The 5-Minute Clinical Consult Standard 2015 PDF
Preview The 5-Minute Clinical Consult Standard 2015
P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 The 5-Minute Clinical Consult Standard 2015 23RD EDITION i P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 ii P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 23:8 The 5-Minute Clinical Consult Standard 2015 Editor-in-Chief FrankJ.Domino,MD Professor DirectorofPredoctoralEducation DepartmentofFamilyMedicineandCommunityHealth UniversityofMassachusettsMedicalSchool Worcester,Massachusetts Associate Editors 23RD EDITION RobertA.Baldor,MD,FAAFP ProfessorandVice-Chairman,EducationalAffairs DepartmentofFamilyMedicineandCommunityHealth Includes 30-Day Free UniversityofMassachusettsMedicalSchool Worcester,Massachusetts Trial to 5minuteconsult.com JeremyGolding,MD,FAAFP ProfessorofFamilyMedicineandObstetrics& Gynecology UniversityofMassachusettsMedicalSchool QualityOfficer DepartmentofFamilyMedicineandCommunityHealth UniversityofMassachusettsMemorialHealthCare HahnemannFamilyHealthCenter Worcester,Massachusetts JillA.Grimes,MD,FAAFP ClinicalInstructor DepartmentofFamilyMedicine UniversityofMassachusettsMedicalSchool Worcester,Massachusetts AttendingPhysician UniversityofTexasHealthServices Austin,Texas iii P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 AcquisitionsEditor:RebeccaGaertner ProductDevelopmentEditor:LeanneVandetty ProductionProjectManager:PriscillaCrater SeniorManufacturingCoordinator:BethWelsh StrategicMarketingManager:StephanieManzo DesignCoordinator:TeresaMallon ProductionService:Aptara,Inc. (cid:2)C 2014WoltersKluwerHealth TwoCommerceSquare 2001MarketStreet Philadelphia,PA19103USA LWW.com Allrightsreserved.Thisbookisprotectedbycopyright.Nopartofthisbookmaybereproducedinanyform byanymeans,includingphotocopying,orutilizedbyanyinformationstorageandretrievalsystemwithout writtenpermissionfromthecopyrightowner,exceptforbriefquotationsembodiedincriticalarticlesand reviews.MaterialsappearinginthisbookpreparedbyindividualsaspartoftheirofficialdutiesasU.S. governmentemployeesarenotcoveredbytheabove-mentionedcopyright. PrintedinChina LibraryofCongressCataloging-in-PublicationData ISBN-13:978-1-4511-9214-8 ISBN-10:1-4511-9214-2 Carehasbeentakentoconfirmtheaccuracyoftheinformationpresentedandtodescribegenerally acceptedpractices.However,theauthors,editors,andpublisherarenotresponsibleforerrorsoromissions orforanyconsequencesfromapplicationoftheinformationinthisbookandmakenowarranty,expressed orimplied,withrespecttothecurrency,completeness,oraccuracyofthecontentsofthepublication. Applicationoftheinformationinaparticularsituationremainstheprofessionalresponsibilityofthe practitioner. Theauthors,editors,andpublisherhaveexertedeveryefforttoensurethatdrugselectionanddosage setforthinthistextareinaccordancewithcurrentrecommendationsandpracticeatthetimeofpublication. However,inviewofongoingresearch,changesingovernmentregulations,andtheconstantflowof informationrelatingtodrugtherapyanddrugreactions,thereaderisurgedtocheckthepackageinsertfor eachdrugforanychangeinindicationsanddosageandforaddedwarningsandprecautions.Thisis particularlyimportantwhentherecommendedagentisaneworinfrequentlyemployeddrug. SomedrugsandmedicaldevicespresentedinthepublicationhaveFoodandDrugAdministration(FDA) clearanceforlimiteduseinrestrictedresearchsettings.Itistheresponsibilityofthehealthcareproviderto ascertaintheFDAstatusofeachdrugordeviceplannedforuseintheirclinicalpractice. Topurchaseadditionalcopiesofthisbook,callourcustomerservicedepartmentat(800)638-3030orfax ordersto(301)223-2320.Internationalcustomersshouldcall(301)223-2300. VisitLippincottWilliams&WilkinsontheInternet:atLWW.com.LippincottWilliams&Wilkinscustomer servicerepresentativesareavailablefrom8:30amto6pm,EST. 10 9 8 7 6 5 4 3 2 1 iv P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 AsIsatdowntowritethis,theradioannouncedthepassingofNelsonMandela.Imaginebeingimprisonedfor yourbeliefsfor27years!NelsonMandelastoodquietlyandsoundlyonhisbeliefs,knowingtheworldwouldbea betterplaceforhispersonalturmoil.History’s highpointsoccurwhensomeonecomesforwardtotakean unpopularstand,believingtheworldwillbeabetterplacefortheirsuffering.Istheworldofmedicinereadyto stepup? ChoosingWisely(http://www.choosingwisely.org/).Thesetwowordsmadeahugeimpactthispastyear,asmost everymedicalspecialtyandhealthcare–relatedgroup(over60!)foundconsensusonwhattestsandtreatments wereofuseandbeneficialtosociety....andwhichwerewastefulandharmful.Despiteeachgroup’s involvement, manycalledthisheresy.Itisnot.Thiseffortisthebeginningofapplyingevidence-basedmedicineandacost effectiveapproachtocareofourpatients. Likeitornot,theAffordableCareAct,completewithflawsandtechnologicalblunders,wasbroughtforwardinan efforttobringhealthinsuranceto47millionUScitizenswhowerepreviouslyuninsured;thatis1in6people. PresidentObamavoluntarilyaddressedsomethingmostAmericansbelievetobenecessary—healthinsurance coverageforall.TheCongressionalBudgetOffice,anonpartisangroupthatprovidestheUSCongresswithreal numbers,continuestoreportlowerthanexpectedcosts,withsignificantpatientbenefits (https://www.cbo.gov/topics/health-care/affordable-care-act). Otherchangesarerapidlyoccurringinhealthcare.Insome,solid,evidence-basedmedicalresearchhasyielded resultsthatshakeupthestatusquo,directingustowardchangesthatwillpreventlongtermmorbidityand mortality: —Headtraumafromsports-relatedactivitiesduringadolescenceandearlyadulthoodcausespermanentdamage. Concussionpreventionisthepriority.Willfootballsoonbeasportplayedonlyincollegeandafter? —Prescription narcotics had a rough year: First, a call for training in appropriate use of long-term agents for nonmalignant pain and a systematic review of data showing no benefit of opioids for chronic low back pain. Accidental prescription opioid death is the most common cause of death in those under the age of 50 in the USandisourresponsibility.Pullingbackonprescribingtheseagentswillbeachallengewemustacceptwiththe graceandstrengthofMandela. —Curing hepatitis C can be at hand, and doing so will move cirrhosis and hepatoma from their leading role as causes of cancer death worldwide. Screen those born between 1945 and 1965 once and all who practice high-risk behaviors (blood transfusion before 1992, long-term hemodialysis, born to an HCV-infected mother, incarceration,intranasaldruguse,gettinganunregulatedtattoo,andotherpercutaneousexposures). —HIVhasbecomeachronicdiseaseandlikehepatitisCshouldnowbepartofouruniversalroutineadulthealth screening; the new guidelines recommend screening all adolescents and adults ages 15 to 65 years, allpregnantwomen,andthoseyoungeradolescentsandolderadultswhoareatincreasedrisk. —Bacteriainourgutmayplayahugeroleinourdegreeofhealth,influencingillnessfromviralURIstocoronary artery disease...and even maybe obesity! In our efforts to overcome obesity, we will need to advocate a more vegetarian-baseddietasaninterventiontoalterthegutmicrobiomeandpreventillness. —Preventionofcardiovascularmorbidityandmortalityisclearlybenefitedbyuseofstatinswherecardiovascular risk is high but is not achieved by reaching a simple LDL goal. Again, we will need to prioritize helping patients to stop smoking and to start exercising. The benefit of medications to prevent heart disease hinges on these interventions,notjustapill. Mandelasaid“resentmentislikedrinkingpoisonandthenhopingitwillkillyourenemies.’’ Cliniciansinalldisciplines shouldrememberthatourdifferencesinopinionaresomuchsmallerthanourcommongoalofhelpingothers. This year’s 5-Minute Clinical Consultis dedicated to those who have suffered long and risked much to make ourpatientsbetter.Let’s makecertaintheireffortswerejustthebeginningofabetterfuture. v P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 vi P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 PREFACE Anymanmayeasilydoharmbutnoteverymancan 5minuteconsult.comdeliversquickaccesstocontinuallyupdated dogoodtoanother. onlinecontent—anidealresourcewhenyou’retreatingpatients.In- tegrate 5-Minute content into your workflow, with online access, —PLATO so you never have to skip a beat. If you purchased the Premium Borninthe3rdcenturyBC,Platounderstoodtheessentialrole Edition your access includes 1 year FREE; the Standard Edition of providing care to those in need. And when you hold this includesafree30-daytrial!Thesitepromisesaneasy-to-useinter- book,youtoohaveenormouspotentialtoservehumanity,one face,allowingsmoothmaneuverabilitybetweentopics,algorithms, personatatime. images, videos, and patient education materials, as well as over WelcometoThe5-MinuteClinicalConsult2015.Oureditorial 1,200online-onlytopics. team has collaborated with hundreds of authors so that you may Evidence-basedhealthcareistheintegrationofthebestmedical deliver your patients the best care. Each topic provides you with informationwiththevaluesofthepatientandyourskillasaclinician. quickanswersyoucantrust,whereandwhenyouneedthemmost, WehaveupdatedourEBMcontentanditsvisibility,soyoucanfocus eitherinprintoronlineatwww.5minuteconsult.com. onhowtobestapplyitinyourpractice. Thishighlyorganizedcontentprovidesyouwith: TheHealthMaintenance1-pagesummarieshavebeenupdated (cid:2) through December 2013 and are based on the US Preventive Differentialdiagnosissupportfromanaccessible,targeted ServicesTaskForcerecommendations. search,deliveringtheanswersyouneedquickly (cid:2) The Algorithm section includes both diagnostic and treatment Currentevidence-baseddesignationshighlightedineachtopic (cid:2) algorithms. This easy-to-use graphic method helps you evaluate ArevisedandupdatedHealthMaintenancesection (cid:2)880+commonlyencountereddiseasesanddisordersinprint, an abnormal finding and prioritize treatment. They are also ex- cellent teaching tools, so share them with the learners in your andmorethan1,200additionaltopicsonline,including500 office. topicsfromThe5-MinutePediatricConsultandover620topics Inourroleasclinicians,caringforthosewhoareillorhelpingto fromThe5-MinuteEmergencyMedicineConsult preventillness,weusetestsandprescribetreatments,hopingthey (cid:2) FREEPointofCareCMEandCE:1/2hourcreditforevery improve outcomes. As importantly, our words and actions, even a digitalsearch sharedsmile,canmakeahugedifference.Wecan“dogood’’forour (cid:2)200+diagnosticandtreatmentalgorithms patients, especially when we meet them at their most vulnerable. (cid:2) Colorimagesandvideosforprocedures,treatment,andphysical Thankyouformakingadifference. therapy The5-MinuteClinicalConsulteditorialteamvaluesyourobser- (cid:2)AtoZDrugDatabasefromFacts&Comparisons(cid:2)R vations,sopleaseshareyourthoughts,suggestions,andconstruc- (cid:2) Morethan1,250patienthandoutsinEnglishandSpanishfrom tivecriticismthroughourWebsite,www.5mintueconsult.com. theAAFP (cid:2) ICD-10CodesandDSM-Vcriteria;inaddition,ICD-9and FRANKJ.DOMINO,MD SNOMEDcodesareavailableonline. January1,2014 vii P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 viii P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 EVIDENCE-BASED MEDICINE WHATISEVIDENCE-BASEDMEDICINE? screeningmammogramsinthisgrouptrulyidentifiedcancer.The other78%arefalsepositives. Rememberwhenweusedtotreateveryotitismediawithan- YoucantellMLonly1outof5abnormalmammogramscorrectly tibiotics?Theserecommendationscameaboutbecausewe identifycancer;the4arefalsepositives,buttheonlywaytoknow appliedlogicalreasoningtoobservationalstudies.Ifbacteria whichmammogramiscorrectistodofurthertesting. causeanacuteotitismedia,thenantibioticsshouldhelpitresolve The corollary of the PPV is the Negative predictive sooner,withlessmorbidity.Yet,whenrigorouslystudied(viaasys- value(NPV),whichisthepercentofnegativetestresultsthat tematicreview),wefoundlittlebenefittothisintervention. aretrulynegative. The underlying premise of evidence-based medicine (EBM) is The PPV and NPV tests are population dependent, while the theevaluationofmedicalinterventions,andtheliteraturethatsup- SensitivityandSpecificityarecharacteristicsofthetest,andhave ports those interventions, in a systematic fashion. EBM hopes to littletodowiththepatientinfrontofyou.Sowhenyoureceivean encouragetreatmentsproventobeeffectiveandsafe.Andwhen abnormallabresult,especiallyascreeningtestlikemammography, insufficient data exists, it hopes to inform you on how to safely understandtheirlimitsbasedontheirPPVandNPV. proceed. EBM uses as endpoints of real patient outcomes; morbidity, TreatmentInformationisalittledifferent.Indiscern- mortalityandrisk.Itfocuseslessonintermediateoutcomes(bone ingthestatisticsofrandomized,controlledtrialsofinterventions, density)andmoreonpatientconditions(hipfractures). first consider an example. The Scandinavian Simvastatin Sur- Implementing EBM requires 3 components: The best medical vivalStudy(4S)(Lancet.1994;344[8934]:1383–1389)found evidence,theskillandexperienceoftheprovider,andthevaluesof using simvastatin in patients at high risk for heart disease for thepatients.Shouldthispatientbescreenedforprostatecancer? 5yearsresultedindeathsin8%ofpatientsvs.12%ofthose Itdependsonwhatisknownaboutthetest,onwhatyouknowof onplacebo;thisresultsinarelativeriskof0.70,arelativerisk itsbenefitsandharms,yourabilitytocommunicatethatinformation, reduction (RRR) of 33%, and a number needed to treat of andthatpatient’sinformedchoice. 25. ThisbookhopestoaddressthefirstEBMcomponent,providing Therearetwowaysofconsideringthebenefitsofanintervention you access to the best information in a quick format. While not withrespecttoagivenoutcome.Theabsoluteriskreduction(ARR) everytestortreatmenthasthislevelofdetail,manyoftheincluded isthedifferenceinthepercentofpeoplewiththeconditionbefore interventionshereusesystematicreviewliteraturesupport. andaftertheintervention.Thus,iftheincidenceofMIwas12%for Thelanguageofmedicalstatisticsisusefultointerpretingthe the placebo group and 8% for the simvastatin group, the ARR is conceptsofEBM.Belowisalistoftheseterms,withexamplesto 4%(12%−8%=4%). helptaketheconfusionandmysteryoutoftheiruse. TheRRRreflectstheimprovementintheoutcomeasapercent- Prevalence:Proportionofpeopleinapopulationwhohave age of the original rate and is commonly used to exaggerate the adisease(intheUS,0.3%[3in1,000]peopleovertheage50 benefitofanintervention.Thus,iftheriskofMIwerereducedbysim- havecoloncancer). vastatinfrom12%to8%,thentheRRRwouldbe33%(4%/12%= Incidence: How many new cases of a disease occur in a 33%);33%mayappearbetterthan4%,the4%thatreflectsthe populationduringanintervaloftime;forexample,“theestimated trueoutcome. incidenceofcoloncancerintheUSis104,000in2005.’’ ARR is usually a better measure of clinical significance of an Sensitivity(Sn):Percentofpeoplewithdiseasewhotest intervention. For instance, in one study, the treatment of mild hy- positive;formammography,thesensitivityis71–96%. pertensionwasbeenshowntohaveaRRRof40%over5years Specificity (Sp): Percent of people without disease who (40%fewerstrokesinthetreatedgroup).However,theARRwas testnegative;formammography,thespecificityis94–97%. only 1.3%. Because mild hypertension is not strongly associated NowsupposeyousawML,a53-year-oldwoman,foraHealth withstrokes,aggressivetreatmentofmildhypertensionyieldsonly Maintenancevisit,orderedascreeningmammogram,andthereport asmallclinicalbenefit.Don’tconfuseRelativeRiskReductionwith demonstratesanirregularareaofmicrocalcifications.Sheiswaiting RelativeRisk. inyourofficetoreceivehertestresults;whatcanyoutellher? Absolute (or attributable) risk (AR): The percent of Sensitivityandspecificityrefertocharacteristicsofpeoplewho peopleintheplaceboorinterventiongroupwhoreachanend areknowntohavedisease(sensitivity)orthosethatareknownnot point; in the simvastatin study, the absolute risk of death was tohavedisease(specificity).But,whatyouhaveisanabnormaltest 8%. result. To better explain this result to ML, you need to know the Relativerisk(RR):Theriskofdiseaseofthosetreatedor positivepredictivevalue. exposedtosomeintervention(i.e.,simvastatin)dividedbythose Positivepredictivevalue(PPV):Percentofpositivetest intheplacebogrouporwhowereuntreated. resultsthataretrulypositive;thePPVforawomanaged50–59 —IfRR<1.0,itreducesrisk—thesmallerthenumber,the isapproximately22%.Thatistosaythatonly22%ofabnormal greatertheriskreduction. ix P1:OSO/OVY P2:OSO/OVY QC:OSO/OVY T1:OSO LWBK1309-Standard-FM LWBK1309-Domino February20,2014 14:55 x (cid:2) (cid:2) (cid:2) Evidence-Based Medicine —IfRR>1.0,itincreasestherisk—thegreaterthenumber, nevergetspublished.Sowhenyoureadofaninterventionthat thegreatertheriskincrease. “works,’’ wonder if other studies were done that did not show Relative risk reduction (RRR): The relative decrease in benefitandwentunpublished. riskofanendpointcomparedtothepercentofthatendpoint Comparatorbiasoccurswhenresearchcomparesanin- intheplacebogroup. terventiontoplacebo,whenplaceboisnotthestandardofcare. Ifyouarestillconfused,justremembertheRRRisanoveresti- Knowinganewantibioticismoreeffectivethanplacebofortreat- mationoftheactualeffect. ingacuteotitismediaisnothelpfulifyoutypicallyuseamoxicillin. Why not release research comparing the new drug to the Number needed to treat (NNT): This is the number of standardofcare?Often,theresearchhasbeendone,andthe peoplewhoneedtobetreatedbyaninterventiontopreventone adverseoutcome.A“good”NNTcanbealargenumber(>100) newdrugprovednobetter.Ifthisstudydoesnotgetpublished, youhaveanexampleofpublicationbias. ifriskofseriousoutcomeisgreat.Iftheriskofanoutcomeis notthatdangerous,thenlower(<25)NNTsarepreferred. Selection bias involves either using a tool that does not discriminate between populations selected or just reporting a TheNNTshouldbecomparedtoasimilarstatistic,theNumber justsubsetofstudyparticipantsfromastudy.Eitherwillresultin NeededtoHarm(NNH).Thisisthenumberofpeoplewhohaveto thedatabeingskewedbecauseitcanonlybeappliedtosmall begiventreatmentbeforeoneexcesssideeffectorharmoccurs. subsetofpeople. WhentheNNTiscomparedtotheNNH,youandthepatientcan Attrition bias and the concept of intention to treat. judge whether the benefit of the intervention is great enough to Attritionbiasiswhenresearchersdonotfullyacknowledgeand outweightheriskofharm. addresshowastudydealswithparticipantswhodonotadhere totheresearchprotocolordropoutcompletely.Intentiontotreat EVIDENCED-BASEDGRADING: analysishopestodiminishattritionbiasbystatisticallyconsider- To help you interpret diagnostic and treatment recommendations ingthenonadheringordroppedoutpatientsasunsuccessfully within The 5-Minute Clinical Consult, we have graded the best benefitingfromtheintervention. informationwithinthetext,andhighlightedthiscontent. Commercial (funder) bias involves who paid for the re- An“A’’grademeansthereferenceisfromthehighest-qualityre- search being done, and do they have a vested interest in the source,likeasystematicreview.Asystematicreviewisasummary outcome.Despiteitssizeandscope,therecentJupiter trialon of the medical literature on a given topic that uses strict, explicit treatinglow-riskadultswithastatinhasbeencalledintoques- methods to perform a thorough search of the literature and then tion, as the company who funded the study makes the brand provides a critical appraisal of individual studies, concluding in a namedrugusedinthestudyandtheleadauthorispartowner recommendation.Themostprestigiouscollectionofsystematicre- oftheuniquetestemployedinthetrial.Thedatamaybeaccu- viewsisfromtheCochraneCollaboration(www.cochrane.org). rate,butuntilthisisstudiedbylessvestedinterests,somefeel A“B’’grademeansthedatareferencedcomesfromhigh-quality itsoutcomecannotbeclinicallyapplied. randomizedcontrolledtrialsperformedtominimizebiasintheirout- Haveyoubeenannoyedhowoneweekyoulearnofarandom- come.Biasisanythingthatinterfereswiththetruth;inthemedical ized controlled trial that supports a treatment, to be followed the literature,itisoftenunintentional,butitismuchmorecommonthan next week with a contradictory article? Statisticians have figured weappreciate.Inshort,alwaysassumesomedegreeofbiasexists outhowtoresolvethisusingsomethingcalledasystematicreview. inanyresearchendeavor. Systematic reviews take all the literature on a topic, say A“C’’ gradeimpliesthereferenceuseddoesnotmeettheAor usingantibioticstotreatotitismedia,andcombinesthedatato Brequirements;theyareoftentreatmentsrecommendedbycon- determineifthesumofallthetrialstellsadifferentstorythan sensusgroups(liketheAmericanCancerSociety).Insomecases, any single trial. The large number of participants in this type they may be the standards of care. But implicit in a group’s rec- of research results in a much more statistically (and clinically) ommendationisthebiasoftheauthororthegroupthatsupports significantconclusionthananysinglepaper.Wantmore?Check thereference.Forexample,theAmericanUrologicalSociety’srec- thisout:http://musculoskeletal.cochrane.org/what-systematic- ommendationaroundscreeningforprostatecancermaybemoti- review. vatedbytheirnarrowscopeandfinancialbenefit.Comparethisto Ameta-analysisisaquantitativesystematicreview,anddemon- the recommendations of the US Preventive Services Task Force stratesitoutcomesintheformofaforestplot.Thebottomlinewith (www.ahrq.gov), who recommends against screening for prostate interpretationofaforestplotislookforthediamondonthebottom. cancer. IfitistoLEFToftheverticalline,itmeansriskofanoutcomewas reducedbytheintervention.IfitisfullytotheRIGHT,thenriskof BIAS: thatoutcomewasincreased.Andifthediamondtouchesthevertical Biasisanythingthatinterfereswiththetruth.Therearemanytypes line,itmeanstherewasnostatisticalinfluenceoftheintervention of bias that should be considered by the publishers of medical on the outcome. To understand these concepts better, here is a information. Below describes a number of bias types that often great resource: http://www.cochrane-net.org/openlearning/html/ affectourcarewithoutusknowingitispresent: mod3-2.htm. Publication bias occurs when research is not published; I hope this brief introduction to EBM has been informative, thisisoftenwhenastudyfindsdatathatdoesnot supportan clear, and helpful. If any of the information above seems unclear, intervention. The motivation to publish information that “didn’t orifyouhaveaquestion,pleasecontactusviawww.5minuteconsult. work’’islow.Itisestimatedthatupto40%ofallmedicalresearch com.
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