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MedicalResearchpaperwritingChaoMiMedicalResearchpaperwritingUnit1PlanningandObservingLOGOMedicalResearchpaperwritingLiteratureSearch
Usedatabase(MEDLAR/MEDLINE)Focusonstudydesign(isyoursuperiortoothers)Avoidderivative/secondaryworkTeambuilding
TalkwithpreviousresearchteamsAwell-knowninvestigator(blindedsystem)Fulltimeresearchnurses(detail/objective)
AtalentedwriterAqualifiedstatisticianMethodology
Statingtheproblem(thepurposeofyourstudy)
LOGOMedicalResearchpaperwriting
e.g.Approximately40%ofpatientswithspinalcordinjurydevelopapressureulcerduringtheinitialhospitalization.However,thereiscurrentlynomethodofquantifyingthisriskthatisaccurateforthispopulation.
Formulatingthehypothesis:
StartwithH0thattherearenoconnectionswiththetwovariables(smokinghistoryisnotassociatedwiththeincidenceoflungcancer)
HaistheoppositeofH0;ButuseitwithH0atleast.
Studydesign:
Bewarethisisthemostcommontypeofflawthatresultsinoutrightrejectionofamanuscript!Categories(Observational/Quasi-experimental/Experimental)LOGOReadingExamples:1.Researcherscomparenewborninfantsfromtwogroups.Inonegroup,themothersusedcocaineduringpregnancy.Intheothergroup,themothersdidnotusecocaineduringpregnancy.2.Researcherscomparetheoutcomeofinfantsbornintwocities.Inonecity,anewlawwasenactedtotestpregnantwomenforcocaineuseandenrollthosewhohadpositivetestresultsinatreatmentprogram.Theothercityhadnosuchlaworprogram.3.Researcherscomparenewbornratsfromtwogroups.Inonegroup,theresearchershadgiventhemotherscocaineduringpregnancy.Themothersoftheratsintheothergroupwerenotgivencocaineduringpregnancy.LOGOReadinghandoutmaterialreading(Case-control;Cohort;Historicalperspective;Cross-sectional)
MinimizingBias:
Selectionbias:asystematicdifferencebetweenpeopleinthestudyandpeoplenotselected.(samearea;longperiodandfollow-upinformation)
Responsebias:respondentsdiffersystematicallyfromnonrespondents.(peoplewithcertaindiseasemaytendtorespondtoamailedquestionnaire)
Informationbias:…differencebetweenmeasurementsindifferentstudygroups.(patientswithriskfactorsmaybetestedmorecarefullyandfrequently)LOGOReading
Confoundingbias:effectofextraneousvariablesthatmustbeadjustedbeforeresearchquestionsareanswered.
Aninner-cityhospitalmayhaveahigherneonatalmortalityratethanthenationalaverage.Sotheconfoundingvariablesassociatedwithinner-citylifemaycreateaconfoundingbias.DataCollection:Usequestionswithdefinedchoicesnotopen-endedquestionsandcoverallpossibilities.Categoricaldataisinferiortocontinuousdata(bellcurve)Dummyquestionsshouldbeused.
LOGOReadingFailuretocollectdataonvariablesthatcouldinfluencetheInterpretationofresults.(outrightrejectionofanarticleSouseothers’experience)Reliabilityandvalidity:
Reliability:measurementusedonthesamepatientunderthesameconditionwouldyieldthesameresults.
e.g.Lowreliability:self-reporteddurationofexposuretopassivesmokingamongwomenbreastfeedingtheirinfant.e.g.Highreliability:nicotineconcentrationinthemothers’breastmilk.Validity:Canatestorproceduremeasurewell.
e.g.Malnutritioncouldbeassessedbyaskingpatientstoscoretheirnutritionalintakeonascaleof1to10,butmeasuringtheirserumalbuminlevelismorevalid
LOGOReadingEligibility(适合性)
Patientsshouldbehomogeneous(includingamixtureofdiseasesorprocedures)Ifyouuseamixedsample,payattentionto:
Inclusionandexclusiondecisions;Distributionofdiseaseseverityofthepatientsandwhy;statisticaladjustmentfordifferencesamongthesepatientsCombiningdifferenttypesofpooroutcomebecauseeachoneissmall.Usetheoutcomethatcouldbepredictablebytheindependentvariablesandexplainwhy.
Alldiagnosesandproceduresmustbeencodedforanalysis(ICD;TheAMACPTCodeBook):
e.g.Indiagnosisfields,hipfractureisrepresentedbyICDcodefrom820.00to820.99(usestandard)
LOGOReadingRandomizationandConfidentialityStrengthenthestudydesignandminimizebias.
Randomizedclinicaltrial:patientsarerandomlyassignedtoeitherreceiveornotreceivetheintervention.
Double-blindeddesign:cliniciannotknowingtheactivetreatmentandplacebo.Triple-blindeddesign:evenstatisticiannotknowingwhoreceiveactivetreatmentandplacebo.
e.g.Astudyisbeingplannedinwhichfourresearchnursesreviewthehospitalchartsoftraumapatientswhoareadmittedto10hospitals…Theyknowthattwoofthenursesaremuchmoreaggressiveinsearchingchartsforcomplications.Tominimizethispotentialbias,theyusearandomnumbertabletoassignmonthlyblocksofchartstobereviewedatthe10hospital.LOGOReadingLOGOAlthoughthisstudyisnotarandomizedclinicaltrial,theuseofrandomizationstrengthensthestudydesignandreducesbias.Protecttheconfidentialityofallparticipants.AbidebythedocumentationofIRB(InstitutionalReviewBoard);Patient,hospital,physician,ect(casenumber1,2,3)EndpointsandOutcome
Unitsofanalysis
e.g.Evaluatingtheaccuracyofscreeningforfetalproblems.(1)apregnantwoman;(2)aninfant;(3)apregnancy;(4)asingletonpregnancythatcontinuesbeyond28weeksofgestation…
Confoundingfactors
Alltheotherthingsthatcouldexplainyourresults.Fromcruderatestoadjustedrates(statisticaltransformationhasbeendonetoeliminatedifferencesbetweengroups)Reading
Whatiscasemixorpatientmix?e.g.Comparesurvivalratesamonghospitalsforpatientswhounderwentaspecificsurgicalprocedure,crudesurvivalratesarealmostmeaningless.Theinvestigatormustadjustforconfoundingfactors,suchasdifferencesinpatients(age),preexistingconditions(diabetes),orwhethertheprocedurewasperformedonanemergencyoranelectivebasis.Thesefactorsarereferredto~
Locateconfoundingfactors
Performaliteraturesearchtoidentifythembeforedatacollectionisfinished.
Classificationofvariables.continuous(bellcurve;hematocrit血细胞比容)categorical(groups;anemia)/dichotomous(just2groups;alivevsdead)
LOGOReadingAnexampleofrecodingandcombiningdata:
Lengthofstayinthehospitalisoftenaskewedcontinuousdependentvariable.Soset0forpatientswhosestayislessthanthemedianandsetto1fortheotherpatients.Amuchsmallersample,butstatisticaltechniquesarebetterapplied.
Dataentry
Alwaysquantify!Trick:useintervalscalewhenpossible.Avoidmixingtextandcode.UsebignumberforMissingdataorUnknown.(9,-99,notNA)Logicalcoding:0=no,1=yes;Illogicalcoding:1=none,2=none,3=two
LOGOReadingExamplesofweakandstrongvariables:1.LowBirthWeightExactBirthWeight2.RespiratorydistresssyndromeLungindex3.NICUadmissionTotalcostof
hospitalization
ordaysintheNICU
(新生儿重症监护室P38)SampleSize
EstimatingSampleSize
Intheplanningphase,reviewsamplesizeinsimilarpublishedstudy(considerbothcontrolandsubgroup)
StatisticalPower
Theprobabilityofrejectingthenullwhereitisfalse.TakenwithPvalue,samplesizeisdeterminedbyusingTableonpage43.LOGOReadingPreparingforStatisticalAnalysis
Levelsofmeasurement
1.Nominal:0=no,1=yes;1=female,2=male;1=white,2=black,3=Asian2.Ordinal:0=nonsmoker,1=lightsmoker,2=moderatesmoker,3=heavysmoker3.Interval:Age,Hematocrit,Serumalbuminlevel,cigarsmokedperday
Planningthefollowing-up
1.Impressivelengthoffollow-up(2~5years)2.Averagetimemaydifferbetweenthetreatmentandcontrolgroup.
LOGOReading3.Intention-to-treatanalysis:datafromallpatientsmustbeincluded.(notonlywhofinishedthestudy,e.gactualontherapyanalysis)AvoidingCommonCriticisms(peers/editors)
Designofthestudy
Poorexperimentaldesign/methodologyNoaccountingforconfoundingfactors/biaseddatasmallsamplesize/improperstatisticalmethods
Interpretationoffindings
Unfounded/unsupportedfindingsOverinterpretationofdataInadequatediscussion/unexplainedinconsistencies
LOGOReadingImportanceofthetopicRehashofestablishedfacts/unimportanttopicNoreaderinterest/notgeneralizableLittleclinicalrelevancePresentationoftheresultsPoorlyfocused/organized/writtenToolong/poorgrammarIntroductionandDiscussiontendtobetoolongMethodsandResultstendtobetooshortCollectingData
Periodicmonitoringofthestudy’sprogressKeepingrecordsLOGOReadingNotesthatincludesdetailedresearchdecisionsDatacodingconventionsandabstractingguidesDatacollectionformReferenceresearchpaperTheinstructionforauthorfromtargetjournalOnerecentarticlefromtargetjournal
e.g.Bothstatisticalandclinicalimplicationsofchangesmustbeconsideredproperly.Numberof,reasonfor,amissingpatient.DetectingpotentialproblemsDistinguishbetweenmissingdataandtheanswer“no”Monitoringthesamplesize–reevaluatethesamplesizewithnewrealisticestimates.
LOGOReadingStatisticalAnalysis
Layingthegroundwork
Buildadatabaseforstatisticalanalysis;
Uselogical,easytorememberfieldname;Don’taskinexperiencedprogrammerormedicalstudenttocustomizeadatabase.
e.g.FixedfieldFormatFileCASEGROUPBPsSEXRACEAGELOSICU131201124.62292280230.51513313015-99.9100
LOGOReading
PreparingtheData
“Clean”and“freeze”thedata
1Avoiddifferentunits(week/month/year)2Completethemissingcode(asunknown/dropthecasewhenessentialdataismissingafterdiscussion)3Documentthechangemadeinthedata4Freezingmeansnodatawillbeaddedorchangedduringnextphaseofanalysis.
Interpretingthedata
Preparingfordataanalysis
Donotforcenumberstoproveyourpoint.CannotsimplypressabuttonandletPCanalyzeyourdataConsultadataanalystwithadequateexperience
LOGOReadingCreateequal-sizedgroupsofpatientsforcontinuousvariables
e.g.Youmaynothaveenoughdataforcertainsubgroupstocarryoutanalysis.Groupingofpatientsbyagedecades(0-9,10-19,20-29…)mightbereplacedbydeciles(0-6.4,6.5-14.9,15.0-22.7)Avoidcommonproblems
Don’tforgettorepeatyourexperiments.Controlgroupsshouldnotbepoorlymatched.Epidemiologictechniquescanbeusedtostrengthenclinicalresearch.Forexamples:
1.Person-years:thenumberofyearsthateachmemberofapopulationhasbeenafflictedbyacertaincondition.(druguse)2.Survivalanalysisandfollow-uplifetables:canbeusedtocomparegroupsthatarefollowedupforvaryingperiods.
LOGOReading
Dose-responserelationshipisachangeintheamount,intensity,ordurationofexposureassociatedwithachangeintheriskofaspecifiedoutcome.
e.g.Theincidenceoflungcancerincreaseswiththenumberofcigarettessmokedperday.
UnivariateAnalysis
Mostcommonunivariatetestsused
Chi-squaretestandStudent’sT-test(simplisticbutessentialfirststep)
UsingChi-squaretest
Testcategoricalvariables(Whethertheactualproportioninthegroupsdifferssignificantlyfromtheproportionexpectedbychancealone)
LOGOReadingUsingStudent’sTtest
Thistestcanhelpdetectwhetherthemeansforthetwounmatchedgroupsaresignificantlydifferent.(Bellshapeddata)
WhenStudent’sTtestisnotpreferred:a.Morethan2groups(one-wayanalysisofvariance:ANOVA)b.Dataisnotbell-shaped(nonparametrictest)c.Skeweddata(2groups/Mann-WhitneyUtest)d.Skeweddata(>2groups/Krushal-Wallistest)
Sometimesmorethanonetestsareusedtogether,butneverusetheimproperonetofishforsignificance,whichwillleadtofalseconclusions.Nonparametrictest
Datanotnormallydistributedorordinal2groups:Mann-WhitneyUtest;>2groups:Krushal-Wallistest
LOGOReading
2groups(matched):Wilcoxonsigned-ranktest;>2groups(matched):FriedmanANOVAbyranksMatching:Purpose:
Anefficientwayofcreatingacontrolgroupbasedonconfoundingfactors.(Bestbeforedataiscollected)
e.g.Preventabledeathsintraumacare:statisticallycontrollingfortheseverityofinjurywithineachspecificmechanismofinjury.(Actuallyadjustingbothseverityandmechanismisnotrealistic;andeventhiscausesproblems;P87)MultivariateAnalysis
Whento
use?
Onedependentvariablevsmultipleindependentvariables.Butlookatthefollowingexample:
LOGOReading
e.g.ComparetheinfectionrateofpatientsreceivingdrugAwiththatofpatientsreceivingdrugB.Afterrandomizingthepatientsintotwogroups,youfindonegroupissignificantlyolderthantheother.Nowyoucanusemultivariateanalysistoadjustfortheageofthepatients
Sousemultivariateanalysistodealwithconfoundingfactorsanddomentionthisisdoneinyourpaper.Forthis,youcanrefertoresearchpapersinyourfieldforvariablesthatarepotentiallyconfoundingfactors.
Logisticregressionanalysis
Examinethe
independentcontributionofmorethanonepredictorvariable.(Thelogisticregressionmodelshowedthatamongmotherswhosmokedcigarettesduringtheirpregnancy,theinfantoutcomecannotbepredictedbytheriskfactorunderstudy.)
LOGOReading
Giveitasecondthoughtbeforeconclude:therearenodifferencebetweenthestudygroup(Interaction)
e.g.Investigatorsfoundthatamongpeoplewithspinalcordinjury,bothdiabetesandsmokingweremoderateriskfactorsforpressureulcers.However,allofthepatientswhohaddiabetesandalsosmokedhadahistoryofpressureulcers.Thiseffectfromacombinationoffactorsisaninteraction.
AlwaystranslatemultivariateanalysisintoplainEnglishbecausereviewersandeditorsarenotstatisticalexperts.Presenttheresultsofmultivatiateanalysisinaclinicallyusefulformat.
Useevidencetosupporteachstepoftheanalysis.(Usespecificdatatojustproveyourmodelbad!)
LOGOReadingPvalueisnottheonlystandard;considerwhatmakessenseclinically.(preexistingdiseases;injuryseverity;time;treatment)
LearnCoxProportional-HazardsRegressiontoPublishPapersinaHigh-QualityJournal.
LOGOReading
Unit2TitleandAbstract(1)
LOGOTitlePrinciples:
1Accuracy准确2Brevity简洁3Clarity清楚4Effectiveness有效5Attractive吸引
Mistake1:toobigortoosmall
e.g.Transplantationofcornealstemcellsculturedonamnioticmembraneforcornealburn:experimentalandclinicalstudy(CMJ,2002,115(5):767-769)
experimentalandclinical--invitroandinvivo(toobig)
LOGOTitle
Mistake2:notaccurate
e.g.Experimentalstudyonmechanismandrarityofmetastasesinskeletalmuscle.(CMJ,2002,115(11))
没有把研究对象、问题说清楚。
Betternomorethan100characters(title+subtitle)
Agoodexample:Importanceofreplicationinmicroarraygeneexpressionstudies:statisticalmethodandevidencefromrepetitivecDNAhybridization(ProcNatlAcadSciUSA)
Attractiveness(醒目)
e.g.IdentificationofhumantumorinitiatingcellsNature,2004-11-18,432(7015):396-401
对比:Mechanismofligustraziniagainstthrombosis(CMJ)
Toogeneral
LOGOReading
两个省略不当的例子:1.Adhesionkinasecontrolsactinassembly2.Mousebehavior
LOGOReading
Correct:
AdhesionkinasecontrolsactinassemblyviaaFERM-mediatedinteractionwithArp2/3complex
(介词)AndrogenAdministrationtoagedMaleMiceIncreasesAnti-AnxietyBehaviorandEnhancesCognitivePerformance(verb)
LOGOReading
几点注意事项:
1.PlainEnglish2.NounderlineorItalics3.OnlyStandardAbbr4.Capitalizetheinitialletterofeachword5.Seldomuse“TheStudyof”or“TheResearchon”e.g.ThestudyofArgonaute2inmammaliangastrulationandpropermesodermformation
Argonaute2
isessentialformammaliangastrulationandpropermesodermformation
LOGOReading
句法结构:
词序非常重要;多由名词性短语构成;动名词或分词;少用陈述句。
如:你想表达B7-H4蛋白主要表达在非增生性肿瘤细胞中,其中一部分为肿瘤肝细胞:修改前:B7-H4mostexpressesonKi67negativebriantumorcellsandcanexpressonsomebraintumorstemcells.
修改后:
LOGOReading
句法结构:
词序非常重要;多由名词性短语构成;动名词或分词;少用陈述句。
修改后:B7-H4ispredominantlyrestrictedtoKi67-negativebraintumorincludingasmallsubpopulation
ofbraintumorstem-likecells.
LOGOReading
结构类型(国内较高水平级期刊):
1.短语型:(1)名词短语:
a.名词+介词短语
用食管镜检查以预计曲张静脉出血
b.定语+名词
原发性肝癌二级预防的随机分组前沿性研究
c.名词+分词短语
何杰金病放射治疗引起的甲状腺癌
LOGOReading
结构类型(国内较高水平级期刊):
1.短语型:(1)名词短语:
a.名词+介词短语
用食管镜检查以预计曲张静脉出血
Predictionofvaricosehaemorrhagebyesophagealendoscopyb.定语+名词
原发性肝癌二级预防的随机分组前沿性研究Randomizedcontrolledprospectivestudyofsecondarypreventionforprimarylivercancerc.名词+分词短语
何杰金病放射治疗引起的甲状腺癌
ThyroidcarcinomainducedbyirradiationforHodgkin’sdisease
LOGOReading
(2)动名词短语:
心房纤颤患者中风预防
(3)介词短语:
原发性肝癌临床诊断探讨
句子型:(1)陈述句:
人类hR24L基因参与DNA切除修复和重组修复的研究
(2)疑问句(常见于评述性文章):尚未解决的问题——饮酒者冠心病少吗?
LOGOReading
(2)动名词短语:
心房纤颤患者中风预防
Preventingstrokeinpatientswithatrialfibrillation
(3)介词短语:
原发性肝癌临床诊断探讨Onclinicaldiagnosisofprimarycarcinomaofliver
句子型:(1)陈述句:
人类hR24L基因参与DNA切除修复和重组修复的研究
HumanhR24LgeneisinvolvedinDNAexcisionrepairand
recombinationrepair.
(2)疑问句(常见于评述性文章):尚未解决的问题——饮酒者冠心病少吗?
LOGOReadingUnresolvedissue:Dodrinkershavelesscoronaryheartdisease?中心词的使用:(一般放在句首)
e.g.针疗对冠心病心绞痛患者左心功能状态的影响
e.g.氟烷麻醉治疗新生儿受损肺功能
LOGOReadingUnresolvedissue:Dodrinkershavelesscoronaryheartdisease?中心词的使用:(一般放在句首)
e.g.针疗对冠心病心绞痛患者左心功能状态的影响
Theacupunctureeffectonleftventricularfunctionin
patientswithcoronaryheartdiseaseandanginapectorise.g.氟烷麻醉治疗新生儿受损肺功能
Halothaneanesthesiarebuildsimpairedpulmonaryfunctioninnewborns.(麻醉专家)
Impairedpulmonaryfunctioninnewbornsanesthetized
withhalothane.(儿科专家)
LOGOReading
Practice:
1.探讨:discussionof/on,aprobeinto,investigationof…
心源性猝死51例临床病理探讨
2.意义:significance/importanceof/in/at
血清肌浆球蛋白临床评价对诊断急性心肌梗塞的意义
3.观察(报告、结果):anobservationof/on/in(有时可略去)窒息后多器官功能受损新生儿细胞内外钙水平观察4.调查、实验:surveyof/on;test/trial慢性肾功能衰竭的甲状腺切除疗法38例调查
LOGOReading
Practice:
1.心源性猝死51例临床病理探讨:Suddencardiacdeath:clinicopathologicinvestigationof51cases
2.血清肌浆球蛋白临床评价对诊断急性心肌梗塞的意义:
Significanceofclinicalassessmentofserummyosininthediagnosisofacutemyocardialinfarction
3.窒息后多器官功能受损新生儿细胞内外钙水平观察:Levelsofplasmacalcuimandredcellcalcuiminnewbornswithmulti-organdamageafterasphyxia.4.慢性肾功能衰竭的甲状旁腺切除疗法38例调查:Surveyof38casesofparathyroidectomyinchronicrenalfailure
LOGOReading
5.总结:experience/experienceof
35例恶性高血压治疗总结
6.报告:areportof/on
青少年桡骨远端骨骺损伤附51例报告
7.技术、特征、模式等:technique,characteristics,model…结肠腺癌细胞线SW620生物特征
8.(药物)治疗:A治疗B/AtreatmentofB
大量剂氨甲喋呤治疗急性淋巴细胞性白血病
LOGOReading
5.35例恶性高血压治疗总结
Treatmentformalignanthypertension:Anexperienceof35cases
6.青少年桡骨远端骨骺损伤附51例报告
Distalepiphysisinjuryofradiusinadolescence:Areportof51cases
7.结肠腺癌细胞线SW620生物特征
BiologicalpropertiesofhumancolonicadenocarcinomacelllinesSW620
8.大量剂氨甲喋呤治疗急性淋巴细胞性白血病
Treatmentofacutelymphocyticleukemia
withhighdosemethotrexate
LOGOReading
9.(非药物)治疗:A治疗B/AinthetreatmentofB
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