Annals of Internal Medicine Current Issue

Action to Stop Smoking in Suspected Tuberculosis (ASSIST) in Pakistan A Cluster Randomized, Controlled Trial

Siddiqi K, Khan A, Ahmad M, et al. — Tue, 07 May 2013 00:00:00 GMT

Background:

Tobacco use is responsible for a large proportion of the total disease burden from tuberculosis. Pakistan is one of the 10 high-burden countries for both tuberculosis and tobacco use.

Objective:

To assess the effectiveness of a behavioral support intervention and bupropion in achieving 6-month continuous abstinence in adult smokers with suspected pulmonary tuberculosis.

Design:

Cluster randomized, controlled trial. (Current Controlled Trials: ISRCTN08829879)

Setting:

Health centers in the Jhang and Sargodha districts in Pakistan.

Patients:

1955 adult smokers with suspected tuberculosis.

Intervention:

Health centers were randomly assigned to provide 2 brief behavioral support sessions (BSS), BSS plus 7 weeks of bupropion therapy (BSS+), or usual care.

Measurements:

The primary end point was continuous abstinence at 6 months after the quit date and was determined by carbon monoxide levels in patients. Secondary end points were point abstinence at 1 and 6 months.

Results:

Both treatments led to statistically significant relative risks (RRs) for abstinence compared with usual care (RR for BSS+, 8.2 [95% CI, 3.7 to 18.2]; RR for BSS, 7.4 [CI, 3.4 to 16.4]). Equivalence between the treatments could not be established. In the BSS+ group, 275 of 606 patients (45.4% [CI, 41.4% to 49.4%]) achieved continuous abstinence compared with 254 of 620 (41.0% [CI, 37.1% to 45.0%]) in the BSS group and 52 of 615 (8.5% [CI, 6.4% to 10.9%]) in the usual care group. There was substantial heterogeneity of program effects across clusters.

Limitations:

Imbalances in the urban and rural proportions and smoking habits among treatment groups, and inability to confirm adherence to bupropion treatment and validate longer-term abstinence or the effect of smoking cessation on tuberculosis outcomes.

Conclusion:

Behavioral support alone or in combination with bupropion is effective in promoting cessation in smokers with suspected tuberculosis.

Primary Funding Source:

International Development Research Centre.

An Acute Change in Lung Allocation Score and Survival After Lung Transplantation A Cohort Study

Tsuang* WM, Vock* DM, Finlen Copeland C, et al. — Tue, 07 May 2013 00:00:00 GMT

Chinese translation

Background:

Lung transplantation is an effective treatment for patients with advanced lung disease. In the United States, lungs are allocated on the basis of the lung allocation score (LAS), a composite measure of transplantation urgency and utility. Clinical deteriorations result in increases to the LAS; however, whether the trajectory of the LAS has prognostic significance is uncertain.

Objective:

To determine whether an acute increase in the LAS before lung transplantation is associated with reduced posttransplant survival.

Design:

Retrospective cohort study of adult lung transplant recipients listed for at least 30 days between 4 May 2005 (LAS implementation) and 31 December 2010 in the United Network for Organ Sharing registry. An acute increase in the LAS was defined as an LAS change (LASΔ) greater than 5 units between the 30 days before and the time of transplantation. Multivariable Cox proportional hazard models were used to examine the relationship between an LASΔ >5 and posttransplant graft survival.

Setting:

All U.S. lung transplantation centers.

Patients:

5749 lung transplant recipients.

Measurements:

Survival time after lung transplantation.

Results:

702 (12.2%) patients experienced an LASΔ >5. These patients had significantly worse posttransplant survival (hazard ratio, 1.31 [95% CI, 1.11 to 1.54]; P = 0.001]) after adjustment for the LAS at transplantation (LAS-T) and other clinical covariates. The effect of an LASΔ >5 was independent of the LAS-T, underlying diagnosis, center volume, or donor characteristics.

Limitation:

Analysis was based on center-reported data.

Conclusion:

An acute increase in LAS before transplantation is associated with posttransplant survival after adjustment for LAS-T. Further emphasis on serial assessment of the LAS could improve the ability to offer accurate prediction of survival after transplantation.

Primary Funding Source:

National Institutes of Health.

HIV, Age, and the Severity of Hepatitis C Virus–Related Liver Disease A Cohort Study

Kirk GD, Mehta SH, Astemborski J, et al. — Tue, 07 May 2013 00:00:00 GMT

Chinese translation

Background:

Persons with HIV infection have been reported to develop age-related diseases at younger ages than those without HIV. Whether this finding is related to HIV infection or failure to control for other risk factors is unknown.

Objective:

To investigate whether persons with HIV infection develop hepatitis C virus (HCV)–related liver disease at younger ages than similar persons without HIV.

Design:

Comparison of the severity of liver fibrosis by age among persons who have HCV with and without HIV followed concurrently in the same protocol.

Setting:

Observational cohort from Baltimore, Maryland, participating in the ALIVE (AIDS Linked to the IntraVenous Experience) study.

Participants:

1176 current and former injection drug users with antibodies to HCV.

Measurements:

Liver fibrosis assessed semiannually from 2006 to 2011 by elastography (FibroScan, Echosens, Paris, France) and using previously validated thresholds for clinically significant fibrosis and cirrhosis; concurrent assessment of medical history, alcohol and illicit drug use, HCV RNA levels, hepatitis B virus surface antigen level, body mass index, and (for those with HIV) CD4⁺ lymphocyte count and HIV RNA levels.

Results:

Among 1176 participants with antibodies to HCV, the median age was 49 years and 34% were coinfected with HIV and HCV. Participants contributed 5634 valid liver fibrosis measurements. The prevalence of clinically significant fibrosis without cirrhosis (12.9% vs. 9.5%) and of cirrhosis (19.5% vs. 11.0%) was greater in persons coinfected with HIV and HCV than in those with only HCV (P < 0.001). Increasing age and HIV infection were independently associated with liver fibrosis, as were daily alcohol use, chronic hepatitis B virus infection, body mass index greater than 25 kg/m², and greater plasma HCV RNA levels. When these factors were kept constant, persons with HIV had liver fibrosis measurements equal to those of persons without HIV, who were, on average, 9.2 years older.

Limitation:

The process of liver fibrosis began before the study in most persons.

Conclusion:

In this cohort, persons who have HCV with HIV have liver fibrosis stages similar to those without HIV who are nearly a decade older.

Primary Funding Source:

National Institute on Drug Abuse.

Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan A Parallel, Randomized Trial

Raghu G, Behr J, Brown KK, et al. — Tue, 07 May 2013 00:00:00 GMT

Chinese translation

Background:

Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ET_A) receptor.

Objective:

To determine whether ambrisentan, an ET_A receptor–selective antagonist, reduces the rate of IPF progression.

Design:

Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300)

Setting:

Academic and private hospitals.

Participants:

Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans.

Intervention:

Ambrisentan, 10 mg/d, or placebo.

Measurements:

Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function.

Results:

The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point.

Limitation:

The study was terminated early.

Conclusion:

Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations.

Primary Funding Source:

Gilead Sciences.

Management Strategies for Asymptomatic Carotid Stenosis A Systematic Review and Meta-analysis

Raman G, Moorthy D, Hadar N, et al. — Tue, 07 May 2013 00:00:00 GMT

Background:

Adults with asymptomatic carotid artery stenosis are at increased risk for ipsilateral carotid territory ischemic stroke.

Purpose:

To examine comparative evidence on management strategies for asymptomatic carotid stenosis and the incidence of ipsilateral stroke with medical therapy alone.

Data Sources:

MEDLINE, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration documents, and review of references through 31 December 2012.

Study Selection:

Randomized, controlled trials (RCTs) and prospective or retrospective nonrandomized, comparative studies of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting (CAS) plus medical therapy for adults with asymptomatic carotid stenosis, as well as single-group prospective cohort studies of medical therapy, were reviewed.

Data Extraction:

Two investigators extracted information on study and population characteristics, results, and risk of bias.

Data Synthesis:

Forty-seven studies in 56 publications were eligible. The RCTs comparing CAS and CEA were clinically heterogeneous; 1 RCT reported more but not statistically significant ipsilateral stroke events (including any periprocedural stroke) in CAS compared with CEA, whereas another RCT, in a population at high surgical risk for CEA, did not. Three RCTs showed that CEA reduced the risk for ipsilateral stroke (including any periprocedural stroke) compared with medical therapy alone, but these results may no longer be applicable to contemporary clinical practice. No RCT compared CAS versus medical therapy alone. The summary incidence of ipsilateral stroke across 26 cohorts receiving medical therapy alone was 1.68% per year.

Limitations:

Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best-available medical therapy.

Conclusion:

Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy.

Primary Funding Source:

Agency for Healthcare Research and Quality.

Update in Infectious Diseases: Evidence Published in 2012

Lorber B. — Tue, 07 May 2013 00:00:00 GMT

This Update summarizes studies published in 2012 that the authors consider highly relevant to the practice of infectious disease. Topics include sinusitis, azithromycin toxicity, infective endocarditis, asymptomatic bacteriuria and recurrent urinary tract infection, HIV prevention, a newly discovered pathogen, Lyme disease, and fungal meningitis.

Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement

Moyer VA, . — Tue, 07 May 2013 00:00:00 GMT

Chinese translation

Description:

New U.S. Preventive Services Task Force (USPSTF) recommendation statement on vitamin D and calcium supplementation to prevent fractures in adults.

Methods:

The USPSTF commissioned 2 systematic evidence reviews and a meta-analysis on vitamin D supplementation with or without calcium to assess the effects of supplementation on bone health outcomes in community-dwelling adults, the association of vitamin D and calcium levels with bone health outcomes, and the adverse effects of supplementation.

Population:

These recommendations apply to noninstitutionalized or community-dwelling asymptomatic adults without a history of fractures. This recommendation does not apply to the treatment of persons with osteoporosis or vitamin D deficiency.

Recommendation:

The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men. (I statement)

The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with greater than 400 IU of vitamin D₃ and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (I statement)

The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D₃ and 1000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (D recommendation)

Implementing a Public Health Approach to Gun Violence Prevention: The Importance of Physician Engagement

Frattaroli S, Webster DW, Wintemute GJ. — Tue, 07 May 2013 00:00:00 GMT

Evidence-based, well-implemented, and enforced gun policies can reduce gun violence, and this vision can be realized with the help of physicians. As the details of policy proposals unfold and the public and policymakers weigh the options, this commentary presents 5 strategies for physician engagement in these discussions.

Risk Stratification of Lung Transplant Candidates: Implications for Organ Allocation

Kotloff RM. — Tue, 07 May 2013 00:00:00 GMT

In this issue, Tsuang and colleagues identify a new variable that independently predicts survival after lung transplantation: an increase in the lung allocation score 30 days before transplantation. The editorialist discusses the study and its findings, and concludes that the study should prompt a discussion about whether the current allocation system should be modified to limit access for candidates with unacceptably low predicted posttransplantation survival.

To Supplement or Not to Supplement: The U.S. Preventive Services Task Force Recommendations on Calcium and Vitamin D

Nestle M, Nesheim MC. — Tue, 07 May 2013 00:00:00 GMT

In this issue, the U.S. Preventive Services Task Force plunges headlong into ongoing debates about whether healthy adults—those who show no signs of vitamin D deficiency or osteoporosis—should be advised to take combined supplements of calcium and vitamin D to prevent bone fractures and, if so, at what level. The editorialists discuss the recommendations and their implications.

The Big Problem

Gosain P. — Tue, 07 May 2013 00:00:00 GMT

It is so difficult to bring up the topic of obesity with an obese patient. Yet, the inpatient, admitted with uncontrolled diabetes or hypertension presents a perfect teaching opportunity. But how do you tell someone you met 10 minutes ago that they need to lose weight?

Hepatitis C Virus Testing of Persons Born During 1945–1965

Smith BD, Holtzman D, Ward JW. — Tue, 07 May 2013 00:00:00 GMT

Hepatitis C Virus Testing of Persons Born During 1945–1965

Back E. — Tue, 07 May 2013 00:00:00 GMT

Hepatitis C Virus Testing of Persons Born During 1945–1965

Lynn RB. — Tue, 07 May 2013 00:00:00 GMT

Melanotan and the Posterior Reversible Encephalopathy Syndrome

Kaski D, Stafford N, Mehta A, et al. — Tue, 07 May 2013 00:00:00 GMT

Probiotics for the Prevention of Clostridium difficile –Associated Diarrhea

Johnston BC, Goldenberg JZ, Guyatt GH. — Tue, 07 May 2013 00:00:00 GMT

Probiotics for the Prevention of Clostridium difficile –Associated Diarrhea

Oscherwitz S. — Tue, 07 May 2013 00:00:00 GMT

Probiotics for the Prevention of Clostridium difficile –Associated Diarrhea

Keller D. — Tue, 07 May 2013 00:00:00 GMT

Pulmonary Hypertension

Mandel J, Poch D. — Tue, 07 May 2013 00:00:00 GMT

Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan

Tue, 07 May 2013 00:00:00 GMT

Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement

Tue, 07 May 2013 00:00:00 GMT