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In this trial, eliminating copayments for medications after hospitalization for MI did not reduce the primary outcome (first major vascular event or revascularization) but did improve medication adherence and secondary outcomes, without significantly increasing total spending. The use of medications based on solid clinical evidence has contributed substantially to reductions in cardiovascular morbidity and mortality. 1 , 2 For patients with acute myocardial infarction, prescribing of these highly effective therapies is now nearly universal at the time of hospital discharge in the United States, 3 , 4 but important gaps in care persist thereafter. Some patients never fill their first prescriptions, 5 and most have poor adherence to medication regimens over time. 6 Drug costs are central among the many factors that contribute to medication underuse. 7 , 8 A third of Americans report that they did not fill a prescription or reduced the . . .

The WHO Access, Watch, and Reserve (AWaRe) antibiotic classification framework aims to balance appropriate access to antibiotics and stewardship. We aimed to identify how patterns of antibiotic consumption in each of the AWaRe categories changed across countries over 15 years. Antibiotic consumption was classified into Access, Watch, and Reserve categories for 76 countries between 2000, and 2015, using quarterly national sample survey data obtained from IQVIA. We measured the proportion of antibiotic use in each category, and calculated the ratio of Access antibiotics to Watch antibiotics (access-to-watch index), for each country. Between 2000, and 2015, global per-capita consumption of Watch antibiotics increased by 90·9% (from 3·3 to 6·3 defined daily doses per 1000 inhabitants per day [DIDs]) compared with an increase of 26·2% (from 8·4 to 10·6 DIDs) in Access antibiotics. The increase in Watch antibiotic consumption was greater in low-income and middle-income countries (LMICs; 165·0%; from 2·0 to 5·3 DIDs) than in high-income countries (HICs; 27·9%; from 6·1 to 7·8 DIDs). The access-to-watch index decreased by 38·5% over the study period globally (from 2·6 to 1·6); 46·7% decrease in LMICs (from 3·0 to 1·6) and 16·7% decrease in HICs (from 1·8 to 1·5), and 37 (90%) of 41 LMICs had a decrease in their relative access-to-watch consumption. The proportion of countries in which Access antibiotics represented at least 60% of their total antibiotic consumption (the WHO national-level target) decreased from 50 (76%) of 66 countries in 2000, to 42 (55%) of 76 countries in 2015. Rapid increases in Watch antibiotic consumption, particularly in LMICs, reflect challenges in antibiotic stewardship. Without policy changes, the WHO national-level target of at least 60% of total antibiotic consumption being in the Access category by 2023, will be difficult to achieve. The AWaRe framework is an important measure of the effort to combat antimicrobial resistance and to ensure equal access to effective antibiotics between countries. US Centers for Disease Control and Prevention.

Background. Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). Methods. A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. Results. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4–12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7–$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. Conclusions. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.

Polypharmacy, potentially inappropriate medications and anticholinergic burden (as assessed by the anticholinergic risk scale) are commonly used as quality indicators of pharmacotherapy in older adults. However, their role in clinical practice is undefined. We sought to investigate longitudinal changes in these indicators and their effects on clinical outcomes. We used Taiwan’s Longitudinal Health Insurance Database to retrieve quarterly information about drug use for people aged 65 years and older over a 10-year period. We analyzed the association between indicators and all-cause admission to hospital, fracture-specific admission to hospital and death using generalized estimating equations. The study cohort comprised 59 042 older adults (65–74 yr: 39 358 [66.7%], 75–84 yr: 16 903 [28.6%], and ≥ 85 yr: 2781 [4.7%]). The mean changes in polypharmacy over the course of the study were greatest among patients aged 65–74 years (absolute difference +2.14, 95% confidence interval [CI] 2.10–2.19), then among those aged 75–84 yr (+1.79, 95% CI 1.70–1.88), and finally those aged 85 years and older (+0.71, 95% CI 0.36–1.05). The number of potentially inappropriate medications increased among patients aged 65–74 years (+0.16 [0.15–0.18]) and 75–84 years (+0.09 [0.06–0.08]), but decreased in those aged 85 years and older (−0.15 [−0.26 to −0.04]). Polypharmacy, potentially inappropriate medications and anticholinergic risk scale were each associated with an increased risk of admission to hospital, but not with death. In addition, both polypharmacy (5–9 drugs: odds ratio [OR] 1.18, 95% CI 1.12–1.24; ≥ 10 drugs: OR 1.54, 95% CI 1.42–1.66) and anticholinergic burden (score 1–2: 1.39, 95% CI 1.31–1.48; ≥ 3: 1.53, 95% CI 1.41–1.66) showed dose–response relations with fracture-specific admission to hospital. The total number of drugs taken (polypharmacy), number of potentially inappropriate medications and anticholinergic risk changed during follow-up and varied across age groups in this cohort of older adult patients. These indicators showed dose–response relations with admission to hospital, but not with death.

Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8–12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8–14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67–6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23–0·99; log-rank p value=0·0434). A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.

Many families in developing countries do not have access to medical doctors and instead receive health care from informal providers. Das et al. used “mystery” patients (trained actors) to test whether a 9-month training program improved the quality of care delivered by informal providers in West Bengal (see the Perspective by Powell-Jackson). The patients did not identify themselves to the providers and were not told which providers had participated in the training program. The results of this blinded assessment showed that medical doctors delivered better care than informal providers but that the training program closed much of the gap. Science , this issue p. 80 ; see also p. 34 Training helped informal providers deliver better care for angina, diarrhea, and asthma. [Also see Perspective by Powell-Jackson ] Health care providers without formal medical qualifications provide more than 70% of all primary care in rural India. Training these informal providers may be one way to improve the quality of care where few alternatives exist. We report on a randomized controlled trial assessing a program that provided 72 sessions of training over 9 months to 152 informal providers (out of 304). Using standardized patients (“mystery clients”), we assessed clinical practice for three different conditions to which both providers and trainers were blinded during the intervention, representative of the range of conditions that these providers normally diagnose and treat. Training increased correct case management by 7.9 percentage points (14.2%) but did not affect the use of unnecessary medicines and antibiotics. At a program cost of $175 per trainee, our results suggest that multitopic medical training offers an effective short-run strategy to improve health care.

Antibiotic drug consumption is a major driver of antibiotic resistance. Variations in antibiotic resistance across countries are attributable, in part, to different volumes and patterns for antibiotic consumption. We aimed to assess variations in consumption to assist monitoring of the rise of resistance and development of rational-use policies and to provide a baseline for future assessment. With use of sales data for retail and hospital pharmacies from the IMS Health MIDAS database, we reviewed trends for consumption of standard units of antibiotics between 2000 and 2010 for 71 countries. We used compound annual growth rates to assess temporal differences in consumption for each country and Fourier series and regression methods to assess seasonal differences in consumption in 63 of the countries. Between 2000 and 2010, consumption of antibiotic drugs increased by 35% (from 52 057 163 835 standard units to 70 440 786 553). Brazil, Russia, India, China, and South Africa accounted for 76% of this increase. In most countries, antibiotic consumption varied significantly with season. There was increased consumption of carbapenems (45%) and polymixins (13%), two last-resort classes of antibiotic drugs. The rise of antibiotic consumption and the increase in use of last-resort antibiotic drugs raises serious concerns for public health. Appropriate use of antibiotics in developing countries should be encouraged. However, to prevent a striking rise in resistance in low-income and middle-income countries with large populations and to preserve antibiotic efficacy worldwide, programmes that promote rational use through coordinated efforts by the international community should be a priority. US Department of Homeland Security, Bill & Melinda Gates Foundation, US National Institutes of Health, Princeton Grand Challenges Program.

Medical cannabis has been touted as a solution to the US opioid overdose crisis since Bachhuber et al. [M. A. Bachhuber, B. Saloner, C. O. Cunningham, C. L. Barry, JAMA Intern. Med. 174, 1668–1673] found that from 1999 to 2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. That research received substantial attention in the scientific literature and popular press and served as a talking point for the cannabis industry and its advocates, despite caveats from the authors and others to exercise caution when using ecological correlations to draw causal, individual-level conclusions. In this study, we used the same methods to extend Bachhuber et al.’s analysis through 2017. Not only did findings from the original analysis not hold over the longer period, but the association between state medical cannabis laws and opioid overdose mortality reversed direction from −21% to +23% and remained positive after accounting for recreational cannabis laws. We also uncovered no evidence that either broader (recreational) or more restrictive (low-tetrahydrocannabinol) cannabis laws were associated with changes in opioid overdose mortality. We find it unlikely that medical cannabis—used by about 2.5% of the US population—has exerted large conflicting effects on opioid overdose mortality. A more plausible interpretation is that this association is spurious. Moreover, if such relationships do exist, they cannot be rigorously discerned with aggregate data. Research into therapeutic potential of cannabis should continue, but the claim that enacting medical cannabis laws will reduce opioid overdose death should be met with skepticism.

Estimating the impact of child health investments on adult living standards entails multiple methodological challenges, including the lack of experimental variation in health status, an inability to track individuals over time, and accurately measuring living standards and productivity in low-income settings. This study exploits a randomized school health intervention that provided deworming treatment to Kenyan children, and uses longitudinal data to estimate impacts on economic outcomes up to 20 y later. The effective respondent tracking rate was 84%. Individuals who received two to three additional years of childhood deworming experienced a 14% gain in consumption expenditures and 13% increase in hourly earnings. There are also shifts in sectors of residence and employment: treatment group individuals are 9% more likely to live in urban areas, and experience a 9% increase in nonagricultural work hours. Most effects are concentrated among males and older individuals. The observed consumption and earnings benefits, together with deworming’s low cost when distributed at scale, imply that a conservative estimate of its annualized social internal rate of return is 37%, a high return by any standard.

The UN should promote targets, funding, and governance After decades of neglect, antimicrobial resistance (AMR) has captured the attention and concern of the public health community and global leaders. In September 2016, a high-level meeting of the United Nations General Assembly (UNGA) will discuss how countries can cooperate to preserve global access to effective antimicrobials. This will be only the fourth health issue (and the first One Health issue, integrating human, animal, and environmental health) to bring together heads of state at the UNGA for a rare opportunity to set a global agenda to combat the crisis. We believe that (i) setting targets for reducing drug-resistant infections, (ii) adequate financing for global action, and (iii) defining the global health architecture to address AMR should be elements of a UN plan.