " measure of overall cancer treatment satisfaction . RESULTS We found the bowel and vitality/hormonal domains to have the lowest MID range ( a 4 - 6 point change should be considered clinical ly relevant ) , whereas the sexual domain had the greatest MID values ( 10 - 12 ) . Urinary incontinence appeared to have a greater MID range ( 6 - 9 ) than the urinary irritation/obstruction domain ( 5 - 7 ) . CONCLUSION Using 2 independent approaches , we established the MIDs for each EPIC-26 domain . A definition of these MID values is essential for the research er or clinician to underst and when changes in symptom burden among prostate cancer survivors are clinical ly relevant BACKGROUND The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology . We aim ed to compare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks . METHOD In this r and omised controlled phase 3 study , men who had newly diagnosed clinical ly localised prostate cancer and who had chosen surgery as their treatment approach , were able to read and speak English , had no previous history of head injury , dementia , or psychiatric illness or no other concurrent cancer , had an estimated life expectancy of 10 years or more , and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women 's Hospital ( Brisbane , QLD ) . Participants were r and omly assigned ( 1:1 ) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy . R and omisation was computer generated and occurred in blocks of ten . This was an open trial ; however , study investigators involved in data analysis were masked to each patient 's condition . Further , a masked central pathologist review ed the biopsy and radical prostatectomy specimens . Primary outcomes were urinary function ( urinary domain of EPIC ) and sexual function ( sexual domain of EPIC and IIEF ) at 6 weeks , 12 weeks , and 24 months and oncological outcome ( positive surgical margin status and biochemical and imaging evidence of progression at 24 months ) . The trial was powered to assess health-related and domain-specific quality of life outcomes over 24 months . We report here the early outcomes at 6 weeks and 12 weeks . The per- protocol population s were included in the primary and safety analyses . This trial was registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , number ACTRN12611000661976 . FINDINGS Between Aug 23 , 2010 , and Nov 25 , 2014 , 326 men were enrolled , of whom 163 were r and omly assigned to radical retropubic prostatectomy and 163 to robot-assisted laparoscopic prostatectomy . 18 withdrew ( 12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy ) ; thus , 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group . 121 assigned to radical retropubic prostatectomy completed the 12 week question naire versus 131 assigned to robot-assisted laparoscopic prostatectomy . Urinary function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery ( 74·50 vs 71·10 ; p=0·09 ) or 12 weeks post-surgery ( 83·80 vs 82·50 ; p=0·48 ) . Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery ( 30·70 vs 32·70 ; p=0·45 ) or 12 weeks post-surgery ( 35·00 vs 38·90 ; p=0·18 ) . Equivalence testing on the difference between the proportion of positive surgical margins between the two groups ( 15 [ 10 % ] in the radical retropubic prostatectomy group vs 23 [ 15 % ] in the robot-assisted laparoscopic prostatectomy group ) showed that e quality between the two techniques could not be established based on a 90 % CI with a Δ of 10 % . However , a superiority test showed that the two proportions were not significantly different ( p=0·21 ) . 14 patients ( 9 % ) in the radical retropubic prostatectomy group versus six ( 4 % ) in the robot-assisted laparoscopic prostatectomy group had postoperative complications ( p=0·052 ) . 12 ( 8 % ) men receiving radical retropubic prostatectomy and three ( 2 % ) men receiving robot-assisted laparoscopic prostatectomy experienced intraoperative adverse events . INTERPRETATION These two techniques yield similar functional outcomes at 12 weeks . Longer term follow-up is needed . In the interim , we encourage patients to choose an experienced surgeon they trust and with whom they have rapport , rather than a specific surgical approach . FUNDING Cancer Council Queensl and In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Background Prostate cancer is the most common male cancer in the Western world however there is ongoing debate about the optimal treatment strategy for localised disease . While surgery remains the most commonly received treatment for localised disease in Australia more recently a robotic approach has emerged as an alternative to open and laparoscopic surgery . However , high level data is not yet available to support this as a superior approach or to guide treatment decision making between the alternatives . This paper presents the design of a r and omised trial of Robotic and Open Prostatectomy for men newly diagnosed with localised prostate cancer that seeks to answer this question . Methods / design 200 men per treatment arm ( 400 men in total ) are being recruited after diagnosis and before treatment through a major public hospital outpatient clinic and r and omised to 1 ) Robotic Prostatectomy or 2 ) Open Prostatectomy . All robotic prostatectomies are being performed by one surgeon and all open prostatectomies are being performed by one other surgeon . Outcomes are being measured pre-operatively and at 6 weeks and 3 , 6 , 12 and 24 months post-surgery . Oncological outcomes are being related to positive surgical margins , biochemical recurrence + /− the need for further treatment . Non-oncological outcome measures include : pain , physical and mental functioning , fatigue , summary ( preference-based utility scores ) and domain-specific QoL ( urinary incontinence , bowel function and erectile function ) , cancer specific distress , psychological distress , decision-related distress and time to return to usual activities . Cost modelling of each approach , as well as full economic appraisal , is also being undertaken . Discussion The study will provide recommendations about the relative benefits of Robotic and Open Prostatectomy to support informed patient decision making about treatment for localised prostate cancer ; and to assist in treatment services planning for this patient group . Trial registration Background Few studies to date have directly compared outcomes of retropubic ( RRP ) and laparoscopic ( LRP ) radical prostatectomy . We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes . Methods 168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution . Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction ( ED ) of the two cohorts were examined . Results Patients had bilateral , unilateral and no nerve sparing technique performed in 83.3 % , 1.8 % and 14.9 % of cases for RRP and 23.4 % , 22.8 % and 53.8 % of cases for LRP , respectively ( p < 0.001 ) . Overall positive surgical margin rates were 22.2 % among patients who underwent RRP compared to 26.5 % of patients who underwent LRP ( p = 0.435 ) . Based upon pads/day , urinary continence postoperatively was achieved in 83.2 % and 82.8 % for RRP and LRP , respectively ( p = 0.872 ) . Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status . However , postoperatively there were no differences with respect to ED between the two cohorts ( p = 0.151 ) . Based on ICIQ-scores , surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique ( p = 0.001 and p < 0.001 for continuous and stratified data , respectively ) . Conclusions RRP and LRP represent effective surgical approaches for the treatment of clinical ly localized prostate cancer . Pathological outcomes are excellent for both surgical techniques . Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts . Surgeon experience is more relevant than surgical technique applied PURPOSE We prospect ively evaluated the morbidity , and minor and major complications of laparoscopic radical prostatectomy performed by a single surgical team . MATERIAL S AND METHODS Between January 28 , 1998 and February 28 , 2001 , 567 patients 42 to 77 years old ( mean age plus or minus st and ard deviation 63.5 + /- 6 ) with clinical ly localized prostate cancer underwent laparoscopic radical prostatectomy , including 458 ( 80.6 % ) , without lymphadenectomy . Mean body mass index was 25.3 + /- 2.9 ( range 17.3 to 37.5 ) . American Society of Anesthesiologists score was 1 to 3 in 65 % , 27 % and 8 % of cases , respectively . A total of 12 patients ( 2.1 % ) had undergone intra-abdominal surgery below the mesocolon and 40 had undergone urological surgery . Intraoperative and postoperative data were recorded as well as all complications and their severity score within the initial 30 days postoperatively . RESULTS A total of 105 complications were observed in 97 patients ( 17.1 % ) , including 21 major ( 3.7 % ) and 83 minor ( 14.6 % ) complications . Of the patients 21 ( 3.7 % ) underwent reoperation for a postoperative complication , including 10 ( 1.76 % ) who required an intensive care unit stay . Seven cases ( 1.2 % ) were converted to conventional retropubic radical prostatectomy . Mean blood loss was 380 + /- 195 ml . and the overall transfusion rate was 4.9 % . In 2 patients ( 0.3 % ) deep vein thrombosis was associated with another surgical complication but not with pulmonary embolism . Urological , bowel and hemorrhagic complications represented 66.6 % , 16.2 % and 7.6 % ( total 89.4 % ) of all complications , and 20 % , 33.3 % and 33.3 % of all repeat interventions , respectively . CONCLUSIONS Laparoscopic radical prostatectomy was performed according to the defined protocol with no complications in 82.9 % of patients . The morbidity of this approach compares favorably with that of retropubic surgery . Growing experience and knowledge sharing concerning the prevention and early management of these complications would make possible a further decrease in the morbidity of laparoscopic radical prostatectomy Objective —To determine whether minimum clinical ly significant difference in visual analogue scale ( VAS ) pain score varies according to the severity of pain reported . Method — Prospect i ve descriptive study of adult patients in an urban emergency department ( ED ) . On presentation to the ED , patients marked the level of their pain on a 100 mm , non-hatched VAS scale . At 20 minute intervals thereafter they were asked to give a verbal categorical rating of their pain as “ a lot better ” , “ a little better ” , “ much the same ” , “ a little worse ” or “ much worse ” and to mark the level of pain on a VAS scale of the same type as used previously . It was pre-defined that patients with VAS pain scores of 30 mm or less would be categorised as having mild pain , those with scores of 70 mm or more were categorised as having severe pain and those from 31 mm to 69 mm , moderate pain . The minimal clinical ly significant difference ( MCSD ) in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported “ a little worse ” or “ a little better ” pain . Results —156 patients were enrolled in the study , yielding 88 evaluable comparisons where pain was rated as “ a little better ” or “ a little worse ” . The MCSD in VAS score in the group overall was 12 mm ( 95%CI 9 mm to 15 mm ) . MCSD in VAS score for the “ mild pain ” group was 11 mm ( 95%CI 4 mm to 18 mm ) , for the “ moderate pain ” group 14 mm ( 95%CI 10 mm to 18 mm ) and for the severe pain group , 10 mm ( 95%CI 6 mm to 14 mm ) . There is no statistical difference between the MCSD in VAS score between the severity groups . Conclusions —The MCSD in VAS pain score does not differ with the severity of pain being experienced BACKGROUND Despite widespread adoption of the six-item erectile function ( EF ) domain of the International Index of Erectile Function ( IIEF ) as a clinical trial end point , there are currently no objective data on what constitutes a minimal clinical ly important difference ( MCID ) in the EF domain . OBJECTIVE Estimate the MCID for the IIEF EF domain . DESIGN , SETTING , AND PARTICIPANTS Anchor-based MCIDs were estimated using data from 17 r and omized , double-blind , placebo-controlled , parallel-group clinical trials of the phosphodiesterase type 5 inhibitor ( PDE5-I ) tadalafil for 3345 patients treated for 12 wk . MEASUREMENTS The anchor for the MCID is the minimal improvement measure calculated using change from baseline to 12 wk on IIEF question 7 : " Over the past 4 weeks , when you attempted sexual intercourse how often was it satisfactory for you ? " MCIDs were developed using analysis of variance (ANOVA)- and receiver operating characteristic (ROC)-based methods in a subset of studies ( n=11 ) by comparing patients with and without minimal improvement ( n=863 ) . MCIDs were vali date d in the remaining six studies ( n=377 ) . RESULTS AND LIMITATIONS The ROC-based MCID for the EF domain was 4 , with estimated sensitivity and specificity of 0.74 and 0.73 , respectively . MCIDs varied significantly ( p<0.0001 ) according to baseline ED severity ( mild : 2 ; moderate : 5 ; severe : 7 ) . MCIDs consistently distinguished between patients in the validation sample classified as no change or minimally improved overall and by geographic region , ED etiology , and age group . MCIDs did not differ by age group , geographic region , or ED etiology . Current analyses were based on 17 clinical trials of tadalafil . Results need to be replicated in studies using other PDE5-Is or in nonpharmacologic intervention studies . CONCLUSIONS The context ualization of treatment-related changes in terms of clinical ly relevant improvement is essential to underst and ing treatment efficacy , to interpreting results across studies , and to managing patients effectively . This analysis provides , for the first time , anchor-based estimates of MCIDs in the EF domain score of the IIEF PURPOSE Given the lack of r and omized trials comparing robot-assisted radical prostatectomy ( RARP ) and open radical prostatectomy ( ORP ) , we sought to re-examine the outcomes of these techniques using a cohort of patients treated in the postdissemination era . PATIENTS AND METHODS Overall , data from 5,915 patients with prostate cancer treated with RARP or ORP within the SEER-Medicare linked data base diagnosed between October 2008 and December 2009 were abstract ed . Postoperative complications , blood transfusions , prolonged length of stay ( pLOS ) , readmission , additional cancer therapies , and costs of care within the first year after surgery were compared between the two surgical approaches . To decrease the effect of unmeasured confounders , instrumental variable analysis was performed . Multivariable logistic regression analyses were then performed . RESULTS Overall , 2,439 patients ( 41.2 % ) and 3,476 patients ( 58.8 % ) underwent ORP and RARP , respectively . In multivariable analyses , patients undergoing RARP had similar odds of overall complications , readmission , and additional cancer therapies compared with patients undergoing ORP . However , RARP was associated with a higher probability of experiencing 30- and 90-day genitourinary and miscellaneous medical complications ( all P ≤ .02 ) . Additionally , RARP led to a lower risk of experiencing blood transfusion and of having a pLOS ( all P < .001 ) . Finally , first-year reimbursements were greater for patients undergoing RARP compared with ORP ( P < .001 ) . CONCLUSION RARP and ORP have comparable rates of complications and additional cancer therapies , even in the postdissemination era . Although RARP was associated with lower risk of blood transfusions and a slightly shorter length of stay , these benefits do not translate to a decrease in expenditures OBJECTIVES To prospect ively compare intra- and peri-operative outcomes of open radical retropubic prostatectomy ( RRP ) and laparoscopic prostatectomy ( LRP ) by a single surgeon . PATIENTS AND METHODS One-hundred-twenty , consecutive , age-matched patients diagnosed with clinical ly localized prostate cancer were eligible for surgery . Sixty patients underwent RRP and 60 , LRP . Intra- and peri-operative parameters , pathologic findings and early complications were recorded . A vali date d visual analogue scale was used to assess pain in the recovery room , 3 h after the operation and on post-operative days 1 , 2 and 3 . A cystogram was performed on post-operative day 5 . RESULTS Operating time was significantly shorter in the RRP group versus the LRP group ( mean+/-SD , 170+/-34 . 2 vs 235+/-49.9 min , p<0.001 ) . Blood loss was significantly less in the LRP group versus the RRP group ( mean+/-SD , 853.3+/-485 vs 257.3+/-177 ml , p<0.001 ) , but no patient in either group underwent early re-intervention for bleeding . The RRP group showed a trend for higher use of analgesia . A watertight anastomosis was shown at cystourethrography and the catheter removed in 86 % and 66 % of LRP and RRP patients , respectively . The overall percentage of post-operative complications and positive margins were comparable . CONCLUSION Laparoscopic prostatectomy is an attractive alternative to open prostatectomy , offering the advantages of reduced blood loss and safe early catheter removal . Furthermore , the laparoscopic procedure proved to be safe oncologically . Long-term follow-up is required to compare functional results in terms of continence and potency Holmberg L , Bill-Axelson A , Helgesen F , Salo JO , Folmerz P , Haggman M , et al. A r and omized trial comparing radical prostatectomy with watchful waiting in early prostate cancer . N Engl J Med 2002;347 : 781 - 9 . Background : The clinical importance and disease burden of prostate cancer — the PURPOSE We evaluate the impact of GreenLight High-Performance System ( HPS ™ ) laser photoselective vaporization prostatectomy ( PVP ) on sexual function after treatment of lower urinary tract symptoms ( LUTS ) secondary to benign prostatic hyperplasia ( BPH ) . PATIENTS AND METHODS We prospect ively evaluated our initial single surgeon experience with GreenLight HPS ™ laser PVP . All patients had American Urological Association Symptom Score ( AUASS ) , Sexual Health Inventory for Men ( SHIM ) , maximum flow rate ( Qmax ) , and postvoid residual ( PVR ) determinations . Transurethral PVP was performed using a 120W GreenLight HPS ™ side-firing laser system . AUASS , SHIM , Qmax , and PVR were evaluated 1 , 4 , 12 , 24 , and 52 weeks postsurgery . Wilcoxon signed rank test and the Student t-test were used to assess the changes from baseline . RESULTS Seventy-two patients completed 52 weeks of follow-up , having a median age of 69 ( 45 - 89 ) years . The median prostate volume was 62 ( 21 - 263 ) mL. Median AUASS improved significantly from 23 to 8 , 6 , 5 , 5 , and 4 ( P < 0.05 ) at 1 , 4 , 12 , 24 , and 52 weeks , respectively . Median SHIM changed from 15 to 12 , 16 , 19 , 16 , and 17 during the follow-up period ( P = 0.032 , 0.427 , 0.074 , 0.081 , and 0.259 ) . Minimum change ( 0 ± 5 ) in SHIM occurred in 85.5 % , 90.5 % , 78.8 % , 77.5 % , and 73.7 % of patients ; 11.3 % , 6.3 % , 6.0 % , 4.8 % , and 7.0 % of patients had deterioration of erectile function ( SHIM reduction > 5 ) ; and 3.2 % , 3.2 % , 15.2 % , 17.7 % , and 19.3 % of patients had improvement of erectile function ( SHIM increase > 5 ) . Incidence of new-onset retro grade ejaculation was 30 % . CONCLUSION GreenLight HPS ™ laser PVP appears to not have a detrimental effect on erectile function PURPOSE To cure localized prostate cancer , the entire prostate must be eliminated , which is what all forms of treatment must achieve . Although there is no better way to cure localized disease than total surgical removal , the challenge is whether this can be accomplished with acceptable morbidity . MATERIAL S AND METHODS To evaluate quality of life following radical retropubic prostatectomy , patient reported outcomes of 62 men who underwent radical retropubic prostatectomy at this institution were recorded during the first 18 months of followup . By 18 months 93 % of the patients were dry ( wearing no pads ) and 93 % to 98 % characterized urinary bothersomeness as none or small . Potency , defined as the ability to achieve unassisted intercourse with or without the use of sildenafil , improved gradually and by 18 months 86 % of the patients were potent and 84 % considered sexual bothersomeness as none or small . In an effort to improve the outcome of radical prostatectomy , the surgical procedures on these 62 patients were videotaped prospect ively . The videotapes were review ed 18 months after the study was initiated and 4 specific steps in the surgical procedure were correlated with patient reported outcomes . Surgeons who wish to improve their outcomes should consider using this technique to identify in their own h and s other important arbitrary variations that may improve results . RESULTS The probability of maintaining an undetectable prostate specific antigen was evaluated in men with similar pathological stages of disease who were or were not potent following surgery . Men who were potent had the same outcome as those who were impotent , supporting the premise that preservation of sexual function does not compromise cancer control . Cancer control and quality of life following brachytherapy were analyzed and the following conclusions were made : 1 ) high dose intensification is necessary if radiation therapy is expected to cure prostate cancer but I doubt that any form of radiotherapy will produce durable cancer control for 20 to 30 years ; 2 ) although brachytherapy is rarely adequate as monotherapy , I am not certain that brachytherapy combined with external beam radiotherapy is any better than 3-dimensional conformal therapy alone and the side effects are uncertain , and 3 ) I believe that a prostate specific antigen nadir of less than 0.2 ng./ml . is necessary to confirm an adequate response to radiation . CONCLUSIONS I believe that there is no better way to cure organ confined cancer than total surgical removal . Today continence and potency rates should be high . If not , a review of intraoperative videotapes of successful and unsuccessful cases can improve results . In men treated with radiotherapy stringent criteria for treatment response and quality of life outcomes are needed The terms applicability , generalizability , external validity and transferability are related , sometimes used interchangeably and have in common that they lack a clear and consistent definition in the classic epidemiological literature . However , all of these terms generally describe one overarching theme : whether or not available research evidence can be directly utilized to answer the healthcare questions at h and , ideally supported by a judgment about the degree of confidence for this utilization . This concept has been called directness . The objectives of this paper were to delineate how non-r and omized studies ( NRS ) inform judgments in relation to directness and the concepts that it encompasses in the context of systematic review s. We will briefly review what is known and describe the theoretical and practical issues as well as offer guidance to those tackling the challenges of judging directness and using research evidence to answer healthcare questions with evidence from NRS . In particular , we suggest a framework in which authors can use NRS as a complement , sequence or replacement for r and omized controlled trials ( RCTs ) by focusing on judgments about the population , intervention , comparison and outcomes . Authors of systematic review s will use NRS to complement judgments about the inconsistencies , the rationale and credibility of subgroup analysis , the baseline risk estimates for the determination of absolute benefits and downsides , and the directness of surrogate outcomes . This evidence includes context ual or supplementary evidence . Authors of systematic review and other summaries of the evidence use NRS as sequential evidence to provide evidence when insufficient evidence is available for an outcome from RCTs , but NRS evidence is available ( e.g. , long-term harms ) . Use of evidence from NRS may also serve to replace RCT evidence when NRS provide equivalent ( or potentially higher ) confidence in the evidence ( i.e. quality ) compared to indirect evidence from RCTs . These judgments will be made in the context of other domains that influence the overall quality of the body of evidence , including the risk of bias , publication bias ( i.e. limitations in the detailed study design and execution ) , inconsistency , imprecision and factors that increase our confidence in effects . This article will support systematic review ers in their interaction with decision makers , that is , those who use the systematic review to develop guidelines , address health policy makers , and make clinical decisions , by making these judgments transparent . Copyright © 2013 John Wiley & Sons , Objective : To evaluate the technical feasibility , oncological efficacy and intraoperative and postoperative morbidity of laparoscopic radical prostatectomy . Method : We describe an original technique of laparoscopic radical prostatectomy performed in 40 patients between 26th January and 12th October , 1998 . Results : Radical prostatectomy was performed entirely by laparoscopy in 35 patients ( 87.5 % ) and only one conversion was performed in the last 26 patients ( 4 % ) . Pelvic lymphadenectomy was performed in the light of preoperative staging data in 14 patients ( 35 % ) . The median total operating time was 270 min . The only major complication was a rectal injury ( patient 8) , sutured laparoscopically with an uneventful postoperative course . Postoperative vesical catheterization lasted an average of 7.65 days . Seven patients were transfused ( 17.5 % ) with an average of 2.8 units of packed cells ( range : 2–3 ) . The reduction of postoperative pain is an element allowing for a rapid discharge of the patients by the 3rd postoperative day . The oncological results were as follows : 36 patients had a pT2 tumor ( 90 % ) ; prostate tumor was staged as N0 in 14 cases and NX in 26 cases . Surgical margins were negative in 33 patients ( 82.5 % ) . Two patients had a doubtful resection margin ( 1 at the apex and 1 at the bladder neck ) and 5 patients had positive margins . The last PSA level was undetectable ( < 0.1 ng/ml ) in 26 ( 89.7 % ) of the 29 patients in whom PSA level was available more than 1 month after the operation . Functional results are not yet available and will be published later . Conclusions : Radical prostatectomy is an operation which can be routinely performed by laparoscopy by a team experienced with this technique . Operative and postoperative morbidity was low . Short-term oncological data appear identical to the results of conventional retropubic surgery . The improvement of operative visibility was considerable allowing a much more precise dissection . The laparoscopic approach appears to represent a technical improvement of the radical prostatectomy if the functional results of this operation improve parallel to the quality of dissection . A long-term follow-up is needed to define definitively the place of this new approach to radical prostatectomy OBJECTIVE Our aim was to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the screening , diagnosis , and treatment of clinical ly localised cancer of the prostate ( PCa ) . METHODS The working panel performed a literature review of the new data emerging from 2007 to 2010 . The guidelines were up date d , and level of evidence and grade of recommendation were added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. RESULTS A full version is available at the EAU office or Web site ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy . PSA doubling time in <3 yr or a biopsy progression indicates the need for active intervention . In men with locally advanced PCa in whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) with equivalent oncologic efficacy . Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial . Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables . Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk PCa , respectively . For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice . Follow-up after local therapy is largely based on PSA , and a disease-specific history with imaging is indicated only when symptoms occur . CONCLUSIONS The knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice A r and omised trial of robotic and open prostatectomy commenced in October 2010 and is progressing well . Clinical and quality of life outcomes together with economic costs to individuals and the health service are being examined critically to compare outcomes |
13,483 | 32,294,111 | The last remaining study included both ICU and non-ICU subgroups and showed conflicting results , with a positive association for non-ICU patients but no association for ICU patients .
Our systematic review did not find a strong evidence for the association between ED boarding and IHM but there is a tendency toward this association . | IMPORTANCE Boarding in the emergency department ( ED ) is a critical indicator of quality of care for hospitals .
It is defined as the time between the admission decision and departure from the ED .
As a result of boarding , patients stay in the ED until inpatient beds are available ; moreover , boarding is associated with various adverse events .
STUDY OBJECTIVE The objective of our systematic review was to determine whether ED boarding ( EDB ) time is associated with in-hospital mortality ( IHM ) . | OBJECTIVE Survival from acute coronary syndromes and major trauma has been shown to depend on timely access to definitive treatment . We sought to identify the significance of intensive care unit ( ICU ) admission delay ( lead-time ) on the outcome of critically-ill medical patients with other diagnoses . METHODS From 1 January 1997 to 31 December 2003 , a prospect i ve cohort study was performed in critically-ill patients requiring mechanical ventilatory support ( MV ) and /or renal replacement therapy ( RRT ) , admitted directly to the Northern Hospital ICU within 24 hours of arrival in the emergency department ( ED ) . Patients were excluded if , a ) they were admitted following surgery , major trauma or transfer from another hospital , or b ) their duration of ICU stay was < 8 hours . Data collected included de-identified patient demographics , final diagnosis , APACHE II mortality risk ( pm ) and lead-time ( i.e. difference between times of entrance to the ED and ICU . ) The primary outcome measure was hospital discharge status . RESULTS Six hundred and nineteen consecutive ICU admissions from the ED met the inclusion criteria and required MV ( n = 557 ) and /or RRT ( n = 162 . ) Non-survivors were older ( median age 73 vs. 54 yrs ) and sicker ( median pm 0.72 vs. 0.23 ) compared with survivors . Multivariate analysis using logistic regression identified lead-time as a significant predictor of mortality ( RR = 1.06 per hour , 95 % CI = 1.01 - 1.10 ; p=0.015 ) in addition to age , diagnosis and illness severity . CONCLUSIONS ICU admission delay ( lead-time ) is associated with a greater mortality-risk in critically ill medical patients requiring MV and /or RRT Introduction When the number of patients who require intensive care is greater than the number of beds available , intensive care unit ( ICU ) entry flow is obstructed . This phenomenon has been associated with higher mortality rates in patients that are not admitted despite their need , and in patients that are admitted but are waiting for a bed . The purpose of this study is to evaluate if a delay in ICU admission affects mortality for critically ill patients . Methods A prospect i ve cohort of adult patients admitted to the ICU of our institution between January and December 2005 were analyzed . Patients for whom a bed was available were immediately admitted ; when no bed was available , patients waited for ICU admission . ICU admission was classified as either delayed or immediate . Confounding variables examined were : age , sex , originating hospital ward , ICU diagnosis , co-morbidity , Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , therapeutic intervention , and Sequential Organ Failure Assessment ( SOFA ) score . All patients were followed until hospital discharge . Results A total of 401 patients were evaluated ; 125 ( 31.2 % ) patients were immediately admitted and 276 ( 68.8 % ) patients had delayed admission . There was a significant increase in ICU mortality rates with a delay in ICU admission ( P = 0.002 ) . The fraction of mortality risk attributable to ICU delay was 30 % ( 95 % confidence interval ( CI ) : 11.2 % to 44.8 % ) . Each hour of waiting was independently associated with a 1.5 % increased risk of ICU death ( hazard ratio ( HR ) : 1.015 ; 95 % CI 1.006 to 1.023 ; P = 0.001 ) . Conclusions There is a significant association between time to admission and survival rates . Early admission to the ICU is more likely to produce positive outcomes STUDY OBJECTIVE We describe the frequency of undesirable events among patients boarding at a single , urban , tertiary , teaching emergency department ( ED ) through retrospective chart abstract ion . METHODS This was a chart review of all patients admitted during 3 r and omly selected days in 2003 ( n=162 ) to track the frequency of undesirable events such as missed relevant home medications , missed laboratory test results , arrhythmias , or other adverse events . RESULTS One hundred fifty-one charts were abstract ed ( 93.2 % ) ; 27.8 % had an undesirable event , 17.9 % missed a relevant home medication , and 3.3 % had a preventable adverse event . There was a higher frequency of undesirable events among older patients ( 35.9 % , aged > 50 years ; 7.3 % , aged 20 to 49 years ; 28.6 % , aged 0 to 19 years ) and those with more comorbidities ( 44.4 % among Charlson score > or=3 ; 30.8 % score 2 ; 36.1 % score 1 ; 14.5 % score 0 ) . CONCLUSION A substantial frequency of undesirable events occurs while patients board in the ED . These events are more frequent in older patients or those with more comorbidities . Future studies need to compare the rates of undesirable events among patients boarding in the ED versus inpatient units Background The dem and for critical care beds is increasing out of proportion to bed availability . As a result , some critically ill patients are kept in the Emergency Department ( ED boarding ) awaiting bed availability . The aim of our study is to examine the impact of boarding in the ED on the outcome of patients admitted to the Intensive Care Unit(ICU ) . Methods This was a retrospective analysis of ICU data collected prospect ively at King Abdulaziz Medical City , Riyadh from ED between January 2010 and December 2012 and all patients admitted during this time were evaluated for their duration of boarding . Patients were stratified into three groups according to the duration of boarding from ED . Those admitted less than 6 h were classified as Group I , between 6 and 24 h , Group II and more than 24 h as Group III . We carried out multivariate analysis to examine the independent association of boarding time with the outcome adjusting for variables like age , sex , APACHE , Mechanical ventilation , Creatinine , Platelets , INR . Results During the study period , 940 patients were admitted from the ED to ICU , amongst whom 227 ( 25 % ) were admitted to ICU within 6 h , 358 ( 39 % ) within 6–24 h and 355 ( 38 % ) after 24 h. Patients admitted to ICU within 6 h were younger [ 48.7 ± 22.2(group I ) years , 50.6 ± 22.6 ( group II ) , 58.2 ± 20.9 ( group III ) ( P = 0.04)]with less mechanical ventilation duration [ 5.9 ± 8.9 days ( Group I ) , 6.5 ± 8.1 ( Group II ) and 10.6 ± 10.5 ( Group III ) , P = 0.04 ] . There was a significant increase in hospital mortality [ 51(22.5 ) , 104(29.1 ) , 132(37.2 ) , P = 0.0006 ) and the ICU length of stay(LOS ) [ 9.55 days ( Group I ) , 9.8 ( Group II ) and 10.6 ( Group III ) , ( P = 0.002 ) ] with increase in boarding duration . In addition , the delay in admission was an independent risk factor for ICU mortality(OR for group III vs group I is 1.90 , P = 0.04 ) and hospital mortality(OR for group III vs Group I is 2.09 , P = 0.007 ) . Conclusion Boarding in the ED is associated with higher mortality . This data highlights the importance of this phenomenon and suggests the need for urgent measures to reduce boarding and to improve patient flow OBJECTIVE We hypothesized that critically ill patients who remain in the ED for more than 24 hours experience worse outcomes and longer lengths of stay than those transferred to the medical intensive care unit ( MICU ) within 24 hours . METHODS Medical records were examined of all patients admitted to the MICU directly from the ED of a 325-bed community teaching hospital between 2001 and 2002 . RESULTS Of 443 patients , 104 remained in the ED for 24 hours or longer ( ED > or=24 ) before being transferred to the MICU . There were no significant differences in demographic characteristics of the 339 who were in the ED for less than 24 hours ( ED < 24 ) as compared with ED > or=24 . APACHE II scores were 18.9+/-1.0 for a r and om sample of ED<24 and 20.5+/-0.9 for ED > or=24 ( P=.2 ) . Lengths of hospital stay were 10.9+/-0.8 days for ED<24 and 9.8+/-0.9 days for ED > or=24 ( P=.7 ) . Mortality rates were 26.8 % for ED<24 and 26.9 % for ED > or=24 ( P=.5 ) . CONCLUSIONS These data suggest that outcomes of critically ill patients transferred from the ED to our MICU within 24 hours were not better than those who remained in the ED for longer duration s. Larger studies are required to examine this hypothesis OBJECTIVE To assess the impact of delay in emergency department ( ED ) on outcome of critically ill patients admitted to the medical intensive care unit ( MICU ) . Outcome was defined as hospital mortality and as health-related quality of life ( HRQoL ) at 6 months after intensive care assessed by the 15D measure . The 15D is a generic , 15-dimensional , st and ardized measure of HRQoL. We hypothesized that prolonged stay in the ED is related to worse outcome . DESIGN AND SETTING A prospect i ve follow-up cohort study in university hospital . SUBJECTS All consecutive 1675 patients admitted to the MICU between July 2002 and June 2004 . RESULTS The 15D question naire was mailed to all patients alive at 6 months after admission . Of all MICU patients , 64 % were admitted from ED . The mean length of stay in the ED was 6.2 h ( 95%CI 5.9 - 6.5 h ) . The hospital mortality rate was 24.4 % ( 20.0 % in the ED vs. 33.0 % in the non-ED cohort , P < 0.001 ) and it was associated with higher age and degree of physiological derangement at admission . Neither the length of ED stay was associated with hospital mortality ( P = 0.82 ) nor with HRQoL at 6 months after MICU admission ( P = 0.34 ) . Altogether , HRQoL at 6 months was significantly lower compared with the age- and sex-matched general population ( P < 0.001 ) . CONCLUSIONS In a university hospital , the length of ED stay was not associated with the outcome of critically ill medical patients . However , we feel that the effect of ED treatment and delay on outcome and outcome prediction in the critically ill patients deserves further evaluation We hypothesized that a " closed " intensive care unit ( ICU ) was more efficient that an " open " one . ICU admissions were retrospectively analyzed before and after ICU closure at one hospital ; prospect i ve analysis in that ICU with an open ICU nearby was done . Illness severity was gauged by the Mortality Prediction Model ( MPM0 ) . Outcomes included mortality , ICU length of stay ( LOS ) , hospital LOS , and mechanical ventilation ( MV ) . There were no differences in age , MPM0 , and use of MV . ICU and hospital LOS were lower when " closed " ( ICU LOS : prospect i ve 6.1 versus 12.6 d , p < 0.0001 ; retrospective 6.1 versus 9.3 d , p < 0.05 ; hospital LOS : prospect i ve 19.2 versus 33.2 d , p < 0.008 ; retrospective 22.2 versus 31.2 d , p < 0.02 ) . Days on MV were lower when " closed " ( prospect i ve 2.3 versus 8.5 d , p < 0.0005 ; retrospective 3.3 versus 6.4 d , p < 0.05 ) . Pooled data revealed the following : MV predicted ICU LOS ; ICU organization and MPM0 predicted days on MV ; MV and ICU organization predicted hospital LOS ; mortality predictors were open ICU ( odds ratio [ OR ] 1.5 , p < 0.04 ) , MPM0 ( OR 1.16 for MPM0 increase 0.1 , p < 0.002 ) , and MV ( OR 2.43 , p < 0.0001 ) . We conclude that patient care is more efficient with a closed ICU , and that mortality is not adversely affected OBJECTIVES The authors assessed the effect of emergency department ( ED ) crowding on the nontreatment and delay in treatment for analgesia in patients who had acute abdominal pain . METHODS This was a secondary analysis of prospect ively enrolled nonpregnant adult patients presenting to an urban teaching ED with abdominal pain during a 9-month period . Each patient had four vali date d crowding measures assigned at triage . Main outcomes were the administration of and delays in time to analgesia . A delay was defined as waiting more than 1 hour for analgesia . Relative risk ( RR ) regression was used to test the effects of crowding on outcomes . RESULTS A total of 976 abdominal pain patients ( mean [ + /-st and ard deviation ] age = 41 [ + /-16.6 ] years ; 65 % female , 62 % black ) were enrolled , of whom 649 ( 67 % ) received any analgesia . Of those treated , 457 ( 70 % ) experienced a delay in analgesia from triage , and 320 ( 49 % ) experienced a delay in analgesia after room placement . After adjusting for possible confounders of the ED administration of analgesia ( age , sex , race , triage class , severe pain , final diagnosis of either abdominal pain not otherwise specified or gastroenteritis ) , increasing delays in time to analgesia from triage were independently associated with all four crowding measures , comparing the lowest to the highest quartile of crowding ( total patient-care hours RR = 1.54 , 95 % confidence interval [ CI ] = 1.32 to 1.80 ; occupancy rate RR = 1.64 , 95 % CI = 1.42 to 1.91 ; inpatient number RR = 1.57 , 95 % CI = 1.36 to 1.81 ; and waiting room number RR = 1.53 , 95 % CI = 1.31 to 1.77 ) . Crowding measures were not associated with the failure to treat with analgesia . CONCLUSIONS Emergency department crowding is associated with delays in analgesic treatment from the time of triage in patients presenting with acute abdominal pain Objective To explore the relationship between hospital mortality and time spent by patients on hospital wards before admission to the intensive care unit ( ICU ) . Design Observational study of prospect ively collected data . Setting Participating intensive care units within the North East Thames Regional Data base . Patients and participants Patients , 7,190 , admitted to ICU from the hospital wards of 24 hospitals . Interventions None . Measurements and results Of ICU admissions from the wards , 40.1 % were in hospital for more than 3 days and 11.7 % for more than 15 days . ICU patients who died in hospital were in- patients longer ( p=0.001 ) before admission ( median 3 days ; interquartile range 1–9 ) than those discharged alive ( median 2 days ; interquartile range 1–5 ) . Hospital mortality increased significantly ( p<0.0001 ) in relation to time on hospital wards before ICU : 47.1 % ( st and ardised mortality ratio 1.09 ) for patients in hospital 0–3 days before ICU admission up to 67.2 % ( st and ardised mortality ratio 1.39 ) for patients on the wards for more than 15 days before ICU . Length of stay before ICU admission was an independent predictor of hospital mortality ( odds ratio per day 1.019 ; 95 % confidence interval 1.014–1.024 ) . There were significant differences ( p<0.001 ) in patient age , APACHE II score and predicted mortality in relation to time on wards before ICU admission . Conclusions Mortality was high among patients admitted from the wards to ICU ; many were in patients for days or weeks before admission . The longer these patients were in hospital before ICU admission , the higher their mortality . Patients with delayed admission differed in some respects compared to those admitted earlier OBJECTIVE To evaluate the influence of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease . DESIGN Data were collected prospect ively over a 1-yr period ( study year ) and compared with previously collected prospect i ve data recorded in our chronic obstructive pulmonary disease data base during a 5-yr period . SETTING The medical intensive care unit ( ICU ) of a university hospital . PATIENTS Eighty-seven patients with chronic obstructive pulmonary disease . Fifteen patients had chronic obstructive pulmonary disease that required mechanical ventilation for acute exacerbation of their disease ( study year ) , and 72 were patients with chronic obstructive pulmonary disease from the previously collected data . INTERVENTIONS The ICU course ( duration of mechanical ventilation , mortality ) was recorded , as well as several respiratory parameters ( pulmonary function tests and arterial blood gases in stable conditions , and nutritional status ) , and they were compared with an " index of nursing . " MEASUREMENTS AND MAIN RESULTS We developed an " index of nursing " , comparing the effective workforce of the nurses ( number and qualifications ) with the ideal workforce required by the number of patients and the severity of their diseases . A value of 1.0 represented a perfect match between the needed and the effectively present nurses , whereas a lesser value signified a diminished available workforce . This index was compared with the complications and duration of weaning from mechanical ventilation . During the first 5 yrs , the duration of mechanical ventilation increased progressively from 7.3 + /- 8.0 to 38.2 + /- 25.8 days ( p = .006 ) . A significant inverse correlation between the duration of mechanical ventilation and the nursing index ( p = .025 ) was found . In the sixth comparative year , the number of nurses increased ( nursing index = 1.05 ) and the duration of mechanical ventilation decreased to 9.9 + /- 13 days ( p < .001 , yr 5 vs. yr 6 ) . CONCLUSIONS The quality of nursing appears to be a measurable and critical factor in the weaning from mechanical ventilation of patients with chronic obstructive pulmonary disease . Below a threshold in the available workforce of ICU nurses , the weaning duration of patients with chronic obstructive pulmonary disease increases dramatically . Therefore , very close attention should be given to the education and number of ICU nurses STUDY OBJECTIVE To determine whether nonemergency patients can be prospect ively identified by triage nurses and safely triaged out of the emergency department without treatment . METHODS All adult patients ( 16 years or older ) who presented to a university ED were provided an evaluation by a triage nurse . For a patient 's case to be defined as nonemergency , four criteria were required : vital signs within a specific range , presence of 1 of 50 potentially nonemergent chief complaints , absence of key indicators found on screening examination , and absence of chest pain , abdominal pain , any severe pain , and inability to walk . Between July 1988 and July 1993 , patients who satisfied these criteria were defined as nonemergency , refused care in the ED , and triaged out of the ED . Patients were referred to off-site clinics . The clinics had agreed to see patients in advance of the study , and the referral lists were frequently up date d. Outcome data were obtained by telephone surveys to both triaged individuals and other health care providers . RESULTS In this 5-year study , 176,074 adults presented to the ambulatory triage area in the ED , and 31,165 ( 18 % ) were defined as nonemergency , were not treated , and were referred elsewhere . Letters and telephone calls to all referral clinics , eight local EDs , and the coroner 's office identified no instances of gross mistriage and only a small number of insignificant adverse outcomes . Telephone follow-up to individuals triaged away was successful in 34 % of calls and showed that 39 % of persons received care elsewhere on the same day , 35 % received care within 3 days , and 26 % decided not to seek medical care . A group of 1.0 % sought care at other hospital EDs for minor complaints . CONCLUSION A subset of patients with nonemergency problems can be prospect ively identified and triaged out of the ED without significant adverse outcomes provided there is community support for follow-up care STUDY OBJECTIVE We identify differences in the process of care for admitted patients who board in the emergency department ( ED ) compared with admitted patients who are transferred to an inpatient care area . METHODS This is a retrospective study of a r and om sample of adult patients admitted through the ED at one urban teaching hospital . Patients who boarded in the ED for at least 6 hours after the decision to admit were matched to similar control patients . Data were collected by 2 trained medical students using a st and ardized data abstract ion tool . All physician orders placed in the first 24 hours after admission orders were signed were identified . The medical record was search ed for documentation of order completion . Each order was classified as being executed on time , delayed , or missed . RESULTS Of 848 patients screened for inclusion in the study , a total of 145 matched case-control pairs were included , making a total of 290 patients . A total of 9,260 distinct orders were identified . Use of a generalized estimating equation that controlled for correlation within subjects showed that orders were less likely to be completed on time for boarders than for controls ( odds ratio [ OR ] 0.46 ; 95 % confidence interval [ CI ] 0.38 to 0.55 ) . Among boarders , orders were more likely to be either delayed ( OR 1.84 ; 95 % CI 1.46 to 2.30 ) or missed entirely ( OR 2.58 ; 95 % CI 1.94 to 3.42 ) . Boarders missed a median of 11 orders during their first 24 hours of admission compared with 6 orders for control patients . CONCLUSION This study detected an important process difference between boarded patients compared with control patients , which could explain previously suggested outcome differences between these 2 groups . This provides additional support for efforts to move patients to inpatient care areas in a timely fashion rather than board in the ED OBJECTIVE To compare the effects of change from an open to a closed intensive care unit ( ICU ) format on clinical outcomes , re source utilization , teaching , and perceptions regarding quality of care . DESIGN Prospect i ve cohort study ; prospect i ve economic evaluation . SETTING Medical ICU at a university-based tertiary care center . For the open ICU , primary admitting physicians direct care of patients with input from critical care specialists via consultation . For the closed ICU , critical care specialists direct patient care . PATIENTS Consecutive sample s of 124 patients admitted under an open ICU format and 121 patients admitted after changing to a closed ICU format . Readmissions were excluded . MAIN OUTCOME MEASURES Comparison of hospital mortality with mortality predicted by the Acute Physiology and Chronic Health Evaluation II ( APACHE II ) system ; duration of mechanical ventilation ; length of stay ; patient charges for radiology , laboratory , and pharmacy departments ; vascular catheter use ; number of interruptions of formal teaching rounds ; and perceptions of patients , families , physicians , and nurses regarding quality of care and ICU function . RESULTS Mean + /- SD APACHE II scores were 15.4 + /- 8.3 in the open ICU and 20.6 + /- 8.6 in the closed ICU ( P=.001 ) . In the closed ICU , the ratio of actual mortality ( 31.4 percent ) to predicted mortality ( 40.1 percent ) was 0.78 . In the open ICU , the ratio of actual mortality ( 22.6 percent ) to predicted mortality ( 25.2 percent ) was 0.90 . Mean length of stay for survivors in the open ICU was 3.9 days , and mean length of stay for survivors in the closed ICU was 3.7 days ( P=.79 ) . There were no significant differences between periods in patient charges for radiology , laboratory , or pharmacy re sources . Nurses were more likely to say that they were very confident in the clinical judgment of the physician primarily responsible for patient care in the closed ICU compared with the open ICU ( 41 percent vs 7 percent ; P<.Ol ) , and nurses were the group most supportive of changing to a closed ICU format before and after the study . CONCLUSIONS Based on comparison of actual to predicted mortality , changing from an open to a closed ICU format improved clinical outcome . Although patients in the closed ICU had greater severity of illness , re source utilization did not increase Prospect i ve and retrospective access block hospital intervention studies from 1998 to 2008 were review ed to assess the evidence for interventions around access block and ED overcrowding , including over 220 documents reported in Medline and data extracted from The State of our Public Hospitals Reports . There is an estimated 20 - 30 % increased mortality rate due to access block and ED overcrowding . The main causes are major increases in hospital admissions and ED presentations , with almost no increase in the capacity of hospitals to meet this dem and . The rate of available beds in Australia reduced from 2.6 beds per 1000 ( 1998 - 1999 ) to 2.4 beds per 1000 ( 2002 - 2007 ) in 2002 , and has remained steady at between 2.5 - 2.6 beds per 1000 . In the same period , the number of ED visits increased over 77 % from 3.8 million to 6.74 million . Similarly , the number of public hospital admissions increased at an average rate of 3.4 % per year from 3.7 to 4.7 million . Compared with 1998 - 1999 rates , the number of available beds in 2006 - 2007 is thus similar ( 2.65 vs 2.6 beds per 1000 ) , but the number of ED presentations has almost doubled . All patient groups are affected by access block . Access block interventions may temporarily reduce some of the symptoms of access block , but many measures are not sustainable . The root cause of the problem will remain unless hospital capacity is addressed in an integrated approach at both national and state levels |
13,484 | 28,232,473 | Conclusions The prevalence of gastro-oesophageal reflux symptoms varied strikingly among countries , even when similar definitions were used to define their presence .
Prevalence was significantly higher in subjects ≥50 years , smokers , NSAID users and obese individuals , although these associations were modest | Objectives Gastro-oesophageal reflux symptoms are common in the community , but there has been no definitive systematic review and meta- analysis of data from all studies to estimate their global prevalence , or potential risk factors for them . | Objective . Gastroesophageal reflux disease has been reported to be a common burden on health-care re sources in the Western world , but its manifestations in the general population are as yet unclear . The aim of this study was to estimate the prevalence of , and to identify the risk factors for gastroesophageal reflux symptoms ( GERS ) and erosive esophagitis ( EE ) in the adult population of two Swedish municipalities . Material and methods . A r and om sample ( n=3000 ) of the adult population ( 20–81 years of age ) of two Swedish municipalities ( n=21,610 ) was surveyed using a vali date d postal question naire assessing gastrointestinal symptoms . The response rate was 74 % . A sub sample ( n=1000 ) of the responders was subsequently invited , in r and om order , for esophago-gastro-duodenoscopy with evaluation of GERS , risk factors and tests for Helicobacter pylori . Results . GERS were reported by 40.0 % and EE was found in 15.5 % of the population that had undergone endoscopy . Of those with GERS , 24.5 % had EE while 36.8 % of those with EE reported no GERS . Hiatus hernia and obesity remained significant risk factors for GERS and /or EE , with or without symptoms in a main effect model ( OR up to 14 at EE ) . Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection ( OR=1.71 ( 1.23–2.38 ) ) . Conclusions . GERS and EE ( of which one-third is asymptomatic ) are highly prevalent in the Swedish adult population . H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux AIM To clarify the association between physical activity and gastroesophageal reflux disease ( GERD ) in non-obese and obese people . METHODS A Swedish population -based cross-sectional survey was conducted . Participants aged 40 - 79 years were r and omly selected from the Swedish Registry of the Total Population . Data on physical activity , GERD , body mass index ( BMI ) and the covariates age , gender , comorbidity , education , sleeping problems , and tobacco smoking were obtained using vali date d question naires . GERD was self-reported and defined as heartburn or regurgitation at least once weekly , and having at least moderate problems from such symptoms . Frequency of physical activity was categorized into three groups : ( 1 ) " high " ( several times/week ) ; ( 2 ) " intermediate " ( approximately once weekly ) ; and ( 3 ) " low " ( 1 - 3 times/mo or less ) . Analyses were stratified for participants with " normal weight " ( BMI < 25 kg/m² ) , " overweight " ( BMI 25 to ≤ 30 kg/m² ) and " obese " ( BMI > 30 kg/m² ) . Multivariate logistic regression was used to calculate odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) , adjusted for potential confounding by covariates . RESULTS Of 6969 eligible and r and omly selected individuals , 4910 ( 70.5 % ) participated . High frequency of physical activity was reported by 2463 ( 50 % ) participants , GERD was identified in 472 ( 10 % ) participants , and obesity was found in 680 ( 14 % ) . There were 226 ( 5 % ) individuals with missing information about BMI . Normal weight , overweight and obese participants were similar regarding distribution of gender and tobacco smoking status , while obese participants were on average slightly older , had fewer years of education , more comorbidity , slightly more sleeping problems , lower frequency of physical activity , and higher occurrence of GERD . Among the 2146 normal-weight participants , crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity ( OR : 0.59 , 95 % CI : 0.39 - 0.89 ) , compared to low frequency of physical activity . However , after adjustment for potential confounding factors , neither intermediate ( OR : 1.30 , 95 % CI : 0.75 - 2.26 ) nor high ( OR : 0.99 , 95 % CI : 0.62 - 1.60 ) frequency of physical activity was followed by decreased risk of GERD . Sleeping problems and high comorbidity were identified as potential confounders . Among the 1859 overweight participants , crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity , compared to low frequency . After adjustment for confounding , neither intermediate ( OR : 0.75 , 95 % CI : 0.46 - 1.22 ) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants . Sleeping problems and high comorbidity were identified as potential confounders for overweight participants . In obese individuals , crude ORs were similar to the adjusted ORs and no particular confounding factors were identified . Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity ( adjusted OR : 0.41 , 95 % CI : 0.22 - 0.77 ) . CONCLUSION Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals , while no influence of physical activity on GERD was found in non-obese people BACKGROUND Two types of reflux episodes have been identified : upright or daytime and supine or nocturnal . The population -based prevalence of symptoms of nocturnal gastroesophageal reflux disease ( GERD ) and the impact of those symptoms on health-related quality of life ( HRQL ) have not been established . METHODS A national r and om- sample telephone survey was conducted to estimate the prevalence of frequent GERD and nocturnal GERD-like symptoms and to assess the relationship between HRQL , GERD , and nocturnal GERD symptoms . Respondents were classified as controls , subjects with symptomatic nonnocturnal GERD , and subjects with symptomatic nocturnal GERD . The HRQL was assessed using the Medical Outcomes Study Short-Form 36 Health Survey ( SF-36 ) . RESULTS The prevalence of frequent GERD was 14 % , with an overall prevalence of nocturnal GERD of 10 % . Seventy-four percent of those with frequent GERD symptoms reported nocturnal GERD symptoms . Subjects with nonnocturnal GERD had significant decrements on the SF-36 physical and mental component summary scores compared with the US general population . Subjects reporting nocturnal GERD symptoms were significantly more impaired than subjects reporting nonnocturnal GERD symptoms on both the physical component summary ( 38.94 vs 41 . 52 ; P<.001 ) and mental component summary ( 46.78 vs 49.51 ; P<.001 ) and all 8 subscales of the SF-36 ( P<.001 ) . Subjects with nocturnal GERD demonstrated considerable impairment compared with the US general population and chronic disease population s. Subjects with nocturnal GERD had significantly more pain than those with hypertension and diabetes ( P<.001 ) and similar pain compared with those with angina and congestive heart failure . CONCLUSIONS Nocturnal symptoms are commonly experienced by individuals who report frequent GERD symptoms . In addition , HRQL is significantly impaired in those persons who report frequent GERD symptoms , and HRQL impairment is exacerbated in those who report nocturnal GERD symptoms Symptoms suggestive of gastro-oesophageal reflux disease are very common . The aim of the study was to assess the prevalence of these symptoms and factors influencing them in an unselected adult population . A question naire was mailed to a r and om sample of 2500 people aged > or = 20 years . The questions concerned heartburn , regurgitation , dysphagia , chest and upper abdominal pain , as well as medication and medical consultations for these symptoms . Of the 1700 ( 68 % ) responders , 9 % had experienced heartburn on the day of response and 15 % , 21 % and 27 % during the preceding week , month and year , respectively . The corresponding figures for regurgitation were 5 , 15 , 29 and 45 % . During the past year 43 % of the study group had had no such symptoms . Age , overweight , pregnancy and cigarette smoking significantly influenced the prevalence of symptoms . Using daily heartburn and /or regurgitation as dominant indicators 10.3 % ( 95 % CI 12 - 11.7 ) of the responders had gastro-oesophageal reflux disease . Medication ( most commonly antacids ) was used by only 16 % of the symptomatic people , and only 5.5 % had sought medical advice for symptoms during the past year . Thus , despite commonness of symptoms suggestive of gastro-oesophageal reflux disease only a minority of the individuals suffering from such symptoms use medication or have medical consultation BACKGROUND The prevalence of gastroesophageal reflux disease ( GERD ) in Asian population s is reported to be lower than that in the West . Population -based data on the prevalence and symptom profile of GERD in developing Caucasian countries is lacking . Our objective was to determine the prevalence of gastrointestinal symptoms and clinical spectrum of GERD in Tehran , northern Iran and their association with patient characteristics . METHODS One thous and seven hundred telephone numbers were r and omly selected from Tehran telephone directory using a simple r and om method . A two-step screening telephone survey was then performed . In each answered call a second rapid survey was done to select a subject 18 - 65 years old from that household . A vali date d question naire was then filled out for that individual . Patient characteristics ( age , education , and gender ) and history of acid regurgitation and heartburn during the last week , as well as the previous three months were inquired about . RESULTS Of the 1,700 selected numbers , 278 either did not answer or did not have an eligible case ; 220 refused to participate . A total of 1,202 subjects ( 42 % males , mean age : 36 years , range : 18 - 65 yr ) were surveyed . The prevalence of heartburn occurring monthly , weekly , and daily was 4.7 % ( CI95 % : 3.5 - 6.0 % ) , 1.6 % ( CI95 % : 1.0 - 2.5 % ) , and 0.6 % ( CI95 % : 0.3 - 1.3 % ) , respectively . The corresponding figures for acid regurgitation were 15.6 % ( CI95 % : 13.6 - 17.7 % ) , 5.7 % ( CI95 % : 4.4 - 7.1 % ) and 1.5 % ( CI95 % : 0.9 - 2.4 % ) , respectively . The prevalence of GERD , defined as heartburn and /or acid regurgitation experienced daily , weekly and monthly was 1.9 % ( CI95 % : 1.2 - 2.9 % ) , 6.8 % ( CI95 % : 5.4 - 8.3 % ) , and 18.4 % ( CI95 % : 16.2 - 20.6 % ) . There was no relationship between the prevalence of GERD and either gender , age , or education . CONCLUSION Monthly GERD symptoms occur in 18.4 % of the general population in Tehran . Acid regurgitation is more common ( 4 - 5 times ) than heartburn . Gender , age , and level of education do not affect the prevalence of GERD symptoms in the community studied Background We aim ed to determine the prevalence of gastroesophageal reflux disease ( GERD ) and associated risk factors , and assess quality of life ( QoL ) in relation to the frequency and severity of reflux symptoms . Methods A r and om sample of 1000 residents of Western Sydney were mailed a vali date d self-report question naire . GERD symptoms , risk factors , psychologic distress , QoL , and demographics were measured . Results The response rate was 73 % ( n=672 ; mean age , 46 y ; 52 % female ) . A total of 78 [ 12 % , 95 % confidence interval ( CI ) : 9 - 14 ] had GERD ( at least weekly heartburn and /or acid regurgitation ) . Independent risk factors for GERD were high cholesterol [ odds ratio ( OR ) = 3.28 , 95 % CI : 1.42 - 7.57 , P=0.005 ] and current smoker ( OR=2.47 , 95 % CI : 1.07 - 5.70 , P=0.03 ) . Anxiety , depression , and neuroticism were not risk factors . Worse physical functioning was the only QoL domain associated with GERD ( OR=0.98 , 95 % CI : 0.97 - 0.99 , P=0.006 ) . QoL was significantly impaired regardless of the severity of GERD for the QoL domains physical function , body pain , vitality , and social function . The frequency of heartburn and acid regurgitation were not associated with significantly reduced QoL domain scores . Conclusions Cardiac risk factors ( high cholesterol and smoking ) were independently associated with GERD . Increasing GERD symptom severity is associated with worse QoL scores , whereas GERD symptom frequency did not impact the QoL scores OBJECTIVES Dyspepsia and irritable bowel syndrome ( IBS ) share aetiopathogenic factors , and may therefore be part of a single disorder . This study was intended to determine their prevalence in the general population , and the degree of overlap between these two digestive disorders . DESIGN Descriptive study . METHODS A sample of 264 subjects chosen r and omly from the population census of a city in Spain , and considered representative of the general population in this city , was surveyed by question naire . RESULTS The prevalence of dyspepsia was 23.9 % , and that of IBS was 13.6 % . Of the subjects with dyspepsia , 31.6 % had IBS , and of the subjects with IBS , 55.6 % reported symptoms of dyspepsia . The prevalence of IBS was higher among subjects with dyspepsia ( 31.7 % ) than among those who reported no symptoms of dyspepsia ( 7.9 % ; P < 0.05 ) . Moreover , the prevalence of IBS was similar in three subgroups identified according to the type of dyspepsia described ( ulcer-like , reflux-like or dysmotility-like ) . When we compared subjects with both dyspepsia and IBS and those with dyspepsia alone , we found no significant differences in clinical characteristics except for abdominal pain and fear of cancer , which were more frequent in the former . Of the entire sample , 27.7 % of the subjects sought medical attention for IBS and 17 % missed work because of IBS . CONCLUSION Our findings suggest that functional dyspepsia and IBS are two manifestations of a single , more extensive digestive system disorder Many people with gastro-esophageal reflux symptoms do not consult a physician ; therefore studies on gastro-esophageal reflux in general practice or in hospitals may not accurately describe the burden of gastro-esophageal reflux symptoms in the general population . The aim of this study was to assess the prevalence of gastro-esophageal reflux disease and its association with some life-style parameters in Rasht-Iran . A telephone survey was performed . Phone numbers was r and omly collected from the telecommunication service center of Rasht . 1473 people ( Mean age : 38.31 ± 13.09 ) were included in the study . People who did n't answer the phone after three times or did n't have consent to enter the study were excluded . Data were collected by an examiner using a GerdQ question naire . The validity and reliability of the question naire was tested by translation and retranslation and a pilot study was performed to assess its appropriateness . The prevalence of gastro-esophageal reflux was achieved 2.4 % daily , 9.1 % weekly and 11.3 % monthly . Among the patients with gastro-esophageal reflux , 69.5 % were female . There was a significant positive association between gastro-esophageal reflux prevalence and body mass index , smoking habits , eating salted or smoked foods , lying down immediately after the meal , taking certain drugs as non-steroidal anti-inflammatory drugs/Amino salicylic acid and the age group of 30 - 45 year old . Overall , the prevalence of the weekly gastro-esophageal reflux in the present survey was 9.1 % which was less than other similar studies in Iran and some other countries BACKGROUND Previous research suggests that females have a poorer outcome than do males after surgery for gastroesophageal reflux . OBJECTIVE To evaluate reflux and esophageal symptoms in males and females in a community sample and in patients undergoing antireflux surgery . DESIGN Face-to-face interview . SETTING A South Australian community . PARTICIPANTS R and om sample of 2973 individuals from the community and 2153 patients presenting for antireflux surgery . MAIN OUTCOME MEASURES In a r and om sample of 2973 individuals from the community , the prevalence of reflux and other esophageal symptoms was determined and compared with symptoms in 2153 patients presenting for antireflux surgery . Identical questions were used to assess frequency and severity of heartburn and dysphagia and medication use . Analog scales assessed heartburn and dysphagia ( 0 indicating no symptoms and 10 , severe symptoms ) . Outcomes for males vs females were compared across both groups . RESULTS In the community , females were more likely to report heartburn , and when reported , symptom severity was higher . The prevalence of dysphagia was similar for males and females , although females reported higher dysphagia scores for solid foods . A similar proportion of males and females took antireflux medications . Females presenting for antireflux surgery were , on average , 7 years older than males , had a higher body mass index , and had higher heartburn and dysphagia symptom scores . At endoscopy , men were more likely to have ulcerative esophagitis and Barrett esophagus , and at surgery they were less likely to have a hiatal hernia . CONCLUSIONS Significant differences were noted between males and females in the frequency and severity of gastroesophageal reflux-associated symptoms in the community and in patients presenting for surgery . These might reflect differences in symptom perception , which explain previously reported better outcomes in men undergoing antireflux surgery Background and aims Population -based data regarding the prevalence of gastroesophageal reflux disease ( GERD ) in Greece are very poor . This study estimated the prevalence of GERD symptoms and their risk factors in the Greek adult population . Methods A self-administered question naire was answered by a r and omly selected population of 340 subjects . The question regarding “ heartburn , chest pain , indigestion , or stomach acid coming up ” as included in the Reflux Symptom Index was used for prevalence assessment . Results The monthly prevalence of GERD symptoms was found to be 52.0 % in the Greek general population , with no statistically significant difference between the two sexes ( P>0.05 ) . The age group of 65–79 years showed a higher prevalence rate of GERD . Symptom severity was found to be mild ( 59.3 % ) or moderate ( 27.1 % ) . The number of cigarettes smoked daily ( but not smoking duration ) as well as the number of alcoholic drinks consumed daily ( but not the duration of alcohol drinking ) were found to be related to GERD symptoms . No reported concomitant disease or medication was found to be related with GERD symptoms . Conclusion The prevalence of GERD symptoms in the Greek general population was found to be 52.0 % . Tobacco smoking and alcohol drinking but not concomitant disease or medications were found to be related with GERD symptoms Background Gastro-oesophageal reflux disease ( GORD ) is a frequently occurring disease that may be considered a public health issue , particularly in developed countries . The specificity of heartburn for the diagnosis of GORD is good . Our aim was to define the prevalence of heartburn in Belgium , characterizing both its impact on everyday life and the ensuing use of medical re sources . Methods Two thous and people living in Belgium , selected r and omly after stratification , were interviewed face to face . The main question in the question naire used in this interview concerned the presence over the previous 12 months of a burning sensation in the epigastric and /or retrosternal region . This was followed by 21 secondary questions on the characteristics of the population studied , the impact of heartburn on everyday life , and the medical re sources used . Results Twenty-eight per cent of the population interviewed reported heartburn . This symptom was present at least once a week in 42 % of sufferers . Heartburn was more frequent in women than men ( P < 0.05 ) and was not distributed uniformly throughout the various regions of the country ( P < 0.05 ) . Seventy-seven per cent of the people with heartburn found that it had a significantly negative impact on their daily lives ( in 27 % , this effect was strong ) . Heartburn associated with a substantial negative impact on daily life was characterized by a higher frequency of symptoms ( P < 0.0001 ) , a longer duration of the problem ( P = 0.006 ) , and the presence of pain ( P < 0.0001 ) and anxiety ( P < 0.0001 ) . Fifty-six per cent of individuals with heartburn had already sought medical advice , 45 % had undergone an upper-gastrointestinal tract endoscopy , and 59 % were taking medications . Among patients complaining that heartburn had a substantial negative effect on their everyday lives , 21.6 % had not sought medical advice and 22.2 % did not take any medication . Conclusion Heartburn is very frequent in Belgium and is associated with a considerable negative impact on everyday life . It also generates a significant use of medical re sources . However , among the patients complaining of a substantial negative effect on their daily lives , one-fifth ( which would represent 1.5 % of the Belgian population ) seemed to lack appropriate care Aim . We aim ed to assess the prevalence and lifestyle correlates of gastroesophageal reflux disease ( GERD ) in the adult population of Albania , a Mediterranean country in Southeast Europe which has experienced major behavioral changes in the past two decades . Methods . A cross-sectional study , conducted in 2012 , included a population -representative sample of 845 individuals ( ≥18 years ) residing in Tirana ( 345 men , mean age : 51.3 ± 18.5 ; 500 women , mean age : 49.7 ± 18.8 ; response rate : 84.5 % ) . Assessment of GERD was based on Montreal definition . Covariates included socioeconomic characteristics , lifestyle factors , and body mass index . Logistic regression was used to assess the association of socioeconomic characteristics and lifestyle factors with GERD . Results . The overall prevalence of GERD was 11.9 % . There were no significant sex differences , but a higher prevalence among the older participants . In fully adjusted models , there was a positive relationship of GERD with smoking , physical inactivity , fried food consumption , and obesity , but not so for alcohol intake and meat consumption . Conclusion . We obtained important evidence on the prevalence and lifestyle correlates of GERD in a Western Balkans ' country . Smoking , physical inactivity , and obesity were strong “ predictors ” of GERD in this population . Findings from this study should be replicated in prospect i ve studies in Albania and other transitional setting BACKGROUND This paper reports the 3-month prevalence rates of gastrointestinal ( GI ) symptoms from the Domestic/International Gastroenterology Surveillance Study ( DIGEST ) , and their relationship with demographic factors ; namely age , gender and body mass index ( BMI ) . METHODS Subjects were recruited from 10 international sites by a total of 5581 face-to-face interviews conducted with r and omly selected members of the general population aged 18 years and over ( 50.6 % female ; mean age 44 years ) . The sample was divided according to whether subjects reported 1 or more of 14 GI symptoms , or no GI symptoms . Those with any of 11 upper GI symptoms were then subdivided according to their most bothersome symptom : gastro-oesophageal reflux (GORD)-like symptoms , ulcer-like symptoms or dysmotility-like symptoms . Symptoms were classified as relevant if they were of at least moderate severity and /or occurred at least once a week . RESULTS A mean of 46.4 % of subjects reported experiencing one or more of the 14 GI symptoms , with 28.1 % experiencing upper GI symptoms classified as relevant . Significant differences between the prevalences of relevant symptoms were evident between sampling sites . The estimated prevalence of GORD-like symptoms for the pooled sample was 7.7 % . For ulcer-like symptoms , prevalence was 4.1 % , and for dysmotility-like symptoms 15.5 % . Significant differences were observed in the prevalence rates of symptom groups between countries . Women were significantly more likely than men to experience relevant symptoms , with gender differences also observed in the rates of GORD-like and dysmotility-like symptoms . The proportion of those with relevant symptoms experiencing GORD-like symptoms increased significantly with age ; ulcer-like symptoms showed no significant relationship with age ; and dysmotility-like symptoms decreased significantly with age . The prevalence of relevant symptoms increased with increasing BMI . CONCLUSIONS In conclusion , the DIGEST has provided valuable data on the cross-country prevalence of upper GI symptoms , and their association with biological factors Background —The current classification dividing patients with functional gastrointestinal symptoms into subgroups remains controversial . Aims —To determine whether distinct symptom groupings exist in the community . Methods —A r and om sample of Sydney residents in Penrith , Australia was mailed a vali date d self report question naire . Gastrointestinal symptoms including the Rome criteria for irritable bowel syndrome ( IBS ) and dyspepsia were measured . Results —Among 730 respondents , the 12 month age and gender adjusted prevalence ( adjusted to the Australian population ) of IBS , dyspepsia , and gastro-oesophageal reflux were 11.8 % ( 95 % confidence interval ( CI ) 9.3 to 14.3 % ) , 11.5 % ( 95 % CI 9.6 to 14.6 % ) , and 17.5 % ( 95 % CI 14.2 to 19.9 % ) , respectively . In total , 60 % of the population reported four or more gastrointestinal symptoms . There was considerable overlap of IBS with dyspepsia and among the dyspepsia subgroups by application of the Rome criteria . Independently , 10 symptom groupings were identified by factor analysis . The underlying constructs measured by these factors were generally the major abdominal syndromes recognised by the Rome classification : dyspepsia , IBS , reflux , painless constipation , painless diarrhoea , and bloating , in addition to a number of more specific symptom groupings . Conclusion —Gastrointestinal symptoms are common and overlap in the community , but distinct upper and lower abdominal symptom groupings can be identified Dysphagia is an alarming symptom that raises the possibility of stricture or malignancy . This study compares the prevalence and severity of dysphagia symptoms in subjects with or without gastroesophageal reflux ( GERD ) . In a population -based study , 500 residents of Cologne between the ages of 20 and 90 years [ 232 ( 46 % ) males and 268 ( 54 % ) females ] were r and omly selected from the city register and sent question naires with reflux-related questions . Two hundred sixty-eight replies ( 54 % ) were accepted into the study . Of these , 45 % were men with a median age of 58 years . The median female age was 54 years . Thirty-four percent of the respondents ( n = 92 ) admitted having heartburn symptoms . There was no significant gender-based difference . There was little variation in reflux frequency between individual age groups . Twenty-three ( 25 % ) of the 92 respondents with reflux reported symptoms more than twice per week . Forty-five percent of this “ reflux ” group took medications for their heartburn . Swallowing difficulties , predominantly mild , were reported in 11.3 % of the respondents . Dysphagia was significantly increased in the reflux group ( 28 % ) versus the normal group ( 3 % ) ( p < 0.001 ) . Sixteen percent of respondents with mild and 65 % of those with moderate to severe reflux symptoms reported additional dysphagia symptoms ( p < 0.001 ) . Swallowing problems are common in patients with GERD . Approximately two thirds of patients with long-term and severe reflux symptoms also have dysphagia symptoms . Dysphagia should always be investigated by a physician Objectives : Gastroesophageal reflux disease ( GERD ) is a highly prevalent disorder . This study assessed the risk factors of new-onset gastroesophageal reflux symptoms ( GERS ) . Methods : The study was based on the HUNT study , a prospect i ve population -based cohort study conducted in 1995–1997 and 2006–2009 in Nord-Trøndelag County , Norway . All inhabitants from 20 years of age were invited . Risk factors of new-onset heartburn or acid regurgitation were examined using logistic regression , providing odds ratios ( OR ) and 95 % confidence intervals ( CI ) . Results : A total of 29,610 individuals were included ( 61 % response rate ) . Participants reporting no GERS at baseline and severe GERS at follow-up ( new-onset GERS ; n=510 ) were compared with participants reporting no complaints at both times ( n=14,406 ) . Increasing age ( OR 1.01 per year , 95 % CI 1.00–1.02 ) was positively associated , whereas male sex ( OR 0.81 , 95 % CI 0.66–0.98 ) and higher education ( OR 0.69 , 95 % CI 0.56–0.86 ) were negatively associated with new-onset GERS . Gain in body mass index ( BMI ) was dose-dependently associated with new-onset GERS ( OR 1.30 per unit increase in BMI , 95 % CI 1.25–1.35 ) , irrespective of baseline BMI . Previous and current tobacco smoking were associated with new-onset GERS ( OR 1.37 , 95 % CI 1.07–1.76 and OR 1.29 , 95 % CI 1.00–1.67 , respectively ) . Tobacco smoking cessation was associated with new-onset GERS among those with gain in BMI upon quitting ( OR 2.03 , 95 % CI 1.31–3.16 , with > 3.5 BMI units increase ) . Conclusions : New-onset GERS were associated with increasing age , female sex , lower education , gain in BMI , and ever tobacco smoking . Tobacco smoking cessation was associated with new-onset GERS among those who gained weight upon quitting Objective There are few data on the epidemiology of gastroesophageal reflux disease ( GERD ) in South China . The aim of this study was to assess the prevalence of GERD symptoms in South China and to evaluate the impact on health-related quality of life . Material and methods A face-to-face interview was carried out in South China using a vali date d Chinese version of the Reflux Disease Question naire to assess the prevalence of GERD symptoms . A r and omly clustered sampling of permanent inhabitants aged 18 to 90 years was carried out under stratification of urban and suburban areas . The impact of GERD symptoms on health-related quality of life was evaluated using the Chinese version of SF-36 . Results A total of 3338 residents ( 1468 M , 1870 F ) were investigated . Mean age of the responders was 42.6±16.4 years ; response rate was 95 % . The prevalence of heartburn and /or acid eructation occurring at least weekly was 6.2 % . The age- and gender-adjusted point prevalence of GERD symptoms in South China is 2.3 % ( 95 % CI , 1.8 % , 2.8 % ) according to the definition in this study . There was no difference in prevalence between male ( 2.6 % ) and female ( 2.4 % ) subjects and there was no significant association between age and prevalence of GERD symptoms . Divorced/widowed/separated subjects ( OR 4.61 ; 95 % CI , 2.15 % , 9.89 % ) and subjects with a heavy burden of work ( OR 3.43 , 95 % CI , 1.72 % , 6.84 % ) were significantly more likely to report GERD symptoms . As compared with the general population , subjects with GERD symptoms experienced considerable impairment in quality of life . Conclusions The prevalence of GERD symptoms in South China was much lower than that reported in Western countries . GERD had a negative impact on quality of life A question naire study was conducted to assess the prevalence and severity of symptoms suggestive of esophageal disorders in a general population . The study included 407 r and omly selected subjects , evenly distributed in terms of sex and age , within the age span of 20 - 79 years . A total of 337 subjects replied ( 85 % ) . Symptoms suggestive of gastroesophageal reflux were found among 25 % of the participants . Cough on swallowing was common ( 27 % ) , as was globus ( 16 % ) and chest pain ( 13 % ) . In addition , dysphagia was reported by 10 % and vomiting by 9 % . The symptoms were usually mild , and moderate to severe symptoms were reported only occasionally ( 1 - 4 % ) . No statistical correlation was found between esophageal symptoms and age , sex , or the reported consumption of tobacco , alcohol , or non-steroidal anti-inflammatory drugs . The frequency of heartburn and /or acid regurgitation was twice as common among those with symptoms of respiratory disease as among those with no respiratory complaints . A stepwise logistic regression analysis showed that a chronic cough and /or breathing difficulties were significantly related to the presence of symptoms suggestive of gastroesophageal reflux BACKGROUND / AIMS Dyspepsia and gastroesophageal reflux disease are common chronic diseases . In the clinical setting , some patients express both problems together ; however , little is known about the real prevalence of the presence of the two symptoms . Turkey is particularly interesting because of differences observed from developed countries . We aim ed to derive data from our previous prevalence of gastroesophageal reflux disease study and evaluate the overlap of the two symptoms . METHODS We used a previously vali date d and culturally adapted reflux question naire , which was translated into Turkish . The question naire was applied to 630 r and omly selected subjects older than 20 years living in a population of 8857 adults . RESULTS 28.6 % ( 180/630 ) of all responders defined dyspepsia within the last 12-month period . When symptom prevalence was considered at least weekly , the prevalence was 10 % for heartburn , 15.6 % for acid regurgitation , and 20 % for either symptom . While the prevalence of gastroesophageal reflux disease was 29.4 % in patients with dyspepsia , dyspepsia was found in 43.1 % of patients with gastroesophageal reflux disease . Only 21 % of symptomatic subjects or 8.4 % of the entire study population had both symptoms . Dyspepsia was defined as the most bothersome symptom . 54.3 % of all dyspeptic patients and 67.3 % with both gastroesophageal reflux disease and dyspepsia used a gastric medication ( p>0.05 ) . 29.9 % of subjects with dyspeptic symptoms defined antacid consumption and 28.3 % acid inhibitor therapy . CONCLUSION Dyspepsia was defined as the most bothersome symptom compared to gastroesophageal reflux disease symptoms . The prevalence of dyspepsia in patients with gastroesophageal reflux disease is more common than vice versa . However , the overlap of the two symptom groups was lower than expected in this low-income , Caucasian population The study presents results from a five-year follow-up on abdominal symptoms in an age and sex stratified r and om sample of 4,581 Danes . Abdominal pain occurred significantly more often among women ( prevalence : 49 % , incidence : 21 % ) compared to men ( prevalence : 38 % , incidence : 15 % ) . Five years later the pain had disappeared in 43 % of the men and 31 % of the women ( p=0.003 ) . Distension , borborygmi , and altering consistency of stools occurred with a prevalence of approximately 50 % and an incidence of approximately 30 % , significantly more often among women compared to men . Five years later these symptoms had disappeared in about 20 % . Prevalence of both heartburn and acid regurgitation were significantly higher among men ( 38 % ) than women ( 30 % ) , whereas no sex difference was observed regarding incidence of these symptoms ( 16 % ) . Approximately 30 % of subjects who had experienced heartburn or acid regurgitation did not do so five years later . In conclusion , abdominal symptoms occur frequently and recurrently in the general population . This information is of importance to doctors when they evaluate patients with abdominal complaints , but no obvious organic etiology BACKGROUND AND AIMS : This study estimated the prevalence and clinical spectrum of gastroesophageal reflux disease ( GERD ) in Asan-si , Korea , as the prevalence is believed to be lower than in Western countries . METHODS : A cross-sectional survey , using a reliable and valid question naire , was performed on r and omly selected 2,240 Asan-si residents aged between 18 and 69 yr . All respondents were interviewed at their homes or offices by a team of interviewers . RESULTS : Of the 1,902 eligible subjects , 1,417 ( 78.4 % : male 762 ; female 655 ) were surveyed . The prevalence of heartburn occurring at least once a month , at least once a week , and at least twice a week was 4.71 % ( 95 % confidence interval ( CI ) , 3.6–5.8 ) , 2.0 % ( 95 % CI , 1.2–2.7 ) , and 1.3 % ( 95 % CI , 0.7–1.9 ) , respectively . The corresponding figures for acid regurgitation were 4.4 % ( 95 % CI , 3.3–5.5 ) and 2.0 % ( 95 % CI , 1.3–2.8 ) , respectively . The prevalence of GERD , defined as heartburn and /or acid regurgitation experienced at least weekly , was 3.5 % ( 95 % CI , 2.6–4.5 ) . No significant difference was detected between sexes . The prevalence of heartburn was associated with increasing age ( p < 0.001 ) . Nineteen percent of our population reported at least one of the atypical symptoms , for instance , chest pain , dysphagia , globus sensation , asthma , bronchitis , pneumonia , or hoarseness . The frequency of frequent GERD among subjects reporting any of the atypical symptoms was 12.6 % , which was higher than that of the subjects without atypical symptoms . Patients with typical reflux symptoms were more common among those with atypical symptoms , compared to those without such symptoms ( p < 0.001 ) . Using a logistic regression model after adjusting for age and sex , typical reflux symptoms were associated with chest pain ( odds ratio ( OR ) , 9.3 ; 95 % CI , 5.9–14.7 ) , dysphagia ( OR , 6.4 ; 95 % CI , 2.8–14.7 ) , globus sensation ( OR , 3.9 ; 95 % CI , 1.5–9.7 ) , hoarseness ( OR , 4.3 ; 95 % CI , 1.4–13.1 ) , asthma ( OR , 2.6 ; 95 % CI , 1.4–4.8 ) , and bronchitis ( OR , 1.2 ; 95 % CI , 0.6–2.3 ) . CONCLUSION : The prevalence of GERD was 3.5 % in this Korean population . Heartburn and acid regurgitation were significantly associated with chest pain , dysphagia , globus sensation , hoarseness , and asthma Background : Different definitions of dyspepsia are applied by research ers yet measurement of the influence of these on prevalence estimates is uncertain . Despite continued debate regarding dyspepsia subgroups , few studies have used a data -drive approach to assess the existence and relevance of symptom clusters . We aim ed to address both these issues . Methods : A r and om population sample ( n = 2300 ) identified in New South Wales . Prevalence estimates of dyspepsia were calculated by applying four st and ardized dyspepsia definitions . Principal components analyses , using firstly the presence/absence of symptoms and then secondly severity of symptoms , were undertaken to determine if symptom factors existed . Results : Prevalence estimates ranged from 11 % to 36 % . Similar prevalence rates for men and women were observed for all definitions except Rome II . Over one-third of respondents nominated heartburn or epigastric pain as their most bothersome symptom . However , 22 % of respondents were unable to answer this question . The principal components analysis produced four symptom factors : a nausea factor , dysmotility-like dyspepsia ( early satiety and fullness ) , ulcer-like ( epigastric pain and bloating ) and reflux-like ( heartburn and acid regurgitation ) . However , the factors accounted for less than 50 % of the variance . Similar factors were identified in men and women for dysmotility-like and reflux-like dyspepsia . Use of presence/absence or severity of symptoms made little difference to the symptom factors produced or the amount of variance explained . Conclusions : The prevalence of dyspepsia depends on the definition applied . While there is some empirical evidence of symptom subgroups , they appear to be of little clinical utility BACKGROUND AND STUDY AIMS Gastro-oesophageal reflux disease ( GERD ) and dyspepsia are common digestive disorders that inflict serious harm , burden and economic consequences on individuals worldwide . The aim of this study was to estimate the direct and indirect economic burden of GERD and dyspepsia in the whole population of Tehran , the capital of Iran . PATIENTS AND METHODS The study was performed on a total of 18,180 adult subjects ( age>18 years ) taken as a r and om sample in Tehran province , Iran ( 2006 - 2007 ) . A valid and reliable question naire was used to enquire about the symptoms of GERD , dyspepsia and the frequency of the utilization of health services including physician visits , hospitalisations and productivity loss due to GERD/dyspepsia symptoms in the preceding 6 months . RESULTS GERD was found in 518 ( 41.9 % males ) patients and dyspepsia in 404 patients ( 38.9 % males ) . Further 1007 subjects had both GERD and dyspepsia . The total direct costs of disease per patient for GERD , dyspepsia and their overlap were PPP$97.70 , PPP$108.10 and PPP$101.30 , respectively ( PPP , purchasing power parity dollars ) . The total indirect cost of disease per patient was PPP$13.7 , PPP$12.1 and PPP$32.7 , for GERD , dyspepsia and their overlap , respectively . CONCLUSION According to our results , hospitalisation and physician visits were the main cost of disease that could be minimised by revision of the insurance business in Iran BACKGROUND few studies have reported the onset and disappearance rates of gastroesophageal reflux symptoms ( GERS ) in the population . AIM to assess the occurrence and disappearance rates of GERS in Spain , and their impact on health-related quality of life ( HRQL ) . PARTICIPANTS AND METHODS participants were selected at r and om from the general population of Madrid in age and sex strata . They were interviewed at home twice , 6 months apart . Heartburn , acid regurgitation and consultation were assessed with the gastroesophageal reflux question naire , and HRQL with the SF-36 . RESULTS 709 individuals were included , and 451 ( 63.6 % ) were re-interviewed 6 months later . Among the 325 individuals without GERS , 9 developed weekly symptoms ( 2.2 % [ 95 % CI : 0.8 , 3.4 % ] ) ; 2 ( 22 % ) consulted because of GERS . Among the 34 subjects reporting weekly GERS initially , 26 did not report them at 6-months . Onset of GERS was associated with worsening scores in the physical summary of SF-36 ( delta = -6.6 [ 95 % CI : -11.8 , -1.42 ] ) , while disappearance with an improved score ( delta = -3.0 [ 95 % CI : 0.0 , 5.9 ] ) . CONCLUSION despite the lower prevalence of GERS in Spain , the occurrence rate is 2.2 % in 6 months ; however symptoms disappeared in more than half of subjects six months later . Developing GERS was associated with reduced HRQL , and their disappearance with improvement Background : Upper oesophagogastroduodenoscopy is considered to be the gold st and ard for upper gastrointestinal disease assessment , but is currently seldom used in epidemiological studies . One concern is that the procedure may bias sampling among volunteers in a general adult population . The aim of this study was to explore whether the procedure affects symptom reporting . Methods : A r and om sample of 3000 adults aged 20 - 81 years ( mean age 50.4 ) , from two Swedish municipalities ( n = 21,610 ) was surveyed using a vali date d postal question naire ( the Abdominal Symptom Question naire ) assessing gastrointestinal symptoms . A sub sample of the responders was invited , in r and om order , to undergo an upper endoscopy and repeated symptom reporting using the same question naire , as well as a serology test for Helicobacter pylori . Results : The response rate to the initial question naire was 74.2 % and the participation rate for those eligible for the upper endoscopy was 73.3 % ( n = 1001 , mean age 54.0 years , 48.8 % male ) . No major social or symptom sampling error was encountered from the selection process , with the exception of an excess of symptom reporters among the youngest subjects . The prevalence of reflux symptoms , dyspeptic symptoms and irritable bowel symptoms was 40 % , 37.6 % and 29.6 % , respectively , which is relatively high , but in no way extreme . Conclusions : The upper endoscopy survey strategy was successful . The response rate was high and there was no major selection bias of clinical relevance . The cohort selected for this study appears to be representative of the general Swedish adult population Background : Population ‐based data on gastro‐oesophageal reflux disease in Chinese are lacking . The prevalence , clinical spectrum and health care‐seeking behaviour of subjects with gastro‐oesophageal reflux disease were studied BACKGROUND : The heterogeneity of the dyspepsia symptom complex is well known . Several attempts to classify dyspepsia into subgroups have been proposed as a basis for diagnosis and therapy , but data are conflicting . We postulated that dyspepsia comprises three distinct subsets , characterized by pain , early satiety , or nausea/vomiting . We aim ed to identify these subsets of dyspepsia : “ frequent upper abdominal pain ( UAP ) , ” “ early satiety ( ES ) , ” and “ nausea/vomiting ( NV ) . ” METHODS : A population -based , cross-sectional survey study was conducted by mailing a valid question naire to an age- and gender-stratified r and om sample of residents of Olmsted County , MN , aged 20–94 yr ( response rate 55 % ) . Dyspepsia and irritable bowel syndrome ( IBS ) prevalence were estimated by Rome II criteria ; gastroesophageal reflux ( GERD ) by weekly or more frequent heartburn or acid regurgitation . Dyspepsia subgroups were categorized based on a priori defined symptoms . RESULTS : The prevalence ( 95 % CI ) of dyspepsia was 15 % ( 14 , 17 ) . Of 351 dyspeptic subjects , 51 % ( 46 , 56 ) reported UAP , 21 % ( 16 , 25 ) NV , and 47 % ( 42 , 52 ) ES . The overlap of the subgroups was significantly less than expected by chance . Among the three groups , the subjects were similar in age , educational level , IBS status , and overall symptom severity . A high somatic symptom checklist score and those with GERD were associated with greater odds for reporting combination symptoms compared with the upper abdominal pain subgroup of dyspepsia or the early satiety subgroup of dyspepsia , respectively . CONCLUSION : Distinct subgroups of uninvestigated dyspepsia do exist in the general population , suggesting that separate evaluation and treatment strategies are needed AIMS To describe the prevalence and severity of dyspepsia and gastro-oesophageal reflux in the community , to investigate their association with lifestyle factors and to evaluate the consultation pattern for these conditions . METHOD A previously vali date d question naire was posted to 1000 adults r and omly selected from the electoral rolls of the greater Wellington region . It investigated symptoms of dyspepsia , reflux , lifestyle and consultation pattern over the previous twelve months . RESULTS Response rate was 81.7 % . Prevalence of dyspepsia was 34.2 % . Prevalence of reflux was 30 % . The overall prevalence of both symptom groups combined was 45.2 % . Most subjects had multiple symptoms . Results indicated 63 % of subjects with reflux also had symptoms of dyspepsia and 56 % of subjects with dyspepsia showed symptoms of reflux . Although 69 % of subjects with heartburn used over-the-counter medications , only 17 % consulted medical practitioners . Current and ex-smokers had a higher prevalence of reflux . Dyspeptic symptoms were not associated with alcohol intake or aspirin use . Prevalence of dyspeptic symptoms did not change with increasing age . CONCLUSIONS Dyspepsia is very common in the community . Significant overlap among the subgroups of dyspepsia makes a classification , based on symptoms alone , of question able value . Frequency and severity of symptoms should be incorporated in the definition to exclude those subjects with trivial symptoms AIM To evaluate the prevalence of chronic gastrointestinal symptoms and their impact on health-related quality of life ( HRQOL ) in the Korean population . METHODS A cross-sectional survey , using a reliable and valid Rome II based question naire , was performed on r and omly selected residents , between 18 and 69 years in age . All respondents were interviewed at their homes or offices by a team of interviewers . The impact of chronic gastrointestinal symptoms on HRQOL was assessed using the Korean version of the 36-item Short-Form general health survey ( SF-36 ) . RESULTS Of the 1807 eligible subjects , 1417 ( 78.4 % : male 762 ; female 655 ) were surveyed . Out of the respondents , 18.6 % exhibited at least one chronic gastrointestinal symptom . The prevalence of gastroesophageal reflux disease ( GERD ) , defined as heartburn and /or acid regurgitation experienced at least weekly , was 3.5 % ( 95 % CI , 2.6 - 4.5 ) . The prevalence of uninvestigated dyspepsia , irritable bowel syndrome ( IBS ) and chronic constipation based on Rome II criteria were 11.7 % ( 95 % CI , 10.1 - 13.5 ) , 2.2 % ( 95 % CI , 1.5 - 3.1 ) , and 2.6 % ( 95 % CI , 1.8 - 3.5 ) respectively . Compared with subjects without chronic gastrointestinal symptoms ( n=1153 ) , those with GERD ( n=50 ) , uninvestigated dyspepsia ( n=166 ) and IBS ( n=31 ) had significantly worse scores on most domains of the SF-36 scales . CONCLUSION The prevalence of GERD , uninvestigated dyspepsia and IBS were 3.5 % , 11.7 % and 2.2 % respectively , in the Korean population . The health-related quality of life was significantly impaired in subjects with GERD , uninvestigated dyspepsia and IBS in this community OBJECTIVE : Population -based data on gastroesophageal reflux disease ( GERD ) in Iran are limited . Current study is going to determine the prevalence of GERD in Tehran , Iran , and its association with potential risk factors . METHODS : In this cross-sectional study , a r and om clustered sample of Tehran province permanent households was selected from the latest postcodes . Data were collected by direct interview for each person aged 18–65 yr . GERD was defined as the existence of at least weekly episodes of heartburn and /or acid regurgitation during the last 6 months . All participants were asked about past and recent sanitary conditions , oral hygiene , and smoking . Odds ratios and 95 % confidence intervals ( CI ) were calculated using multivariable analysis . RESULTS : Interview was performed with 2,561 eligible subjects ( 42.3 % men ) . Response rate was 84.8 % . The prevalence of GERD was 21.2 % ( 95 % CI 18.7–23.7 ) . According to multivariable logistic regression analyses , individuals whose drinking water was obtained from well or tank during childhood were more prone to experience GERD symptoms ( OR 1.54 , 95 % CI 1.03–1.77 and OR 2.46 , 95 % CI 1.53–3.96 , respectively ) . We also detected significant associations with increasing number of missing teeth ( P value for linear trend = 0.02 ) and history of unpurified water consumption during past 10 yr ( P < 0.001 ) . Current smokers had a higher prevalence of reflux ( OR 1.82 , 95 % CI 1.32–2.51 ) . CONCLUSION : The prevalence of GERD in our Iranian population was considerably higher than that reported from other Asian studies approaching western figures . GERD prevalence was significantly associated with the history of unpurified water consumption , poor sanitary conditions of childhood , number of missing teeth , and smoking in this population OBJECTIVE To examine the relationship between body mass and gastro-oesophageal reflux in a large population -representative sample from the UK . DESIGN AND SETTING Cross-sectional population -based study , as part of a r and omized controlled trial of eradication of Helicobacter pylori infection , in Southwest Engl and . Subjects In all , 10 537 subjects , aged 20 - 59 years , were recruited from seven general practice s. Subjects provided data on frequency and severity of dyspeptic symptoms and anthropometric measurements were taken . MAIN OUTCOME MEASURE Relationship between overweight ( body mass index [ BMI ] > /=25 kg/m(2 ) and < /=30 kg/m(2 ) ) or obesity ( BMI > 30 kg/m(2 ) ) and frequency and severity of heartburn and acid regurgitation . RESULTS Body mass index was strongly positively related to the frequency of symptoms of gastro-oesophageal reflux . The adjusted odds ratios ( OR ) for frequency of heartburn and acid regurgitation occurring at least once a week in overweight participants compared with those of normal weight were 1.82 ( 95 % CI : 1.33 - 2.50 ) and 1.50 ( 95 % CI : 1.13 - 1.99 ) respectively . Corresponding OR ( 95 % CI ) relating to obese patients were 2.91 ( 95 % CI : 2.07 - 4.08 ) and 2.23 ( 95 % CI : 1.44 - 3.45 ) respectively . The OR for moderate to severe reflux symptoms were raised in overweight and obese subjects but not to the same extent as frequency of symptoms and only the relationship between obesity and severity of heartburn reached conventional statistical significance : OR = 1.19 ; 95 % CI : 1.07 - 1.33 . CONCLUSIONS Being above normal weight substantially increases the likelihood of suffering from heartburn and acid regurgitation and obese people are almost three times as likely to experience these symptoms as those of normal weight BACKGROUND Although patients with gastroesophageal reflux are often instructed to change their lifestyle , population -based data on the risk factors for reflux in the United States are lacking . METHODS We performed a cross-sectional study in an age- and gender-stratified r and om sample of the population of Olmsted County , Minnesota . Residents aged 25 to 74 years were mailed a valid self-report question naire that measured reflux symptoms and potential risk factors . Logistic regression was used to estimate the odds ratios ( OR ) with 95 % confidence intervals ( CI ) for reflux symptoms ( heartburn or acid regurgitation ) associated with potential risk factors . RESULTS Overall , 1,524 ( 72 % ) of 2,118 eligible subjects responded . A body mass index > 30 kg/m2 ( OR = 2.8 ; CI , 1.7 to 4.5 ) , reporting an immediate family member with heartburn or disease of the esophagus or stomach ( OR = 2.6 ; CI , 1.8 to 3.7 ) , a past history of smoking ( OR = 1.6 ; CI , 1.1 to 2.3 ) , consuming more than seven drinks per week ( OR = 1.9 ; Cl , 1.1 to 3.3 ) , and a higher psychosomatic symptom checklist score ( OR per 5 units = 1.4 ; CI , 1.3 to 1.6 ) were independently associated with frequent ( at least weekly ) reflux symptoms . CONCLUSION Obesity is a strong risk factor for gastroesophageal reflux , although the value of weight reduction remains to be proven . That family history was also a risk factor suggests that there may be a genetic component to the disorder OBJECTIVE To determine the prevalence and determinants of uninvestigated dyspepsia in the Iranian population . METHODS A cross-sectional study conducted in Tehran province from May 2006 to December 2007 , included 18,180 adult persons selected r and omly . The study took place at Shahid Beheshti University , MC , Tehran , Iran . A question naire was completed in 2 steps . In the first part , personal characteristics and 11 gastrointestinal symptoms were inserted . Those who reported at least one of these 11 symptoms were referred for the second interview , which consisted of questions on different gastrointestinal disorders based on Rome III criteria , including uninvestigated dyspepsia . RESULTS The prevalence rate of uninvestigated dyspepsia was 8.5 % ( 10.9 % in women and 6.4 % in men ) . Among the subjects diagnosed with dyspepsia , bothersome postpr and ial fullness was the most common symptom ( 41.5 % ) . Uninvestigated dyspepsia was more common in low educated and widowed participants . Approximately 41.4 % of patients had a history of depression , and 66.1 % had self report of stress . The prevalence of functional irritable bowel syndrome in patients with uninvestigated dyspepsia was 8.3 % and gastroesophageal reflux disease was 64.9 % . CONCLUSION Uninvestigated dyspepsia has a less common prevalence in the general Iranian population than developed countries . Women , older , obese , widowed , and low education subjects are more likely to suffer from dyspepsia The Rome II criteria and question naires developed to identify functional gastrointestinal disorders have not been evaluated . Our objectives were to determine the prevalence of functional gastrointestinal disorders in Canada , compare our results with data from other published studies , assess concordance of Rome I and Rome II criteria for irritable bowel syndrome , and suggest improvements in the Rome II question naire . An independent research firm was employed to conduct a r and om digit dial national survey , inviting household members ≥18 years of age to participate in a study examining personal health issues . Subjects recruited by telephone , who agreed to participate , were mailed a question naire , and the data were retrieved by a follow-up phone call . The Rome II question naire and algorithms were used and where possible Rome I algorithms were also applied . At least one functional gastrointestinal disorder occurred in 61.7 % of 1149 respondents ( 65.6 % female versus 57.6 % male ; P < 0.05 ) . The most prevalent were the functional bowel disorders at 41.6 % followed by esophageal disorders at 28.9 % . Irritable bowel syndrome prevalence by Rome II and I criteria were 12.1 % and 13.5 % , respectively ( kappa = 0.76 ) . Because the Rome II criteria have added exclusion items that are not present in the Rome I criteria , the prevalence of esophageal , gastroduodenal , and anorectal disorders is lower than the figures from a US market survey . In conclusion , functional gastrointestinal disorders are highly prevalent in Canada , with a significantly higher rate in women . There is substantial agreement between Rome I and Rome II criteria for irritable bowel syndrome . Rome criteria and question naire remain works in progress OBJECTIVES : There is limited information on the relationship between gastroesophageal reflux symptoms and well-being in the general population . This study aim ed to investigate this relationship and determine the severity threshold at which reflux symptoms meaningfully affect patients ' well-being . METHODS : A r and om sample of the population of Malmö , Sweden ( n=4,624 ) , was sent the Gastrointestinal Symptom Rating Scale , the Subjective Symptom Assessment Profile , and the Psychological General Well-Being Index . The relationship between well-being and the severity of heartburn , acid regurgitation , stomach pain , and abdominal pain was investigated by analysis of covariance ( ANCOVA ) . RESULTS : Complete data were obtained from 1,476 subjects ( 43 % male ; mean age [ st and ard deviation ] , 49.9 [ 14.2 ] yr ) . The mean Psychological General Well-Being Index score was 102 ( 95 % CI : 101–103 ) . Increasing symptom severity was associated with a decrease in well-being , and correlations between Psychological General Well-Being Index score and symptom severity ratings were statistically significant . At least mild symptoms of heartburn or abdominal pain ( a mean Gastrointestinal Symptom Rating Scale score of ≥3 ) were associated with a clinical ly meaningful reduction in well-being ( a Psychological General Well-Being Index score of less than 98 ) . CONCLUSIONS : Reflux symptoms are associated with impaired well-being in the general population . Individuals with symptoms that are mild or more severe report a meaningful reduction in well-being similar to that seen in other diseases . This may represent an appropriate threshold for patient selection in trials of GERD therapy and for more detailed evaluation of patients consulting with reflux symptoms in clinical practice OBJECTIVE : Upper gastrointestinal disorders are common in the community , yet the determinants of these symptoms are poorly characterized . The association between upper gastrointestinal symptoms and Helicobacter pylori ( H. pylori ) , socioeconomic status , nonsteroidal antiinflammatory drug ( NSAID ) use , smoking , alcohol , and coffee intake was assessed in a cross-sectional survey . METHODS : Subjects between the ages of 40–49 yr were r and omly selected from the lists of 36 primary care centers . Participants attended their local primary care center and were interviewed by a research er using a vali date d dyspepsia question naire . H. pylori status was determined by a nonfasting 13C-urea breath test . RESULTS : A total of 32,929 subjects were invited , and 8,407 ( 25 % ) attended and were eligible . Of these , 2,329 ( 28 % ) were H. pylori positive and 3,177 ( 38 % ) had dyspepsia . Also , 44 % of H. pylori-infected participants reported dyspepsia compared with 36 % of uninfected subjects [ odds ratio = 1.39 ; 95 % confidence interval ( CI ) 1.26–1.53 ] . H. pylori infection remained a significant risk factor for dyspepsia in a multiple logistic regression model ( odds ratio = 1.21 ; 95 % CI 1.09–1.34 ) , suggesting that 5 % of dyspepsia in the population is attributable to H. pylori . NSAIDs , low educational attainment , renting accommodation , absence of central heating , sharing a bed with siblings , and being married were also significantly associated with dyspepsia in this model . Smoking , but not drinking alcohol or coffee , was marginally associated with dyspepsia , but this finding was not robust . These factors were not associated with any dyspepsia subtype . CONCLUSIONS : H. pylori is significantly associated with dyspepsia and may be responsible for 5 % of upper gastrointestinal symptoms in the community AIM To study the natural history and prevalence of heartburn at a 10-year interval , and to study the effect of heartburn on various symptoms and activities . METHODS A population -based postal study was carried out . Question naires were mailed to the same age- and gender-stratified r and om sample of the Icel and ic population ( aged 18 - 75 years ) in 1996 and again in 2006 . Subjects were classified with heartburn if they reported heartburn in the preceding year and /or week , based on the definition of heartburn . RESULTS Heartburn in the preceding year was reported in 42.8 % ( 1996 ) and 44.2 % ( 2006 ) of subjects , with a strong relationship between those who experienced heartburn in both years . Heartburn in the preceding week was diagnosed in 20.8 % . There was a significant relationship between heartburn , dyspepsia and irritable bowel syndrome . Individuals with a body mass index ( BMI ) below or higher than normal weight were more likely to have heartburn . Heartburn caused by food or beverages was reported very often by 20.0 % of subjects . CONCLUSION Heartburn is a common and chronic condition . Subjects with a BMI below or higher than normal weight are more likely to experience heartburn . Heartburn has a great impact on daily activities , sleep and quality of life The factors that drive subjects with dyspepsiain the community to seek medical care are uncertain . We aim ed to identify whether psychological factors explainhealth care utilization among subjects with dyspepsia . A sample of residents of westernSydney selected r and omly from the electoral rolls wasmailed a vali date d self-report question naire . Dyspepsiawas defined as pain or discomfort centered in the upper abdomen . Potential predictors ofphysician visits tested included gastrointestinalsymptoms , neuroticism ( by the Eysenck Personality Question naire ) , psychological morbidity ( General Health Question naire ) , and sexual , physical , and emotional abuse(based on st and ardized criteria ) . Among 730 subjects,13 % ( 95 % CI 10.3 - 15.2 % ) had dyspepsia and 70 % ( 95 % CI59.8 - 79.5 % ) had sought medical care . Subjects with dyspepsia had significantly higher neuroticism and psychological morbidity scores and reportedchildhood emotional abuse more often than those withoutdyspepsia ( all P < 0.05 ) , but none of these wereindependent predictors . Male gender ( OR = 0.58 , 95 % CI0.37- 0.91 ) , greater pain severity ( OR = 2.49 , 95 % CI2.12 - 2.91 , P < 0.01 ) , and meeting the Rome criteria for irritable bowel ( OR = 2.0 , 95 % CI 1.06 - 3.78 ) wereassociated with dyspepsia subjects seeing a physician oralternative therapist for abdominal pain or discomfort , explaining 32 % of the deviance . Pain severity ( OR = 1.39 , 95 % CI 1.22 - 1.58 ) and symptoms of five or more years duration ( OR = 5.73 , 95 % CI 3.71 - 8.87)were predictive of dyspepsia subjects ever seeking carefor abdominal pain or discomfort , explaining 15 % of thedeviance . Psychological factors were not significant predictors of seeking medical attention indyspepsia . Health care seeking among community subjectswith dyspepsia is explained in part by symptom severity and duration but not by neuroticism , psychological morbidity , or a history of abuse Our objective was to obtain national data of the estimated prevalence , sociodemographic relationships , and health impact of persons with functional gastrointestinal disorders . We surveyed a stratified probability r and om sample of U.S householders selected from a data base of a national market firm ( National Family Opinion , Inc. ) . Questions were asked about bowel symptoms , sociodemographic associations , work absenteeism , and physician visits . The sampling frame was constructed to be demographically similar to the U.S. householder population based on geographic region , age of householder , population density , household income and household size . Of 8250 mailings , 5430 were returned suitable for analysis ( 66 % response ) . The survey assessed the prevalence of 20 functional gastrointestinal syndromes based on fulfillment of multinational diagnostic ( Rome ) criteria . Additional variables studied included : demographic status , work absenteeism , health care use , employment status , family income , geographic area of residence , population density , and number of persons in household . For this sample , 69 % reported having at least one of 20 functional gastrointestinal syndromes in the previous three months . The symptoms were attributed to four major anatomic regions : esophageal ( 42 % ) , gastroduodenal ( 26 % ) , bowel ( 44 % ) , and anorectal ( 26 % ) , with considerable overlap . Females reported greater frequencies of globus , functional dysphagia , irritable bowel syndrome , functional constipation , functional abdominal pain , functional biliary pain and dyschezia ; males reported greater frequencies of aerophagia and functional bloating . Symptom reporting , except for incontinence , declines with age , and low income is associated with greater symptom reporting . The rate of work/school absenteeism and physician visits is increased for those having a functional gastrointestinal disorder . Furthermore , the greatest rates are associated with those having gross fecal incontinence and certain more painful functional gastrointestinal disorders such as chronic abdominal pain , biliary pain , functional dyspepsia and IBS . Preliminary information on the prevalence , socio-demographic features and health impact is provided for persons who fulfill diagnostic criteria for functional gastrointestinal disorders Despite a common disorder population -based data on gastro-esophageal reflux disease ( GERD ) in Bangladesh is lacking . This epidemiological study was design ed to determine the prevalence of GERD and its association with lifestyle factors . This population -based cross-sectional study was done by door to door interview of r and omly selected persons in both urban and rural areas of North Eastern part of Bangladesh by using a vali date d question naire . A cutoff point 3 was chosen as a valid and reliable scale to confirm GERD . Statistical analysis was done by SPSS-12 version and the level of significance was set at P < or = 0.05 . A total of 2000 persons with an age range of 15 to 85 years were interviewed ; 1000 subjects from urban area and 1000 from rural area . Among the study subjects 1064 were male and 936 were female . A total of 110 persons ( 5.5 % ) were found to have GERD symptoms and among them 47 were men and 67 were women . The monthly , weekly and daily prevalence of heart-burn and or acid regurgitation was 5.5 % , 5.25 % and 2.5 % respectively . Female sex , increased age and lower level of education were significantly associated with GERD symptoms . Prevalence was found more among city dwellers ( approximately 6.0 % versus 4.8 % ) , married ( 6.23 % , n = 86 ) , widowed/widowers ( 16.83 % , n = 17 ) and day labourer ( 8.78 % ) . Level of education inversely influenced the prevalence . No significant association of GERD was found with body mass index ( BMI ) and smoking . Prevalence of GERD in North-Eastern part of Bangladesh was lower than that of western world . Prevalence was found higher in urban population , women , married , widowed/widowers and in poor an dilliterate persons . BMI and smoking had no significant association with GERD Background / Aims : People may have symptoms of multiple disorders at the same time . We aim ed to determine prevalence and risk factors for overlaps between gastroesophageal reflux disease ( GERD ) , dyspepsia and irritable bowel syndrome ( IBS ) in a Korean population . Methods : A cross-sectional survey was performed on 1,688 r and omly selected Korean subjects . Data on 1,443 subjects could be analyzed . Dyspepsia and IBS were diagnosed using modified Rome II criteria . Results : The prevalences of GERD , dyspepsia and IBS were 8.5 , 9.5 and 9.6 % . Overlaps between GERD and dyspepsia , GERD and IBS , and dyspepsia and IBS were observed in 2.3 ( 95 % CI 1.4–3.0 ) , 2.0 ( 95 % CI 1.2–2.6 % ) and 1.3 % ( 95 % CI 0.6–1.8 % ) of the population . 27 and 24 % of GERD subjects suffered from dyspepsia and IBS . 24 and 14 % of dyspeptic subjects had GERD and IBS . 21 and 14 % of IBS subjects had GERD and dyspepsia . Anxiety was significantly associated with GERD overlap ( OR 2.73 , 95 % CI 1.13–6.57 ) , dyspepsia overlap ( OR 3.19 , 95 % CI 1.33–7.63 ) and IBS overlap ( OR 4.92 , 95 % CI 2.04–11.84 ) , compared with GERD alone , dyspepsia alone and IBS alone . Conclusions : Overlaps between GERD , dyspepsia , and IBS are common in the general population . These overlaps occur predominantly in individuals with anxiety BACKGROUND / AIMS Epidemiological data of gastroesophageal reflux disease from Turkey is scarce . For this reason , we aim ed to determine the gastroesophageal reflux disease prevalence in our region and to compare it with both the Western part of Turkey and with other countries in the world . MATERIAL AND METHODS We used a previously vali date d reflux question naire and applied it to a r and om sample of 1345 subjects stratified by socio-economic status , who were older than 20 years and were living in the city center of Sivas . The question naire was conducted by medical students who were attending Public Health internship . RESULTS We estimated a prevalence rate of 19.3 % for gastroesophageal reflux disease , defined as heartburn and /or acid regurgitation at least once a week or more frequent . We found a significant association of gastroesophageal reflux disease with age , obesity , lying down within two hours after meals , and being under stress within the last one year , but not with smoking . Comorbid diseases associated with gastroesophageal reflux disease presence included recurrent pharyngitis , chronic cough , asthma , diabetes mellitus , hypertension , and chronic obstructive pulmonary disease , but not coronary heart disease . 50.8 % of our subjects had visited a physician for gastroesophageal reflux disease symptoms . The most common drug they used was proton pump inhibitors . CONCLUSION The prevalence of gastroesophageal reflux disease in a city of the Middle Anatolian region of Turkey was similar to that in developed countries and also to the results of another study performed in the Western part of Turkey . Further studies are needed to eluci date the role of environmental factors in the development of gastroesophageal reflux disease BACKGROUND / AIMS A link between abuse and irritable bowel syndrome ( IBS ) has been reported in out patients but remains controversial . No population -based studies have investigated this issue . The aim of this study was to determine the prevalence of abuse and its association with symptoms in a representative community sample . METHODS An age- and sex-stratified r and om sample of residents of Olmsted County , Minnesota ranging in age from 30 to 49 years was mailed a valid self-report symptom question naire . Abuse was assessed by st and ard published criteria . RESULTS Of the 919 responders ( 74 % ) , the age-adjusted prevalence of any abuse was 41 % in women and 11 % in men , result ing in an age- and sex-adjusted prevalence of 26 % . Symptoms of IBS , dyspepsia , and frequent heartburn were reported by 14 % , 23 % , and 12 % , respectively . There was a significant association between IBS and sexual abuse , emotional or verbal abuse , and abuse in childhood and adulthood . Similarly , dyspepsia and heartburn were both significantly associated with abuse . In the population , 31 % had visited a physician for gastrointestinal symptoms ; the odds of visiting a physician were highest in those reporting abuse in adulthood and childhood . CONCLUSIONS Self-reported abuse is common in middle-aged subjects ; those who report abuse are more likely to have symptoms consistent with IBS , dyspepsia , or heartburn and to visit a physician for bowel symptoms Abstract Introduction . Gastroesophageal reflux disease ( GERD ) , functional dyspepsia ( FD ) and irritable bowel syndrome ( IBS ) are common functional gastrointestinal conditions with significant impact on the daily lives of individuals . The objective was to investigate the prevalence and overlap of the three conditions in a Western general population . Material and methods . A nationwide study of 100,000 individuals 20 years and above , r and omly selected in the general population . A web-based question naire survey formed the basis of this study . Questions regarding FD and IBS were extracted from the ROME III adult question naire . Questions regarding GERD were developed based on the Montreal definition . Prevalence estimates for GERD , FD IBS were calculated in total and for each sex separately and for four age groups . A Venn diagram was constructed , illustrating the overlap between the three conditions . Results . The overall response rate was 52.2 % . The prevalence of GERD , FD and IBS was 11.2 % , 7.7 % and 10.5 % , respectively , and overlap between two or three of these conditions was seen among 6.5 % of the respondents . Among individuals meeting the criteria of one or more of the conditions GERD , FD and IBS , 30.7 % had overlap between two or all three conditions . Conclusion . GERD , FD and IBS are common conditions in the general population and the overlap between these conditions is also quite common . When diagnosing patients with GERD , FD and IBS , physicians should keep in mind that these patients could be suffering from more than one of these conditions To study the prevalence of dyspepsia in the community a postal question naire was sent to 2697 patients who were selected at r and om from the lists of patients registered in two health centres in Hampshire . A total of 2066 returned question naires were suitable for analysis ( response rate 77 % ) . It was found that the six month prevalence of dyspepsia was 38 % . There was considerable overlap between symptoms of heartburn and upper abdominal pain , with over half of patients with dyspepsia experiencing both . One in four of these patients had consulted their general practitioner during that time . The proportion of patients with dyspepsia who consulted their general practitioner varied widely among the eight doctors who participated in the study , from 17 % to 45 % . Frequency of symptoms tended to fall with age , particularly in men , while the proportion of patients with dyspepsia who sought medical advice increased with age . Almost one in five of the 2066 patients had been investigated with radiology or endoscopy at some time , and 143 ( 7 % ) of them cl aim ed to have had a diagnosis of peptic ulcer : The prevalence of reflux‐type symptoms among community individuals in Singapore is low We aim ed to determine the prevalence and clinical spectrum of GERD in the urban population of 6 cities in different parts of Russia ( St. Petersburg , Ryazan , Kazan , Kemerovo , Krasnoyarsk and Saransk ) . A previously vali date d reflux question naire developed at the Mayo Clinic was translated into Russian , culturally adapted and administered . Data was collected from 7812 r and omly selected subjects greater than 18 years old with the assistance of the yellow pages . ' Frequent symptoms ' were defined as a major symptom ( heartburn and /or regurgitation ) occurring at least once a week or more . " Occasional symptoms " were defined as an episode of one of the major symptoms occurring less than once a week within the past 12 months . Patients were defined as having GERD if they reported frequent heartburn and /or regurgitation . The average prevalence of frequent and occasional GERD symptoms in Russia was 9 % and 38.5 % for heartburn and 7.6 % and 35.3 % for regurgitation respectively within the last 12 months . The average prevalence of GERD in Russia was 13.3 % ( 11.3 - 14.3 % ) . The prevalence of frequent heartburn decreased with age ( r = -0.3 ) ; however , frequent regurgitation increased ( r = 0.7 ) with age . As a result , we found that prevalence of GERD increased with age . The average prevalence of GERD was statistically the same in men ( 12.5 % ) and in women ( 13.9 % ) . This prevalence did n't change with age in men but did increase with age in elderly women to 24 % . Frequent heartburn and regurgitation ( GERD ) were significantly associated with frequent belching ( 24.3 % ) , chronic cough ( 22.9 % ) , dyspepsia ( 19.8 % ) , non-cardiac chest pain ( 15.1 % ) , nausea ( 14.9 % ) , hoarseness ( 11.4 % ) , dysphagia ( 8.1 % ) , odynophagia ( 7.3 % ) and constipation ( 37.8 % ) . Alcohol consumption ( prevalence of 60.4 % among respondents ) and smoking ( prevalence of 25.4 % among respondents ) did n't yield any significant difference in subjects with frequent symptoms . Importantly , we also found that only 52.8 % of subjects with frequent chest pain and 29.3 % of respondents with frequent heartburn had seen a physician for these symptoms Limited data exist to determine the prevalence and clinical spectrum of gastroesophageal reflux disease ( GERD ) in the Russian population , which might be different from those in Western countries . This study was performed in Moscow on r and omized 1065 adults aged ≥15 years . A vali date d reflux question naire comprising 72 questions and an additional 29 sub- questions were used . The questions assessed ( heartburn and regurgitation ) and related ( dyspepsia , dysphagia , odynophagia and chest pain ) symptoms , the triggering factors of these symptoms , family history and data on demographic and socioeconomic features . GERD was defined as heartburn and /or regurgitation once a week or common . Of the 1065 participants , 42.1 % were male and 57.9 % were female . The prevalences of frequent and occasional symptoms were 17.6 and 22.1 % for heartburn and 17.5 and 21.8 % for regurgitation , respectively , over the last 12 months . The prevalence of GERD was found to be 23.6 % . The rate of GERD was significantly higher in females than in males ( 15.4 vs. 29.5 % , P < 0.001 ) and significantly increased as the age of the participants increased ( P = 0.011 ) . GERD was present in 20.4 % of smokers , 24.2 % of coffee drinkers , 21.5 % of alcohol consumers and 45.9 % of stressed participants . Although the rate of alcohol consumers was lower in those with GERD compared with those without GERD , the rate of coffee drinkers and stressed participants was higher among those with GERD . The rate of additional symptoms was higher even in participants complaining of regurgitation/heartburn rarely , compared with those without complaints . Using the same question naire , which makes it possible to compare the present results with those from different countries , we found the prevalence of GERD in Moscow to be 23.6 % , one of highest in the Western population s. The rates of heartburn and regurgitation were found to be similar , which constitutes a different result than has been found in similar studies . Additional symptoms should be assessed , in all GERD patients even in the presence of rare complaints of regurgitation/heartburn The prevalence of gastroesophageal reflux disease ( GERD ) in China is lower than that in the Western countries , but appears to be increasing . The aim of this pilot study was to evaluate the prevalence of GERD in Shanghai , China , and to explore which population characteristics where associated with GERD . A sample of 1200 adult inhabitants of Shanghai , selected using r and omized , stratified , multi-stage sampling , completed M and arin translations of the Reflux Disease Question naire and GERD Impact Scale . Potential risk factors for GERD were examined by nested case-control analysis , using Cochran-Armitage trend testing and logistic regression analysis . The response rate was 86.2 % ; 919 responses were suitable for analysis . The prevalence of GERD , defined as heartburn and /or regurgitation of any frequency during the previous week , was 6.2 % in Shanghai . Obesity and urban dwelling were associated with GERD ( odds ratio 3.4 , 95 % confidence interval 1.3 - 9.3 ; and odds ratio 3.6 , 95 % confidence interval 1.2 - 10.4 , respectively ) . The prevalence of GERD in Shanghai agreed with previous Chinese studies . GERD in Shanghai was associated with obesity and residency in an urban environment |
13,485 | 21,459,874 | The search results indicated that many aspects of sensorimotor function continue to mature throughout adolescence , and at least some children experience delays or regressions in at least some sensorimotor mechanisms . | BACKGROUND Although adolescent motor awkwardness and increased injury susceptibility have often been speculated and research ed , studies regarding adolescent regressions in motor control have yielded inconsistent conclusions .
Thus , the relationship between adolescent maturation and injury risk remains unclear .
The purpose of this study was to systematic ally review the literature relative to two questions : ( 1 ) Which sensorimotor mechanisms are not fully mature by the time children reach adolescence ?
and ( 2 ) Is adolescence a period when children exhibit delays or regressions in sensorimotor mechanisms ? | The sensory and motor functioning of normal children ( N = 119 ) ages 4 to 13 years old were examined for developmental and sex differences in relation to neuropsychological functioning . Sensory and motor subtests of the Dean-Woodcock Neuropsychological Assessment System ( D-WNAS ) , a st and ardized instrument , were administered . Significant differences between the older and younger children were found , suggesting that developmental differences exist for sensory and motor functioning . The older children significantly outperformed the younger children on all subtests except for visual confrontation . Differences between males and females and the interaction between sex and age were not significant . The present findings coincide with previous research showing clear maturational differences in sensory and motor functions Background Neuromuscular training may reduce risk factors that contribute to ACL injury incidence in female athletes . Multi-component , ACL injury prevention training programs can be time and labor intensive , which may ultimately limit training program utilization or compliance . The purpose of this study was to determine the effect of neuromuscular training on those classified as " high-risk " compared to those classified as " low-risk . " The hypothesis was that high-risk athletes would decrease knee abduction moments while low-risk and control athletes would not show measurable changes . Methods Eighteen high school female athletes participated in neuromuscular training 3 × /week over a 7-week period . Knee kinematics and kinetics were measured during a drop vertical jump ( DVJ ) test at pre/post training . External knee abduction moments were calculated using inverse dynamics . Logistic regression indicated maximal sensitivity and specificity for prediction of ACL injury risk using external knee abduction ( 25.25 Nm cutoff ) during a DVJ . Based on these data , 12 study subjects ( and 4 controls ) were grouped into the high-risk ( knee abduction moment > 25.25 Nm ) and 6 subjects ( and 7 controls ) were grouped into the low-risk ( knee abduction < 25.25 Nm ) categories using mean right and left leg knee abduction moments . A mixed design repeated measures ANOVA was used to determine differences between athletes categorized as high or low-risk . Results Athletes classified as high-risk decreased their knee abduction moments by 13 % following training ( Dominant pre : 39.9 ± 15.8 Nm to 34.6 ± 9.6 Nm ; Non-dominant pre : 37.1 ± 9.2 to 32.4 ± 10.7 Nm ; p = 0.033 training X risk factor interaction ) . Athletes grouped into the low-risk category did not change their abduction moments following training ( p > 0.05 ) . Control subjects classified as either high or low-risk also did not significantly change from pre to post-testing . Conclusion These results indicate that " high-risk " female athletes decreased the magnitude of the previously identified risk factor to ACL injury following neuromuscular training . However , the mean values for the high-risk subjects were not reduced to levels similar to low-risk group following training . Targeting female athletes who demonstrate high-risk knee abduction loads during dynamic tasks may improve efficacy of neuromuscular training . Yet , increased training volume or more specific techniques may be necessary for high-risk athletes to substantially decrease ACL injury risk Abstract . The development of proprioceptive sensitivity was studied in 140 children between the ages of 5.8 and 11.8 years using a so-called foot-h and task . Ten boys and ten girls were included in each age group . The task required the children to locate a target pin with the " big toe " ( felt target ) and match the located target position with the h and , without vision . There were four conditions : location of targets by the right big toe : matching located target position with the right h and ( RfRh ) and left h and ( RfLh ) ; and location of targets by the left big toe : matching located target position with the left h and ( LfLh ) and right h and ( LfRh ) . The results showed a significant developmental trend in proprioceptive sensitivity , when the absolute error scores for boys and girls were combined , with most of the improvement occurring between the ages of 5.8 and 7.8 years . The most interesting and novel finding seems to be the significant two-way interaction between age and sex – the clearest differences manifesting themselves in the age group 9.9 years . Separate within-sex group analyses showed the trend to be determined by the results for the girls , the trend being absent in the results for the boys . Furthermore only the boys showed a significant difference between the intra- and inter-hemispheric conditions . We propose that these differences may only manifest themselves in particular tasks , i.e. there may be a sex-task interaction . The implication s of this proposal for theoretical interpretations of the phenomenon of inter-hemispheric processing as well as possible sources of the task differences are briefly discussed To identify sex differences and developmental trends in motor performance and coordination across three stages of development : prepubertal , pubertal and postpubertal , 60 participants , 30 males and 30 females , were assessed on 13 motor tasks . Physical characteristics that accompany puberty were used to classify the participants into the stages . Analysis of variance and covariate analyses demonstrated that motor performance improves throughout adolescence in both males and females and that sex differences exist in motor performance , males performing better than females . The magnitude of the stage and sex differences were demonstrated by large effect sizes ( eta 2 ) . The motor tasks of long jump , running speed , and throwing a ball principally distinguished between the males and females . Female performance differed less from male performance after puberty . Results showed OBJECTIVE To investigate the developmental trajectory of response inhibition and , more specifically , whether there is a dissociation of function in the prefrontal cortex over the course of development of executive function and associated response inhibition abilities . METHOD Nineteen typically developing subjects , ranging in age from 8 to 20 , performed a Go/NoGo task while behavioral and functional magnetic resonance imaging ( fMRI ) data were collected . RESULTS All subjects performed the task with few errors of omission and commission . No relationship between accuracy and age emerged , but the ability to inhibit responses significantly improved with age . Analyses of fMRI data revealed a positive correlation between activation and age in the left inferior frontal gyrus/insula/orbitofrontal gyrus , and a negative correlation between activation and age in the left middle/superior frontal gyri . CONCLUSION These data provide the first evidence of dissociable processes occurring in the prefrontal cortex during development of executive functions associated with response inhibition : ( 1 ) Younger subjects activate more extensively than older subjects in discrete regions of the prefrontal cortex , presumably due to increased dem and s and inefficient recruitment of brain regions subserving executive functions including working memory . ( 2 ) Older subjects show increasingly focal activation in specific regions thought to play a more critical role in response inhibition In very young children , immature control of posture and gait results in unsteady locomotion . In children of approximately 3 yr of age , gait appears relatively mature ; however , it is unknown whether the dynamics of walking change beyond this age . Because stride dynamics depend on neural control , we hypothesized that motor control would continue to develop beyond age 3 . To test this hypothesis , we measured the gait cycle duration on a stride-by-stride basis in 50 healthy 3- to 14-yr-old children ( 25 girls ) . Measurements of stride-to-stride variability were significantly larger both in the 3- and 4-yr-old children , compared with the 6- and 7-yr-old children , and in the 6- and 7-yr-old children , compared with the 11- to 14-yr-old children . Measurements of the temporal organization of gait also revealed significant age-dependent changes . The effects of age persisted even after adjusting for height . These findings indicate that mature stride dynamics may not be completely developed even in healthy 7-yr-old children and that different aspects of stride dynamics mature at different ages This study presents a method to quantify a child ’s sensitivity to passive limb motion , which is an important aspect of kinaesthesia not easily examined clinical ly . Psychophysical detection thresholds to passive forearm motion were determined in a group of 20 typically developing pre‐adolescent children ( mean age 12y 6mo , SD 10mo , range 11−13y ) and a group of 10 healthy adults ( mean age 29y 10mo , SD 10y 7mo , range 18−50y ) . A newly design ed passive motion apparatus was used to measure the time to detection of forearm motion and the errors in determining movement direction . Results showed that limb motion sensitivity became increasingly variable below 0.3 ° /s in children and adults . In comparison with adults , movement detection times in the pediatric group were increased by between 4 % and 108 % for the range of tested velocities ( 0.075−1.35 ° /s ) . At 0.075 ° /s , 5 % of the children , but 50 % of the adults , made no directional error , indicating that motion perception became unreliable at such low velocity in both groups . The findings demonstrate that sensitivity to passive forearm motion in children should be tested at a range between 0.075 and 0.3 ° /s . They further suggest that passive motion sensitivity may not be fully developed in pre‐adolescent children Prevailing theories of implicit or unaware learning propose a developmental invariance model , with implicit function maturing early in infancy or childhood despite prolonged improvements in explicit or intentional learning and memory systems across childhood . Neuroimaging studies of adult visuomotor sequence learning have associated fronto-striatal brain regions with implicit learning of spatial sequences . Given evidence of continued development in these brain regions during childhood , we compare implicit sequence learning in adults and 7- to 11-year-old children to examine potential developmental differences in the recruitment of fronto-striatal circuitry during implicit learning . Participants performed a st and ard serial reaction time task . Stimuli alternately followed a fixed 10-step sequence of locations or were presented in a pseudor and om order of locations . Adults outperformed children , achieving a significantly larger sequence learning effect and showing learning more quickly than children . Age-related differences in activity were observed in the premotor cortex , putamen , hippocampus , inferotemporal cortex , and parietal cortex . We observed differential recruitment of cortical and subcortical motor systems between groups , presumably reflecting age differences in motor response execution . Adults showed greater hippocampal activity for sequence trials , whereas children demonstrated greater signal during r and om trials . Activity in the right cau date correlated significantly with behavioral measures of implicit learning for both age groups , although adults showed greater signal change than children overall , as would be expected given developmental differences in sequence learning magnitude . These results challenge the idea of developmental invariance in implicit learning and instead support a view of parallel developments in implicit and explicit learning systems Recent research using measures to assess the time-dependent structure of postural fluctuations has provided new insights into the stability and adaptability of human postural control in adults . To date , little research has examined how postural dynamics reflecting the stability and adaptability of postural control may change as a function of development , especially during supra-postural tasks . The goal of this study was to examine the dynamics of postural fluctuations during a manual-fitting task in which precision , visual and postural task constraints were altered in children and adults . Three age groups were tested : 7- , 10-year olds and college aged adults . Recurrence quantification analysis ( RQA ) was used to assess the regularity ( percent determinism ) and complexity ( entropy ) of the center of pressure ( CoP ) in the anterior – posterior ( AP ) and medial-lateral ( ML ) directions . The CoP patterns exhibited by adults were more deterministic and more complex ( higher entropy ) than those of the 7-year-old children under the different experimental manipulations . No differences between the adults and the 10-year-old children were observed . The increase in determinism with a corresponding increase in entropy exhibited by the adults and older-children during a manual fitting task may be a prospect i ve mechanism over which postural movements follow a more predictable path allowing for stable and flexible task performance . Our results also support the notion that complex postural fluctuations ( as measured by RQA entropy ) are functional and typically increase as the precision requirements of a manual task increase Past research has shown that spectral frequency characteristics of a balance control system may be useful for early detection of minor changes in the system . Since there is a lack of information regarding the frequency spectrum of children 's balance control system , this study was undertaken to investigate and compare the spectral frequency characteristics of st and ing balance control between children and young adults under altered sensory environments . Seventeen children ( 9 females , 8 males , mean age 7.8+/-0.9 years ) and the same number of female and male young adults ( mean age 21.1+/-1.3 years ) were tested for st and ing balance under six sensory conditions . These conditions were created by crossing the three levels of the visual factor ( open eye , closed eye , sway-referenced vision ) with the two levels of the somatosensory factor ( fixed foot support , compliant foot support ) . The median spectral frequencies of the shear forces in the anterior-posterior ( A/P ) and the medial-lateral ( M/L ) directions were used as dependent variables . The results showed that children had higher median spectral frequency of the A/P shear force than young adults and this difference was not affected by the somatosensory factor . The median spectral frequency in the M/L direction was not different between the groups . The higher rate of body mass vibration of children in the A/P direction implies that children may not have fully developed the ankle strategy for maintaining st and ing balance , but nonetheless have developed the same efficiency of using vision for their reference of st and ing balance Traditional posturographic analysis and four statistical mechanics techniques were applied to center-of-pressure ( COP ) trajectories of young , older " low-fall-risk " and older " high-fall-risk " individuals . Low-fall-risk older adults were active 3 days per week in a cardiac rehabilitation program , while high-fall-risk older adults were diagnosed with perilymph fistula . Subjects diagnosed with perilymph fistula must have experienced two of the following vestibular findings : constant disequilibrium , positional vertigo and /or a positive fistula test . Non-parametric statistical tests were used to determine whether the posturographic measures could detect differences between the young and older " low-fall-risk " groups ( age comparison ) and between the older " low- " and " high-risk " groups ( risk of falling comparison ) . The statistical mechanics techniques were more sensitive than the traditional measures : detecting significant differences between the young and older " low-risk " groups , while none of the traditional measures were significantly different . In addition , interpretation of the statistical mechanics techniques may offer more insight into the nature of the process controlling the COP trajectories . However , the methods offered slightly different explanations . For instance , the Hurst rescaled range analysis suggests that the movement of the COP is governed solely by anti-persistent behavior , whereas the stabilogram diffusion analysis suggests a short-term persistence balanced by a long-term anti-persistence . These discrepancies highlight the need for a model that incorporates the biological systems responsible for maintaining balance and experimental methods to directly quantify their status and roles . Until such a model exists , however , the statistical mechanics techniques appear to have some advantages over traditional posturographic measures for study ing balance control Abilities to discriminate forms defined by motion continue to develop throughout childhood . To investigate late development of the visual motion system , we measured brain activity with event-related EEG potentials ( ERPs ) and functional magnetic resonance imaging ( fMRI ) in groups of adolescents ( 15 - 17 years ) and adults ( 20 - 30 years ) during a visual form discrimination task -- with forms being either defined by motion or luminance contrast . We further explored whether possible developmental changes varied with the degree of motion coherence reflecting maturation specific to global motion processing . Both the fMRI activation patterns and ERP topographies were very similar between adolescents and adults , suggesting that the basic visual networks for processing motion and form are established by the age of 15 - 17 . The ERP response to luminance- and motion-defined forms was dominated by a posterior negativity ( N1 : 120 - 270 ms ) . The N1 of the motion contrast was delayed in adolescents , whereas the N1 of the static condition did not differ between groups . Since the motion-evoked N1 is thought to arise in the middle temporal area MT/V5 , our results indicate that visual motion processing in MT continues to get faster , becoming still more efficient during late development . Neither the ERP nor the fMRI results revealed maturation effects specific to motion coherence . This indicates that the specific mechanisms to process global dot motion are already mature in adolescence . The present findings support the view that static perception matures earlier than dynamic perception , and that these visual systems have different developmental courses Both the motor system and the frontal executive control system show a late maturation in humans which continues into school-age and even adolescence . We investigated the maturation of preparation processes towards a fast motor reaction in 74 healthy right-h and ed children aged 6 to 18 years and analyzed the topography of the late component of contingent negative variation ( lCNV ) in a 64-electrode high density sensor array . While adolescents from about 12 years on showed a bilaterally distributed centro-parietal maximum like adults do , younger children almost completely missed the negativity over the left central area contralaterally to the side of the anticipated movement . The reason , as revealed by current source density , was that only adolescents showed significant evoked activity of the left pre-/ primary motor and supplementary/cingulate motor areas , while in contrast both age groups displayed significant current sinks over the right ( ipsilateral ) centro-temporal area and right posterior parietal cortex . Spatio-temporal source analysis confirmed that negativity over the right posterior parietal area could not be explained by a projection via volume conduction from frontal areas involved in motor preparation but represented an independent component with a different maturational course most likely related to sensory attention . Significant event-related desynchronization of alpha-power over the contralateral sensorimotor cortex was found in the younger age group , indicating that also 6- to 11-year-old children were engaged in motor preparation . Thus , the missing current sink over the contalateral sensorimotor cortex during late CNV in 6- to 11-year-old children might reflect the immaturity of a specific subcomponent of the motor preparation system which is related to evoked ( late CNV ) but not induced activity ( alpha-ERD ) Transcranial magnetic stimulation and motor performance tests were used to study the correlation between corticospinal maturation and actual motor performance in a group of young school children ( n = 10 , mean age = 7 years , age range = 6 - 9 years ) . The results were compared with normal adults ( n = 10 , mean age = 24 years , age range = 22 - 26 years ) . In children the central conduction time under the preinnervation condition of facilitation and the postexcitatory silent period was similar to that in adults . However , the central conduction time under relaxation , the latency jump ( defined as the difference between the two preinnervation conditions ) , and the stimulus intensity were statistically different between children and adults ( P < 0.01 - 0.001 ) . Children did not reach the same level of performance as adults in any of the motor performance tasks ( simple acoustic reaction time , tapping , ballistic movement , tracking , and diadochokinesis ) ( P < 0.05 - 0.01 ) . The results indicate that at an early school age , children already possess mature fast corticospinal pathways able to access spinal motoneurons through the pyramidal tract . However , despite the partially adult-like level of neuronal maturation , young school children were not able to perform deliberate motor actions with the same proficiency as adults OBJECTIVE To determine in a prospect i ve population -based cohort study relationships between different measures of body mass and the incidence of severe knee and hip osteoarthritis defined as arthroplasty of knee or hip due to osteoarthritis . MATERIAL S AND METHODS Body mass index ( BMI ) , waist circumference , waist-hip ratio ( WHR ) , weight and percentage of body fat ( BF% ) were measured at baseline in 11,026 men and 16,934 women from the general population . The incidence of osteoarthritis over 11 years was monitored by linkage with the Swedish hospital discharge register . RESULTS 471 individuals had knee osteoarthritis and 551 had hip osteoarthritis . After adjustment for age , sex , smoking and physical activity , the relative risks ( RR ) of knee osteoarthritis ( fourth vs first quartile ) were 8.1 ( 95 % CI 5.3 to 12.4 ) for BMI , 6.7 ( 4.5 to 9.9 ) for waist circumference , 6.5 ( 4.6 to 9.43 ) for weight , 3.6 ( 2.6 to 5.0 ) for BF% and 2.2 ( 1.7 to 3.0 ) for WHR . Corresponding RR for hip osteoarthritis were 2.6 ( 2.0 to 3.4 ) for BMI , 3.0 ( 2.3 to 4.0 ) for weight , 2.5 ( 1.9 to 3.3 ) for waist , 1.3 ( 0.99 to 1.6 ) for WHR and 1.5 ( 1.2 to 2.0 ) for BF% . CONCLUSION All measures of overweight were associated with the incidence of knee osteoarthritis , with the strongest relative risk gradient observed for BMI . The incidence of hip osteoarthritis showed smaller but significant differences between normal weight and obesity . Our results support a major link between overweight and biomechanics in increasing the risk of knee and hip osteoarthritis in men and women Background Female athletes participating in high-risk sports suffer anterior cruciate ligament injury at a 4- to 6-fold greater rate than do male athletes . Hypothesis Prescreened female athletes with subsequent anterior cruciate ligament injury will demonstrate decreased neuromuscular control and increased valgus joint loading , predicting anterior cruciate ligament injury risk . Study Design Cohort study ; Level of evidence , 2 . Methods There were 205 female athletes in the high-risk sports of soccer , basketball , and volleyball prospect ively measured for neuromuscular control using 3-dimensional kinematics ( joint angles ) and joint loads using kinetics ( joint moments ) during a jump-l and ing task . Analysis of variance as well as linear and logistic regression were used to isolate predictors of risk in athletes who subsequently ruptured the anterior cruciate ligament . Results Nine athletes had a confirmed anterior cruciate ligament rupture ; these 9 had significantly different knee posture and loading compared to the 196 who did not have anterior cruciate ligament rupture . Knee abduction angle ( P < . 05 ) at l and ing was 8 ° greater in anterior cruciate ligament-injured than in uninjured athletes . Anterior cruciate ligament-injured athletes had a 2.5 times greater knee abduction moment ( P < . 001 ) and 20 % higher ground reaction force ( P < . 05 ) , whereas stance time was 16 % shorter ; hence , increased motion , force , and moments occurred more quickly . Knee abduction moment predicted anterior cruciate ligament injury status with 73 % specificity and 78 % sensitivity ; dynamic valgus measures showed a predictive r2 of 0.88 . Conclusion Knee motion and knee loading during a l and ing task are predictors of anterior cruciate ligament injury risk in female athletes . Clinical Relevance Female athletes with increased dynamic valgus and high abduction loads are at increased risk of anterior cruciate ligament injury . The methods developed may be used to monitor neuromuscular control of the knee joint and may help develop simpler measures of neuromuscular control that can be used to direct female athletes to more effective , targeted interventions The Neurobehavioral Evaluation System was design ed for field studies of workers , but many NES tests can be performed satisfactorily by children as young as 7 or 8 years old and a few tests , such as simple reaction time , can be performed by preschool children . However , little comparative data from children of different ages or grade levels are available . Studies of school children in the Czech Republic indicate that 2nd- grade children could perform the following NES tests satisfactorily : Finger Tapping , Visual Digit Span . Continuous Performance , Symbol-Digit Substitution , Pattern Comparison , and simpler conditions of Switching Attention . Comparative scores of boys and girls from the 2nd , 4th , and 8th grade s and power analyses to estimate appropriate sample size were presented . Performance varied systematic ally with grade level and gender . Larger sample s were needed with younger children to achieve comparable levels of statistical power . Gender comparisons indicated that boys responded faster , but made more errors than girls This study examined whether age-related improvements observed in the motor performance of children result from a reduction of noise in the output of the sensori-motor system . Children ages 6 , 8 , and 10 years and young adults ( N = 48 , 12 per group ) performed continuous , constant isometric force contractions with the index finger at four different force levels with and without visual feedback . The results revealed that : ( a ) performance improved with increases in age , ( b ) the force output signal exhibited increased irregularity and a more broadb and frequency profile with increases in age under conditions with feedback , and ( c ) there were no age differences in the irregularity of the force signal and smaller age differences in the frequency profiles under conditions without feedback . It is proposed that the age-related enhancements in performance throughout childhood are primarily due to a more appropriate mapping of the organization of the sensori-motor system to the task constraints rather than to reduction of system noise Background Athletes who return to sport participation after anterior cruciate ligament reconstruction ( ACLR ) have a higher risk of a second anterior cruciate ligament injury ( either reinjury or contralateral injury ) compared with non — anterior cruciate ligament— injured athletes . Hypotheses Prospect i ve measures of neuromuscular control and postural stability after ACLR will predict relative increased risk for a second anterior cruciate ligament injury . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-six athletes underwent a prospect i ve biomechanical screening after ACLR using 3-dimensional motion analysis during a drop vertical jump maneuver and postural stability assessment before return to pivoting and cutting sports . After the initial test session , each subject was followed for 12 months for occurrence of a second anterior cruciate ligament injury . Lower extremity joint kinematics , kinetics , and postural stability were assessed and analyzed . Analysis of variance and logistic regression were used to identify predictors of a second anterior cruciate ligament injury . Results Thirteen athletes suffered a subsequent second anterior cruciate ligament injury . Transverse plane hip kinetics and frontal plane knee kinematics during l and ing , sagittal plane knee moments at l and ing , and deficits in postural stability predicted a second injury in this population ( C statistic = 0.94 ) with excellent sensitivity ( 0.92 ) and specificity ( 0.88 ) . Specific predictive parameters included an increase in total frontal plane ( valgus ) movement , greater asymmetry in internal knee extensor moment at initial contact , and a deficit in single-leg postural stability of the involved limb , as measured by the Biodex stability system . Hip rotation moment independently predicted second anterior cruciate ligament injury ( C = 0.81 ) with high sensitivity ( 0.77 ) and specificity ( 0.81 ) . Conclusion Altered neuromuscular control of the hip and knee during a dynamic l and ing task and postural stability deficits after ACLR are predictors of a second anterior cruciate ligament injury after an athlete is released to return to sport |
13,486 | 29,234,452 | Among CETP variants , the rs9989419 best represented this genome wide association signal across all population s , based on LD r2 estimates from 1000 genomes references .
Regarding the rs708272 ( Taq1B ) , individuals with the B1 risk allele showed better responses to dietary interventions than those with B2B2 genotype , whereas with I405V , inconsistent results have been reported .
Modest alcohol consumption was associated with decreased risk of coronary heart disease among B2 carriers of rs708272.It is concluded that variations in the CETP gene may modulate the effects of dietary components on metabolic traits . | Data on diet – genotype interactions in the prevention or treatment of dyslipidemia have increased remarkably .
This systematic review aim ed to assess nutrigenetic studies regarding the modulating effect of diet on cholesteryl ester transfer protein ( CETP ) polymorphisms in relation to metabolic traits . | Recent work suggests that plant sterol ( PS ) consumption may lower triglyceride ( TG ) concentrations ; however , human clinical trial evidence is inconsistent . We associated SNP r5882 in cholesteryl ester transfer protein with changes in TG concentrations following PS consumption ( 2 g/day for 4 weeks ) in a dual-centre , single-blind , r and omized , crossover trial . TG concentrations were lowered in homozygotes for the minor G-allele of rs5882 ( -0.46 ± 0.13 mmol/L , p = 0.002 , n = 10 ) ; there was no effect in the A-allele carriers Background —Recent trial data have challenged the hypothesis that cholesteryl ester transfer protein ( CETP ) and high-density lipoprotein cholesterol ( HDL-C ) have causal roles in atherothrombosis . One method to evaluate this issue is to examine whether polymorphisms in the CETP gene that impact on HDL-C levels also impact on the future development of myocardial infa rct ion . Methods and Results —In a prospect i ve cohort of 18 245 initially healthy American women , we examined over 350 000 singe-nucleotide polymorphisms ( SNPs ) first to identify loci associated with HDL-C and then to evaluate whether significant SNPs within these loci also impact on rates of incident myocardial infa rct ion during an average 10-year follow-up period . Nine loci on 9 chromosomes had 1 or more SNPs associated with HDL-C at genome-wide statistical significance ( P<5 × 10−8 ) . However , only SNPs near or in the CETP gene at 16q13 were associated with both HDL-C and risk of incident myocardial infa rct ion ( 198 events ) . For example , SNP rs708272 in the CETP gene was associated with a per-allele increase in HDL-C levels of 3.1 mg/dL and a concordant 24 % lower risk of future myocardial infa rct ion ( age-adjusted hazard ratio , 0.76 ; 95 % CI , 0.62 to 0.94 ) , consistent with recent meta- analysis . Independent and again concordant effects on HDL-C and incident myocardial infa rct ion were also observed at the CETP locus for rs4329913 and rs7202364 . Adjustment for HDL-C attenuated but did not eliminate these effects . Conclusion —In this prospect i ve cohort of initially healthy women , SNPs at the CETP locus impact on future risk of myocardial infa rct ion , supporting a causal role for CETP in atherothrombosis , possibly through an HDL-C mediated pathway Fruit and vegetables are key elements of a cardioprotective diet , but benefits on plasma lipids , especially HDL-cholesterol ( HDL-C ) , are inconsistent both within and between studies . In the present study , we investigated whether four selected HDL-C-related polymorphisms ( cholesteryl ester transfer protein ( CETP ) Taq1B , APOA1 - 75G/A , hepatic lipase ( LIPC ) - 514C → T , and endothelial lipase ( LIPG ) I24582 ) modulate the plasma lipid response to a kiwifruit intervention . This is a retrospective analysis of data collected during a 12-week r and omised controlled cross-over trial . A total of eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in period before being r and omised to one of two 4-week intervention sequences of two green kiwifruit/d plus healthy diet ( kiwifruit intervention ) or healthy diet alone ( control intervention ) . The measurement of anthropometric parameters and collection of fasting blood sample s were carried out at baseline 1 and after the run-in ( baseline 2 ) and intervention periods . At baseline 2 , B1/B1 homozygotes of the CETP Taq1B gene had significantly higher total cholesterol : HDL-C , TAG : HDL-C , and apoB : apoA1 ratios and small-dense LDL concentrations than B2 carriers . A significant CETP Taq1B genotype × intervention interaction was observed for the TAG : HDL-C ratio ( P= 0·03 ) . B1/B1 homozygotes had a significantly lower TAG : HDL-C ( - 0·23 ( sd 0·58 ) mmol/l ; P= 0·03 ) ratio after the kiwifruit intervention than after the control intervention , whereas the ratio of B2 carriers was not affected . The lipid response was not affected by other gene polymorphisms . In conclusion , the significant decrease in the TAG : HDL-C ratio in B1/B1 homozygotes suggests that regular inclusion of green kiwifruit as part of a healthy diet may improve the lipid profiles of hypercholesterolaemic men with this genotype There are no definitive explanations as to why individuals with hypercholesterolemia , a major cardiovascular risk factor , respond differently to dietary change . Fifty five free-living individuals completed a double crossover trial with two dietary regimens , a high saturated fat diet ( providing 21 % energy from saturated fat and 3 % energy from polyunsaturated fat ) and a high polyunsaturated fat diet ( providing 11 % energy as saturated fat and 10 % energy as polyunsaturated fat ) , each phase continuing for 4 weeks . Extensive genotyping and several measures of dietary compliance have provided further insights regarding the determinants of extent of cholesterol response to changes in the nature of dietary fat . Individuals with the CETP B1B1 genotype and the LPL X447 + allele showed an average 0 . 44 ( 95 % CI : 0.22 , 0.66 ) and 0.45 ( 95 % CI : 0.18 , 0.72 ) mmol/l greater change in total cholesterol , respectively , than those with one or more CETP B2 allele or homozygous for the LPL S447 allele when comparing diets high and low in saturated fat . Indices of dietary compliance including changes in reported saturated and polyunsaturated fat intake and change in triglyceride linoleate were not significantly different between the CETP genotypes . Change in reported saturated ( r=0.36 , P=0.04 ) and polyunsaturated ( r=0.22 , P=0 . 05 ) fat intake and change in triglyceride linoleate ( reflecting polyunsaturated fat intake ) ( r=0.21 , P=0.07 ) , also predicted total cholesterol response to dietary fat changes . In multivariate analyses , variation in the cholesterol ester transfer protein and lipoprotein lipase genes predicted response independent of measures of dietary compliance , suggesting that these two genes are important determinants of variation in cholesterol response to dietary change in free-living individuals Little is known about whether cholesteryl ester transfer protein ( CETP ) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels . We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year r and omized weight-loss trial [ Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) ] , and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [ Dietary Intervention R and omized Controlled Trial ( DIRECT ) ] . In the POUNDS LOST , participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol ( P = 0.001 ) and decreases in triglycerides ( P = 0.007 ) than those on the low-fat diet at 6 months , while no significant difference between these two diets was observed among participants carrying other genotypes . The gene-diet interactions on changes in HDL-cholesterol and triglycerides were replicated in the DIRECT ( pooled P for interaction ≤ 0.01 ) . Similar results on trajectory of changes in HDL cholesterol and triglycerides over the 2 year intervention were observed in both trials . Our study provides replicable evidence that individuals with the CETP rs3764261 CC genotype might derive greater effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet We examined the relationships of I405V cholesteryl ester transfer protein ( CETP ) , Taq1B CETP and apolipoprotein (apo)E polymorphisms with the pattern of response to dietary plant sterol ester ( PSE ) by plasma lipids and CETP concentrations as well as lecithin-cholesterol acyltransferase ( LCAT ) activity . Subjects with moderate primary hypercholesterolemia ( 20 - 60 y old ; 50 women ; 10 men ) consumed margarine ( 20 g/d ) without ( placebo ) or with PSE ( 2.8 g/d = 1.68 g/d phytosterols ) for 4 wk each period , in a crossover , double-blind study . Plasma CETP concentration was measured by ELISA ; endogenous LCAT activity was expressed as the percentage of esterification ( 30 min incubation ) of the subjects ' (14)C-unesterified cholesterol HDL . PSE reduced concentrations of plasma total cholesterol ( TC ) ( 10 % ) and LDL cholesterol ( LDL-C ) ( 12 % ) . In relation to the I405V CETP polymorphism , the percentage reductions in TC with consumption of PSE for the II , IV and VV phenotypes were 7.2 , 4.2 and not significant , respectively , whereas LDL-C significant reductions occurred only for II ( 9.5 % ) . However , the CETP concentration diminished only in the II phenotype The possible role of four c and i date genes in lipid and lipoprotein response to diet was examined in 214 members of two large kibbutz settlements in Israel . Four site polymorphisms ( signal peptide insertion/deletion , XbaI , EcoRI and MspI ) of the apo B gene , the common apo E genotypes , three common mutations ( T-93 G , S447stop and N291S ) of the LPL gene and the CETP I405V RFLP were determined . The average reduction induced by diet in participants with the absence of the EcoRI restriction site ( L4154 ) of the apo B gene compared with those found to be homozygotes for the restriction site ( G/G4154 ) were : 16.2 and 8.0 mg/dl for total cholesterol ( TC ) ( P=0 . 01 ) ; and 15.6 and 6.2 mg/dl for LDL-C ( P=0.007 ) , respectively . TC and LDL-C baseline levels were significantly different among the apo-E genotypes , yet there were no significant effects on lipid and lipoprotein dietary response . Triglyceride baseline values were significantly lower ( P=0.007 ) among subjects with the LPL S447stop mutation and HDL-C was significantly lower ( P=0.008 ) among subjects found to be heterozygous for the LPL N291S mutation . A heterogeneous response for triglyceride was observed for individuals with the S291 allele as compared to those individuals who were found to be homozygous for the N291 allele . No differences in dietary responsiveness were observed among the apo E and CETP genotypes . In conclusion , our results suggest that sequence variation(s ) in the coding region of the apo B gene linked to the EcoRI polymorphism are associated with total cholesterol and LDL-C responsiveness to dietary manipulation . In our study population , LPL mutations had a significant effect on TG and HDL-C baseline levels and on their response to diet Cholesteryl ester transfer protein ( CETP ) , as a c and i date gene for dyslipoproteinemia and coronary heart disease , was studied in 105 men with low plasma concentrations of high density lipoprotein cholesterol ( HDL-C ) and established coronary heart disease as well as in 515 r and omly selected men and women . A one-nucleotide substitution ( G to A ) in exon 15 , which changes arginine ( 451 ) to glutamine in CETP protein , was detected by PCR-SSCP and direct sequencing and screened in the population sample by a simple PCR-based restriction assay . In the r and om population sample the allele frequency of the R451Q mutation was 1.9 % . Men heterozygous for the R451Q mutation ( n = 7 ) had 27 % higher CETP activity than age- , body mass index- , smoking- and alcohol consumption-matched controls with normal genotype ( n = 21 ; P = 0.003 ) . Women heterozygous for the R451Q mutation ( n = 7 ) had 16 % lower total cholesterol compared to matched controls ( n = 21 ; P = 0.07 ) , but no such difference was detected in men . In the r and om population sample the correlation between plasma total cholesterol level and CETP activity was 0.19 ( P = 0.044 ) , both in men and women . When women with total cholesterol over 5.2 mmol/l were excluded from analysis , heterozygotes ( n = 4 ) had plasma CETP activity of 113 nmol/h/ml plasma , whereas those of normal genotype ( n = 12 ) had 103 nmol/h/ml plasma , but this difference was not statistically significant . Women heterozygous for the R451Q mutation and consuming less than 10 g alcohol a week had 23 % lower HDL-C compared to women with the normal genotype ( P = 0.032 ) . In conclusion , we describe a mutation in the CETP gene associated with high plasma CETP activity in men and with low total cholesterol in women . Further studies are needed to evaluate the effect of mutation on the risk of coronary heart disease A preponderance of dense low density lipoprotein ( LDL ) particles is associated with an increased risk of coronary heart disease . It has been shown that dense LDL levels can be modified by diet . We investigated the contribution of polymorphisms in the genes for apolipoprotein ( apo ) B , apo AIV , lipoprotein lipase ( LPL ) and cholesterol ester transfer protein ( CETP ) to variation in the changes in plasma concentrations of dense LDL between a high saturated and a high polyunsaturated fatty acid diet . A total of 46 freeliving individuals ( 19 men and 27 women ) completed a crossover trial with two dietary interventions of 4 weeks each , a high saturated fat diet ( providing 21 % energy from saturated fat and 3 % energy from polyunsaturated fat ) and a high polyunsaturated fat diet ( providing 11 % energy as saturated fat and 10 % energy as polyunsaturated fat ) . Overall , the change in dense LDL between the saturated and polyunsaturated fat period was 0.17+/-0.33 mmol/L and this change was similar in men and women . Of the polymorphisms studied only variation in the apo AIV gene causing the substitution of histidine for glutamine at position 360 ( Q360H ) was associated with significant differences in the change in dense LDL concentration . Apo AIV Q/H individuals ( n=6 ) showed a three-fold greater change in dense LDL cholesterol unadjusted for Lp(a ) levels than Q/Q individuals ( 0.46+/-0.27 versus 0.12+/-0.31 mmol/L , p=0.02 ) . The greater decrease in dense LDL cholesterol with an increase in polyunsaturated fat seen in those with the apo AIV H360 variant , who represent roughly 10 % of the general population , suggests that they may benefit most from a PUFA rich lipid lowering diet BACKGROUND AND AIMS Some individuals respond to a greater extent than others to changes in dietary fat and cholesterol even when dietary intake is consistent . A prospect i ve study has been undertaken in which two groups of individuals according to cholesteryl ester transfer protein ( CETP ) genotype were compared in terms of plasma lipid response to altering the nature of dietary fat in a free-living situation . METHODS AND RESULTS Following genotyping , 35 individuals with the CETP Taq1 B1B1 genotype were paired with age and sex-matched individuals with one or two CETP B2 alleles , to undertake a single crossover trial with a diet high in saturated fat and a diet high in polyunsaturated fat . There was no washout period between the two 4-week phases . Plasma lipoproteins were measured at the beginning and end of each phase . The difference ( 95 % CI ) in plasma LDL-cholesterol concentration at the end of the PUFA and SAFA diets was 0.95 ( 0.71 , 1.19 ) mmol/l in the CETP B1B1 group and 0.80 ( 0.57 , 1.04 ) mmol/l in the group with at least one CETP B2 allele . The dietary induced changes in the two genotype groups were not significantly different ( p=0.38 ) from each other . Comparable results were observed for plasma total cholesterol . The high PUFA and SAFA diets did not significantly alter plasma HDL concentration in either of the CETP genotype groups . Response was also similar according to apolipoprotein E genotype ( E3E3 vs E4 + ) and lipoprotein lipase genotype ( S447X ) . CONCLUSIONS The results of this study do not support previous studies in which CETP genotype predicted plasma LDL-cholesterol response to diet . CETP genotype does not significantly affect the change in plasma total and LDL-cholesterol concentrations that occur when altering the nature of dietary fat . These data suggest that the influence of genetic factors on total and LDL-cholesterol may be relatively small in comparison with the effect of dietary manipulation Background : This study aim ed to examine the changes in serum lipids in children with mild hypercholesterolemia after the use of skim milk or olive-oil-enriched skim milk in their diet and the modulation of lipid levels by the Taq 1B polymorphism in the cholesteryl-ester transfer protein gene . Methods : Thirty-six prepubertal children with mild hypercholesterolemia were r and omly assigned in a crossover design into 2 groups of 16 and 20 individuals . Both groups received , in sequential inverse order , the 2 types of milk for 2 periods of 6 weeks . Results : Carriers of at least 1 B2 allele had an adjusted basal HDL cholesterol level significantly higher than children with the B1B1 genotype ( 1.291 mmol/l , 95 % CI : 1.184–1.397 , vs. 1.082 mmol/l , 95 % CI : 0.931–1.233 ; p = 0.027 ) . In contrast , there were no significant differences in the adjusted basal levels of apolipoprotein A-I ( B2 carriers : 1.292 g/l , 95 % CI : 1.218–1.367 ; B1B1 genotype : 1.215 g/l , 95 % CI : 1.109–1.320 ; p = 0.223 ) . The intake of olive-oil-enriched skim milk caused significant increases in HDL cholesterol and apolipoprotein A-I , both in B2 ( 0.089 mmol/l , 95 % CI : 0.032–0.146 , p = 0.005 ; 0.55 g/l , 95 % CI : 0.012–0.098 ; p = 0.018 ) and in B1B1 carriers ( 0.179 mmol/l , 95 % CI : 0.096–0.262 ; p < 0.001 ; and 0.095 g/l , 95 % CI : 0.032–0.157 ; p = 0.003 ) . This increase in HDL cholesterol was significantly higher in the B1B1 group ( p = 0.049 ) . Conclusion : The consumption of skim milk enriched with olive oil increases the HDL cholesterol and apolipoprotein A-I levels in children with hypercholesterolemia , this effect being more intense in carriers of the B1B1 genotype BACKGROUND The preference of the apolipoprotein ( apo ) B/apoA-I ratio over the total cholesterol/HDL cholesterol ( TC/HDL-C ) ratio in cardiovascular risk prediction is disputed . Cholesteryl ester transfer protein ( CETP ) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins . We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event ( MACE ) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio . METHODS A prospect i ve case-cohort study was performed ( PREVEND cohort ; no previous cardiovascular disease and no use of lipid-lowering drugs initially ) . Fasting serum TC/HDL-C , apoB/apoA-I , triglycerides , and common CETP variations ( TaqIB [ rs708272 ] and -629C > A [ rs1800775 ] polymorphisms ) were measured at baseline . The composite end point was incident MACE . RESULTS A total of 532 of 6780 subjects experienced a first MACE during 10.8 years follow-up . The age- and sex-adjusted hazard ratio was 1.31 ( 95 % confidence interval 1.23 - 1.41 ) for the apoB/apoA-I ratio and 1.22 ( 95 % confidence interval 1.26 - 1.39 ) for the TC/HDL-C ratio ( both P < .001 ) . These relationships were essentially similar within each TaqIB and -629C > A CETP genotype group . No interactions of the apoB/apoA-I ratio and the TC/HDL-C ratio with the TaqIB and the -629C > A CETP variations on incident MACE were observed ( P > .20 for all ) . CONCLUSION The relationship of first MACE with the TC/HDL-C and the apoB/apoA-I ratio is not to an important extent dependent on common CETP variations . CETP variations are unlikely to affect the strength of the relationship of first MACE with the apoB/apoA-I ratio compared with the TC/HDL-C ratio |
13,487 | 26,412,799 | FINDINGS Niacin may reduce cardiovascular events as monotherapy ; however , recent trials in combination with statins have failed to show a benefit .
Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes .
Fibrates may improve cardiovascular outcomes as monotherapy ; however , trials in combination with statins have failed to show a benefit , except in those with elevated triglycerides ( > 200 mg/dL ) or low HDL-C ( < 40 mg/dL ) .
There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events .
IMPLICATION S Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline -directed statin therapy .
In certain clinical situations , such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy , those with persistent severe elevations in triglycerides , or patients with high cardiovascular risk , some nonstatin therapies may be useful in reducing cardiovascular events . | PURPOSE Cardiovascular disease ( CVD ) is the leading cause of morbidity and mortality in the United States .
Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD .
However , the optimal treatment strategy for patients who can not tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy .
The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes , to provide recommendations for use of nonstatin therapies in clinical practice , and to review emerging nonstatin therapies for management of dyslipidemia .
Ezetimibe-statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome . | The British Regional Heart Study ( BRHS ) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol ( HDLC ) and incidence of coronary heart disease was eliminated by covariance adjustment . Using the proportional hazards model and adjusting for age , blood pressure , smoking , body mass index , and low-density lipoprotein cholesterol , we analyzed this relation separately in the Framingham Heart Study ( FHS ) , Lipid Research Clinics Prevalence Mortality Follow-up Study ( LRCF ) and Coronary Primary Prevention Trial ( CPPT ) , and Multiple Risk Factor Intervention Trial ( MRFIT ) . In CPPT and MRFIT ( both r and omized trials in middle-age high-risk men ) , only the control groups were analyzed . A 1-mg/dl ( 0.026 mM ) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2 % in men ( FHS , CPPT , and MRFIT ) and 3 % in women ( FHS ) . In LRCF , where only fatal outcomes were documented , a 1-mg/dl increment in HDLC was associated with significant 3.7 % ( men ) and 4.7 % ( women ) decrements in cardiovascular disease mortality rates . The 95 % confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably , and all contained the range 1.9 - 2.9 % . HDLC levels were essentially unrelated to non-cardiovascular disease mortality . When differences in analytic methodology were eliminated , a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies BACKGROUND In observational analyses , higher levels of high-density lipoprotein ( HDL ) cholesterol have been associated with a lower risk of coronary heart disease events . However , whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain . Inhibition of cholesteryl ester transfer protein ( CETP ) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes . METHODS We r and omly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib , at a dose of 600 mg daily , or placebo , in addition to the best available evidence -based care . The primary efficacy end point was a composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , unstable angina , or cardiac arrest with resuscitation . RESULTS At the time of r and omization , the mean HDL cholesterol level was 42 mg per deciliter ( 1.1 mmol per liter ) , and the mean low-density lipoprotein ( LDL ) cholesterol level was 76 mg per deciliter ( 2.0 mmol per liter ) . Over the course of the trial , HDL cholesterol levels increased from baseline by 4 to 11 % in the placebo group and by 31 to 40 % in the dalcetrapib group . Dalcetrapib had a minimal effect on LDL cholesterol levels . Patients were followed for a median of 31 months . At a prespecified interim analysis that included 1135 primary end-point events ( 71 % of the projected total number ) , the independent data and safety monitoring board recommended termination of the trial for futility . As compared with placebo , dalcetrapib did not alter the risk of the primary end point ( cumulative event rate , 8.0 % and 8.3 % , respectively ; hazard ratio with dalcetrapib , 1.04 ; 95 % confidence interval , 0.93 to 1.16 ; P=0.52 ) and did not have a significant effect on any component of the primary end point or total mortality . The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo ( P<0.001 for both comparisons ) . CONCLUSIONS In patients who had had a recent acute coronary syndrome , dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events . ( Funded by F. Hoffmann-La Roche ; dal- OUTCOMES Clinical Trials.gov number , NCT00658515 . ) Background — There is no r and omized , double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline -adjusted treatment of acute myocardial infa rct ion . Methods and Results — OMEGA is a r and omized , placebo-controlled , double-blind , multicenter trial testing the effects of omega-3-acid ethyl esters-90 ( 1 g/d for 1 year ) on the rate of sudden cardiac death in survivors of acute myocardial infa rct ion , if given in addition to current guideline -adjusted treatment . Secondary end points were total mortality and nonfatal clinical events . Patients ( n=3851 ; female , 25.6 % ; mean age , 64.0 years ) were r and omized in 104 German centers 3 to 14 days after acute myocardial infa rct ion from October 2003 until June 2007 . Acute coronary angiography was performed in 93.8 % and acute percutaneous coronary intervention in 77.8 % of all patients . During a follow-up of 365 days , the event rates were ( omega and control groups ) as follows : sudden cardiac death , 1.5 % and 1.5 % ( P=0.84 ) ; total mortality , 4.6 % and 3.7 % ( P=0.18 ) ; major adverse cerebrovascular and cardiovascular events , 10.4 % and 8.8 % ( P=0.1 ) ; and revascularization in survivors , 27.6 % and 29.1 % ( P=0.34 ) . Conclusions — Guideline -adjusted treatment of acute myocardial infa rct ion results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up , which could not be shown to be further reduced by the application of omega-3 fatty acids . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00251134 BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients Bococizumab is a humanized monoclonal antibody binding proprotein convertase subtilisin/kexin type 9 , which may be a potential therapeutic option for reducing low-density lipoprotein cholesterol ( LDL-C ) levels in patients with hypercholesterolemia . In this 24-week , multicenter , double-blind , placebo-controlled , dose-ranging study ( NCT01592240 ) , subjects with LDL-C levels≥80 mg/dl on stable statin therapy were r and omized to Q14 days subcutaneous placebo or bococizumab 50 , 100 , or 150 mg or Q28 days subcutaneous placebo or bococizumab 200 or 300 mg . Doses of bococizumab were reduced if LDL-C levels persistently decreased to ≤25 mg/dl . The primary end point was the absolute change in LDL-C levels from baseline to week 12 after placebo or bococizumab administration . Continuation of bococizumab administration through to week 24 enabled the collection of safety data over an extended period . Of the 354 subjects r and omized , 351 received treatment ( placebo [ n=100 ] or bococizumab [ n=251 ] ) . The most efficacious bococizumab doses were 150 mg Q14 days and 300 mg Q28 days . Compared with placebo , bococizumab 150 mg Q14 days reduced LDL-C at week 12 by 53.4 mg/dl and bococizumab 300 mg Q28 days reduced LDL-C by 44.9 mg/dl ; this was despite dose reductions in 32.5 % and 34.2 % of subjects at week 10 or 8 , respectively . Pharmacokinetic/pharmacodynamic model-based simulation assuming no dose reductions predicted that bococizumab would lower LDL-C levels by 72.2 and 55.4 mg/dl , respectively . Adverse events were similar across placebo and bococizumab groups . Few subjects ( n=7 ; 2 % ) discontinued treatment because of treatment-related adverse events . In conclusion , bococizumab significantly reduced LDL-C across all doses despite dose reductions in many subjects . Model-based simulations predicted greater LDL-C reduction in the absence of bococizumab dose reduction . The Q14 days regimen is being evaluated in phase 3 clinical trials A total of 96 patients with moderate elevations of low-density lipoprotein ( LDL ) cholesterol were r and omly assigned to 4 different double-blind treatment regimens : placebo ; colestipol 5 g and lovastatin 20 mg/day ( C5 + L20 ) ; colestipol 10 g and lovastatin 20 mg/day ( C10 + L20 ) ; and lovastatin 40 mg/day ( L40 ) . During 12 weeks of therapy , C10 + L20 achieved the greatest reduction in total cholesterol ( -32 % ) and LDL cholesterol ( -48 % ) levels from baseline . This combination also exhibited significantly greater reductions in LDL cholesterol levels than the C5 + L20 and L40 groups ( p < 0.01 ) . The differences in total and LDL cholesterol reduction between the C5 + L20 and L40 groups were not significant . Similar changes and differences between treatments were seen in apolipoprotein B levels . Whereas mean total apolipoprotein A-I levels increased with all treatments ( p < 0.05 ) , lipoprotein particles A-I were significantly increased in the C10 + L20 group ( p < 0.01 ) only . Results demonstrate that the combination of low-dose lovastatin ( 20 mg/day ) with low-dose colestipol ( 5 or 10 g/day ) produces LDL cholesterol reductions equal to or greater than higher doses of lovastatin ( 40 mg/day ) . In addition , low-dose combinations are > 25 % more cost-effective than high-dose monotherapy In a double-blind clinical trial of clofibrate versus identical quantity of corn oil 497 patients with ischaemic heart disease were observed over a period of five years . The death rate and the rate of non-fatal infa rcts were significantly less among the clofibrate group , and the difference was greatest in respect of sudden deaths and among patients who had previously suffered from angina rather than infa rct ion . The cholesterol- and triglyceride-reducing properties of clofibrate were maintained throughout the period of the trial and side effects were very few . But the protective action of the drug against new infa rcts and death bore no apparent relation to these properties Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infa rct ion , ischaemic stroke , and the need for coronary revascularisation in people without kidney disease , but its effects in people with moderate-to-severe kidney disease are uncertain . The SHARP trial aim ed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients . Methods This r and omised double-blind trial included 9270 patients with chronic kidney disease ( 3023 on dialysis and 6247 not ) with no known history of myocardial infa rct ion or coronary revascularisation . Patients were r and omly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo . The key prespecified outcome was first major atherosclerotic event ( non-fatal myocardial infa rct ion or coronary death , non-haemorrhagic stroke , or any arterial revascularisation procedure ) . All analyses were by intention to treat . This trial is registered at Clinical Trials.gov , NCT00125593 , and IS RCT N54137607 . Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo . Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L ( SE 0·02 ; with about two-thirds compliance ) during a median follow-up of 4·9 years and produced a 17 % proportional reduction in major atherosclerotic events ( 526 [ 11·3 % ] simvastatin plus ezetimibe vs 619 [ 13·4 % ] placebo ; rate ratio [ RR ] 0·83 , 95 % CI 0·74–0·94 ; log-rank p=0·0021 ) . Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infa rct ion or died from coronary heart disease ( 213 [ 4·6 % ] vs 230 [ 5·0 % ] ; RR 0·92 , 95 % CI 0·76–1·11 ; p=0·37 ) and there were significant reductions in non-haemorrhagic stroke ( 131 [ 2·8 % ] vs 174 [ 3·8 % ] ; RR 0·75 , 95 % CI 0·60–0·94 ; p=0·01 ) and arterial revascularisation procedures ( 284 [ 6·1 % ] vs 352 [ 7·6 % ] ; RR 0·79 , 95 % CI 0·68–0·93 ; p=0·0036 ) . After weighting for subgroup-specific reductions in LDL cholesterol , there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined , and , in particular , they were similar in patients on dialysis and those who were not . The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination ( 9 [ 0·2 % ] vs 5 [ 0·1 % ] ) . There was no evidence of excess risks of hepatitis ( 21 [ 0·5 % ] vs 18 [ 0·4 % ] ) , gallstones ( 106 [ 2·3 % ] vs 106 [ 2·3 % ] ) , or cancer ( 438 [ 9·4 % ] vs 439 [ 9·5 % ] , p=0·89 ) and there was no significant excess of death from any non-vascular cause ( 668 [ 14·4 % ] vs 612 [ 13·2 % ] , p=0·13 ) . Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease . Funding Merck/Schering-Plough Pharmaceuticals ; Australian National Health and Medical Research Council ; British Heart Foundation ; UK Medical Research Council AIMS High-density lipoprotein cholesterol ( HDL-C ) is inversely associated with cardiovascular ( CV ) events and thus an attractive therapeutic target . However , in spite of marked elevations in HDL-C , the first cholesterol transport protein ( CETP ) inhibitor torcetrapib raised blood pressure ( BP ) , impaired endothelial function , and increased CV mortality and morbidity . Dalcetrapib is a novel molecule acting on CETP with a different chemical structure to torcetrapib . As HDL stimulates nitric oxide ( NO ) , suppresses inflammation , and exerts protective CV effects , we investigated the effects of dalcetrapib on endothelial function , blood pressure , inflammatory markers , and lipids in patients with , or at risk of , coronary heart disease ( CHD ) in a double-blind r and omized placebo-controlled trial ( clinical trials.gov number NCT00655538 ) . METHODS AND RESULTS Patients with target low-density lipoprotein cholesterol ( LDL-C ) levels received dalcetrapib 600 mg/day or placebo for 36 weeks on top of st and ard therapy ( including statins ) . The primary outcome measures were the change from baseline of flow-mediated dilatation ( % FMD ) of the right brachial artery after 5 min of cuff occlusion at 12 weeks and the 24 h ambulatory blood pressure monitoring ( ABPM ) at week 4 . Secondary outcomes included change from baseline in FMD after 36 weeks and the change in ABPM at 12 and 36 weeks , changes in HDL-C , LDL-C , triglycerides , CETP activity , as well as st and ard safety parameters . Four hundred seventy-six patients were r and omized . Baseline FMD was 4.1 ± 2.2 and 4.0 ± 2.4 % with placebo or dalcetrapib , respectively and did not change significantly from placebo after 12 and 36 weeks ( P = 0.1764 and 0.9515 , respectively ) . After 4 , 24 , and 36 weeks of treatment with dalcetrapib , CETP activity decreased by 51 , 53 , and 56 % ( placebo corrected , all P < 0.0001 ) , while at weeks 4 , 12 , and 36 HDL-C increased by 25 , 27 , and 31 % ( placebo corrected , all P < 0.0001 ) . Low-density lipoprotein cholesterol levels did not change . At baseline , ABPM was 125 ± 12/74 ± 8mmHg in the placebo and 128 ± 11/75 ± 7mmHg in the dalcetrapib group ( P = 0.3372 and 0.1248 , respectively , placebo-corrected change from baseline ) and did not change for up to 36 weeks . Biomarkers of inflammation , oxidative stress , and coagulation did not change during follow-up except for Lp-PLA(2 ) mass levels which increased by 17 % ( placebo corrected ) . Overall 7 patients given dalcetrapib and 8 patients given placebo experienced at least one pre-specified adjudicated event ( 11 events with dalcetrapib and 12 events with placebo ) . CONCLUSION The dal-VESSEL trial has established the tolerability and safety of CETP-inhibition with dalcetrapib in patients with or at risk of CHD . Dalcetrapib reduced CETP activity and increased HDL-C levels without affecting NO-dependent endothelial function , blood pressure , or markers of inflammation and oxidative stress . The dal- OUTCOMES trial ( NCT00658515 ) will show whether dalcetrapib improves outcomes in spite of a lack of effect on endothelial function BACKGROUND Inhibition of proprotein convertase subtilisin/kexin type 9 serine protease ( PCSK9 ) result ed in large reductions of low-density lipoprotein cholesterol ( LDL-C ) in phase 1 trials . We assessed the efficacy and safety of various doses and dosing intervals of REGN727 , a monoclonal antibody to PCSK9 , added to statins , to further lower LDL-C in patients with heterozygous familial hypercholesterolaemia . METHODS This multicentre , r and omised , placebo-controlled phase 2 trial was done at 16 lipid clinics in the USA and Canada . Between Jan 18 , 2011 , and Nov 7 , 2011 , we enrolled adults with heterozygous familial hypercholesterolaemia and LDL-C concentrations of 2·6 mmol/L or higher on stable diet and statin dose , with or without ezetimibe . Patients were r and omly assigned to receive REGN727 150 mg , 200 mg , or 300 mg every 4 weeks , or 150 mg every 2 weeks , or placebo every 2 weeks ( ratio 1:1:1:1:1 ) . R and omisation was stratified by concomitant use of ezetimibe at baseline . Investigators , study staff , and patients were masked to treatment group . Blinding was maintained by administration of placebo alternating with REGN727 for the groups of 4 week dosing . The primary endpoint was mean percent reduction in LDL-C from baseline at week 12 and was analysed in the modified intention-to-treat population with an analysis of covariance ( ANCOVA ) model with treatment group . This trial is registered in Clinical Trials.gov , number NCT 01266876 . FINDINGS 77 patients were r and omly assigned to study groups ( 15 - 16 patients per group ) and all were analysed . Least-squares ( LS ) mean LDL-C reduction from baseline to week 12 was 28·9 % ( SE 5·08 ) for 150 mg every 4 weeks ( p=0·0113 ) , 31·54 % ( 4·91 ) for 200 mg every 4 weeks ( p=0·0035 ) , 42·53 % ( 5·09 ) for 300 mg every 4 weeks ( p<0·0001 ) , and 67·90 % ( 4·85 ) for 150 mg every 2 weeks ( p<0·0001 ) , compared with 10·65 % ( 5·04 ) with placebo . One serious adverse event was reported with placebo and none with REGN727 . No increases of more than three times the upper limit of normal were reported for hepatic transaminases or creatinine kinase . The most common adverse event was injection-site reaction with one patient in the group of 300 mg REGN727 terminating treatment . INTERPRETATION REGN727 was well tolerated and achieved substantial further LDL-C reduction in patients with heterozygous familial hypercholesterolaemia and elevated LDL-C treated with high-dose statins , with or without ezetimibe . REGN727 has the potential to provide optimum control of LDL-C in patients with this disorder . FUNDING Sanofi US and Regeneron Pharmaceuticals Incorporated There is a large body of scientific evidence that has been confirmed in r and omized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish . For alpha-linolenic acid ( ALA ) , which is the omega-3 fatty acid from plants , the relation to cardiovascular health is less clear . We review ed the recent literature on dietary ALA intake , ALA tissue concentrations , and cardiovascular health in humans . Short-term trials ( 6–12 weeks ) in generally healthy participants mostly showed no or inconsistent effects of ALA intake ( 1.2–3.6 g/d ) on blood lipids , low-density lipoprotein oxidation , lipoprotein(a ) , and apolipoproteins A-I and B. Studies of ALA in relation to inflammatory markers and glucose metabolism yielded conflicting results . With regard to clinical cardiovascular outcomes , there is observational evidence for a protective effect against nonfatal myocardial infa rct ion . However , no protective associations were observed between ALA status and risk of heart failure , atrial fibrillation , and sudden death . Findings from long-term trials of ALA supplementation are awaited to answer the question whether food-based or higher doses of ALA could be important for cardiovascular health in cardiac patients and the general population BACKGROUND Alirocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , has been shown to reduce low-density lipoprotein ( LDL ) cholesterol levels in patients who are receiving statin therapy . Larger and longer-term studies are needed to establish safety and efficacy . METHODS We conducted a r and omized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter ( 1.8 mmol per liter ) or more and were receiving treatment with statins at the maximum tolerated dose ( the highest dose associated with an acceptable side-effect profile ) , with or without other lipid-lowering therapy . Patients were r and omly assigned in a 2:1 ratio to receive alirocumab ( 150 mg ) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks . The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24 . RESULTS At week 24 , the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points ( P<0.001 ) ; the treatment effect remained consistent over a period of 78 weeks . The alirocumab group , as compared with the placebo group , had higher rates of injection-site reactions ( 5.9 % vs. 4.2 % ) , myalgia ( 5.4 % vs. 2.9 % ) , neurocognitive events ( 1.2 % vs. 0.5 % ) , and ophthalmologic events ( 2.9 % vs. 1.9 % ) . In a post hoc analysis , the rate of major adverse cardiovascular events ( death from coronary heart disease , nonfatal myocardial infa rct ion , fatal or nonfatal ischemic stroke , or unstable angina requiring hospitalization ) was lower with alirocumab than with placebo ( 1.7 % vs. 3.3 % ; hazard ratio , 0.52 ; 95 % confidence interval , 0.31 to 0.90 ; nominal P=0.02 ) . CONCLUSIONS Over a period of 78 weeks , alirocumab , when added to statin therapy at the maximum tolerated dose , significantly reduced LDL cholesterol levels . In a post hoc analysis , there was evidence of a reduction in the rate of cardiovascular events with alirocumab . ( Funded by Sanofi and Regeneron Pharmaceuticals ; ODYSSEY LONG TERM Clinical Trials.gov number , NCT01507831 . ) CONTEXT An estimated 10 % to 20 % of patients can not tolerate statins or adequate doses to achieve treatment goals . Plasma proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) binds to low-density lipoprotein ( LDL ) receptors , promoting their degradation and increasing LDL cholesterol levels . In phase 1 studies , a human monoclonal antibody to PCSK9 , AMG145 , was well tolerated and reduced LDL cholesterol levels . OBJECTIVE To assess the efficacy and tolerability of AMG145 in patients with statin intolerance due to muscle-related side effects . DESIGN , SETTING , AND PATIENTS A 12-week , r and omized , double-blind , placebo- and ezetimibe-controlled , dose-ranging study conducted between July 2011 and May 2012 in statin-intolerant adult patients at 33 international sites . INTERVENTION Patients were r and omized equally to 1 of 5 groups : AMG145 alone at doses of 280 mg , 350 mg , or 420 mg ; AMG145 at 420 mg plus 10 mg of ezetimibe ; or 10 mg of ezetimibe plus placebo . AMG145 or placebo was administered subcutaneously every 4 weeks . MAIN OUTCOME MEASURES The primary end point was percentage change from baseline to week 12 in ultracentrifugation-measured LDL cholesterol . Other end points included measures of safety and tolerability of different doses of AMG145 and AMG145 plus ezetimibe . RESULTS Of 236 patients screened , 160 were r and omized ( mean age , 62 years ; 64 % female ; mean baseline LDL cholesterol , 193 mg/dL ) ; all patients had intolerance to 1 or more statins because of muscle-related events . At week 12 , mean changes in LDL cholesterol levels were -67 mg/dL ( -41 % ; 95 % CI , -49 % to -33 % ) for the AMG145 , 280-mg , group ; -70 mg/dL ( -43 % ; 95 % CI , -51 % to -35 % ) for the 350-mg group ; -91 mg/dL ( -51 % ; 95 % CI , -59 % to -43 % ) for the 420-mg group ; and -110 mg/dL ( -63 % ; 95 % CI , -71 % to -55 % ) for the 420-mg/ezetimibe group compared with -14 mg/dL ( -15 % ; 95 % CI , -23 % to -7.0 % ) for the placebo/ezetimibe group ( P < .001 ) . Four serious adverse events were reported with AMG145 ( coronary artery disease , acute pancreatitis , hip fracture , syncope ) . Myalgia was the most common treatment-emergent adverse event during the study , occurring in 5 patients ( 15.6 % ) in the 280-mg group ( n = 32 ) ; 1 patient ( 3.2 % ) in the 350-mg group ( n = 31 ) , 1 patient ( 3.1 % ) in the 420-mg group ( n = 32 ) , 6 patients ( 20.0 % ) receiving 420-mg AMG145/ezetimibe , and 1 patient ( 3.1 % ) receiving placebo/ezetimibe . CONCLUSION In this phase 2 study in statin-intolerant patients , subcutaneous administration of a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels and was associated with short-term tolerability . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01375764 BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . ) BACKGROUND High-density lipoprotein cholesterol ( HDL-C ) levels are inversely associated with cardiovascular risk . Cholesteryl ester transfer protein inhibition is one strategy for increasing HDL-C. This study evaluated the lipid-altering efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy or coadministered with atorvastatin in patients with dyslipidemia . METHODS A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia ( 53.8 % of the study population had low HDL-C ) were r and omized equally to one of 10 groups : 5 groups received background statin therapy of atorvastatin 20 mg and 5 did not , and each of these was r and omized to placebo , anacetrapib 10 , 40 , 150 , and 300 mg once daily for 8 weeks . An equal proportion of patients had triglycerides > 150 mg/dL in each group . RESULTS For placebo and anacetrapib monotherapy ( 10 , 40 , 150 , and 300 mg ) , least squares mean percent changes from baseline to week 8 for low-density lipoprotein cholesterol ( LDL-C ) were 2 % , -16 % , -27 % , -40 % , and -39 % , respectively , and for HDL-C were 4 % , 44 % , 86 % , 139 % , and 133 % , respectively ( P < .001 vs placebo for all doses ) . Coadministration of anacetrapib with atorvastatin produced significant incremental LDL-C reductions and similar HDL-C increases versus atorvastatin monotherapy . For both anacetrapib monotherapy and coadministration with atorvastatin , the LDL-C reductions were similar in patients with baseline triglyceride levels greater than and less than or equal to the median . Anacetrapib was well tolerated , and the incidence of adverse events was similar for placebo and all active treatment groups . There were no increases in systolic or diastolic blood pressure in any treatment arm . CONCLUSIONS Anacetrapib , as monotherapy or coadministered with atorvastatin , produced significant reductions in LDL-C and increases in HDL-C ; the net result of treatment with anacetrapib + atorvastatin was approximately 70 % lowering of LDL-C and more than doubling of HDL-C. Anacetrapib was generally well tolerated with no discernable effect on blood pressure Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids , or both , could prevent major cardiovascular events in patients with a history of ischaemic heart disease or stroke . Design Double blind , r and omised , placebo controlled trial ; factorial design . Setting Recruitment throughout France via a network of 417 cardiologists , neurologists , and other physicians . Participants 2501 patients with a history of myocardial infa rct ion , unstable angina , or ischaemic stroke . Intervention Daily dietary supplement containing 5-methyltetrahydrofolate ( 560 μg ) , vitamin B-6 ( 3 mg ) , and vitamin B-12 ( 20 μg ) or placebo ; and containing omega 3 fatty acids ( 600 mg of eicosapentanoic acid and docosahexaenoic acid at a ratio of 2:1 ) or placebo . Median duration of supplementation was 4.7 years . Main outcome measures Major cardiovascular events , defined as a composite of non-fatal myocardial infa rct ion , stroke , or death from cardiovascular disease . Results Allocation to B vitamins lowered plasma homocysteine concentrations by 19 % compared with placebo , but had no significant effects on major vascular events ( 75 v 82 patients , hazard ratio , 0.90 ( 95 % confidence interval 0.66 to 1.23 , P=0.50 ) ) . Allocation to omega 3 fatty acids increased plasma concentrations of omega 3 fatty acids by 37 % compared with placebo , but also had no significant effect on major vascular events ( 81 v 76 patients , hazard ratio 1.08 ( 0.79 to 1.47 , P=0.64 ) ) . Conclusion This study does not support the routine use of dietary supplements containing B vitamins or omega 3 fatty acids for prevention of cardiovascular disease in people with a history of ischaemic heart disease or ischaemic stroke , at least when supplementation is introduced after the acute phase of the initial event . Trial registration Current Controlled Trials IS RCT N41926726 The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infa rct ion . The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects . No evidence of efficacy was found for the clofibrate treatment . Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infa rct ion but did not decrease total mortality . With a mean follow-up of 15 years , nearly 9 years after termination of the trial , mortality from all causes in each of the drug groups , except for niacin , was similar to that in the placebo group . Mortality in the niacin group was 11 % lower than in the placebo group ( 52.0 versus 58.2 % ; p = 0.0004 ) . This late benefit of niacin , occurring after discontinuation of the drug , may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfa rct ion or a result of the cholesterol-lowering effect of niacin , or both BACKGROUND AND METHODS The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography . Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter , documented coronary artery disease , and a family history of vascular disease , 120 completed the 2 1/2-year double-blind study , which included arteriography at base line and after treatment . Patients were given dietary counseling and were r and omly assigned to one of three treatments : lovastatin ( 20 mg twice a day ) and colestipol ( 10 g three times a day ) ; niacin ( 1 g four times a day ) and colestipol ( 10 g three times a day ) ; or conventional therapy with placebo ( or colestipol if the low-density lipoprotein [ LDL ] cholesterol level was elevated ) . RESULTS The levels of LDL and high-density lipoprotein ( HDL ) cholesterol changed only slightly in the conventional-therapy group ( mean changes , -7 and + 5 percent , respectively ) , but more substantially among patients treated with lovastatin and colestipol ( -46 and + 15 percent ) or niacin and colestipol ( -32 and + 43 percent ) . In the conventional-therapy group , 46 percent of the patients had definite lesion progression ( and no regression ) in at least one of nine proximal coronary segments ; regression was the only change in 11 percent . By comparison , progression ( as the only change ) was less frequent among patients who received lovastatin and colestipol ( 21 percent ) and those who received niacin and colestipol ( 25 percent ) , and regression was more frequent ( lovastatin and colestipol , 32 percent ; niacin and colestipol , 39 percent ; P less than 0.005 ) . Multivariate analysis indicated that a reduction in the level of apolipoprotein B ( or LDL cholesterol ) and in systolic blood pressure , and an increase in HDL cholesterol correlated independently with regression of coronary lesions . Clinical events ( death , myocardial infa rct ion , or revascularization for worsening symptoms ) occurred in 10 of 52 patients assigned to conventional therapy , as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol ( relative risk of an event during intensive treatment , 0.27 ; 95 percent confidence interval , 0.10 to 0.77 ) . CONCLUSIONS In men with coronary artery disease who were at high risk for cardiovascular events , intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions , increased the frequency of regression , and reduced the incidence of cardiovascular events Objective In a r and omized 5-yr multi-intervention trial , we tested the efficacy of intensified health education ( IHE ) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease ( IHD ) . Research Design and Methods Within the intervention group , the benefit of clofibric acid was evaluated in a double-blind study . One thous and one hundred thirty-nine newly diagnosed middle-aged ( 30- to 55-yr-old ) patients with non-insulindependent diabetes mellitus ( NIDDM ) entered the study . They were classified as diet controlled after a 6- wk screening phase with conventional dietary treatment . During the follow-up , the control group ( n = 378 ) was cared for at different diabetes outpatient clinics with a st and ardized surveillance . The intervention group ( n = 761 ) had a structured IHE that included dietary advice , antismoking and antialcohol education , and ways to enhance physical activity . Results R and omly , 379 of the IHE patients received 1.6 g clofibric acid/day , and the others received placebo . IHE result ed in improved glucose control ( adjusted fasting blood glucose ) levels after 5 yr ( control subjects 9.27 mM , IHE group 8.71 mM , and IHE plus clofibric acid group 8.60 mM , P < 0.01 ) . The better glycemic control was achieved with fewer antidiabetic drugs . After 5 yr , antidiabetic drugs were prescribed to 47 % of the control subjects , 28 % of the IHE group , and 34 % of the IHE plus clofibric acid group ( cutoff limit for drug application was postpr and ial blood glucose of ≥13.87 mM ) . The ratio of polyunsaturated to saturated fatty acids ( 0.26 vs. 0.40 , P < 0.01 ) and physical activity ( 174 vs. 327 scores , P < 0.01 ) were increased , and blood pressure , tobacco , and alcohol consumption were significantly reduced by IHE . However , IHE had no effect on calorie intake , percentage of fat in the diet ( 45 % ) , and body weight . The most important finding was the significant increase of blood cholesterol in all three groups ( + 0.47 , + 0.36 , and + 0.34 mM , respectively ) . Clofibric acid only prevented the increase of triglyceride levels ( + 0.56 , + 0.24 , and + 0.05 mM , respectively ) . The incidence rate per 1000 for myocardial infa rct ion was 30.3 for control subjects , 53.6 for the IHE group , and 55.6 for the IHE plus clofibric acid group . The corresponding rates for IHD incidence were 90.9 , 97.8 , and 98.8 , respectively . Men suffered more frequently from myocardial infa rct ion , whereas women developed ECG criteria for IHD more frequently . Among the 35 cases of death , besides cardiovascular diseases , liver cirrhosis and neoplasia were the predominant causes . The death rate per 1000 in control subjects was 46.2 , 30.6 in the IHE group , and 27 among patients with IHE plus clofibric acid . Conclusions IHE was of substantial benefit for the control of glycemia , significantly diminished the need for antidiabetic drugs , and reduced a cluster of risk factors but had no effect on the control of blood lipids . This could be one major reason for the failure of IHE , effective lowering of blood pressure , and clofibric acid to prevent cardiovascular complications . Clofibric acid was only effective in reducing triglycerides The Cholesterol Lowering Atherosclerosis Study ( CLAS ) was a r and omized , placebo-controlled , angiographic trial testing combined colestipol-niacin therapy in 162 subjects . Two-year results ( CLAS-I ) showed decreased atherosclerosis progression and increased regression . We now describe a subgroup of 103 subjects treated for 4 years ( CLAS-II ) . Changes in blood lipid , lipoprotein-cholesterol , and apolipoprotein levels were maintained , and at 4 years significantly more drug-treated subjects demonstrated nonprogression ( 52 % drug- vs 15 % placebo-treated ) and regression ( 18 % drug- vs 6 % placebo-treated ) in native coronary artery lesions . Significantly fewer drug-treated subjects developed new lesions in native coronary arteries ( 14 % drug- vs 40 % placebo-treated ) and bypass grafts ( 16 % drug- vs 38 % placebo-treated ) . These results confirm CLAS-I findings and indicate that regression can continue for 4 years . They reaffirm the need for early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects Consecutive survivors of a myocardial infa rct ion from the Southern Hospital , below 70 years of age , were r and omized into a Control group ( n = 276 ) and a Treatment group ( n = 279 ) . The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering . Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital . The concentration of serum cholesterol and triglyceride was lowered by 13 % and 19 % , respectively , in the Treatment group compared to the Control group . Total mortality was 82 cases in the Control group and 61 in the Treatment group , a 26 % reduction ( p less than 0.05 ) . For patients above 60 years of age in the Treatment group the reduction in mortality was 28 % ( p less than 0.05 ) . IHD mortality was reduced by 36 % ( p less than 0.01 ) in the Treatment group compared to the Control group . The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways . First , it only occurred in patients with a triglyceride level greater than 1.5 mmol/l ( n = 216 ) . Secondly , it was most pronounced in the 44 % of the treated patients who had a lowering of the serum triglyceride by 30 % or more , and in this subgroup the reduction of IHD mortality was 60 % ( p less than 0.01 ) . For serum cholesterol there were no such relations . The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients , occurring in 50 % , while hypercholesterolaemia only occurred in 13 % . Caution should be exercised in the interpretation of the results as the trial was not blind . However , the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was responsible for the beneficial effect of the treatment The Cholesterol-Lowering Atherosclerosis Study ( CLAS ) was a r and omized , placebo-controlled , angiographic trial testing combined colestipol hydrochloride and niacin therapy in 162 nonsmoking men aged 40 to 59 years with previous coronary bypass surgery . During two years of treatment there was a 26 % reduction in total plasma cholesterol , a 43 % reduction in low-density lipoprotein cholesterol , plus a simultaneous 37 % elevation of high-density lipoprotein cholesterol . This result ed in a significant reduction in the average number of lesions per subject that progressed ( P less than .03 ) and the percentage of subjects with new atheroma formation ( P less than .03 ) in native coronary arteries . Also , the percentage of subjects with new lesions ( P less than .04 ) or any adverse change in bypass grafts ( P less than .03 ) was significantly reduced . Deterioration in overall coronary status was significantly less in drug-treated subjects than placebo-treated subjects ( P less than .001 ) . Atherosclerosis regression , as indicated by perceptible improvement in overall coronary status , occurred in 16.2 % of colestipol-niacin treated vs 2.4 % placebo treated ( P = .002 ) Objective : To see whether mortality among men with angina can be reduced by dietary advice . Design : A r and omized controlled factorial trial . Setting : Male patients of general practitioners in south Wales . Subjects : A total of 3114 men under 70 y of age with angina . Interventions : Subjects were r and omly allocated to four groups : ( 1 ) advised to eat two portions of oily fish each week , or to take three fish oil capsules daily ; ( 2 ) advised to eat more fruit , vegetables and oats ; ( 3 ) given both the above types of advice ; and ( 4 ) given no specific dietary advice . Mortality was ascertained after 3–9 y. Results : Compliance was better with the fish advice than with the fruit advice . All-cause mortality was not reduced by either form of advice , and no other effects were attributable to fruit advice . Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised ; the adjusted hazard ratio was 1.26 ( 95 % confidence interval 1.00 , 1.58 ; P=0.047 ) , and even greater for sudden cardiac death ( 1.54 ; 95 % CI 1.06 , 2.23 ; P=0.025 ) . The excess risk was largely located among the subgroup given fish oil capsules . There was no evidence that it was due to interactions with medication . Conclusion : Advice to eat more fruit was poorly complied with and had no detectable effect on mortality . Men advised to eat oily fish , and particularly those supplied with fish oil capsules , had a higher risk of cardiac death . This result is unexplained ; it may arise from risk compensation or some other effect on patients ' or doctors ' behaviour . Sponsorship : British Heart Foundation , Seven Seas Limited , Novex Pharma Limited , The Fish Foundation BACKGROUND Coronary risk factors related to the insulin resistance syndrome tend to cluster in the same individual . Our previous studies have shown that the dyslipidemia characteristic of this syndrome -- low HDL cholesterol and high triglyceride ( TG ) levels -- responds well to treatment with gemfibrozil . Most factors related to insulin-resistance syndrome decrease fibrinolytic capacity , whereas a recent study showed that gemfibrozil improves it and thus may attenuate thrombotic events . To discover whether subjects with clustering of factors related to this resistance might in particular benefit from gemfibrozil , we reanalyzed the Helsinki Heart Study data . METHODS AND RESULTS We used Cox regression models to explore the effects of gemfibrozil among overweight subjects with additional coronary risk factors in this hypercholesterolemic male population of 2046 subjects r and omized to gemfibrozil and 2035 to placebo . The effect of gemfibrozil was largely confined to overweight subjects : among those with body mass index ( BMI ) > 26 kg/m2 , the net difference in cardiac end points between gemfibrozil and placebo groups was 21 ( 25 of 1119 versus 46 of 1081 ) , and in those with BMI < or = 26 kg/m2 , it was 7 ( 31 of 927 versus 38 of 954 ) . The risk reduction with gemfibrozil was 78 % ( P = .002 ) among those with BMI > 26 kg/m2 and dyslipidemia ( TG > or = 2.3 mmol/L and HDL cholesterol < 1.08 mmol/L ) . Among those with BMI > 26 kg/m2 and three or four of the following factors present -- smoking , sedentary lifestyle , blood pressure > or = 140/90 mm Hg , or blood glucose > 4.4 mmol/L -- the risk reduction was 68 % ( P = .03 ) . CONCLUSIONS Gemfibrozil reduced the coronary risk mainly in overweight subjects with additional risk factors known to contribute to the insulin-resistance syndrome or predispose to it BACKGROUND The inhibition of cholesteryl ester transfer protein ( CETP ) is considered a potential new mechanism for treatment of dyslipidaemia . Anacetrapib ( MK-0859 ) is a CETP inhibitor currently under development . We aim ed to assess anacetrapib 's effects as monotherapy on low-density lipoprotein cholesterol ( LDL-C ) and high-density lipoprotein cholesterol ( HDL-C ) and on 24-h ambulatory blood pressure . METHODS We did two double-blind , r and omised , placebo-controlled phase I studies . In the first study , 50 patients with dyslipidaemia ( LDL-C 100 - 190 mg/dL ; 40 active , 10 placebo ) aged 18 - 75 years received anacetrapib doses of 0 , 10 , 40 , 150 , or 300 mg orally once a day with a meal for 28 days . St and ard lipid and lipoprotein monitoring , safety monitoring , and anacetrapib concentrations for pharmacokinetics were done . In the second study , 22 healthy participants aged 45 - 75 years received either 150 mg of anacetrapib once a day or matching placebo with a meal for 10 days in each crossover period , in a r and omised sequence , with at least a 14-day washout between the treatment periods . Continuous 24-h ambulatory blood pressure monitoring was done on day -1 and day 10 of each treatment period in this study . The primary or secondary endpoints of safety and tolerability were assessed in both studies by monitoring clinical adverse experiences , physical examinations , vital signs , 12-lead electrocardiogram , and laboratory safety . Analysis was per protocol . These trials are registered with Clinical Trials.gov , number NCT00565292 and NCT00565006 . FINDINGS In the dyslipidaemia study , one patient withdrew consent and one was excluded from the data analysis for HDL-C and LDL-C because complete pre-dose measurements were not available . Anacetrapib produced dose-dependent lipid-altering effects with peak lipid-altering effects of 129 % ( mean 51.1 [ SD 3.8]-114.9 [ 7.9 ] mg/dL ) increase in HDL-C and a 38 % ( 138.2 [11.4]-77.6 [ 7.9 ] mg/dL ) decrease in LDL-C in patients with dyslipidaemia . In the 24-h ambulatory blood pressure study in healthy individuals , least squares difference between anacetrapib and placebo groups on day 10 were 0.60 ( 90 % CI -1.54 to 2.74 ; p=0.634 ) mm Hg for systolic blood pressure and 0.47 ( 90 % CI -0.90 to 1.84 ; p=0.561 ) mm Hg for diastolic blood pressure . INTERPRETATION Anacetrapib seems to exhibit HDL-C increases greater than those seen with other investigational drugs in this class and LDL-C lowering effects similar to statins . Despite greater lipid-altering effects relative to other members of this class , anacetrapib seems not to increase blood pressure , suggesting that potent CETP inhibition by itself might not lead to increased blood pressure BACKGROUND Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in short-term studies . We conducted two extension studies to obtain longer-term data . METHODS In two open-label , r and omized trials , we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ( " parent trials " ) of evolocumab . Regardless of study -group assignments in the parent trials , eligible patients were r and omly assigned in a 2:1 ratio to receive either evolocumab ( 140 mg every 2 weeks or 420 mg monthly ) plus st and ard therapy or st and ard therapy alone . Patients were followed for a median of 11.1 months with assessment of lipid levels , safety , and ( as a prespecified exploratory analysis ) adjudicated cardiovascular events including death , myocardial infa rct ion , unstable angina , coronary revascularization , stroke , transient ischemic attack , and heart failure . Data from the two trials were combined . RESULTS As compared with st and ard therapy alone , evolocumab reduced the level of LDL cholesterol by 61 % , from a median of 120 mg per deciliter to 48 mg per deciliter ( P<0.001 ) . Most adverse events occurred with similar frequency in the two groups , although neurocognitive events were reported more frequently in the evolocumab group . The risk of adverse events , including neurocognitive events , did not vary significantly according to the achieved level of LDL cholesterol . The rate of cardiovascular events at 1 year was reduced from 2.18 % in the st and ard-therapy group to 0.95 % in the evolocumab group ( hazard ratio in the evolocumab group , 0.47 ; 95 % confidence interval , 0.28 to 0.78 ; P=0.003 ) . CONCLUSIONS During approximately 1 year of therapy , the use of evolocumab plus st and ard therapy , as compared with st and ard therapy alone , significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis . ( Funded by Amgen ; OSLER-1 and OSLER-2 Clinical Trials.gov numbers , NCT01439880 and NCT01854918 . ) Clinical trial evidence exists that supports a role for the omega-3 polyunsaturated fatty acids in coronary heart disease prevention . However , the results from these clinical trials have varied and were conducted in diverse population groups using several different types of omega-3 polyunsaturated fatty acids , including eicosapentaenoic acid , docosahexaenoic acid , and alpha-linolenic acid ( ALA ) . Thus , we systematic ally review ed previously published reports assessing the different types of omega-3 polyunsaturated fatty acid interventions and cardiovascular outcomes . Fourteen r and omized clinical trials were included in the review . Six trials were included with fish oil , with 1 large trial ( 10,000 patients ) dominating the analysis . In aggregate , the fish oil trials demonstrated a reduction in total mortality and sudden death without a clinical ly significant reduction in nonfatal myocardial infa rct ion . The 6 trials with ALA supplements or an ALA-enriched diet were of poorer design than the fish oil trials and had limited power . Many of the trials with ALA involved other changes in dietary components . In aggregate , the ALA trials demonstrated possible benefits in reducing sudden death and nonfatal myocardial infa rct ion , but with wider confidence intervals than in the fish oil trials . In conclusion , the evidence suggests a role for fish oil ( eicosapentaenoic acid , docosahexaenoic acid ) or fish in secondary prevention because recent clinical trial data have demonstrated a significant reduction in total mortality , coronary heart disease death , and sudden death . The data on ALA have been limited by studies of smaller sample size and limited quality BACKGROUND Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein ( LDL ) cholesterol level . Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein ( HDL ) cholesterol level , but its clinical efficacy and safety are uncertain . METHODS After a prer and omization run-in phase to st and ardize the background statin-based LDL cholesterol-lowering therapy and to establish participants ' ability to take extended-release niacin without clinical ly significant adverse effects , we r and omly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily . The primary outcome was the first major vascular event ( nonfatal myocardial infa rct ion , death from coronary causes , stroke , or arterial revascularization ) . RESULTS During a median follow-up period of 3.9 years , participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter ( 0.25 mmol per liter as measured in the central laboratory ) lower and an HDL cholesterol level that was an average of 6 mg per deciliter ( 0.16 mmol per liter ) higher than the levels in those assigned to placebo . Assignment to niacin-laropiprant , as compared with assignment to placebo , had no significant effect on the incidence of major vascular events ( 13.2 % and 13.7 % of participants with an event , respectively ; rate ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.90 to 1.03 ; P=0.29 ) . Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious ( absolute excess as compared with placebo , 3.7 percentage points ; P<0.001 ) and with an increased incidence of diabetes diagnoses ( absolute excess , 1.3 percentage points ; P<0.001 ) , as well as increases in serious adverse events associated with the gastrointestinal system ( absolute excess , 1.0 percentage point ; P<0.001 ) , musculoskeletal system ( absolute excess , 0.7 percentage points ; P<0.001 ) , skin ( absolute excess , 0.3 percentage points ; P=0.003 ) , and unexpectedly , infection ( absolute excess , 1.4 percentage points ; P<0.001 ) and bleeding ( absolute excess , 0.7 percentage points ; P<0.001 ) . CONCLUSIONS Among participants with atherosclerotic vascular disease , the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events . ( Funded by Merck and others ; HPS2-THRIVE Clinical Trials.gov number , NCT00461630 . ) PURPOSE To examine the efficacy and safety of colesevelam hydrochloride , a novel , nonsystemic , lipid-lowering agent , when coadministered with starting doses of simvastatin in a multicenter , r and omized , double-blind , placebo-controlled trial . PATIENTS AND METHODS Subjects with hypercholesterolemia ( plasma low density lipoprotein [ LDL ] cholesterol level > 160 mg/dL and triglyceride level < or = 300 mg/dL ) were r and omly assigned to receive daily doses of placebo ( n = 33 ) , colesevelam 3.8 g ( recommended dose , n = 37 ) , simvastatin 10 mg ( n = 35 ) , colesevelam 3.8 g with simvastatin 10 mg ( n = 34 ) , colesevelam 2.3 g ( low dose , n = 36 ) , simvastatin 20 mg ( n = 39 ) , or colesevelam 2.3 g with simvastatin 20 mg ( n = 37 ) , for 6 weeks . RESULTS Mean LDL cholesterol levels decreased relative to baseline in the placebo group ( P < 0.05 ) and in all active treatment groups ( P < 0.0001 ) . For groups treated with combination therapy , the mean reduction in LDL cholesterol level was 42 % ( -80 mg/dL ; P < 0.0001 compared with baseline ) , which exceeded the reductions for simvastatin 10 mg ( -26 % , -48 mg/dL ) or 20 mg ( -34 % , -61 mg/dL ) alone , or for colesevelam 2.3 g ( -8 % , -17 mg/dL ) or 3.8 g ( -16 % , -31 mg/dL ) alone ( P < 0.001 ) . The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone . Side effects were similar among treatment groups , and there were no clinical ly important changes in laboratory parameters . CONCLUSION Coadministration of colesevelam and simvastatin was effective and well tolerated , providing additive reductions in LDL cholesterol levels compared with either agent alone BACKGROUND Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) increases serum LDL-cholesterol ( LDL-C ) concentrations . We assessed the effects of AMG 145 , a human monoclonal antibody against PCSK9 , in patients with hypercholesterolaemia in the absence of concurrent lipid-lowering treatment . METHODS In a phase 2 trial done at 52 centres in Europe , the USA , Canada , and Australia , patients ( aged 18 - 75 years ) with serum LDL-C concentrations of 2·6 mmol/L or greater but less than 4·9 mmol/L were r and omly assigned equally through an interactive voice response system to subcutaneous injections of AMG 145 70 mg , 105 mg , or 140 mg , or placebo every 2 weeks ; subcutaneous AMG 145 280 mg , 350 mg , or 420 mg or placebo every 4 weeks ; or oral ezetimibe 10 mg/day . The primary endpoint was percentage change from baseline in LDL-C concentration at week 12 . Analysis was by modified intention to treat . Study personnel and patients were masked to treatment assignment of AMG 145 or placebo . Ezetimibe assignment was open label . This trial is registered with Clinical Trials.gov , number NCT01375777 . FINDINGS 406 patients were assigned to AMG 145 70 mg ( n=45 ) , 105 mg ( n=46 ) , or 140 mg ( n=45 ) every 2 weeks ; AMG 145 280 mg ( n=45 ) , 350 mg ( n=45 ) , or 420 mg ( n=45 ) every 4 weeks ; placebo every 2 weeks ( n=45 ) or every 4 weeks ( n=45 ) ; or ezetimibe ( n=45 ) . AMG 145 significantly reduced LDL-C concentrations in all dose groups ( mean baseline LDL-C concentration 3·7 mmol/L [ SD 0·6 ] ; changes from baseline with every 2 weeks AMG 145 70 mg -41·0 % [ 95 % CI -46·2 to -35·8 ] ; 105 mg -43·9 % [ -49·0 to -38·7 ] ; 140 mg -50·9 % [ -56·2 to -45·7 ] ; every 4 weeks AMG 145 280 mg -39·0 % [ -44·1 to -34·0 ] ; 350 mg -43·2 % [ -48·3 to -38·1 ] ; 420 mg -48·0 % [ -53·1 to -42·9 ] ; placebo every 2 weeks -3·7 % [ -9·0 to 1·6 ] ; placebo every 4 weeks 4·5 % [ -0·7 to 9·8 ] ; and ezetimibe -14·7 % [ -18·6 to -10·8 ] ; p<0·0001 for all doses vs placebo or ezetimibe ) . Treatment-emergent adverse events occurred in 136 ( 50 % ) of 271 patients in the AMG 145 groups , 41 ( 46 % ) of 90 patients in the placebo groups , and 26 ( 58 % ) of 45 patients in the ezetimibe group ; no deaths or serious treatment-related adverse events were reported . INTERPRETATION The results of our study support the further assessment of AMG 145 in long-term studies with larger and more diverse population s including patients with documented statin intolerance . FUNDING Amgen Objective : Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery . This was a prospect i ve r and omized , open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a 12-month prognosis after vascular surgery . Methods : Patients were r and omly assigned to receive rosuvastatin ( RSV ) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe ( RSV/EZT ) 10 mg/d , starting prior to scheduled surgical procedure . The primary end point was the first major cardiovascular event , including death from cardiac causes , nonfatal myocardial infa rct ion , ischemic stroke , and unstable angina . Results : A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol . As many as 6.6 % of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6 % in the RSV/EZT group ( P = .72 ) . From month 1 to 12 of the follow-up period , primary end point was observed ( 9 taking RSV vs 2 in the RSV/EZT group [ P = .04 ] ) . Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV ( 75.87 ± 31.64 vs 87.19 ± 31.7 , P = .004 ) , while no differential effect on triglyceride , high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups . Conclusion : Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery . Nonetheless , whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies In the Lipid Research Clinics Coronary Primary Prevention Trial ( LRC-CPPT ) , a 19 % lower incidence of coronary heart disease ( CHD ) in cholestyramine-treated men was accompanied by mean falls of 8 % and 12 % in plasma total ( TOTAL-C ) and low-density lipoprotein ( LDL-C ) cholesterol levels relative to levels in placebo-treated men . When the cholestyramine treatment group was analyzed separately , a 19 % reduction in CHD risk was also associated with each decrement of 8 % in TOTAL-C or 11 % in LDL-C levels ( P less than .001 ) . Moreover , CHD incidence in men sustaining a fall of 25 % in TOTAL-C or 35 % in LDL-C levels , typical responses to the prescribed dosage ( 24 g/day ) of cholestyramine resin , was half that of men who remained at pretreatment levels . Adherence to medication was associated with reduced incidence of CHD only when accompanied by falls in TOTAL-C and LDL-C levels . Small increases in high-density lipoprotein cholesterol levels , which accompanied cholestyramine treatment , independently accounted for a 2 % reduction in CHD risk . Thus , the reduction of CHD incidence in the cholestyramine group seems to have been mediated chiefly by reduction of TOTAL-C and LDL-C levels BACKGROUND Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) is a regulator of LDL-cholesterol receptor homeostasis and emerges as a therapeutic target in the prevention of cardiovascular ( CV ) disease . This prospect i ve cohort study analyzes risk prediction with PCSK9 serum concentrations in patients with stable coronary artery disease ( CAD ) on statin treatment . METHODS AND RESULTS Fasting PCSK9 concentrations were measured in 504 consecutive patients with stable CAD confirmed by angiography . Oral glucose tolerance tests were performed in all patients without known diabetes . Patients were followed up for 48months . The primary outcome was the composite of cardiovascular death and unplanned cardiovascular hospitalization . Serum concentrations of PCSK9 predicted CV outcomes ( PCSK9>622 ng/ml vs. < 471 ng/ml : HR 1.55 , 95%-CI 1.11 - 2.16 , p=0.009 ) . Higher PCSK9 concentrations were associated with female gender , hypertension , statin treatment , C-reactive protein , HbA1c , insulin , total cholesterol and fasting triglycerides , but not with LDL- or HDL-cholesterol . The association of PCSK9 levels with CV events was reduced after adjustment for fasting TG . CONCLUSION PCSK9 concentrations predict cardiovascular events in patients with coronary artery disease on statin treatment . Serum triglycerides are correlated with PCSK9 and modify risk prediction by PCSK9 Colesevelam hydrochloride is a novel , potent , non-absorbed lipid-lowering agent previously shown to reduce low density lipoprotein ( LDL ) cholesterol . To examine the efficacy and safety of coadministration of colesevelam and atorvastatin , administration of these agents alone or in combination was examined in a double-blind study of 94 hypercholesterolemic men and women ( baseline LDL cholesterol > or = 160 mg/dl ) . After 4 weeks on the American Heart Association Step I diet , patients were r and omized among five groups : placebo ; colesevelam 3.8 g/day ; atorvastatin 10 mg/day ; coadminstered colesevelam 3.8 g/day plus atorvastatin 10 mg/day ; or atorvastatin 80 mg/day . Fasting lipids were measured at screening , baseline and 2 and 4 weeks of treatment . LDL cholesterol decreased by 12 - 53 % in all active treatment groups ( P<0.01 ) . LDL cholesterol reductions with combination therapy ( 48 % ) were statistically superior to colesevelam ( 12 % ) or low-dose atorvastatin ( 38 % ) alone ( P<0.01 ) , but similar to those achieved with atorvastatin 80 mg/day ( 53 % ) . Total cholesterol decreased 6 - 39 % in all active treatment groups ( P<0.05 ) . High density lipoprotein cholesterol increased significantly for all groups including placebo ( P<0.05 ) . Triglycerides decreased in patients taking atorvastatin alone ( P<0.05 ) , but were unaffected by colesevelam alone or in combination . The frequency of side effects did not differ among groups . At recommended starting doses of each agent , coadministration of colesevelam and atorvastatin was well tolerated , efficacious and produced additive LDL cholesterol reductions comparable to those observed with the maximum atorvastatin dose Aortic valve stenosis and atherosclerotic disease have several risk factors in common , in particular , hypercholesterolemia . Histologically , the diseased valves appear to have areas of inflammation much like atherosclerotic plaques . The effect of lipid-lowering therapy on the progression of aortic stenosis ( AS ) is unclear , and there are no r and omized treatment trials evaluating cardiovascular morbidity and mortality in such patients . The Simvastatin and Ezetimibe in Aortic Stenosis ( SEAS ) Study is a r and omized , double-blind , placebo-controlled , multicenter study of a minimum 4 years ' duration investigating the effect of lipid lowering with ezetimibe/simvastatin 10/40 mg/day in patients with asymptomatic AS with peak transvalvular jet velocity 2.5 to 4.0 m/s . Primary efficacy variables include aortic valve surgery and ischemic vascular events , including cardiovascular mortality , and second , the effect on echocardiographically evaluated progression of AS . The SEAS Study r and omly assigned 1,873 patients ( age 68+/-10 years , 39 % women , mean transaortic maximum velocity 3.1+/-0.5 m/s ) from 173 sites . Other baseline characteristics were mean blood pressure of 145+/-20/82+/-10 mm Hg ( 51 % hypertensive ) ; 55 % were current or previous smokers ; and most were overweight ( mean body mass index 26.9 kg/m2 ) . At baseline , mean total cholesterol was 5.7+/-1.0 mmol/L ( 222 mg/dl ) , low-density lipoprotein cholesterol was 3.6+/-0.9 mmol/L ( 139 mg/dl ) , high-density lipoprotein cholesterol was 1.5+/-0.4 mmol/L ( 58 mg/dl ) , and triglycerides were 1.4+/-0.7 mmol/L ( 126 mg/dl ) . The SEAS Study is the largest r and omized trial to date in patients with AS and will allow determination of the prognostic value of aggressive lipid lowering in such patients BACKGROUND Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids ( PUFA ) can exert favourable effects on atherothrombotic cardiovascular disease , including arrhythmias . We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause . METHODS We undertook a r and omised , double-blind , placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy . We enrolled patients with chronic heart failure of New York Heart Association class II-IV , irrespective of cause and left ventricular ejection fraction , and r and omly assigned them to n-3 PUFA 1 g daily ( n=3494 ) or placebo ( n=3481 ) by a concealed , computerised telephone r and omisation system . Patients were followed up for a median of 3.9 years ( IQR 3.0 - 4.5 ) . Primary endpoints were time to death , and time to death or admission to hospital for cardiovascular reasons . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00336336 . FINDINGS We analysed all r and omised patients . 955 ( 27 % ) patients died from any cause in the n-3 PUFA group and 1014 ( 29 % ) in the placebo group ( adjusted hazard ratio [ HR ] 0.91 [ 95.5 % CI 0.833 - 0.998 ] , p=0.041 ) . 1981 ( 57 % ) patients in the n-3 PUFA group and 2053 ( 59 % ) in the placebo group died or were admitted to hospital for cardiovascular reasons ( adjusted HR 0.92 [ 99 % CI 0.849 - 0.999 ] , p=0.009 ) . In absolute terms , 56 patients needed to be treated for a median duration of 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons . In both groups , gastrointestinal disorders were the most frequent adverse reaction ( 96 [ 3 % ] n-3 PUFA group vs 92 [ 3 % ] placebo group ) . INTERPRETATION A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care Abstract A controlled trial of Clofibrate in 95 patients with established cerebral vascular disease is described . The level of serum cholesterol is significantly lowered in patients on treatment compared with control patients . There is no evidence to indicate that lowering the level of serum cholesterol in patients with established cerebral vascular disease has affected either the incidence of further episodes of cerebral ischaemia or the mortality rate 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 The cardiovascular effects of seafood-derived n-3 polyunsaturated fatty acids ( n-3 PUFA ) have been examined in a diverse and continually exp and ing array of studies ranging from in vitro molecular experiments to large r and omised controlled trials . In contrast to earlier trials , recent clinical trials have not observed significant effects of n-3 PUFA supplementation on cardiovascular disease ( CVD ) events.1 , 2 These mixed findings have stimulated renewed debate and interest about the role of n-3 PUFA for CVD prevention and treatment . Sekikawa and colleagues investigated whether circulating n-3 PUFA levels were associated with differences in new-onset of coronary artery calcification ( CAC ) between middle-aged men in Japan and the USA.3 Measurement of CAC by electron beam CT provides an estimate of overall coronary atherosclerotic burden . While CAC does not necessarily identify with plaque morphology or propensity for rupture , overall CAC burden does predict future risk of clinical CVD events . In this case , investigating the association of circulating n-3 PUFA with serial measures of CAC addresses the interesting hypothesis that these fats might slow atherosclerosis progression , providing mechanistic insight that would be complimentary to studies of clinical endpoints . In this investigation , Japanese men had substantially ( ∼150 % ) higher circulating n-3 PUFA than did US men , consistent with much higher levels of seafood consumption in Japan . Japanese men also had a substantially lower incidence of new CAC ( rate ratio=0.26 , 95%CI=0.09 to 0.73 ) , compared with US men , which was not explained by adjustment for conventional CVD risk factors including age , systolic blood pressure , cholesterol , triglycerides , BMI , diabetes , smoking and hypertension medication . In contrast , the association between country ( Japan vs USA ) and incident CAC was attenuated following adjustment for serum n-3 PUFA . The authors concluded that n-3 PUFA may have antiatherosclerotic effects at levels observed in Japan . While this analysis has several strengths , including use of objective Abstract Serum cholesterol-lowering ability and safety of colestipol hydrochloride were evaluated in a r and omized , placebo-controlled , multiclinic trial in 2278 hypercholesterolemic patients treated for up to 3 yr . After one month of treatment , serum cholesterol declined more ( P ≤ 0.001 ) in the colestipol group ( 32 mg/dl ) than in the placebo group ( 1 mg/dl ) . Serum cholesterol reduction over all observation periods averaged 37 mg/dl in the colestipol group and 7 mg/dl in the placebo group . Colestipol produced no serious side effects . The coronary heart disease ( CHD ) mortality rate was lower in the colestipol-treated men than in the placebo-treated men ( P ≤ 0.02 ) . The total mortality rate as well as the CHD mortality rate was significantly lower ( P ≤ 0.01 in both instances ) in colestipol-treated men with preexisting CHD than in placebo-treated men with preexisting CHD . Mortality rates in women did not differ significantly in the two treatment groups CONTEXT Interest remains high in cholesteryl ester transfer protein ( CETP ) inhibitors as cardioprotective agents . Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins . OBJECTIVE To examine the biochemical effects , safety , and tolerability of evacetrapib , as monotherapy and in combination with statins , in patients with dyslipidemia . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted among 398 patients with elevated low-density lipoprotein cholesterol ( LDL-C ) or low high-density lipoprotein cholesterol ( HDL-C ) levels from April 2010 to January 2011 at community and academic centers in the United States and Europe . INTERVENTIONS Following dietary lead-in , patients were r and omly assigned to receive placebo ( n = 38 ) ; evacetrapib monotherapy , 30 mg/d ( n = 40 ) , 100 mg/d ( n = 39 ) , or 500 mg/d ( n = 42 ) ; or statin therapy ( n = 239 ) ( simvastatin , 40 mg/d ; atorvastatin , 20 mg/d ; or rosuvastatin , 10 mg/d ) with or without evacetrapib , 100 mg/d , for 12 weeks . MAIN OUTCOME MEASURES The co- primary end points were percentage changes from baseline in HDL-C and LDL-C after 12 weeks of treatment . RESULTS The mean baseline HDL-C level was 55.1 ( SD , 15.3 ) mg/dL and the mean baseline LDL-C level was 144.3 ( SD , 26.6 ) mg/dL. As monotherapy , evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL ( 53.6 % to 128.8 % ) compared with a decrease with placebo of -0.7 mg/dL ( -3.0 % ; P < .001 for all compared with placebo ) and decreases in LDL-C of -20.5 to -51.4 mg/dL ( -13.6 % to -35.9 % ) compared with an increase with placebo of 7.2 mg/dL ( 3.9 % ; P < .001 for all compared with placebo ) . In combination with statin therapy , evacetrapib , 100 mg/d , produced increases in HDL-C of 42.1 to 50.5 mg/dL ( 78.5 % to 88.5 % ; P < .001 for all compared with statin monotherapy ) and decreases in LDL-C of -67.1 to -75.8 mg/dL ( -11.2 % to -13.9 % ; P < .001 for all compared with statin monotherapy ) . Compared with evacetrapib monotherapy , the combination of statins and evacetrapib result ed in greater reductions in LDL-C ( P < .001 ) but no greater increase in HDL-C ( P = .39 ) . Although the study was underpowered , no adverse effects were observed . CONCLUSIONS Compared with placebo or statin monotherapy , evacetrapib as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels . The effects on cardiovascular outcomes require further investigation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01105975 BACKGROUND Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease , partly owing to dyslipidaemia , which can be amenable to fibrate therapy . We design ed the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study to assess the effect of fenofibrate on cardiovascular disease events in these patients . METHODS We did a multinational , r and omised controlled trial with 9795 participants aged 50 - 75 years , with type 2 diabetes mellitus , and not taking statin therapy at study entry . After a placebo and a fenofibrate run-in phase , we r and omly assigned patients ( 2131 with previous cardiovascular disease and 7664 without ) with a total-cholesterol concentration of 3.0 - 6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0 - 5.0 mmol/L to micronised fenofibrate 200 mg daily ( n=4895 ) or matching placebo ( n=4900 ) . Our primary outcome was coronary events ( coronary heart disease death or non-fatal myocardial infa rct ion ) ; the outcome for prespecified subgroup analyses was total cardiovascular events ( the composite of cardiovascular death , myocardial infa rct ion , stroke , and coronary and carotid revascularisation ) . Analysis was by intention to treat . The study was prospect ively registered ( number IS RCT N 64783481 ) . FINDINGS Vital status was confirmed on all but 22 patients . Averaged over the 5 years ' study duration , similar proportions in each group discontinued study medication ( 10 % placebo vs 11 % fenofibrate ) and more patients allocated placebo ( 17 % ) than fenofibrate ( 8 % ; p<0.0001 ) commenced other lipid treatments , predominantly statins . 5.9 % ( n=288 ) of patients on placebo and 5.2 % ( n=256 ) of those on fenofibrate had a coronary event ( relative reduction of 11 % ; hazard ratio [ HR ] 0.89 , 95 % CI 0.75 - 1.05 ; p=0.16 ) . This finding corresponds to a significant 24 % reduction in non-fatal myocardial infa rct ion ( 0.76 , 0.62 - 0.94 ; p=0.010 ) and a non-significant increase in coronary heart disease mortality ( 1.19 , 0.90 - 1.57 ; p=0.22 ) . Total cardiovascular disease events were significantly reduced from 13.9 % to 12.5 % ( 0.89 , 0.80 - 0.99 ; p=0.035 ) . This finding included a 21 % reduction in coronary revascularisation ( 0.79 , 0.68 - 0.93 ; p=0.003 ) . Total mortality was 6.6 % in the placebo group and 7.3 % in the fenofibrate group ( p=0.18 ) . Fenofibrate was associated with less albuminuria progression ( p=0.002 ) , and less retinopathy needing laser treatment ( 5.2%vs 3.6 % , p=0.0003 ) . There was a slight increase in pancreatitis ( 0.5%vs 0.8 % , p=0.031 ) and pulmonary embolism ( 0.7%vs 1.1 % , p=0.022 ) , but no other significant adverse effects . INTERPRETATION Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events . It did reduce total cardiovascular events , mainly due to fewer non-fatal myocardial infa rct ions and revascularisations . The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 ( PCSK9 ) . Although statins and fibrates have been reported to increase plasma PCSK9 levels , the effect of niacin on PCSK9 is unknown . We investigated the impact of niacin , atorvastatin , and fenofibrate on PCSK9 levels in 3 distinct studies . A statin-only study r and omized 74 hypercholesterolemic patients to placebo , atorvastatin 10 mg/day , or atorvastatin 80 mg/day for 16 weeks . A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean + 27 % ( 95 % confidence interval [ CI ] + 12 to + 42 ) , confirming the effect of statin therapy on raising PCSK9 . A second study r and omized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day , simvastatin 80 mg/day , or simvastatin 20 mg/extended-release ( ER ) niacin 2 g/day . PCSK9 levels were increased with statin therapy , but decreased with the simvastatin 20 mg/ER niacin combination ( mean -13 % , CI -3 to -23 ) . A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day . Fenofibric acid led to a + 23 % ( CI + 10 to + 36 , p = 0.001 ) increase in PCSK9 ; the addition of niacin result ed in a subsequent -17 % decrease ( CI -19 to -5 , p = 0.004 ) . A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels ( r = 0.62 , p = 0.006 ) with the addition of niacin . In conclusion , niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy . A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9 BACKGROUND Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein ( HDL ) cholesterol level or further lower the low-density lipoprotein ( LDL ) cholesterol level . METHODS We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent , who were receiving long-term statin therapy , and in whom an LDL cholesterol level under 100 mg per deciliter ( 2.6 mmol per liter ) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women ( 1.3 or 1.4 mmol per liter , respectively ) had been achieved . The patients were r and omly assigned to receive extended-release niacin ( target dose , 2000 mg per day ) or ezetimibe ( 10 mg per day ) . The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months . The trial was terminated early , on the basis of efficacy , according to a prespecified analysis conducted after 208 patients had completed the trial . RESULTS The mean HDL cholesterol level in the niacin group increased by 18.4 % over the 14-month study period , to 50 mg per deciliter ( P < 0.001 ) , and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2 % , to 66 mg per deciliter ( 1.7 mmol per liter ) ( P < 0.001 ) . Niacin therapy significantly reduced LDL cholesterol and triglyceride levels ; ezetimibe reduced the HDL cholesterol and triglyceride levels . As compared with ezetimibe , niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months ( P = 0.003 ) , leading to significant reduction of both mean ( P = 0.001 ) and maximal carotid intima-media thickness ( P < or = 0.001 for all comparisons ) . Paradoxically , greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness ( R = -0.31 , P < 0.001 ) . The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group ( 1 % vs. 5 % , P = 0.04 by the chi-square test ) . CONCLUSIONS This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe . ( Clinical Trials.gov number , NCT00397657 . BACKGROUND Results from prospect i ve cohort studies and r and omized , controlled trials have provided evidence of a protective effect of n-3 fatty acids against cardiovascular diseases . We examined the effect of the marine n-3 fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) and of the plant-derived alpha-linolenic acid ( ALA ) on the rate of cardiovascular events among patients who have had a myocardial infa rct ion . METHODS In a multicenter , double-blind , placebo-controlled trial , we r and omly assigned 4837 patients , 60 through 80 years of age ( 78 % men ) , who had had a myocardial infa rct ion and were receiving state-of-the-art antihypertensive , antithrombotic , and lipid-modifying therapy to receive for 40 months one of four trial margarines : a margarine supplemented with a combination of EPA and DHA ( with a targeted additional daily intake of 400 mg of EPA-DHA ) , a margarine supplemented with ALA ( with a targeted additional daily intake of 2 g of ALA ) , a margarine supplemented with EPA-DHA and ALA , or a placebo margarine . The primary end point was the rate of major cardiovascular events , which comprised fatal and nonfatal cardiovascular events and cardiac interventions . Data were analyzed according to the intention-to-treat principle , with the use of Cox proportional-hazards models . RESULTS The patients consumed , on average , 18.8 g of margarine per day , which result ed in additional intakes of 226 mg of EPA combined with 150 mg of DHA , 1.9 g of ALA , or both , in the active-treatment groups . During the follow-up period , a major cardiovascular event occurred in 671 patients ( 13.9 % ) . Neither EPA-DHA nor ALA reduced this primary end point ( hazard ratio with EPA-DHA , 1.01 ; 95 % confidence interval [ CI ] , 0.87 to 1.17 ; P=0.93 ; hazard ratio with ALA , 0.91 ; 95 % CI , 0.78 to 1.05 ; P=0.20 ) . In the prespecified subgroup of women , ALA , as compared with placebo and EPA-DHA alone , was associated with a reduction in the rate of major cardiovascular events that approached significance ( hazard ratio , 0.73 ; 95 % CI , 0.51 to 1.03 ; P=0.07 ) . The rate of adverse events did not differ significantly among the study groups . CONCLUSIONS Low-dose supplementation with EPA-DHA or ALA did not significantly reduce the rate of major cardiovascular events among patients who had had a myocardial infa rct ion and who were receiving state-of-the-art antihypertensive , antithrombotic , and lipid-modifying therapy . ( Funded by the Netherl and s Heart Foundation and others ; Clinical Trials.gov number , NCT00127452 . ) BACKGROUND Serum proprotein convertase subtilisin/kexin 9 ( PCSK9 ) binds to low-density lipoprotein ( LDL ) receptors , increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation . REGN727/SAR236553 ( design ated here as SAR236553 ) , a fully human PCSK9 monoclonal antibody , increases the recycling of LDL receptors and reduces LDL cholesterol levels . METHODS We performed a phase 2 , multicenter , double-blind , placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter ( 2.6 mmol per liter ) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks . Patients were r and omly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks , 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks , or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment . RESULTS The least-squares mean ( ±SE ) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553 , as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo ( P<0.001 ) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553 . All the patients who received SAR236553 , as compared with 52 % of those who received 80 mg of atorvastatin plus placebo , attained an LDL cholesterol level of less than 100 mg per deciliter , and at least 90 % of the patients who received SAR236553 , as compared with 17 % who received 80 mg of atorvastatin plus placebo , attained LDL cholesterol levels of less than 70 mg per deciliter ( 1.8 mmol per liter ) . CONCLUSIONS In a r and omized trial involving patients with primary hypercholesterolemia , adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin result ed in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone . ( Funded by Sanofi and Regeneron Pharmaceuticals ; Clinical Trials.gov number , NCT01288469 . ) Background — Despite statin treatment , many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol ( LDL-C ) targets . AMG 145 , a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) serine protease , demonstrated significant reductions in LDL-C in phase 1 studies . This phase 2 , multicenter , double-blind , r and omized , placebo-controlled , dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients . Methods and Results — Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L ( 100 mg/dL ) despite statin therapy with or without ezetimibe were r and omized 1:1:1 to AMG 145 350 mg , AMG 145 420 mg , or placebo-administered subcutaneously every 4 weeks . The primary end point was percentage change from baseline in LDL-C at week 12 . Of 168 patients r and omized , 167 received investigational product and were included in the full analysis set ( mean [ SD ] age , 50 [ 13 ] years ; 47 % female ; 89 % white ; mean [ SD ] baseline LDL-C , 4.0 [ 1.1 ] mmol/L ( 156 [ 42 ] mg/dL ) ) . At week 12 , LDL-C reduction measured by preparative ultracentrifugation ( least squares mean [ st and ard error ( SE ) ] ) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg , respectively , compared with 1 (3)% increase with placebo ( P<0.001 for both dose groups ) . Serious adverse events ( not considered treatment-related ) occurred in 2 patients on AMG 145 . Conclusions — AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use , with or without ezetimibe , with minimal adverse events and good tolerability . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01375751 BACKGROUND LDL cholesterol ( LDL-C ) is a well established risk factor for cardiovascular disease . Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) binds LDL receptors , targeting them for degradation . We therefore assessed the efficacy , safety , and tolerability of AMG 145 , a human monoclonal IgG2 antibody against PCSK9 , in stable patients with hypercholesterolemia on a statin . METHODS In a phase 2 , dose-ranging study done in 78 centres in the USA , Canada , Denmark , Hungary , and Czech Republic , patients ( aged 18 - 80 years ) with LDL-C greater than 2·2 mmol/L on a stable dose of statin ( with or without ezetimibe ) , were r and omly assigned equally , through an interactive voice response system , to subcutaneous injections of AMG 145 70 mg , 105 mg , or 140 mg , or matching placebo every 2 weeks ; or subcutaneous injections of AMG 145 280 mg , 350 mg , or 420 mg , or matching placebo every 4 weeks . Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules . The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks . Analysis was by modified intention to treat . This study is registered with Clinical Trials.gov , number NCT01380730 . FINDINGS 631 patients with hypercholesterolaemia were r and omly assigned to AMG 145 70 mg ( n=79 ) , 105 mg ( n=79 ) , or 140 mg ( n=78 ) , or matching placebo ( n=78 ) every 2 weeks ; or AMG 145 280 mg ( n=79 ) , 350 mg ( n=79 ) , and 420 mg ( n=80 ) , and matching placebo ( n=79 ) every 4 weeks . At the end of the dosing interval at week 12 , the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks ( ranging from 41·8 % to 66·1 % ; p<0·0001 for each dose vs placebo ) and AMG 145 every 4 weeks ( ranging from 41·8 % to 50·3 % ; p<0·0001 ) . No treatment-related serious adverse events occurred . The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups ( 39 [ 8 % ] of 474 vs 11 [ 7 % ] of 155 ) ; none of these events were severe or life-threatening . INTERPRETATION The results suggest that PCSK9 inhibition could be a new model in lipid management . Inhibition of PCSK9 warrants assessment in phase 3 clinical trials . FUNDING Amgen |
13,488 | 10,796,560 | Data incorporating considerable assumptions about the many people who left early suggest that global state and psychotic symptoms - both positive and negative - may be more helped by quetiapine than placebo .
While the incidences of extrapyramidal side effects are not different between quetiapine and placebo , side effects such as dizziness and dry mouth are more prevalent in the quetiapine treated group .
Quetiapine is as potent as chlorpromazine and haloperidol as regards global and mental state but it may cause higher incidences of dry mouth and sleepiness .
Extrapyramidal side effects are the same as those of chlorpromazine but may be less than haloperidol .
There are no clear differences between high and low dose groups in respect of extrapyramidal side effects . | BACKGROUND Quetiapine is a novel atypical antipsychotic with low propensity for movement disorder adverse effects .
It is used for treatment of schizophrenia and other psychoses .
OBJECTIVES To determine the effects of quetiapine for schizophrenia in comparison to placebo , classical and other atypical antipsychotics . | BACKGROUND The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous population s that may not be typical of patients seen in clinical practice . OBJECTIVE The Quetiapine Experience with Safety and Tolerability ( QUEST ) study compared the relative safety , tolerability , and efficacy of quetiapine and risperidone in out patients with a broad range of psychotic symptoms . METHODS This was a multicenter , 4-month , open-label , r and omized clinical trial . Patients were r and omized in a 3:1 ratio to receive quetiapine or risperidone . Doses were adjusted to maximize efficacy and to minimize adverse events . Extrapyramidal symptoms ( EPS ) were assessed with an EPS checklist ; adverse events were recorded . Efficacy was assessed using the Clinical Global Impression ( CGI ) scale , Positive and Negative Symptom Scale ( PANSS ) , and Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS A total of 728 patients were r and omized , 553 to quetiapine and 175 to risperidone . Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone . At the end of 4 months , EPS declined in both treatment groups , but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication ( P < 0.001 ) . The most common adverse events in the quetiapine and risperidone groups were somnolence ( 31.3 % and 15.4 % , respectively ) , dry mouth ( 14.5 % and 6.9 % ) , and dizziness ( 12.7 % and 6.9 % ) . Overall , tolerance to side effects with the 2 drugs , measured by dropout rates , was comparable . At each visit , a higher percentage of quetiapine-treated patients showed improvement on the CGI scale , but there were no significant between-group differences on the PANSS . At end point , quetiapine-treated patients had significantly lower HAM-D scores ( P = 0.028 ) . CONCLUSIONS The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms , is more effective for depressive symptoms , may have a more favorable EPS profile , and has comparable overall tolerability BACKGROUND Quetiapine ( ICI 204,636 , ' Seroquel ' ) is a new atypical antipsychotic agent with a similar binding profile to the original atypical antipsychotic , clozapine . Its clinical efficacy has already been demonstrated at multiple fixed doses ( 150 - 750 mg/day ) and has been suggested to be comparable with haloperidol ( 12 mg/day ) . METHODS This international , 6-week , multicentre , double-blind , r and omized , parallel-group trial compared quetiapine with haloperidol ( 455 mg and 8 mg mean total daily doses , respectively ) in 448 hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia ( DSM-III-R ) , in order to establish their equivalence in terms of efficacy , and the nature of their tolerability profiles , especially in terms of extrapyramidal symptoms ( EPS ) and serum prolactin levels . RESULTS Both quetiapine and haloperidol produced a clear reduction in the Positive and Negative Syndrome Scale ( PANSS ) scores and Clinical Global Impression ( CGI ) Severity of Illness and Global Improvement scores . At day 42 , the PANSS total score was reduced by -18.7+/-1.63 in the quetiapine group , and -22.1+/-1.63 in the haloperidol group ( P = 0.13 , between-treatment ) . Quetiapine was better tolerated than haloperidol in terms of EPS as demonstrated by the significant differences in the Simpson Scale and Abnormal Involuntary Movement Scale scores ( P < 0.05 ) . Although patients in both groups had elevated serum prolactin concentrations at baseline , mean serum prolactin concentration decreased ( by 16.5 microg/l ) in quetiapine-treated patients , yet increased ( by 5.9 microg/l ) in patients treated with haloperidol . CONCLUSION Quetiapine is an effective and well tolerated antipsychotic of comparable efficacy to haloperidol and lacks the latter compound 's effect on prolactin and EPS Treating schizophrenia is expensive . Preventing rehospitalization of patients with schizophrenia provides an attractive opportunity for cost savings , especially for patients with ' revolving-door ' or multiple-episode schizophrenia . Reducing the occurrence of extrapyramidal symptoms and other adverse events associated with st and ard antipsychotic agents may increase compliance and reduce the rate of rehospitalization of patients with schizophrenia . Quetiapine ( ' Seroquel ' , ICI 204,636 , Zeneca Pharmaceuticals ) is a new dibenzothiazepine antipsychotic agent with a low propensity for extrapyramidal symptoms . We describe here a unique methodology to compare quetiapine with usual-care medications in real-world treatment setting s. The trial objective is to determine if therapy with this new atypical antipsychotic agent can reduce the rate of rehospitalization and , therefore , treatment costs . Using two secondary medical-cl aims data bases , we defined the minimal threshold for revolving-door status as 1.0 admission per year ; this definition allows our trial to focus on the sub population of schizophrenic patients with the greatest potential for cost savings by either the new atypical antipsychotic quetiapine or usual-care therapy . We describe here the approach used in our trial Abstract We investigated the striatal dopamine-2 ( D2 ) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients ( 16 with schizophrenic and two with schizoaffective disorder according to DSM-IV ) with single photon emission computed tomography ( SPECT ) using 123I-iodobenzamide ( IBZM ) as tracer substance . Four patients were treated with the novel antipsychotic compound quetiapine ( 300–700 mg/day ) , six with clozapine ( 300–600 mg/ day ) and eight with haloperidol ( 10–20 mg/day ) . They were compared with eight healthy controls . Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol . In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group , there were no extrapyramidal motor side-effects ( EPS ) in the quetiapine and clozapine treatment groups . Therefore , the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS Abstract Quetiapine ( Seroquel , ICI 204,636 ) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia , and has a low propensity to cause extrapyramidal symptoms . The compound has a relatively short plasma elimination half-life ( approximately 7 h ) . However , since dopamine D2 receptor occupancies correlate poorly with plasma concentrations of antipsychotics , plasma elimination half-life may not predict either duration of clinical effect or dosing frequency . Accordingly , the efficacy and tolerability of three dosing regimens ( 450 mg/day given in two or three divided doses daily , and 50 mg/day given twice daily ) were compared in a 6-week , double-blind , r and omized , multicentre , parallel-group study . The study recruited hospitalized men and women aged 18–65 years meeting DSM-IIIR criteria for acute exacerbation of chronic or subchronic schizophrenia . Six hundred and eighteen patients were r and omly assigned to treatment with quetiapine 150 mg tid ( n = 209 ) , 225 mg bd ( n = 200 ) , or a comparator dose of 25 mg bd ( n = 209 ) . At day 42 , the last day of r and omized treatment and the primary timepoint for efficacy , quetiapine 450 mg/day was more effective than 50 mg/day : 225 mg bd was consistently superior to 25 mg bd in all measures of efficacy ( total BPRS , P = 0.006 ; CGI severity , CGI improvement and SANS , P < 0.03 ) , and 150 mg tid was statistically significantly superior to 25 mg bd with respect to BPRS total score ( P = 0.05 ) . The 225 mg bd and 150 mg tid groups were not significantly different from each other with respect to any efficacy measure . Quetiapine was generally well tolerated . Extrapyramidal symptom ( EPS ) adverse events were generally rare , and occurred with similar frequencies in the two 450 mg/day groups . Quetiapine was not associated with sustained increases in plasma prolactin at any dose . These data support the atypical profile developed from pre clinical studies and show that quetiapine is an effective , well tolerated antipsychotic that can be given twice daily OBJECTIVE To assess the efficacy of quetiapine , a recently introduced second generation antipsychotic medication , in reducing cognitive impairment in patients with schizophrenia . DESIGN Prospect i ve , r and omized , double-blind clinical trial . PATIENTS 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , ( DSM-IV ) criteria for schizophrenia were recruited from 3 Canadian hospitals . INTERVENTION AND OUTCOME MEASURES After a 48-hour washout period , 25 patients with schizophrenia were r and omly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms , mood and extrapyramidal side effects , as well as st and ardized neuropsychological measures sensitive to 6 cognitive domains : fine motor skill , attention span , verbal reasoning and fluency , visuospatial construction and fluency , executive skills and visuomotor tracking , and immediate recall of verbal and nonverbal material s. The measures were repeated 8 weeks and 6 months after treatment was initiated . RESULTS Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms . Quetiapine also had beneficial effects on cognitive skills , particularly verbal reasoning and fluency skills and immediate recall , with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment . Patients taking haloperidol showed improvements in general clinical status , but no specific improvements on the positive syndrome , the negative syndrome , depression ratings or cognitive skills . CONCLUSIONS These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic In a double-blind study , 135 in patients with a diagnosis of chronic schizophrenia were r and omly assigned to 8 weeks of treatment with one of six parallel treatments : risperidone ( a new central 5-hydroxytryptamine2 and dopamine D2 antagonist ) , 2 , 6 , 10 , 16 mg/day ; haloperidol , 20 mg/day ; or placebo , after a single-blind placebo washout period . Doses were increased in fixed increments up to a fixed maintenance dose reached after 1 week . On the Clinical Global Impression-Severity of Illness and Improvement , all active medications were superior to placebo except for risperidone ( 2 mg ) on the Clinical Global Impression-Improvement . On the total Positive and Negative Syndrome Scale ( PANSS ) score and positive subscale , superiority to placebo was observed for all treatment groups except for haloperidol and risperidone ( 2 mg ) , which tended to be superior to placebo on total PANSS and the positive subscale , respectively . On the PANSS negative subscale , only risperidone ( 6 mg/day ) was significantly better than placebo . Risperidone ( 6 mg ) was superior to haloperidol on the total PANSS , General Psychopathology , and Brief Psychiatric Rating Scale subscales . Although there was a linear increase in parkinsonism with increasing risperidone dosage , there were no statistically significant differences between risperidone ( 2 , 6 , and 16 mg/day ) and placebo . At doses of 6 to 16 mg , risperidone displayed a marked antidyskinetic effect compared with placebo . This effect was more pronounced in patients with severe dyskinesia . By contrast , haloperidol produced significantly more parkinsonism than placebo and risperidone ( 2 , 6 and 16 mg ) , with no effect on tardive dyskinesia . These data suggest that risperidone , at the optimal therapeutic dose of 6 mg/day , produced significant improvement in both positive and negative symptoms without an increase in drug-induced parkinsonian symptoms and with a significant beneficial effect on tardive dyskinesia The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients & NA ; Quetiapine ( ‘ Seroquel ’ ) is a well‐tolerated , novel , atypical antipsychotic with consistent efficacy in the treatment of schizophrenia . To date , no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics , yet this type of patient is most frequently seen by psychiatrists . Therefore , this international , multicentre , double‐blind study was conducted to compare the efficacy and tolerability of 8 weeks ' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine ( 20 mg/day ) treatment . Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure , mean Positive and Negative Symptom Scale ( PANSS ) score , after 4 weeks ' treatment ( ‐9.05 , ‐5.82 , respectively , P = 0.061 ) and at study end ( ‐11.50 , ‐8.87 , respectively , P = 0.234 ) . Similarly , there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures ( Clinical Global Impression , PANSS subscale and Brief Psychiatric Rating Scale scores ) [ week 4 ( baseline ) to week 12 ( end ) ] , but the difference between treatments did not reach significance . Significantly more patients on quetiapine than on haloperidol showed a clinical response — patient response rates , defined as ≥ 20 % reduction in PANSS total score between weeks 4 and 12 , were 52.2 % for quetiapine and 38.0 % for haloperidol ( P = 0.043 ) . Patients receiving quetiapine required less anticholinergic medication ( P ≤ 0.011 ) , had greater reduction in extrapyramidal symptoms ( EPS ) ( P = 0.005 ) and fewer treatment‐emergent EPS‐related adverse events compared to those on haloperidol ( P < 0.001 ) . Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73 % of patients . Between weeks 4 and 12 , elevated serum prolactin concentrations significantly decreased in quetiapine‐treated patients compared to those receiving haloperidol ( P < 0.001 ) . At the end of quetiapine treatment , 83 % of patients had normal prolactin levels while only 21 % of patients receiving haloperidol were within the normal range . These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics We evaluated the effects of ICI 204,636 in 12 hospitalized patients with schizophrenia in a double-blind , placebo-controlled , parallel-group , rising-dose study . Patients met the Diagnostic and Statistical Manual of Mental Disorders , Third Edition , Revised criteria for chronic or subchronic schizophrenia and had a total score > or = 30 on the 18-item Brief Psychiatric Rating Scale ( BPRS ) and a score > or = 3 on the Clinical Global Impression ( CGI ) Severity of Illness item . Patients received 21 days of double-blind treatment with increasing doses of ICI 204,636 ( 25 to 250 mg/d ) or placebo . Efficacy was assessed using the BPRS and CGI . Response to treatment was defined as a > or = 30 % decrease in the BPRS total score from baseline . Extrapyramidal symptoms and abnormal involuntary movements were assessed using the Simpson Scale and Abnormal Involuntary Movement Scale . Changes from baseline in the BPRS and CGI were significantly greater at end point for patients who received ICI 204,636 versus placebo ( BPRS , -20.9 vs -4.8 ; CGI , -2.9 vs -1.0 ; P < 0.05 , analysis of covariance ; P < or = 0.06 , Wilcoxon rank sum test ) . All patients in the ICI 204,636 group responded to treatment ( P < 0.10 ) versus only two patients in the placebo group . Mild somnolence occurred in 50 % of ICI 204,636-treated patients . No treatment-emergent extrapyramidal symptoms or dystonic reactions were observed . ICI 204,636 showed efficacy in the positive and negative symptoms of schizophrenia and was well tolerated OBJECTIVE This international , multicenter double-blind trial was design ed to compare the therapeutic profile of an atypical antipsychotic , olanzapine , with that of a conventional dopamine D2 antagonist , haloperidol . METHOD A total of 1,996 patients at 174 sites in Europe and North America were r and omly assigned to treatment with olanzapine ( N = 1,336 ) or haloperidol ( N = 660 ) over 6 weeks . The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale ( BPRS ) . Secondary analyses included comparisons of the mean change in positive and negative symptoms , comorbid depression , extrapyramidal symptoms , and overall drug safety . RESULTS Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure , including depression . Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events . Substantially more olanzapine-treated patients ( 66.5 % ) than haloperidol-treated patients ( 46.8 % ) completed 6 weeks of therapy . Statistically significant advantages of olanzapine treatment were related to 1 ) change in negative symptoms , 2 ) extrapyramidal symptom profile , 3 ) effect on prolactin levels , and 4 ) response rate . CONCLUSIONS Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology , with a substantially more favorable safety profile , than haloperidol . It meets several of the criteria for a novel atypical antipsychotic agent BACKGROUND Quetiapine fumarate ( Seroquel [ ICI 204,636 ] ) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 ( 5-HT2 ) receptors than for D2 dopamine receptors ; its efficacy in patients with schizophrenia was shown in early phase 2 trials ( maximum dose , 750 mg/d ) . METHODS In this multicenter , double-blind , placebo-controlled trial , 286 patients hospitalized with chronic or subchronic schizophrenia ( DSM-III-R ) were r and omized to 6 weeks of treatment with high-dose quetiapine fumarate ( < or = 750 mg/d ) , n = 96 ; low-dose quetiapine fumarate ( < or = 250 mg/d ) , n = 94 ; or placebo , n = 96 . The Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables . Secondary efficacy variables included the BPRS positive-symptom cluster score , the Modified Scale for the Assessment of Negative Symptoms summary score ( United States only ) , and the total score from the negative scale of the Positive and Negative Syndrome Scale ( Europe only ) . Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward . The model included baseline score ( covariate ) , center , and treatment . Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale ; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale . Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests . RESULTS Of 280 patients in whom the efficacy of quetiapine was evaluated , 159 ( 42 % of those receiving high-dose treatment ; 57 % , low-dose treatment ; and 59 % , placebo ) withdrew before trial completion , primarily because of treatment failure . Significant ( P < .001 , BPRS ; P = .003 , Clinical Global Impression Severity of Illness item ; and P = .003 , BPRS positive-symptom cluster ) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables , with end point differences in the BPRS positive-symptom cluster score showing quetiapine 's consistency in reducing positive symptoms . The reduction of negative symptoms was less consistent ; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale . Quetiapine was well tolerated and did not induce extrapyramidal symptoms , sustained elevations of prolactin , or clinical ly significant changes in hematologic parameters . CONCLUSIONS Quetiapine is an effective antipsychotic with a favorable safety profile . The optimum dose is probably greater than 250 mg/d Five fixed doses of the atypical antipsychotic " Seroquel " ( quetiapine ) were evaluated to delineate a dose-response relationship , as measured by changes from baseline in Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) , and Modified Scale for the Assessment of Negative Symptoms ( SANS ) summary scores , and to compare efficacy and tolerability opposite placebo and haloperidol . Three hundred sixty-one patients from 26 North American centers entered this double-blind , placebo-controlled trial with acute exacerbation of chronic schizophrenia ( DSM-III-R ) . Patients who completed a single-blind , placebo washout phase were r and omized to double-blind treatment with quetiapine ( 75 , 150 , 300 , 600 , or 750 mg daily ) , haloperidol ( 12 mg daily ) , or placebo and evaluated weekly for 6 weeks . At end point , significant differences ( p < 0.05 , analysis of covariance ) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total , BPRS positive-symptom cluster , and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score . Differences between quetiapine and haloperidol were not significant . Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables . Notably , no significant safety concerns were identified as dose increased . Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations . Quetiapine is well tolerated and clinical ly effective in the treatment of schizophrenia . It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day OBJECTIVE The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic patients and determine its optimal dose . METHOD This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States . Patients were r and omly assigned to 8 weeks ' treatment with placebo , one of four doses of risperidone ( 2 , 6 , 10 , or 16 mg ) , or 20 mg of haloperidol daily . RESULTS Clinical improvement ( 20 % reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia ) at the study end point was shown by 35 % of the patients receiving 2 mg of risperidone , 57 % receiving 6 mg , 40 % receiving 10 mg , and 51 % receiving 16 mg ; and by 30 % receiving haloperidol and 22 % receiving placebo . Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol . Positive symptom scores were significantly lower after 6 , 10 , and 16 mg of risperidone and 20 mg of haloperidol than placebo ; negative symptom scores , however , were reduced significantly , compared with placebo , only after 6 and 16 mg of risperidone . The incidence of extra-pyramidal side effects ( measured by the Extrapyramidal Symptom Rating Scale ) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo . The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg ; this dose was as effective as 16 mg , and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo . CONCLUSIONS Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia ICI 204,636 is a new , potentially atypical antipsychotic . In early phase II trials , the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia . The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week , multicenter , double-blind trial . Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation , as well as other criteria , were r and omized to ICI 204,636 ( 75 to 750 mg daily ) ( N = 54 ) or placebo ( N = 55 ) . Patients were assessed weekly by use of the Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Negative Symptoms ( SANS ) , and Clinical Global Impression Scale ( CGI ) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects ( EPS ) . Significant differences ( p < or = 0.05 ) between treatment groups , which favored ICI 204,636 , were identified throughout the trial . Endpoint differences were significant ( by analysis of covariance ) for BPRS factor IV ( activation ) and SANS scores and were marginally significant for total BPRS , BPRS factor III ( thought disturbance ) , BPRS positive-symptom cluster , and CGI Severity of Illness item scores ( p = 0.07 , 0.09 , 0.06 , and 0.09 , respectively ) . ICI 204,636 was well tolerated , although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo . In the dose range studied , treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions . Furthermore , ICI 204,636 did not produce sustained levels of prolactin ; the mean change from baseline at endpoint ( -7.2 micrograms/L ) was comparable ( p = 0.44 ) to that for placebo ( -8.2 micrograms/L ) . These findings distinguish ICI 204,636 from st and ard antipsychotics and confirm pre clinical predictions that ICI 204,636 is an atypical antipsychotic A 6‐week , double‐blind , r and omized , multicentre , parallel‐group study was conducted to compare the efficacy of quetiapine ( “ Seroquel ” ) ( n=101 ) with that of chlorpromazine ( n=100 ) in hospitalized patients with acute exacerbation of subchronic or chronic schizophrenia , or schizophreniform disorder . The tolerabilities of the two treatments were also compared . The mean daily doses of quetiapine and chlorpromazine at the end of the study were 407 mg and 384 mg , respectively . Both treatments were effective in the treatment of positive and negative symptoms , with a trend towards superior efficacy for quetiapine . The quetiapine group had a lower incidence of adverse events than the chlorpromazine group , and a low incidence of treatment‐emergent extrapyramidal symptoms . Quetiapine was not associated with a sustained increase in serum prolactin . These clinical data support the pre clinical profile of quetiapine as an atypical antipsychotic agent A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors This article describes the system for rating the quality of medical evidence developed and used during creation of the Agency for Health Care Policy and Research -sponsored heart failure guideline . Previous approaches to rating evidence were not design ed for use in the setting of clinical practice guidelines . The present system is based on the tenet that flaws in research design are serious to the extent they threaten the validity of the results of studies . A taxonomy of major and minor flaws based on that tenet was developed for r and omized controlled trials and for cohort and medical registry studies . The use of the system is described in the context of two difficult clinical issues considered by the Panel : the role of coronary artery revascularization and the use of metoprolol |
13,489 | 28,886,231 | In conclusion , Gd-EOB-DTPA-enhanced MRI demonstrated higher sensitivity and overall diagnostic accuracy than MDCT , and thus should be the preferred imaging modality for diagnosing small HCCs measuring up to 2 cm . | Early detection of small hepatocellular carcinoma ( HCC ) lesions can improve longterm patient survival . | Abstract Objectives To prospect ively compare the diagnostic performance of ultrasound ( US ) , multidetector computed tomography ( MDCT ) and contrast-enhanced magnetic resonance imaging ( MRI ) in cirrhotic patients who were c and i date s for liver transplantation . Methods One hundred and forty consecutive patients with 163 hepatocellular carcinoma ( HCC ) nodules underwent US , MRI and MDCT . Diagnosis of HCC was based on pathological findings or substantial growth at 12-month follow-up . Four different image data sets were evaluated : US , MDCT , MRI unenhanced and dynamic phases , MRI unenhanced dynamic and hepatobiliary phase . Diagnostic accuracy , sensitivity , specificity , PPV and NPV , with corresponding 95 % confidence intervals , were determined . Statistical analysis was performed for all lesions and for three lesion subgroups ( < 1 cm , 1 - 2 cm , > 2 cm ) . Results Significantly higher diagnostic accuracy , sensitivity and NPV was achieved on dynamic + hepatobiliary phase MRI compared with US , MDCT and dynamic phase MRI alone . The specificity and PPV of US was significantly lower than that of MDCT , dynamic phase MRI and dynamic + hepatobiliary phase MRI . Similar results were obtained for all sub-group analyses , with particular benefit for the diagnosis of smaller lesions between 1 and 2 cm . Conclusions Dynamic + hepatobiliary phase MRI improved detection and characterisation of HCC in cirrhotic patients . The greatest benefit is for diagnosing lesions between 1 and 2 cm . Key Points• US , CT and MRI can all identify HCC in cirrhotic patients • US has good sensitivity but suffers from false-positive findings • Dynamic CT and MR have similar diagnostic performance for diagnosing HCC • Dynamic + hepatobiliary phase MRI significantly improves detection and characterisation of HCC • The greatest benefit is for the diagnosis of lesions between 1 and 2 PURPOSE To compare two different injection rates for gadoxetic acid-enhanced hepatic arterial phase images on hepatic dynamic MRI . MATERIAL S AND METHODS Hepatic arterial phase images were obtained after an intravenous bolus injection of gadoxetic acid at a rate of 1 mL/second in 62 patients and 2 mL/second in 64 patients on a 3 Tesla MR scanner using a test-bolus injection method . The signal-to-noise ratios ( SNR ) of the liver , portal vein , hepatic vein , aorta , spleen and pancreas were measured . The contrast-to-noise ratio ( CNR ) of hypervascular hepatic tumors was calculated . Two radiologists independently scored items to evaluate image quality of hepatic arterial phase and detected hypervascular hepatocellular carcinoma ( HCC ) . RESULTS The SNR of the aorta on the arterial phase images was significantly higher in the 1 mL/second group ( 235.43 + /- 82.59 ) than in the 2 mL/second group ( 190.94 + /- 96.90 , P < 0.05 ) . The SNRs of the liver , spleen and pancreas , the CNRs of hypervascular hepatic tumors , the detection rate of hypervascular HCC and subjective ratings for the optimal arterial enhancement were comparable between the two groups . CONCLUSION Injection rates of 2 mL/second and 1 mL/second provided comparable image qualities on arterial phase images of hepatic dynamic MRI using gadoxetic acid BACKGROUND & AIMS To prospect ively assess the diagnostic accuracy of the incorporation of additional magnetic resonance imaging ( MRI ) parameters in those based on contrast enhancement pattern for the diagnosis of solitary nodules between 5 and 20 mm , detected during surveillance in patients with cirrhosis . METHODS Between November 2003 and January 2010 , we prospect ively included 159 cirrhotic patients with a newly detected solitary nodule between 5 and 20 mm in diameter by screening ultrasonography ( US ) . Hepatic MRI and fine-needle biopsy were performed in all patients . RESULTS Final diagnoses were hepatocellular carcinoma ( HCC ) ( n=103 ) , other malignant lesions ( intrahepatic cholangiocarcinoma/metastases ) ( n=4 ) , and benign lesions ( n=52 ) . The specific enhancement pattern ( arterial enhancement followed by washout ) yielded a sensitivity and specificity of 58.3 % and 96.4 % , respectively . Peritumoral capsule was present in 43 HCC and in 2 non-HCC lesions . Intralesional fat was detected in 24 nodules ; 5 nodules were non-HCC . Finally , the presence of both capsule and fat was observed in 10 cases , all of them HCC ( 100 % specificity ) , but all of them also displayed the specific enhancement pattern , thus adding no sensitivity or specificity . CONCLUSIONS Conclusive non-invasive diagnosis of HCC in cirrhosis should be based only on the contrast enhancement pattern , while other characteristics at MRI do not increase the diagnostic accuracy PURPOSE To prospect ively compare gadoxetate disodium-enhanced magnetic resonance ( MR ) imaging with multiphasic 64-section multidetector computed tomography ( CT ) in the detection of hepatocellular carcinoma ( HCC ) in patients with cirrhosis . MATERIAL S AND METHODS Institutional review board approval and informed patient consent were obtained for this prospect i ve study . Fifty-eight patients ( 39 men , 19 women ; mean age , 63 years ; age range , 35 - 84 years ) underwent gadoxetate disodium-enhanced MR imaging and multiphasic 64-section multidetector CT . The imaging examinations were performed within 30 days of each other . The two sets of images were qualitatively analyzed in r and om order by three independent readers in a blinded and retrospective fashion . Using strict diagnostic criteria for HCC , readers classified all detected lesions with use of a four-point confidence scale . The reference st and ard was a combination of pathologic proof , conclusive imaging findings , and substantial tumor growth at follow-up CT or MR imaging ( range of follow-up , 90 - 370 days ) . The diagnostic accuracy , sensitivity , and positive predictive value were compared between the two image sets . Interreader variability was assessed . The accuracy of each imaging method was determined by using an adjusted modified chi(2 ) test . RESULTS Eighty-seven HCCs ( mean size + /- st and ard deviation , 1.8 cm + /- 1.5 ; range , 0.3 - 7.0 cm ) were confirmed in 42 of the 58 patients . Regardless of lesion size , the average diagnostic accuracy and sensitivity for all readers were significantly greater with gadoxetate disodium-enhanced MR imaging ( average diagnostic accuracy : 0.88 , 95 % confidence interval [ CI ] : 0.80 , 0.97 ; average sensitivity : 0.85 , 95 % CI : 0.74 , 0.96 ) than with multidetector CT ( average diagnostic accuracy : 0.74 , 95 % CI : 0.65 , 0.82 ; average sensitivity : 0.69 , 95 % CI : 0.59 , 0.79 ) ( P < .001 for each ) . No significant difference in positive predictive value was observed between the two image sets for each reader . Interreader agreement was good to excellent . CONCLUSION Compared with multiphasic 64-section multidetector CT , gadoxetate disodium-enhanced MR imaging yields significantly higher diagnostic accuracy and sensitivity in the detection of HCC in patients with cirrhosis BACKGROUND & AIMS To determine the optimal imaging scan or combinations in terms of diagnostic performance and re source utilization for 1 - 2 cm nodules found on surveillance for hepatocellular carcinoma . METHODS Eighty-four cirrhotic patients with 101 , 1 - 2 cm nodules ( 34 malignant , 67 non-malignant ) prospect ively underwent st and ardized contrast-enhanced ultrasound , CT , and MRI scans . Sensitivity/specificity and potential imaging/biopsy utilization of individual imaging modalities and two-modality combinations performed at the same time ( coincidental ) or in sequence were measured . Final diagnosis was determined by biopsy ( 23 ) , growth ( 10 ) , recurrence ( 1 ) , or stability in size for ≥ 18 months ( 67 ) . RESULTS For single imaging scans , sensitivities/specificities ranged between 53 - 62 % and 91 - 100 % . When two scans were combined requiring both to be positive , sensitivities/specificities ranged between 29 - 41 % and 99 - 100 % . When two scans were combined sequentially , requiring only one to be positive , sensitivities/specificities ranged between 74 - 89 % and 91 - 99 % . When comparing combination of two positive tests ( MRI and CT ) to MRI alone , there was a significant drop in sensitivity ( 41 % vs. 62 % , p=0.02 ) , no change in specificity ( both 100 % ) , with twice as many scans performed , and 9 % rise in potential biopsies or 7 % rise in follow-up scans . When comparing the combination of MRI then CT ( if MRI negative ) to MRI alone , there was an insignificant rise in sensitivity ( 74 % vs. 62 % , p=0.13 ) , drop in specificity ( 97 % vs. 100 % ) , with 77 % more scans performed , and 6 % drop in potential biopsies or 7 % drop in potential follow-up scans . CONCLUSIONS Single imaging scans have similar specificity to two coincidental positive scans with much less re source utilization . Sequential imaging provides the best sensitivity but with diminished specificity Objective To prospect ively assess the additional value of the hepatobiliary ( HB ) phase of Gd-EOB-DTPA-MRI in identifying and characterising small ( ≤2 cm ) hepatocellular carcinomas ( HCCs ) undetermined in dynamic phases alone because of their atypical features , according to the AASLD criteria . Methods 127 cirrhotic patients were evaluated with Gd-EOB-DTPA-MRI in two sets : unenhanced and dynamic phases ; unenhanced , dynamic and HB phases . Sixty-two out of 215 nodules ( 29 % ) were atypical in 42 patients ( 33 % ) . Results 62 atypical nodules were reported at histology : high- grade dysplastic nodules (HGDN)/early HCC ( n = 20 ) , low- grade DN ( LGDN ) ( n = 21 ) , regenerative nodules ( n = 17 ) and nodular regenerative hyperplasia ( n = 4 ) . The sensitivity , specificity , accuracy , positive and negative predictive value ( PPV , NPV ) were increased by the addition of the HB phase : 88.4–99.4 % , 88–95 % , 88–98.5 % , 97–99 % , and 65–97.5 % , respectively . Twenty atypical nodules were malignant ( 32 % ) , 19 of which were characterised only during the HB phase . Conclusions The HB phase is 11 % more sensitive in the classification of HGDN/early HCC than dynamic MRI , with an added value of 32.5 % in the NPV . The high incidence ( 33 % ) of atypical nodules and their frequent malignancy ( 32 % ) suggest the widespread employment of Gd-EOB-DTPA-MRI in the follow-up of small nodules ( ≤2 cm ) in cirrhosis 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 ( EASL ) recommendations , as a criterion for characterizing small ( 1‐3 cm ) nodules in cirrhosis . A total of 72 nodules ( 1‐2 cm , n = 41 ; 2.1‐3 cm , n = 31 ) detected by ultrasonography in 59 patients with cirrhosis were included in the study . When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography , the lesion was considered to be hepatocellular carcinoma ( HCC ) according to EASL criteria . When one or both techniques showed negative results , ultrasound‐guided biopsy was performed . In cases with negative results for malignancy or high‐ grade dysplasia , biopsy was repeated when an increase in size was detected at the 3‐month follow‐up examination . Coincidental hypervascularity was found in 44 of 72 nodules ( 61 % ; 44 % of 1‐2‐cm nodules and 84 % of 2‐3‐cm nodules ) . Fourteen nodules ( 19.4 % ) had negative results with both techniques ( hypovascular nodules ) . Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique . All nodules larger than 2 cm finally result ed to be HCC . Not satisfying the EASL imaging criteria for diagnosis were 38 % of HCCs 1 to 2 cm ( 17 % hypovascular ) and 16 % of those 2 to 3 cm ( none hypovascular ) . In conclusion , the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61 % of small nodules in cirrhosis ; thus , biopsy frequently is required in this setting . Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38 % of cases . Any nodule larger than 2 cm should be regarded as highly suspicious for HCC . ( HEPATOLOGY 2005 . Background Gadoxetic acid-enhanced magnetic resonance imaging ( MRI ) has an important role in preoperative evaluation of hepatocellular carcinoma ( HCC ) . However , no studies have prospect ively performed intraindividual comparison of gadoxetic acid-enhanced 3 T MRI and multidetector-row computed tomography ( MDCT ) with histopathological examination for the detection of HCCs . We prospect ively compared the efficacies of gadoxetic acid-enhanced MRI and multiphasic contrast-enhanced MDCT with that of histopathological examination , used as a reference st and ard , for the detection of HCC in surgical c and i date s. Methods The study was approved by the institutional review boards at each of four centers . Patients scheduled to undergo multiphasic CT , gadoxetic acid-enhanced MRI , and liver surgery were prospect ively included in this study . The diagnostic abilities of MRI and CT were evaluated and compared on the basis of sensitivity and positive predictive value for detection of and differentiation between HCCs and benign lesions . Results Fifty-four patients with 83 histopathologically confirmed HCCs were included in the study . Combined interpretation of the dynamic and hepatobiliary phases of gadoxetic acid-enhanced MRI showed statistically higher sensitivity for lesion detection ( 83 % ) than did interpretation of multiphasic MDCT images ( 70 % ; p < 0.001 ) . The mean area under each alternative free-response receiver operating characteristics curve was significantly higher for MR images ( 0.927 ) than for CT images ( 0.864 , p < 0.01 ) . Conclusions The sensitivity for preoperative detection of HCCs was higher for gadoxetic acid-enhanced MRI than for multiphasic MDCT imaging Objectives : To determine the characteristic enhancing features of hepatocellular carcinoma ( HCC ) and arterial-enhancing pseudolesion ( AEP ) on gadoxetic acid (Primovist ® )-enhanced magnetic resonance imaging ( MRI ) and to assess its performance compared with that of multirow detector computed tomography ( MDCT ) for differentiating small HCC ( ≤2 cm in diameter ) from AEP in cirrhotic liver . Material s and Methods : A total of 69 patients with 97 small , arterial enhancing hepatic lesions ( 0.5–2 cm in diameter ) , ie , 44 HCCs and 53 AEPs , detected on gadoxetic acid-enhanced MRI , were included in this study . HCCs were diagnosed either through histopathology confirmation ( n = 16 ) or by a combination of liver computed tomography ( CT ) , angiographic findings , lipiodol CT , and AFP levels ( n = 28 ) . AEPs were diagnosed either through histopathology confirmation ( n = 2 ) or were based on the angiographic findings , liver CT , and follow-up imaging ( n = 51 ) . Two radiologists jointly analyzed the morphologic features and the enhancement characteristics on the gadoxetic acid-enhanced MRI . Of the 69 study patients , 42 patients with 60 arterial enhancing lesions underwent quadruple-phase CT in addition to their MRI examination within 4 weeks before or after the MRI , and 2 other radiologists who were blinded to the final diagnosis independently review ed the MRI and CT images in r and om order , at an interval of 2 weeks . Diagnostic performance was evaluated using receiver operating characteristics . The Kappa test was used to evaluate interobserver agreement . Results : Among 44 HCCs , 42 ( 95.4 % ) demonstrated low signal intensity ( SI ) and only 2 showed iso- or high SI on the hepatobiliary phase of gadoxetic acid-enhanced MRI . Alternatively , most AEPs showed iso SI on the hepatobiliary ( n = 50 , 94.3 % ) phase , and only 2 AEPs showed low SI . Compared with the diagnostic performance of the 2 imaging modalities , the mean areas under the receiver-operator characteristic curves on MR imaging were 0.975 for review er 1 and 0.966 for review er 2 , whereas those of CT imaging were 0.892 for review er 1 and 0.888 for review er 2 ( P = 0.069 and P = 0.106 , respectively ) . The sensitivity for each review er with MR imaging ( 93.9 % and 90.9 % , respectively ) was significantly higher than that with multiphasic CT ( 54.5 % , in both ) ( P = 0.001 and 0.0018 , respectively ) . Conclusion : HCCs and AEPs show different enhancing features on the delayed dynamic and hepatobiliary phases of gadoxetic acid-enhanced MRI . Gadoxetic acid-enhanced MRI may , therefore , help to differentiate between HCC and AEP OBJECTIVE The purpose of this study was to assess the effect of two injection rates of contrast material ( 3 mL/sec and 5 mL/sec ) in hepatic arterial dominant phase MDCT for the detection of small ( < 2 cm ) hepatocellular carcinomas . MATERIAL S AND METHODS The injection rates 3 mL/sec and 5 mL/sec were used prospect ively in imaging examinations of patients with the suspected diagnosis of hepatocellular carcinoma . Each group consisted of 30 patients by chance . The group that received injections at 3 mL/sec had 35 hepatocellular carcinoma lesions , and the 5 mL/sec group had 41 lesions . In all patients the dose and concentration of contrast material were 100 mL and 350 mg/mL iodine ( total dose of iodine , 35 g ) . In each patient a mini-test-bolus technique was used with an additional 15 mL of contrast material to determine optimal scan delay after administration of contrast material . Receiver operating characteristic analysis was used to assess diagnostic performance with the two injection rates of contrast material . RESULTS There were no statistically significant differences between the two groups in regard to area under the curve and sensitivity . These values for the 3 mL/sec group were 0.97 and 28/35 ( 80 % ) and for the 5 mL/sec group were 0.96 and 36/41 ( 88 % ) . However , the specificity and positive predictive values at 3 mL/sec ( 236/250 [ 95 % ] and 28/42 [ 67 % ] ) were significantly higher than those at 5 mL/sec ( 227/265 [ 86 % ] and 36/73 [ 49 % ] ) ( p < 0.05 ) . These results suggest there were more false-positive findings of contrast-enhanced lesions in cirrhotic livers on hepatic arterial dominant phase images obtained after injection of contrast material at 5 mL/sec than on images obtained after injection at 3 mL/sec . CONCLUSION In the detection of small hypervascular hepatocellular carcinoma in cirrhotic liver , the risk of false-positive findings of lesions on hepatic arterial dominant phase images is significantly greater with the higher injection rate ( 5 mL/sec ) than with the medium rate ( 3 mL/sec ) OBJECTIVE The purpose of this study was to identify the essential number of phases from multiphasic CT for 1- to 2-cm hepatocellular carcinoma ( HCC ) on surveillance ultrasound and to compare the results with the American Association for the Study of Liver Disease ( AASLD ) st and ard ( arterial phase hypervascularity and portal venous phase [ PVP ] or delayed phase hypovascularity ) . MATERIAL S AND METHODS The study included 110 newly detected nodules ( 1 - 2 cm ; 36 HCC , 74 benign ) in 96 patients detected in an HCC surveillance program . Three radiologists prospect ively evaluated the attenuation of each nodule relative to the liver on each phase of quadriphasic CT . Univariate and multivariate logistic regression analyses were used to identify parameters associated with HCC . Multiple combinations of phases were compared with the AASLD st and ard . RESULTS Only arterial phase hypervascularity and delayed phase hypovascularity were significantly associated with HCC both on univariate ( odds ratio , arterial phase 7.51 [ 95 % CI , 2.79 - 20.20 ] ; delayed phase , 2.80 [ 1.14 - 6.90 ] ) and multivariate analyses ( arterial phase , 11.30 [ 4.30 - 29.68 ] ; delayed phase , 4.39 [ 1.20 - 16.13 ] ) . The combination of arterial phase and delayed phase yielded the highest specificity ( 99 % ) and sensitivity ( 57 % ) . There was no significant difference between AASLD st and ard ( sensitivity , 57 % ; specificity , 98 % ) versus biphasic ( arterial phase hypervascularity and delayed phase hypovascularity : sensitivity , 57 % ; p = 1 and specificity , 99 % ; p = 0.32 ) , triphasic ( arterial phase hypervascularity and unenhanced or PVP hypovascularity : sensitivity , 53 % ; p = 0.325 and specificity , 97 % ; p = 0.32 ) , or quadriphasic combination ( arterial phase hypervascularity and unenhanced , PVP or delayed phase hypovascularity : sensitivity , 57 % ; specificity , 97 % ) , whereas the sensitivity of biphasic arterial phase and PVP was significantly lower ( 39 % vs 57 % , p = 0.022 ) . CONCLUSION For diagnosing 1- to 2-cm HCC detected on surveillance ultrasound , arterial phase and delayed phase are two essential phases , providing higher sensitivity than the combination of arterial phase and PVP , and equal performance with triphasic and quadriphasic combinations . The biphasic combination of arterial phase and delayed phase may replace quadriphasic CT recommended by AASLD |
13,490 | 10,632,626 | The results of the Delphi study indicated that the four most important research priorities for the NHS , in descending order of their importance , are : ( 1 ) the relative cost-effectiveness of ( a ) full ring PET , ( b ) gamma camera PET using coincidence imaging and ( c ) existing diagnostic strategies to determine staging prior to operative intervention for lung cancer ; ( 2 ) partial ring PET compared with full ring PET in oncology ( 3 ) the relative cost-effectiveness of ( a ) full ring PET , ( b ) gamma camera PET using coincidence imaging and ( c ) existing diagnostic strategies to stage and monitor treatment response in breast cancer ; ( 4 ) the relative cost-effectiveness of ( a ) gamma camera PET using coincidence imaging and ( b ) 511 keV collimated positron imaging for assessing myocardial viability when selecting patients for revascularisation surgery .
The findings of this project , which was undertaken rapidly in order to inform HTA research prioritization in the UK , provide a contemporary overview of the potential clinical role for PET in the NHS .
Evidence is needed that using PET as a | BACKGROUND Positron emission tomography ( PET ) is an expensive diagnostic imaging technology .
Despite the long history of PET development , the costs and effectiveness of its use in routine clinical practice remain unknown .
Against this background of uncertainty regarding the clinical role of PET , the UK St and ing Group on Health Technology requested a review of its current and potential role which would enable research priorities in this area to be established .
OBJECTIVES This 3-month project had two explicit objectives : ( 1 ) to review the state of knowledge regarding the clinical applications of PET ; ( 2 ) to determine the key health technology assessment ( HTA ) research questions relating to the use of PET in the UK .
RESULTS Clinical applications for PET have been advocated in three broad disease groups : oncology , cardiology and neuropsychiatric disorders . | OBJECTIVES Firstly , to compare the findings of interictal 18F-fluorodeoxyglucose ( FDG ) positron emission tomography ( PET ) and of single photon emission computed tomography ( SPECT ) using 99mTc-hexamethyl propylene-amine-oxime ( HMPAO ) and 123I-iomazenil in localising the epileptogenic cortex in patients who were c and i date s for epilepsy surgery , but in whom clinical findings , video EEG monitoring ( V-EEG ) , MRI , and neuropsychological evaluations did not give any definite localisation of the seizure onset . Secondly , to assess the ability of these functional methods to help in the decision about the epilepsy surgery . METHODS Eighteen epileptic patients were studied with FDG-PET and iomazenil-SPECT . HMPAO-SPECT was performed in 11 of these 18 patients . Two references for localisation was used — ictal subdural EEG recordings ( S-EEG ) and the operated region . RESULTS Fifteen of 18 patients had localising findings in S-EEG . FDG-PET findings were in accordance with the references in 13 patients and iomazenil-SPECT in nine patients . HMPAO-SPECT visualised the focus less accurately than the two other methods . In three patients S-EEG showed independent bitemporal seizure onset . In these patients FDG-PET showed no lateralisation . However , iomazenil-SPECT showed temporal lobe lateralisation in two of them . CONCLUSION FDG-PET seemed to localise the epileptogenic cortex more accurately than interictal iomazenil-SPECT in patients with complicated focal epilepsy Despite advances in morphological imaging , some patients with lung cancer are found to have nonresectable disease at surgery or die of recurrence within yr of surgery . We performed a prospect i ve study in 109 patients to compare the accuracy of whole-body positron emission tomography ( PET ) using fluorine-18 deoxyglucose ( 18FDG ) and conventional imaging ( CI ) methods for the staging of non-small cell lung cancer ( NSCLC ) . When CI or PET study suggested metastatic disease , confirmation was obtained by biopsy or follow-up information . As compared to CI , 18FDG-PET correctly changed the N stage in 22 patients ( 33 % ) and the M stage in 15 patients ( 14 % ) . For the detection of distant metastases , PET study showed five false-positive sites and no false-negative cases . Currently , the accuracy of PET in the detection of M stage is 96 % . Our study shows that visual interpretation of whole-body fluorine-18 deoxyglucose-positron emission tomography images can improve the diagnostic accuracy in the staging of non-small cell lung cancer . Further experience is needed to establish if metabolic imaging would be a cost-effective tool in the future management of lung cancer The main aim of the study was to evaluate the use of positron emission tomography using fluoro-deoxyglucose ( PET-FDG ) imaging for the detection of squamous cell carcinoma of the head and neck . Fifty-four consecutive patients with malignancies involving the head and neck were studied prospect ively . Thirty-one patients presented with primary disease and 23 were suspected of recurrent or residual disease . All patients underwent full clinical staging , PET-FDG scans and anatomical imaging , 37 underwent computed tomography ( CT ) , 13 magnetic resonance ( MR ) and four had both CT and MR . Clinical assessment , CT/MR , PET-FDG and histological examination were all evaluated independently of each other . All 31 primary head and neck malignant tumours were detected by PET-FDG . Based on 16 patients who underwent neck dissections , the sensitivity and specificity of PET-FDG for detecting nodal disease was 67 % and 100 % respectively , compared with clinical assessment of 58 % and 75 % and CT/MR of 67 % and 25 % . In all 12 patients , PET-FDG correctly identified the presence of absence or recurrent or residual disease . PET-FDG staged 13 post-treatment necks with an accuracy of 100 % as compared to CT/MR which was accurate in 7 of 13 and clinical assessment which was accurate in eight . Three sites of abnormal tracer uptake unrelated to malignancy were recorded as incidental findings ( m and ibular osteomyelitis , 1 : post glossectomy site , 2 ) . PET-FDG was more accurate than CT/MR for identifying primary and recurrent tumours as well as metastatic lesions in the neck . If these diagnostic properties of PET-FDG are confirmed in further prospect i ve studies , it could prove a valuable adjunct for the management of head and neck cancer During an 18 month period 39 patients were evaluated with [ 18F ] fluorodeoxyglucose-PET ( FDG-PET ) for primary brain tumours . These included patients with suspected newly diagnosed tumours and patients with known tumours who were being evaluated for possible recurrence or increasing tumour grade . Scans were performed on a 951 - 31 Siemen 's PET scanner with 4 mm resolution . Scanning time was about 20 minutes per patient . All patients had undergone recent cerebral MRI . These patients were divided into two groups . In the first group ( 30 ) MRI and PET concurred on the diagnosis . The second group ( nine ) comprised those where the interpretation of MRI and PET was different or there was a question of the diagnosis on MRI . This group comprised three patients in whom MRI suggested recurrent tumour and PET inaccurately suggested radiation necrosis ; two patients with newly diagnosed enhancing lesions on MRI in whom PET was useful in distinguishing strokes from tumour ; two patients with prior gliomas with new enhancing isolated lesions on MRI in whom PET scan accurately depicted radiation necrosis ; and two patients with newly diagnosed enhancing lesions on MRI in whom PET scan was helpful in distinguishing multiple sclerosis from tumour in one but not in the other . Therefore , of the 39 patients , PET was helpful in five in distinguishing tumour from other disease processes ; but , in so far as influencing treatment , it seemed helpful in only two . Thus PET seems to be of limited value as an aid to evaluating and treating patients with suspected or known primary brain tumours UNLABELLED The aim of this prospect i ve study was to investigate if high uptake of 18F-fluoro-2-deoxy-D-glucose ( FDG ) is associated with aggressiveness in head and neck cancer and low probability of survival . METHODS Thirty-seven patients with squamous-cell carcinoma of the head and neck underwent FDG-PET in the fasting state before cancer treatment . FDG uptake in primary tumor was quantitated as the st and ardized uptake value of FDG normalized to the predicted lean body mass ( SUVlean , n = 37 ) and as the graphically determined metabolic rate for FDG ( rMR[FDG ] , n = 34 ) . Paraffin-embedded tumor sample s were used for histologic evaluation , and expression of cytokeratin and Ki-67 antigen were assessed by immunohistochemistry . RESULTS Interobserver agreement for the determination of quantitative uptake of FDG in tumors was excellent ( r2 = 0.996 , p < 0.00001 ) , and all 37 primary tumors were visualized . A high uptake of FDG as assessed by SUVlean was associated with a higher than the median mitotic count ( p = 0.01 ) , absence of keratinization ( p = 0.03 ) , low or moderate histological grade of differentiation ( p = 0.046 ) and advanced stage ( p = 0.03 ) , but not with Ki-67 expression ( p = 0.11 ) . The overall survival of patients with a SUVlean lower than or equal to the median value ( 9.0 ) was clearly better in univariate analysis than that of patients with a SUVlean higher than the median ( 3-yr survival 73 % versus 22 % , relative risk of death ( RR ) 4.2 , 1.6 - 11.0 ) . However , in a multivariate analysis the only independent predictors of survival were the mitotic count ( RR 4.0 , 1.4 - 11.7 ) and stage ( 3.8 , 1.2 - 12.2 ) . CONCLUSION High uptake of FDG in untreated head and neck cancer is associated with advanced disease , and may portend poor survival . Aggressive treatment approaches should be considered for patients presenting with a tumor with high uptake of FDG UNLABELLED This study evaluated various quantitative criteria for analysis of breast imaging with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose ( FDG ) . METHODS In a prospect i ve study , 73 patients with abnormal mammography or palpable breast masses scheduled for biopsy were investigated with PET . A total of 97 breast tumors were evaluated by histology , including 46 benign and 51 malignant tumors . Using a whole-body PET scanner , attenuation-corrected images were acquired between 40 and 60 min after tracer injection . For Patlak analysis , dynamic data acquisition was obtained in 24 patients . To differentiate between benign and malignant breast tumors , receiver operating characteristic curves were calculated using incrementally increasing threshold values for tumor/ nontumor ratios based on average and maximum activity values per region of interest , st and ardized uptake values ( corrected for partial volume effect , normalized to blood glucose , partial volume effect and blood glucose , using the lean body mass as well as the body surface area ) and calculating the FDG influx rate ( K ) assessed by Patlak analysis . RESULTS Quantification of FDG uptake in breast tumors provided objective criteria for differentiation between benign and malignant tissue with similar diagnostic accuracy as compared with visual analysis . Applying correction for partial volume effect and normalization by blood glucose yielded the highest diagnostic accuracy . CONCLUSIONS These quantitative methods provided accurate evaluation of PET data for differentiating benign from malignant breast tumors . Quantitative assessment is recommended to complement visual image interpretation with the potential benefit of reduced interobserver variability Recent studies have shown limitations of morphological imaging in staging mediastinal lymph node involvement in lung cancer . In contrast to computed tomography ( CT ) , which depends primarily on anatomical imaging features , positron emission tomography ( PET ) with 18-fluorodeoxyglucose ( FDG ) depends mainly on the metabolic characteristics of a tissue for the diagnosis of disease . We have performed a prospect i ve study comparing FDG-PET and CT of the thorax in the presurgical assessment of the mediastinum in 50 patients with newly diagnosed non-small cell lung cancer ( NSCLC ) . CT and PET scans were interpreted separately , and results were compared to pathological staging obtained during thoracotomy . Hilar or mediastinal lymph node involvement was present in 58 % . In staging for lymph node involvement , CT had a sensitivity of 72 % and specificity of 81 % , whereas PET had a sensitivity and specificity of 90 % and 86 % , respectively . When the PET study was compared to histological results , there were four cases showing more advanced mediastinal involvement with PET and four cases showing less involvement with PET . From our preliminary results , we conclude that positron emission tomography with 18-fluorodeoxyglucose is significantly more accurate than computed tomography in the mediastinal staging of non-small cell lung cancer PURPOSE To prospect ively compare the accuracy of positron emission tomography ( PET ) with 2-[fluorine-18 ] fluoro-2-deoxy-D-glucose ( FDG ) with that of computed tomography ( CT ) in the nodal staging of non-small cell lung cancer . MATERIAL S AND METHODS PET and contrast material -enhanced CT were performed in 47 patients suspected of having or with newly diagnosed non-small cell lung cancer . Each imaging study was evaluated separately , and nodal stations were localized according to the American Thoracic Society mapping system . Extensive lymph node sampling ( 599 nodes from 191 nodal stations ) of the ipsi- and contralateral tracheobronchial and mediastinal nodal stations was performed at thoracotomy and /or mediastinoscopy . Imaging findings were correlated with histopathologic staging results . RESULTS The sensitivity of PET and CT was 89 % and 57 % , respectively , for the staging of N2 or N3 disease in mediastinal nodes ; specificity was 99 % and 94 % , respectively ; positive predictive value was 96 % and 76 % , respectively ; negative predictive value was 97 % and 87 % , respectively ; and accuracy was 96 % and 85 % , respectively . In assigning the correct N stage , PET was correct in 96 % and CT in 79 % of cases . CONCLUSION PET with FDG appears to be superior to CT for nodal staging of non-small cell lung cancer The noninvasive staging of axillary lymph nodes for metastases is investigated in patients with breast cancer prior to surgery by positron emission tomography ( PET ) with fluorine- l8-fluoro-2-deoxy-d-glucose ( 18F-FDG ) . In 124 patients with newly diagnosed breast cancer , whole-body PET was performed to determine the average differential uptake ratio ( DUR ) of18F-FDG in the axillary lymph nodes . Results were correlated with the number of the dissected lymph nodes , size of the primary tumor , tumor type , tumor grade , estrogen and progesterone receptors , DNA ploidy , and the proportion of cells in the synthetic phase of the cell cycle ( S-phase ) . In this prospect i ve study of 124 patients with breast carcinoma , PET correctly categorized all 44 tumor-positive axillary lymph nodes , a sensitivity of 100 % . Sixty tumor-negative axillary lymph nodes were negative by PET and 20 tumor-negative axillary lymph nodes were positive by PET . No false-negative PET findings were encountered . A weak correlation was found between DUR and tumor size as well as between DUR and the S-phase of the tumor . In patients with breast carcinoma,18F-FDG PET can be of value in evaluating axillary lymph nodes for metastatic involvement prior to surgery . It is of particular importance that no false-negative PET findings were encountered , and axillary lymph node dissection might not be necessary in patients without axillary uptake by PET . The DUR of the positive axillary lymph nodes seems to bear a relationship with some of the purported prognostic parameters of the primary tumor UNLABELLED The optimal method for analyzing PET scans in children being considered for epilepsy surgery is unresolved : Fully quantified methods are invasive , and the required controls are generally unavailable . We sought to compare visual inspection with semiquantitative analysis for the detection of cortical metabolic defects . METHODS Thirty-two children with cryptogenic epileptic encephalopathies were studied prospect ively with 18F-fluorodeoxyglucose ( FDG ) PET . Visual inspection was performed on separate occasions by independent observers . Four-millimeter circular regions of interest were used to sample radiotracer uptake in selected cortical regions . Asymmetry between homologous regions were calculated to detect focal abnormalities . Bilateral and diffuse abnormalities were assessed by comparing the ratio of cortical-to-cerebellar uptake in patients with historical age-matched controls . The sensitivity and specificity of visual inspection was compared with that of semiquantitative analysis for the detection of focal , bilateral and diffuse cortical metabolic abnormalities . RESULTS Visual inspection revealed full inter-rater agreement for the presence of major focal abnormalities . The sensitivity and specificity for visual inspection compared to semiquantitative analysis were 77 % and 92 % , respectively , with semiquantitative analysis often revealing abnormalities to be more extensive than had been suspected visually . Compared with semiquantitative analysis , visual inspection had a low sensitivity but high specificity for the detection of bilateral and diffuse hypometabolism . CONCLUSION Semiquantitative analysis gives clinical ly useful information additional to that obtained from visual inspection METHODS The presurgical , noninvasive staging of axillary nodes for metastases was prospect ively investigated in 68 patients who were diagnosed with primary breast cancer using PET with 18F-fluorodeoxyglucose ( FDG ) . Four patients had bilateral nodules ; therefore , the total number of evaluable cases was 72 . Visual analyses of attenuation-corrected PET images and st and ardized uptake values ( SUVs ) of FDG uptake in carcinomas were compared with histopathological surgical findings . The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and receiver operating characteristics analyses . RESULTS PET correctly classified 64 of the 72 cases ; four false-positive and four false-negative PET results were found . The overall sensitivity , specificity and accuracy of PET for axillary metastases were 85 % , 91 % and 89 % , respectively . With respect to the clinical axillary stage of the patients ( TNM , or tumor-node-metastasis , classification ) , we obtained the following results : N0 patients , sensitivity = 70 % , specificity = 92 % , accuracy = 86 % ; N1a patients , sensitivity = 85.5 % , specificity = 100 % , accuracy = 95 % ; and N1b-2 patients , sensitivity = 100 % , specificity = 67 % , accuracy = 87 % . The median SUV in carcinomas with axillary metastases ( 4.6 ) was significantly higher than that in carcinomas without metastases ( 2.9 ) , but there was a great SUV overlap between the two groups ( interquartile ranges = 2.7 - 7.2 and 1.9 - 4.5 , respectively ) . Analysis of the receiver operating characteristics curve showed that a high sensitivity of SUV in predicting axillary metastases was associated with a very low specificity and vice versa . With the best SUV cutoff value of 2.9 , the sensitivity and specificity were 74 % and 56 % , respectively . CONCLUSION PET showed good overall diagnostic accuracy in the detection of axillary metastases ( 86 % ) . The very high accuracy ( 95 % ) in N1a patients is of particular importance . False-negative PET findings , however , can be encountered . SUVs of breast carcinoma can not predict the spread of the disease to the axilla , even if higher values are often associated with axillary metastases . Any decision on the use of PET in the presurgical staging of breast cancer should be incorporated into a more general debate on axillary management . In selected patients with a very low probability of axillary metastases ( T1a ) , in whom axillary surgery can already be avoided according to data from follow-up studies , 18F-FDG PET could be proposed as a noninvasive imaging modality to improve the diagnosis of axillary relapses The purpose of this study was to prospect ively evaluate positron emission tomography ( PET ) for delineating lung cancers preradiotherapy and to assess PET 's ability to distinguish residual tumor from scarring following radiotherapy . Between April 1991 and October 1992 , 20 patients underwent 18fluoro-2-deoxyglucose ( 18FDG ) PET scanning of the chest prior to radiotherapy for lung cancer . Tumor volumes on chest x-ray ( CXR ) and computerized tomography ( CT ) scan were correlated with abnormalities on PET scans . Follow-up PET studies were compared to postradiotherapy chest x-ray and /or CT scans , and correlated with clinical outcome . Six of seven well-demarcated tumors showed increased uptake of 18FDG correlating with the CT/CXR tumor volume . Twelve poorly demarcated tumors demonstrated increased 18FDG uptake . In seven of 12 , the CT/CXR abnormality correlated with changes on PET scan . In three of 12 , CT/CXR abnormalities were larger than on PET , whereas in two of 12 , abnormalities on PET extended outside the region of CT/CXR changes . The 13th patient in the poorly demarcated category had diffuse carcinoma in situ at the surgical margin that demonstrates increased 18FDG uptake , but was not visible by CT/CXR . Of 12 patients with follow-up studies , all had changes on CXR and /or CT that made it difficult to assess response . Four of 12 had a complete response by PET ; all remain locally controlled . The remaining eight patients had either a partial response ( n = 6 ) or no response ( n = 2 ) by PET . Four of these eight patients remain alive and well 11 - 24 months after therapy . 18FDG PET may be useful for delineation of lung cancer volumes that are poorly defined by CXR and /or CT scan . The value of PET in differentiating tumor from fibrosis after radiotherapy for lung cancer remains to be established OBJECTIVE The purpose of this study was to assess the usefulness of positron emission tomography ( PET ) with 18F-fluorodeoxyglucose ( FDG ) when differentiating benign from metastatic adrenal masses in patients with bronchogenic carcinoma . SUBJECTS AND METHODS For our prospect i ve study , any patient presenting to our institution with pathologically proven bronchogenic carcinoma and an adrenal mass was eligible . Thirty-three adrenal masses ( mean size , 3 cm ; range , 1 - 9 cm ) in 27 patients were revealed by CT . PET was performed in all 27 patients and interpreted as positive when FDG uptake in the adrenal mass was greater than background activity or negative when FDG uptake in the adrenal mass was equal to or less than background activity . In addition , semiquantitative analysis was performed by computing a st and ardized uptake ratio . All studies were review ed independently by three radiologists and then correlated with biopsy and CT findings . Specificity and sensitivity for determining metastatic disease to the adrenal gl and were calculated . RESULTS FDG uptake was positive ( abnormally increased ) in 25 adrenal masses . Twenty-three ( 92 % ) of the 25 masses were metastatic disease . The mean st and ardized uptake ratio of these was 6.28 ( range , 3.22 - 14.41 ) . The remaining two masses ( 8 % ) that had positive FDG uptake showed no tumor at percutaneous biopsy . The st and ardized uptake ratio values for these two masses were 3.0 and 3.7 . FDG uptake was negative ( normal ) in eight adrenal masses . All these lesions were benign as proven by biopsy ( n = 2 ) and CT attenuation values of less than 10 H ( n = 6 ) . The mean st and ardized uptake ratio value for these eight lesions classified as benign was 1.77 ( range , 0.93 - 3.70 ) . The sensitivity for detecting metastatic disease was 100 % , and the specificity was 80 % . CONCLUSION PET with FDG is an accurate , noninvasive way to differentiate benign from metastatic adrenal masses in patients with bronchogenic carcinoma The clinical usefulness of FDG-PET in the prediction and assessment of response to radiation therapy in patients with bronchogenic carcinoma was evaluated . Thirty patients with untreated bronchogenic carcinoma were included in the study . All patients received FDG-PET before the initiation of radiation therapy , while 20 also received it after completing the therapy . The tumor to muscle ratio ( TMR ) was used as an index of the FDG uptake . The tumor response to therapy was classified as either a partial response ( PR , n = 21 ) or no change ( NC , n = 9 ) according to changes in the tumor size . Prognosis was made 6 months after the initiation of therapy , and was classified as either relapse ( n = 19 ) or non-relapse ( n = 9 ) . The FDG uptakes both before and after therapy were compared with tumor response and prognosis . A high FDG uptake was noted in all 30 lesions before therapy . No significant differences in the uptake before therapy was observed according to the histological types nor T factors ( UICC ) . The lesions with a higher uptake ( TMR more than 7 ) responded better to therapy than those with a lower uptake ( p < 0.05 ) . The decrease in the uptake after therapy tended to be more prominent in the PR group than in the NC group . The rate of relapse was higher in lesions with a higher uptake before therapy ( TMR more than 10 ) than in those with a lower uptake . The relapse group also showed a higher uptake after therapy than the non-relapse group . In addition , all 6 lesions showing a higher uptake ( TMR more than 5 ) after therapy eventually relapsed ( p < 0.05 ) . Two lesions demonstrating a lower uptake both before and after therapy did not relapse , although no tumor regression due to the therapy was observed . These results indicate that FDG-PET plays a complementary role in both predicting and assessing the therapeutic response and prognosis in patients with bronchogenic carcinoma The objective of this study was to compare the cost of intravenous adenosine and intravenous dipyridamole in positron emission tomography ( PET ) in patients with coronary artery disease . A retrospective , open-label , case-control , cost-effectiveness analysis was performed in the out-patient nuclear medicine department of a university hospital . Thirty-six patients underwent dipyridamole PET , and 72 matched patients underwent adenosine PET . A cost-effectiveness analysis was conducted using a direct cost accounting approach to estimate institutional costs . Key costs evaluated included acquisition cost , administration cost , monitoring cost , cost of management of side effects , and cost of follow-up care . The total cost of adenosine PET and dipyridamole PET was divided by their respective predictive accuracies to provide a total cost adjusted for efficacy . Adenosine increased heart rate and lowered systolic blood pressure to a significantly greater extent than dipyridamole . The number of patients experiencing adverse drug reactions was significantly greater for adenosine ( 82 % ) than for dipyridamole ( 67 % ) , but the frequency of prolonged ( > 5 minutes ) and late-onset side effects was significantly greater for dipyridamole than for adenosine . The frequency of side effects requiring medical intervention was also significantly greater for dipyridamole ( 53 % ) than for adenosine ( 6 % ) . Although adenosine had a significantly greater acquisition cost than dipyridamole , costs of monitoring , management of side effects , and follow-up care were significantly less for adenosine than for dipyridamole . As a result , the total cost of using dipyridamole is significantly greater ( $ 928.00 per patient ) than the total cost of using adenosine ( $ 672.00 per patient ) . Based on these results , adenosine may be the drug of choice for pharmacologic vasodilation for PET |
13,491 | 29,226,307 | AUTHORS ' CONCLUSIONS At present , the quality of the evidence on the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults is low , implying that we are uncertain about the estimated treatment effect .
There is no statistically significant difference between the available therapeutic alternatives for the treatment of sexually active adults with genital ulcers compatible with chancroid .
Low quality evidence suggests that azithromycin could be considered as the first therapeutic alternative , based on their mono-dose oral administration , with a similar safety and effectiveness profile , when it is compared with long-term erythromycin use . | BACKGROUND Chancroid is a genital ulcerative disease caused by Haemophilus ducreyi .
This microorganism is endemic in Africa , where it can cause up to 10 % of genital ulcers .
Macrolides may be an effective alternative to treat chancroid and , based on their oral administration and duration of therapy , could be considered as first line therapy .
OBJECTIVES To assess the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults . | Human subjects were infected with Haemophilus ducreyi . All subjects developed papules and were r and omized to treatment with a single dose of azithromycin ( 1 g ) or ciprofloxacin ( 500 mg ) . At weekly intervals , volunteers were reinoculated with H. ducreyi , and drug concentrations were measured in peripheral blood mononuclear cells ( P BMC ) . When papules developed , the subjects were treated with antibiotics and dismissed from the study . Eight of the ciprofloxacin-treated subjects developed papules 1 week after the initial treatment , and the ninth subject developed disease 2 weeks after treatment . The 9 azithromycin-treated subjects developed papules 4 - 10 weeks ( mean , 6.8 ) after the initial treatment ( P < .001 ) . Azithromycin was detected in P BMC for 3 - 6 weeks ( mean , 4 ) . Pre- and posttreatment lesions had histology typical of experimental chancroid or were culture positive . Azithromycin prevents experimental chancroid for nearly 2 months . These findings have implication s for strategies to prevent chancroid Background and Objectives : Cotrimoxazole has traditionally been used as first drug for treatment of chancroid in India . With reports of increasing resistance to the drug , this study was conducted to compare treatment response of clinical chancroid between ciprofloxacin , 500 mg twice daily for 3 days , erythromycin , 500 mg four times daily for 7 days , and double‐strength cotrimoxazole ( trimethoprim 160 mg + sulfamethoxazole 800 mg ) , twice daily for 7 days . Study Design : Forty‐six patients with a clinical diagnosis of chancroid were r and omly divided into 3 groups . Sixteen patients received ciprofloxacin , whereas 15 each received erythromycin and cotrimoxazole . Patients were seen on day 7 , 14 , and if needed day 21 . Clinical response was noted in terms of cure , improvement , or failure . Results : Excellent response was observed to both ciprofloxacin and erythromycin therapy with cure rates of 93.7 % and 93.3 % , respectively . Improvement was observed in 6.7 % cases in both groups . There were no failures with either ciprofloxacin or erythromycin . Poor response to cotrimoxazole therapy was observed with 53.3 % cure rates and a high failure rate of 46.7 % . Conclusion : Ciprofloxacin and erythromycin are equally effective in chancroid . Ciprofloxacin is better in terms of dosage schedule , duration of treatment , and low cost . Cotrimoxazole should be discontinued as drug of choice because of high failure rates A r and omized , double-blind , placebo-controlled clinical trial was conducted in Nairobi , Kenya , to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid . In all , 208 men and 37 women presenting with genital ulcers clinical ly compatible with chancroid were enrolled . Ulcer etiology was determined using culture techniques for chancroid , serology for syphilis , and a multiplex polymerase chain reaction for chancroid , syphilis , and herpes simplex virus ( HSV ) . Ulcer etiology was 31 % unmixed chancroid , 23 % unmixed syphilis , 16 % unmixed HSV , 15 % mixed etiology , and 15 % unknown . For 111 participants with chancroid , cure rates were 92 % with ciprofloxacin and 91 % with erythromycin . For all study participants , the treatment failure rate was 15 % , mostly related to ulcer etiologies of HSV infection or syphilis , and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others , mostly owing to HSV infection . Ciprofloxacin is an effective single-dose treatment for chancroid , but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection One hundred and thirty six patients with chancroid were treated with four different treatment regimens ; ( A ) Sulphaphenazole 1 g 12 hourly by mouth x 10 days ( B ) Inj streptomycin 1 g intramuscularly daily with sulphaphenazole 1 g 12 hourly orally x 10 days ; ( C ) trimethoprim 200 mg 12 hourly by mouth x 7 - 10 days , and ( D ) erythromycin 500 mg 6 hourly orally x 7 - 10 days . Cure rates of 9 % with sulphaphenazole alone , 48 % with streptomycin and sulphaphenazole combination , 93 % with trimethoprim and 100 % with erythromycin were obtained . Sulphaphenazole alone or in combination with streptomycin were thus inferior in the treatment of chancroid . There is need for modification of treatment regimens recommended for chancroid in the textbooks of dermatology and venereology . Trimethoprim can be recommended as first line of treatment for chancroid in developing countries like India where resistance to trimethoprim is uncommon and erythromycin is suggested as a second line of therapy because by that time syphilis can be easily ruled out We conducted a r and omized , unblinded , prospect i ve study design ed to determine the efficacy of single-dose azithromycin for the treatment of chancroid . Men and women 16 years of age and older who had darkfield-negative genital ulcers that were clinical ly suspected to be caused by Haemophilus ducreyi and who attended urban sexually transmitted disease clinics or presented to hospital emergency departments were enrolled in the study . Patients were r and omized to receive 250 mg of ceftriaxone i m or 1 g of azithromycin orally , both given as a single dose . They were followed for up to 23 days after treatment . For 65 patients , cultures were positive for H. ducreyi ; there were 68 patients whose cultures were negative for both H. ducreyi and herpes simplex virus and who had no evidence of syphilis . All 133 patients returned for at least one follow-up visit . At the time of the last follow-up visit , all 32 patients whose cultures were positive for H. ducreyi and who were treated with azithromycin were clinical ly cured . In all 33 culture-positive cases in which ceftriaxone was used , there was either clinical improvement or cure at the time of the patient 's last follow-up visit . In addition , azithromycin and ceftriaxone were equally effective in healing ulcers for which cultures were negative . We conclude that a single 1-g oral dose of azithromycin is as effective as a 250-mg i m dose of ceftriaxone for the treatment of chancroid Background and Objectives Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 ( HIV-1 ) . Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi , the causative agent of chancroid , and has pharmacokinetic properties that are suitable for single dosing . Study Design In a r and omized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid , we compared the efficacy of azithromycin , administered as a single 1 g dose , with erythromycin 500 mg given 4 times daily for 7 days . Results : Cure rates were 89 % ( 73 of 82 ) in the azithromycin group and 91 % ( 41 of 45 ) in the erythromycin group . A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision . Both regimens were well tolerated . Conclusions Azithromycin , given as a single 1 g oral dose , is an effective treatment for chancroid in men , and offers major prescribing advantages over erythromycin Tetracyclines and sulfonamides are no longer effective for the treatment of chancroid in many parts of the world . Rifampin and trimethoprim both possess in vitro activity against Haemophilus ducreyi , the causative agent of chancroid . In a r and omized , controlled study , 22 patients with H. ducreyi-positive genital ulcers received 600 mg of rifampin once daily for three days , and 32 patients received 600 mg of rifampin plus 160 mg of trimethoprim once daily for three days . Both regimens rapidly eradicated H. ducreyi from ulcers , with subsequent healing of ulcers and buboes . Two relapses of ulcers and one therapeutic failure were observed in the rifampin-trimethoprim group , whereas no relapses or failures were noted in the rifampin group . In addition , all of 16 H. ducreyi-negative ulcers responded rapidly to treatment with either regimen . In an uncontrolled , open study , 22 H. ducreyi-positive ulcers were treated with a single dose of rifampin ( 600 mg ) plus trimethoprim ( 160 mg ) . Ulcers and buboes resolved by day 14 in all but one patient . Thus , these short-course and single-dose regimens are effective against chancroid In a r and omized , controlled study , 55 patients with genital ulcerations , culture-positive for Haemophilus ducreyi , were treated with a single intramuscular injection of 2 g spectinomycin . A further 61 patients were treated with a five-day oral course of erythromycin base ( 500 mg , three times daily ) . Treatment failure occurred in seven patients who received spectinomycin ( 13 % ) , whilst no treatment failures were recorded among patients who received erythromycin . This difference in efficacy was statistically significant . In contrast , spectinomycin proved significantly more effective than erythromycin in the treatment of the lymphadenopathy associated with primary chancroid lesions |
13,492 | 30,523,651 | PtDAs were shown to significantly increase fertility preservation knowledge and decrease decisional conflict .
Overall satisfaction with decision aids was high .
PtDAs can serve as effective complements to current fertility counselling practice s by increasing information satisfaction and decision-making outcomes . | OBJECTIVE Despite recommendations internationally for the timely provision of fertility information , cancer patients report unmet information needs , with poor provision and inadequate written information to assist in fertility preservation decision-making .
Patient decision aids ( PtDAs ) may be a useful re source in this setting to inform patients and guide decision-making .
A systematic review of the literature on decision aids for fertility preservation in cancer patients would determine the effectiveness of these tools in supporting decision-making about fertility preservation and indicate their current use in clinical care . | PURPOSE Impairment of fertility is a common sequela of successful cancer treatment . Therefore , fertility preservation ( FP ) should be discussed with all young cancer patients . Decisions about FP are challenging . Patients wish more specific support and the first results concerning the helpfulness of decision aids ( DA ) were promising . Aside from describing the process of development and the content of an online DA in German , the objective of this study was to pilot test users ' satisfaction with the DA and its effect on knowledge about FP and decisional conflict ( DC ) . METHODS In this prospect i ve consecutive study , a control group ( n = 20 , fertility counseling ) was followed by and compared with an intervention group ( n = 20 , counseling and additional use of the DA , developed by an interdisciplinary team ) of recently diagnosed female cancer patients between 18 and 40 years . RESULTS Nearly all participants who applied the DA considered it helpful for decision-making and recommendable . Knowledge about FP was high with regard to FP techniques women went for . DC was moderate according to the mean score ( M = 27.92 , st and ard deviation = 13.27 ) and only in 20 % , the score was above the threshold for high DC . There was no difference between the control and intervention group for knowledge and DC . CONCLUSION The DA seems to serve as additional and well-accepted support tool in decision-making for patients and professionals . Referral to a reproductive specialist is crucial to warrant comprehensive information . These results need to be confirmed with the current ongoing r and omized controlled study Abstract This paper reports on the feasibility and preliminary effects of a decision aid ( DA ) about female fertility preservation ( FP ) . We conducted a pilot multicentre r and omized controlled trial of women with breast cancer aged 18–40 who were r and omized to brochures or the DA . Over 18 months , 62 women were eligible , of which 42 were invited by their healthcare provider ( 74 % ) to participate in the study . A total of 36 women signed up for participation and 26 ( 72 % ) were r and omized to brochures ( n = 13 ) or the DA ( n = 13 ) . In both groups , many women ( 87 % ) read the brochures and eight women used all available brochures . In the intervention group , 7/13 women logged in to the DA . Women who received brochures had slightly less decisional conflict , whereas knowledge improved in both groups . Our results indicate that both brochures about FP and a detailed DA have beneficial effects with regard to knowledge , but the DA seemed to introduce slightly more decisional conflict ( DC ) than the brochures . Although we encountered challenges with recruitment , our design and measurements seem feasible and the effects of the information material s seem promising , hence justifying conducting a larger study Background We aim ed to evaluate the effect of a decision aid ( DA ) with information only compared to a DA with values clarification exercise ( VCE ) , and to study the role of personality and information seeking style in DA-use , decisional conflict ( DC ) and knowledge . Methods Two scenario-based experiments were conducted with two different groups of healthy female participants . Dependent measures were : DC , knowledge , and DA-use ( time spent , pages viewed , VCE used ) . Respondents were r and omized between a DA with information only ( VCE- ) and a DA with information plus a VCE(VCE+ ) ( experiment 1 ) , or between information only ( VCE- ) , information plus VCE without referral to VCE(VCE+ ) , and information plus a VCE with specific referral to the VCE , requesting participants to use the VCE(VCE++ ) ( experiment 2 ) . In experiment 2 we additionally measured personality ( neuroticism/conscientiousness ) and information seeking style ( monitoring/blunting ) . Results Experiment 1 . There were no differences in DC , knowledge or DA-use between VCE- ( n=70 ) and VCE+ ( n=70 ) . Both DAs lead to a mean gain in knowledge from 39 % at baseline to 73 % after viewing the DA . Within VCE+ , VCE-users ( n=32 , 46 % ) reported less DC compared to non-users . Since there was no difference in DC between VCE- and VCE+ , this is likely an effect of VCE-use in a self-selected group , and not of the VCE per se . Experiment 2 . There were no differences in DC or knowledge between VCE- ( n=65 ) , VCE+ ( n=66 ) , VCE++ ( n=66 ) . In all groups , knowledge increased on average from 42 % at baseline to 72 % after viewing the DA . Blunters viewed fewer DA-pages ( R=0.38 , p<.001 ) . More neurotic women were less certain ( R=0.18 , p<.01 ) and felt less supported in decision making ( R=0.15 , p<.05 ) ; conscientious women felt more certain ( R=-0.15 , p<.05 ) and had more knowledge after viewing the DA ( R=0.15 , p<.05 ) . Conclusions Both DAs lead to increased knowledge in healthy population s making hypothetical decisions , and use of the VCE did not improve knowledge or DC . Personality characteristics were associated to some extent with DA-use , information seeking styles with aspects of DC . More research is needed to make clear recommendations regarding the need for tailoring of information provision to personality characteristics , and to assess the effect of VCE use in actual patients Background : Fertility is a priority for many young women with breast cancer . Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions . This study aim ed to prospect ively evaluate the efficacy of a fertility-related decision aid ( DA ) . Methods : A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics , aged 18–40 years and desired future fertility , were assessed on decisional conflict , knowledge , decision regret , and satisfaction about fertility-related treatment decisions . These were measured at baseline , 1 and 12 months , and were examined using linear mixed effects models . Results : Compared with usual care , women who received the DA had reduced decisional conflict ( β=−1.51 ; 95%CI : −2.54 to 0.48 ; P=0.004 ) and improved knowledge ( β=0.09 ; 95%CI : 0.01–0.16 ; P=0.02 ) , after adjusting for education , desire for children and baseline uncertainty . The DA was associated with reduced decisional regret at 1 year ( β=−3.73 ; 95%CI : −7.12 to −0.35 ; P=0.031 ) , after adjusting for education . Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility ( P<0.001 ) , fertility options ( P=0.005 ) , and rated it more helpful ( P=0.002 ) , than those who received st and ard care . Conclusion : These findings support widespread use of this DA shortly after diagnosis ( before chemotherapy ) among younger breast cancer patients who have not completed their families PURPOSE This study was undertaken to determine the effect , if any , of treatment for cancer diagnosed during childhood or adolescence on fertility . PATIENTS AND METHODS We review ed the fertility of female participants in the Childhood Cancer Survivor Study ( CCSS ) , which consisted of 5-year survivors , and a cohort of r and omly selected siblings who responded to a question naire . Medical records of all members of the cohort were abstract ed to obtain chemotherapeutic agents administered ; the cumulative dose of drug administered for several drugs of interest ; and the doses , volumes , and date s of administration of all radiation therapy . RESULTS There were 5,149 female CCSS participants , and there were 1,441 female siblings of CCSS participants who were age 15 to 44 years . The relative risk ( RR ) for survivors of ever being pregnant was 0.81 ( 95 % CI , 0.73 to 0.90 ; P < .001 ) compared with female siblings . In multivariate models among survivors only , those who received a hypothalamic/pituitary radiation dose > or = 30 Gy ( RR , 0.61 ; 95 % CI , 0.44 to 0.83 ) or an ovarian/uterine radiation dose greater than 5 Gy were less likely to have ever been pregnant ( RR , 0.56 for 5 to 10 Gy ; 95 % CI , 0.37 to 0.85 ; RR , 0.18 for > 10 Gy ; 95 % CI , 0.13 to 0.26 ) . Those with a summed alkylating agent dose ( AAD ) score of three or four or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant . CONCLUSION This large study demonstrated that fertility is decreased among female CCSS participants . The risk factors identified may be utilized for pretreatment counseling of patients and their parents Introduction Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services while undergoing treatment of their cancer with oncology services . Oncologists identify a need for re sources enabling them to support women 's fertility preservation decisions more effectively ; women report wanting more specialist information to make these decisions . The overall aim of the ‘ Cancer , Fertility and Me ’ study is to develop and evaluate a new evidence -based patient decision aid ( PtDA ) for women with any cancer considering fertility preservation to address this unmet need . Methods and analysis This is a prospect i ve mixed- method observational study including women of reproductive age ( 16 years + ) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire , UK . The research involves three stages . In stage 1 , the aim is to develop the PtDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information . In stage 2 , the aim is to assess the face validity of the PtDA . Feedback on its content and format will be ascertained using question naires and interviews with patients , user groups and key stakeholders . Finally , in stage 3 the acceptability of using this re source when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated . This will involve a quantitative and qualitative evaluation of the PtDA in clinical practice . Measures chosen include using count data of the PtDAs administered in clinics and accessed online , decisional and patient-reported outcome measures and qualitative feedback . Quantitative data will be analysed using descriptive statistics , paired sample t-tests and CIs ; interviews will be analysed using thematic analysis . Ethics and dissemination Research Ethics Committee approval ( Ref : 16/EM/0122 ) and Health Research Authority approval ( Ref : 194751 ) has been granted . Findings will be published in open access peer- review ed journals , presented at conferences for academic and health professional audiences , with feedback to health professionals and program managers . The Cancer , Fertility and Me patient decision aid ( PtDA ) will be disseminated via a diverse range of open-access media , study and charity websites , professional organisations and academic sources . External endorsement will be sought from the International Patient Decision Aid St and ards ( IPDAS ) Collaboration inventory of PtDAs and other relevant professional organisations , for example , the British Fertility Society . Trial registration number NCT02753296 ; pre- results The aim of this prospect i ve study is to assess the reliability and validity of a multi-dimensional measure of informed choice ( MMIC ) . Participants were 225 pregnant women in two general hospitals in the UK , women receiving low-risk results following serum screening for Down syndrome . The MMIC was administered before testing and the Ottawa Decisional Conflict Scale was administered 6 weeks later . The component scales of the MMIC , knowledge and attitude , were internally consistent ( alpha values of 0.68 and 0.78 , respectively ) . Those who made a choice categorised as informed using the MMIC rated their decision 6 weeks later as being more informed , better supported and of higher quality than women whose choice was categorised as uninformed . This provides evidence of predictive validity , whilst the lack of association between the MMIC and anxiety shows construct ( discriminant ) validity . Thus , the MMIC has been shown to be psychometrically robust in pregnant women offered the choice to undergo prenatal screening for Down syndrome and receiving a low-risk result . Replication of this finding in other groups , facing other decisions , with other outcomes , should be assessed in future research OBJECTIVES We conducted pilot studies of the feasibility and efficacy of an interactive , computerized educational tool , Banking on Fatherhood ( BOF ) . METHODS Two small r and omized trials were conducted , with 20 male cancer patients eligible to bank sperm in Study 1 and 19 oncology fellows or residents in Study 2 . In each trial , half of the subjects viewed BOF before completing question naires , and half viewed it afterward . Outcome measures included a knowledge test in both trials and a Decisional Conflict scale in the patient trial . All participants , plus a panel of 10 experts , ultimately viewed BOF and completed a form evaluating its usability and value . RESULTS Patients who completed question naires after viewing BOF had significantly less decisional conflict about banking sperm than those who had not viewed it ( P=0.0065 ) , but knowledge scores were not significantly different between groups . Physicians who filled out question naires after viewing BOF scored significantly higher on the knowledge test ( P<0.006 ) . Patients , physicians and experts rated BOF as easy to use , informative and addressing important psychosocial concerns , with videos and animations adding to the value of the educational tool . CONCLUSION Pilot studies suggest that BOF is a feasible intervention that could enhance decisions about sperm banking . Research with larger groups is needed to vali date its effectiveness |
13,493 | 31,046,441 | When added to endurance training , dynamic strength training leads to significantly greater improvements in peripheral muscle strength and power output in patients with cardiovascular disease , which may be relevant to enhance the patient ’s prognosis .
Moreover , multiple studies report that high-intensity strength training causes fewer increments in (intra-)arterial blood pressure and cardiac output , as opposed to low-intensity strength training , thus potentially pointing towards sufficient medical safety for the cardiovascular system . | As a result , dynamic strength training is recommended in the rehabilitative treatment of many different cardiovascular diseases .
However , what strength training intensity should be selected remains under intense debate . | PURPOSE Investigate hemodynamic responses of resistance exercise ( RE ) with moderate load ( i.e. , international guidelines for RE of patients ) versus RE with high load in patients with coronary artery disease ( CAD ) . METHODS Medically stable male ( n = 11 ) and female patients ( n = 4 ) treated with PCI or percutaneous coronary intervention , or coronary artery bypass surgery a minimum of 6 months before this study , performed three sets of 15RM and 4RM RE in a r and omized order on separate days . Beat-to-beat systolic ( SBP ) , diastolic ( DBP ) blood pressure , heart rate ( HR ) , stroke volume ( SV ) , cardiac output ( CO ) , and systemic vascular resistance ( SVR ) were monitored at preexercise , and continuously during RE . RESULTS Compared with preexercise , SBP and DBP ( mean of three sets ) increased by 12 % to 13 % ( both ; P < 0.001 ) and 35 % to 40 % after 15RM RE ( both ; P < 0.001 ) . 15RM SBP and DBP were higher than 4RM SBP and DBP ( both ; P < 0.001 ) . The SBP of the fourth repetition of 15 RM RE was similar to the SBP of the fourth repetition of 4RM RE . Compared with preexercise , SV increased moderately after 4RM and 15 RM RE , respectively ( both , P < 0.001 ) . HR increased more after 15RM compared with 4RM RE ( P < 0.05 ) ; thus , higher CO after 15RM ( compared with 4RM RE ; P < 0.05 ) was mainly caused by higher HR . SVR decreased by 15 % ( P < 0.001 ) and 50 % ( P < 0.01 ) after 4RM and 15RM RE . CONCLUSIONS SBP and DBP increased significantly more during moderate load RE ; thus , the magnitude of the external load is not the prime determinant of the pressure response during RE . If management of blood pressure is of concern , high load/low rep RE is preferable to medium load/high rep RE OBJECTIVE : The aim of this study was to describe blood pressure responses during resistance exercise in hypertensive subjects and to determine whether an exercise protocol alters these responses . INTRODUCTION : Resistance exercise has been recommended as a complement for aerobic exercise for hypertensive patients . However , blood pressure changes during this kind of exercise have been poorly investigated in hypertensives , despite multiple studies of normotensives demonstrating significant increases in blood pressure . METHODS : Ten hypertensive and ten normotensive subjects performed , in r and om order , two different exercise protocol s , composed by three sets of the knee extension exercise conducted to exhaustion : 40 % of the 1-repetition maximum ( 1RM ) with a 45-s rest between sets , and 80 % of 1RM with a 90-s rest between sets . Radial intra-arterial blood pressure was measured before and throughout each protocol . RESULTS : Compared with normotensives , hypertensives displayed greater increases in systolic BP during exercise at 80 % ( + 80±3 vs. + 62±2 mmHg , P<0.05 ) and at 40 % of 1RM ( + 75±3 vs. + 67±3 mmHg , P<0.05 ) . In both exercise protocol s , systolic blood pressure returned to baseline during the rest periods between sets in the normotensives ; however , in the hypertensives , BP remained slightly elevated at 40 % of 1RM . During rest periods , diastolic blood pressure returned to baseline in hypertensives and dropped below baseline in normotensives . CONCLUSION : Resistance exercise increased systolic blood pressure considerably more in hypertensives than in normotensives , and this increase was greater when lower-intensity exercise was performed to the point of exhaustion BACKGROUND Resistance training has been introduced in cardiac rehabilitation to give more benefit than traditional training . Haemodynamic evaluation of cardiac patients to resistance training has generally consisted of continuous HR monitoring and discontinuous blood pressure measurements . DESIGN AND METHODS Blood pressure ( BP ) and heart rate ( HR ) responses to resistance training were evaluated using continuous monitoring ( Finapres ) during low ( four sets of 17 repetitions at 40 % of the one-repetition maximum strength [ 1-RM ] ) and high intensity resistance training ( four sets of 10 repetitions at 70 % of 1-RM ) on a leg extension machine in 14 patients who participated in a rehabilitation programme . Work volume was identical in the low- and high-level resistance training . RESULTS The HR and systolic blood pressure ( SBP ) during low intensity resistance training were always larger than during high intensity ( P<0.001 ) . Peak SBP increased from set 1 to set 3 and 4 during both low and high intensity resistance training ( P<0.05 ) . Peak HR was larger in set 4 ( 95+/-11 bpm ) than in set 1 only during low intensity resistance training ( 91+/-12 bpm ) ( P<0.05 ) . One-minute recovery periods did not allow a return to baseline HR and SBP during both low and high intensity modalities . CONCLUSIONS The SBP and HR responses to resistance training are related to the duration of exercise . Sets with < or = 10 repetitions of high intensity should be preferred to longer sets with low intensity . Pauses between exercise sets should exceed 1 min . Blood pressure should be measured during the last repetitions of the exercise set BACKGROUND The aim of this study was to compare the acute hemodynamic and cardiovascular responses of high load/low repetition resistance training ( RT ) to low load/high repetition RT . METHODS Thirteen healthy men performed four sets of 4 repetition maximum ( RM ) and 20RM leg-extensions without breath-holding . The RT was conducted in a r and omized order and with 48 hours between bouts . Non-invasive beat-to-beat systolic and diastolic blood-pressure ( SBP/DBP ) was measured on the finger , while non-invasive cardiac output ( CO ) was assessed beat-to-beat by impedance-cardiography . RESULTS Mean±SD resting SBP/DBP and CO were 126±14/73±9 mmHg and 5.6±9 L min-1 , respectively . Exercise SBP/DBP values increased to 154±22/99 ±18 and 203±33/126±19 mmHg following 4RM and 20RM RT , respectively ( compared to rest , all ; P<0.001 ) , and 20RM SBP/DBP values were higher than 4RM values ( both , P<0.001 ) . The SBP increased from the first to the fourth set of exercise following the 20RM load ( P<0.01 ) , but not so for the 4RM load . Exercise SBP/DBP values following the 4th rep of 20RM exercise ( 154±18/91±14 ) , was similar to the 4RM values , but different to the 20th rep of the 20 RM loading ( both ; P<0.001 ) . CO increased to 10.8±2.6 and 13.9±2.2 L min-1 , following 4RM and 20RM RT , respectively ( compared to rest , both ; P<0.001 ) and 20RM CO was higher than 4RM CO ( P<0.01 ) . CONCLUSIONS 20RM RT result ed in higher blood-pressure than 4RM RT when performed to voluntary exhaustion . Differences in hemodynamic responses seems to be related to training duration and not to difference in loading We examined the neuromuscular adaptations following 3 and 6 weeks of 80 vs. 30 % one repetition maximum ( 1RM ) resistance training to failure in the leg extensors . Twenty-six men ( age = 23.1 ± 4.7 years ) were r and omly assigned to a high- ( 80 % 1RM ; n = 13 ) or low-load ( 30 % 1RM ; n = 13 ) resistance training group and completed leg extension resistance training to failure 3 times per week for 6 weeks . Testing was completed at baseline , 3 , and 6 weeks of training . During each testing session , ultrasound muscle thickness and echo intensity , 1RM strength , maximal voluntary isometric contraction ( MVIC ) strength , and contractile properties of the quadriceps femoris were measured . Percent voluntary activation ( VA ) and electromyographic ( EMG ) amplitude were measured during MVIC , and during r and omly ordered isometric step muscle actions at 10–100 % of baseline MVIC . There were similar increases in muscle thickness from Baseline to Week 3 and 6 in the 80 and 30 % 1RM groups . However , both 1RM and MVIC strength increased from Baseline to Week 3 and 6 to a greater degree in the 80 % than 30 % 1RM group . VA during MVIC was also greater in the 80 vs. 30 % 1RM group at Week 6 , and only training at 80 % 1RM elicited a significant increase in EMG amplitude during MVIC . The peak twitch torque to MVIC ratio was also significantly reduced in the 80 % , but not 30 % 1RM group , at Week 3 and 6 . Finally , VA and EMG amplitude were reduced during submaximal torque production as a result of training at 80 % 1RM , but not 30 % 1RM . Despite eliciting similar hypertrophy , 80 % 1RM improved muscle strength more than 30 % 1RM , and was accompanied by increases in VA and EMG amplitude during maximal force production . Furthermore , training at 80 % 1RM result ed in a decreased neural cost to produce the same relative submaximal torques after training , whereas training at 30 % 1RM did not . Therefore , our data suggest that high-load training results in greater neural adaptations that may explain the disparate increases in muscle strength despite similar hypertrophy following high- and low-load training programs PURPOSE The purpose of this study was to compare resistance training ( RT ) ( one set vs three sets ) combined with aerobic training ( AT ) versus AT alone in persons with coronary artery disease . METHODS Subjects ( n = 72 ) were r and omized to AT ( 5 d x wk(-1 ) ) or combined AT ( 3 d x wk(-1 ) ) with either one set ( AT/RT1 ) or three sets ( AT/RT3 ) of RT performed 2 d x wk(-1 ) . VO2peak , ventilatory anaerobic threshold ( VAT ) , strength and endurance , body composition , and adherence were measured before and after 29 wk of training . RESULTS Fifty-three subjects ( mean + /- SEM age 61 + /- 2 ) completed the training . The increase from baseline in VO2peak ( L x min(-1 ) ) averaged 11 % for AT ( P < 0.05 ) , 14 % for AT/RT1 ( P < 0.01 ) , and 18 % for AT/RT3 ( P < 0.001 ) , however , the difference between groups was not significant . VAT improved significantly in the AT/RT3 group only ( P < 0.05 ) . The AT/RT3 group gained more lean mass than the AT group ( 1.5 versus 0.4 kg , P < 0.01 ) , yet gains between AT/RT1 and AT were similar ( P = 0.2 ) . Only AT + RT groups demonstrated a reduction in body fat ( P < 0.05 ) . Strength and endurance increased more in the AT + RT groups than AT alone ( P < 0.05 ) . Adherence to number of sets performed was lower in AT/RT3 than AT/RT1 ( P < 0.02 ) . CONCLUSIONS Combined AT + RT yields more pronounced physiological adaptations than AT alone and appears to be superior in producing improvements in VO2peak , muscular strength and endurance , and body composition . The data support the use of multiple set RT for patients desiring an increased RT stimulus which may further augment parameters that affect VO2peak , VAT , lower body endurance , and muscle mass in a cardiac population |
13,494 | 27,658,982 | No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children .
INTERPRETATION In adults with previously untreated immune thrombocytopenia , high-dose dexamethasone did not improve durable platelet count responses compared with st and ard-dose prednisone . | BACKGROUND Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear .
We did a systematic review and a meta- analysis of r and omised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response . | Introduction Immune thrombocytopenia ( ITP ) is an immune disorder commonly presents as isolated thrombocytopenia . Generally corticosteroids are the main treatment of ITP . This study was design ed to evaluate effectiveness of high dose dexamethasone comparing conventional corticosteroid therapy in the treatment of ITP . Material s and methods In a r and omized prospect i ve study , sixty adult patients with newly diagnosed primary symptomatic ITP ( Platelet count < 20,000 ) were evaluated . Patients divided into two groups . In group A , thirty patients ( mean age of 24.9 years ) received Dexamethasone 40 mg/IV/daily for four days ( 10 mg/q6h ) ; and then Prednisolone 1 mg/kg/day/PO with rapid tapering of prednisolone ( 10 mg/week ) . From the other h and , in group B , thirty patients ( mean age of 27.2 years ) were treated with Prednisolone 1 mg/kg/day/PO for four weeks , then the drug tapered weekly . Results All the patients in group A showed favorable response within the first seven days , 27 cases presented complete response ( CR ) and three cases revealed response ( R ) . In group B , 11 cases had CR , 13 cases showed R and six cases had No response ( NR ) . After three months , rates of CR were 80 % and 23.3 % in group A and B ; respectively . Responses were 16.7 % and 33.3 % , NRs were 6.6 % and 43.3 % in group A and B ; respectively ( P < 0.0001 ) . After 6 months , CR was 73.3 % vs.16.7 % , and R was 16.7 % vs.36.7 % and NR was 10 % vs. 46.7 % in group A and B ; respectively ( P < 0.0001 ) . After 12 months , there was no change in response rate in group A , but in group B 53 % were non responsive , 40 % showed R ( chronic ITP ) and complete response was observed only in 6.7 % ( P < 0.0001 ) . Three cases in group A and 12 cases in group B had needed splenectomy ( P < 0.00002 ) . Conclusion We showed that high dose dexamethasone is more effective than conventional steroid therapy in newly diagnosed ITP as initial treatment with less relapses and toxicities We report the results of a r and omized clinical trial of two different coricosteroids ( prednisone versus deflazacort ) in patients affected by autoimmune thrombocytopenic purpura ( ATP ) . We have evaluated the efficacy of the two steroids on platelet count , antiplatelet antibodies , lymphocyte subsets and the occurrence of side effects . Twenty-seven patients were evaluable : 13 were treated with PDN and 14 with DFC . After 24 weeks of treatment , 4/12 ( 33 % ) , subjects treated with PDN were refractory while complete responses were obtained in 2/12 ( 17 % ) and partial responses in 6/12 ( 50 % ) . Among patients treated with DFC , 4/11 ( 36 % ) were considered as refractory , 2/11 ( 18 % ) had a complete response and 5/11 ( 46 % ) a partial response . A statistically significant decrease of antiplatelet antibodies was recorded in both groups after 4 weeks of therapy , but only in subjects receiving PDN did the reduction last until the 24th week . We observed an increase of T lymphocyte subsets ( CD3 , CD2 , CD4 , CD8 ) in absolute number , due to an increase in circulating lymphocytes , after 4 weeks . No substantial modifications were observed in these population s regarding the percentage or the CD4/CD8 ratio . After 24 weeks , 91 % ( 10/11 ) of patients treated with PDN presented an increase of body weight and 1 had a stable increase in blood pressure . Among the subjects treated with DFC , 64 % ( 7/11 ) showed an increase of body weight after the same follow-up . In conclusion , no difference was observed the two steroids studied In idiopathic thrombocytopenic purpura ( ITP ) , corticosteroids have been widely recognized as the most appropriate first-line treatment , even if the best therapeutic approach is still a matter of debate . Recently , a single high-dose dexamethasone ( HD-DXM ) course was administered as first-line therapy in adult patients with ITP . In this paper we show the results of 2 prospect i ve pilot studies ( monocentric and multicentric , respectively ) concerning the use of repeated pulses of HD-DXM in untreated ITP patients . In the monocenter study , 37 patients with severe ITP , age at least 20 years and no more than 65 years , were enrolled . HD-DXM was given in 4-day pulses every 28 days , for 6 cycles . Response rate was 89.2 % ; relapse-free survival ( RFS ) was 90 % at 15 months ; long-term responses , lasting for a median time of 26 months ( range 6 - 77 months ) were 25 of 37 ( 67.6 % ) . In the multicenter study , 95 patients with severe ITP , age at least 2 years and no more than 70 years , were enrolled . HD-DXM was given in 4-day pulses every 14 days , for 4 cycles ; 90 patients completed 4 cycles . Response rate ( 85.6 % ) was similar in patients classified by age ( < 18 years , 36 of 42=85.7 % ; > or=18 years , 41 of 48=85.4 % , P = not significant ) , with a statistically significant difference between the second and third cycle ( 75.8 % vs 89 % , P=.018 ) . RFS at 15 months 81 % ; long-term responses , lasting for a median time of 8 months ( range 4 - 24 months ) were 67 of 90 ( 74.4 % ) . In both studies , therapy was well tolerated . A schedule of 3 cycles of HD-DXM pulses will be compared with st and ard prednisone therapy ( eg , 1 mg/kg per day ) in the next r and omized Gruppo Italiano Malattie EMatologiche dell'Adulto ( GIMEMA ) trial BACKGROUND Treatment of adults with autoimmune thrombocytopenic purpura ( AITP ) is based more on individual experience than on results of controlled studies . We compared intravenous immunoglobulin with high-dose methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo . Primary outcome was number of days with platelet count greater than 50 x 10(9)/L within the first 21 days . METHODS We did a r and omised multicentre trial based on a 232 design . 122 adults with severe AITP ( platelet count < or = 20 x 10(9)/L ) were r and omly assigned to receive either intravenous immunoglobulin or high-dose methylprednisolone on days 1 - 3 ( r and omisation A ) , and then to receive either oral prednisone or placebo ( r and omisation B ) on days 4 - 21 . Analysis was by intention to treat . FINDINGS Six patients were excluded from the analysis . The number of days on which platelet counts were above 50 x 10(9)/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone ( p=0.02 ) . Percentage of patients who had platelet counts over 50 x 10(9)/L on days 2 and 5 was 7 % and 79 % , respectively , in the intravenous immunoglobulin group compared with 2 % and 60 % , respectively , in the high-dose methylprednisolone group ( p=0.04 ) . During the second treatment period , prednisone was more effective than placebo for all short-term endpoints . Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50 x 10(9)/L for 18.5 days ( p=0.005 ) , and those treated with high-dose methylprednisolone and prednisone had this count for 17.5 days . INTERPRETATION Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP , although the latter treatment is effective and well tolerated 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 T-cell dysregulation and T-cell-related cytokine abnormalities are involved in the pathogenesis of immune thrombocytopenia ( ITP ) . One of our previous studies showed that elevated IL-22 correlated to Th1 and Th22 cells plays an important role in the immunopathogenesis of ITP . In this study , we aim ed to investigate the effects of high-dose dexamethasone ( HD-DXM ) on IL-22 production and on the IL-22-producing T-cell subsets in ITP patients . Methods IL-22 plasma levels and the percentages of Th1 , Th17 , and Th22 cells were determined by enzyme-linked immunosorbent assay and flow cytometry in 25 ITP patients receiving DXM 40 mg/day for 4 consecutive days . Results Plasma IL-22 concentrations and the percentages of Th1 and Th22 cells were significantly increased in pre-therapy patients relative to controls ( P < 0.05 ) , but the percentage of Th17 cells was not . HD-DXM administration reduced IL-22 production and corrected the imbalance between Th1 and Th22 subsets . IL-22 levels were positively correlated with Th1 and Th22 cells in ITP patients before and after HD-DXM treatment . Conclusion These results suggest that HD-DXM may regulate the production of IL-22 in ITP , possibly by correcting Th1 and Th22 polarization This study compared the efficacy and safety of high-dose dexamethasone ( HD-DXM ) and conventional prednisone ( PDN ) on the largest cohort to date as first-line strategies for newly diagnosed adult primary immune thrombocytopenia ( ITP ) . Patients enrolled were r and omized to receive DXM 40 mg/d for 4 days ( n = 95 , nonresponders received an additional 4-day course of DXM ) or prednisone 1.0 mg/kg daily for 4 weeks and then tapered ( n = 97 ) . One or 2 courses of HD-DXM result ed in a higher incidence of overall initial response ( 82.1 % vs 67.4 % , P = .044 ) and complete response ( 50.5 % vs 26.8 % , P = .001 ) compared with prednisone . Time to response was shorter in the HD-DXM arm ( P < .001 ) , and a baseline bleeding score ≥8 was associated with a decreased likelihood of initial response . Sustained response was achieved by 40.0 % of patients in the HD-DXM arm and 41.2 % in the PDN arm ( P = .884 ) . Initial complete response was a positive indicator of sustained response , whereas presence of antiplatelet autoantibodies was a negative indicator . HD-DXM was generally tolerated better . We concluded that HD-DXM could be a preferred corticosteroid strategy for first-line management of adult primary ITP . This study is registered at www . clinical trials.gov as # NCT01356511 Background : To tackle the problems associated with high-dose dexamethasone ( HD-DXM ) in patients with immune thrombocytopenia ( ITP ) . Aim : To compare the efficacy of HD-DXM with or without low-dose dexamethasone maintenance in untreated ITP patients . Results : Dexamethasone ( 40 mg/day ) was given in 4-day pulses every 14 days for 3 cycles in 61 patients with ITP . Among them , 30 cases were given dexamethasone ( 0.035 mg/kg per day ) for maintenance between pulsed HD-DXM and after 3 HD-DXM courses ( HD-DXM-M group ) and another 31 cases did not receive dexamethasone maintenance ( HD-DXM-nM group ) . The control group comprised the patients who received prednisone ( prednisone group ) . The following results were obtained : ( 1 ) at the end of the 3rd cycle , the overall response rate ( ORR ) was higher in the HD-DXM group than in the prednisone group ; ( 2 ) the ORR of the HD-DXM group peaked after the 3rd cycle ; ( 3 ) the ORR after each course was higher in the HD-DXM-M group than in the HD-DXM-nM group ; ( 4 ) in the 12th month after HD-DXM discontinuation , the relapse rate of the HD-DXM-M group was lower than that of the other groups ( prednisone and HD-DXM-nM ) . Conclusion : Treatment with 3 cycles of HD-DXM pulses with low-dose dexamethasone maintenance is an effective method for untreated ITP We compared very high doses of methylprednisolone with intravenously administered immune globulin for treatment of acute idiopathic thrombocytopenic purpura . Fifty-seven children were r and omly assigned to receive the immune globulin preparation , 0.5 gm/kg per day for 5 consecutive days ( n = 19 ) , orally administered methylprednisolone , 30 mg/kg per day for 7 days ( n = 19 ) , or orally administered methylprednisolone , 50 mg/kg per day for 7 days ( n = 19 ) . There were no differences in the response of the platelet counts among the groups . We conclude that these two therapies were equally effective ; choice between them may be made according to cost and therapy-related risks Immune thrombocytopenia ( ITP ) results from platelet destruction and production suppression . Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients . We performed a single-arm study to assess the response to a single course of dexamethasone ( 40 mg by mouth , days 1 - 4 ) in combination with eltrombopag ( 50 mg , days 5 - 32 ) in 12 adults with newly diagnosed ITP in an outpatient setting . Median follow-up was 12.5 months . After therapy ( day 33 ) , 100 % of patients achieved at least ≥30 × 10(9)/L platelets . Four patients relapsed . Complete response at 6 months ( platelets ≥100 × 10(9)/L ) was achieved in 50 % of patients and response at 6 months ( platelets ≥30 < 100 × 10(9)/L ) was achieved in another 25 % ; relapse-free survival was 66.7 % at 12 months ( median response duration of 8.3 months ) . In conclusion , eltrombopag/dexamethasone is a feasible frontline therapy for ITP . This trial is registered at www . clinical trials.gov as NCT01652599 Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia ( ITP ) . This r and omized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 x 10(9)/L or less . One hundred three patients were r and omly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m(2 ) rituximab weekly for 4 weeks . Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab . Sustained response ( ie , platelet count > or = 50 x 10(9)/L at month 6 after treatment initiation ) , evaluable in 101 patients , was greater in patients treated with dexamethasone plus rituximab ( n = 49 ) than in those treated with dexamethasone alone ( n = 52 ; 63 % vs 36 % , P = .004 , 95 % confidence interval [ 95 % CI ] , 0.079 - 0.455 ) . Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events ( 10 % vs 2 % , P = .082 , 95 % CI , -0.010 to 0.175 ) , but incidences of serious adverse events were similar in both arms ( 6 % vs 2 % , P = .284 , 95 % CI , -0.035 to 0.119 ) . Dexamethasone plus rituximab was an effective salvage therapy in 56 % of patients refractory to dexamethasone . The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone . Thus , combination therapy may represent an effective treatment option before splenectomy . This study is registered at http:// clinical trials.gov as NCT00770562 To determine the minimal essential treatment for childhood acute idiopathic thrombocytopenic purpura ( ITP ) , a prospect i ve , r and omized trial was conducted focusing on hemorrhagic manifestation as well as platelet count . Subjects with a platelet count of < 10 x 10(3)/microL or 10 to 29 x 10(3)/microL and mucosal bleeding ( group 1 ) were r and omly assigned to receive intravenous immunoglobulin ( IVIg ) at 1 to 2 g/kg , conventional oral prednisolone ( o-PSL ) ( 2 mg/kg for 2 weeks ) . parenteral methylprednisolone ( mPSL ) ( 5 mg/kg for 5 days ) , or pulsed parenteral methylprednisolone ( PmPSL ) ( 30 mg/kg for 3 days ) . Subjects with a platelet count of 10 to 29 x 10(3)/microL without mucosal bleeding ( group 2 ) were r and omized to receive either o-PSL or no treatment . In subjects with a platelet count of 30 x 10(3)/microL or higher ( group 3 ) , patients undergoing no specific treatment were monitored . In group 1 , IVIg offered faster platelet enhancement compared with o-PSL and mPSL , although neither mPSL no PmPSL showed any advantage , even over o-PSL . Platelet response was uniformly excellent when pretreatment platelet coun was > or = 10 x 10(3)/microL. Furthermore , the presence or absence of mucosal bleeding in subjects with a platelet count < 10 x 10(3)/microL had no effect on the response to treatment . In group 2 , platelet increase was indifferently attained with or without o-PSL . These data suggest that childhood acute ITP with a platelet count > or = 10 x 10(3)/microL may be left untreated or may be treated with o-PSL when mucosal bleeding is evident , whereas for those with a platelet count < 10 x 10(3)/microL , IVIg is the most predictable platelet enhancer . Thus , a platelet count of 10 x 10(3)/microL seems to be informative enough to decide whether to treat childhood acute ITP A r and omized clinical trial was performed in 160 children and 223 adults with acute immune thrombocytopenic purpura ( ITP ) . The role of corticoids at this phase of the disease is still controversial . Therefore , patients were r and omized to receive either conventional doses ( 1 mg/kg/day ) of corticotherapy or low doses ( 0.25 mg/kg/day ) for 3 weeks . The remission , defined by platelet count superior to 100,000/microliter was studied for adults and children after 6 months and 12 months , respectively . The statistical analysis showed no significant difference between the two corticotherapy regimens neither in children nor in adults . Overall , 74 % of children and 41 % of adults were in remission . For the first time in acute ITP , a r and omized prospect i ve trial showed that both in children and adults low dose corticotherapy ( 0.25 mg/kg/day ) proves to have the same efficacy as conventional doses ( 1 mg/kg/day ) 350 patients with idiopathic thrombocytopenic purpura ( ITP ) aged 2/12 - 15 years ( mean 6.3 + /- 2.7 ) were followed up during the period January 1st , 1975 to March 31 , 1992 . They constituted 40 % of cases with hemorrhagic diathesis attending the Hematology/Oncology Clinic , Children 's Hospital , Ain Shams University ( relative frequency of 37.4/100.000 of the general Out-Patient Clinic in the same hospital ) . These patients presented with acute ( 71.4 % ) , chronic ( 22.9 % ) and recurrent ( 5.7 % ) forms . The age of presentation was younger in acute ITP . In the recurrent form there was significant female predominance . Most cases of acute ITP ( 66 % ) presented in winter and spring , with a positive history of preceding viral illness in 50 % in contrast to 10 % in chronic form . Four chronic ITP cases developed lupus erythematosus ; all were females > 9 years . As regards therapy , acute ITP cases with initial platelet count ( PC ) < 10 x 10(9)/l were r and omized to receive either high-dose methyl prednisolone ( HDMP ) 10 mg/kg/day for 5 days i.v . ( n = 10 ) or intravenous immunoglobulin ( IVIG ) 0.4 g/kg/day for 5 days ( n = 10 ) or conventional-dose prednisone ( CDP ) 2 mg/kg/day 4 weeks p.o . ( n = 10 ) . A dramatic response was noticed in the first two groups . In chronic ITP , ( n = 80 ) CDP induced complete response ( CR ) in 30 % and partial response ( PR ) in 20 % ; 50 % were nonresponders . Twenty-four refractory ITP with persistent PC < or = 20 x 10(9)/l received second-line therapy : vincristine 1.5 mg/m2/week i.v . 4 doses ( n = 4 ) with no clinical or hematological improvement . IVIG 0.4 g/kg/day for 5 days ( n = 8) with sustained CR only in 2 patients ( 25 % ) and PR in 2 patients ( 25 % ) . Splenectomy was performed ( n = 12 ) with CR in 50 % ; out of them , 2 patients had shown no improvement on prior IVIG therapy . In conclusion , ITP is a benign condition with no fatality reported , but it could run a chronic refractory course |
13,495 | 19,649,408 | Presence or absence of HBeAg and pre-treatment alanine aminotransferase ( ALT ) levels were considered important factors in the initial therapeutic indication .
Treatment with conventional interferon enables lasting disease inactivation and can result in HBsAg seroconversion .
PEG2a showed better efficacy than interferon and LAM and similar side effects to interferon .
LAM presents advantages such as its sensitivity in the HbeAg-negative phenotype , while its main disadvantage is the development of resistance | Chronic hepatitis B is considered a major public health problem , and its treatment entails increasing health budget expenses with high-cost drugs covered by Unified National Health System . | Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus ( HBV ) DNA and histological features of chronic hepatitis B has been largely unsuccessful . In a pilot study of long-term treatment , 42 such patients were r and omly assigned to 6 million units of interferon alfa 2b ( IFN-alpha2b ) three times per week for 24 consecutive months ( n = 21 , 4 with cirrhosis ) or to no therapy ( n = 21 , 3 with cirrhosis ) . Five patients ( 24 % ) discontinued therapy because of treatment-related adverse reactions . Serum levels of alanine transaminase ( ALT ) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls ( 38 % vs. 10 % ; P = .03 ) . Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls ( 81 % vs. 29 % ; P < .001 ) . During a median period of 22 months after interferon was stopped , 2 treated patients ( 10 % ) lost serum hepatitis B surface antigen ( HBsAg ) and seroconverted to antibodies to hepatitis B surface antigen ( anti-HBs ) . Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder , compared with none of the 21 untreated controls ( sustained response : 33 % vs. 0 ; P < .001 ) . Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group ( 10.3 to 5.3 ; P = .01 ) , but not in the untreated group ( 9.3 to 9.8 ; not significant ) . In conclusion , a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients , led to sustained suppression of HBV in one third , and attenuated hepatitis in 81 % of patients Current therapies for chronic hepatitis B ( CHB ) have a number of limitations , and better treatment options are needed . Peginterferon alpha-2a ( 40 kDa ) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a ( 40 kDa ) in the treatment of CHB . In this phase II study , 194 patients with CHB not previously treated with conventional interferon-alpha were r and omized to receive weekly subcutaneous doses of peginterferon alpha-2a ( 40 kDa ) 90 , 180 or 270 microg , or conventional interferon alpha-2a 4.5 MIU three times weekly . Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up . All subjects were assessed for loss of hepatitis B e antigen ( HBeAg ) , presence of hepatitis B antibody ( anti-HBe ) , suppression of hepatitis B virus ( HBV ) DNA , and normalization of serum alanine transaminase ( ALT ) after follow-up . At the end of follow-up , HBeAg was cleared in 37 , 35 and 29 % of patients receiving peginterferon alpha-2a ( 40 kDa ) 90 , 180 and 270 microg , respectively , compared with 25 % of patients on conventional interferon alpha-2a . The combined response ( HBeAg loss , HBV DNA suppression , and ALT normalization ) of all peginterferon alpha-2a ( 40 kDa ) doses combined was twice that achieved with conventional interferon alpha-2a ( 24%vs 12 % ; P = 0.036 ) . All treatment groups were similar with respect to frequency and severity of adverse events . These results indicate that peginterferon alpha-2a ( 40 kDa ) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg , suppression of HBV DNA , and normalization of ALT A r and omized controlled trial of recombinant interferon alfa-2b has been initiated in patients with chronic active hepatitis who were negative for serum hepatitis B e antigen but positive for serum hepatitis B virus DNA and hepatitis B core antigen expression in the liver . Twenty-five patients received interferon alfa-2b 3 million units thrice weekly for 14 - 16 weeks and 25 served as untreated controls . Seventeen patients in the treatment and 18 in the control group have already completed a 12-month period of observation . Interferon alfa-2b was well tolerated by all patients . At the end of therapy , complete responses , defined as disappearance of hepatitis B virus DNA from serum and return of alanine aminotransferase to normal , were observed in 10 ( 59 % ) of the 17 treated patients compared to none in the control group ( p less than 0.01 ) . Twelve months after the onset of interferon alfa-2b therapy , 11 ( 65 % ) of the 17 treated patients were complete responders compared to 2 ( 11 % ) of 18 in the control group ( p less than 0.01 ) . Fifty per cent ( 4/8 ) of complete responders to interferon alfa-2b therapy , followed for 16 - 24 months , experienced reactivations of hepatitis B virus replication with reappearance of serum hepatitis B virus DNA and a return of serum alanine aminotransferase activity . The response to interferon alfa-2b therapy appeared to be independent of pre-treatment serum alanine aminotransferase and hepatitis B virus DNA levels In a multicentre trial , 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year , with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy , were r and omized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice weekly for 4 months or no treatment . At the end of therapy , viral DNA clearance and aminotransferase normalization were significantly ( p less than 0.05 ) more frequent in treated patients than in controls . After 16 months ' follow up , the difference was still significant for hepatitis B e antigen clearance and transaminase normalization . Hepatitis B virus DNA reactivation was observed during follow up in 43 % of treated patients and 50 % of controls . Improvements in liver inflammation were observed in patients on interferon . High pre-treatment serum aminotransferase levels , female sex and a low score for fibrosis in the initial biopsy were predictive factors significantly ( p less than 0.05 ) associated with termination of hepatitis B virus replication in treated cases . These results indicate that interferon is effective in inducing clearance of HBV from serum and improvement of biochemical and histological parameters of liver disease . However , a more prolonged regimen of therapy may be required to obtain stable suppression of hepatitis B virus replication A total of 58 patients with histologically confirmed chronic viral hepatitis B and presence of hepatitis B surface antigen and hepatitis B virus DNA ( HBV DNA ) in the serum were r and omized in a prospect ively controlled trial . Thirty patients were treated with 3 megaunits of recombinant interferon alfa-2b ( INTRON A , R Schering-Plough , Essex Corporation ) subcutaneously thrice weekly for 4 months . Twenty-eight controls received no treatment . The post-treatment follow-up period consisted of 6 months . Twenty-eight treated patients and 27 controls completed the protocol . One female patient of the treatment group showed a complete response , and eight other treated patients ( 32 % ) showed a partial response to therapy . Three patients in the control group ( 11 % ) lost hepatitis B e antigen and HBV DNA spontaneously . This finding is statistically significant ( p less than 0.05 ) . The elimination of hepatitis B virus markers from the serum was associated with a normalization of aminotransferase activities in the serum . Reactivation of hepatitis was not observed after seroconversion To determine the antiviral effect of recombinant-interferon (rIFN)-alpha in hepatitis B virus ( HBV ) chronic infection , a controlled study was carried out . A total of 20 HBsAg chronic carriers ( 18 chronic active hepatitis and 2 chronic persistent hepatitis ) were included . All of them had remained HBeAg , HBV-DNA and HBV-DNA polymerase ( HBV-DNAp ) positive at least six months before treatment . The patients were r and omly assigned to two groups : control ( n = 10 ) , and treatment ( n = 10 ) . A dose of 5.5 megaunits of rIFN-alpha/m2 body surface was administered every day for 21 days ( induction ) and twice a week for six months thereafter ( maintenance ) . No basal differences were observed between the two groups . No case of intolerable toxicity was observed . One treated patient died in a car crash in the second month . At the end of the first week of therapy , 7/10 ( 70 % ) of the treated patients became HBV-DNAp negative . However , in the fifth month only 2 patients remained HBV-DNAp negative and also became HBV-DNA and HBeAg negative . In contrast , no changes in viral markers among control cases were observed . In conclusion , rIFN-alpha has an antiviral effect on chronic HBV infection ; however , the induction plus maintenance schedule is not useful to obtain a permanent effect Interferon alfa ( IFN‐α ) is the primary treatment for chronic hepatitis B. The st and ard duration of IFN‐α therapy is considered 16 weeks ; however , the optimal treatment length is still poorly defined . We evaluated the efficacy and acceptability of prolonged IFN‐α treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen ( HBeAg ) seroconversion , we conducted a prospect i ve , controlled , multicenter trial in which all patients were treated with a st and ard regimen of 10 million units IFN‐α 3 times per week over 16 weeks . Patients who were still HBeAg‐positive after 16 weeks of therapy were r and omized to prolongation of the identical regimen up to 32 weeks ( prolonged therapy ) or discontinuation of treatment ( st and ard therapy ) . Among the 162 patients who entered the study , 27 ( 17 % ) were HBeAg‐negative after the first 16 weeks of treatment , and 118 were r and omized to st and ard or prolonged therapy . After r and omization , a response ( HBeAg seroconversion and sustained hepatitis B virus [HBV]‐DNA negativity ) was observed in 7 of the 57 ( 12 % ) patients assigned to st and ard therapy versus 17 of the 61 ( 28 % ) patients assigned to prolonged therapy ( P = .04 ) . A low level of viral replication after 16 weeks of treatment , as indicated by serum HBV‐DNA values under 10 pg/mL , was found to be the only independent predictor of response ( 52 % vs. 0 % ; P < .001 ) during prolonged therapy . The prolonged IFN‐α schedule was well tolerated in the large majority of patients . In chronic hepatitis B , prolongation of IFN‐α therapy up to 32 weeks is superior to a st and ard course of 16 weeks . Those patients who exhibit a low level of viral replication at the end of the st and ard regimen benefit most from prolonged treatment 72 Chinese patients who had been positive for hepatitis B surface antigen ( HBsAg ) and hepatitis B e antigen ( HBeAg ) for more than six months with stable serum hepatitis B virus DNA were r and omised to receive recombinant alpha 2-interferon at doses of 2.5 , 5 , or 10 X 10(6 ) U/m2 intramuscularly thrice weekly for 12 - 24 weeks , or no treatment . 6 ( 11 % ) of 54 treated and 1 ( 6 % ) of 18 control patients became HBeAg-negative at the end of therapy or after 24 weeks of follow-up . 9 ( 17 % ) of treated but none of the control patients became HBeAg-negative between completion of therapy and 12 months . Reactivation of HBV replication subsequently occurred in 7 ( 13 % ) of the treated patients and in 1 control . Thus , sustained clearance of HBeAg was achieved only in 8 ( 15 % ) of treated patients at 12 months . Between 12 and 24 months 3 ( 9 % ) of treated patients and 1 control became negative for HBeAg . None of the patients became HBsAg-negative . alpha 2-interferon in the dose regimen used has little long-term effect in the suppression of HBV replication in Chinese patients with chronic HBV infection Hepatitis B virus ( HBV ) infection after liver transplantation ( LT ) may lead to severe and rapidly progressive graft failure . Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT . The aim of this prospect i ve open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection . The median time from LT to study enrollment was 51 months , all patients were hepatitis B surface antigen positive , and 75 % and 94 % of subjects had detectable hepatitis B e antigen ( HBeAg ) and HBV DNA at entry , respectively . The median duration of lamivudine treatment on study was 85 weeks , during which time median HBV DNA levels became undetectable by 16 weeks and 9 % of patients lost previously detectable HBeAg . Serum alanine aminotransferase ( ALT ) levels improved in most patients and normalized in 27 % of patients with elevated values pretreatment . Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry ( P < .05 ) . Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested . None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine . Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up . Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However , the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population . Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection , as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence A total of 24 chronic carriers of HBsAg , HBeAg and hepatitis B virus (HBV)-DNA were included in a controlled trial . The patients were r and omly assigned to four groups : Group I ( n = 6 ) : control ; group II ( n = 6 ) : 2.5 MU ; group III ( n = 6 ) : 5 MU and group IV ( n = 6 ) : 10 MU rIFN-alpha/m2 body surface 3 times weekly i.m . during 6 months . At the end of the treatment , all patients under therapy , as well as 4 belonging to the control group , lost HBV-DNA polymerase . HBV-DNA became negative in 3 ( 50 % ) , 1 ( 17 % ) , and 2 ( 33 % ) patients from groups II , III , and IV , respectively , while all patients from the control group maintained HBV-DNA . At 15 months of follow-up , 6 patients ( 33 % ) under therapy ( 2 from each group ) and 1 from the control group remained HBV-DNA-negative . Knodell 's index decreased significantly on comparing basal and final liver biopsies among patients in group IV ( 16.0 + /- 1.9 vs 7.0 + /- 1.9 , p less than 0.01 ) , while no changes were observed in the other groups . Five patients ( 27 % ) developed anti-IFN antibodies during treatment . In summary , although low doses of rIFN-alpha ( 2.5 - 5 MU ) had an antiviral effect on HBV replication , only patients treated with 10 MU showed a significant decrease in liver histological activities . In addition , the effectiveness of rIFN-alpha therapy may be negatively influenced by the appearance of anti-IFN antibodies BACKGROUND / AIMS The histological and clinical outcome of lamivudine 100mg/day was assessed in 76 HBeAg-negative chronic hepatitis B patients previously r and omised to a double-blind comparison study of lamivudine and placebo . METHODS Paired liver biopsies were available before 1 year of r and omised lamivudine treatment and after 2 years of further open-label treatment for 48 patients . Serum sample s were analysed for hepatitis B markers and ALT levels ( n=74 ) . RESULTS The histological activity index improved , remained unchanged and worsened in 64 , 32 and 5 % , respectively , for patients without YMDD-variant HBV compared to 15 , 54 and 31 % with the variant . None of the 42/48 patients without cirrhosis at baseline progressed to cirrhosis . Of 24/48 patients without bridging fibrosis at pre-treatment , 83 % ( 20/24 ) did not progress to bridging fibrosis . Median HBV DNA remained below the lower limit of detection and ALT < or = 1 times the ULN for patients without the variant whereas levels gradually increased to 11.3Meq/ml ( bDNA assay ) and 2 times the upper limit of normal by month 24 for patients with variant . CONCLUSIONS The clinical benefit of lamivudine is greatest for patients without YMDD variants over 2 years of extended treatment . Additional therapies should be considered for patients with YMDD variants BACKGROUND & AIMS Data on the long-term safety of lamivudine are limited . The aim of this analysis was to determine the incidence of hepatitis flares , hepatic decompensation , and liver-disease-related ( LDR ) serious adverse events ( SAE ) during long-term lamivudine treatment . METHODS We review ed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years ( median , 4 years ) and 200 patients who received placebo for 1 year . RESULTS Hepatitis flares occurred in 10 % of the lamivudine-treated patients in year 1 and in 18%-21 % in years 2 - 5 . A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43 % in year 1 to > 80 % in year 3 . Ten hepatic decompensation events occurred in 8 ( < 1 % ) lamivudine-treated patients . Fifty-three ( 5 % ) lamivudine-treated patients experienced a total of 60 LDR SAEs . Four patients died , 2 from liver-related causes . The proportion of patients with a documented lamivudine-resistant mutation increased from 23 % in year 1 to 65 % in year 5 . During each year of the study , patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations ( P < 0.005 ) . The occurrence of hepatic decompensation ( 0%-2 % ) and LDR SAEs ( 1%-10 % ) among patients with lamivudine resistance remained stable during the first 4 years with mutations and increased afterward to 6 % ( P = 0.03 ) and 20 % ( P = 0.009 ) , respectively . CONCLUSIONS This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease , but patients with long-st and ing lamivudine-resistant mutations may experience worsening liver disease Context Because current treatment options for chronic hepatitis B virus ( HBV ) infection have varying effects and costs , choosing among them is often difficult . Contribution Using a third-party payer perspective and lifetime horizon , this costutility analysis found that monotherapy with interferon but not lamivudine or adefovir was cost-effective . A salvage strategy that used adefovir only in case of lamivudine-associated viral resistance also seemed cost-effective . Caution s The findings apply only to patients with persistently elevated aminotransferase levels and no cirrhosis . The authors did not model the cost-effectiveness of nucleoside analogue salvage after interferon therapy failure . The Editors Chronic hepatitis B virus ( HBV ) infection is a prevalent and expensive condition , affecting 350 million people worldwide and 1.25 million people in the United States ( 1 ) at a cost of more than $ 700 million annually ( 2 ) . Chronic HBV infection can progress to cirrhosis , liver failure , and hepatocellular carcinoma and is a major cause of morbidity and mortality ( 1 , 3 ) . Traditional therapy for chronic HBV infection with either interferon-2b ( interferon ) or lamivudine is difficult and has limited long-term efficacy ( 4 ) . Interferon has clinical ly significant side effects and results in durable virologic response in only 15 % to 30 % of patients ( 5 - 8 ) . Lamivudine is easy to administer and is associated with minimal side effects ( 9 - 11 ) , but it has a higher rate of viral resistance ( 12 ) , lower durable response rate ( 9 - 11 ) , and greater need for prolonged therapy ( 9 , 11 ) compared with interferon . The efficacy of both interferon and lamivudine is even more limited in patients with hepatitis B e antigennegative ( HBeAg-negative ) disease ( 4 ) . This burgeoning population now accounts for more than half of patients with HBV in the United States ( 13 ) and up to 80 % of patients with HBV in Asia ( 14 , 15 ) . Data from 2 r and omized , controlled trials indicate that adefovir is efficacious in HBeAg-positive and HBeAg-negative patients ( 16 , 17 ) . Adefovir has a low risk for side effects and viral resistance ( 18 ) compared with interferon and lamivudine , but it is more expensive ( 19 ) . Therefore , the improved therapeutic benefits of adefovir in chronic HBV infection may offset its increased cost compared with interferon and lamivudine , therapies that are less effective yet less expensive . The most effective and cost-effective therapeutic approach to chronic HBV infection must be established . Given the uncertainty on how best to initiate therapy in HBV , this information may assist clinicians in everyday clinical decision making . We therefore performed an economic analysis to estimate the cost-effectiveness of 5 competing strategies for managing chronic HBV infection in patients with elevated liver enzyme levels and no evidence of cirrhosisthe most prevalent and clinical ly relevant presentation of chronic HBV infection in the primary care setting . We sought to determine whether and under what circumstances the improved therapeutic benefits of adefovir offset its increased cost compared with lamivudine or interferon in managing chronic HBV infection . Methods Decision Model Framework Model Overview Using decision analysis software ( DATA , version 4.0 , TreeAge Software , Inc. , Williamstown , Massachusetts ) , we evaluated a hypothetical cohort of patients 40 years of age with chronic HBV infection , elevated aminotransferase levels , and no clinical or histologic evidence of cirrhosis . To emulate the case mix in clinical practice in the United States ( 13 ) , we assumed that 55 % of the cohort was HBeAg-negative . We subsequently varied this estimate between 0 % and 100 % in our sensitivity analysis . Patients entered the hypothetical model without previous treatment for HBV infection and received 1 of 5 competing strategies for managing chronic HBV infection : 1 ) no pharmacologic treatment of chronic HBV infection ( do nothing strategy ) , 2 ) interferon monotherapy , 3 ) lamivudine monotherapy , 4 ) adefovir monotherapy , or 5 ) lamivudine with crossover to adefovir upon development of viral resistance ( adefovir salvage strategy ) . Because the clinical course , prognosis , and response to therapy vary in patients with HBeAg-positive and HBeAg-negative HBV ( 4 ) , we stratified our analysis by HBeAg status and assigned separate probability estimates for each group . Patients entering the model received either no treatment ( do nothing strategy ) or active treatment for chronic HBV infection . We then followed the cohort over a lifetime horizon through a series of Markov cycles governing patient transitions between relevant health states . The Appendix describes the model structure in detail . Competing Strategies Do Nothing Strategy . In this strategy , which served as the referent case for our analysis , we assumed that patients were followed clinical ly but did not receive pharmacologic therapy for chronic HBV infection . Patients followed the natural history of chronic HBV infection according to their HBeAg status . We further assumed that all patients received regular ongoing care , including hepatocellular cancer screening , and that patients developing cirrhosis were managed for complications , as outlined by published management guidelines ( 4 , 20 ) . We assumed that a proportion of patients with cirrhosis became eligible for liver transplantation and that a subgroup of these patients subsequently underwent liver transplantation at the rate reported by the United Network for Organ Sharing ( 21 ) . Interferon Monotherapy Strategy . Patients in this strategy received up-front active therapy with interferon , 10 million units subcutaneously 3 times per week . We assumed that HBeAg-positive and HBeAg-negative patients received 4 and 12 months of treatment , respectively , as suggested by published guidelines ( 4 , 20 ) . Patients without virologic response did not receive additional HBV therapy and followed the natural history of chronic HBV infection . Lamivudine Monotherapy Strategy . Patients in this strategy received up-front lamivudine , 100 mg orally once daily . Lamivudine therapy was discontinued 6 months after a virologic response . Patients without virologic response , including those developing viral resistance , continued to receive long-term lamivudine therapy as recommended by published guidelines ( 4 , 20 ) . We then assigned patients to receive lifetime lamivudine therapy and discontinued therapy if patients developed a subsequent virologic response . Adefovir Monotherapy Strategy . Patients in this strategy received up-front adefovir , 10 mg orally once daily . Adefovir therapy was discontinued 6 months after a virologic response . Patients without virologic response , including those developing viral resistance , continued to receive long-term adefovir therapy as recommended by published guidelines ( 20 ) . We then assigned patients to receive lifetime adefovir therapy and discontinued therapy if patients developed a subsequent virologic response . Adefovir Salvage Strategy ( Lamivudine to Adefovir Crossover ) . A relevant therapeutic alternative available to clinicians is a hybrid strategy of up-front lamivudine followed by adefovir salvage if lamivudine-related viral resistance develops . We assumed that patients in this strategy initially received lamivudine as described in the lamivudine monotherapy strategy . We then crossed patients over to adefovir when they developed viral resistance , and we subsequently managed patients as described in the adefovir monotherapy strategy . Patients without viral resistance continued to receive lamivudine . Therefore , we reserved adefovir therapy only for patients developing viral resistance while they were receiving lamivudine therapy . Tables 1 and 2 and the Appendix describe the probability estimates governing all 5 strategies . Table 1 . Base-Case Probability Estimates Table 2 . Base-Case Treatment-Related Probability Estimates Model Assumptions The Appendix contains information about our key model assumptions , including base-case patient characteristics , survival assumptions , definition of virologic response , relationship between virologic response or resistance and subsequent health , and effect of treatment-related adverse events . Clinical Probability Estimates Our base-case model incorporated a wide range of estimates governing relevant clinical probabilities in the management and natural history of chronic HBV infection ( Tables 1 and 2 ) . To derive these estimates , we systematic ally review ed MEDLINE to identify relevant English- language studies published from January 1970 to February 2005 . The Appendix describes our systematic review methods . Outcomes Because the main objective of cost-effectiveness analysis is to permit comparisons among different interventions in medicine , and because quality -adjusted life-years ( QALYs ) are the exchange currency that allows these comparisons to be made , we adopted QALYs as our main outcome ( 120 ) . Our analysis reports the incremental cost per QALY gained among the competing strategies , along with the respective 2.5th and 97.5th percentiles around the point estimates as generated by a Monte Carlo analysis of 1000 trials ( see Sensitivity Analyses section for details ) . Utilities We incorporated a wide range of relevant health state utilities in our model . Table 1 contains the specific utility estimates , and the Appendix describes these estimates in detail . Cost Estimates We conducted our analysis from the perspective of a third-party payer and incorporated the direct health care costs for many therapies , physician visits , diagnostic tests , and complications of chronic liver disease ( Table 3 ) . We obtained costs for physician services and procedures from the 2004 American Medical Association Current Procedural Terminology codebook and the 2004 Medicare Fee Schedule ( 121 ) and derived our base-case pharmaceutical costs from the average wholesale prices listed in the 2004 Red Book ( 19 ) . Because large buying consortiums can often obtain prices lower Elevated alanine transaminase ( ALT ) levels and low serum hepatitis B virus ( HBV ) DNA predict a higher likelihood of hepatitis B e antigen ( HBeAg ) loss in patients with chronic hepatitis B treated with interferon . Predictors of HBeAg loss in patients treated with lamivudine are not known . The objective of this analysis of 4 lamivudine-controlled Phase III trials was to determine patient-dependent or laboratory variables that predict HBeAg loss . Predictors of HBeAg loss in patients treated with interferon , lamivudine plus interferon , or placebo are also described . A total of 805 adults with chronic hepatitis B were treated either with lamivudine ( n = 406 ) , matching placebo ( n = 196 ) , interferon ( n = 68 ) , or the combination of lamivudine plus interferon ( n = 135 ) . Demographic and baseline disease characteristics were used in stepwise multivariate analyses to identify features that were predictive of lamivudine-induced HBeAg loss . HBeAg loss correlated with increased pretreatment ALT levels in all groups . The rate of HBeAg loss was highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal ( ULN ) and was most pronounced in the lamivudine group ( 56 % ) . Multivariate modeling indicated that elevated baseline ALT levels ( P < .001 ) and histologic activity index ( HAI ) score ( P < .001 ) were important predictors of HBeAg loss in response to lamivudine . The effect of pretreatment ALT levels on HBeAg loss was similar for Asians and Caucasians . In conclusion , elevated pretreatment ALT levels and /or active histologic disease were the most important predictors of lamivudine-induced HBeAg loss . Asians and Caucasians had similar rates of response to lamivudine at comparable ALT levels Forty subjects with chronic hepatitis B and hepatitis B e antigen ( HBeAg ) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses . Patient follow-up began a median of 4.3 months after completion of therapy in previous trials . At months 2 , 4 , 6 , 9 , and 12 of year 1 , and every 6 months thereafter , we tested for HBeAg and hepatitis B surface antigen ( HBsAg ) , hepatitis B virus ( HBV ) DNA , and alanine aminotransferase ( ALT ) . After a median ( range ) of 36.6 ( 4.8 - 45.6 ) months of follow-up monitoring , HBeAg seroconversion was demonstrated at the last visit by 77 % ( 30 of 39 ) of patients . In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials , the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64 % . Nine ( 9 of 40 , 23 % ) patients were HBsAg negative at the last assessment . Seventy-four percent ( 17 of 23 ) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit . Eight patients ( 8 of 40 , 20 % ) initiated retreatment for reappearance of HBV markers , and 7 showed biochemical and /or virologic improvement ( including regained HBeAg seroconversion in 2 ) . No safety issues of concern emerged . In conclusion , most HBeAg responses achieved during lamivudine therapy were durable , and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine . Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression BACKGROUND Lamivudine was approved for the treatment of chronic hepatitis B in China in 1999 ; however the long-term result has not yet been reported in detail . This clinical trial was to evaluate the long-term efficacy and safety of 3-year lamivudine treatment for chronic hepatitis B and the impact of emergence of YMDD mutation of hepatitis B virus ( HBV ) . METHODS This multi-center , r and omized , double-blind , placebo controlled trial began from 1996 to 1999 . A total of 429 patients with serum HBsAg , HBeAg and HBV DNA positive were r and omized to receive either lamivudine 100 mg daily ( 322 patients ) or placebo ( 107 ) for the first 12 weeks . All patients were given subsequently open labelled lamivudine 100 mg/d for a total of 156 weeks . RESULTS After 12-week lamivudine therapy , the levels of serum HBV DNA decreased rapidly . The negativity of HBV DNA ( < 1.6 pg/ml ) at week 12 was 92.2 % in the lamivudine group , whereas it was only 14.1 % in the placebo group ( P<0.01 ) . After 1-year lamivudine treatment , 72.7 % of the patients showed undetectable serum HBV DNA ( < 1.6 pg/ml ) . At the end of 3 years , serum HBV DNA continued to be substantially suppressed with a median level below a detectable level in patients with non-YMDD variant HBV , which was increased to 86 mEq/ml ( bDNA method , equivalent hybridization method 10 pg/ml ) in patients with YMDD mutation . At the end of 1 , 2 and 3 years , the rates of HBeAg loss were 9.5 % , 16.8 % and 20.0 % respectively and the rates of HBeAg/anti-HBe seroconversion were 8.3 % , 11.5 % and 17.3 % . The rates of HBeAg loss and seroconversion were correlated with the baseline level of ALT . In patients with a baseline level of alanine transaminase (ALT)>2 x upper limit of normal ( ULN ) and ALT > 5xULN , the rates of HBeAg loss were 42.2 % and 66.7 % , and the rates of seroconversion were 34.4 % and 61.1 % respectively ( P<0.01 ) at the end of year 3 . The levels of ALT at year 3 remained normal in 58.8 % of patients whose baseline level of ALT was elevated , and in 79.1 % of patients whose level of ALT was normal before treatment . YMDD mutations occurred in 12.1 % , 49.7 % and 70.5 % of patients respectively at year 1 , 2 and 3 . In patients with YMDD mutation , the levels of HBV DNA were increased slightly with mild to moderate elevation of ALT level . HBeAg loss and seroconversion were 20.0 % and 15.1 % in patients with YMDD mutation at the end of year 3 , which were lower than those in non-variant patients ( P<0.01 ) . Adverse drug reactions or events varied generally from mild to moderate . In 2 patients serious adverse events ( fatigue and abdominal distension ) were related to medication . ALT flares ( ALT>5xULN ) occurred in 17 patients : 10 were YMDD mutants and 7 were non-mutants ; all of them were relieved . No death occurred in the period of 3 years . CONCLUSION Sustained inhibition of HBV replication and clinical improvement could be obtained after 3-year lamivudine therapy of good tolerance and safety Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B ( CHB ) were r and omly assigned to receive human lymphoblastoid interferon ( ly-IFN ) at a dose of 5 MU/m2 i.m . three times a week for 6 months ( ten cases ) or no treatment ( eight cases ) . All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy . During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels , and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values . None of the untreated patients became persistently HBV-DNA-negative or showed significant variations of ALT levels . During the post-treatment follow-up , from 1 to 17 months after ly-IFN discontinuation , eight of the nine responders ( 89 % ) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity , with an ALT peak in four of them . On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen . Histological features improved in four treated patients , worsened in one untreated case and were unchanged in the remaining patients . These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti-HBe- and HBV-DNA-positive CHB . The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation To determine the efficacy of interferon-alpha 2a in chronic active hepatitis B , 238 patients were r and omly divided , into four groups : three groups received either 2.5 MIU m-2 , 5.0 MIU m-2 or 10.0 MIU m-2 , three times weekly by intramuscular injection for 12 - 24 weeks ; and a control group received no treatment . Patients were followed for up to 12 months after treatment was discontinued . There was a statistically significant difference in response [ clearance of hepatitis B e antigen ( HBeAg ) and hepatitis B viral DNA ( HBV-DNA ) ] between treated and untreated patients ( 37 vs 13 % ) but no statistically significant difference was seen between treatment groups ( 33 % , 34 % and 43 % for the 2.5 , 5.0 and 10.0 MIU m-2 groups , respectively ) . A transient rise in transaminases ( seroconversion hepatitis ) was seen in responders , but levels returned to within the normal range after response to treatment . In patients responding to interferon therapy there was a significant reduction in the severity of the hepatitis . Interferon-alpha 2a was generally well tolerated with respect to vital signs and laboratory parameters BACKGROUND AND METHODS Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy . To assess the efficacy of treatment with interferon , we r and omly assigned patients with chronic hepatitis B to one of the following regimens : prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks ; placebo followed by 5 million units of interferon daily for 16 weeks ; placebo followed by 1 million units of interferon daily for 16 weeks ; or observation with no treatment . RESULTS Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon ( 16 of 44 patients , or 36 percent ) or 5 million units of interferon alone ( 15 of 41 ; 37 percent ) than in the untreated controls ( 3 of 43 ; 7 percent ; P less than 0.001 ) ; the difference between those given 1 million units of interferon ( 7 of 41 ; 17 percent ) and the controls was not significant . The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry ( P less than 0.0001 ) . Of the 38 patients who responded to interferon , 33 ( 87 percent ) had normal serum aminotransferase levels after therapy ; 11 patients who responded ( 29 percent ) , but no controls , lost the hepatitis B surface antigen . Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients ( P = 0.03 ) . CONCLUSIONS In chronic hepatitis B , treatment with interferon alfa-2b ( 5 million units per day for 16 weeks ) was effective in inducing a sustained loss of viral replication and achieving remission , assessed biochemically and histologically , in over a third of patients . Moreover , in about 10 percent of the patients treated with interferon , hepatitis B surface antigen disappeared from serum BACKGROUND Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses . As a result , nucleoside and nucleotide analogues are typically continued indefinitely , a strategy associated with the risk of resistance and unknown long-term safety implication s. METHODS We compared the efficacy and safety of peginterferon alfa-2a ( 180 microg once weekly ) plus placebo , peginterferon alfa-2a plus lamivudine ( 100 mg daily ) , and lamivudine alone in 177 , 179 , and 181 patients with HBeAg-negative chronic hepatitis B , respectively . Patients were treated for 48 weeks and followed for an additional 24 weeks . RESULTS After 24 weeks of follow-up , the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus ( HBV ) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy ( 59 percent and 43 percent , respectively ) and peginterferon alfa-2a plus lamivudine ( 60 percent and 44 percent ) than with lamivudine monotherapy ( 44 percent , P=0.004 and P=0.003 , respectively ; and 29 percent , P=0.007 and P=0.003 , respectively ) . Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy , 20 percent with combination therapy , and 7 percent with lamivudine alone ( P<0.001 for both comparisons with lamivudine alone ) . Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups , as compared with 0 patients in the group given lamivudine alone . Adverse events , including pyrexia , fatigue , myalgia , and headache , were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy . CONCLUSIONS Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response , sustained for 24 weeks after the cessation of therapy , with peginterferon alfa-2a than with lamivudine . The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates BACKGROUND / AIMS To evaluate the therapeutic efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. METHODS One hundred and fifty-one patients were r and omly assigned to receive either recombinant interferon alpha-2b ( nine million units three times per week ) and lamivudine ( 100 mg/daily per os ) for 24 weeks or lamivudine alone ( 100 mg/daily per os ) for 52 weeks . Patients were followed up for a further 48 weeks . RESULTS Sustained HBeAg seroconversion with undetectable serum levels of HBV DNA was observed in 25 of 76 patients ( 33 % ) treated with the combination therapy and in 11 of 75 patients ( 15 % ) treated with monotherapy ( P=0.014 ) . Histological improvement defined as a reduction of at least two points in the inflammation score as compared with pretreatment score was observed in 35 of 76 patients ( 46 % ) treated with combination therapy and in 20 of 75 patients ( 27 % ) treated with monotherapy ( P=0.021 ) . Both therapeutic regimens were well tolerated . CONCLUSIONS Six-month treatment with interferon alpha-2b and lamivudine in combination appeared to increase the rate of sustained HBeAg seroconversion compared to 1-year lamivudine monotherapy . However , the potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy BACKGROUND AND METHODS In preliminary trials , lamivudine , an oral nucleoside analogue , has shown promise for the treatment of chronic hepatitis B. We conducted a one-year , double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were r and omly assigned to receive 25 mg of lamivudine ( 142 patients ) , 100 mg of lamivudine ( 143 ) , or placebo ( 73 ) orally once daily . The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen . The primary end point was a reduction of at least two points in the Knodell necroinflammatory score . RESULTS Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine , 49 percent of those receiving 25 mg of lamivudine , and 25 percent of those receiving placebo ( P<0.001 and P=0.001 , respectively , for the comparisons of lamivudine treatment with placebo ) . Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine , 8 percent of those receiving 25 mg , and 26 percent of those receiving placebo . The 100-mg dose of lamivudine was associated with a reduced progression of fibrosis ( P=0.01 for the comparison with placebo ) and with the highest rate of hepatitis B e antigen ( HBeAg ) seroconversion ( loss of HBeAg , development of antibody to HBeAg , and undetectable HBV DNA ) ( 16 percent ) , the greatest suppression of HBV DNA ( 98 percent reduction at week 52 as compared with the base-line value ) , and the highest rate of sustained normalization of alanine aminotransferase levels ( 72 percent ) . Ninety-six percent of the patients completed the study . The incidence of adverse events was similar in all groups , and there were few serious events . CONCLUSIONS In a one-year study , lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg BACKGROUND / AIMS The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization . In a r and omized trial we investigated a regimen where the initially given hepatitis B immunoglobulin ( HBIg ) is replaced by long-term lamivudine treatment . METHODS Twenty-four liver transplant recipients ( all HBsAg-positive/HBV DNA-negative before transplantation ) , who had received HBIg for at least 6 months without HBV recurrence , were r and omized to receive lamivudine ( n = 12 ) or HBIg ( n = 12 ) for 52 weeks . The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver . RESULTS Twenty-one of 24 patients completed the study without hepatitis B virus ( HBV ) recurrence ( 11 on HBIg , ten on lamivudine ) , while three patients became HBsAg-positive . Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction , intermittently in serum and lymphocytes , and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine . YMDD variant was found in four cases with no viral antigen expression . Eight patients continued lamivudine after the study and during an additional 6 - 22 months remained HBsAg-negative with normal graft function . CONCLUSIONS Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis A study in Chinese patients with chronic hepatitis B showed that treatment with lamivudine for 1 year significantly improves liver histology and enhances hepatitis B e antigen ( HBeAg ) seroconversion compared with placebo . Fifty‐eight patients from this 1‐year study have received long‐term treatment with lamivudine 100 mg ; the outcome of 3 years of lamivudine is reported here . Before treatment , all patients had detectable HBeAg . HBeAg seroconversion ( HBeAg‐negative , anti‐HBe – positive ) , hepatitis B virus (HBV)‐DNA suppression , alanine transaminase ( ALT ) normalization , emergence of YMDD variant HBV , liver histology , and long‐term safety were assessed . After 3 years of continuous treatment with lamivudine 100 mg daily , 40 % ( 23 of 58 ) of patients achieved HBeAg seroconversion . In patients with baseline serum ALT > 2 × upper limit of normal ( ULN ) , the rate of HBeAg seroconversion was 65 % ( 17 of 26 ) . Median serum HBV‐DNA concentrations were below the level of detection , and median ALT concentrations were within the normal range throughout 3 years of treatment . YMDD variant HBV emerged in 33 of 58 ( 57 % ) patients during the 3 years , of whom 9 ( 27 % ) achieved HBeAg seroconversion ( 6 after emergence of YMDD variant HBV ) . ALT levels and histologic scores after emergence of YMDD variant HBV did not show major deterioration . Lamivudine was well tolerated during 3 years of therapy . In conclusion , these data in Chinese patients with chronic hepatitis B show enhanced seroconversion rates with extended lamivudine treatment . Up to two thirds of patients with moderately elevated pretreatment ALT achieved HBeAg seroconversion after 3 years of therapy BACKGROUND & AIMS Therapy with interferon alfa ( IFN-alpha ) leads to remission of disease in one third of patients with chronic hepatitis B. The aim of this study was to better define the long-term prognosis of this outcome . METHODS One hundred three patients with chronic hepatitis B who underwent IFN-alpha therapy in three clinical trials between 1984 and 1991 were followed up for serological status , biochemical evidence of liver disease , and liver complications or mortality through 1994 . RESULTS Among 103 patients , 31 ( 30 % ) responded to therapy with loss of hepatitis B e antigen and viral DNA from serum . Responders were more likely than nonresponders to be women , black , and to have more severe liver disease including cirrhosis ( P < 0.05 ) . Up to 11 years ( mean , 6.2 years ) after therapy , a higher percentage of responders than nonresponders were still negative for hepatitis B e antigen ( 94 % vs. 40 % ; P < 0.001 ) and hepatitis B surface antigen ( 71 % vs 8.3 % ; P < 0.001 ) . Overall , the rate of liver-related complications and death did not differ by IFN-alpha response , but with adjustment for cirrhosis , nonresponders had higher rates of liver-related complications and mortality ( hazard ratio , 13.7 ; 95 % confidence interval , 3.0 - 63.5 ) . CONCLUSIONS The response to IFN-alpha therapy in chronic hepatitis B is usually a sustained improvement in disease markers and , when cirrhosis is considered , patient outcome Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease . These forms of chronic hepatitis B have been described as having a poor prognosis . We have conducted a r and omized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis . Patients received 5 million U/m2 interferon three times a week for 6 mo , or no treatment . Final evaluation 18 mo after r and omization showed hepatitis B virus DNA negativity and ALT normalization in 53 % of treated patients and in 17 % of controls ( p less than 0.01 ) . The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls ( p less than 0.005 ) . Blinded histological assessment revealed improvement in 50 % of treated patients compared with 33 % of controls . Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response . The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50 % of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis . This rate of response is higher than that reported previously Context Few studies have evaluated combination therapies for chronic hepatitis B. Contribution In this single-center , open-label trial , 100 patients with hepatitis B e antigenpositive chronic hepatitis B and moderately elevated alanine aminotransferase levels were r and omly assigned to a staggered regimen of pegylated interferon-2b for 32 weeks plus lamivudine for 52 weeks or lamivudine monotherapy . Patients receiving combination therapy more often had virologic responses and less often developed lamivudine-resistant mutants than those receiving monotherapy . Transient influenza-like symptoms , alopecia , and local erythematous reactions were more common with combination therapy . Caution s Patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy . The Editors Chronic hepatitis B virus ( HBV ) infection affects more than 300 million people globally ( 1 ) . Patients who have HBV infection with positivity for hepatitis B e antigen ( HBeAg ) and persistently active disease have increased risks for progressive disease leading to liver cirrhosis and hepatocellular carcinoma ( 2 ) . Conventional interferon treatment with injections given up to 3 times per week for 12 to 24 weeks may lead to HBeAg seroconversion in 33 % of treated patients compared with 12 % of untreated controls ( 3 ) . The treatment response to conventional interferon treatment among Asian patients seems less satisfactory ( 4 , 5 ) . Pegylated interferon-2b is synthesized by bonding recombinant interferon-2b to polyethylene glycol and is given once weekly rather than 3 times weekly ( 6 ) . The antiviral efficacy of pegylated interferon-2b for treating chronic hepatitis C is superior to that of conventional interferon ( 7 , 8) , but few studies have evaluated pegylated interferon in patients with chronic hepatitis B. Lamivudine is an oral nucleoside analogue that effectively suppresses HBV replication ( 9 , 10 ) . Studies suggest that only 16 % to 18 % of patients treated with lamivudine for 1 year develop HBeAg seroconversion ( 9 - 11 ) . Extending lamivudine treatment for up to 4 years is associated with development of drug-resistant viral mutants in about 70 % of patients ( 12 ) . The durability of HBeAg seroconversion is estimated to be 46 % to 64 % up to 3 years after the cessation of lamivudine treatment ( 13 - 15 ) . Successful elimination of HBV depends on a durable immune clearance of the existing pool of intrahepatic HBV , particularly the closed covalent circular DNA ( 16 ) . Combining an immunomodulator ( such as interferon ) and an antiviral agent ( such as lamivudine ) is an appealing approach for treating chronic hepatitis B. However , past studies in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B showed conflicting results about the superiority of combination therapy over lamivudine monotherapy ( 11 , 17 - 20 ) . We evaluated whether the combination of pegylated interferon-2b and lamivudine improves antiviral efficacy and increases HBeAg seroconversion rates more than lamivudine monotherapy in patients with HBeAg-positive chronic hepatitis B and moderately elevated alanine aminotransferase ( ALT ) levels . Since extending interferon treatment from 16 to 32 weeks is associated with higher rates of HBeAg seroconversion ( 21 ) , combination therapy includes pegylated interferon-2b given for 32 weeks . Methods Patients We recruited consecutive patients 18 to 65 years of age with chronic hepatitis B from the Hepatitis Clinic of the Prince of Wales Hospital , Hong Kong , China , a secondary referral center serving around 1 million people . All patients had been positive for hepatitis B surface antigen ( HBsAg ) for at least 6 months , were HBeAg-positive , and had a serum HBV DNA level of at least 500000 copies/mL and an ALT level that was 1.3 to 5 times the upper limit of normal . We excluded patients who had decompensated liver disease or a history of interferon or antiviral agent use . Other exclusion criteria were co-infection with hepatitis C virus , hepatitis D virus , or HIV ; history of hepatocellular carcinoma ; other causes of liver disease , including autoimmune hepatitis ; Wilson disease ; hemochromatosis and 1-antitrypsin deficiency ; serious medical or psychiatric illness ; concurrent use of corticosteroid or immunosuppressive agents ; and pregnancy . We conducted the study in accordance with the guidelines of the Declaration of Helsinki . The ethics committee of The Chinese University of Hong Kong approved the protocol , and all patients gave witnessed , written informed consent . Study Design The study was a phase III , open-label , r and omized trial . Within 4 weeks of screening for eligibility criteria , patients were r and omly assigned to either combination therapy with pegylated interferon-2b ( PegIntron , Shering-Plough Corp. , Kenilworth , New Jersey ) and lamivudine ( Zeffix , GlaxoSmithKline , Middlesex , United Kingdom ) or lamivudine monotherapy in a ratio of 1:1 . We based study group assignment on a computer-generated list , and research staff who were not involved in patient management placed the r and om numbers in opaque envelopes . A research nurse prescribed study drugs after receiving the information about treatment allocation at the baseline visit . Figure 1 shows the study design . Pegylated interferon-2b was given as a subcutaneous injection at a dosage of 1.5 g/kg of body weight per week for patients who weighed less than 65 kg or 100 g per week for patients who weighed more than 65 kg for 32 weeks ( 6 ) . Lamivudine was administered as 100 mg orally daily for 52 weeks in both groups of patients . In patients receiving combination therapy , pegylated interferon-2b was administered 8 weeks before lamivudine was administered . Then both treatments were given in combination for 24 weeks , followed by lamivudine monotherapy for a further 28 weeks . Patients in the combination group were asked to return at weeks 1 , 2 , 4 , 8 , 12 , 16 , 20 , 24 , 32 , 40 , 52 , and 60 ( end of treatment ) . Patients in the lamivudine monotherapy group received lamivudine for 52 weeks and were asked to return for follow-up at weeks 4 , 8 , 12 , 16 , 24 , 32 , 40 , 48 , and 52 ( end of treatment ) . We followed patients in both groups every 8 weeks in the post-treatment period for 24 more weeks . We gave open-label lamivudine treatment to patients who experienced severe post-treatment relapse of chronic hepatitis B ( defined as an ALT level > 10 times the upper limit of normal and HBV DNA level > 500000 copies/mL ) . Figure 1 . Study design . Safety The investigators interviewed patients for symptomatic adverse effects and closely monitored laboratory tests at each follow-up visit . They recorded symptoms and events that patients reported spontaneously , symptoms and events elicited in response to open-ended questions , and adverse effects observed at the follow-up visits . They assessed all adverse events on the likelihood of causality by the study drug or drugs . They assessed the severity of adverse events according to a preset table and classified the event as mild ( grade 1 ) , moderate ( grade 2 ) , severe ( grade 3 ) , or life-threatening ( grade 4 ) . The dosage of pegylated interferon was reduced , as necessary , according to the severity of the adverse events . The dosage was reduced from 100 g per week ( or 1.5 g/kg per week if body weight < 65 kg ) to 50 g per week ( or 1.0 g/kg per week if body weight < 65 kg ) for grade 3 adverse events ( or sometimes grade 2 adverse events at the discretion of the investigator ) . The dosage could be further reduced to 25 g per week ( or 0.5 g/kg per week if body weight < 65 kg ) if the adverse recurred despite initial dosage reduction . Pegylated interferon therapy was stopped in case of grade 4 adverse events . Patients receiving combination treatment were allowed to continue lamivudine if investigators thought that the adverse effect was related to pegylated interferon use . Lamivudine therapy was stopped if the adverse event persisted despite cessation of pegylated interferon therapy . We tested serum for HBV DNA levels , HBeAg , and antibody to HBeAg ( at baseline , then 8 weekly until the end of treatment , and weeks 8 , 16 , and 24 after treatment ) and HBsAg and antibody to HBsAg ( at baseline , end of treatment , and 24 weeks after treatment ) . We determined the presence of lamivudine-resistant mutations in the serum sample at the end of treatment . Liver biopsy was performed within 4 weeks before treatment began and at the end of treatment . Laboratory Assays Serologic Assays We tested for HBsAg and antibodies to hepatitis C virus , hepatitis D virus , and HIV by using commercially available enzyme-linked immunosorbant assay kits ( Abbott GmBH Diagnostika , Wiesbaden-Delkenheim , Germany ) . We measured HBeAg and antibody to HBeAg by using an enzyme-linked immunosorbant assay ( Sanofi Diagnostics , Pasteur , France ) . Virologic Assays We based our sample size calculations and initial screening for eligibility on the DNA cross-linking assay ( NAXCOR XLnt , NAXCOR , Menlo Park , California ) , which has a lower limit of detection of 500000 copies/mL for quantification of HBV DNA ( 22 ) . Since the TaqMan real-time polymerase chain reaction assay ( Applied Biosystem , Foster City , California ) became available in our laboratory , we used this assay to measure HBV DNA levels at baseline and in all follow-up visits ( 23 , 24 ) . The range of HBV DNA detection was from 102 to 109 copies/mL ; the correlation coefficient of the st and ard curve was routinely greater than 0.990 . We performed HBV genotyping by restriction fragment length polymorphism in a residual serum sample taken from each patient at their initial visit ( 25 , 26 ) . We determined the presence of lamivudine-resistant mutants by using the INNO-LiPA HBV DR line probe assay ( Innogenetics N.V. , Ghent , Belgium ) according to the instruction of the manufacturer ( 27 ) . End Points We defined virologic response as HBeAg seroconversion ( that is , loss of HBeAg ) , detection of antibody to HBeAg , and HBV DNA level less than 500000 copies/mL and biochemical response as normalization This study was performed to evaluate the long-term effects of interferon-alpha 2a ( IFN-alpha 2a ) vs no treatment in patients with chronic hepatitis B and to determine whether viral clearance , following therapy or occurring spontaneously , was sustained . Patients originating from three previously published multicentre , r and omized , controlled trials were analysed . Information about survival and response during long-term follow-up was available in 340 ( 73 % ) and 308 ( 66 % ) of 469 r and omized patients respectively . Response to therapy ( viral clearance ) was defined as : loss of hepatitis B virus ( HBV ) DNA and loss of hepatitis B e antigen ( HBeAg ) and improvement in alanine aminotransferase level . Scheduled treatment-free follow-up was 12 months in all studies . Median long-term follow-up time after inclusion in the individual studies was 4.7 years ( range : 0.2 - 7.5 years ) . Viral clearance after IFN-alpha 2a , or occurring spontaneously , was sustained in 70 out of 80 evaluable patients ( 88 % ) who were responders at the end of the original trials and 21 ( 30 % ) lost hepatitis B surface antigen ( HBsAg ) . A total of 80 patients received (re)treatment during the long-term follow-up period and 33 % of them responded , irrespective of previous treatment category . Overall response rate was not significantly affected by gender , sexual inclination or ethnic origin . Durability of response did not depend upon ethnic origin or presence of cirrhosis . At the end of the original trial periods , 253 patients were histologically evaluated and 22 ( 9 % ) had histologically confirmed progression to cirrhosis . During long-term follow-up an additional five patients developed cirrhosis . Hepatocellular carcinoma developed in three patients ( 1 % ) : in one patient during the follow-up period of the original trial and in two patients ( one untreated ) during the long-term follow-up period . Ten of 25 deaths were liver-related ( hepatocellular carcinoma in three , gastrointestinal bleeding in two and liver failure in five ) . The distribution of clinical events ( progression to cirrhosis , hepatocellular carcinoma and liver-related deaths ) was unrelated to original treatment category and response to treatment . Hence , 90 % of responding patients will , irrespective of treatment category , have a sustained response . At least 30 % of responding patients will eventually lose HBsAg . For a number of reasons , the present patient population and observation period are insufficient to establish a presumed beneficial effect of IFN-alpha 2a on disease progression and survival Thirty three heterosexual chronic hepatitis B virus ( HBV ) carriers were r and omized , with stratification for disease activity , to receive intramuscular recombinant interferon alpha-2a ( r-IFN ) at doses of 4.5 megaunits thrice weekly for 4 months , or no treatment . During r-IFN treatment , serum HBV-DNA levels fell in all , but 2 patients . Final evaluation at 16 months after r and omization revealed that the rate of complete response , i.e. , loss of both HBV-DNA and HBeAg with ALT normalization was 22.2 % ( 2 of 9 cases ) in patients on interferon and 12.5 % ( 1 of 8 cases ) in untreated patients for the group with high serum alanine aminotransferase ( ALT ) and with piecemeal necrosis on liver biopsy on entry . The corresponding value was 25 % ( 2 of 8 cases ) in treated and 12.5 % ( 1 of 8 cases ) in untreated patients with low liver disease activity . Overall , a complete response was thus observed in 23.5 % of treated patients and in 12.5 % of controls . None of the patients on therapy became HBsAg negative . It is concluded that treatment of heterosexual patients with chronic hepatitis B with r-IFN in the dose regimen used here was not associated with a significant higher rate of serologic and clinical response compared to controls , independently of pretreatment biochemical and histologic activity of liver disease BACKGROUND / AIMS Interferon therapy has been shown to be effective in Western patients with chronic hepatitis due to hepatitis B viral infection , but not in Asian Chinese . Its efficacy in Asian Indian subjects with chronic HBV infection is not known . METHODS Forty-one patients with HBV-related chronic liver disease received r and omly either : ( a ) recombinant alpha 2b interferon ( n = 20 ) 3 MIU , subcutaneously , three times a week for 4 months , or ( b ) no treatment ( n = 21 ) . Patients were followed up for 12 months after completion of therapy . RESULTS In the interferon-treated group , complete response ( loss of HBV-DNA and HBeAg ) was significantly higher than spontaneous clearance in the control group ( 50 % vs. 4.8 % p < 0.05 ) . Seroconversion to anti-HBe was seen in 35 % of the treated and 4.8 % of the control group ( p < 0.05 ) at 4 months ; it was noticeably higher in patients with chronic hepatitis than in those with cirrhosis . In the responders , alanine aminotransferase levels nearly normalized . One year after interferon therapy , HBeAg and HBV-DNA clearance was observed in 65 % of patients , with HBsAg clearance in 15 % . Reactivation was not seen in any patient . Side-effects were transient and minimal . CONCLUSION Low-dose recombinant alpha interferon therapy is quite effective and safe in Asian Indians with chronic liver disease due to hepatitis B infection Fifty-seven patients with chronic hepatitis B , hepatitis B virus ( HBV ) e antigen ( HBeAg ) and HBV DNA positivity , and aminotransferase elevation despite a previous course of any type of adequate interferon alfa ( IFN-alpha ) therapy were included in a multicenter prospect i ve r and omized controlled trial . The objective of the study was to compare a second course of IFN-alpha therapy ( 9 million units [ MU ] of IFN-alpha-2a , Roferon-A , thrice weekly for 6 months ) versus no therapy in terms of loss of HBV DNA and HBeAg . At the end of the study , a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 ( 33.3 % ) patients who had received retreatment with IFN-alpha compared with 3/30 ( 10 % ) patients who spontaneously cleared these markers in the untreated control group ( chi2 = 4.66 , P = .031 ; odds ratio : 4.5 , 95 % ; confidence interval : 1.1 - 18.9 ) . None of the responders lost HBsAg . Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance ( 5/27 , 18.5 % ) compared with untreated patients ( 1/30 , 3 . 3 % ; Fisher 's exact test P = .09 ) . Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment , consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis ; there was no change in the degree of liver fibrosis . Side effects were similar to those previously reported during IFN-alpha treatment ; these were mild and reversible on IFN-alpha discontinuation . None of the baseline features were associated with response by Cox 's regression analysis . In summary , viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha . Thus , retreatment with IFN-alpha may be considered a therapeutic option The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented . However , its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known . In this study , we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months . All patients responded to lamivudine , but viral breakthrough occurred in 13 patients ( 59 % ) between 9 and 42 months of therapy due to the emergence of a mutant strain . During the follow-up , 11 developed hepatocellular carcinoma . Of these , 10 occurred soon after the emergence of viral resistance , generally showing aggressive behaviour , and one in the nine long-term responder patients ( P = 0.013 ) . Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development ( risk ratio : 10.4 ; 95 % CI : 1.3 - 84.9 ) . Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research |
13,496 | 29,149,140 | DEX had no effect on the incidence of hypotension or bradycardia , which was also confirmed by the TSA .
The GRADE level of evidence was high for postoperative nausea , moderate for pain intensity at rest at 24 hours postoperatively , morphine-equivalent requirement during 0 - 24 hours postoperatively , and postoperative vomiting , pruritus , and bradycardia , and low for postoperative hypotension .
LIMITATIONS The risk of introducing potentially significant heterogeneity exists , and this study did not evaluate the effects of DEX combined with opioids on long-term outcomes including chronic pain and patients ' satisfaction after hospital discharge .
Postoperative PCA strategies with opioid-DEX combinations decreased postoperative pain , opioid requirement , and opioid-related adverse events .
DEX is a useful adjuvant to opioid-based PCA . | BACKGROUND It is still a challenge to optimize postoperative pain management .
The effects of adding dexmedetomidine ( DEX ) to opioid-based postoperative intravenous patient-controlled analgesia ( PCA ) are not fully understood .
OBJECTIVES The aim of this study is to assess the efficacy and safety of opioid-DEX combinations for postoperative PCA , and a trial sequential analysis ( TSA ) is utilized to evaluate the robustness of the current evidence . | 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 Thirty-four patients scheduled for elective inpatient surgery were r and omized equally to receive either dexmedetomidine ( initial loading dose of 1-&mgr;g/kg over 10 min followed by 0.4 & mgr;g · kg−1 · h−1 for 4 h ) or morphine sulfate ( 0.08 mg/kg ) 30 min before the end of surgery . We determined heart rate ( HR ) , mean arterial blood pressure ( MAP ) , respiratory rate ( RR ) , sedation and analgesia ( visual analog scale ) , and use of additional morphine in the postanesthesia care unit ( PACU ) and up to 24 h after surgery . Groups were similar for patient demographics , ASA physical status , surgical procedure , baseline hemodynamics , and intraoperative use of drugs and fluids . Dexmedetomidine-treated patients had slower HR in the PACU ( by an average of 16 bpm ) , whereas MAP , RR , and level of sedation were similar between groups . During Phase I recovery , dexmedetomidine-treated patients required significantly less morphine to achieve equivalent analgesia ( PACU dexmedetomidine group , 4.5 ± 6.8 mg ; morphine group , 9.2 ± 5.2 mg ) . Sixty minutes into recovery only 6 of 17 dexmedetomidine patients required morphine in contrast to 15 of 17 in the morphine group . The administration of dexmedetomidine before the completion of major inpatient surgical procedures significantly reduced , by 66 % , the early postoperative need for morphine and was associated with a slower HR in the PACU Abstract Smoking is one of the most common addictions in the world . Nicotine inhalation could increase the risk of cardiorespiratory diseases . However , the solution that improved postoperative analgesia for highly nicotine-dependent patients undergoing thoracic surgery has not been specifically addressed . This CONSORT- prospect i ve , r and omized , double-blinded , controlled trial investigated the efficacy of combination of dexmedetomidine and sufentanil for highly nicotine ( Fagerstrom test of nicotine dependence ≥6)-dependent patients after thoracic surgery . One hundred seventy-four male patients who underwent thoracic surgery were screened between February 2014 and November 2014 , and a total of forty-nine were excluded . One hundred thirty-two highly nicotine-dependent male patients who underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia were divided into 3 groups after surgery in this double-blind , r and omized study : sufentanil ( 0.02 & mgr;g/kg/h , Group S ) , sufentanil plus dexmedetomidine ( 0.02 & mgr;g/kg/h each , Group D1 ) , or sufentanil ( 0.02 & mgr;g/kg/h ) plus dexmedetomidine ( 0.04 & mgr;g/kg/h ) ( Group D2 ) . The patient-controlled analgesia ( PCA ) program was programmed to deliver a bolus dose of 2 ml , with background infusion of 2 ml/h and a lockout of 5 min , 4-hour limit of 40 ml , as our retrospective study . The primary outcome measure was the cumulative amount of self-administered sufentanil ; the secondary outcome measures were pain intensity ( numerical rating scale , NRS ) , level of sedation ( LOS ) , Bruggrmann comfort scale ( BCS ) , functional activity score ( FAS ) , and concerning adverse effects . The amount of self-administered sufentanil were lower in group D2 compared with S and D1 groups during the 72 hours after surgery ( P < 0.05 ) , whereas the total dosage and dosage per body weight of sufentanil were significantly lower in D1 group than that of S group only at 4 , 8 , and 16 hours after surgery ( P < 0.05 ) . Compared with S group , the NRS scores at rest at 1 , 4 , and 8 hours after surgery and with coughing at 4 , 8 , 16 , and 24 hours after surgery were significantly lower in D2 group ( P < 0.05 ) . However , compared with D1 group , the NRS scores both at rest and with coughing at 4 and 8 hours after surgery were significantly lower in D2 group ( P < 0.05 ) . The NRS scores both at rest and with coughing show that there were no significant differences between D1 group and S group at each time point after surgery ( P > 0.05 ) . LOS of group D2 was higher than S and D1 groups at 1 hour after surgery ( P < 0.05 ) , BCS of group D2 was higher than S and D1 groups at 4 , 8 , and 16 hours after surgery ( P < 0.05 ) , and FAS of group D2 was higher than S and D1 groups at 48 and 72 hours after surgery ( P < 0.05 ) . The number of rescue analgesia during 72 hours after surgery in D2 group was lower than S and D1 groups ( P < 0.05 ) . There were no significant differences among the 3 groups in terms of baseline clinical characteristics and postoperative adverse effects except for itching ( P > 0.05).Among the tested patient-controlled analgesia options , the addition of dexmedetomidine ( 0.04 & mgr;g/kg/h ) and sufentanil ( 0.02 & mgr;g/kg/h ) showed better analgesic effect and greater patient satisfaction without other clinical ly relevant side effects for highly nicotine-dependent patients during the initial 72 hours after thoracic surgery . Trial Registration : chictr.org ( ChiCTR-TRC-14004191 ) BACKGROUND Perioperative use of dexmedetomidine is associated with reduction in postoperative analgesic requirements . This study examined whether dexmedetomidine added to i.v . patient-controlled analgesia ( PCA ) morphine could improve analgesia while reducing opioid-related side-effects . METHODS In this double-blinded , r and omized , controlled study , 100 women undergoing abdominal total hysterectomy were allocated to receive either morphine 1 mg ml(-1 ) alone ( Group M ) or morphine 1 mg ml(-1 ) plus dexmedetomidine 5 microg ml(-1 ) ( Group D ) for postoperative i.v . PCA , which was programmed to deliver 1 ml per dem and with a 5 min lockout interval and no background infusion . Cumulative PCA requirements , pain intensities , cardiovascular and respiratory variables , and PCA-related adverse events were recorded for 24 h after operation . RESULTS Compared with Group M , patients in Group D required 29 % less morphine during the 0 - 24 h postoperative period and reported significantly lower pain levels from the second postoperative hour onwards and throughout the study . Whereas levels of sedation were similar between the groups at each observational time point , decreases in heart rate and mean blood pressure from presurgery baseline at 1 , 2 , and 4 h after operation were significantly greater in Group D ( by a range of 5 - 7 beats min(-1 ) and 10 - 13 % , respectively ) . The 4 - 24 h incidence of nausea was significantly lower in Group D ( 34 % vs 56.3 % , P<0.05 ) . There was no bradycardia , hypotension , oversedation , or respiratory depression . CONCLUSIONS The addition of dexmedetomidine to i.v . PCA morphine result ed in superior analgesia , significant morphine sparing , less morphine-induced nausea , and was devoid of additional sedation and untoward haemodynamic changes Introduction Only limited information exists on the pharmacokinetics of prolonged ( > 24 hours ) and high-dose dexmedetomidine infusions in critically ill patients . The aim of this study was to characterize the pharmacokinetics of long dexmedetomidine infusions and to assess the dose linearity of high doses . Additionally , we wanted to quantify for the first time in humans the concentrations of H-3 , a practically inactive metabolite of dexmedetomidine . Methods Thirteen intensive care patients with mean age of 57 years and Simplified Acute Physiology Score ( SAPS ) II score of 45 were included in the study . Dexmedetomidine infusion was commenced by using a constant infusion rate for the first 12 hours . After the first 12 hours , the infusion rate of dexmedetomidine was titrated between 0.1 and 2.5 μg/kg/h by using predefined dose levels to maintain sedation in the range of 0 to -3 on the Richmond Agitation-Sedation Scale . Dexmedetomidine was continued as long as required to a maximum of 14 days . Plasma dexmedetomidine and H-3 metabolite concentrations were measured , and pharmacokinetic variables were calculated with st and ard noncompartmental methods . Safety and tolerability were assessed by adverse events , cardiovascular signs , and laboratory tests . Results The following geometric mean values ( coefficient of variation ) were calculated : length of infusion , 92 hours ( 117 % ) ; dexmedetomidine clearance , 39.7 L/h ( 41 % ) ; elimination half-life , 3.7 hours ( 38 % ) ; and volume of distribution during the elimination phase , 223 L ( 35 % ) . Altogether , 116 steady-state concentrations were found in 12 subjects . The geometric mean value for clearance at steady state was 53.1 L/h ( 55 % ) . A statistically significant linear relation ( r2 = 0.95 ; P < 0.001 ) was found between the areas under the dexmedetomidine plasma concentration-time curves and cumulative doses of dexmedetomidine . The elimination half-life of H-3 was 9.1 hours ( 37 % ) . The ratio of AUC0-∞ of H-3 metabolite to that of dexmedetomidine was 1.47 ( 105 % ) , ranging from 0.29 to 4.4 . The ratio was not statistically significantly related to the total dose of dexmedetomidine or the duration of the infusion . Conclusions The results suggest linear pharmacokinetics of dexmedetomidine up to the dose of 2.5 μg/kg/h . Despite the high dose and prolonged infusions , safety findings were as expected for dexmedetomidine and the patient population .Trial Registration Clinical Trials.gov : Abstract Both dexmedetomidine and sufentanil modulate spinal analgesia by different mechanisms , and yet no human studies are available on their combination for analgesia during the first 72 hours after abdominal hysterectomy . This CONSORT- prospect i ve , r and omized , double-blinded , controlled trial sought to evaluate the safety and efficacy of the combination of dexmedetomidine and sufentanil in intravenous patient-controlled analgesia ( PCA ) for 72 hours after abdominal hysterectomy . Ninety women undergoing total abdominal hysterectomy were divided into 3 equal groups that received sufentanil ( Group C ; 0.02 & mgr;g/kg/h ) , sufentanil plus dexmedetomidine ( Group D1 ; 0.02 & mgr;g/kg/h , each ) , or sufentanil ( 0.02 & mgr;g/kg/h ) plus dexmedetomidine ( 0.05 & mgr;g/kg/h ) ( Group D2 ) for 72 hours after surgery in this double-blinded , r and omized study . The primary outcome measure was the postoperative sufentanil consumption , whereas the secondary outcome measures were pain intensity ( visual analogue scale ) , requirement of narcotic drugs during the operation , level of sedation , Bruggrmann comfort scale , and concerning adverse effects . The postoperative sufentanil consumption was significantly lower in Groups D1 and D2 than in Group C during the observation period ( P < 0.05 ) , but lower in Group D2 than in Group D1 at 24 , 48 , and 72 hours after surgery ( P < 0.05 ) . The heart rate after intubation and incision was lower in Groups D1 and D2 than in Group C ( P < 0.05 ) . On arrival at the recovery room , Groups D1 and D2 had lower mean blood pressure than Group C ( P < 0.05 ) . The intraoperative requirement of sevoflurane was 30 % lesser in Groups D1 and D2 than in Group C. The sedation levels were greater in Groups D1 and D2 during the first hour ( P < 0.05 ) . Compared with Groups C and D1 , Group D2 showed lower levels of the overall incidence of nausea and vomiting ( P < 0.05).Among the tested PCA options , the addition of dexmedetomidine ( 0.05 & mgr;g/kg/h ) and sufentanil ( 0.02 & mgr;g/kg/h ) showed better analgesic effect and greater patient satisfaction without other clinical ly relevant side effects for patients undergoing hysterectomy during the first 72 hours after abdominal hysterectomy BACKGROUND Few studies have investigated the use of dexmedetomidine in obstetric anaesthesia . OBJECTIVE To evaluate the effect of dexmedetomidine combined with sufentanil for patient-controlled analgesia ( PCA ) after caesarean section under spinal anaesthesia . DESIGN An interventional , r and omised , double-blinded , placebo-controlled clinical study . SETTING Department of Anaesthesiology , Obstetrics and Gynecology Hospital of Fudan University , Shanghai , China . PATIENTS One hundred and twenty parturients ( American Society of Anesthesiologists class 1 or 2 ) scheduled for elective caesarean delivery under spinal anaesthesia r and omly allocated into three groups ( n = 40 each ) . INTERVENTIONS Group 1 : physiological saline bolus after delivery and sufentanil PCA , Group 2 : dexmedetomidine bolus ( 0.5 & mgr;g kg−1 ) after delivery and sufentanil PCA , Group 3 : dexmedetomidine bolus ( 0.5 & mgr;g kg−1 ) after delivery and sufentanil with dexmedetomidine PCA ( background infusion of 0.045 & mgr;g kg−1 h−1 with a bolus of 0.07 & mgr;g kg−1 ) . MAIN OUTCOME MEASURES The total consumption of sufentanil . Pain scores at rest evaluated with a visual analogue scale ( VAS ) and Ramsay sedation score ( RSS ) were recorded at the 4 , 8 and 24 h after surgery . The patients ’ pain threshold ( PTh ) and pain tolerance threshold ( PTTh ) were measured before surgery and 1 h after initial study drug administration . Satisfaction scores were collected 24 h after surgery . RESULTS Sufentanil consumption in group 3 was 43.9 ± 19.2 & mgr;g , significantly lower than in group 1 ( 54.5 ± 23.9 & mgr;g ) and group 2 ( 56.3 ± 20.6 & mgr;g ) ( P < 0.05 ) . Compared with group 3 , VAS was increased at 4 , 8 and 24 h after surgery in groups 1 and 2 ( P < 0.05 ) ; there was no difference between groups 1 and 2 . PTh and PTTh were significantly increased 1 h after drug administration in groups 2 ( 1.59 ± 0.45 , 2.57 ± 0.46 mA ) and 3 ( 1.74 ± 0.37 , 2.56 ± 0.48 mA ) compared with group 1 ( 1.49 ± 0.49 , 2.42 ± 0.62 mA ) ( P < 0.05 ) . CONCLUSION The combination of sufentanil and dexmedetomidine for PCA after caesarean section can reduce sufentanil consumption and improve parturients ’ satisfaction compared with sufentanil PCA alone . TRIAL REGISTRATION ChiCTR-TRC-11001442 OBJECTIVE To investigate if the addition of dexmedetomidine to meperidine in a patient-controlled analgesia ( PCA ) device would reduce postoperative meperidine consumption when compared with meperidine alone . METHODS Forty patients scheduled for elective abdominal surgery under general anesthesia in Suleyman Demirel University Medical School , Isparta , Turkey between February and September 2006 , were r and omly allocated into 2 groups . Group I : meperidine 0.25 mg kg-1 intravenous bolus and dexmedetomidine 0.5 mcg kg-1 in 50 ml of saline solution infusion before the end of surgery . Group II : meperidine 0.25 mg kg-1 intravenous bolus and 50 ml of saline solution infusion . In the postanesthesia care unit ( PACU ) patients in both groups received intravenous meperidine 10 mg with 5-minutes intervals until the patient`s verbal pain score is lower than 2 . Patients in both groups received PCA during the 24 hours after surgery ( meperidine 5 mg + dexmedetomidine 10 mcg bolus for group I , meperidine 5 mg for group II ) . The verbal rating score of pain and meperidine requirement is recorded during PACU stay . Meperidine consumption with PCA is recorded until 24 hours postoperatively . RESULTS Verbal rating score of pain in the PACU was lower in group I than group II ( p<0.05 ) . Meperidine consumption was lower in group I than group II during the PACU stay and until 24 hours postoperatively ( p<0.01 ) . CONCLUSION When compared with meperidine PCA , meperidine-dexmedetomidine PCA reduces postoperative meperidine consumption OBJECTIVE To investigate the effect of a continuous infusion of low-dose dexmedetomidine on patient-controlled analgesia ( PCA ) with fentanyl in elderly patients after total hip replacement . METHODS Forty patients ( ASA I-II ) aged 66 - 81 years after total hip replacement were r and omized equally into the control and test groups . The patients in the test group received continuous infusion of dexmedetomidine at the rate of 0.2 µg·kg(-1)·h(-1 ) from the beginning to the end of PCA with fentanyl after the surgery , while those in the control group received normal saline . The cumulative fentanyl dose , VAS pain scores and Ramsay sedation score were recorded at 0 , 4 , 8 , 12 and 24 h after the surgery . RESULTS All the patients in the two groups reported good pain relief and none needed additional fentanyl . The VAS pain score was significantly lower ( P<0.05 or 0.01 ) , while the Ramsay sedation scores higher ( P<0.05 ) in the test group than in the control group . The cumulative fentanyl dose was significantly lower in the test group ( P<0.05 or 0.01 ) . The incidence of such adverse effects as nausea and vomiting was significantly lower in the test group ( P<0.05 ) . CONCLUSION PCA with fentanyl combined with low-dose dexmedetomidine infusion is safe for elderly patients , and can decrease fentanyl consumption and improve the effect of PCA with fentanyl OBJECTIVE To investigate the effect of the combination of oxycodone and dexmedetomidine for patient-controlled analgesia ( PCA ) after video-assisted thoracoscopic ( VATS ) lobectomy . DESIGN A prospect i ve , r and omized , double-blind , controlled trial . SETTING Sh and ong Cancer Hospital and Institute in Jinan , China . PARTICIPANTS Eighty-four patients with lung cancer undergoing VATS lobectomies were recruited . INTERVENTIONS Patients were r and omly assigned to one of the following two groups : oxycodone and dexmedetomidine ( group OD ) or oxycodone alone ( group O ) . Before induction of anesthesia , patients in group OD received 0.5 μg/kg , dexmedetomidine diluted to 20 mL with physiologic saline and infused for 10 minutes intravenously . The PCA protocol was 50 mg of oxycodone and 0.05 μg/kg/h dexmedetomidine diluted to 100 mL. Patients in group O received 20 mL of physiologic saline infused for 10 minutes . Their PCA protocol consisted of 50 mg of oxycodone diluted to 100 mL. Intravenous PCA was used for postoperative analgesia ( lasting for 48 h ) . MEASUREMENTS AND MAIN RESULTS Pain at rest and during movement was assessed by a blinded observer using the Visual Analog Scale pain score ( VAS ) at 4 , 6 , 24 , and 48 hours after surgery , and the level of sedation simultaneously was assessed using the Ramsay Sedation Scale . Total oxycodone consumption , requirements for rescue analgesia , side effects , and satisfaction with pain management were recorded within 48 hours after surgery . Eighty patients ' data were analyzed at the end of the study ( 40 in each group ) . Visual Analog Scale scores decreased at 4 , 6 , and 24 hours at rest and during movement in group OD compared with group O ( p<0.05 ) . The level of patient satisfaction in group OD was significantly higher than that in group O ( p<0.05 ) . Oxycodone consumption in group OD was significantly lower than that in group O ( p<0.001 ) . Group O experienced more nausea and vomiting 6 hours after surgery than did group OD ( p < 0.05 ) . CONCLUSION The combination of oxycodone and dexmedetomidine for PCA after VATS lobectomy can reduce oxycodone consumption , improve patient satisfaction , and provide better analgesia with fewer side effects ( nausea and vomiting ) compared with PCA with oxycodone alone Background : Dexmedetomidine is an alpha2 -adrenergic agonist with sedative and analgesic properties . This study aim ed to investigate if the use of a continuous dexmedetomidine infusion with i.v . morphine patient-controlled analgesia ( PCA ) could improve postoperative analgesia while reducing opioid consumption and opioid-related side effects . Methods : In this prospect i ve r and omized , double-blinded , controlled study , 39 patients with obstructive sleep apnea syndrome undergoing uvulopalatopharyngoplasty were assigned to two groups . Group D ( dexmedetomidine group ) received a loading dose of dexmedetomidine 1 μg.kg-1 i.v . , 30 minutes before the anticipated end of surgery , followed by infusion at 0.6 μg.kg-1 h-1 for 24 hours . Group P ( placebo group ) received a bolus and infusion of placebo . In both groups , postoperative pain was initially controlled by i.v . morphine titration and then PCA with morphine . Cumulative PCA morphine consumption , pain intensities , sedation scores , cardiovascular and respiratory variables and opioid-related adverse effects were recorded for 48 hours after operation . Results : Compared with placebo group , patients in the dexmedetomidine group required 52.7 % less PCA morphine during the first 24 hours postoperatively , with significantly better visual analogue scale scores , less incidence of respiratory obstruction ( 5 vs. 12 patients , respectively ; P = .037 ) and longer time to first analgesic request ( 21 ( 11 ) vs. 9 ( 4 ) minutes ; P = .002 ) . Fewer patients in group D experienced nausea and vomiting than those in group P ( 7 vs. 24 patients , respectively ; P < .05 ) . Conclusion : Continuous dexmedetomidine infusion may be a useful analgesic adjuvant for patients susceptible to opioid-induced respiratory depression OBJECTIVE To observe the effect of postoperative analgesia with dexmedetomidine on the survival rate of amputated finger replantation . METHODS 91 cases , who was going to receive amputated finger replantation , were r and omly divided into group A ( n = 48 ) and B ( n = 43 ) . PCIA ( patient-controlled intravenous analgesia ) was set immediately after operation in group A ( fentanyl 1.0 mg + tropisetron 4.0 mg + 10 mg + dexmedetomidine 200 microg + saline 100 ml ) and group B ( same as group A except dexmedetomidine ) . Background infusion is 2 ml/h with a bolous of 0.5 ml and lockout time is 15 min . postoperative VAS score , Ramsay score , condition of replanted fingers and other adverse events at the 0 - 6 h , 6 - 12 h , 12 - 24 h and 24 - 48 h were recorded and analyzed . RESULTS The age , sex , height , weight , amputated time ( Ts ) , revascularized time ( Tt ) in the two groups were not statistically different ( P > 0.05 ) . Postoperative VAS score in the two groups was significantly different at the 0 - 6 h , 6 - 12 h , 12 - 24 h and 24 - 48 h ( P < 0.05 ) , but Ramsay score was not ( P > 0.05 ) . The highest and lowest postoperative VAS score and Ramsay score were markedly different between two groups ( P < 0.05 ) . 3 of the 60 fingers in group A experienced vascular crisis and 2 underwent vascular explore surgery . 13 of 56 fingers in group B occurred vascular crisis , and 10 underwent vascular explore surgery , showing significant difference between the two groups ( P < 0.05 ) . PCIA adverse reactions showed no difference between the two groups ( P > 0.05 ) . Bradycardia and hypotension did n't happen in any patients in the two groups . 4 weeks after surgery , the survival rate was 96.7 % ( 58/60 ) in group A , and 83.9 % ( 47/56 ) in group B ( P < 0.05 ) . CONCLUSION Postoperative analgesia with dexmedetomidine as an adjuvant can increase the survival rate of replantation fingers with high safety Patients undergoing a lateral thoracotomy for pulmonary resection have moderate to severe pain postoperatively that is often treated with opioids . Opioid side effects such as respiratory depression can be devastating in patients with already compromised respiratory function . This prospect i ve double-blinded clinical trial examined the analgesic effects and safety of a dexmedetomidine infusion for postthoracotomy patients when administered on a telemetry nursing floor , 24 to 48 hours after surgery , to determine if the drug 's known early opioid-sparing properties were maintained . Thirty-eight thoracotomy patients were administered dexmedetomidine intraoperatively and overnight postoperatively and then r and omized to receive placebo or dexmedetomidine titrated from 0.1 to 0.5 μg·kg·h−1 the day following surgery for up to 24 hours on a telemetry floor . Opioids via a patient-controlled analgesia pump were available for both groups , and vital signs including transcutaneous carbon dioxide , pulse oximetry , respiratory rate , and pain and sedation scores were monitored . The dexmedetomidine group used 41 % less opioids but achieved pain scores equal to those of the placebo group . The mean heart rate and systolic blood pressure were lower in the dexmedetomidine group but sedation scores were better . The mean respiratory rate and oxygen saturation were similar in the two groups . Mild hypercarbia occurred in both groups , but periods of significant respiratory depression were noted only in the placebo group . Significant hypotension was noted in one patient in the dexmedetomidine group in conjunction with concomitant administration of a beta-blocker agent . The placebo group reported a higher number of opioid-related adverse events . In conclusion , the known opioid-sparing properties of dexmedetomidine in the immediate postoperative period are maintained over 48 hours BACKGROUND Dexmedetomidine , an & agr;2 adrenergic receptor agonist , has analgesic , sedative and sympatholytic properties , with a lack of respiratory depression . It is licensed only for intensive care sedation . OBJECTIVE The objective of this study is to investigate whether intravenous ( i.v . ) patient-controlled analgesia ( PCA ) with dexmedetomidine added to a fentanyl-based drug mixture could reduce postoperative nausea and vomiting ( PONV ) in highly susceptible patients undergoing lumbar spinal surgery . DESIGN A r and omised , double-blinded study . SETTING At a tertiary university hospital between September 2012 and September 2013 . PATIENTS One hundred and eight patients undergoing level 1 or 2 posterior lumbar spinal fusion who had at least three risk factors for PONV ( female , nonsmoker , use of postoperative opioids ) were r and omised into two groups . Three patients were excluded from analysis and 105 patients completed the study . METHODS Patients received either dexmedetomidine 0.5 & mgr;g kg−1 i.v . ( dexmedetomidine group ) or 0.9 % normal saline ( control group ) 30 min before the completion of surgery followed by fentanyl 0.5 & mgr;g kg−1 and 4 mg ondansetron . Postoperatively , the PCA ( fentanyl 10 & mgr;g kg−1 with 120 mg ketorolac , with or without dexmedetomidine 10 & mgr;g kg−1 made up to a total volume of 100 ml ) was programmed to deliver 1 ml bolus ( lockout 15 min ) with a continuous background infusion of 2 ml h−1 . The PCA was used for the first 48 h postoperatively . MAIN OUTCOME MEASURES The incidence and severity of PONV , cumulative dose of PCA fentanyl consumed and pain scores were assessed for 48 h. RESULTS The dexmedetomidine group experienced less nausea during the time interval 1 to 3 h postoperatively compared with the control group [ odds ratio ( OR ) 0.32 ; 95 % confidence interval ( CI ) 0.13 to 0.77 ; P = 0.019 ] . The intensity of nausea between the groups during the first 48 h was comparable , but the dexmedetomidine group had a lower incidence of moderate to severe nausea ( OR 0.28 ; 95 % CI 0.12 to 0.67 ; P < 0.003 ) . Pain scores were not significantly different between the groups , but patients in the dexmedetomidine group required less fentanyl and less rescue analgesia in the first 12 h. Compared with the control group , patients in the dexmedetomidine group experienced almost twice as many episodes of hypotension and bradycardia , but this failed to reach statistical significance . CONCLUSION Adding dexmedetomidine to a fentanyl-based PCA drug mixture reduces the frequency and severity of acute postoperative nausea in highly susceptible patients . TRIAL REGISTRATION Clinical trials.gov identifier : NCT01840254 OBJECTIVE To explore the effect of patient-controlled intravenous analgesia ( PCIA ) with dexmedetomidine and sufentanil on early postoperative cognition in elderly patients after spine surgery . METHODS One hundred fifty-two patients aged more than 60 yr with ASA I-III undergoing elective spine surgery were r and omly assigned into two groups : Group S received PCIA with only sufentanil ( n=77 ) ; Group D received PCIA with dexmedetomidine and sufentanil ( n=75 ) . The severity of pain at rest and upon movement was measured at 1 , 2 , 6 , 12 , 24 and 48 h after surgery using the 11-point numerical rating scale ( NRS ) . Delirium was assessed daily within three days after surgery via the confusion assessment method . Cognitive function was measured at the day before surgery and at one week after surgery using a battery of neuropsychologic tests including Digit Span ( forward and backward ) subtests and Visual Retention and Paired Associate Verbal Learning subtests of Wechsler Memory Scale , Stroop Color Word Interference Test , Digit Symbol Substitution subtest of Wechsler Adult Intelligence Scale ( DSST ) and Trail Making Test ( Part A ) . RESULTS The NRS scores at rest and upon movement at 6 to 48 h after surgery were lower in Group D than those in Group S ( P<0.05 ) . Postoperative delirium ( POD ) was present in 8 ( 10.4 % ) patients in Group S and 3 ( 4.0 % ) patients in Group D ( χ2=4.206 , P>0.05 ) . Two patients with POD in Group S were treated with risperidone . Postoperative cognitive dysfunction ( POCD ) was present in 15 ( 19.5 % ) patients in Group S and 6 ( 8.0 % ) patients in Group D ( χ2=4.206 , P<0.05 ) . Compared with the preoperative baselines , the scores of Digit Span backward , Visual Retention and DSST were significantly lower ( 3.7±1.3 vs 4.1±1.1 , 7.7±2.0 vs 8.8±1.8 , 25.2±7.8 vs 28.2±7.6 ; t=2.132 , 3.585 , 2.427 , respectively , P<0.05 ) and the time to complete Stroop test was significantly longer in Group S ( 56.9±14.8 vs 50.2±14.7 , t=-2.822 , P<0.05 ) , while only the score of Digit Span backward was significantly lower in Group D ( 3.6±1.2 vs 4.0±1.2 , t=2.144 , P<0.05 ) . CONCLUSION Dexmedetomidine combined with sufentanil in postoperative PCIA can result in superior analgesia and improve early postoperative cognitive function |
13,497 | 18,554,422 | Conclusion Our meta- analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension | Background Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level .
Animal studies have suggested that garlic reduces blood pressure , but primary studies in humans and non- systematic review s have reported mixed results .
With interest in complementary medicine for hypertension increasing , it is timely to up date a systematic review and meta- analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure . | AIM To evaluate a hypotensive action of long-acting garlic powder tablets allicor in patients with mild or moderate hypertension and to compare allicor effects with those of foreign analog -- kwai garlic tablets . MATERIAL AND METHODS A double-blind , r and omized and placebo-controlled study enrolled 85 patients with mild or moderate hypertension . The patients were divided into 4 groups : group 1 received allicor in a dose 600 mg/day , group 2 - -2400 mg/day , group 3 - -kwai in a dose 900 mg/day , group 4 - -placebo . RESULTS Allicor produced reaction in both systolic and diastolic pressure . An increase of allicor daily dose to 2400 mg does not provide an additional hypotensive effect . Kwai results in only systolic but not diastolic arterial pressure lowering . CONCLUSION Allicor is more effective than kwai in reduction of diastolic blood pressure . It can be recommended as a hypotensive treatment in mild and moderate arterial hypertension This study examined the effects of garlic and fish-oil supplementation ( alone and in combination ) on fasting serum lipids and lipoproteins in hypercholesterolemic subjects . After an initial run-in phase , 50 male subjects with moderate hypercholesterolemia were r and omly assigned for 12 wk to one of four groups : 1 ) 900 mg garlic placebo/d + 12 g oil placebo/d ; 2 ) 900 mg garlic/d + 12 g oil placebo/d ; 3 ) 900 mg garlic placebo/d + 12 g fish oil/d , providing 3.6 g n-3 fatty acids/d ; and 4 ) 900 mg garlic/d + 12 g fish oil/d . In the placebo group , mean serum total cholesterol , low-density-lipoprotein cholesterol ( LDL-C ) , and triacylglycerols were not significantly changed in relation to baseline . Mean group total cholesterol concentrations were significantly lower with garlic+fish oil ( -12.2 % ) and with garlic ( -11.5 % ) after 12 wk but not with fish oil alone . Mean LDL-C concentrations were reduced with garlic+fish oil ( -9.5 % ) and with garlic ( -14.2 % ) but were raised with fish oil ( + 8.5 % ) . Mean triacylglycerol concentrations were reduced with garlic+fish oil ( -34.3 % ) and fish oil alone ( -37.3 % ) . The garlic groups ( with and without fish oil ) had significantly lower ratios of total cholesterol to high-density-lipoprotein cholesterol ( HDL-C ) and LDL-C to HDL-C. In summary , garlic supplementation significantly decreased both total cholesterol and LDL-C whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentrations in hypercholesterolemic men . The combination of garlic and fish oil reversed the moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil was well-tolerated and had a beneficial effect on serum lipid and lipoprotein concentrations by providing a combined lowering of total cholesterol , LDL-C , and triacylglycerol concentrations as well as the ratios of total cholesterol to HDL-C and LDL-C to A double-blind crossover study comparing the effect of aged garlic extract with a placebo on blood lipids was performed in a group of 41 moderately hypercholesterolemic men [ cholesterol concentrations 5.7 - 7.5 mmol/L ( 220 - 290 mg/dL ) ] . After a 4-wk baseline period , during which the subjects were advised to adhere to a National Cholesterol Education Program Step I diet , they were started on 7.2 g aged garlic extract per day or an equivalent amount of placebo as a dietary supplement for a period of 6 mo , then switched to the other supplement for an additional 4 mo . Blood lipids , blood counts , thyroid and liver function measures , body weight , and blood pressure were followed over the entire study period . The major findings were a maximal reduction in total serum cholesterol of 6.1 % or 7.0 % in comparison with the average concentration during the placebo administration or baseline evaluation period , respectively . Low-density-lipoprotein cholesterol was also decreased by aged garlic extract , 4 % when compared with average baseline values and 4.6 % in comparison with placebo period concentrations . In addition , there was a 5.5 % decrease in systolic blood pressure and a modest reduction of diastolic blood pressure in response to aged garlic extract . We conclude that dietary supplementation with aged garlic extract has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects The efficacy and tolerance of a garlic preparation ( Sapec , Kwai ) was investigated in a r and omized double-blind study vs. bezafibrate . This multi-centre study was conducted in 5 general medical practice s and involved 98 patients with primary hyperlipoproteinaemia . The daily doses of the active substances were 900 mg of garlic powder ( st and ardized as to 1.3 % alliin ) and 600 mg of bezafibrate , respectively . The pre-phase with placebo lasted 6 weeks , the treatment period covered 12 weeks . All patients were advised to observe a low-fat " step-1 diet " for the duration of the study . The 98 case report forms allowed the statistical evaluation of total cholesterol , HDL cholesterol and triglyceride levels for 94 patients , and of LDL cholesterol values for 92 patients . In the course of the treatment both study medications caused a statistically highly significant reduction in total cholesterol , in LDL cholesterol and triglycerides , and an increase in HDL cholesterol . However , there was no significant difference in the efficacies of both medication groups . Side effects were mentioned by 5 patients each in both treatment groups , none of which led to the withdrawal of the patients . Concerning the garlic preparation , there was no correlation between the perception of garlic odour and the influence on the cholesterol level BACKGROUND Prehypertension is considered a precursor of stage 1 hypertension and a predictor of excessive cardiovascular risk . We investigated whether pharmacologic treatment of prehypertension prevents or postpones stage 1 hypertension . METHODS Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower , or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg , were r and omly assigned to receive two years of c and esartan ( Atac and , AstraZeneca ) or placebo , followed by two years of placebo for all . When a participant reached the study end point of stage 1 hypertension , treatment with antihypertensive agents was initiated . Both the c and esartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial . RESULTS A total of 409 participants were r and omly assigned to c and esartan , and 400 to placebo . Data on 772 participants ( 391 in the c and esartan group and 381 in the placebo group ; mean age , 48.5 years ; 59.6 percent men ) were available for analysis . During the first two years , hypertension developed in 154 participants in the placebo group and 53 of those in the c and esartan group ( relative risk reduction , 66.3 percent ; P<0.001 ) . After four years , hypertension had developed in 240 participants in the placebo group and 208 of those in the c and esartan group ( relative risk reduction , 15.6 percent ; P<0.007 ) . Serious adverse events occurred in 3.5 percent of the participants assigned to c and esartan and 5.9 percent of those receiving placebo . CONCLUSIONS Over a period of four years , stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension ( the placebo group ) . Treatment of prehypertension with c and esartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period . Thus , treatment of prehypertension appears to be feasible . ( Clinical Trials.gov number , NCT00227318 . ) OBJECTIVE To determine whether garlic extract therapy is efficacious and safe in children with hypercholesterolemia . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING Specialized pediatric lipid disorders ambulatory clinic . PARTICIPANTS Thirty pediatric patients , aged 8 to 18 years , who had familial hyperlipidemia and a minimum fasting total cholesterol level greater than 4.8 mmol/L ( > 185 mg/dL ) . INTERVENTION An 8-week course of a commercially available garlic extract ( Kwai [ Lichtwer Pharma , Berlin , Germany ] , 300 mg , 3 times a day ) or an identical placebo . MAIN OUTCOME MEASURES Absolute and relative changes in fasting lipid profile parameters . RESULTS The groups were equivalent at baseline and compliance was similar in the 2 groups ( P = .45 ) . There was no significant relative attributable effect of garlic extract on fasting total cholesterol ( + 0.6 % [ 95 % confidence interval , -5.8 % to + 6.9%1 ) or low-density lipoprotein cholesterol ( -0.5 % [ 95 % confidence interval , -8.7 % to + 7.6 % ] ) . The lower limits of the confidence intervals did not include -10 % , the minimum relative attributable effect believed to be clinical ly important . Likewise , no significant effect was seen on the levels of high-density lipoprotein , triglycerides , apolipoprotein B-100 , lipoprotein ( a ) , fibrinogen , homocysteine , or blood pressure . There was a small effect on apolipoprotein A-I ( + 10.0 % [ 95 % confidence interval , + 1.2 % to + 16.5 % ] P=.03 ) . There were no differences in adverse effects between groups . CONCLUSION Garlic extract therapy has no significant effect on cardiovascular risk factors in pediatric patients with familial hyperlipidemia PURPOSE To assess the effects of st and ardized garlic powder tablets on serum lipids and lipoproteins , glucose , and blood pressure . SUBJECTS AND METHODS Forty-two healthy adults ( 19 men , 23 women ) , mean age of 52 + /- 12 years , with a serum total cholesterol ( TC ) level of greater than or equal to 220 mg/dL received , in a r and omized , double-blind fashion , either 300 mg three times a day of st and ardized garlic powder in tablet form or placebo . Diets and physical activity were unchanged . This study was conducted in an outpatient , clinical research unit . RESULTS The baseline serum TC level of 262 + /- 34 mg/dL was reduced to 247 + /- 40 mg/dL ( p < 0.01 ) after 12 weeks of st and ard garlic treatment . Corresponding values for placebo were 276 + /- 34 mg/dL before and 274 + /- 29 mg/dL after placebo treatment . Low-density lipoprotein cholesterol ( LDL-C ) was reduced by 11 % by garlic treatment and 3 % by placebo ( p < 0.05 ) . There were no significant changes in high-density lipoprotein cholesterol , triglycerides , serum glucose , blood pressure , and other monitored parameters . CONCLUSIONS Treatment with st and ardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo . The garlic formulation was well tolerated without any odor problems The ingestion of garlic has been reported to have many cardiovascular effects , including a reduction in plasma cholesterol concentration and the susceptibility of LDL to oxidation . A double-blind , placebo-controlled , r and omised crossover study was conducted in subjects with mild to moderate hypercholesterolaemia who were subject to strict dietary supervision and assessment . After a baseline dietary period of 28 days , subjects took Kwai garlic powder tablets 300 mg three times daily or matching placebo for 12 weeks , followed by 28 days washout , followed by a 12 weeks crossover on the alternative preparation . In the analysis hypercholesterolaemia was defined as those subjects in the range 5.5 - 8.05 mmol/l . Three subjects were withdrawn , one allocated to garlic and complaining of garlic body odour , one using placebo having intercurrent health problems , and one with a baseline cholesterol below 5.5 mmol/l , yielding analysable results in 28 subjects . Comparing the period on garlic with that on placebo , there were no significant differences in plasma cholesterol , LDL cholesterol , HDL cholesterol , plasma triglycerides , lipoprotein(a ) concentrations , or blood pressure . Mean LDL cholesterol concentration was 4.64 + /- 0.52 mmol/l on garlic and 4.60 + /- 0.59 mmol/l on placebo . There was no demonstrable effect of garlic on oxidisability of LDL , on the ratio of plasma lathosterol/cholesterol ( a measure of cholesterol synthesis ) , nor on LDL receptor expression in lymphocytes . This study found no demonstrable effect of garlic ingestion on lipids and lipoproteins Summary For the first time , a weak clinical efficacy of a 12-week therapy with garlic powder ( daily dose , 800 mg ) is demonstrated in patients with peripheral arterial occlusive disease stage II . The increase in walking distance in the verum group by 46 m ( from 161.0 ± 65.1 to 207.1 ± 85.0 m ) was significantly higher ( P<0.05 ) than in the placebo group ( by 31 m , from 172.0 ± 60.9 to 203.1 ± 72.8 ) . Both groups received physical therapy twice a week . The diastolic blood pressure , spontaneous thrombocyte aggregation , plasma viscosity , and cholesterol concentration also decreased significantly . Body weight was maintained . It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment , connected with a simultaneous decrease in spontaneous thrombocyte aggregation . Therefore , garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication A double-blind study of 40 hypercholesterolaemic out- patients was carried out over a period of four months to examine the effects of a garlic powder preparation*. The drug group received 900 mg garlic powder per day , equivalent to 2,700 mg of fresh garlic . During the therapy , the drug group showed significantly lower total cholesterol , triglycerides and blood pressure than those of the placebo group . In addition , results of a self-evaluation question naire indicated that patients in the drug group had a greater feeling of ' well-being ' Recent studies have cast doubt on the proposed lipid-lowering and blood pressure-lowering effects of garlic . We tested the effect of dried garlic ( Allium sativum ) powder on blood lipids , blood pressure and arterial stiffness in a 12-week r and omised , double-blind , placebo-controlled trial . Seventy-five healthy , normo-lipidaemic volunteers ( men and women aged 40 - 60 years ) were assigned to dried garlic powder tablets ( 10.8 mg alliin ( 3-(2-propenylsulfinyl)-L-alanine)/d , corresponding to about three garlic cloves ) or placebo . Sixty-two subjects were eligible for the per- protocol analysis . The primary outcome measure was serum total cholesterol concentration . Secondary outcome measures were LDL-cholesterol , HDL-cholesterol and triacylglycerol concentrations , blood pressure and arterial stiffness ( assessed by pulse wave velocity ) . No significant differences between the garlic and placebo groups were detected for any of the outcome measures . However , garlic powder was associated with a near-significant decrease ( 12 % ) in triacylglycerol concentration ( P=0.07 ) . In conclusion , garlic powder tablets have no clinical ly relevant lipid-lowering and blood pressure-lowering effects in middle-aged , normo-lipidaemic individuals . The putative anti-atherosclerotic effect of garlic may be linked to risk markers other than blood lipids Clinical trials have shown that garlic can reduce elevated blood cholesterol levels . No information , however , exist on its effects on normal lipid patterns . Therefore a r and omised , double-blind , placebo-controlled trial was conducted to determine the effects on blood lipids of 15 weeks ' medication of garlic ( 600 mg dried garlic powder per day , Kwai , Lichtwer Pharma Berlin , st and ardised on 1.3 % allicin ) in 68 normal volunteers . During a two week " wash-out " period all measurements were stable . There was a significant drop ( from 223 to 214mg/dl ) in total cholesterol after 10 weeks ' medication , triglycerides decreased numerically ( from 124 to 118mg/dl ) without reaching the level of significance . Blood pressure remained constant throughout . No changes occurred in the placebo group . It is concluded that the medication of garlic induces changes in blood lipids , even if these variables had been normal to start with Significant positive effects could be achieved in a placebo-controlled double-blind study through the administration of 800 mg of garlic powder over a period of four weeks . Spontaneous thrombocyte aggregation disappeared , the microcirculation of the skin increased by 47.6 % ( from 0.63 + /- 0.13 to 0.93 + /- 0.22 mm/s ) , plasma viscosity decreased by 3.2 % ( from 1.25 + /- 0.34 to 1.21 + /- 0.43 mPas ) , diastolic blood pressure by 9.5 % ( from 74 + /- 9 to 67 + /- 5 mmHg ) , and blood glucose concentration by 11.6 % ( from 89.4 + /- 8.8 to 79.0 + /- 11.9 mg/dl ) . The vascular protection of garlic as atherosclerosis prevention by influencing the mentioned risk parameters for cardiovascular diseases must be pointed out . Especially interesting is the thrombocyte aggregation inhibiting effect . Thus , the application of garlic may be useful in case of acetylsalicyclic acid intolerance Forty-seven non-hospitalised patients with mild hypertension took part in a r and omised , placebo-controlled , double-blind trial conducted by 11 general practitioners . The patients who were admitted had diastolic blood pressures between 95 and 104 mmHg after a two-week acclimatization phase . The patients then took either a preparation of garlic powder ( Kwai ) or a placebo of identical appearance for 12 weeks . Blood pressure and plasma lipids were monitored during treatment after four , eight and 12 weeks . Significant differences between the placebo and the drug group were found during the course of therapy . For example , the supine diastolic blood pressure in the group having garlic treatment fell from 102 to 91 mmHg after eight weeks ( p less than 0.05 ) and to 89 mmHg after 12 weeks ( p less than 0.01 ) . The serum cholesterol and triglycerides were also significantly reduced after eight and 12 weeks of treatment . In the placebo group , on the other h and , no significant changes occurred Most trials of bulb garlic and garlic powder tablets indicate reduced coronary heart disease ( CHD ) risk in elevated-risk subjects . Most persons taking garlic supplements lack overt risk of CHD . However , no trials have tested steam-distilled garlic oil ( GO ) capsules with healthy subjects . The objectives of the present r and omized , double-blind , placebo-controlled study were to determine whether GO capsules reduce CHD risk in trained male runners . Twenty-seven volunteers ( mean age , 28.8 years ) completed the study . Each took 12.3 mg/day GO ( or placebo ) capsules for 16 weeks . Main outcome measures were 95 % confidence intervals ( CIs ) between GO and placebo groups for differences in changes of blood pressure ( BP ) , plasma lipids , total antioxidant status ( TAS ) , low-density lipoprotein ( LDL ) composition and blood clotting factors . Principal results as mean differences ( 95 % CI ) between GO and placebo are : pulse , 2.9 beats/min ( −0.8 to 6.7 ) , P= 0.12 ; systolic BP , −4.5 mmHg ( −10.8 to 1.9 ) , P= 0.16 ; plasma total cholesterol , 0.01 mmol/l ( −0.34 to 0.37 ) , P= 0.95 ; plasma triglycerides , −0.20 mmol/l ( −0.43 to 0.03 ) , P= 0.09 ; plasma TAS , 45 μmol Trolox equivalent/l ( −35 to 124 ) , P= 0.26 ; LDL density , 0.0019 g/ml ( −0.0005 to 0.0043 ) , P= 0.12 ; LDL triglycerides/protein , −0.078 mg/mg ( −0.149 to −0.007 ) , P= 0.03 ; LDL cholesterol/protein , −0.24 mg/mg ( −0.69 to 0.22 ) , P= 0.3 ; LDL TAS/triglycerides , 29 nmol/mg ( 11 , 68 ) , P= 0.15 ; prothrombin time , 0.99 s ( −0.36 to 2.35 ) , P= 0.14 ; partial thromboplastin time , 3.0 s ( −1.0 to 7.1 ) , P= 0.13 . Results were null statistically . Trends with GO were mostly towards lower CHD risk , and a larger study ( ~150 subjects ) is required to test their validity The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics . Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal |
13,498 | 27,350,573 | CONCLUSION Compared with cTACE , DEB-TACE therapy significantly improved 1- , 2- , and 3-year OS rates and the 1- and 2-year RFS rates | BACKGROUND AND OBJECTIVES Transcatheter arterial chemoembolization ( TACE ) is the first-line treatment for unresectable hepatocellular carcinoma ( HCC ) .
It consists of conventional TACE ( cTACE ) and drug-eluting beads TACE ( DEB-TACE ) .
The comparative outcomes of the two methods remain controversial .
The study aim to research the optimal TACE strategy for unresectable HCC . | PURPOSE To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead ( DEB ) transarterial chemoembolization in hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Patients with unresectable HCC unsuitable for ablative therapies were r and omly assigned to undergo conventional or DEB chemoembolization . The primary endpoints of the study were safety , toxicity , and tumor response at 1 month . Secondary endpoints were number of repeated chemoembolization cycles , time to recurrence and local recurrence , time to radiologic progression , and survival . RESULTS In total , 67 patients ( mean age , 70 y ± 7.7 ) were evaluated . Mean follow-up was 816 days ± 361 . Two periprocedural major complications occurred ( 2.9 % ) that were treated by medical therapy without the need for other interventions . A significant increase in alanine aminotransferase levels 24 hours after treatment was reported , which was significantly greater after conventional chemoembolization ( n = 34 ) than after DEB chemoembolization ( n = 33 ; preprocedure , 60 IU ± 44 vs 74 IU ± 62 , respectively ; at 24 h , 216 IU ± 201 vs 101 IU ± 89 , respectively ; P = 0.007 ) . No other differences were observed in liver toxicity between groups . At 1 month , complete and partial tumor response rates were 70.6 % and 29.4 % , respectively , in the conventional chemoembolization group and 51.5 % and 48.5 % , respectively , in the DEB chemoembolization group . No differences were observed between groups in time to recurrence and local recurrence , radiologic progression , and survival . CONCLUSIONS Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes Transcatheter arterial chemoembolization ( TACE ) offers a survival benefit to patients with intermediate hepatocellular carcinoma ( HCC ) . A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge — conventional TACE . Recently , a drug-eluting bead ( DC Bead ® ) has been developed to enhance tumor drug delivery and reduce systemic availability . This r and omized trial compares conventional TACE ( cTACE ) with TACE with DC Bead for the treatment of cirrhotic patients with HCC . Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and /or multinodular , unresectable , N0 , M0 HCCs were r and omized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin . R and omization was stratified according to Child-Pugh status ( A/B ) , performance status ( ECOG 0/1 ) , bilobar disease ( yes/no ) , and prior curative treatment ( yes/no ) . The primary endpoint was tumor response ( EASL ) at 6 months following independent , blinded review of MRI studies . The drug-eluting bead group showed higher rates of complete response , objective response , and disease control compared with the cTACE group ( 27 % vs. 22 % , 52 % vs. 44 % , and 63 % vs. 52 % , respectively ) . The hypothesis of superiority was not met ( one-sided P = 0.11 ) . However , patients with Child-Pugh B , ECOG 1 , bilobar disease , and recurrent disease showed a significant increase in objective response ( P = 0.038 ) compared to cTACE . DC Bead was associated with improved tolerability , with a significant reduction in serious liver toxicity ( P < 0.001 ) and a significantly lower rate of doxorubicin-related side effects ( P = 0.0001 ) . TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease Background To compare the overall survival of patients with hepatocellular carcinoma ( HCC ) who were treated with lipiodol-based conventional transarterial chemoembolization ( cTACE ) with that of patients treated with drug-eluting bead transarterial chemoembolization ( DEB-TACE ) . Methods By an electronic search of our radiology information system , we identified 674 patients that received TACE between November 2002 and July 2013 . A total of 520 patients received cTACE , and 154 received DEB-TACE . In total , 424 patients were excluded for the following reasons : tumor type other than HCC ( n = 91 ) , liver transplantation after TACE ( n = 119 ) , lack of histological grading ( n = 58 ) , incomplete laboratory values ( n = 15 ) , other reasons ( e.g. , previous systemic chemotherapy ) ( n = 114 ) , or were lost to follow-up ( n = 27 ) . Therefore , 250 patients were finally included for comparative analysis ( n = 174 cTACE ; n = 76 DEB-TACE ) . Results There were no significant differences between the two groups regarding sex , overall status ( Barcelona Clinic Liver Cancer classification ) , liver function ( Child-Pugh ) , portal invasion , tumor load , or tumor grading ( all p > 0.05 ) . The mean number of treatment sessions was 4 ± 3.1 in the cTACE group versus 2.9 ± 1.8 in the DEB-TACE group ( p = 0.01 ) . Median survival was 409 days ( 95 % CI : 321–488 days ) in the cTACE group , compared with 369 days ( 95 % CI : 310–589 days ) in the DEB-TACE group ( p = 0.76 ) . In the subgroup of Child A patients , the survival was 602 days ( 484–792 days ) for cTACE versus 627 days ( 364–788 days ) for DEB-TACE ( p = 0.39 ) . In Child B/C patients , the survival was considerably lower : 223 days ( 165–315 days ) for cTACE versus 226 days ( 114–335 days ) for DEB-TACE ( p = 0.53 ) . Conclusion The present study showed no significant difference in overall survival between cTACE and DEB-TACE in patients with HCC . However , the significantly lower number of treatments needed in the DEB-TACE group makes it a more appealing treatment option than cTACE for appropriately selected patients with unresectable HCC Background : Transcatheter arterial chemoembolization ( TACE ) is the st and ard treatment in selected patients with unresectable hepatocellular carcinoma ( HCC ) . Drug-eluting particles are developed to reduce side effects and improve efficacy . We present safety data of a prospect i ve r and omized phase II study with doxorubicin-eluting superabsorbent polymer ( SAP ) microspheres . Material and Methods : We prospect ively included 30 HCC patients with different Barcelona Clinic Liver Cancer ( BCLC ) stages ( A = 3 , B = 19 , C = 8) and r and omly assigned them to receive conventional TACE ( n = 14 ) ( control group ) or doxorubicin-eluting SAP microspheres ( n = 16 ) . The doxorubicin plasma level was assessed at different time points , biochemical analysis was performed , and side effects were reported following the Common Toxicity Criteria . Tumor response was assessed at 6 weeks according to the modified Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria . Results : There was a significantly lower plasma peak concentration ( Cmax ) of doxorubicin and smaller area under the curve ( AUC ) with SAP microspheres ( mean Cmax 495 ± 293.9 ng/ml , mean AUC 69.7 ± 26.9 ng/ml min ) compared to controls ( mean Cmax 1,928 ± 560.8 ng/ml , mean AUC 165 ± 32.3 ng/ml/min ; both p < 0.001 ) . Furthermore , there were less grade 3 and no grade 4 adverse events in the SAP microsphere group . Tumor response was comparable between the groups . Conclusions : TACE with SAP microspheres leads to low plasma levels of the cytotoxic drug and therefore minimizes toxicity compared to conventional TACE Background : Transcatheter arterial chemoembolisation ( TACE ) is the treatment of choice for intermediate stage hepatocellular carcinoma ( HCC ) . Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE ( cTACE ) . The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression ( TTP ) , adverse events ( AEs ) , and 2-year survival . Methods : Patients were r and omised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death . Transcatheter arterial chemoembolisation was repeated ‘ on-dem and ’ . Results : We enrolled 177 patients : 89 underwent DEB-TACE and 88 cTACE . The median number of procedures was 2 in each arm , and the in-hospital stay was 3 and 4 days , respectively ( P=0.323 ) . No differences were found in local and overall tumour response . The median TTP was 9 months in both arms . The AE incidence and severity did not differ between the arms , except for post-procedural pain , more frequent and severe after cTACE ( P<0.001 ) . The 1- and 2-year survival rates were 86.2 % and 56.8 % after DEB-TACE and 83.5 % and 55.4 % after cTACE ( P=0.949 ) . Eastern Cooperative Oncology Group ( ECOG ) , serum albumin , and tumour number independently predicted survival ( P<0.05 ) . Conclusions : The DEB-TACE and the cTACE are equally effective and safe , with the only advantage of DEB-TACE being less post-procedural abdominal pain Objective Lipiodol transcatheter arterial chemoembolization ( TACE ) is widely used to treat hepatocellular carcinoma ( HCC ) . Recently , a drug-eluting bead ( DEB ) has been developed to enhance drug delivery to the tumor and reduce its systemic availability . The purpose of this study was to compare the efficacy and safety of intra-arterial injection of DEB loaded with doxorubicin versus conventional , Lipiodol-based TACE regimens in Asian patients with HCC . Methods The study was design ed as a case – control , single-institution clinical trial . Twenty patients with HCC who received DEB loaded with 50 mg doxorubicin ( ‘ cases ’ ) were matched with 20 patients who had undergone conventional TACE ( ‘ controls ’ ) . The primary efficacy endpoint was tumor response at 1 month according to modified Response Evaluation Criteria in Solid Tumors . The primary safety endpoint was liver toxicity . Results The rate of objective response by modified Response Evaluation Criteria in Solid Tumors was 85 % ( 17 of 20 patients ) in the DEB arm versus 30 % ( six of 20 patients ) in the conventional TACE arm ( P=0.001 ) . Subgroup analyses conducted in patients with large ( > 5 cm ) or multinodular tumor confirmed significantly higher objective response rates in patients receiving DEB as compared with those treated with conventional TACE ( P=0.003 and P=0.005 , respectively ) . At the dose of 50 mg doxorubicin , there was no statistically significant difference in liver toxicity between DEB and conventional TACE ( P>0.05 ) . Conclusion In Asian patients with HCC , transcatheter treatment with DEB loaded with doxorubicin offers a distinct advantage in objective tumor response rate as compared with conventional , Lipiodol-based TACE regimens Chemoembolization with lipiodol ( TACE ) improves survival of selected patients with unresectable hepatocellular carcinoma ( HCC ) , but results in substantial toxicity . To improve treatment tolerance , we conducted this phase II study using doxorubicin-loaded beads ( DC Beads ® ) delivered by selective transcatheter arterial chemoembolization ( DEB-TACE ) . We compared the results with those obtained with TACE in our historical controls . Thirty-five patients were recruited with diagnoses of HCC . Patients received DEB-TACE with doxorubicin loaded on DC Beads . Computed tomography of the upper abdomen was performed one month after DEB-TACE . Historical controls were a group of 70 patients with matched characteristics treated with TACE . After a median follow-up of 14.1 months ( range , 6 - 36 months ) , 22 patients ( 63 % ) had an objective response . There was a statistically significant decrease in liver enzymes ( p<0.001 ) , lactate dehydrogenase , ( p<0.001 ) in DEB-TACE-treated patients compared to TACE-treated patients . DEB-TACE with doxorubicin-loaded DC Beads , a safe and reliable treatment for HCC , leads to decreased toxicity compared to TACE |
13,499 | 17,054,280 | No severe adverse events were judged to be related to RTS , S vaccine , although the frequencies of injection site pain , swelling , arm motion limitation , headache , and malaise were increased in the vaccine groups .
RTS , S vaccine was effective in preventing a significant number of clinical malaria episodes , including good protection against severe malaria in children for 18 months .
No severe adverse events were attributable to the vaccine . | BACKGROUND Vaccines against all stages of the malaria parasite are in development , mainly for Plasmodium falciparum , which causes the most serious form of malaria .
Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream .
OBJECTIVES To assess the efficacy and safety of pre-erythrocytic malaria vaccines against any type of human malaria . | RTS , S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein ( CSP ) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen . It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers . In a recently completed trial in semi-immune Gambian adults , vaccine efficacy against natural infection was 34 % ( 95 % confidence interval = 8 - 53 % , P = 0.014 ) during the malaria season following vaccination . Breakthrough P. falciparum parasites sample d from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes ( csp-th2r and csp-th3r ) to determine if the vaccine conferred a strain-specific effect . The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups . Also , the mean number of genotypes per infection in the RTS , S/AS02 group was not reduced compared with the controls Background Many malaria vaccines are currently in development , although very few have been evaluated for efficacy in the field . Plasmodium falciparum multiple epitope (ME)– thrombospondin-related adhesion protein ( TRAP ) c and i date vaccines are design ed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action . ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen . Two vaccine vectors encoding ME-TRAP , plasmid DNA and modified vaccinia virus Ankara ( MVA ) , when used sequentially in a prime-boost immunisation regime , induce high frequencies of effector T cells and partial protection , manifest as delay in time to parasitaemia , in a clinical challenge model . Methods and Findings A total of 372 Gambian men aged 15–45 y were r and omised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine ( control ) . Of these men , 296 received three doses of vaccine timed to coincide with the beginning of the transmission season ( 141 in the DNA/MVA group and 155 in the rabies group ) and were followed up . Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination . Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season . The primary endpoint was time to first infection with asexual P. falciparum . Analysis was per protocol . DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated . Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group . Vaccine efficacy , adjusted for confounding factors , was 10.3 % ( 95 % confidence interval , −22 % to + 34 % ; p = 0.49 ) . Incidence of malaria infection decreased with increasing age and was associated with ethnicity . Conclusions DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area . But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers , this first generation T cell – inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults In animals , effective immune responses against malignancies and against several infectious pathogens , including malaria , are mediated by T cells . Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally , followed by intradermal recombinant modified vaccinia virus Ankara ( MVA ) , induces high frequencies of interferon (IFN)-γ-secreting , antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen , thrombospondin-related adhesion protein ( TRAP ) . These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone , and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum . Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans ICC-1132 , a recombinant virus-like particle comprising of a modified hepatitis B core protein with a B cell ( NANP ) and two T cell epitopes of Plasmodium falciparum circumsporozoite protein ( CSP ) , was administered i.m . as a single 50 microg dose in Seppic ISA 720 to 11 volunteers . Local reactogenicity and systemic side effects were acceptable with the predominant finding being mild pain at the injection site . This regimen induced anti-NANP antibodies in 10/11 and modest T cell responses . There was no evidence of protection from experimental challenge with P. falciparum sporozoites . Other formulations and /or multi-dose regimens will be required to enhance the immunogenicity and efficacy of ICC-1132 After initial successful evaluation of the circumsporozoite-based vaccine RTS , S/SBAS2 , developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research , protective efficacy of several regimens against Plasmodium falciparum challenge was determined . A controlled phase 1/2a study evaluated 1 or 2 st and ard doses of RTS , S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received st and ard , one-half , or one-fifth doses . RTS , S/SBAS2 was safe and immunogenic in all groups . Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge , malaria developed in 7 of 10 who received 1 dose , in 7 of 14 who received 2 doses , in 3 of 6 who received 3 st and ard doses , in 3 of 7 who received 3 one-half doses , in 3 of 4 who received 3 one-fifth doses , and in 22 of 23 control subjects . Overall protective efficacy of RTS , S/SBAS2 was 41 % ( 95 % confidence interval , 22%-56 % ; P=.0006 ) . This and previous studies have shown that 2 or 3 doses of RTS , S/SBAS2 protect against challenge with P. falciparum sporozoites BACKGROUND Development of an effective malaria vaccine could greatly contribute to disease control . RTS , S/AS02A is a pre-erythrocytic vaccine c and i date based on Plasmodium falciparum circumsporozoite surface antigen . We aim ed to assess vaccine efficacy , immunogenicity , and safety in young African children . METHODS We did a double-blind , phase IIb , r and omised controlled trial in Mozambique in 2022 children aged 1 - 4 years . The study included two cohorts of children living in two separate areas which underwent different follow-up schemes . Participants were r and omly allocated three doses of either RTS , S/AS02A c and i date malaria vaccine or control vaccines . The primary endpoint , determined in cohort 1 ( n=1605 ) , was time to first clinical episode of P falciparum malaria ( axillary temperature > or = 37.5 degrees C and P falciparum asexual parasitaemia > 2500 per microL ) over a 6-month surveillance period . Efficacy for prevention of new infections was determined in cohort 2 ( n=417 ) . Analysis was per protocol . FINDINGS 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per- protocol analysis . Vaccine efficacy for the first clinical episodes was 29.9 % ( 95 % CI 11.0 - 44.8 ; p=0.004 ) . At the end of the 6-month observation period , prevalence of P falciparum infection was 37 % lower in the RTS , S/AS02A group compared with the control group ( 11.9 % vs 18.9 % ; p=0.0003 ) . Vaccine efficacy for severe malaria was 57.7 % ( 95 % CI 16.2 - 80.6 ; p=0.019 ) . In cohort 2 , vaccine efficacy for extending time to first infection was 45.0 % ( 31.4 - 55.9 ; p<0.0001 ) . INTERPRETATION The RTS , S/AS02A vaccine was safe , well tolerated , and immunogenic . Our results show development of an effective vaccine against malaria is feasible A multiple antigen peptide ( MAP ) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes . The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1 * 0603 , DRB1 * 0401 , or DRB1 * 1101 class II molecules . In contrast , volunteers of other HLA genotypes were low responders or nonresponders . A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype . This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids ( N , A , V , D , and P ) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes . Moreover , the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro , thus facilitating the rational design of epitope-based peptide vaccines for malaria , as well as for other pathogens This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens A recombinant DNA Plasmodium vivax sporozoite vaccine containing the repeating region of the Salvador I strain circumsporozoite ( CS ) protein was produced in Escherichia coli . This vaccine was tested in 13 naive volunteers at doses of 10 - 1,000 micrograms . No serious adverse reactions were noted . None of 4 volunteers receiving the 10 micrograms dose developed antibodies measurable by ELISA . Six of 9 volunteers in the other dose groups developed measurable antibodies : 5 of 5 volunteers receiving 100 micrograms and 1 of 4 receiving 1,000 micrograms . Antibody responses measured by immunofluorescence assays paralleled those seen by ELISA . None of the volunteers developed antisera that inhibited sporozoite invasion of human hepatoma cells in vitro . Lack of a classical anamnestic response and lack of a typical dose response to increasing amounts of antigen suggests the possible presence of an immunosuppressive epitope in the repetitive region of the CS protein BACKGROUND The c and i date vaccines against malaria are poorly immunogenic and thus have been ineffective in preventing infection . We developed a vaccine based on the circumsporozoite protein of Plasmodium falciparum that incorporates adjuvants selected to enhance the immune response . METHODS The antigen consists of a hybrid in which the circumsporozoite protein fused to hepatitis B surface antigen ( HBsAg ) is expressed together with unfused HBsAg . We evaluated three formulations of this antigen in an unblinded trial in 46 subjects who had never been exposed to malaria . RESULTS Two of the vaccine formulations were highly immunogenic . Four subjects had adverse systemic reactions that may have result ed from the intensity of the immune response after the second dose , which led us to reduce the third dose . Twenty-two vaccinated subjects and six unimmunized controls underwent a challenge consisting of bites from mosquitoes infected with P. falciparum . Malaria developed in all six control subjects , seven of eight subjects who received vaccine 1 , and five of seven subjects who received vaccine 2 . In contrast , only one of seven subjects who received vaccine 3 became infected ( relative risk of infection , 0.14 ; 95 percent confidence interval , 0.02 to 0.88 ; P<0.005 ) . CONCLUSIONS A recombinant vaccine based on fusion of the circumsporozoite protein and HBsAg plus a potent adjuvant can protect against experimental challenge with P. falciparum sporozoites . After additional studies of protective immunity and the vaccination schedule , field trials are indicated for this new vaccine against P. falciparum malaria We calculated the number and growth rate of Plasmodium falciparum parasites emerging in recipients of c and i date preerythrocytic malaria vaccines and unvaccinated control subjects undergoing mosquito-bite challenge . This was done to measure vaccine efficacy and to distinguish the effects on blood-stage multiplication from those on liver-stage parasites . Real-time polymerase chain reaction measurements of parasite densities were analyzed by nonlinear regression and mixed-effects models . Substantial reductions in numbers of liver parasites result ed from the use of 2 immunization regimens : FP9 boosted by modified virus Ankara ( MVA ) encoding the malaria epitope-thrombospondin-related adhesion protein insert ( 92 % reduction ) and RTS , S/AS02 used in heterologous prime-boost immunization regimens , with MVA encoding the circumsporozoite protein ( 97 % reduction ) . Forty-eight-hour growth rates in blood from control subjects were not different from those in blood from any vaccination group ( mean , 14.4-fold [ 95 % confidence interval , 11 - 19-fold ] ) RTS , S/AS02A is a pre-erythrocytic malaria vaccine c and i date in which a portion of the circumsporozoite surface protein ( CSP ) of Plasmodium falciparum is genetically linked to hepatitis B surface antigen ( HBsAg ) coexpressed in yeast with unfused HBsAg . The result ing particulate antigen is formulated with the adjuvant system AS02A . We have initiated the paediatric clinical development of this vaccine by conducting two sequential Phase I studies in children : a study in older children ( 6 - -11 years ) , followed by a second study in younger children ( 1 - -5 years ) . In each study , a double-blind , r and omised controlled , staggered , dose-escalation design was used to evaluate 10 microg RTS , S dose ( 10 microg RTS , S in 0.1mL AS02A ) , 25 microg dose ( 25 microg RTS , S in 0.25mL AS02A ) and finally a 50 microg dose ( 50 microg RTS , S in 0.5mL AS02A ) of the RTS , S/AS02A c and i date malaria vaccine administered according to a 0- , 1- and 3-month vaccination schedule . Safety and reactogenicity were evaluated before moving to a higher dose level . The RTS , S/AS02A vaccine was safe at all dose levels , in both age groups . No serious adverse events related to vaccination were reported . The frequency of local Grade 3 symptoms was low but tended to increase with increasing dose level . Grade 3 general adverse events in the RTS , S/AS02A groups were infrequent and of short duration . The majority of local and general Grade 3 symptoms resolved or decreased in intensity within 48h . The pattern and intensity of reactogenicity seen in these studies are similar to those of previous studies with RTS , S/AS02A . All doses were highly immunogenic for anti-CSP and anti-HBsAg antibodies . The pooled anti-CSP antibody data from the two studies showed that the 25 microg dose and 50 microg dose anti-CSP antibody response were similar at both dose levels . However , the immunogenicity of the 10 microg dose anti-CSP response was significantly lower than that of either the 50 microg or 25 microg dose . The 25 microg dose was selected for future studies of RTS , S/AS02A in paediatric population Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite ( CS ) protein of Plasmodium falciparum conjugated to Toxin A ( detoxified ) of Pseudomonas aeruginosa ( R32Tox-A ) to evaluate its safety , immunogenicity and efficacy . In a r and omized , double-blind manner , 199 volunteers received either R32Tox-A or a control vaccine at 0 , 8 and 16 weeks . Immunization was performed in a malaria non-transmission area , after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection . The vaccine was found to be safe and to elicit antibody responses in all vaccinees . Peak CS antibody ( IgG ) concentrations in malaria-experienced vaccinees exceeded those in malaria-naive vaccinees ( mean 40.6 versus 16.1 micrograms ml-1 ; p = 0.005 ) as well as those induced by previous CS protein-derived vaccines and observed in association with natural infections . A log-rank comparison of time to falciparum malaria revealed no differences between vaccinated and non-vaccinated subjects . Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases , 3 and 5 months after the third dose of vaccine ( p = 0.06 and p = 0.014 , respectively ) . Because antibody levels had fallen substantially before peak malaria transmission occurred , the question of whether high levels of CS antibody are protective remains to be resolved Successful vaccination against intracellular pathogens , including liver-stage Plasmodium falciparum , will require induction of strong antigen-specific T lymphocyte responses . The multiple epitope (ME)-thrombospondin-related adhesion protein ( TRAP ) construct includes CD8(+ ) and CD4(+ ) T cell epitopes from pre-erythrocytic P. falciparum antigens fused in-frame to the entire pre-erythrocytic antigen TRAP . Three carriers for this construct -- plasmid DNA and 2 recombinant nonreplicating poxviruses ( modified vaccinia virus Ankara [ MVA ] and fowlpox strain 9 [FP9])--were administered at 3-week intervals in a heterologous prime-boost combination to 29 Gambian men aged 18 - 45 years . Doses of DNA ME-TRAP , MVA ME-TRAP , and FP9 ME-TRAP were 2 mg and 1.5x10(8 ) and 1x10(8 ) plaque-forming units , respectively . DNA ME-TRAP was injected intramuscularly ; MVA ME-TRAP and FP9 ME-TRAP were injected intradermally . There were no clinical ly relevant laboratory abnormalities and no severe or serious adverse events related to vaccination . DNA/MVA and FP9/MVA regimens were the most potent inducers of circulating effector T cells seen to date in sub-Saharan Africa . Twelve months after the final vaccination , a single booster vaccination exp and ed the effector T cell pool to a similar or higher magnitude than that after the primary vaccinations . These results highlight optimized combination regimens with general relevance to the development of vaccines targeting intracellular pathogens Twenty malaria-naive volunteers received a recombinant Plasmodium falciparum malaria vaccine ( RTS , S ) containing 19 NANP repeats and the carboxy terminus ( amino acids 210 - 398 ) of the circumsporozoite ( CS ) antigen coexpressed in yeast with hepatitis B surface antigen . Ten received vaccine adjuvanted with alum , and 10 received vaccine adjuvanted with alum plus 3-deacylated monophosphoryl lipid A ( MPL ) . Both formulations were well tolerated and immunogenic . MPL enhanced CS antibody levels ( measured by ELISA , immunofluorescence , and inhibition of sporozoite invasion assays ) . After sporozoite challenge , 6 of 6 in the alum group and 6 of 8 in the alum-MPL group developed patent malaria . Protected subjects had higher levels of CS antibody titers on day of challenge than did nonprotected subjects . After immunization , 1 protected subject had increased cytotoxic T lymphocyte activity against CS and recall of memory T cell responses to RTS , S and selected CS BACKGROUND RTS , S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults . A previous report showed that this vaccine reduced risk of clinical malaria , delayed time to new infection , and reduced episodes of severe malaria over 6 months in African children . An important remaining issue is the durability of protection against clinical disease in these children . METHODS We did a r and omised , controlled , phase IIb trial of RTS , S/AS02A given at 0 , 1 , and 2 months in 2022 Mozambican children aged 1 - 4 years . We previously determined vaccine efficacy ( VE ) against clinical malaria in a double-blind phase that included study months 2.5 - 8.5 ( VE(2.5 - 8.5 ) ) . We now report VE in a single-blind phase up to month 21 ( VE(8.5 - 21 ) ) . The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria ( axillary temperature 37.5 degrees C and P falciparum asexual parasitaemia > 2500 per microL ) detected through a passive case detection system . We also determined VE for other case definitions and for episodes of severe malaria . This study is registered with the Clinical Trials.gov identifier NCT00197041 . FINDINGS During the single-blind phase , VE(8.5 - 21 ) was 28.9 % ( 95 % CI 8.4 - 44.8 ; p=0.008 ) . At month 21 , prevalence of P falciparum infection was 29 % lower in the RTS , S/AS02A group than in the control ( p=0.017 ) . Considering the entire study period , VE(2.5 - 21 ) was 35.3 % ( 95 % CI 21.6 - 46.6 ; p<0.0001 ) and VE(2.5 - 21 ) for severe malaria was 48.6 % ( 95 % CI 12.3 - 71.0 ; p=0.02 ) . INTERPRETATION These results show that RTS , S/AS02A confers partial protection in African children aged 1 - 4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months , and confirm the potential of malaria vaccines to become credible control tools for public-health use RTS , S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein ( CSP ) of Plasmodium falciparum linked to hepatitis B surface antigen ( HBs ) and combined with a novel adjuvant system ( SBAS2 ) . We have conducted a Phase I trial with three doses of this vaccine given at 0 , 1 , and 6 months to 20 semi-immune , adult , male volunteers in The Gambia to assess its safety and immunogenicity . Eighteen of the 20 volunteers completed the study . There were no clinical ly significant local or systemic adverse events following each vaccination . Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity . Antibody titers to both CSP and HBs showed a significant increase after vaccination ; these were the largest after the third dose . We conclude that the RTS , S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria . In a malaria endemic region of Kenya , 76 volunteers , in 38 pairs sleeping adjacently , were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A , or hepatitis B vaccine . After quinine and doxcycycline , volunteers were followed for illness daily , parasitemia weekly , antibody , T-lymphocyte responses , and treated if indicated . Anopheles mosquitoes resting in houses were collected , and tested for P. falciparum antigen , or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen . Vaccine was safe , with side-effects similar in both groups , and immunogenic , engendering IgG antibody as high as 600 micrograms ml-1 , but did not increase the proportion of volunteers with T-lymphocyte responses . Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day . Mosquito blood meals showed no difference in biting intensity between vaccine and control groups . Both groups had similar malaria-free survival curves , cumulative positive blood slides , cumulative parasites mm-3 , and numbers of parasites mm-3 on first positive blood slide , during three post-vaccination observation periods . Every volunteer had P. falciparum parastemia at least once . Vaccinees had 82 % and controls 89 % incidences of symptomatic parasitemia ( P = 0.514 , efficacy 9 % , statistical power 95 % probability of efficacy < 50 % ) . Vaccine-induced anti-sporozoite antibody was not protective in this study . Within design ed statistical precisions the present study is in agreement with efficacy studies in Colombia , Venezuela and Tanzania A Plasmodium falciparum circumsporozoite protein ( PfCSP ) recombinant fusion protein , R32NS1(81 ) , formulated with monophosphoryl lipid A , cell wall skeleton of mycobacteria , and squalane ( Detox ) was administered to 12 volunteers . One volunteer had malaise and self-limited painful in duration at the injection site after the second dose and declined further immunization . The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine , but most complained of sore arms ; in five cases the pain or malaise was severe enough to interfere with work or sleep . Two weeks after the third dose of vaccine , four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum . Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites . The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia . These data are consistent with other studies , and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans . The challenge is to improve the immunogenicity of PfCSP-based vaccines , and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines The malaria sporozoite vaccine c and i date RTS , S , formulated with an oil-in-water emulsion plus the immunostimulants monophosphoryl lipid A and the saponin derivative QS21 ( vaccine 3 ) , recently showed superior efficacy over two other experimental formulations . Immunized volunteers were followed to determine the duration of protective immune responses . Antibody levels decreased to between one-third and one-half of peak values 6 months after the last dose of vaccine . T cell proliferation and interferon-gamma production in vitro were observed in response to RTS , S or hepatitis B surface antigen . Seven previously protected volunteers received sporozoite challenge , and 2 remained protected ( 1/1 for vaccine 1 , 0/1 for vaccine 2 , and 1/5 for vaccine 3 ) . The prepatent period was 10.8 days for the control group and 13.2 days for the vaccinees ( P < .01 ) . Immune responses did not correlate with protection . Further optimization in vaccine composition and /or immunization schedule will be required to induce longer-lasting protective immunity We tested the clinical reactions to a synthetic , Plasmodium falciparum , circumsporozoite multiple antigen peptide ( MAP ) vaccine in 39 volunteers immunized two to three times over 2 - 8 months using a dose escalation design . Immediate pain at the injection site was associated with the adjuvant QS-21 ( P<0.001 ) , and delayed local inflammatory reactions were associated with high-titered circulating IgG anti-MAP antibody ( P=0.03 ) . Because two volunteers developed acute , systemic urticaria after the third immunization associated with development of serum IgE MAP antibody , we employed immediate-type hypersensitivity skin tests ( ITH-STs ) using intradermal injections of diluted MAP vaccine to identify persons sensitized to the vaccine . ITH-STs were negative in seven volunteers tested 27 days after the first vaccination , but six of these individuals developed positive wheal and flare reactions when tested 14 or 83 days after the second vaccination ; IgE MAP antibody was detected in only one of them . Another cohort of 16 volunteers , including the 2 allergic individuals , were ITH-ST negative when first tested late after their second or third vaccination at 6 - 7 months . Five of five non-immunized persons were also ITH-ST negative . ITH-STs may help identify individuals sensitized to malaria peptides and at potential risk of developing systemic allergic reactions after re-vaccination Optimal protection against malaria may require induction of high levels of protective antibody and CD8(+ ) and CD4(+ ) T cell responses . In humans , malaria DNA vaccines elicit CD8(+ ) cytotoxic T cells ( CTL ) and IFNgamma responses as measured by short-term ( ex vivo ) ELISPOT assays , and recombinant proteins elicit antibodies and excellent T cell responses , but no CD8(+ ) CTL or CD8(+ ) IFNgamma-producing cells as measured by ex vivo ELISPOT . Priming with DNA and boosting with recombinant pox virus elicits much better T cell responses than DNA alone , but not antibody responses . In an attempt to elicit antibodies and enhanced T cell responses , we administered RTS , S/AS02A , a partially protective Plasmodium falciparum recombinant circumsporozoite protein ( CSP ) vaccine in adjuvant , to volunteers previously immunized with a P. falciparum CSP DNA vaccine ( VCL-2510 ) and to naïve volunteers . This vaccine regimen was well tolerated and safe . The volunteers who received RTS , S/AS02A alone had , as expected , antibody and CD4(+ ) T cell responses , but no CD8(+ ) T cell responses . Volunteers who received PfCSP DNA followed by RTS , S/AS02A had antibody and CD8(+ ) and CD4(+ ) T cell responses ( Wang et al. , su bmi tted ) . Sequential immunization with DNA and recombinant protein , also called heterologous prime-boost , led to enhanced immune responses as compared to DNA or recombinant protein alone , suggesting that it might provide enhanced protective immunity The present study is an investigation of the safety and immunogenicity of DNA and modified vaccinia virus Ankara ( MVA ) c and i date vaccines , each encoding the malaria DNA sequence multiple epitope-thrombospondin related adhesion protein ( ME-TRAP ) , against Plasmodium falciparum . DNA ME-TRAP and MVA ME-TRAP are safe and immunogenic for effector and memory T cell induction . MVA ME-TRAP , with or without prior DNA ME-TRAP immunization , was more immunogenic and more cross-reactive in malaria-exposed individuals than in malaria-naive individuals , a finding suggesting that recombinant MVA vaccines are particularly promising for the development of a malaria vaccine for exposed population s. Both CD4(+ ) and CD8(+ ) T cells were induced by these vaccines DNA-based vaccines are considered to be potentially revolutionary due to their ease of production , low cost , long shelf life , lack of requirement for a cold chain and ability to induce good T-cell responses . Twenty healthy adult volunteers were enrolled in a Phase I safety and tolerability clinical study of a DNA vaccine encoding a malaria antigen . Volunteers received 3 intramuscular injections of one of four different dosages ( 20 , 100 , 500 and 2500 microg ) of the Plasmodium falciparum circumsporozoite protein ( PfCSP ) plasmid DNA at monthly intervals and were followed for up to twelve months . Local reactogenicity and systemic symptoms were few and mild . There were no severe or serious adverse events , clinical ly significant biochemical or hematologic changes , or detectable anti-dsDNA antibodies . Despite induction of excellent CTL responses , intramuscular DNA vaccination via needle injection failed to induce detectable antigen-specific antibodies in any of the volunteers BACKGROUND RTS , S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg , incorporating a new adjuvant ( AS02 ) . We did a r and omised trial of the efficacy of RTS , S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia . METHODS 306 men aged 18 - 45 years were r and omly assigned three doses of either RTS , S/AS02 or rabies vaccine ( control ) . Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3 , and kept under surveillance throughout the malaria transmission season . Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria . The primary endpoint was time to first infection with P. falciparum . Analysis was per protocol . FINDINGS 250 men ( 131 in the RTS , S/AS02 group and 119 in the control group ) received three doses of vaccine and were followed up for 15 weeks . RTS , S/AS02 was safe and well tolerated . P. falciparum infections occurred significantly earlier in the control group than the RTS , S/AS02 group ( Wilcoxon 's test p=0.018 ) . Vaccine efficacy , adjusted for confounders , was 34 % ( 95 % CI 8.0 - 53 , p=0.014 ) . Protection seemed to wane : estimated efficacy during the first 9 weeks of follow-up was 71 % ( 46 - 85 ) , but decreased to 0 % ( -52 to 34 ) in the last 6 weeks . Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses . Protection was not limited to the NF54 parasite genotype from which the vaccine was derived . 158 men received a fourth dose the next year and were followed up for 9 weeks ; during this time , vaccine efficacy was 47 % ( 4 - 71 , p=0.037 ) . INTERPRETATION RTS , S/AS02 is safe , immunogenic , and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection |
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