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Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 168, No 5

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% (risk difference, −0.033 [95% CI, −0.062 to −0.004]) compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I 2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

In-State and Interstate Associations Between Gun Shows and Firearm Deaths and Injuries: A Quasi-experimental Study: Annals of Internal Medicine: Vol 167, No 12

Background: Gun shows are an important source of firearms, but no adequately powered studies have examined whether they are associated with increases in firearm injuries. Objective: To determine whether gun shows are associated with short-term increases in local firearm injuries and whether this association differs by the state in which the gun show is held. Design: Quasi-experimental. Setting: California. Participants: Persons in California within driving distance of gun shows. Measurements: Gun shows in California and Nevada between 2005 and 2013 (n = 915 shows) and rates of firearm-related deaths, emergency department visits, and inpatient hospitalizations in California. Results: Compared with the 2 weeks before, postshow firearm injury rates remained stable in regions near California gun shows but increased from 0.67 injuries (95% CI, 0.55 to 0.80 injuries) to 1.14 injuries (CI, 0.97 to 1.30 injuries) per 100 000 persons in regions near Nevada shows. After adjustment for seasonality and clustering, California shows were not associated with increases in local firearm injuries (rate ratio [RR], 0.99 [CI, 0.97 to 1.02]) but Nevada shows were associated with increased injuries in California (RR, 1.69 [CI, 1.16 to 2.45]). The pre–post difference was significantly higher for Nevada shows than California shows (ratio of RRs, 1.70 [CI, 1.17 to 2.47]). The Nevada association was driven by significant increases in firearm injuries from interpersonal violence (RR, 2.23 [CI, 1.01 to 4.89]) but corresponded to a small increase in absolute numbers. Nonfirearm injuries served as a negative control and were not associated with California or Nevada gun shows. Results were robust to sensitivity analyses. Limitation: Firearm injuries were examined only in California, and gun show occurrence was not randomized. Conclusion: Gun shows in Nevada, but not California, were associated with local, short-term increases in firearm injuries in California. Differing associations for California versus Nevada gun shows may be due to California's stricter firearm regulations. Primary Funding Source: National Institutes of Health; University of California, Berkeley; and Heising-Simons Foundation.

Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review: Annals of Internal Medicine: Vol 168, No 1

Background: Structured activities to stimulate brain function—that is, cognitive training exercises—are promoted to slow or prevent cognitive decline, including dementia, but their effectiveness is highly debated. Purpose: To summarize evidence on the effects of cognitive training on cognitive performance and incident dementia outcomes for adults with normal cognition or mild cognitive impairment (MCI). Data Sources: Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO through July 2017, supplemented by hand-searches. Study Selection: Trials (published in English) lasting at least 6 months that compared cognitive training with usual care, waitlist, information, or attention controls in adults without dementia. Data Extraction: Single-reviewer extraction of study characteristics confirmed by a second reviewer; dual-reviewer risk-of-bias assessment; consensus determination of strength of evidence. Only studies with low or medium risk of bias were analyzed. Data Synthesis: Of 11 trials with low or medium risk of bias, 6 enrolled healthy adults with normal cognition and 5 enrolled adults with MCI. Trainings for healthy older adults were mostly computer based; those for adults with MCI were mostly held in group sessions. The MCI trials used attention controls more often than trials with healthy populations. For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient. Adverse events were not reported. Limitation: Heterogeneous interventions and outcome measures; outcomes that mostly assessed test performance rather than global function or dementia diagnosis; potential publication bias. Conclusion: In older adults with normal cognition, training improves cognitive performance in the domain trained. Evidence regarding prevention or delay of cognitive decline or dementia is insufficient. Primary Funding Source: Agency for Healthcare Research and Quality.

Risk-Targeted Lung Cancer Screening: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 168, No 3

Background: Targeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency. Objective: To quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria. Design: Cost-effectiveness analysis using a multistate prediction model. Data Sources: NLST. Target Population: Current and former smokers eligible for lung cancer screening. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Risk-targeted versus NLST-based screening. Outcome Measures: Incremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk. Results of Base-Case Analysis: Participants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups. Results of Sensitivity Analysis: Alternative assumptions did not substantially alter our findings. Limitation: Our model did not account for all correlated differences between lung cancer mortality risk and quality of life. Conclusions: Although risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness. Primary Funding Source: National Institutes of Health (U01NS086294).

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review: Annals of Internal Medicine: Vol 167, No 3

Background: Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage. Purpose: To evaluate the risks and benefits of antithrombotic therapy in adults with ET. Data Sources: Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017. Study Selection: Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence. Data Synthesis: No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31 711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes. Limitation: No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes. Conclusion: Available evidence about the risk–benefit ratio of antiplatelet therapy in adults with ET is highly uncertain. Primary Funding Source: Regional Medical Associates. (PROSPERO: CRD42015027051)

Benefits and Harms of Osteoporosis Medications in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 166, No 9

Background: Complications of chronic kidney disease (CKD) include weak bones and increased fracture risk. Purpose: To review the benefits and harms of osteoporosis medications (bisphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active control in terms of bone mineral density (BMD), fractures, and safety in patients with CKD. Data Sources: PubMed and the Cochrane Central Register of Controlled Trials from December 2006 through December 2016. Study Selection: Paired reviewers independently screened abstracts and full-text articles for English-language, randomized, controlled trials that had at least 6 months of follow-up; evaluated osteoporosis medications among patients with CKD; and reported on BMD, fractures, or safety (mortality and adverse events). Data Extraction: Two reviewers serially abstracted data and independently assessed risk of bias and graded the strength of evidence (SOE). Data Synthesis: There were 13 trials (n = 9850) that included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials). Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients (moderate SOE), but their effects on fractures and safety in transplant recipients and others with CKD are unclear. Raloxifene may prevent vertebral fractures but may not improve BMD (low SOE). Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE), and these medications may increase risk for some safety outcomes. Limitation: Unclear rigor of evidence, possible reporting biases, and scant evidence among patients with stage 3 to 5 CKD. Conclusion: Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established. Primary Funding Source: Kidney Disease: Improving Global Outcomes.

Discontinuing Inappropriate Medication Use in Nursing Home Residents: A Cluster Randomized Controlled Trial: Annals of Internal Medicine: Vol 167, No 9

Background: Inappropriate prescribing is a well-known clinical problem in nursing home residents, but few interventions have focused on reducing inappropriate medication use. Objective: To examine successful discontinuation of inappropriate medication use and to improve prescribing in nursing home residents. Design: Pragmatic cluster randomized controlled trial, with clustering by elder care physicians and their wards. (ClinicalTrials.gov: NCT01876095) Setting: 59 Dutch nursing home wards for long-term care. Patients: Residents with a life expectancy greater than 4 weeks who consented to treatment with medication. Intervention: Multidisciplinary Multistep Medication Review (3MR) consisting of an assessment of the patient perspective, medical history, critical appraisal of medications, a meeting between the treating elder care physician and the pharmacist, and implementation of medication changes. Measurements: Successful discontinuation of use of at least 1 inappropriate drug (that is, without relapse or severe withdrawal symptoms) and clinical outcomes (neuropsychiatric symptoms, cognitive function, and quality of life) after 4 months of follow-up. Results: Nineteen elder care physicians (33 wards) performed the 3MR, and 16 elder care physicians (26 wards) followed standard procedures. A total of 426 nursing home residents (233 in the intervention group and 193 in the control group) were followed for an average of 144 days (SD, 21). In an analysis of all participants, use of at least 1 inappropriate medication was successfully discontinued for 91 (39.1%) residents in the intervention group versus 57 (29.5%) in the control group (adjusted relative risk, 1.37 [95% CI, 1.02 to 1.75]). Clinical outcomes did not deteriorate between baseline and follow-up. Limitations: The 3MR was done only once. Some withdrawal symptoms or relapses may have been missed. Conclusion: The 3MR is effective in discontinuing inappropriate medication use in frail nursing home residents without a decline in their well-being. Primary Funding Source: Netherlands Organisation for Health Research and Development.

Safety-Net Hospitals, Neighborhood Disadvantage, and Readmissions Under Maryland's All-Payer Program: An Observational Study: Annals of Internal Medicine: Vol 171, No 2

Background: Safety-net hospitals have higher-than-expected readmission rates. The relative roles of the mean disadvantage of neighborhoods the hospitals serve and the disadvantage of individual patients in predicting a patient's readmission are unclear. Objective: To examine the independent contributions of the patient's neighborhood and the hospital's service area to risk for 30-day readmission. Design: Retrospective observational study. Setting: Maryland. Participants: All Maryland residents discharged from a Maryland hospital in 2015. Measurements: Predictors included the disadvantage of neighborhoods for each Maryland resident (area disadvantage index) and the mean disadvantage of each hospital's discharged patients (safety-net index). The primary outcome was unplanned 30-day hospital readmission. Generalized estimating equations and marginal modeling were used to estimate readmission rates. Results were adjusted for clinical readmission risk. Results: 13.4% of discharged patients were readmitted within 30 days. Patients living in neighborhoods at the 90th percentile of disadvantage had a readmission rate of 14.1% (95% CI, 13.6% to 14.5%) compared with 12.5% (CI, 11.8% to 13.2%) for similar patients living in neighborhoods at the 10th percentile. Patients discharged from hospitals at the 90th percentile of safety-net status had a readmission rate of 14.8% (CI, 13.4% to 16.1%) compared with 11.6% (CI, 10.5% to 12.7%) for similar patients discharged from hospitals at the 10th percentile of safety-net status. The association of readmission risk with the hospital's safety-net index was approximately twice the observed association with the patient's neighborhood disadvantage status. Limitations: Generalizability outside Maryland is unknown. Confounding may be present. Conclusion: In Maryland, residing in a disadvantaged neighborhood and being discharged from a hospital serving a large proportion of disadvantaged neighborhoods are independently associated with increased risk for readmission. Primary Funding Source: National Institute on Minority Health and Health Disparities and Maryland Health Services Cost Review Commission.

The Scientific Basis of Guideline Recommendations on Sugar Intake: A Systematic Review: Annals of Internal Medicine: Vol 166, No 4

Background: The relationship between sugar and health is affected by energy balance, macronutrient substitutions, and diet and lifestyle patterns. Several authoritative organizations have issued public health guidelines addressing dietary sugars. Purpose: To systematically review guidelines on sugar intake and assess consistency of recommendations, methodological quality of guidelines, and the quality of evidence supporting each recommendation. Data Sources: MEDLINE, EMBASE, and Web of Science (1995 to September 2016); guideline registries; and gray literature (bibliographies, Google, and experts). Study Selection: Guidelines addressing sugar intake that reported their methods of development and were published in English between 1995 and 2016. Data Extraction: Three reviewers independently assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II), instrument. To assess evidence quality, articles supporting recommendations were independently reviewed and their quality was determined by using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods. Data Synthesis: The search identified 9 guidelines that offered 12 recommendations. Each of the reviewed guidelines indicated a suggested decrease in the consumption of foods containing nonintrinsic sugars. The guidelines scored poorly on AGREE II criteria, specifically in rigor of development, applicability, and editorial independence. Seven recommendations provided nonquantitative guidance; 5 recommended less than 25% to less than 5% of total calories from nonintrinsic sugars. The recommendations were based on various health concerns, including nutrient displacement, dental caries, and weight gain. Quality of evidence supporting recommendations was low to very low. Limitation: The authors conducted the study independent of the funding source, which is primarily supported by the food and agriculture industry. Conclusion: Guidelines on dietary sugar do not meet criteria for trustworthy recommendations and are based on low-quality evidence. Public health officials (when promulgating these recommendations) and their public audience (when considering dietary behavior) should be aware of these limitations. Primary Funding Source: Technical Committee on Dietary Carbohydrates of the North American branch of the International Life Sciences Institute. (PROSPERO: CRD42015029182)

Public Opinion Regarding Whether Speaking With Patients About Firearms Is Appropriate: Results of a National Survey: Annals of Internal Medicine: Vol 165, No 8

Background: Health care providers have been encouraged to discuss firearms with patients; whether patients view these discussions as appropriate is unclear. Objective: To estimate, in a national sample, the perceived appropriateness of provider discussions about firearms. Design: Probability-based online survey conducted in April 2015. Analyses used survey weights to generate nationally representative estimates. Setting: U.S. adults. Participants: 3914 English-speaking adults (55% participation rate). Measurements: Participants were asked, “In general, would you think it is never, sometimes, usually, or always appropriate for physicians and other health professionals to talk to their patients about firearms?” Results: A majority (66% [95% CI, 63% to 69%]) of participants said that it is at least sometimes appropriate for providers to talk to patients about firearms. Specifically, 23% (CI, 20% to 25%) said that provider discussions about firearms were always appropriate, 14% (CI, 11% to 16%) said that they were usually appropriate, and 30% (CI, 27% to 33%) thought they were sometimes appropriate; 34% (CI, 31% to 37%) felt that such discussions were never appropriate. Views varied by firearm ownership: 54% (CI, 52% to 57%) of gun owners said that provider discussions are at least sometimes appropriate, compared with 67% (CI, 62% to 71%) of nonowners living with an owner and 70% (CI, 66% to 74%) of nonowners not living with an owner. Firearm owners who were more likely to think that firearm discussions are at least sometimes appropriate included those with children at home (62% [CI, 57% to 67%]), those who thought that having a gun at home increases suicide risk (75% [CI, 67% to 83%), and those who thought that provider discussions of seat belts are at least sometimes appropriate (73% [CI, 70% to 75%]). Limitations: The provider discussion question did not specify clinical context. Conclusion: Two thirds of non–firearm owners and over one half of firearm owners in the United States believe that health care provider discussions about firearms are at least sometimes appropriate. The observed heterogeneity underscores the need to better understand assumptions that may underlie these views, particularly among firearm owners. Primary Funding Source: Fund for a Safer Future and Joyce Foundation.

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