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NEJM Journal Watch

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After hearing and assimilating this program, the listener willbe better able to: ( 1 )Increase his/her basic knowledge of important advances in medicine; ( 2 ) Identify a broad range ofclinical research reported in the medical literature; ( 3 ) Synthesize research findingsthrough one-on-one interviews with authors and editorialists; ( 4 ) Integrate new treatmentsreviewed in the summaries into current practice; ( 5 ) Challenge oneself with thoughtful, clinicallyrelevant questions. Disclosure In adherence to the ACCME Standards for Commercial Support,Audio-Digest requires all faculty and members of the planning committee todisclose relevant financial relationships within the past 12 months that mightcreate any personal conflicts of interest. Any identified conflicts wereresolved to ensure that this educational activity promotes quality in healthcare and not a proprietary business or commercial interest. For this program,Dr. Michael Gould reported receiving salary support from Archimedes, Inc. tohelp develop computer models of lung-cancer screening, serving as a guestmember of the Medicare Evidence Development and Coverage Advisory Committee forlung-cancer screening, and participating in the development of Lung-RADS forthe American College of Radiology. Dr. Darren Taichman and the planningcommittee members reported that they had nothing to disclose. GUIDELINE WATCH: PERIOPERATIVE CVEVALUATION AND MANAGEMENT OF PATIENTS UNDERGOINGNONCARDIACSURGERY Back in 2007, the American College of Cardiology and the AmericanHeart Association jointly published recommendations entitled Guidelines on Perioperative CardiovascularEvaluation and Care for Noncardiac Surgery ( http://dx.doi.org/10.1016/j.jacc.2007.09.003 ).Relevant evidence has been published since that time, so a new guideline isappropriate. Plus, the scientific integrity of a large body of researchpublished by Poldermans et al. in the Netherlands was challenged in 2011; thatresearch informed the guideline from 2007, but not the updated one from 2014,which appears on the website of the Journalof the American College of Cardiology ( http://dx.doi.org/10.1016/j.jacc.2014.07.944 ). This years guideline states that patients should be categorizedeither as low risk (a less than 1% risk for a major adverse cardiac event,based on patient and procedural factors) or as elevated risk (1% or greater).Recommendations for interventions fall into four categories, namely, should be performed ; is reasonable to perform ; may be considered , and is not beneficial or is potentially harmful . In terms of perioperative management: Stress testing may be reasonable before noncardiac surgery inpatients who are both at an elevated cardiovascular risk and have poor (orunknown) functional capacity but only if an abnormal result would changepatient management. This recommendation obviously doesnt apply to patients whoneed emergency surgery or to patients who have active cardiac conditions thatneed immediate intervention (like acute coronary syndrome or decompensatedheart failure). Patients who chronically take β-blockers should continue to takethem perioperatively. Although routinely starting β-blocker therapy beforenoncardiac surgery isnt recommended, clinicians might reasonably prescribethem for selected patients at a substantially elevated cardiovascular risk; ifthis is done, β-blockers should be started well in advance of the surgery andnot on the day of (or the day before) surgery. Patients who chronically take statins should continue to takethem perioperatively. In selected high-risk patients, the perioperativeinitiation of statins is reasonable or may be considered. Based on the recently published POISE-2 trial ( www.jwatch.org/na34173 ),starting aspirin perioperatively (or continuing it perioperatively in patientsalready taking chronic aspirin) to prevent adverse cardiovascular events isntgenerally recommended. But continuing aspirin may be reasonable in selectedpatients whose ischemic risk is thought to outweigh their bleeding risk. Routine preoperative echocardiography isnt recommended, butecho is reasonable or may be considered in patients with unexplained dyspnea orwith a history of left ventricular dysfunction. The guideline also provides detailed information on managingpatients with coronary disease, valvular heart disease, or heart failure, andthose with recent stent placement. This guideline is an impressive100-page compendium of the literature and evidence relevant to theperioperative cardiovascular management of patients undergoing noncardiacsurgery. Some clinicians might be frustrated by the tentative language is reasonable or may be considered that accompanies the recommendations. For clinicians oriented tointervention, this language will be an open invitation to intervene; forothers, it will justify less perioperative testing and less preventive-drugtherapy. At the time that NEJMJournal Watch reviewed this paper, its publisher noted that itwasnt in its final form and that subsequent changes might be made. PERIOPERATIVE β -BLOCKADE,REVISITED A 2014 guideline from the American College of Cardiology and theAmerican Heart Association recommends that patients who are long time users of β-blockersand who undergo noncardiac surgery should continue to take β-blockersperioperatively ( http://dx.doi.org/10.1016/j.jacc.2014.07.944 ).In a study in the Octoberissue of JAMASurgery ( http://dx.doi.org/10.1001/jamasurg.2014.351 ),researchers identified 14,000 patients at United States Veterans Affairshospitals who were getting outpatient β-blocker therapy, underwent noncardiacsurgery, and spent at least 2days in the hospital postoperatively. Eightypercent of the patients got β-blockers both within the immediate perioperativeperiod (that is to say, 24hours before incision through discharge fromthe postanesthesia care unit) and on at least 1 of the first 2 postoperativedays; 20% of the patients didnt get β-blockers in this manner. Overall, 3% of the patients experienced major adversecardiovascular or cerebrovascular events within a month. In adjusted analyseswith propensity-score matching, the patients who continued to takeperioperative β-blockade were significantly less likely to experience theseadverse events than were the patients who didnt take β-blockers in therecommended way. Thirty-day mortality was also significantly lower in the β-blockercontinuationgroup. The apparent benefit of β-blocker continuation was limited to high-riskpatients those with scores of 3 or higher on the Revised Cardiac RiskIndex ( www.jwatch.org/jw199909170000001 ). Most of the observational studies (including this one) about thequestion of continuing perioperative β-blockade are necessarily messy:Unmeasured confounding variables are likely, how long these patients took β-blockersbefore their surgeries isnt clear, and we dont know whether β-blockers weregiven continuously after the first or second perioperative day. Even so, theseresults support current recommendations to continue β-blockers perioperatively. STATINS AND PAIN IN OLDER CANCER PATIENTS Determining whether statins are responsible for nonspecific achesand pains can be difficult, especially in elderly patients. In a cohort studyin the October Journal of theAmerican Geriatrics Society ( http://dx.d oi.org/10.1111/jgs.13051 ),researchers in Australia explored this association in nearly 400 patients withcancer who were 70 or older and were referred to a geriatric oncologyoutpatient unit. Half of the patients were referred for palliative care, 40%were taking statins, and half of the statin use was for primary prevention. Self-reported general pain was evaluated on a 10-point visualanalog scale. In the patients 80 or older, having a pain score of 5 or higherwas significantly associated with statin use, after adjusting for variablesincluding age, comorbidities, and the use of analgesics. In the younger group(those in their 70s), there was no significant association. Two points stand out from this study. First, many older patientswith cancer were getting statins often for primary prevention. Thisobservation suggests therapeutic inertia, in which clinicians fail to stopunnecessary medications; in fact, its not clear that statins should beprescribed for primary prevention even in 80-year-old patients without cancer.Second, although this study doesnt prove causality, it supports the impressionof many clinicians that older patients are especially prone to themusculoskeletal side effects of statins. COST-EFFECTIVENESS OF CTSCREENING FOR LUNG CANCER Three years ago, the National Lung Screening Trial showed thatcomputed tomography screening lowered lung cancerrelated mortality. Becausethe difference in mortality (1.7% in the control group vs . 1.3% with CT screening) wasrelatively modest and since screening is relatively expensive, thecost-effectiveness of screening has become a key issue for policy-makers andhealthcare systems. In a cost-effectiveness analysis in the November6th New England Journal of Medicine ( http://dx.doi.org/10.1056/NEJMoa1312547 ),researchers scrutinized the outcomes of the National Lung Screening Trial andMedicare costs. Averaged across the entire screened population, life wasextended by 0.03years per person. The incremental cost of screening(which included the cost of CT plus the downstream costs of evaluation andtreatment) was roughly US$1600 per person. So the cost per life-year gained wasabout US$50,000. The cost per quality-adjusted life-year gained was US$80,000. But the cost per quality-adjusted life-year gained variedsubstantially when assumptions in the model were changed and when subgroupswere examined. For example, the cost per quality-adjusted life-year gained wasUS$615,000 for former smokers ( vs .US$40,000 for current smokers) and was US$120,000 to US$270,000 for thepatients whose multivariable estimated risk for lung cancer was low ( vs .US$30,000 to US$50,000 forthose at higher risk). The analytic model described in this paper is impressivelycomprehensive, but its necessarily built on so many assumptions and estimatesthat one has to wonder how it would translate into real-world screening for lung cancer across thecountry. The analysis does suggest that computed tomography screening for lungcancer is substantially more cost-effective when its targeted to high-risksubgroups. SCREENING MEDICARE-ELIGIBLE PEOPLE FOR LUNG CANCER The National Lung Screening Trial showed that screening high-riskpatients with low-dose computed tomography vs .radiography lowered lung cancerrelated mortality during 6years offollow-up ( www.jwatch.o rg/jw201107140000001 ).But we dont know whether this finding applies to older patients. In asecondary analysis on the website of the Annalsof Internal Medicine ( http://dx.doi.org/10.7326/M14-148 4 ), researchersreexamined data from the trial by age: 20,000 patients between the ages of 55and 64 vs . 7000 patientsbetween 65 and 74. The older patients, compared with the younger ones, had asignificantly higher incidence of screen-detected lung cancer, a higherfalse-positive rate, and a higher incidence of major complications frominvasive procedures. Positive predictive values were low (less than 5%) forboth of the groups, and resection rates were similar in the two groups.Five-year survival was lower in the older group, whereas the number needed toscreen to prevent one lung cancer death was also lower in the older group. This analysis addresses some concerns about applying the findingsof the National Lung Screening Trial to older patients. Although complicationrates were higher in the older patients, the benefits of screening were alsogreater, because of a higher incidence of lung cancer ( http://dx.doi.org/10.7326/M14-2006 ).Although the study didnt include patients older than 74, the United StatesPreventive Services Task Force recently recommended CT-based lung cancerscreening for patients as old as 80 ( www.jwatch.org/na33375 ). EMBRYONIC STEM CELL TRANSPLANTS SHOW PROMISE INMACULARDEGENERATION In developed nations, atrophic (so-called dry ) age-related maculardegeneration is a leading cause of blindness among adults and Stargardt maculardystrophy is a leading cause of blindness in children. Generally, any attemptto transplant adult retinal pigmented epithelial cells to halt the progressionof or to cure these diseases hasnt been successful. Until now. In a multisite study on thewebsite of TheLancet ( http://dx.doi.org/10.1016/S0140-6736(14)61376-3 ), researchers in the United States report ontheir creation of retinal pigment epithelial cells from human embryonic stemcells. Nine patients with age-related macular degeneration and nine adults withStargardt macular dystrophy each got transplants of these cells into thesubretinal space of one eye, with the other eye left untreated as a control.The patients were placed on 3-month immunosuppressive regimens and werefollowed for a median of 22months. Visual acuity improved in 10 of thetreated eyes and remained the same in 7 treated eyes. Improvements werent seenin the untreated eyes. There were no serious side effects, like the formationof teratomas, rejection, or retinal detachment. These findings on human embryonic stem cellderived retinalpigment epithelium in patients with age-related macular degeneration andStargardts macular dystrophy are encouraging. But we need larger studies withlonger follow-up before concluding that the improved vision is durable and thatserious side effects dont emerge later. Recently, researchers in Japanreported that they are trying the same approach with induced pluripotent stemcells created from the patients own adult cells, thereby lowering the risk forimmune rejection. IS THERE SUCH A THING AS TOO MUCH MILK? Dairy products are promoted tolower the risk for fracture. But milk contains d -galactose,which induces oxidative stress and chronic inflammation in animal models and somight have deleterious long-term health effects. In an observational study onthe website of The BMJ ( http://dx.doi.org/10.1136/bmj.g6015 ), researchers in Sweden administeredfood-frequency questionnaires to 60,000 women and 45,000 men to determinewhether high milk consumption is associated with an excess risk for fracturesand death. During an average follow-up of 20years, women who drank 3or more glasses/day of milk (compared with those who drank less than 1glass/day) had higher risks for all-cause death, cardiovascular-related death,cancer-related death, any fracture, and hip fracture; there was a significantdose-response effect. During an average follow-up of 11years, men whodrank 3 or more glasses/day of milk had higher risks for all-cause death andcardiovascular-related death. Milk consumption was positively associated withelevated urinary and serum levels of biomarkers for oxidative stress andinflammation in both sexes. But eating cheese and fermented milk products (likeyogurt) wasnt associated with these effects. The researchers theorize that d -galactoseaccounts for the excess risks for death and fracture that are associated withhigh milk consumption. This theory is supported by the observation thatconsuming cheese and fermented milk products which dont contain d -galactose wasnt associatedwith these negative health effects. So although the researchers cant rule outthe possibility of residual confounding and reverse causation, maybe milk isnta magic bullet. ANTICHOLINERGIC DRUGS MIGHT LEAD TO HOSPITALIZATION FORDELIRIUM Many drugs that are widely prescribed to older patients haveanticholinergic properties. In a study in the October Journal of the American Geriatrics Society ( http://dx.doi.org/10.1111/jgs.13054 ),researchers in Australia examined whether anticholinergic drug use wasassociated with a higher risk for hospitalization for altered mental status innearly 40,000 patients with an average age of 83. Based on two published anticholinergic risk scales, 30 drugs wereconsidered to have strong anticholinergic potential, including drugs used forbladder and bowel overactivity, antipsychotics, tricyclic antidepressants,paroxetine, antihistamines, and several anti-Parkinsonism drugs. All of thepatients had taken at least one of these drugs during the year before theyentered the study. Then, during 2years of study, the researchers comparedthe rates of hospitalization for confusion, delirium, or dementia during thetimes when the patients were exposed or unexposed to anticholinergics. After adjusting for demographic and clinical variables, a higherrisk for hospitalization conferred by taking one anticholinergic drug was ofborderline significance. But the risk was markedly elevated for the patientstaking two or more anticholinergic drugs. To minimize reverse causality, theanalysis was repeated after excluding patients who took antipsychotic drugs(because they are prescribed for behavioral symptoms in patients withpreexisting cognitive dysfunction); the results were similar to those of theoverall analysis. Anyone who does hospital medicine has surely seen patientsadmitted for anticholinergic druginduced delirium. Sometimes, a nuancedbenefit-harm evaluation favors a careful trial of an anticholinergic drug in anolder patient. But in many cases, the potential side effects dont justify themarginal expected benefit. IN SEARCH OF A DISCHARGE INTERVENTION THAT WORKS The implementation of discharge support programs to preventhospital readmissions has yielded mixed results. Recent meta-analyses of theseprograms have suggested that multicomponent interventions at the healthcaresystems level are needed to influence care outcomes ( www.jwatch.org/hm201209170000001 ).Individual components that lead to better outcomes have yet to be elucidated. In a study in the October7th Annals of Internal Medicine ( http://dx.doi.org/10.7326/M14-0094 ),researchers randomized 700 low-income, ethnically diverse patients with anaverage age of 66 at a single safety net hospital either to usual care or to anurse-led, in-hospital, discharge support intervention. The usual-care patientsgot registered nurse reviews of discharge instructions and, if indicated,pharmacy or social-worker consultations. The intervention patients got usual careplus language-concordant nurse coaching and teach-back techniques (on symptomrecognition, medication reconciliation, and strategies to navigate the healthsystem) at study enrollment and again at discharge. Plus, the primary caredoctors of the intervention patients were notified of inpatient providerscontact information, and nurse practitioners called the patients at home ondays 1 to 3 as well as on days 6 to 10 after discharge. Despite theseinterventions, the primary outcome of emergency department visits orreadmissions were similar in the groups at 1, 2, and 6months. Three elements might have contributed to these negative results.First, the patients in the usual-care group had excellent access to primarycare, with most reporting outpatient follow-up within a month of discharge.Second, the usual-care groups readmission rate of 15% was below the nationalaverage of 18%. And third, registered nurses werent empowered to expediteurgent follow-up. Until we understand which interventions work and in whatpopulations, the search for the ideal readmission-prevention strategycontinues. DOES MY PATIENT HAVE A CENTRALLINE? A key strategy for preventing complications from central venouscatheters (namely, triple-lumen catheters or peripherally inserted centralcatheters) is to remove the lines when they are no longer needed. The firststep in knowing when to remove the lines is recognizing their presence. In a study in the October21st Annals of Internal Medicine ( http://dx.doi.org/10.7326/M14-0703 ),researchers at three academic medical centers in the United States examinednearly 1000 patients and identified more than 200 with central venous cathetersin place. Subsequent surveys, given to more than 1800 primary inpatientclinicians (namely, attending physicians, residents, and advanced practiceproviders [like physician assistants and nurse practitioners]) followingmorning rounds on their patients, showed that 20% of the clinicians werent awareof central venous catheters in their patients. The lack of central lineawareness was significantly higher in settings outside of intensive care unitsand among attending physicians (namely, hospitalists who primarily cared forpatients or teaching attendings), compared with residents and advanced practiceproviders. With the paramount individual and collective responsibility toprovide safe patient care, recognizing that invasive devices are present andremoving them when they are no longer needed is essential to preventing centralline infections and thromboses. This trial documents a larger problem ofinertia in medical practice: Frequently, clinicians forget to stop medications, lab testing, urinarycatheters, and other interventions when they no longer benefit the patient.This inertia can be overcome by a meticulous daily review of all interventionsand orders, backed up by systems solutions like prompts, checklists, andinterdisciplinary rounding ( htt p://dx.doi.org/10.7326/M14-2005 ). FOR PATIENTS WITH NEWLYDIAGNOSED TYPE 2 DIABETES,METFORMIN IS THE BESTFIRSTCHOICE Metformin is recommended by several organizations and guidelinesas first-line therapy for patients with newly diagnosed type2 diabetes,but clinicians often start with other classes of hypoglycemics. In aretrospective cohort study on the website of JAMAInternal Medicine ( http://dx.doi.org/10.1001/jamainternmed.20 14.5294 ),researchers used pharmacy and claims data from a large national healthinsurance plan to evaluate the consequences of first-line treatment in about15,000 patients who started therapy with metformin, sulfonylureas, dipeptidylpeptidase 4 inhibitors, or thiazolidinediones. Follow-up was approximately ayear. In adjusted analyses, the patients who started therapy with drugclasses other than metformin were about 60% more likely to need a second agent,either another oral drug or insulin. The second drug was most commonlymetformin. Initial sulfonylurea use was associated with an excess risk for newadverse cardiovascular events and for emergency department or hospitaladmissions for hypoglycemia. Limitations of this study include its retrospective nature andthe researchers inability to adjust for certain potentially importantvariables, like hemoglobin A 1c and serum creatinine levels. Even so,these results reinforce recommendations for using metformin as first-linetherapy for patients with new diagnoses of type2 diabetes; they also addto increasing concern about using sulfonylureas. The finding that metformin wasthe initial choice in fewer than 60% of patients suggests that clinicians needto develop approaches to change prescribing behavior. FLUOROQUINOLONE ANTIBIOTICS AND POLYNEUROPATHY Primarily on the basis of case reports submitted to the Food andDrug Administration, the agency recently required a change in the labeling offluoroquinolone antibiotics to include a warning about an increased risk forpolyneuropathy ( www.jwatch.org/na32044 ).But no data have been available to quantify this risk. Now, a case-controlstudy in the September30th issue of Neurology ( http://dx.doi.o rg/10.1212/WNL.0000000000000846 )sheds light on this question. Using claims data from the LifeLink database (which only includesdata from men), researchers identified 6200 patients with incident idiopathicpolyneuropathy and 25,000 age- and disease durationmatched controls; they thencompared fluoroquinolone use in each group. Any use was defined as getting aprescription within a year before the index date, and current use was definedas getting a prescription within 2weeks; current new use was getting afirst fluoroquinolone prescription within 2weeks. Patients with diabetesor hereditary peripheral neuropathy were excluded. After adjusting forpotential confounders, current users of fluoroquinolones, especially currentnew users, were found to be at a significantly higher risk for developingpolyneuropathy. Because of their widespread use and the observed twofold higherrisk for polyneuropathy after treatment with oral fluoroquinolones, this classof antibiotic might be an important (and often underrecognized) cause ofpolyneuropathy. The available data suggest that fluoroquinolone-inducedneuropathy is typically acute, affects sensory fibers more than motor fibers,and might not be fully reversible after drug discontinuation. RIFAMPICIN PLUS TMP/SMX IS NONINFERIOR TO LINEZOLID FOR MRSAINFECTIONS Standard treatment for methicillin-resistant Staphylococcus aureus infectionsnamely, vancomycin requires intravenous in-hospital administration inmost cases. Oral linezolid is well absorbed and exhibits potent anti-MRSAactivity, but high cost, drug interactions, and adverse events limit its use.Trimethoprim/sulfamethoxazole, administered orally with or without rifampicin,is also well absorbed and exhibits good anti-MRSA activity, but is it aseffective as linezolid? In a noninferiority study on the website of the Journal of Antimicrobial Chemotherapy ( http://dx.doi.org/10.1093/jac/dku352 ),researchers in Switzerland sought to answer this question. The researchers randomized 150 patients with various types ofmethicillin-resistant Staphylococcusaureus infections (including severe and deep-seated infections)either to 600mg of linezolid twice/day, or, to 160mg oftrimethoprim and 800mg of sulfamethoxazole three times/day plus600mg of rifampicin once/day for 7 or more days. In intent-to-treat andper-protocol analyses, at least three quarters of both the linezolid patientsand the trimethoprim/sulfamethoxazolerifampicin patients achieved clinicalcure. There were 4 adverse drug reactions in the linezolid group vs . 9 in thetrimethoprim/sulfamethoxazolerifampicin group. In regions with susceptible methicillin-resistant Staphylococcus aureus strains,trimethoprim/sulfamethoxazole plus rifampicin seems to be an equally effective,equally well-tolerated, cheaper alternative to linezolid for the oral treatmentof patients with MRSA infections, including deep-seated ones. But clinicianshave to consider the risks for thrombocytopenia and hepatotoxicity withlinezolid, hematotoxicity and nephrotoxicity withtrimethoprim/sulfamethoxazole, and hepatotoxicity and drug interactions withrifampicin. With any oral regimen, patients should be closely monitored foradverse events. HIGHER RISK FOR MAJOR BLEEDING WITH DABIGATRAN vs . WARFARIN IN CERTAINAF PATIENTS The original trials that led to the approval of dabigatran (tradename: Pradaxa) for preventing strokes in patients with nonvalvular atrialfibrillation showed that the risk for major bleeding was similar withdabigatran and warfarin ( www.jwatch.org/jc200909010000003 ).But some (although not all) postmarketing case reports and analyses suggestedthat the risk was greater with dabigatran in high-risk patients and in patientswith reduced renal function ( http://dx.doi.org/10.1001/jamainternmed.2013.12217 ). In a retrospective cohort study on the website of JAMA Internal Medicine ( http://dx.doi.org/10.1001/jamainternmed.2014.5398 ),researchers identified more than 9000mostly white Medicare patients withnewly diagnosed atrial fibrillation and an average age of 75; 1300 of thepatients got dabigatran, and 8000 got warfarin. Follow-up was about6months. Adjusted analyses showed that the dabigatran patients had asignificantly higher risk for any bleeding and for major bleeding, comparedwith the warfarin patients. The between-groups differences were even morepronounced for black patients and for patients who had chronic kidney disease.Intracranial bleeding was more common in the warfarin patients, butgastrointestinal bleeding was more common in the dabigatran patients. In this study, chronic kidney disease was a single entity,abstracted from claims data (not stratified into specific ranges based onglomerular filtration rate). Plus, the researchers couldnt determine whetherthe doses of dabigatran were lowered, as recommended by the manufacturer, forthe patients with glomerular filtration rates lower than 30mL/minute/1.73m 2 . So these retrospective results dont necessarily contradict theabove-referenced randomized trials, which excluded patients with estimatedglomerular filtration rates lower than 30mL/minute/1.73 m 2 andshowed no excess risk for major bleeding with dabigatran, compared withwarfarin. Even so, these findings suggest the need for caution in certainsubgroups, like black patients and patients with renal impairment. IN THE LONG TERM, COILING BESTS CLIPPING FOR RUPTUREDINTRACRANIAL ANEURYSMS Twenty years ago, researchers in the United Kingdom began aninternational randomized trial of neurosurgical clipping vs . endovascular coiling in 2000patients with ruptured intracranial aneurysms ( www.jwatch.org/jw200510070000001 ).After a year, the patients in the coiling group experienced a lower risk fordeath or dependency; after 5years, the coiling patients had more-frequentrebleeding from target aneurysms, but with no substantial effects on survivalor dependency. Now, in a study on the website of The Lancet ( http://dx.doi.org/10.1016/S0140-6736(14)60975-2 ),the researchers present data from national registries and annual questionnairesaccrued from 10 to 18years of follow-up in 1600 patients. Ten years after the intervention, significantly more patients inthe coiling group were still alive, roughly 80% of the survivors in each groupwere living independently, and significantly more coiling patients were bothalive and independent. Thirteen patients in the coiling group and 4 in theclipping group had late rebleeds from target aneurysms, resulting in death ordependency in 6 coiling patients and all 4 clipping patients. This landmark trial transformed the treatment of patients withintracranial aneurysms; the researchers report that, in the United Kingdom, 85%of these aneurysms are now managed with endovascular coiling. These findingsconfirm that, in the long term, coiling is more effective than clipping (withless morbidity) in appropriately selected patients who can be treated usingeither modality, and the risk for rebleeding after coiling is low. RECALLED DIETARY SUPPLEMENTS: STILL AVAILABLE, STILLADULTERATED Recently, the Food and Drug Administration has recalled nearly300 dietary supplements because of contamination or purposeful adulterationwith potentially dangerous drugs (primarily stimulants and anabolic steroids).Many of these branded supplements are now available commercially but arethey still tainted? To find out, researchers selected 30 supplements subjected to aclass I recall (meaning that there was a reasonable possibility of seriousadverse events or death) and available for sale 6 or more months later with thesame names, manufacturers, and distributors. Details appear in theOctober22nd and 29th issue of JAMA ( http://dx.doi.org/10.1001/jama.2014.10308 ). Pharmaceutical adulterants were identified in two thirds of allof the samples, including 11 of 13 supplements for sports enhancement (2 ofwhich had been recalled twice), 6 of 9 supplements for weight loss, and 1 of 5supplements for sexual enhancement. The most common adulterants were anabolicsteroids or steroid-like analogues, followed by sibutramine and sildenafil orrelated compounds. Clinicians can use these findings to advise their patients thatmany dietary supplements (even those with recalls purportedly addressed by themanufacturer) might contain potentially dangerous adulterants or contaminants.In overseeing recalls, particularly those involving possible fraud, the Foodand Drug Administration can issue warning letters ( www.fda.gov/ForConsumers/ProtectYourself/HealthFraud/ucm255474.htm ),carry out seizures and injunctions ( www.fda.gov/ForConsumers/ProtectYourself/HealthFraud/ucm272203.htm ),and seek criminal prosecution. But these results show that these enforcementmeasures arent 100% effective. COMBINATION THERAPY MIGHT ALLOW MEDICATION TAPERING ORCESSATION IN RA PATIENTS Treating patients with rheumatoid arthritis has beenrevolutionized by biologic therapies, but these drugs are costly (often morethan US$30,000 a year). Lower-cost options are triple therapy withhydroxychloroquine, sulfasalazine, and methotrexate ( www.jwatch.org/jw201210230000002 and www.jwatch.org/na31743 )and reducing or even stopping biologic therapies. In a study in the November6th New England Journal of Medicine ( http://dx.doi.org/10.1056/ NEJMoa1316133 ),300 patients with early moderate-to-severe rheumatoid arthritis (a duration ofless than a year) were initially treated with 50mg/mL/week of etanercept(trade name: Enbrel) plus methotrexate for a year. The 200 patients who achievedlow disease activity or remission at a year were then randomized to25mg/0.5mL/week of etanercept plus methotrexate, placebo plusmethotrexate, or double placebo for 10months more. As expected, thepatients on combination therapy were significantly more likely to achieveremission during the double-blind phase of the study. At 10months, 130patients still exhibited low disease activity; their drugs were withdrawn, andthey were observed for 6months. Eighty of these patients were able tocomplete the treatment-withdrawal phase. There was no statistical difference inthe radiographic progression of disease in any of the groups. This study shows that once remission is achieved with etanerceptplus methotrexate, patients do better on a lower dose of etanercept plusmethotrexate than on methotrexate alone. But some patients were able to stopetanercept or both therapies without disease flares; and the x-ray progressionof disease, at least for 10months, was unchanged among the groups. Thiswithdrawal strategy might be helpful to control costs, but clinicians cantprospectively identify those patients in whom the reduction or the withdrawalof therapy will be successful. This study was manufacturer-sponsored. HAND THERAPY MIGHT HELP HANDFUNCTIONIN PATIENTS WITH RA Treatment success for patients with rheumatoid arthritis improveddramatically since the introduction of the first biologic agent, etanercept(trade name: Enbrel). But adjunctive modalities, like hand exercises andoccupational therapy, which were aggressively used by rheumatologists in thepre-biologic era, are no longer extensively used. In a multicenter study on the website of The Lancet ( http://dx.doi.org/10.1016/S0140-6736(14)6099 8-3 ),researchers in the United Kingdom evaluated 500 patients who had gotten stablemedical regimens for 3months or longer. The patients were randomized toeither usual care or usual care plus a hand-strengthening and hand-exerciseprogram. The intervention involved six sessions with a therapist who promotedpatient-directed goal-setting and instructed the patients in mobility andstrength-and-endurance exercises that were to be performed at home every day.At 4months and again at a year, compared with the usual-care group, theexercise group had significant improvements in overall hand function, theactivities of daily living, satisfaction, and the confidence to self-managesymptoms. An editorialist notes ( http://dx.doi.org/10.1016/S0140 6736(14)61285-X )that the feasibility of strengthening regimens for patients with rheumatoidarthritis has been questioned. In this British study, only 20% of the patientswere getting biologic disease-modifying antirheumatic drugs; in many Americancenters, at least twice that percentage get these drugs. But appropriate handtherapy should become more of a standard of care, even in the United States, asit provides clear benefits at marginal costs. Of course, therapists would needspecial training to effectively implement this intervention. USING MOTIVATIONAL INTERVIEWINGTECHNIQUES TO IMPROVEADHERENCE TO CPAP Many patients with obstructive sleep apnea have difficulty inadhering to the prescribed use of continuous positive airway pressure. In astudy in the Septemberissue of Chest ( http://dx.doi.org/10.1378/chest.13-2228 ),researchers in Hong Kong examined whether a briefmotivational enhancement education program would improve adherenceto CPAP. The researchers randomized 100 patients with documentedobstructive sleep apnea (half with mild-to-moderate disease and half withsevere disease) to either an intervention group or a control group followingovernight CPAP titration. The controls each attended a 15-minute session thatfocused on the importance of CPAP and care of the equipment. The interventionpatients each attended a 45-minute session that included a video and aninterview based on motivational interviewing theory; the session was designedto enhance the perception of the risk conferred by obstructive sleep apnea, toimprove confidence in the patients ability to apply CPAP, and to reinforce theassociation between treatment and desired outcomes. Two days later, theintervention patients got 10-minute follow-up phone calls. At 3months, the average nightly use of continuous positiveairway pressure was significantly longer in the intervention group than in thecontrol group (4 vs .2hours), and average scores on the Epworth Sleepiness Scale ( http://web.stanford.edu/~dement/epworth.html )were significantly lower in the intervention group. Because evaluating and managing obstructive sleep apnea is anexpensive and fairly intrusive process, anything that could improve adherenceto continuous positive airway pressure would be welcome. The short-term effectof this relatively modest intervention was remarkable, and the study deservesreplication in other clinical settings.

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Learning Format 6 Hours
Self-Study

Credit Type(s)
Neurology Geriatrics Cardiology Radiology Internal Medicine