Message from the Editor-in-Chief

Dear Subscriber,

One thing that never fails to surprise me is the number of features in UpToDate® that gounnoticed. For example, while most users have now discovered our Summary andRecommendations sections, where we have our graded treatment recommendations, manyhave not discovered What’s New or the related Practice Changing UpDates, which showwhat our editors feel are the most important updates to the program, including those thatactually change practice. Both of these can be accessed by simply searching on “what’s new”or by clicking on the What’s New tab at the top of the UpToDate page.

I’ve also found that many users aren’t aware that we have a drug interactions program. Thiscan be accessed either by clicking on the link under the search box on the main searchscreen, or by clicking on the link within the interactions sections of the drug informationtopics.

Other feedback we’ve received is helping us prioritize our development efforts on mobile,EMR integration and other product enhancements, so that we can continue to improve theUpToDate user experience. So thanks for the input — we’re listening.

On the content side, we are continuing to work on new specialties, with geriatrics very closeto release and general surgery following close behind. Perhaps your clinicians have alsonoticed the increasing psychiatry and dermatology content; these specialties are growingnicely as well. You may also be interested to know that our users sent us close to 10,000feedback communications in 2010, 16% of which led directly to changes in our content. Yourclinicians’ contributions in this area are obviously invaluable.

Thank you again for your support of UpToDate.

Denise S. Basow, MDPresident and Editor-in-Chief

19.1 NEWSM A R C H 2 0 1 1

As part of our commitment to helping yourclinicians get the most from UpToDate, we’vecreated a new web page informing them aboutnew content and providing access to our recentnewsletters. To get to this page, users simplyclick on the News from UpToDate link at thetop of their screen.

News from UpToDate

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Add the UpToDate Search Box to YourIntranet

Get more value from your UpToDatesubscription by providing additional accesspoints within your institution. Put theUpToDate search widget on your intranet tosave your clinicians a click and get them totheir answer faster. For more information andto get the widget code, click on “AboutUpToDate” at the top of the screen andchoose “Get the Professional Widget” fromthe menu.

More Ways to Access UpToDateEncourage Your Clinicians to MakeUpToDate a Search Option

Clinicians using Internet Explorer orFireFox can also add UpToDate as one oftheir search options — or even make ittheir default search engine! Once on theUpToDate website, users just need toclick on the down arrow within thebrowser search box and add UpToDate asa search option. We encourage you toforward this information to the cliniciansat your institution.

Do your clinicians want to review UpToDate’s table of contents? Would they like more informationabout our grading system or donations program? They’ll find it — plus a lot more — underAbout UpToDate, which they can link to from the top of their screen.

Don’t Forget “About UpToDate”

Upcoming Release Schedule Version 19.2 July 2011 • Version 19.3 November 2011 • Version 20.1 March 2012

In December, UpToDate launched a newsection of patient information for subscribers.“The Basics” are short (1-3 page) articleswritten at a 5th-6th grade reading level thatuse drawings, graphics and other visualelements to reinforce key messages. They’redesigned to answer the 4 or 5 most importantquestions a person might have about amedical condition and can be easily printedor emailed to share with patients. Since thelaunch of The Basics, we’ve developed anadditional 105 topics!

Our original patient content, now referred toas “Beyond the Basics,” consists of longerarticles (about 5-10 pages) that are ideal forpatients who already have a basicunderstanding of their condition and arelooking for more in-depth information.

UpToDate offers a total of over 700 patienttopics, all of which can be easily accessedthrough your subscription. Clinicians just needto search our content as they normally wouldand then click “Prioritize patient topics” tobring our patient content to the top of theirsearch results. Each patient topic is labeledeither “The Basics” or “Beyond the Basics” tohelp users easily distinguish between the two.

Our full patient information library can also beaccessed by clicking on the Patient Info tab atthe top of the page. Patient topics are

Patient Information Update

organized by level and category so thatclinicians can find what they need quicklyand easily.

Finally, we are pleased to announce thatUpToDate’s patient topics now include linksto Lexi-Comp™ Patient Drug Informationhandouts, so your clinicians can educate theirpatients about their medications as well.

“Thank you so much for creating ‘The Basics’ and forcontinuing the ‘What’s New’ section. I LOVE it, it isexactly what I was looking for and exactly what Iwanted. Keep on making medicine easier to learn! AndI will keep on recommending you to my colleagues.”

Matthias Muenzer, MDMedford, MA

See where we’ll be in 2011! View our updatedcalendar, located in the About UpToDatesection of our site.

2011 Events Calendar

Do your clinicians access UpToDate online?If so, make sure their bookmarks point towww.uptodate.com/online so they get to thenew search page faster!

Logging in with theCorrect URL

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Adult and Pediatric Emergency MedicineBasic and advanced life support: 2010resuscitation guidelines

The American Heart Association (AHA) theInternational Liaison Committee on Resuscitation(ILCOR) published updated guidelines for basiclife support and advanced life support in childrenand adults in 2010. The guidelines emphasize theimportance of excellent CPR and recommendbeginning chest compressions immediately forany unresponsive child or adult who is notbreathing, is breathing abnormally (eg, gasping),or in whom a pulse cannot be readily palpatedwithin 10 seconds. The new sequence for basiclife support (BLS) is chest compressions, airwayopening, and then rescue breathing (“C-A-B”).(See “Basic life support (BLS) in adults”, sectionon ‘Recognition of cardiac arrest’ and “Basic lifesupport in infants and children”, section on‘Initiate CPR’and See “Guidelines for pediatricadvanced life support” and “Advanced cardiac lifesupport (ACLS) in adults”.)

Adult Primary CareStatins for all patients with coronary heartdisease

UpToDate now recommends that patients withcoronary heart disease (CHD) or a CHD riskequivalent who can tolerate statin therapy betreated with at least a moderate dose of a statin(eg, 40 mg of lovastatin, pravastatin, or simvastatin,20 mg of atorvastatin, or 5 to 10 mg ofrosuvastatin) independent of the baseline LDL-C.That is, even for providers who choose an LDL-goal-based strategy of lipid management, and evenif a patient’s baseline LDL-C is below goal, or isclose to goal such that a low dose of a statinwould be expected to reduce the LDL-C below theATP-III goal, we would initiate a statin at a

moderate dose. (See “Treatment of lipids (includinghypercholesterolemia) in secondary prevention”and “Intensity of lipid lowering therapy insecondary prevention of coronary heart disease”.)

Allergy and ImmunologyFood allergy guidelines

The US National Institute of Allergy and InfectiousDiseases, in conjunction with 34 professionalorganizations, federal agencies, and patientadvocacy groups, developed clinical guidelines forthe diagnosis and management of food allergy.The guideline recommendations are consistentwith previously published food allergy topics inUpToDate, a few of which are listed here. (See“The natural history of childhood food allergy”and “History and physical examination in thepatient with possible food allergy” and “Diagnostictools for food allergy” and “Food-inducedanaphylaxis” and “Anaphylaxis: Rapid recognitionand treatment” and “Introducing formula and solidfoods to infants at risk for allergic disease”.)

Cardiovascular MedicineAldosterone antagonist therapy beneficial inmild heart failure

Aldosterone antagonist therapy has been shown toreduce mortality in patients with moderate tosevere heart failure. The EMPHASIS-HF trialdemonstrated the efficacy of eplerenone inreducing mortality as well as risk of hospitalizationin patients with systolic heart failure and mildsymptoms. We now recommend aldosteroneantagonist therapy to treat heart failure in patientswith NYHA functional class II HF and LVEF 30percent, or NYHA functional class III to IV heartfailure and LVEF <35 percent, if they can becarefully monitored for serum potassium and renalfunction. (See “Use of aldosterone antagonists inheart failure”, section on ‘Eplerenone inEMPHASIS-HF trial’.)

PRACTICE-CHANGING UPDATE

PRACTICE-CHANGING UPDATE

PRACTICE-CHANGING UPDATE

What’s New in UpToDate 19.1In “What’s New,” UpToDate summarizes the most important new medical findings since the last release.In some cases, the results of newly published studies may have important and immediate implicationsthat may affect the way clinicians practice. A compilation of these Practice Changing UpDates across allspecialties appear in “What’s New” and in the main table of contents.

Below are sample “What’s New” topics, including Practice Changing UpDates, thought to be of particularinterest by our editors. For a complete list, click What’s New on the UpToDate search page toolbar.

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Endocrinology and DiabetesThe Institute of Medicine released an updatedreport on dietary intake requirements forvitamin D

The Recommended Dietary Allowance (RDA) ofvitamin D for children 1 to 18 years and adultsthrough age 70 years is 600 International Units(15 mcg) with the RDA increasing to 800International Units (20 mcg) after age 71. Thecommittee concluded that a serum25-hydroxyvitamin D concentration of 20 ng/mL(50 nmol/L) was sufficient for most individuals.(See “Overview of vitamin D”.)

Family MedicineAntibiotics for young children with acuteotitis media

Meta-analyses had suggested that many childrenwith acute otitis media (AOM) improve withoutantimicrobial therapy, however many of theincluded studies did not use stringent diagnosticcriteria and did not focus on children <2 years ofage, a group that is more difficult to treat. In tworecent randomized trials comparing amoxicillin-clavulanate and placebo in young children (6 to 23or 35 months) that used a strict definition of AOM,antibiotic therapy shortened the duration of signsand symptoms of AOM and led to fewer treatmentfailures and lower rates of residual middle eardisease, thus confirming the benefit ofantimicrobial therapy for children younger thantwo years of age with strictly defined AOM. (See“Acute otitis media in children: Treatment”, sectionon ‘Antibiotic therapy versus observation’.)

Gastroenterology and HepatologyTumor markers aid with differentiation ofinvasive from noninvasive intraductalpapillary mucinous neoplasms of the pancreas

Determination of carbohydrate antigen (CA) 19-9and carcinoembryonic antigen levels may aid inthe differentiation of invasive from noninvasiveintraductal papillary mucinous neoplasm (IPMN).In a study of patients undergoing surgicalresection for IPMN, significantly more patientswith invasive IPMN had elevations in one or bothmarkers compared with patients with noninvasiveIPMN. These tumor markers may help in thedifferentiation of invasive from noninvasive IPMN.(See “Intraductal papillary mucinous neoplasm ofthe pancreas”, section on ‘Tumor markers’.)

HematologyMaintenance lenalidomide for multiplemyeloma after autologous transplantassociated with increased rate of secondcancers

Since virtually all patients who receivedautologous hematopoietic cell transplantation(HCT) for multiple myeloma (MM) eventuallydevelop relapsed disease, trials have investigatedthe use of maintenance therapy to eliminateresidual malignant cells after HCT. Our practicehad been to use maintenance lenalidomide forpatients with high risk MM and to not usemaintenance therapy of any kind for standardrisk MM. Two trials that did not stratify patientsaccording to risk status have reported animprovement in progression free survival whenlenalidomide is administered as maintenancetherapy following HCT. In both the trials anincreased number of second cancers occurred inthe lenalidomide treated arm. Upon considerationof these results, we have changed our practicefor patients with high risk MM, and administer abortezomib-based maintenance therapy, ratherthan lenalidomide, after completion of autologousHCT. (See “Initial chemotherapy for patients withhigh risk multiple myeloma”, section on‘Transplant or maintenance therapy’ and“Autologous hematopoietic cell transplantation inmultiple myeloma”, section on ‘Lenalidomide’.)

Hospital MedicineColchicine for pericarditis

Treatment for acute pericarditis has longcentered on the use of non-steroidal anti-inflammatory drugs (NSAIDs). A meta-analysisof three randomized trials found markedlylower rates of treatment failure and recurrentpericarditis in patients treated with colchicineplus NSAIDs rather than NSAIDs alone. Despitean increase in gastrointestinal side effects, wenow suggest colchicine in combination withNSAIDs rather than NSAIDs alone as first-linetherapy for viral or idiopathic acute pericarditis.(See “Treatment of acute pericarditis”, sectionon ‘Colchicine’.)

PRACTICE-CHANGING UPDATE

PRACTICE-CHANGING UPDATE

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Infectious DiseasesTdap vaccination

Waning immunity against tetanus and diphtheriais responsible for the US Advisory Committee onImmunization Practices (ACIP) recommendationfor universal administration of tetanus-diphtheriatoxoid vaccine (Td) boosters every 10 years inadolescents and adults. To address waningimmunity against pertussis, the ACIP alsorecommends a single dose of a vaccinecontaining tetanus toxoid, reduced diphtheriatoxoid, and acellular pertussis (Tdap; ADACEL® orBoostrix®), 0.5 mL IM, in place of Td foradolescents between 11 and 18 years who havecompleted the recommended childhoodimmunizations and for adults aged 19 to 64 years.In the fall of 2010, the ACIP also beganrecommending that, for adults aged 65 years andolder, a single dose of Tdap may be given inplace of the Td for those who have not receivedTdap previously. This is important for adults aged65 years and older who have or anticipate havingclose contact with infants aged younger than oneyear (such as grandparents, child care providers,and health care providers). Tdap should beadministered regardless of the interval since thelast dose of Td. This represents a change fromprevious ACIP guidelines, which recommendedthat Tdap be given a minimum of two years afterthe last dose of Td in most cases. (See“Treatment and prevention of Bordetella pertussisinfection in adolescents and adults” and“Diphtheria, tetanus, and pertussis immunizationin children 7 through 18 years of age”, section on‘10 through 18 years’.)

The ACIP has also issued an updatedrecommendation for off-label use of Tdap ratherthan Td in children 7 to 10 years of age who arenot fully vaccinated against diphtheria, tetanus,and/or pertussis. (See “Diphtheria, tetanus, andpertussis immunization in children 7 through 18years of age”, section on ‘7 to 10 years’.)

Nephrology and HypertensionAzathioprine is better than mycophenolatemofetil for patients with ANCA-associatedvasculitis

A multicenter trial (the IMPROVE trial)demonstrated that azathioprine is superior tomycophenolate mofetil in maintaining remissionamong 156 patients with newly diagnosed

ANCA-associated vasculitis. The rate of adverseevents was not significantly different betweengroups. (See “Maintenance immunosuppressivetherapy in Wegener’s granulomatosis andmicroscopic polyangiitis”, section on‘Azathioprine versus mycophenolate mofetil’.)

NeurologyThe antiplatelet drug Cilostazol likelybeneficial for secondary stroke prevention

The antiplatelet agent cilostazol is aphosphodiesterase 3 inhibitor that is used mainlyto treat intermittent claudication in patients withperipheral artery disease. Several controlled trialsin Asia have found that cilostazol is effective forthe secondary prevention of cerebral infarction.In the largest such trial (CSPS II), cilostazol (100mg twice daily) was not inferior to aspirin (81 mgdaily) in preventing recurrent stroke (infarction orhemorrhage) at a mean follow-up of 29 monthsin 2757 patients in Japan with a recentnoncardioembolic cerebral infarction. Theseresults need to be confirmed in additional high-quality randomized trials. (See “Antiplatelettherapy for secondary prevention of stroke”,section on ‘Cilostazol’.)

Obstetrics, Gynecology andWomen’s HealthReducing blood loss during laparoscopicmyomectomy

Intramyometrial injection of vasopressin iscommonly used during myomectomy to reduceblood loss, but there are few data aboutcombining use of vasopressin with othermeasures. A randomized trial of women whounderwent laparoscopic myomectomy evaluatedthe use of vasopressin combined with ligation ofthe myoma pedicle with a loop of suturecompared with vasopressin alone or no treatment.Blood loss was significantly lower with combineduse of vasopressin/loop ligation compared withvasopressin alone or with no treatment. (See“Techniques to reduce blood loss duringabdominal or laparoscopic myomectomy”, sectionon ‘Vasopressin and other vasoconstrictors’.)

PRACTICE-CHANGING UPDATE

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OncologyBreast cancer surgery

In the setting of clinically node negative breastcancer, sentinel lymph node biopsy (SLNB) reliablyidentifies patients without axillary nodeinvolvement, thereby obviating the need for anaxillary lymph node dissection (ALND). The needfor a completion ALND in patients with a positiveSLNB is more controversial. This question wasstudied in the ACOSOG Z0011 trial, in whichpatients with T1 or T2 breast cancer and fewerthan three positive SLNs were randomly assignedto SLNB followed by ALND or SLNB alone. Allwomen received whole breast radiation therapy(RT), which includes most of level I and a portionof level II axillary nodes. There were no significantdifferences in the locoregional recurrence rate,overall survival, or disease free survival betweenthe two groups at a median follow-up of 6.3 years.Thus, completion ALND may not be necessary forwomen with clinically node negative T1 or T2tumors with less than three positive SLNs who willbe treated with whole breast RT, particularly if theyhave estrogen receptor (ER) positive tumors (whichaccounted for the majority of patients on the trial).

However, the Z0011 study closed prematurelybecause of low accrual and low event rate andalmost 20 percent of the patients were lost to followup. Until additional results become available fromtwo ongoing randomized trials studying the benefitof ALND for clinically node negative women withpositive SLNs (the EORTC 10981-22023 AMAROStrial and Trial 23-01 of the International BreastCancer Study Group), the need for completionALND in clinically node negative women with lessthan three positive SLNs is best resolved on a case-by-case basis, taking into account the patient’s otherrisk factors, comorbidities, and preferences. Whencompletion ALND is omitted in patients with apositive SLNB, breast RT is indicated. (See “Sentinellymph node biopsy for breast cancer: Indicationsand outcomes”, section on ‘When shouldcompletion axillary dissection be performed?’.)

PediatricsNew recommendations for meningococcalconjugate vaccine

The US Advisory Committee on ImmunizationPractices has modified guidelines regarding useof the quadrivalent meningococcal conjugate

vaccines to recommend that adolescents bevaccinated ideally at age 11 or 12 years, with abooster at age 16. In addition, a two-doseprimary series (two months apart) is nowrecommended for individuals with persistentcomplement component deficiency or functionalor anatomic asplenia, as well as for adolescentswith HIV infection. The specific meningococcalvaccine formulation and schedule indicateddepend upon age, host factors (ie, type ofimmunodeficiency), and prior history ofvaccination. (See “Meningococcal vaccines”,section on ‘United States’.)

Pulmonary MedicineHyponatremia appears to be a poorprognostic factor for patients with pulmonaryembolism (PE)

A retrospective cohort study of 13,728 patientswho were discharged over a two year periodwith a primary diagnosis of PE found thathyponatremia (sodium <135 mmol/L) at the timeof presentation was associated with bothincreased mortality and hospital readmission. (See“Overview of acute pulmonary embolism”,section on ‘Prognosis’.)

RheumatologyCardiovascular risk of NSAIDs

The adverse cardiovascular risk ofcyclooxygenase (COX)-2 selective nonsteroidalantiinflammatory drugs (NSAIDs) is wellestablished, but most nonselective NSAIDs alsoadversely impact cardiovascular risk; naproxenhas the greatest relative cardiovascular safetyamong commonly used nonselective NSAIDs. Therisks conveyed by these agents were compared ina network meta-analysis based upon multiplelarge randomized trials involving over 116,000patients. Among the nonselective NSAIDs, whencompared with placebo, the risk of myocardialinfarction (MI) was lower for naproxen ordiclofenac than for ibuprofen. The risk comparedwith placebo of the composite outcome ofnonfatal MI or nonfatal stroke plus cardiovasculardeath was lower for naproxen than for diclofenacor ibuprofen. The absolute cardiovascular riskwith these agents is low, but increases with doseand frequency of use. (See “Nonselective NSAIDs:Cardiovascular effects”, section on ‘Effect oncardiovascular risk’ and “COX-2 selectiveinhibitors: Adverse cardiovascular effects”, sectionon ‘Ischemic cardiovascular disease’.)

PRACTICE-CHANGING UPDATE

ADULT AND PEDIATRICEMERGENCY MEDICINEGary R. Fleisher, MDJohn A. Marx, MDRon M. Walls, MD, FRCPC, FAAEM

ADULT PRIMARY CARE AND INTERNAL MEDICINEMark D. Aronson, MDRobert H. Fletcher, MD, MScSuzanne W. Fletcher, MD

ALLERGY AND IMMUNOLOGYBruce S. Bochner, MDE. Richard Stiehm, MDRobert A. Wood, MD

CARDIOVASCULAR MEDICINEN.A. Mark Estes, III, MDBernard J. Gersh, MB, ChB, DPhil, FRCPSharon A. Hunt, MDCatherine M. Otto, MD

ENDOCRINOLOGY AND DIABETESDavid S. Cooper, MDDavid M. Nathan, MDPeter J. Snyder, MD

FAMILY MEDICINEPatrick Dowling, MD, MPH Carlos R. Jaen, MD, PhD Warren P. Newton, MD, MPHE. Robert Schwartz, MDJeff L. Susman, MD

GASTROENTEROLOGY ANDHEPATOLOGYSanjiv Chopra, MDJ. Thomas LaMont, MD

HEMATOLOGYRichard A. Larson, MDLawrence L.K. Leung, MDStanley L. Schrier, MD

HOSPITAL MEDICINEMark D. Aronson, MD

INFECTIOUS DISEASESJohn G. Bartlett, MDStephen B. Calderwood, MDMartin S. Hirsch, MDDaniel J. Sexton, MDPeter F. Weller, MD

NEPHROLOGY ANDHYPERTENSIONBurton D. Rose, MDDaniel C. Brennan, MDRichard J. Glassock, MD, MACPSteve J. Schwab, MD

NEUROLOGYMichael J. Aminoff, MD, DScTimothy A. Pedley, MDJerome B. Posner, MD

OBSTETRICS, GYNECOLOGYAND WOMEN’S HEALTHRobert L. Barbieri, MD

ONCOLOGYGeorge P. Canellos, MD Lowell Schnipper, MD

PEDIATRICSSheldon L. Kaplan, MDF. Bruder Stapleton, MD

PULMONARY, CRITICAL CAREAND SLEEP MEDICINEPeter J. Barnes, DM, DSc, FRCP, FRSTalmadge E. King, Jr., MDPolly E. Parsons, MDMark H. Sanders, MD

RHEUMATOLOGYPeter H. Schur, MD

UpToDate Editors-in-Chief

FOUNDING EDITORBurton D. Rose, MD

PRESIDENT AND EDITOR-IN-CHIEFDenise S. Basow, MD

Contact InformationUpToDate

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