Showing papers in "JAMA Internal Medicine in 2015"

Leisure Time Physical Activity and Mortality: A Detailed Pooled Analysis of the Dose-Response Relationship

Abstract: Importance The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. Objective To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity. Design, Setting, and Participants We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661 137 men and women (median age, 62 years; range, 21-98 years) and 116 686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. Exposures Leisure time moderate- to vigorous-intensity physical activity. Main Outcomes and Measures The upper limit of mortality benefit from high levels of leisure time physical activity. Results Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose-response relationship was observed for mortality due to cardiovascular disease and to cancer. Conclusions and Relevance Meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate- or vigorous-intensity activities was associated with nearly the maximum longevity benefit. We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum. In regard to mortality, health care professionals should encourage inactive adults to perform leisure time physical activity and do not need to discourage adults who already participate in high-activity levels.

Reducing Inappropriate Polypharmacy: The Process of Deprescribing

Abstract: Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.

Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study.

Abstract: Importance Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. Objective To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. Design, Setting, and Participants Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses. Exposures Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time. Main Outcomes and Measures Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. Results The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P Conclusions and Relevance Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial

Abstract: Importance Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. Objective To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. Design, Setting, and Participants Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevencion con Dieta Mediterranea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. Interventions Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). Main Outcomes and Measures Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. Results Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049) and Color Trail Test part 2 ( P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (−0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (−0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and −0.17 (−0.32 to −0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (−0.25 to 0.31), and −0.33 (−0.57 to −0.09). Changes from baseline of the global cognition composite were 0.05 (−0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, −0.05 (−0.27 to 0.18) for the Mediterranean diet plus nuts, and −0.38 (−0.57 to −0.18) for the control diet. All cognitive composites significantly ( P Conclusions and Relevance In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. Trial Registration isrctn.org Identifier:ISRCTN35739639

Duration of menopausal vasomotor symptoms over the menopause transition.

Abstract: Importance The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. Objectives To determine total duration of frequent VMS (≥6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. Design, Setting, and Participants The Study of Women’s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. Main Outcomes and Measures Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. Results The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. Conclusions and Relevance Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Patients' Expectations of the Benefits and Harms of Treatments, Screening, and Tests A Systematic Review

Abstract: Importance Unrealistic patient expectations of the benefits and harms of interventions can influence decision making and may be contributing to increasing intervention uptake and health care costs. Objective To systematically review all studies that have quantitatively assessed patients’ expectations of the benefits and/or harms of any treatment, test, or screening test. Evidence Review A comprehensive search strategy was used in 4 databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO) up to June 2013, with no language or study type restriction. We also ran cited reference searches of included studies and contacted experts and study authors. Two researchers independently evaluated methodological quality and extracted participants’ estimates of benefit and harms and authors’ contemporaneous estimates. Findings Of the 15 343 records screened, 36 articles (from 35 studies) involving a total of 27 323 patients were eligible. Fourteen studies focused on a screen, 15 on treatment, 3 a test, and 3 on treatment and screening. More studies assessed only benefit expectations (22 [63%]) than benefit and harm expectations (10 [29%]) or only harm (3 [8%]). Fifty-four outcomes (across 32 studies) assessed benefit expectations: of the 34 outcomes with overestimation data available, the majority of participants overestimated benefit for 22 (65%) of them. For 17 benefit expectation outcomes, we could not calculate the proportion of participants who overestimated or underestimated, although for 15 (88%) of these, study authors concluded that participants overestimated benefits. Expectations of harm were assessed by 27 outcomes (across 13 studies): underestimation data were available for 15 outcomes and the majority of participants underestimated harm for 10 (67%) of these. A correct estimation by at least 50% of participants only occurred for 2 outcomes about benefit expectations and 2 outcomes about harm expectations. Conclusions and Relevance The majority of participants overestimated intervention benefit and underestimated harm. Clinicians should discuss accurate and balanced information about intervention benefits and harms with patients, providing the opportunity to develop realistic expectations and make informed decisions.

A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010

Abstract: Importance Heart failure (HF) is commonly referred to as an epidemic, posing major clinical and public health challenges. Yet, contemporary data on its magnitude and implications are scarce. Objective To evaluate recent trends in HF incidence and outcomes overall and by preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Design, Setting, and Participants Incidence rates of HF in Olmsted County, Minnesota (population, approximately 144 248), between January 1, 2000, and December 31, 2010, were assessed. Main Outcomes and Measures Patients identified with incident HF (n = 2762) (mean age, 76.4 years; 43.1% male) were followed up for all-cause and cause-specific hospitalizations (through December 2012) and death (through March 2014). Results The age– and sex–adjusted incidence of HF declined substantially from 315.8 per100 000 in 2000 to 219.3 per 100 000 in 2010 (annual percentage change, −4.6), equating to a rate reduction of 37.5% (95% CI, −29.6% to −44.4%) over the last decade. The incidence declined for both HF types but was greater (interactionP = .08) for HFrEF (−45.1%; 95% CI, −33.0% to −55.0%) than for HFpEF (−27.9%; 95% CI, −12.9% to −40.3%). Mortality was high (24.4% for age 60 years and 54.4% for age 80 years at 5 years of follow-up), frequently ascribed to noncardiovascular causes (54.3%), and did not decline over time. The risk of cardiovascular death was lower for HFpEF than for HFrEF (multivariable-adjusted hazard ratio, 0.79; 95% CI, 0.67-0.93), whereas the risk of noncardiovascular death was similar (1.07; 95% CI, 0.89-1.29). Hospitalizations were common (mean, 1.34; 95% CI, 1.25-1.44 per person-year), particularly among men, and did not differ between HFpEF and HFrEF. Most hospitalizations (63.0%) were due to noncardiovascular causes. Hospitalization rates for cardiovascular causes did not change over time, whereas those for noncardiovascular causes increased. Conclusions and Relevance Over the last decade, the incidence of HF declined substantially, particularly for HFrEF, contrasting with no apparent change in mortality. Noncardiovascular conditions have an increasing role in hospitalizations and remain the most frequent cause of death. These results underscore the need to augment disease-centric management approaches with holistic strategies to reduce the population burden of HF.

Cognitive Tests to Detect Dementia A Systematic Review and Meta-analysis

Abstract: Importance Dementia is a global public health problem. The Mini-Mental State Examination (MMSE) is a proprietary instrument for detecting dementia, but many other tests are also available. Objective To evaluate the diagnostic performance of all cognitive tests for the detection of dementia. Data Sources Literature searches were performed on the list of dementia screening tests in MEDLINE, EMBASE, and PsychoINFO from the earliest available dates stated in the individual databases until September 1, 2014. Because Google Scholar searches literature with a combined ranking algorithm on citation counts and keywords in each article, our literature search was extended to Google Scholar with individual test names and dementia screening as a supplementary search. Study Selection Studies were eligible if participants were interviewed face to face with respective screening tests, and findings were compared with criterion standard diagnostic criteria for dementia. Bivariate random-effects models were used, and the area under the summary receiver-operating characteristic curve was used to present the overall performance. Main Outcomes and Measures Sensitivity, specificity, and positive and negative likelihood ratios were the main outcomes. Results Eleven screening tests were identified among 149 studies with more than 49 000 participants. Most studies used the MMSE (n = 102) and included 10 263 patients with dementia. The combined sensitivity and specificity for detection of dementia were 0.81 (95% CI, 0.78-0.84) and 0.89 (95% CI, 0.87-0.91), respectively. Among the other 10 tests, the Mini-Cog test and Addenbrooke’s Cognitive Examination–Revised (ACE-R) had the best diagnostic performances, which were comparable to that of the MMSE (Mini-Cog, 0.91 sensitivity and 0.86 specificity; ACE-R, 0.92 sensitivity and 0.89 specificity). Subgroup analysis revealed that only the Montreal Cognitive Assessment had comparable performance to the MMSE on detection of mild cognitive impairment with 0.89 sensitivity and 0.75 specificity. Conclusions and Relevance Besides the MMSE, there are many other tests with comparable diagnostic performance for detecting dementia. The Mini-Cog test and the ACE-R are the best alternative screening tests for dementia, and the Montreal Cognitive Assessment is the best alternative for mild cognitive impairment.

Effectiveness of Multicomponent Nonpharmacological Delirium Interventions: A Meta-analysis

Abstract: MAIN OUTCOMES AND MEASURES We identified 14 interventional studies. The results for outcomes of delirium incidence, falls, length of stay, and institutionalization were pooled for the meta-analysis, but heterogeneity limited our meta-analysis of the results for change in functional or cognitive status. Overall, 11 studies demonstrated significant reductions in delirium incidence (odds ratio [OR], 0.47; 95% CI, 0.38-0.58). Four randomized or matched trials reduced delirium incidence by 44% (OR, 0.56; 95% CI, 0.42-0.76). The rate of falls decreased significantly among intervention patients in 4 studies (OR, 0.38; 95% CI, 0.25-0.60); in 2 randomized or matched trials, the rate of falls was reduced by 64% (OR, 0.36; 95% CI, 0.22-0.61). Length of stay and institutionalization also trended toward decreases in the intervention groups, with a mean difference of −0.16 (95% CI, −0.97 to 0.64) day shorter and the odds of institutionalization 5% lower (OR, 0.95; 95% CI, 0.71-1.26). Among higher-quality randomized or matched trials, length of stay trended −0.33 (95% CI, −1.38 to 0.72) day shorter, and the odds of institutionalization trended 6% lower (OR, 0.94; 95% CI, 0.69-1.30).

Human Immunodeficiency Virus Transmission at Each Step of the Care Continuum in the United States

Abstract: Importance Human immunodeficiency virus (HIV) transmission risk is primarily dependent on behavior (sexual and injection drug use) and HIV viral load. National goals emphasize maximizing coverage along the HIV care continuum, but the effect on HIV prevention is unknown. Objectives To estimate the rate and number of HIV transmissions attributable to persons at each of the following 5 HIV care continuum steps: HIV infected but undiagnosed, HIV diagnosed but not retained in medical care, retained in care but not prescribed antiretroviral therapy, prescribed antiretroviral therapy but not virally suppressed, and virally suppressed. Design, Setting, and Participants A multistep, static, deterministic model that combined population denominator data from the National HIV Surveillance System with detailed clinical and behavioral data from the National HIV Behavioral Surveillance System and the Medical Monitoring Project to estimate the rate and number of transmissions along the care continuum. This analysis was conducted January 2013 to June 2014. The findings reflect the HIV-infected population in the United States in 2009. Main Outcomes and Measures Estimated rate and number of HIV transmissions. Results Of the estimated 1 148 200 persons living with HIV in 2009, there were 207 600 (18.1%) who were undiagnosed, 519 414 (45.2%) were aware of their infection but not retained in care, 47 453 (4.1%) were retained in care but not prescribed ART, 82 809 (7.2%) were prescribed ART but not virally suppressed, and 290 924 (25.3%) were virally suppressed. Persons who are HIV infected but undiagnosed (18.1% of the total HIV-infected population) and persons who are HIV diagnosed but not retained in medical care (45.2% of the population) were responsible for 91.5% (30.2% and 61.3%, respectively) of the estimated 45 000 HIV transmissions in 2009. Compared with persons who are HIV infected but undiagnosed (6.6 transmissions per 100 person-years), persons who were HIV diagnosed and not retained in medical care were 19.0% (5.3 transmissions per 100 person-years) less likely to transmit HIV, and persons who were virally suppressed were 94.0% (0.4 transmissions per 100 person-years) less likely to transmit HIV. Men, those who acquired HIV via male-to-male sexual contact, and persons 35 to 44 years old were responsible for the most HIV transmissions by sex, HIV acquisition risk category, and age group, respectively. Conclusions and Relevance Sequential steps along the HIV care continuum were associated with reduced HIV transmission rates. Improvements in HIV diagnosis and retention in care, as well as reductions in sexual and drug use risk behavior, primarily for persons undiagnosed and not receiving antiretroviral therapy, would have a substantial effect on HIV transmission in the United States.

Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era

Abstract: Importance Clostridium difficile is a major cause of health care–associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. Objective To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox−/PCR+) for CDI. Design, Setting, and Participants Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. Main Outcomes and Measures Patients undergoing C difficile testing were grouped by US Food and Drug Administration–approved toxin and PCR tests as Tox+/PCR+, Tox−/PCR+, or Tox−/PCR−. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. Results Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox−/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients ( P P = .003) and was similar to that in Tox−/PCR− patients (2 days; interquartile range, 1-3 days), despite minimal empirical treatment of Tox−/PCR+ patients. No CDI-related complications occurred in Tox−/PCR+ patients vs 10 complications in Tox+/PCR+ patients (0% vs 7.6%, P P = .001). Conclusions and Relevance Among hospitalized adults with suspected CDI, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.

Nationwide Population Science: Lessons From the Taiwan National Health Insurance Research Database.

Abstract: Large population-based studies can inform us on the prevalence, incidence, natural history, treatment, correlates, and associations of disease, as well as the pattern of health care utilization. A special type of large population study encompasses the population of an entire nation. Advantages include enormous sample size and lack of selection and participation bias. These advantages are enhanced further when the databases are rich in clinical, personal, and risk factor information and when different pieces of information are linked to permit joint analysis. Once the process for data accessing is established, vast amounts of information can be obtained at minimal cost, especially when additional collection and update of information is carried out routinely for purposes inherent in medical care and/or insurance coverage and reimbursement. The Taiwan National Health Insurance (NHI) Research Database is one of the largest nationwide population databases in the world, covering approximately 23 million residents in Taiwan.1 The NHI program was established in 1995 to deliver universal coverage provided by a government-run, single-payer compulsory insurance plan to centralize the disbursement of health care funding. The program covered 99.0% of the island population by 2004 and 99.5% of the population by 2010. Universal coverage reduces barriers to health care access for all citizens, regardless of socioeconomic background and/or residential location. In 1997, the National Health Research Institute was authorized to build the NHI Research Database to facilitate research on health care utilization, health economics, and biomedical and behavioral research, as well as to provide information guiding national health policy. Currently, the NHI Research Database includes more than 26 data files containing information on personal characteristics (sex, date of birth, place of residence, details of insurance, employment); family relationships; details of clinical information, including date, expenditures, and diagnosis related to both inpatient and outpatient procedures; prescription details; examinations; and operations. Data are updated biannually. Since 2003, the use of electronic medical records has been mandated and standardized across 321 hospitals, providing the foundation for digital health and data exchange. By law, all Taiwan residents have a unique personal identification number that is used also for tax returns, bank accounts, and all transactions. Thus, NHI Research Database data are linkable to multiple national databases maintained by other departments, including registries of births, deaths, households, immunizations, cancer, reportable infectious diseases, and environmental exposures. This identification is also linked to the national immunization information system and mass population-based screening for cancers of the oral cavity, colon, cervix, and breast, as well as myopia and urine screenings and regular examinations in school children, newborn screening, the rare disease and suicide registries, the Taiwan Pathogenic Microorganism Genome Database, and the blood donor registry. A health cloud is currently being built that will eventually further facilitate data linkage among various registries, databases, and departments. In addition, Academia Sinica is establishing a biobank of more than 200 000 residents; the data in the biobank will be linked with NHI Research Database data. With such extensive linkage, privacy is protected through laws that dictate encryption of the unique personal identification number (23 digits) and strict procedures for data access and human subject review. To date, no breach or leak is known to have occurred. Since 1995, several large data centers have been established in academic universities in Taiwan to mine the NHI Research Database. More than 2016 articles had been published by mid2014 (http://nhipapers.idv.tw/healthdata/advance_ch.php), including studies of drug adverse effects and risk of disease (n = 163), drug safety and efficacy (n = 131), drug prescription and utilization patterns (n = 169), clinical presentation (n = 117), prognosis and health outcomes research (n = 682), costeffectiveness and health economics (n = 90), health services research (n = 81), health care utilization (n = 220), methodology (n = 46), ecologic correlation (n = 46), and risk factor analysis (n = 56), as well as descriptive studies (n = 215) and studies of other topics.2-4 Productivity is rapidly accelerating, with more than 430 studies published in 2013. The large and longitudinal nature of the data (nearly 20 years of follow-up data of the entire population) permits a wide range of study design, including cross-sectional, case-control, and retrospective and prospective cohort analyses, as well as family studies (family members can be linked through parents’ identification numbers on birth certificates). The large sample size provides opportunities for the study of rare conditions. For example, in this issue of JAMA Internal Medicine, Kuo et al5 identified 18 283 patients with systemic lupus erythematosus (SLE) and their family members, including parents, siblings, and twins, to estimate SLE heritability, risk for specific family members, and relationships with other autoimmune diseases. Typically, SLE studies include up to a few hundred cases, and even large consortia, such as those conducting genome-wide association studies, usually include no more than several hundred to several thousand cases. Some other countries (Japan, Korea, and Scandinavian countries [eg, Sweden and Denmark]) also have national databases with associated record linkage capacity. However, relative to Taiwan, the population size for Scandinavian Related article page 1518 Aggregation of Systemic Lupus and Other Autoimmune Diseases Original Investigation Research

Diagnostic Accuracy of Digital Screening Mammography With and Without Computer-Aided Detection

Abstract: Importance After the US Food and Drug Administration (FDA) approved computer-aided detection (CAD) for mammography in 1998, and the Centers for Medicare and Medicaid Services (CMS) provided increased payment in 2002, CAD technology disseminated rapidly. Despite sparse evidence that CAD improves accuracy of mammographic interpretations and costs over $400 million a year, CAD is currently used for most screening mammograms in the United States. Objective To measure performance of digital screening mammography with and without CAD in US community practice. Design, Setting, and Participants We compared the accuracy of digital screening mammography interpreted with (n = 495 818) vs without (n = 129 807) CAD from 2003 through 2009 in 323 973 women. Mammograms were interpreted by 271 radiologists from 66 facilities in the Breast Cancer Surveillance Consortium. Linkage with tumor registries identified 3159 breast cancers in 323 973 women within 1 year of the screening. Main Outcomes and Measures Mammography performance (sensitivity, specificity, and screen-detected and interval cancers per 1000 women) was modeled using logistic regression with radiologist-specific random effects to account for correlation among examinations interpreted by the same radiologist, adjusting for patient age, race/ethnicity, time since prior mammogram, examination year, and registry. Conditional logistic regression was used to compare performance among 107 radiologists who interpreted mammograms both with and without CAD. Results Screening performance was not improved with CAD on any metric assessed. Mammography sensitivity was 85.3% (95% CI, 83.6%-86.9%) with and 87.3% (95% CI, 84.5%-89.7%) without CAD. Specificity was 91.6% (95% CI, 91.0%-92.2%) with and 91.4% (95% CI, 90.6%-92.0%) without CAD. There was no difference in cancer detection rate (4.1 in 1000 women screened with and without CAD). Computer-aided detection did not improve intraradiologist performance. Sensitivity was significantly decreased for mammograms interpreted with vs without CAD in the subset of radiologists who interpreted both with and without CAD (odds ratio, 0.53; 95% CI, 0.29-0.97). Conclusions and Relevance Computer-aided detection does not improve diagnostic accuracy of mammography. These results suggest that insurers pay more for CAD with no established benefit to women.

Cognitive Behavioral Therapy for Insomnia Comorbid With Psychiatric and Medical Conditions: A Meta-analysis

Abstract: Importance Cognitive behavioral therapy for insomnia (CBT-I) is the most prominent nonpharmacologic treatment for insomnia disorders Although meta-analyses have examined primary insomnia, less is known about the comparative efficacy of CBT-I on comorbid insomnia Objective To examine the efficacy of CBT-I for insomnia comorbid with psychiatric and/or medical conditions for (1) remission from insomnia; (2) self-reported sleep efficiency, sleep onset latency, wake after sleep onset, total sleep time, and subjective sleep quality; and (3) comorbid symptoms Data Sources A systematic search was conducted on June 2, 2014, through PubMed, PsycINFO, the Cochrane Library, and manual searches Search terms included (1) CBT-I or CBT or cognitive behavioral [and its variations] or behavioral therapy [and its variations] or behavioral sleep medicine or stimulus control or sleep restriction or relaxation therapy or relaxation training or progressive muscle relaxation or paradoxical intention ; and (2) insomnia or sleep disturbance Study Selection Studies were included if they were randomized clinical trials with at least one CBT-I arm and had an adult population meeting diagnostic criteria for insomnia as well as a concomitant condition Inclusion in final analyses (37 studies) was based on consensus between 3 authors’ independent screenings Data Extraction and Synthesis Data were independently extracted by 2 authors and pooled using a random-effects model Study quality was independently evaluated by 2 authors using the Cochrane risk of bias assessment tool Main Outcomes and Measures A priori main outcomes (ie, clinical sleep and comorbid outcomes) were derived from sleep diary and other self-report measures Results At posttreatment evaluation, 360% of patients who received CBT-I were in remission from insomnia compared with 169% of those in control or comparison conditions (pooled odds ratio, 328; 95% CI, 230-468; P g = 091 [95% CI, 074 to 108]; sleep onset latency: Hedges g = 080 [95% CI, 060 to 100]; wake after sleep onset: Hedges g = 068; sleep quality: Hedges g = 084; all P g = 039 [95% CI, 060-098]; P g = 020 [95% CI, 009-030]; χ 2 test for interaction = 1230; P Conclusions and Relevance Cognitive behavioral therapy for insomnia is efficacious for improving insomnia symptoms and sleep parameters for patients with comorbid insomnia A small to medium positive effect was found across comorbid outcomes, with larger effects on psychiatric conditions compared with medical conditions Large-scale studies with more rigorous designs to reduce detection and performance bias are needed to improve the quality of the evidence

Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness a randomized clinical trial

Abstract: DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings.

Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial.

Abstract: Importance Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer. Objective To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. Design, Setting, and Participants The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians. Interventions Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Main Outcomes and Measures Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152). Results After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.31 (95% CI, 0.13-0.77) for the Mediterranean diet with extra-virgin olive oil group and 0.53 (95% CI, 0.23-1.26) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90). Conclusions and Relevance This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies. Trial Registration ISRCTN.org Identifier: ISRCTN35739639

Cardiovascular Disease After Hodgkin Lymphoma Treatment: 40-Year Disease Risk

Abstract: Importance Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular diseases. It is unclear, however, how long the increased risk persists and what the risk factors are for various cardiovascular diseases. Objectives To examine relative and absolute excess risk up to 40 years since HL treatment compared with cardiovascular disease incidence in the general population and to study treatment-related risk factors for different cardiovascular diseases. Design, Setting, and Participants This retrospective cohort study included 2524 Dutch patients diagnosed as having HL at younger than 51 years (median age, 27.3 years) who had been treated from January 1, 1965, through December 31, 1995, and had survived for 5 years since their diagnosis. Exposures Treatment for HL, including prescribed mediastinal radiotherapy dose and anthracycline dose. Main Outcomes and Measures Data were collected from medical records and general practitioners. Cardiovascular events, including coronary heart disease (CHD), valvular heart disease (VHD), and cardiomyopathy and congestive heart failure (HF), were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Results After a median follow-up of 20 years, we identified 1713 cardiovascular events in 797 patients. After 35 years or more, patients still had a 4- to 6-fold increased standardized incidence ratio of CHD or HF compared with the general population, corresponding to 857 excess events per 10 000 person-years. Highest relative risks were seen in patients treated before 25 years of age, but substantial absolute excess risks were also observed for patients treated at older ages. Within the cohort, the 40-year cumulative incidence of cardiovascular diseases was 50% (95% CI, 47%-52%). Fifty-one percent of patients with a cardiovascular disease developed multiple events. For patients treated before 25 years of age, cumulative incidences at 60 years or older were 20%, 31%, and 11% for CHD, VHD, and HF as first events, respectively. Mediastinal radiotherapy increased the risks of CHD (hazard ratio [HR], 2.7; 95% CI, 2.0-3.7), VHD (HR, 6.6; 95% CI, 4.0-10.8), and HF (HR, 2.7; 95% CI, 1.6-4.8), and anthracycline-containing chemotherapy increased the risks of VHD (HR, 1.5; 95% CI, 1.1-2.1) and HF (HR, 3.0; 95% CI, 1.9-4.7) as first events compared with patients not treated with mediastinal radiotherapy or anthracyclines, respectively. Joint effects of mediastinal radiotherapy, anthracyclines, and smoking appeared to be additive. Conclusions and Relevance Throughout their lives, HL survivors treated at adolescence or adulthood are at high risk for various cardiovascular diseases. Physicians and patients should be aware of this persistently increased risk.

Mindfulness Meditation and Improvement in Sleep Quality and Daytime Impairment Among Older Adults With Sleep Disturbances: A Randomized Clinical Trial

Abstract: Importance Sleep disturbances are most prevalent among older adults and often go untreated. Treatment options for sleep disturbances remain limited, and there is a need for community-accessible programs that can improve sleep. Objective To determine the efficacy of a mind-body medicine intervention, called mindfulness meditation, to promote sleep quality in older adults with moderate sleep disturbances. Design, setting, and participants Randomized clinical trial with 2 parallel groups conducted from January 1 to December 31, 2012, at a medical research center among an older adult sample (mean [SD] age, 66.3 [7.4] years) with moderate sleep disturbances (Pittsburgh Sleep Quality Index [PSQI] >5). Interventions A standardized mindful awareness practices (MAPs) intervention (n = 24) or a sleep hygiene education (SHE) intervention (n = 25) was randomized to participants, who received a 6-week intervention (2 hours per week) with assigned homework. Main outcomes and measures The study was powered to detect between-group differences in moderate sleep disturbance measured via the PSQI at postintervention. Secondary outcomes pertained to sleep-related daytime impairment and included validated measures of insomnia symptoms, depression, anxiety, stress, and fatigue, as well as inflammatory signaling via nuclear factor (NF)-κB. Results Using an intent-to-treat analysis, participants in the MAPs group showed significant improvement relative to those in the SHE group on the PSQI. With the MAPs intervention, the mean (SD) PSQIs were 10.2 (1.7) at baseline and 7.4 (1.9) at postintervention. With the SHE intervention, the mean (SD) PSQIs were 10.2 (1.8) at baseline and 9.1 (2.0) at postintervention. The between-group mean difference was 1.8 (95% CI, 0.6-2.9), with an effect size of 0.89. The MAPs group showed significant improvement relative to the SHE group on secondary health outcomes of insomnia symptoms, depression symptoms, fatigue interference, and fatigue severity (P Conclusions and relevance The use of a community-accessible MAPs intervention resulted in improvements in sleep quality at immediate postintervention, which was superior to a highly structured SHE intervention. Formalized mindfulness-based interventions have clinical importance by possibly serving to remediate sleep problems among older adults in the short term, and this effect appears to carry over into reducing sleep-related daytime impairment that has implications for quality of life. Trial registration clinicaltrials.gov Identifier: NCT01534338.

Clinical and Radiologic Disease in Smokers With Normal Spirometry

Abstract: Importance Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. Objective To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. Design, Setting, and Participants Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV 1 ] to forced vital capacity >0.7 and FEV 1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. Main Outcomes and Measures Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. Results One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George’s Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P 1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. Conclusions and Relevance Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.

The Influence of Partner’s Behavior on Health Behavior Change: The English Longitudinal Study of Ageing

Abstract: Importance Couples are highly concordant for unhealthy behaviors, and a change in one partner’s health behavior is often associated with a change in the other partner’s behavior. However, no studies have explicitly compared the influence of having a partner who takes up healthy behavior (eg, quits smoking) with one whose behavior is consistently healthy (eg, never smokes). Objective To examine the influence of partner’s behavior on making positive health behavior changes. Design, Setting, and Participants We used prospective data from married and cohabiting couples (n, 3722) participating in the English Longitudinal Study of Ageing, a large population-based cohort of older adults (≥50 years). Studying men and women who had unhealthy behaviors in 3 domains at baseline (ie, smoking, physically inactive, or overweight/obese), we used logistic regression analysis to examine the influence of the partner’s behavior in the same domain on the odds of positive health behavior change over time. Main Outcomes and Measures Smoking cessation, increased physical activity, and 5% weight loss or greater. Results Across all domains, we found that when one partner changed to a healthier behavior (newly healthy), the other partner was more likely to make a positive health behavior change than if their partner remained unhealthy (smoking: men 48% vs 8%, adjusted odds ratio [OR], 11.82 [95% CI, 4.84-28.90]; women 50% vs 8%, OR, 11.23 [4.58-27.52]) (physical activity: men 67% vs 26%, OR, 5.28 [3.70-7.54]; women 66% vs 24%, OR, 5.36 [3.74-7.68]) (weight loss: men 26% vs 10%, OR, 3.05 [1.96-4.74]; women 36% vs 15%, OR, 3.08 [1.98-4.80]). For smoking and physical activity, having a consistently healthy partner also predicted positive change, but for each domain, the odds were significantly higher in individuals with a newly healthy partner than those with a consistently healthy partner (smoking: men OR, 3.08 [1.43-6.62]; women OR, 5.45 [2.44-12.16]) (physical activity: men OR, 1.92 [1.37-2.70]; women OR, 1.84 [1.33-2.53]) (weight loss: men OR, 2.28 [1.36-3.84]; women OR, 2.86 [1.55-5.26]). Conclusions and Relevance Men and women are more likely to make a positive health behavior change if their partner does too, and with a stronger effect than if the partner had been consistently healthy in that domain. Involving partners in behavior change interventions may therefore help improve outcomes.

Potential overtreatment of diabetes mellitus in older adults with tight glycemic control.

Abstract: Importance In older adults with multiple serious comorbidities and functional limitations, the harms of intensive glycemic control likely exceed the benefits Objectives To examine glycemic control levels among older adults with diabetes mellitus by health status and to estimate the prevalence of potential overtreatment of diabetes Design, Setting, and Participants Cross-sectional analysis of the data on 1288 older adults (≥65 years) with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2010 who had a hemoglobin A 1c (HbA 1c ) measurement All analyses incorporated complex survey design to produce nationally representative estimates Exposures Health status categories: very complex/poor , based on difficulty with 2 or more activities of daily living or dialysis dependence; complex/intermediate , based on difficulty with 2 or more instrumental activities of daily living or presence of 3 or more chronic conditions; and relatively healthy if none of these were present Main Outcomes and Measures Tight glycemic control (HbA 1c level, Results Of 1288 older adults with diabetes, 507% (95% CI, 466%-548%), representing 31 million (95% CI, 27-35), were relatively healthy, 281% (95% CI, 248%-315%), representing 17 million (95% CI, 14-20), had complex/intermediate health, and 212% (95% CI, 183%-244%), representing 13 million (95% CI, 11-15), had very complex/poor health Overall, 615% (95% CI, 575%-653%), representing 38 million (95% CI, 34-42), had an HbA 1c level of less than 7%; this proportion did not differ across health status categories (628% [95% CI, 569%-683%]) were relatively healthy, 630% (95% CI, 570%-686%) had complex/intermediate health, and 564% (95% CI, 497%-629%) had very complex/poor health ( P = 26) Of the older adults with an HbA 1c level of less than 7%, 549% (95% CI, 504%-593%) were treated with either insulin or sulfonylureas; this proportion was similar across health status categories (508% [95% CI, 451%-565%] were relatively healthy, 587% [95% CI, 494%-675%] had complex/intermediate health, and 600% [95% CI, 514%-681%] had very complex/poor health; P = 14) During the 10 study years, there were no significant changes in the proportion of older adults with an HbA 1c level of less than 7% ( P = 34), the proportion with an HbA 1c level of less than 7% who had complex/intermediate or very complex/poor health ( P = 27), or the proportion with an HbA 1c level of less than 7% who were treated with insulin or sulfonylureas despite having complex/intermediate or very complex/poor health ( P = 65) Conclusions and Relevance Although the harms of intensive treatment likely exceed the benefits for older patients with complex/intermediate or very complex/poor health status, most of these adults reached tight glycemic targets between 2001 and 2010 Most of them were treated with insulin or sulfonylureas, which may lead to severe hypoglycemia Our findings suggest that a substantial proportion of older adults with diabetes were potentially overtreated

Early Trends Among Seven Recommendations From the Choosing Wisely Campaign

Abstract: Importance The Choosing Wisely campaign consists of more than 70 lists produced by specialty societies of medical practices or procedures of minimal clinical benefit to patients in most situations, with recommendations regarding judicious use. Objective To quantify the frequency and trends of some of the earliest Choosing Wisely recommendations using nationwide commercial health plan population-level data. Design, Setting, and Participants Retrospective analysis of claims data for members of Anthem-affiliated commercial health plans. The low-value services selected were (1) imaging tests for uncomplicated headache; (2) cardiac imaging without history of cardiac conditions; (3) low back pain imaging without red-flag conditions; (4) preoperative chest x-rays with unremarkable history and physical examination results; (5) human papillomavirus testing for women younger than 30 years; (6) use of antibiotics for acute sinusitis; and (7) use of prescription nonsteroidal anti-inflammatory drugs (NSAIDs) for members with hypertension, heart failure, or chronic kidney disease. Main Outcomes and Measures The number of members with medical and/or pharmacy claims for the included low-value services was assessed quarterly over a 2- to 3-year span through 2013. Trend changes in recommendations were evaluated across all quarters using Poisson regression with denominators as offsets. Results Two services had declines: Use of imaging for headache decreased from 14.9% to 13.4% (trend estimate, 0.99 [95% CI, 0.98-0.99]; P P P P P = .16). Use of preoperative chest x-rays (0.2% decrease, ending utilization 91.5%; trend estimate, 1.00 [95% CI, 1.00-1.00]; P = .70) and imaging for low back pain (53.7% utilization throughout study; P = .71) remained high with no statistically significant changes. Conclusions and Relevance For this population-level analysis of 7 low-value services analyzed, changes were modest but showed a desirable decrease for 2 recommendations (imaging for headache, cardiac imaging for low-risk patients). The effect sizes were marginal, however, and although 4 of the 7 lists had statistically significant changes—unsurprising given the large sample size—the clinical significance is uncertain. These results suggest that additional interventions are necessary for wider implementation of Choosing Wisely recommendations.

Barriers to Goals of Care Discussions With Seriously Ill Hospitalized Patients and Their Families: A Multicenter Survey of Clinicians

Abstract: Importance Seriously ill hospitalized patients have identified communication and decision making about goals of care as high priorities for quality improvement in end-of-life care. Interventions to improve care are more likely to succeed if tailored to existing barriers. Objective To determine, from the perspective of hospital-based clinicians, (1) barriers impeding communication and decision making about goals of care with seriously ill hospitalized patients and their families and (2) their own willingness and the acceptability for other clinicians to engage in this process. Design, Setting, and Participants Multicenter survey of medical teaching units of nurses, internal medicine residents, and staff physicians from participating units at 13 university-based hospitals from 5 Canadian provinces. Main Outcomes and Measures Importance of 21 barriers to goals of care discussions rated on a 7-point scale (1 = extremely unimportant; 7 = extremely important). Results Between September 2012 and March 2013, questionnaires were returned by 1256 of 1617 eligible clinicians, for an overall response rate of 77.7% (512 of 646 nurses [79.3%], 484 of 634 residents [76.3%], 260 of 337 staff physicians [77.2%]). The following family member–related and patient-related factors were consistently identified by all 3 clinician groups as the most important barriers to goals of care discussions: family members’ or patients’ difficulty accepting a poor prognosis (mean [SD] score, 5.8 [1.2] and 5.6 [1.3], respectively), family members’ or patients’ difficulty understanding the limitations and complications of life-sustaining treatments (5.8 [1.2] for both groups), disagreement among family members about goals of care (5.8 [1.2]), and patients’ incapacity to make goals of care decisions (5.6 [1.2]). Clinicians perceived their own skills and system factors as less important barriers. Participants viewed it as acceptable for all clinician groups to engage in goals of care discussions—including a role for advance practice nurses, nurses, and social workers to initiate goals of care discussions and be a decision coach. Conclusions and Relevance Hospital-based clinicians perceive family member–related and patient-related factors as the most important barriers to goals of care discussions. All health care professionals were viewed as playing important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication and decision making about goals of care.

Medication Therapy Management Interventions in Outpatient Settings A Systematic Review and Meta-analysis

Abstract: Importance Medication therapy management (MTM) services (also called clinical pharmacy services ) aim to reduce medication-related problems and their downstream outcomes. Objective To assess the effect of MTM interventions among outpatients with chronic illnesses. Data Sources MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts through January 9, 2014. Study Selection Two reviewers selected studies with comparators and eligible outcomes of ambulatory adults. Data Extraction and Synthesis Dual review of titles, abstracts, full-text, extractions, risk of bias, and strength of evidence grading. We conducted meta-analyses using random-effects models. Main Outcomes and Measures Medication-related problems, morbidity, mortality, quality of life, health care use, costs, and harms. Results Forty-four studies met the inclusion criteria. The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P Conclusions and Relevance We graded the evidence as insufficient for most outcomes because of inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions. Medication therapy management interventions may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes.

The Strength of Association Between Surrogate End Points and Survival in Oncology: A Systematic Review of Trial-Level Meta-analyses

Abstract: Importance The strength of association between surrogate end points and survival in oncology is important to understand because surrogate end points are frequently used in oncology clinical trials, supporting US Food and Drug Administration approvals and National Comprehensive Cancer Network guideline recommendations. Objective To identify and evaluate trial-level meta-analyses of randomized clinical trials quantifying the association between a surrogate end point and overall survival in medical oncology. Trial-level correlations test whether treatments that improve the surrogate end point also improve the final end point and are widely considered the strongest evidence to validate a surrogate end point. Evidence Review Our literature search was built on earlier reported data sets and updated with Google Scholar and MEDLINE searches conducted on December 26, 2014. For MEDLINE, search terms included (“regression” or “correlation”) and “surrogate” and “end point [or endpoint]” and (“oncology” or “cancer”). For Google scholar, search terms included (“regression” or “correlation”) and “surrogate end point [or endpoint]” and “overall survival” and “trial level.” A total of 108 abstracts were retrieved, and 62 articles were read in full in addition to articles identified through prior reviews. Findings We found 36 articles in which 65 specific correlations between a surrogate end point and survival were identified. Surrogate end points were studied in the neoadjuvant, adjuvant, locally advanced, and metastatic settings. The most common sources for trials included in the 36 articles were systematic reviews of the published literature (10 of 36; 28%), and published literature and meeting abstracts (14 of 36; 39%). Four meta-analyses (11%) used a convenience sample, and only 5 studies (14%) attempted to include unpublished trials by surveying clinical trial registries. Among these 5 studies, only 352 of 684 eligible trials (51.1%) were included in the analyses. More than half of reported correlations (34 of 65; 52%) were of low strength ( r ≤ 0.7). Approximately a quarter (16 of 65; 25%) were of medium strength ( r > 0.7 to r r ≥ 0.85) with survival. Conclusions and Relevance Most trial-level validation studies of surrogate end points in oncology find low correlations with survival. All validation studies use only a subset of available trials. The evidence supporting the use of surrogate end points in oncology is limited.

Effect of moderate to vigorous physical activity on all-cause mortality in middle-aged and older Australians

Abstract: MAIN OUTCOMES AND MEASURES All-cause mortality during the follow-up period. RESULTS During 1 444 927 person-years of follow-up, 7435 deaths were registered. Compared with those who reported no MVPA (crude death rate, 8.34%), the adjusted hazard ratios for all-cause mortality were 0.66 (95% CI, 0.61-0.71; crude death rate, 4.81%), 0.53 (95% CI, 0.48-0.57; crude death rate, 3.17%), and 0.46 (95% CI, 0.43-0.49; crude death rate, 2.64%) for reporting 10 through 149, 150 through 299, and 300 min/wk or more of activity, respectively. Among those who reported any MVPA, the proportion of vigorous activity revealed an inverse dose-response relationship with all-cause mortality: compared with those reporting no vigorous activity (crude death rate, 3.84%) the fully adjusted hazard ratio was 0.91 (95% CI, 0.84-0.98; crude death rate, 2.35%) in those who reported some vigorous activity (but <30% of total activity) and 0.87 (95% CI, 0.81-0.93; crude death rate, 2.08%) among those who reported 30% or more of activity as vigorous. These associations were consistent in men and women, across categories of body mass index and volume of MVPA, and in those with and without existing cardiovascular disease or diabetes mellitus.

Risk of Bleeding With Dabigatran in Atrial Fibrillation

Abstract: Importance It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice. Objective To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data. Design, Setting, and Participants In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011. Exposures Dabigatran users (n = 1302) and warfarin users (n = 8102). Main Outcomes and Measures We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities. Results Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease. Conclusions and Relevance Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Epidemiology of the Homebound Population in the United States

Abstract: Importance Increasing numbers of older, community-dwelling adults have functional impairments that prevent them from leaving their homes. It is uncertain how many people who live in the United States are homebound. Objectives To develop measures of the frequency of leaving and ability to leave the home and to use these measures to estimate the size of the homebound population in the US population. Design, Setting, and Participants Cross-sectional data from the National Health and Aging Trends Study collected in 2011 in the contiguous United States. Participants were a nationally representative sample of 7603 noninstitutionalized Medicare beneficiaries 65 years and older. Main Outcomes and Measures We defined homebound persons as those who never (completely homebound) or rarely (mostly homebound) left the home in the last month. We defined semihomebound persons as those who only left the home with assistance or had difficulty or needed help leaving the home. We compared demographic, clinical, and health care utilization characteristics across different homebound status categories. Results In 2011, the prevalence of homebound individuals was 5.6% (95% CI, 5.1%-6.2%), including an estimated 395 422 people who were completely homebound and 1 578 984 people who were mostly homebound. Among semihomebound individuals, the prevalence of those who never left home without personal assistance was 3.3% (95% CI, 2.8%-3.8%), and the prevalence of those who required help or had difficulty was 11.7% (95% CI, 10.9%-12.6%). Completely homebound individuals were more likely to be older (83.2 vs 74.3 years,P Conclusions and Relevance In total, 5.6% of the elderly, community-dwelling Medicare population (approximately 2 million people) were completely or mostly homebound in 2011. Our findings can inform improvements in clinical and social services for these individuals.

Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data

Abstract: MAIN OUTCOMES AND MEASURES Difference in SBP and DBP measured in an office setting. RESULTS We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P =. 97;I 2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I 2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P =. 27;I 2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I 2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better