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Reviews | 
Bram Rochwerg, MD; Waleed Alhazzani, MD; Anees Sindi, MD; Diane Heels-Ansdell, MSc; Lehana Thabane, PhD; Alison Fox-Robichaud, MD; Lawrence Mbuagbaw, MSc; Wojciech Szczeklik, MD; Fayez Alshamsi, MD; Sultan Altayyar, MD; Wang-Chun Ip, MD; Guowei Li, MSc; Michael Wang, MD; Anna Włudarczyk, MD; Qi Zhou, PhD; Gordon H. Guyatt, MD; Deborah J. Cook, MD; Roman Jaeschke, MD; and Djillali Annane, MD, PhD, for the Fluids in Sepsis and Septic Shock Group
Includes: Supplemental Content
Background:Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. Purpose:To examine the effect of different resuscitative fluids on mortality in patients with sepsis. Data Sources:MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. Study Selection: Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. Data Extraction:Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. Data Synthesis:14 studies (18 916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). Limitations:These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. Conclusion:Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. Primary Funding Source:The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.
Topics: colloids, septicemia, starch, crystalloid, normal saline, fluid resuscitation, saline solution, albumin solution, crystalloid fluid replacement, colloid fluid replacement, systemic infection, albumins
Original Research | 
Timothy J. Henrich, MD; Emily Hanhauser, BS; Francisco M. Marty, MD; Michael N. Sirignano, BS; Sheila Keating, PhD; Tzong-Hae Lee, MD, PhD; Yvonne P. Robles, BA; Benjamin T. Davis, MD; Jonathan Z. Li, MD; Andrea Heisey, BS; Alison L. Hill, PhD; Michael P. Busch, MD, PhD; Philippe Armand, MD, PhD; Robert J. Soiffer, MD; Marcus Altfeld, MD, PhD; and Daniel R. Kuritzkes, MD
Background:It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. Objective:To characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission. Design:Case report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. Setting:Tertiary care center. Patients:Two men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors. Measurements:Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. Results:No HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients. Limitation:The study only involved 2 patients. Conclusion:Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission. Primary Funding Source:Foundation for AIDS Research and National Institute of Allergy and Infectious Diseases.
Topics: hiv, hiv-1, hiv infection, anti-retroviral agents, allogeneic hematopoietic stem cell transplant, disease remission, hematopoietic stem cell transplantation, allogeneic stem cell transplant
Editorials | 
Sharon R. Lewin, FRACP, PhD
In 2 patients with HIV with undetectable virus years after hematopoietic stem cell transplantation, rebound viremia and acute retroviral syndrome occurred 12 and 32 weeks after stopping antiretroviral therapy. A “functional cure” of HIV infection remains elusive.
Topics: hiv, hematopoietic stem cell transplantation, hiv-1, allogeneic stem cell transplant, hiv infection, anti-retroviral agents, allogeneic hematopoietic stem cell transplant, disease remission
Optimal methods of fluid resuscitation for critically ill patients with sepsis are much debated. In this issue, Rochwerg and colleagues report a network meta-analysis that compares various strategies for fluid resuscitation in sepsis. The editorialist discusses the meta-analysis and raises unanswered questions about the role of crystalloid solutions in fluid resuscitation.
Topics: systemic infection, albumins, colloids, septicemia, starch, crystalloid, normal saline, fluid resuscitation, saline solution, albumin solution, crystalloid fluid replacement, colloid fluid replacement
The National Quality Forum recently convened an expert panel to make recommendations on whether to risk-adjust health care performance measures for patient sociodemographic factors in addition to clinical factors present at the initiation of care. This commentary discusses why the panel chose to recommend such adjustment and why the topic is so hotly debated.
Topics: hospitals, performance measures, patient readmission
Letters | 
Charlene A. Wong, MD; David A. Asch, MD, MBA; Cjloe M. Vinoya, BS; Carol A. Ford, MD; Tom Baker, JD; Robert Town, PhD; and Raina M. Merchant, MD, MSHP
Topics: decision support systems, internet, patient protection and affordable care act, consumer preference, usability testing, health insurance exchanges
Reviews | 
Daniel E. Jonas, MD, MPH; Cynthia Feltner, MD, MPH; Halle R. Amick, MSPH; Stacey Sheridan, MD, MPH; Zhi-Jie Zheng, MD, MPH, PhD; Daniel J. Watford, MD, MPH; Jamie L. Carter, MD, MPH; Cassandra J. Rowe, MPH; and Russell Harris, MD, MPH
Includes: Supplemental Content
Background:Approximately 10% of ischemic strokes are caused by carotid artery stenosis (CAS). Estimated prevalence of asymptomatic CAS is 1%. Purpose:To evaluate evidence on screening and treating asymptomatic adults for CAS. Data Sources:MEDLINE, the Cochrane Library, EMBASE, and trial registries through September 2013; MEDLINE through March 2014 for trials. Study Selection:Good- or fair-quality trials of screening, carotid endarterectomy (CEA), or stenting compared with medical therapy or of intensification of medical therapy; systematic reviews; multi-institution studies reporting harms; and externally validated risk-stratification tools. Data Extraction:Dual extraction and quality assessment. Data Synthesis:No trials compared screening with no screening or stenting with medical therapy or assessed intensification of medical therapy, and no externally validated, reliable risk-stratification tools were found. Given the specificity of ultrasonography (range, 88% to 94% for CAS of ≥50% to ≥70%), its use in low-prevalence populations would yield many false-positive results. Absolute reduction of nonperioperative strokes was 5.5% (95% CI, 3.9% to 7.0%; 3 trials with 5223 participants) over approximately 5 years for CEA compared with medical therapy. The 30-day rates of stroke or death after CEA in trials and cohort studies were 2.4% (CI, 1.7% to 3.1%; 6 trials; n = 3435) and 3.3% (CI, 2.7% to 3.9%; 7 studies; n = 17 474), respectively. Other harms of interventions include myocardial infarction, nerve injury, and hematoma. Limitations:Trials may have overestimated benefits and used highly selected surgeons. Medical therapy used in trials was outdated, and stroke rates have declined in recent decades. Harms may have been underreported. Conclusion:Current evidence does not establish incremental overall benefit of CEA, stenting, or intensification of medical therapy. Potential for overall benefit is limited by low prevalence and harms. Primary Funding Source:Agency for Healthcare Research and Quality.
Topics: carotid stenosis, ischemic stroke, screening
The U.S. Preventive Services Task Force recommends against screening for asymptomatic carotid artery stenosis. However, such screenings are offered throughout the United States. The editorialist discusses the recommendations and warns potential consumers of these services to be aware that the test is unlikely to prevent them from having a stroke.
Topics: carotid stenosis, ischemic stroke, screening
Clinical Guidelines | 
Michael L. LeFevre, MD, MSPH, on behalf of the U.S. Preventive Services Task Force*
Description:Update of the 2007 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for carotid artery stenosis. Methods:The USPSTF commissioned a systematic review to synthesize the evidence on the accuracy of screening tests, externally validated risk stratification tools, the benefits of treatment of asymptomatic carotid artery stenosis with carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAAS), the benefits from medications added to current standard medical therapy, and the harms of screening and treatment with CEA or CAAS. Population:This recommendation applies to adults without a history of transient ischemic attack, stroke, or other neurologic signs or symptoms. Recommendation:The USPSTF recommends against screening for asymptomatic carotid artery stenosis in the general adult population. (D recommendation)
Topics: carotid stenosis, screening, ischemic stroke
Topics: carotid stenosis, ischemic stroke, screening
Topics: abdominal aortic aneurysm, preventive health services, united states preventive services task force
Clinical Guidelines | 
Michael L. LeFevre, MD, MSPH, on behalf of the U.S. Preventive Services Task Force*
Description:Update of the 2005 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for abdominal aortic aneurysm (AAA). Methods:The USPSTF commissioned a systematic review that assessed the evidence on the benefits and harms of screening for AAA and strategies for managing small (3.0 to 5.4 cm) screen-detected AAAs. Population:These recommendations apply to asymptomatic adults aged 50 years or older. Recommendation:The USPSTF recommends 1-time screening for AAA with ultrasonography in men aged 65 to 75 years who have ever smoked. (B recommendation) The USPSTF recommends that clinicians selectively offer screening for AAA in men aged 65 to 75 years who have never smoked. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AAA in women aged 65 to 75 years who have ever smoked. (I statement) The USPSTF recommends against routine screening for AAA in women who have never smoked. (D recommendation)
Topics: abdominal aortic aneurysm, ultrasonography, mortality, american academy of arts and sciences, ruptured abdominal aortic aneurysm, rupture
Medicine and Public Issues | 
Michelle K. Koltov, MPH; and Nitin S. Damle, MD
The U.S. health care system is in the midst of transforming from a fee-for-service system to a value-based system that delivers high-quality and cost-effective care. Quality reporting programs and increasing transparency of performance are meant to encourage physicians and hospitals to invest in improving the delivery of care. In 2006, the Centers for Medicare & Medicaid Services implemented the Physician Quality Reporting System (PQRS). The PQRS is an incentive and penalty payment program for eligible professionals who report data on quality measures for covered professional services furnished to Medicare beneficiaries. The program gives eligible professionals the opportunity to assess the quality of care they are providing to their patients and compare their performance on a given measure with their peers. This article discusses the history of PQRS, the 2014 PQRS, and how it affects other quality programs.
Topics: physician quality reporting system, health policy
On 30 April 2014, the Medicare Evidence Development & Coverage Advisory Committee convened to weigh the evidence for low-dose computed tomography (LDCT) screening for lung cancer. Many were shocked by the outcome: a vote of low confidence about whether the benefits of LDCT screening would outweigh harms among Medicare beneficiaries in a community setting. This commentary discusses potential strategies to implement lung cancer screening with LDCT in a responsible manner that avoids overzealous screening.
Topics: lung cancer screening, low-dose spiral ct
Reviews | 
Devan Kansagara, MD, MCR; Joel Papak, MD; Amirala S. Pasha, DO, MS; Maya O'Neil, PhD; Michele Freeman, MPH; Rose Relevo, MLIS, MS; Ana Quiñones, PhD; Makalapua Motu'apuaka, BS; and Janice H. Jou, MD, MHS
Includes: Supplemental Content
Background:Guidelines recommend routine screening for hepatocellular carcinoma (HCC) in high-risk patients, but the strength of evidence supporting these recommendations is unclear. Purpose:To review the benefits and harms of HCC screening in patients with chronic liver disease. Data Sources:MEDLINE, PsycINFO, and ClinicalTrials.gov from inception to April 2014; Cochrane databases to June 2013; reference lists; and technical advisors. Study Selection:English-language trials and observational studies comparing screening versus no screening, studies of harms, and trials comparing different screening intervals. Data Extraction:Mortality and adverse events were the outcomes of interest. Individual-study quality and the overall strength of evidence were dual-reviewed using published criteria. Data Synthesis:Of 13 801 citations, 22 studies met inclusion criteria. The overall strength of evidence on the effects of screening was very low. One large trial found decreased HCC mortality with periodic ultrasonographic screening (rate ratio, 0.63 [95% CI, 0.41 to 0.98]), but the study was limited by methodological flaws. Another trial in patients with hepatitis B found no survival benefit with periodic α-fetoprotein screening. In 18 observational studies, screened patients had earlier-stage HCC than clinically diagnosed patients, but lead- and length-time bias confounded the effects on mortality. Two trials found no survival differences between shorter (3- to 4-month) and longer (6- to 12-month) screening intervals. Harms of screening were not well-studied. Limitations:Only English-language studies were included. The evidence base is limited by methodological issues and a paucity of trials. Conclusion:There is very-low-strength evidence about the effects of HCC screening on mortality in patients with chronic liver disease. Screening tests can identify early-stage HCC, but whether systematic screening leads to a survival advantage over clinical diagnosis is uncertain. Primary Funding Source:U.S. Department of Veterans Affairs Quality Enhancement Research Initiative.
Topics: carcinoma, hepatocellular, hepatitis b, chronic, hepatitis b virus, liver disease, chronic, liver cancer screening, mortality, liver cirrhosis
Editorials | 
David Atkins, MD, MPH; David Ross, MD, PhD, MBI; and Michael Kelley, MD
Specialty society guidelines recommend screening high-risk patients for hepatocellular carcinoma, but a systematic review in this issue demonstrates that evidence of a mortality benefit of screening remains insufficient to support a strong recommendation for or against screening. In this commentary, physicians who oversee different areas relevant to this clinical puzzle at the Veterans Health Administration discuss what to do in the face of this uncertainty. They agree on much of the evidence, what research is needed, and the policy options necessary to consider while waiting for better evidence.
Topics: liver disease, chronic, liver cirrhosis, carcinoma, hepatocellular, hepatitis b, chronic, veterans, hepatitis b virus, mortality, overdiagnosis, early diagnosis, liver cancer screening
Ideas and Opinions | 
Eric M. Horwitz, MD; and David S. Weinberg, MD, MSc
A cursory evaluation of recently released Medicare data highlights wide variations in payments to individual physicians. The authors caution against superficial evaluation of these data without a deeper understanding of what they can and cannot indicate and point to their potential value in understanding variations in health care.
Topics: health care costs, medicare, health care financing, physician payment, Billing and payment
In April 2014, the U.S. Food and Drug Administration approved the Cobas HPV test to be used alone to screen women aged 25 years or older for cervical cancer. This commentary discusses the advantages and disadvantages of the newly approved test. The authors emphasize that increasing screening rates should be the major focus of efforts to reduce invasive cervical cancer regardless of which test is used.
Topics: cervical cancer, human papillomavirus, vaginal smears, human papilloma virus infection, hpv - human papillomavirus test, cervical cancer screening
Ideas and Opinions | 
Gail R. Wilensky, PhD
In April 2014, the Centers for Medicare & Medicaid Services (CMS) published detailed information on the $77 billion that 880 000 health care practitioners billed for some 6000 types of Medicare Part B services in 2012. This commentary by a former CMS administrator discusses how these data can be helpful, what is missing that might lead to misinterpretation, and why such transparency is here to stay.
Topics: health care costs, medicare, health care financing, physician payment, Billing and payment
Ideas and Opinions | 
Richard J. Baron, MD; and David Johnson, MD
Recent changes in the board certification process are a topic of much debate. This commentary presents the American Board of Internal Medicine’s perspective on changes in the certification process and their importance to professional self-regulation.
Topics: certification, credentialing, internal medicine, professional autonomy, social control, informal, specialty boards

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