伐伦克林对戒除低烟量烟草的帮助随机双盲安慰剂对照研.doc

伐伦克林对戒除低烟量烟草的帮助随机双盲安慰剂对照研 11DecemberxxVolume341,Issue7785一.Research1.Stopping smokeless tobao withvarenicline:randomised doubleblind placebo controlled trial伐伦克林对戒除低烟量烟草的帮助随机双盲安慰剂对照研究2.Risk of recurrence after a firstseizure andimplications fordriving:further analysis of theMulticentre studyof earlyEpilepsy andSingle Seizures首次癫痫发作后再发风险及其对驾驶的影响早期癫痫和单次发作的多中心研究的进一步分析3.Intrauterine exposure to carbamazepineand specifiongenital malformations:systematic reviewand case-control study卡马西平的宫内暴露和先天畸形系统回顾和病例对照研究4.Non-specific effectsof standardmeasles vaine at4.5and9months ofage onchildhood mortality:randomised controlled trial在4.5-9个月时接种标准麻疹疫苗对儿童死亡率的非特异性效果随机对照试验二.Clinical ReviewInvestigating andmanaging chronicscrotal pain调查和处理慢性阴囊疼痛三.Practice1.Easily Missed?:Infective endocarditis容易忽视？感染性心内膜炎2.Lesson of the Week:Acute liverfailure afteradministration ofparacetamol at the maximumremended dailydose inadults本周课程成人扑热息痛每日最大推荐用量使用时的急性肝衰竭四.Analysis Howdo patientsuse informationon healthproviders?病人如何利用关于健康提供者的信息What dopatients wantof performanceinformation?病人想要什么样的表现信息？五.Observations LobbyWatch:The Institutefor FiscalStudies LobbyWatch财政研究学院六.Feature ResearchEthics:The rulesof retraction研究伦理学撤销的法则Briefing:The BriberyAct:what itmeans foryou主要信息受贿艺术对你意味着什么呢？Conflict andRape:After war,what next?冲突和强奸战后，接下来是什么呢？Commentary:what interventionswork forvictims ofconflict relatedrape?评论什么样的噶怒措施对冲突中的强奸受害人有用呢？七.News1.Low doseaspirin reducesrisk ofdying froma rangeof cancers小剂量阿司匹林可降低多种癌症死亡的风险2.Negotiators tryto persuadeJapan,Canada,and Russiato softenopposition toclimate treaty谈判专家努力说服日本，加拿大和俄罗斯软化对气候变化协议的反对3.Consultants should be availableto admitpatients tohospital12hours a day顾问应该对住院病人提供每天12小时可能的服务4.Senior Toryminister isasked toscrutinise Lansleys plansfor NHS保守党资深部长要求审议国民保健服务Lansley计划5.Cuts insocial carecould putpressure onhospitals tocare fordying patients在社会关怀的削减可能把照顾临终病人的压力转嫁给医院6.French doctorsdemand toknow whydrug stayedon themarket forso long法国医生要求知道药物在市场上停留如此久的原因7.European MedicinesAgency widensaess toits documents欧洲药品管理局扩大获取其文件的范围8.New centreopens upclinical trialsto morecancer patients新中心对更多的癌症患者开放临床试验9.Tight regulationof Frenchdrug repsmean Frenchdoctors getmore balancedinformation thandoctors in the US与法国医药代表的紧密关系意味着法国医生获得比美国医生更多的平衡信息10.Independent drugreview group in Canadais squeezedout加拿大独立审查组药物小组财政紧张八.Research摘要1.Stopping smokeless tobao withvarenicline:randomised doubleblind placebocontrolled trial伐伦克林对戒除低烟量烟草的帮助随机双盲安慰剂对照研究Objective Toassess theefficacy andsafety of varenicline(a licensedcigarette smokingcessation aid)in helpingusers of smokeless tobaoto quit.Design Doubleblind,placebocontrolled,parallel group,multicentre,randomised controlled trial.Setting Medicalclinics(mostly primarycare)in Norwayand Sweden.Participants Menand womenaged18who usedsmokeless tobaoat leasteight times aday,with noabstinence periodover three months withinone yearbefore screening,who wantedto quitall tobaouse.Participants wereexcluded if they usedany otherform oftobao(except smokeless tobao)or medicationto stopsmoking withinthreemonths of screeningor hadany pre-existing medicalor psychiatriondition.Interventions Varenicline1mg twicedaily(titrated duringthe firstweek)or placebofor12weeks,with14weeksfollow-up aftertreatment.Main outemeasures Theprimary end point was the fourweek continuous abstinence rate attheend of treatment(weeks9-12)confirmed withcotinine concentration.A secondaryendpointwas continuousabstinence ratefor weeks9-26.Safety andtolerability werealso evaluated.Results431participants(213varenicline;218placebo)were randomisedand receivedat leastone dose of studydrug.Participantsdemographics andbaseline useofsmokelesstobao weresimilar(89% (189)and90% (196),respectively,were men;mean agein bothgroups was43.9;participants usedsmokelesstobaoproducts about15timesaday,and about80%first usedsmokelesstobaowithin30minutes afterawakening).Continuous abstinencerate atweek9-12was higherin the varenicline groupthan the placebo group(59% (125)v39% (85);relative risk1.60,95%confidence interval1.32to1.87,P0.001;risk difference20%;number neededto treat5).The advantageofvareniclineover placebopersisted through14weeks offollow-up(continuousabstinencerateatweek9-26was45% (95)v34% (73);relative risk1.42,1.08to1.79,P=0.012;risk difference11%;number neededto treat9).The mostmon adverse events in thevareniclinegroup pared with theplacebo groupwere nausea(35% (74)v6% (14),fatigue(10% (22)v7% (15),headache(10% (22)v9% (20),and sleepdisorder(10% (22)v7% (15).Few adverseevents ledto discontinuationoftreatment(9% (19)and4% (9),respectively),and seriousadverseeventsourred intwo(1%)and three(1%)participants,respectively.Conclusion Vareniclinecan helppeople togive upsmokelesstobaoand hasan aeptablesafety profile.The responserate in theplacebogroupinthis study was high,suggesting apopulation lessresistant to treatment thansmokers.2.Risk of recurrence aftera firstseizure andimplications fordriving:further analysisof theMulticentre studyof earlyEpilepsy andSingle Seizures首次癫痫发作后再发风险及其对驾驶的影响早期癫痫和单次发作的多中心研究的进一步分析Objective Todetermine forhow longafterafirst unprovoked seizure adriver mustbe seizure-free beforethe risk ofrecurrence in thenext12months fallsbelow20%,enabling themto regaintheir driving licence.Design Randomisedcontrolledtrial:Multicentre studyof earlyEpilepsy andSingle Seizures(MESS).Setting UKhospital outpatientclinics from1January1993to31December2000.Participants Peopleentered MESSiftheyhad hadone ormore unprovoked seizures andboth theparticipant and the clinicianwere uncertainabout theneed tostart antiepilepticdrug treatment.The subsetof peopleused forthis analysisprised participantsaged at least16years with a singleunprovokedseizure.Main outemeasure Riskof seizure recurrenceinthe12months aftera seizure-free periodof6,12,18,or24months from the dateof the first(index)seizure.Regression modellingwas usedto investigatehow antiepileptictreatment andseveral clinicalfactors influencethe risk of seizurerecurrence.Results Atsix months after theindex seizurethe riskofrecurrenceinthenext12months forthose whostart antiepilepticdrugs wassignificantly below20%(unadjusted risk14%,95%confidence interval10%to18%).For patientswho did not starttreatment therisk estimatewas less than20%but theupper limitoftheconfidence intervalwas greaterthan20%(18%,13%to23%).Multivariable analysesidentified subgroupswith asignificantly greaterthan20%riskof seizurerecurrenceinthe12monthsaftera sixmonth seizure-free period,such asthose witha remotesymptomatic seizurewith abnormalelectroencephalogram results.Conclusion Aftera singleunprovokedseizurethis reanalysisof MESSprovides estimatesofseizurerecurrence risksthat willinform policyand guidanceabout regainingan ordinarydrivinglicence.Further guidanceis needed as tohow suchdata shouldbe utilised;in particular,whether apopulation approach shouldbe taken witha focuson theunadjusted resultsor whetherattempts shouldbe madeto individualiserisk.Guidance isalso requiredas to whether thefocus shouldbe onrisk estimatesonly oron theconfidence intervalas well.If thefocus ison theestimate onlyour unadjustedestimates suggestthat treatedand untreatedpatients areeligible todrive afterbeing seizure-free forsix months.If thefocus isalso onconfidence intervals,direction isneededastowhethera conservativeor liberalapproachshouldbetaken.3.Intrauterine exposureto carbamazepineand specifiongenital malformations:systematic reviewand case-control study卡马西平的宫内暴露和先天畸形系统回顾和病例对照研究Objective Toidentify specificmajor congenital malformations associated with useof carbamazepineinthe first trimester of pregnancy.Design Areview ofall publishedcohort studiesto identifykey indicationsand apopulation basedcase-control studyto testthese indications.Setting Reviewof PubMed,Web ofScience,and Embasefor papersabout carbamazepineexposure inthe firsttrimesterofpregnancy andspecific malformations,and theEUROCAT AntiepilepticStudy Database,including datafrom19European populationbased congenitalanomaly registries,1995-xx.Participants Theliterature reviewcovered eightcohort studiesof2680pregnancies with carbamazepine monotherapyexposure,andtheEUROCAT datasetincluded98?075registrations of malformations coveringover3.8million births.Main outemeasures Overallprevalence for a major congenitalmalformationafter exposureto carbamazepine monotherapy inthefirsttrimester.Odds ratiosfor malformationswith exposureto carbamazepineamong cases(five typesofmalformationidentified inthe literature review)pared withtwo groupsof controls:other non-chromosomal registrations of malformationsand chromosomalsyndromes.Results Theliteraturereviewyielded anoverall prevalenceforamajor congenitalmalformation of3.3%(95%confidence interval2.7to4.2)after exposureto carbamazepine monotherapy inthefirsttrimester.In131registrationsofmalformations,the fetushad beenexposed tocarbamazepinemonotherapy.Spina bifidawastheonly specificmajor congenitalmalformation significantlyassociatedwithexposuretocarbamazepinemonotherapy(odds ratio2.6(95%confidence interval1.2to5.3)pared withno antiepilepticdrug),but therisk wassmaller forcarbamazepine thanfor valproicacid(0.2,0.1to0.6).There wasno evidencefor anassociation withtotal anomalouspulmonary venousreturn(no caseswithcarbamazepineexposure),cleft lip(with orwithout palate)(0.2,0.0to1.3),diaphragmatic hernia(0.9,0.1to6.6),or hypospadias(0.7,0.3to1.6)pared withno exposureto antiepilepticdrugs.Further exploratoryanalysis suggesteda higherriskofsingle ventricleand atrioventricularseptal defect.Conclusion Carbamazepieratogenicity isrelatively specificto spinabifida,though therisk islessthanwith valproicacid.Despite thelarge dataset,there was not enoughpower todetect moderaterisks forsome raremajorcongenitalmalformations.4.Non-specific effectsof standardmeasles vaine at4.5and9months ofage onchildhood mortality:randomised controlledtrial在4.5-9个月时接种标准麻疹疫苗对儿童死亡率的非特异性效果随机对照试验Objective Toexamine ina randomisedtrial whethera25%difference inmortality existsbetween4.5months and3years ofage forchildren giventwo standarddoses ofEdmonston-Zagreb measles vaines at4.5and9months ofage paredwith thosegiven onedose ofmeaslesvaine at9months ofage(current policy).Design Randomisedcontrolledtrial.Setting TheBandim HealthProject,Guinea-Bissau,which maintainsa healthand demographicsurveillance systemin anurban area.Participants6648children aged4.5months ofage whohad receivedthree doses of diphtheria-tetanus-pertussis vaine atleastfour weeksbefore enrolment.A largeproportion ofthe children(80%)had previouslytaken partin randomisedtrials ofneonatal vitamin A supplementation.Intervention Childrenwere randomisedto receiveEdmonston-Zagreb measlesvaine at4.5and9months ofage(group A),no vaineat4.5months andEdmonston-Zagreb measlesvaineat9months ofage(group B),or novaineat4.5months andSchwarz measlesvaineat9months ofage(group C).Main outemeasure Mortalityrate ratiobetween4.5and36months ofage forgroup Aparedwithgroups Band C.Secondary outestested thehypothesis thatthe beneficialeffect wasstronger inthe4.5to9months agegroup,in girls,and inthe dryseason,but thestudywasnot poweredto testwhether effectsdiffered significantlybetween subgroups.Results In the intention to treatanalysisofmortality between4.5and36months ofage themortality rate ratio ofchildren who received two dosesofEdmonston-Zagreb vaineat4.5and9months ofage paredwith thosewhoreceiveda singledoseofEdmonston-Zagreb vaineor Schwarzvaineat9months ofage was0.78(95%confidence interval0.59to1.05).Inthe analyses ofsecondary outes,the intention to treat mortality rate