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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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