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JOURNAL WATCH (AND ITS DESIGN) IS A REGISTERED TRADEMARK OF THE MASSACHUSETTS MEDICAL SOCIETY.AN EDITORIALLY INDEPENDENT LITERATURE-SURVEILLANCE NEWSLETTER SUMMARIZING ARTICLES FROM M AJOR MEDICAL JOURNALS. 2013 MASSACHUSETTS MEDICAL

ALL RIGHTS RESERVED. DISCLOSURE INFORMATION ABOUT OUR AUTHORS CAN BE FOUND AThttp://general-medicine.jwatch.org/misc/board_disclosures.dtl

Antihypertensive Therapy plusNonsteroi al Anti-InflammatoryDrugs Contribute to Riskfor Ki ney InjuryTriple therapy ( a diuretic + an ACE inhibitor or ARB + an NSAID)was associated with excess risk.

Patients with hypertension often have

con itions for which nonsteroi al anti-inflammatory rugs (NSAIDs) are in i-cate . However, both NSAIDs an certainantihypertensive rugs (i.e., iuretics,angiotensin-convertingenzyme [ACE] in-hibitors, an angiotensin-receptor blockers[ARBs]) have hemo ynamic effects on theki ney. Investigators retrospectively stu iea U.K. atabase to examine whether anti-hypertensive therapy in combination with

regular NSAID use is associate withexcess risk for acute ki ney injury.

Nearly 490,000 users of antihyper-tensive rugs were inclu e in the stu y.During a mean follow-up of 5.9 years,>2200 cases of ki ney injury were i enti-fie ( efine as first hospital a missionrelate to ki ney injury). A juste formultiple confoun ers, ouble therapy (an NSAID, plus either a iuretic, an ACEinhibitor, or an ARB) was not associate

with any greater likelihoo of ki ney injury than was an antihypertensive rug alone.In contrast, triple therapy (an NSAID, plusa iuretic, plus an ACE inhibitor or an ARB)significantly heightene the inci ence of ki ney injury compare with the sametherapy without an NSAID (rate ratio, 1.3).Notably, highest risk was observe uringthe first 30 ays of triple therapy.

COMMENTIn this large retrospective stu y,triple therapy with a iuretic plusan ACE inhibitor or an ARB plus anNSAID was associate with significant ex-cess risk for ki ney in jury. These results arebiologically plausible: Volume contractioncause by iuretics an renal efferent ar-teriole ilatation cause by ACE inhibitorsan ARBs, together with renal afferentarteriole constriction cause by NSAIDs

( ue to inhibition of prostacyclin synthesis),likely accounts for the excess risk. Paul S. Mueller, MD, MPH, FACP

Lapi F et al. Concurrent use of diuretics, angiotensinconverting enzyme inhibitors, and angiotensin recep-tor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ 2013 Jan 8; 346:e8525.(http://dx.doi.org/10.1136/bmj.e8525)

Recommen e A ult Immunization Sche ulefor 2013Highlights of the updated recommendationsand a link to the CDCs vaccine resources

The U.S. A visory Committee on Immuni-zation Practices has issue up ate gui e-lines for a ult immunization. Highlightsinclu e the following:

13-valent pneumococcal conjugate vaccine (PCV13) is recommen e fora ults (age, 19) with immunocom-promising con itions (in a itionto the pneumococcal polysacchari e vaccine, or PPSV23).

PPSV23 shoul be a ministere toel ers (age, 65) an rea ministereto those who receive one or two osesbefore age 65 if at least 5 years havepasse .

SUMMARY & COMMENTAntihypertensive Therapy

plus Nonsteroidal Anti-Inammatory DrugsContribute to Risk for Kidney Injury ...................... 37

Blood Culture ContaminationIs Lowered Dramaticallyby Change in Technique ..........................................38

More Evidence Supports Early HIV Treatment ...... 38

Pneumocystis PneumoniaAfter Rituximab Treatment ...................................... 39

Diagnosing Pneumoniawith Ultrasound in Children .................................... 39

Bedside Ultrasound in the ICU:Diagnostic Aidor One Test Too Many? ............................................ 39

Dont Rely on Scoring Systems to Predict Clinically Important BleedingDuring Oral Anticoagulant Therapy ...................... 40

Extended VTE Prophylaxisin Acutely Ill Medical Patients:Dont Try This at Home............................................. 40

Selective D-Dimer TestingImproves Efciency of DVT Diagnosis ................. 40

No CV Benet from Vitaminand Antioxidant Supplements ................................41

Rate Control for Atrial Fibrillation:What Is the Best Drug to Use? .............................. 41

Olmesartan vs. Olmesartanplus a Calcium-Channel Blocker .......................... 41

Serial Assessment of Left Ventricular Functionin Chemotherapy Patients ............................ 42

More Evidence That the Biologyof Embryogenesis Explains Metastasis ............... 42

Increasing Doses of AntidepressantsAre Associatedwith QT Interval Prolongation ................................ 43

Early Introduction of Complementary FoodsMight Prevent Allergic Disease............................. 43

A Strategy to Avoid Surgeryfor Acute Anterior Cruciate Ligament Tears ....... 44

CLINICAL PRACTICE GUIDELINE WATCHRecommended Adult Immunization Schedule

for 2013........................................................................ 37

USPSTF Now Recommends Screening Womenfor Intimate Partner Violence ................................. 43

CONTENTS

GENERAL MEDICINE

March 1, 2013 Vol. 33 No. 5

From the publishers of The New England Journal of Medicine

SUMMARY & COMMENT

CLINICAL PRACTICEGUIDELINE WATCH

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Tetanus, iphtheria, an acellularpertussis (T ap) vaccination is recom-men e for el ers (age, 65) an forpregnant women (at 2736 weeksgestation) to help protect newborns.

Live attenuate influenza vaccine(LAIV) for the 20132014 season

likely will be available only as a qua rivalent vaccine (inclu ing 2 influenza Astrains, H3N2 an H1N1, an 2 influ-enza B strains), which is expecte toimprove coverage beyon that of theprevious trivalent vaccine.

Patients who experience only hivesfrom egg exposure shoul receive inac-tivate influenza vaccine (IIV) ratherthan LAIV. IIV might be available inboth the trivalent an qua rivalentforms for 20132014.

Bivalent human papillomavirus vac-cine (HPV2) or qua rivalent vaccine(HPV4) are recommen e for girlsan women, an HPV4 is recom-men e for boys an men.

COMMENTLevels of vaccination a herence remainlow, an a strong recommen ationfrom provi ers is associate withbetter a herence.

Jamaluddin Moloo, MD, MPH

Advisory Committee on Immunization Practices.

Recommended adult immunization schedule: United States, 2013.Ann Intern Med 2013 Feb 5; 158:191.

CDC vaccine information is available athttp://www.c c.gov/vaccines free of charge.

Bloo Culture ContaminationIs Lowere Dramatically

by Change in TechniqueUsing sterile technique and a checklist dropped the contamination rate by half.

As a quality improvement intervention,an aca emic emergency epartment intro-

uce a stan ar ize steri le technique forrawing bloo . Researchers compare con-

tamination rates of bloo cultures rawnuring the 48 weeks before an 48 weeks

after the intervention.

The usual technique before the intervention typically involve nonsterile gloves,local skin preparation with 0.67 mL of 2%chlorhexi ine gluconate/70% isopropylalcohol, an no sterile fiel s. The steriletechnique involve a checklist that out-line optimal technique, a policy change

requiring use of the new stan ar izetechnique, an a sterile bloo culture kit

esigne to be use with steri le gloves. Thekit inclu e an antiseptic skin evice with3 mL of 2% chlorhexi ine gluconate/70%isopropyl alcohol, a fenestrate rape, a21-gauge butterfly nee le, a 10 mL syringe,an two isopropyl alcohol pa s for cleans-ing the tops of culture bottles.

The contamination rate roppe sig-nificantly, from 4.3% in the 7389 bloocultures rawn using the usual techniqueto 1.7% in the 6590 bloo cultures rawnusing the sterile technique a relativere uction of 72%.

COMMENTObtaining bloo cultures now is a part of several performance measures in the careof patients with infectious iseases. To

minimize unnecessary a itional testingor the a ministration of uncalle -for anti-biotics, taking measures to minimize con-tamination rates just makes sense. Thissimple intervention a checklist, changein policy, an sterile technique usingitems available in every emergency

epartment oes the job. Diane M. Birnbaumer, MD, FACEP, Journal Watch Emergency Me icine

Self WH et al. Reducing blood culture contamina-tion in the emergency department: An interrupted time series quality improvement study. Acad Emerg Med 2013 Jan; 20:89.

More Evi ence SupportsEarly HIV Treatment Patients treated within a few months of contracting the virus had higher CD4-cell counts in the long term.

The optimal time to initiate combinationantiretroviral therapy in HIV-positivepeople is ebate wi ely, but most recentevi ence suggests that treatment shoul

start relatively early in infection someexperts say as early as possible. Now, twonew stu ies a support to this argument.

An international team of researchersran omize 366 patients who becameinfecte with HIV within the previous6 months to receive 48 weeks of combi-nation therapy, 12 weeks of combinationtherapy, or no therapy (stan ar of care).After 4 years, the likelihoo of a CD4 countof 350/mm 3 was significantly lower in thegroup who receive 48 weeks of treatment

EDITOR-IN-CHIEFAllan S. Brett, MD, Professor of Medicine andDirector, Division of General Internal Medicine,University of South Carolina School of Medicine

EXECUTIVE EDITOR Charleen M. Hamilton, PhDMassachusetts Medical Society

DEPUTY EDITOR Thomas L. Schwenk, MD, Dean, University

of Nevada School of Medicine; Vice Presidentof Health Sciences, University of Nevada

FOUNDING EDITOR Anthony L. Komaroff, MD,Senior Physician,Division of General Medicine, Brigham andWomens Hospital, Boston; Professor of Medicine,Harvard Medical School

ASSOCIATE EDITORSKirsten E. Fleischmann, MD, MPH, AttendingPhysician, Medical Center at the Universityof California, San Francisco; Professor of ClinicalMedicine, University of California, San FranciscoPatricia Anne Kritek, MD, EdM, AssociateProfessor, Division of Pulmonary and Critical CareMedicine, University of Washington, SeattleJamaluddin Moloo, MD, MPH, Associate Professorof Medicine, Department of Medicine and Radiology,University of Colorado Health Sciences CenterPaul S. Mueller, MD, MPH, FACP, Chair, Division ofGeneral Internal Medicine, Professor of Medicine,Mayo Clinic College of Medicine, Rochester, MNRobert W. Rebar, MD, Executive Director, AmericanSociety for Reproductive Medicine, Birmingham, ALBruce Soloway, MD, Associate Professor and ViceChair, Department of Family and Social Medicine,Albert Einstein College of Medicine and MontefioreMedical Center, NYAbigail Zuger, MD, Associate Professor of ClinicalMedicine, Columbia University College of Physiciansand Surgeons; Senior Attending Physician,St. Lukes-Roosevelt Hospital Center, NY

CONTRIBUTING EDITOR David J. Amrol, MD,Associate Professor of InternalMedicine, Director of the Division of Allergy andImmunology, University of South Carolina Schoolof Medicine

MASSACHUSETTS MEDICAL SOCIETYChristopher R. Lynch, Vice President, Publishing;Jonathan Adler, MD, Publisher; Robert Dall, EditorialDirector; Anne Russ, Business Manager;Sharon S. Salinger, Editorial Operations; Cara Adler,Mary Nastuk, Lyn Whinston-Perry, Staff Editors;Kara OHalloran, Copy Editor;Sioux Waks, Layout;Art Wilschek, Corrie Bridgeman, Christine Miller,Lew Wetzel, Ad Sales; William Paige, PublishingServices; Bette Clancy, Customer ServicePublished 24 times a year. Subscription rates per year:$155 (U.S.), C$199.05 (Canada), US$189 (Intl); Residents/Students/Nurses/PAs: $75 (U.S.), C$99.05 (Canada), US$83(Intl); Institutions: $315 (U.S.), C$333.33 (Canada), US$335(Intl); individual print only: $99 (U.S.). Prices do not include

GST, HST, or VAT. In Canada remit to: MassachusettsMedical Society C/O #B9162, P.O. Box 9100, Postal StationF, Toronto, Ontario, M4Y 3A5. All others remit to:Journal Watch General Medicine, P.O. Box 9085, Waltham, MA02454-9085 or call1-800-843-6356. E-mail inquiries orcomments via the Contact Us page at JWatch.org .Informa tion on our conflict-of-interest policy can befound at JWatch.org/misc/conflict.dtl

Journal Watch is a publication of NEJM Group,a division of the Massachusetts Medical Society.

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(27%) than in the other groups (38% an39%). Rates of progression to AIDS anmortality were similar in all three groups;no substantial me ication-relate a verseeffects were reporte .

In another stu y, researchers retrospec-tively charte CD4-cell patterns among pa-

tients who ha become infecte with HIVrecently: 136 who receive no treatment,97 who starte treatment within 4 monthsof presume infection, an 116 who startetreatment later. After 48 months, bothtreatment groups ha substantially higherCD4-cell counts than the untreate group.Among treate patients, two factors pre-

icte rapi CD4 recovery to normal levels:starting treatment within 4 months of infection an starting treatment whenCD4-cell counts were high.

COMMENTBoth of these stu ies imply that startingHIV treatment close to the moment of infection will preserve immune functionover the long term. However, as e itorial-ists point out, neither stu y can emon-strate clinical benefit from such an aggres-sive (an expensive) approach. Whatshoul clinicians o? The only reasonableoption is to iscuss the current state of uncertainty with newly HIV-positivepatients an make the ecision together.

Abigail Zuger, MD

SPARTAC Trial Investigators. Short -course anti-retroviral therapy in primary HIV infection. N EnglJ Med 2013 Jan 17; 368:207.

Le T et al. Enhanced CD4+ T-cell recovery withearlier HIV-1 antiretroviral therapy. N Engl J Med 2013 Jan 17; 368:218.

Walker BD and Hirsch MS. Antiretroviral therapy in early HIV infection. N Engl J Med 2013 Jan 17;368:279.

Pneumocystis PneumoniaAfter Rituximab Treatment Rituximab was associated with Pneumocystis pneumonia in HIV-negative patients, most of whom had hematologic cancers.

Pneumocystis jiroveciipneumonia (PcP)occurs in patients with impaire T-cellimmunity, such as those who are HIV-positive. Lately, with wi esprea use of immunosuppressive therapy an cytotoxic

rugs, many PcP cases have been associatewith immunocompromising con itionsother than HIV infection. Furthermore, re-cent research has suggeste that B cells also

play an important role in immunity against

Pneumocystis. These cells are eplete by rituximab (Rituxan), a monoclonal anti-bo y commonly use to treat patientswith hematologic malignancies anautoimmune isor ers.

A case series escribes 30 HIV-negativeMayo Clinic patients (me ian age, 70; 90%

with hematologic malignancies) who e- velope PcP between 1998 an 2011 aftertreatment with rituximab. Mean time fromlast rituximab a ministration to PcP onsetwas 77 ays. Sixty percent of the patientspresente with cough, low-gra e fever,malaise, an chest tightness, but 40% hahigh fever, chills, an rapi ly progressiverespiratory istress. Despite treatment withtrimethoprim/sulfamethoxazole in all butone patient, the fatality rate was 30%. Al-though 90% of patients also ha been ex-pose to glucocorticoi s or cytotoxic rugs,10% ha receive rituximab without con-comitant chemotherapy or substantialglucocorticoi exposure.

COMMENTIn rituximab registration trials, no patient

evelope PcP. This case series a lerts usto consi er PcP in patients who eveloppulmonary infections after treatment withrituximab, either alone or in combinationwith cytotoxic rugs or other immuno-suppressive agents. Prophylaxis shoul beconsi ere , because PcP-relate mortality is high in this population.

Thomas Glck, MD, Journal Watch Infectious Diseases

Martin-Garrido I et al. Pneumocystis pneumoniain patients treated with rituximab. Chest 2012 Dec20; [e-pub ahead of print]. (http://dx.doi.org/10.1378/chest.12-0477)

Diagnosing Pneumoniawith Ultrasoun in Chil renCompared with chest radiography,ultrasonography identified pneumoniawith 86% sensitivity and 89% specificity.

Clinicians of ten obtain chest x-rays (CXRs)to iagnose pneumonia in chil ren. Ultra-sonography (US) has shown promise for

iagnosing pneumonia, an smaller evicesmake point-of-care use more feasible. Re-searchers prospectively examine the accu-racy of US in 200 patients (age,

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iagnostic accuracy an , in turn, improvemeaningful patient outcomes. Researchersprospectively teste the effect of a hea -to-toe ultrasoun protocol among 125 con-secutive patients a mitte to a generalICU in Italy.

Each patient un erwent a structure

ultrasoun examination of the venoussystem (neck, upper an lower extremities),thorax, heart, ab omen, an optic nerve(the latter to rule out elevate intracranialpressure in comatose or eeply se atepatients) by an intensivist skille in ultra-soun . The ICU a mitting atten ing relieon history, physical exam, an lab animaging fin ings to reach a iagnosis.

Be si e ultrasoun results mo ifiethe a mitting iagnosis in 26% of patientsan often le to changes in me ical therapy

(18%) or triggere invasive proce ures (22%).Roughly 80% of the changes in me icaltherapy resulte from thoracic an car iacfin ings, an 74% of me ical proce uresprompte by ultrasoun fin ings werethoracenteses. Most patients (81%) wereable to un ergo be si e ultrasoun examsthat were of goo or only slightly impairequality. The me ian t ime for the protocolwas 20 minutes.

COMMENTThis stu y suggests that an ICU ultrasoun

protocol enhances real-time iagnosticability, but the challenge will be to evelopprotocols that improve meaningful patientoutcomes. Many uncertainties about theprotocol (i.e., generalizability, time con-straints, effects on mortality an lengthof stay, over iagnosis, effects of inci entalfin ings) must be eluci ate more rigor-ously before it can be a opte universally.

Aaron J. Calderon, MD, FACP, Journal Watch Hospital Me icine

Manno E et al. Deep impact of ultrasound in theintensive care unit: The ICU-sound protocol.Anesthesiology 2012 Oct; 117:801.

Dont Rely on Scoring Systemsto Pre ict Clinically Important Blee ing DuringOral Anticoagulant Therapy A prospective study indicates that scores arenot better than physicians clinical judgment.

Clinicians are trying constantly to weighrisks an benefits of oral anticoagulanttherapy. For blee ing risk, numerous scoring

systems have been evelope to help gui e

clinical ecision making for patients whotake warfarin. These scores generally areassume to be more accurate than clinical ju gment.

In a single-center prospective stu y,researchers in Switzerlan compare theperformance of seven scoring systems ver-

sus clinical ju gment for pre icting risk forfirst major blee ing event in 515 patients(me ian age, 71) who were receiving vita-min K antagonists that were comparable towarfarin (acenocoumarol or phenprocou-mon). Most patients were anticoagulatefor one of three con itions: atrial f ibrilla-tion (61%), venous thromboembolic is-ease (25%), or artificial heart valves (8%).

During 12 months of follow-up, thepre ictive accuracy of the scores for the35 first major blee ing events was poor an

not significantly ifferent from each other.In fact, the pre ictive ability of six scoringsystems was not better than chance alone,an the remaining system was only slightly better than chance. Moreover, the perfor-mance of each score was not superior tophysicians subjective assessments (me ianclinical experience, 3 years) of blee ingrisk.

COMMENTThis stu y suggests that current score sys-tems for pre icting major blee ing events

in patients taking vitamin K antagonistsare limite an not superior to physicians ju gment. Clinicians shoul not rely onthese scores an , at most, shoul only usethem as complementary tools to evaluateoverall blee ing risk.

Aaron J. Calderon, MD, FACP, Journal Watch Hospital Me icine

Donz J et al. Scores to predict major bleeding riskduring oral anticoagulation therapy: A prospectivevalidation study. Am J Med 2012 Nov; 125:1095.

Exten e VTE Prophylaxisin Acutely Ill Me ical Patients:Dont Try This at HomeExtended venous thromboembolism prophylaxis with rivaroxaban confersmore risk than benefit.

Medical patients at moderate-to-high risk for venous thromboembolism (VTE) ben-efit from pharmacologic VTE prophylaxis( JW Gen Med Mar 15 2012, p. 47, and Chest 2012; 141:Suppl:7S), and some evidencesuggests that VTE risk in medical patients

extends beyond their hospital stay. In this

randomized placebo-controlled trial, morethan 8000 patients (age, 40) who werehospitalized with at least one medical con-dition that placed them at risk for VTEreceived extended-duration rivaroxaban(Xarelto; for 35 days) or short-durationenoxaparin (for 10 days). Median hospitallength of stay was 11 days in both groups.

At 10 ays, VTE inci ence i not ifferbetween the rivaroxaban an enoxaparingroups (2.7%); however, clinically relevantblee ing was significantly more common inthe rivaroxaban group (2.8% vs. 1.2%). At35 ays, VTE ha occurre significantly less often in the rivaroxaban group (4.4% vs. 5.7%), but that positive outcome came atthe expense of significantly more clinically relevant blee ing (4.1% vs. 1.7%).

COMMENT

Although exten e - uration rivaroxabanhas been safe an eff icacious in preventingVTE after hip an knee arthroplasty ( JW Gen Med Aug 15 2008, p. 125;N Engl J Med 2008; 358:2776; an Lancet 2008; 372:31),this stu y reveals a significant blee ing risk associate with exten e rivaroxaban usein acutely ill me ical patients. An oral op-tion for VTE prevention woul be a wel-come a ition in me ical patients, but thisstu y suggests we shoul not be using rivaroxaban. It also a s to the evi ence thatexten ing prophylaxis beyon hospitaliza-tion for me ical patients might be associatewith more harm than benefit ( Am J Med 2011; 124:1143; JW Gen Med Feb 15 2012,p. 33; an N Engl J Med 2011; 365:2167).

Daniel D. Dressler, MD, MSc, SFHM,FACP, Journal Watch Hospital Medicine

Cohen AT et al. Rivaroxaban for thromboprophy-laxis in acutely ill medical patients. N Engl J Med 2013 Feb 7; 368:513.

Selective d-Dimer Testing

Improves Efficiencyof DVT DiagnosisTesting based on pretest probability lowered the number of tests needed to exclude first suspected deep venous thrombosis.

Among patients at high risk for eep ve-nous thrombosis (DVT), d- imer testingprobably is unnecessary, an irect evalu-ation with ultrasoun is more appropriate.Conversely, among low-risk patients,d- imer testing using a higher-than-usualthreshol might rule out DVT in more


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patients without increasing the number of misse DVT cases.

To etermine whether a selective testingstrategy outperforms uniform d- imer test-ing for all patients, researchers ran omize1723 patients (90% outpatients) with firstsuspecte DVTs to a control group in which

all patients un erwent d- imer testing us-ing a single positive threshol for everyone(0.5 g/mL) or to a selective testing groupin which positive d- imer threshol s if-fere for low- an mo erate-risk patients(1.0 g/mL an 0.5 g/mL, respectively).Before testing, all patients were classifie by Wells pre iction score as having a low, mo -erate, or high pretest probability of DVT. Pa-tients in the selective testing group who hahigh pretest probability of DVT (inclu ingall inpatients) skippe d- imer testing anun erwent ultrasoun .

About 6% of patients receive DVTiagnoses uring initial evaluations. Among

patients whose initial evaluations werenegative for DVT, the inci ence of venousthromboembolism (VTE) at 3 months wasthe same in the selective-testing an con-trol groups 0.5%. Fewer d- imer testswere performe among the selective-testinggroup than among the control group (ab-solute re uction, 21.8%). Also, fewer ultra-soun s were performe (absolute re uc-tion, 7.6%).

COMMENTIn this trial, a selective d- imer testingstrategy was as safe as an more efficientthan uniform d- imer testing in iag-nosing first DVTs.


Linkins L-A et al. Selectived -dimer testing for diagnosis of a first suspected episode of deep venousthrombosis: A randomized trial. Ann Intern Med 2013 Jan 15; 158:93.

No CV Benefit from Vitaminan Antioxi ant SupplementsTaking vitamins and antioxidants does not prevent major adverse cardiovascular events.

Although observational stu ies have linkehigher intakes of vitaminan antioxi ant-rich fruits an vegetables with lower car iovascular (CV) risk, ran omize trials of vitamin an antioxi ant supplements haveyiel e conflicting results. Most priormeta-analyses of these trials have involvein ivi ual vitamin or antioxi ant supple-

ments, an no meta-analysis has inclu e

comprehensive ran omize trial ata onthis topic. In this meta-analysis, investi-gators reviewe ata from 50 ran omize ,controlle trials that involve 295,000 par-ticipants to assess the efficacy of vitaminan antioxi ant supplements in preventingmajor a verse CV events.

In the overall analysis, supplemental vitamins an antioxi ants ha no effecton risk for CV-relate eath, myocar ialinfarction, angina, stroke, su en car iac

eath, or transient ischemic attack. Simi-larly, these supplements ha no effect over-all on CV risk in subgroup analyses by typeof prevention trial (primary or secon ary),type of vitamins an antioxi ants, CV out-comes, uration of treatment, supplementsgiven singly or in combination, stu y e-sign, stu y quality, or fun ing source.

COMMENTIn this large meta-analysis, which inclu e

ata from a recently publishe ran omizetrial ( JW Gen Med Dec 15 2012, p. 153, an JAMA2012; 308:1751), vitamin an anti-oxi ant supplementation i not preventmajor a verse CV events. The stu y authorsreasonably conclu e, There is no evi enceto support the use of vitamin or antioxi antsupplements in the prevention of car iovascular isease. Nonetheless, these sup-plements might have other benefits, suchas cancer prevention ( JW Gen Med Sep 152012, p.175, an JAMA2012; 308:1871).

Paul S. Mueller, MD, MPH, FACP

Myung S-K et al. Efficacy of vitamin and antioxi-dant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials. BMJ 2013 Jan 18;346:f10. (http:// dx.doi.org/10.1136/bmj.f10)

Rate Controlfor Atrial Fibrillation:What Is the Best Drug to Use?In a comparison of four commonly prescribed -blockers and calcium-channel blockers, diltiazem emerged as the winner.

Current gui elines recommen either-blockers or calcium-channel blockersas first-line rate-control rugs for patientswith atrial fibril lation (AF), but hea -to-hea trials are lacking. To compare theeffects of four once- aily rug regimenson heart rate an symptoms in patientswith permanent, rapi ly con ucte AF,investigators in Norway con ucte aninvestigator-blin e crossover stu y. Sixty

a ults (mean age, 71) with permanent AFan without congestive heart failure orischemic heart isease receive , in ran-

om or er, iltiazem (360 mg), verapamil(240 mg), metoprolol (100 mg), an carve-

ilol (25 mg); each was given for 3 weeks.Before the first treatment an on the last

ay of each treatment protocol, 24-hourHolter recor ings were obtaine , an pa-tients complete symptom questionnaires.

Mean 24-hour heart rate was signifi-cantly re uce from baseline with all fourtreatments an was significantly lowerwith iltiazem than with any other rug(baseline, 96 beats per minute [bpm]; ilti-azem, 75 bpm; verapamil, 81 bpm; meto-prolol, 82 bpm; carve ilol, 84 bpm). Dilti-azem treatment significantly re uce boththe frequency an severity of symptomsfrom baseline. Verapamil significantly re uce symptom frequency only, anmetoprolol an carve ilol improveneither frequency nor severity.

COMMENTIn this small, single-center stu y, 360 mgof iltiazem ai ly appeare to be the bestchoice. However, these results nee con-firmation in larger clinical trials an in

ifferent populations before efinitiverecommen ation can be ma e.

Joel M. Gore, MD, Journal Watch Car iology

Ulimoen SR et al. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrilla-tion. Am J Cardiol 2013 Jan 15; 111:225.

Olmesartan vs. Olmesartanplus a Calcium-Channel BlockerIn a randomized trial, researchers found no difference between these two regimensin cardiovascular outcomes.

In titrating antihypertensive therapy, many

clinicians prefer mo erate- ose two- rugtherapy over high- ose monotherapy.Japanese researchers compare these prac-tices in a tr ial that involve ol er hyper-tensive patients (age range, 6584; systolicbloo pressure [BP], >140 mm Hg or ia-stolic BP, >90 mm Hg) with either iabetesor car iovascular (CV) isease (sympto-matic or asymptomatic).

Patients initially receive theangiotensin-receptor blocker (ARB)olmesartan (Benicar; 20 mg aily);the 1164 patients whose BP remaine

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>140/90 mm Hg then were ran omizeto receive either higher- ose olmesartan(40 mg aily) or to continue olmesartan(20 mg) an a a calcium-channel blocker(e.g., amlo ipine, 2.5 or 5.0 mg aily).Diuretics or -blockers coul be a eto either regimen, if nee e .

At 3 years, mean BP was slightly lower(by 2 mm Hg) with combination therapy than with high- ose olmesartan. However,the inci ence of a broa ly efine CV en -point was similar in the two groups (8.2% vs. 10.0%;P =0.17). In prespecifie sub-group analysis, patients with preexistingCV isease reache fewer en points withcombine therapy ( P =0.03).

In a separate report, the authors pre-sente a prespecifie subgroup analysis,stratifie by baseline estimate glomerular

filtration rate (GFR). Patients whose GFR was

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Increasing Doses of Anti epressants Are Associatewith QT Interval ProlongationThese observational results support theFDAs warning about cardiac changes.

In 2011, the FDA warne that citalopram,a selective serotonin reuptake inhibitor(SSRI), causes ose- epen ent correcteQT interval (QTc) prolongation, which isassociate with risk for torsa e e pointes.Whether other anti epressants also causesuch prolongation is unclear. In this stu y,investigators use electrocar iogram (ECG),prescription, an clinical ata from a New Englan healthcare system to eterminethe effects of anti epressant use on QTc.

Overall, 20% of >38,000 a ults whoun erwent ECGs after receiving prescrip-tions for anti epressants exhibite abnor-mal QTc. A juste for multiple factors,citalopram, escitalopram (Lexapro), anamitriptyline were associate significantly with ose- epen ent QTc prolongation.In contrast, bupropion was associate withQTc shortening. In patients who un erwentECGs before an after rug ose changes,significant increases in mean QTc wereobserve when citalopram oses were in-crease from 10 to 20 mg (7.8 millisecon s)an from 20 to 40 mg (10.3 millisecon s);in fact, 13% of patients with initially normalQTc exhibite abnormal prolonge QTcafter starting citalopram. Mean QTc short-

ene significantly in patients whose bupro-

pion oses were increase from 100 to200 mg (19.2 millisecon s). Fluoxetine,paroxetine, sertraline, uloxetine, mir-tazapine, nortriptyline, an venlafaxinewere not associate with QTc changes.

COMMENTIn this stu y, increasing oses of citalo-pram, escitalopram, an amitriptyline

were associate with prolonging QTc.These results support the FDA warningabout citalopram, a wi ely prescribe anti-

epressant, an provi e clinicians withgui ance on selecting anti epressants forpatients at risk for QTc prolongation (e.g.,el ers, women, those with histories of myocar ial infarction or rug use).


Castro VM et al. QT interval and antidepressant use: A cross sectional study of electronic healthrecords. BMJ 2013 Jan 29; 346:f288.(http://dx.doi.org/10.1136/bmj.f288)

The FDA warning is available at http://viajwat.ch/Y gS1A free of charge.

Early Intro uctionof Complementary Foo sMight Prevent Allergic DiseaseDuration of total breast-feeding is moreimportant than exclusive breast-feeding for preventing asthma and allergies.

When to intro uce complementary foo sin infants is confusing for parents anclinicians alike. Ol er gui elines recom-

men e avoi ance of airy until age 1 year;eggs until age 2 years; an peanuts, nuts,an seafoo until age 3 years. Currently,the American Aca emy of Pe iatrics rec-ommen s exclusive breast-fee ing for 4to 6 months, followe by intro uction of complementary foo s, without provi inga timeline for when to intro uce specificfoo s (Pediatrics 2012; 129:e827).

Investigators followe 3781 Finnishchil ren for 5 years to examine the associ-ation between uration of breast-fee ingan timing of intro uction of complemen-tary foo s (base on parent report) an

evelopment of allergic isease an specificIgE (sIgE) sensitization to foo s an inhal-ants. Intro uction of wheat, rye, oats, anbarley before age 5.5 months, fish beforeage 9 months, an egg before age 11 monthswas associate with lower rates of asthma,allergic rhinitis , an sIgE sensitization. To-

tal breast-fee ing uration of 9.5 monthswas associate with lower risk for nonatopicasthma, an benefit seeme to correlatewith uration of total breast-fee ing ratherthan exclusive breast-fee ing.

About one thir of women an one quarter of men have reportelifetime intimate partner violence (IPV); moreover, a majority

of women who were injure uring their most recent rape orphysical assault i not receive any me ical treatment. In 2004,the U.S. Preventive Services Task Force (USPSTF) foun no

irect evi ence that IPV screening or intervention le to betteroutcomes. Now, base on a systematic review ( Ann Intern Med 2012; 157:676), the USPSTF has up ate its recommen ations.

The following revisions apply to women without signsor symptoms of abuse:

Clinicians shoul screen women of repro uctive agefor IPV.

Interventions prevent violence, abuse, an physicalor mental harm; hence, women who screen positiveshoul receive or be referre to such services.

COMMENTIn eveloping this up ate gui eline, the USPSTF consi ere

the key factors associate with excess risk for intimate partner violence (young age, substance abuse, marital ifficulties, aneconomic har ship). The Task Force cites several referencesfor screening tools (some as short as 3 questions) an remin sus that man ates for reporting of IPV iffer across the U.S.Notably, for lack of evi ence, no recommen ation for or againstscreening of el ers or vulnerable a ults coul be ma e.


U.S. Preventive Services Task Force (USPSTF). Screening for intimate partner violence and abuse of elderly and vulnerable adults: A U.S. Preventive ServicesTask Force recommendation statement. Ann Intern Med 2013 Jan 22;[e-pub ahead of print]. (http://annals.org/article.aspx?articleid=1558517)

THE USPSTF up ate gui eline is available athttp://www.uspreventiveservicestaskforce.org/uspstf/uspsipv.htmfree of charge.

CLINICAL PRACTICE GUIDELINE WATCH

USPSTF Now Recommen s Screening Women for Intimate Partner ViolenceWomen who screen positive should receive intervention.

Tell us what you think.Correspond with the editors of Journal Watch General Medicine

[email protected]

March 1, 2013 JWatch.org 43

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Journal Watch (ISSN 0896-7210) is published semimonthly by the Massachusetts Medical Society, 860 Winter Street, Waltham, MA02451-1413. Subscription price: $155. 00 per year. Periodicals Postage Paid at Boston, MA. Postmaster: send address changes toJournal Watch, P.O. Box 803, Waltham, MA 0245 4-08 03.No part of this newsletter may be reproduced or otherwise incorporated into any information retrieval system without the writ tenpermission of the Massachusetts Medical Society. Printed in the USA.

Massachusetts Me ical Society 860 Winter StreetWaltham, MA 02451-1413JWatch.org PERIODICALS

COMMENT

By telling parents for years to elay intro-ucing allergenic complementary foo s,

we might have cause more harm thangoo . On the basis of these results an re-cent gui elines ( J Allergy Clin Immunol: InPractice 2013; 1:29), I recommen exclusivebreast-fee ing for only 4 months followeby continue breast-fee ing with comple-mentary foo s until age 12 months. Grainsshoul be starte at 4 months, followe by all other foo s uring the first year. A recentran omize trial showe similar growth

rates an better iron status in breast-feinfants when complementary grains werestarte at 4 versus 6 months of age (Pediatrics 2012; 130:e1038).

David J. Amrol, MD

Nwaru BI et al. Timing of infant feeding in relationto childhood asthma and allergic diseases. J Allergy Clin Immunol 2013 Jan; 131:78.

A Strategy to Avoi Surgeryfor Acute AnteriorCruciate Ligament Tears Among young active patients, 5-year outcomes were no worse for optional later reconstruction than for early reconstruction.

In a recent stu y, European investigatorsfoun no ifferences in patient-reporte2-year outcomes between early reconstruc-tion an optional later reconstructionamong young active patients with acuteanterior cruciate ligament (ACL) tears ( JW Gen Med Sep 1 2010, p. 140, an N Engl J Med 2010; 363:331). Now, the same investigators report outcomes at 5 years.

Overall, 121 patients (mean age, 26)with acute ACL tears in previously un-injure knees participate in the trial. Allpatients receive structure rehabilitationan were ran omize to early reconstruc-tion or optional later reconstruction. Thirty of the 59 patients (51%) in the latter groupun erwent elaye reconstruction (7 of these after year 2). At 5 years, no ifferenceswere note between the groups in the re-

sults of knee injury, osteoarthritis, activity,an health scales. In a ition, no ifferenceswere foun in inci ent ra iographic kneeosteoarthritis or the number of knees thatrequire meniscus surgery (about half ineach group).

COMMENTThis stu y confirms earlier fin ings thatrehabilitation plus early reconstruction

oes not result in better outcomes thanrehabilitation with optional later recon-struction in young active patients withacute ACL tears. Using the latter strategy,about half of these patients coul avoisurgery. The authors note that the results

o not apply to less-active patients or toprofessional athletes, but they shoul en-courage clinicians an young active a ultpatients to consi er rehabilitation as aprimary treatment option.


Frobell RB et al. Treatment for acute anterior cruciateligament tear: Five year outcome of randomised trial.BMJ 2013 Jan 24; 346:f232. (http://dx.doi.org/ 10.1136/bmj.f232)

JW ONLINE CME

JOURNAL WATCH SUBSCRI BERSHAVE 10 FREE CREDITS!

This is one of four questions in a recent Journal Watch Online CME exam.

from Serial Assessment of Left VentricularFunction in Chemotherapy Patients (p. 42)

Investigators compared different echo-cardiographic techniques that are used to

screen for cardiac toxicity in chemotherapypatients. Which method was the mostreproducible with the least temporalvariability?

A. noncontrast two-dimensional (2-D)echocardiography (echo)

B. noncontrast three-dimensional (3-D)echo

C. 2-D echo with contrastD. 3-D echo with contrastCategory: Cardiovascular DiseasesExam Title:JW Online: Echo Techniques, AEDs,Rate vs. Rhythm ControlPosted Date: Feb 13 2013

View this exam and others at http://cme.jwatch.org

User name and password are required.CME FACULTY: Allison Oler, MD

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