Search

ImportanceAmid efforts in the US to promote health equity, there is a need to assess recent progress in reducing excess deaths and years of potential life lost among the Black population compared with the White population.ObjectiveTo evaluate trends in excess mortality and years of potential life lost among the Black population compared with the White population.Design, setting, and participantsSerial cross-sectional study using US national data from the Centers for Disease Control and Prevention from 1999 through 2020. We included data from non-Hispanic White and non-Hispanic Black populations across all age groups.ExposuresRace as documented in the death certificates.Main outcomes and measuresExcess age-adjusted all-cause mortality, cause-specific mortality, age-specific mortality, and years of potential life lost rates (per 100 000 individuals) among the Black population compared with the White population.ResultsFrom 1999 to 2011, the age-adjusted excess mortality rate declined from 404 to 211 excess deaths per 100 000 individuals among Black males (P for trend P for trend = .98) and increased in 2020 to 395—rates not seen since 2000. Among Black females, the rate declined from 224 excess deaths per 100 000 individuals in 1999 to 87 in 2015 (P for trend P for trend = .71) and in 2020 rates increased to 192—levels not seen since 2005. The trends in rates of excess years of potential life lost followed a similar pattern. From 1999 to 2020, the disproportionately higher mortality rates in Black males and females resulted in 997 623 and 628 464 excess deaths, respectively, representing a loss of more than 80 million years of life. Heart disease had the highest excess mortality rates, and the excess years of potential life lost rates were largest among infants and middle-aged adults.Conclusions and relevanceOver a recent 22-year period, the Black population in the US experienced more than 1.63 million excess deaths and more than 80 million excess years of life lost when compared with the White population. After a period of progress in reducing disparities, improvements stalled, and differences between the Black population and the White population worsened in 2020.

This study describes the degree to which blood draws occurred among hospitalized patients during traditional sleep hours and investigates trends over time.

ImportanceIn the US, nearly all medical devices progress to market under the 510(k) pathway, which uses previously authorized devices (predicates) to support new authorizations. Current regulations permit manufacturers to use devices subject to a Class I recall—the FDA’s most serious designation indicating a high probability of adverse health consequences or death—as predicates for new devices. The consequences for patient safety are not known.ObjectiveTo determine the risk of a future Class I recall associated with using a recalled device as a predicate device in the 510(k) pathway.Design and SettingIn this cross-sectional study, all 510(k) devices subject to Class I recalls from January 2017 through December 2021 (index devices) were identified from the FDA’s annual recall listings. Information about predicate devices was extracted from the Devices@FDA database. Devices authorized using index devices as predicates (descendants) were identified using a regulatory intelligence platform. A matched cohort of predicates was constructed to assess the future recall risk from using a predicate device with a Class I recall.Main Outcomes and MeasuresDevices were characterized by their regulatory history and recall history. Risk ratios (RRs) were calculated to compare the risk of future Class I recalls between devices descended from predicates with matched controls.ResultsOf 156 index devices subject to Class I recall from 2017 through 2021, 44 (28.2%) had prior Class I recalls. Predicates were identified for 127 index devices, with 56 (44.1%) using predicates with a Class I recall. One hundred four index devices were also used as predicates to support the authorization of 265 descendant devices, with 50 index devices (48.1%) authorizing a descendant with a Class I recall. Compared with matched controls, devices authorized using predicates with Class I recalls had a higher risk of subsequent Class I recall (6.40 [95% CI, 3.59-11.40]; PConclusions and RelevanceMany 510(k) devices subjected to Class I recalls in the US use predicates with a known history of Class I recalls. These devices have substantially higher risk of a subsequent Class I recall. Safeguards for the 510(k) pathway are needed to prevent problematic predicate selection and ensure patient safety.

This study uses national death certificate data to characterize trends in death and excess mortality from drug overdoses, homicides, unintentional injuries, motor vehicle crashes, and suicide during the first 6 months of the pandemic in the US.

Importance The elimination of racial and ethnic differences in health status and health care access is a US goal, but it is unclear whether the country has made progress over the last 2 decades. Objective To determine 20-year trends in the racial and ethnic differences in self-reported measures of health status and health care access and affordability among adults in the US. Design, Setting, and Participants Serial cross-sectional study of National Health Interview Survey data, 1999-2018, that included 596 355 adults. Exposures Self-reported race, ethnicity, and income level. Main Outcomes and Measures Rates and racial and ethnic differences in self-reported health status and health care access and affordability. Results The study included 596 355 adults (mean [SE] age, 46.2 [0.07] years, 51.8% [SE, 0.10] women), of whom 4.7% were Asian, 11.8% were Black, 13.8% were Latino/Hispanic, and 69.7% were White. The estimated percentages of people with low income were 28.2%, 46.1%, 51.5%, and 23.9% among Asian, Black, Latino/Hispanic, and White individuals, respectively. Black individuals with low income had the highest estimated prevalence of poor or fair health status (29.1% [95% CI, 26.5%-31.7%] in 1999 and 24.9% [95% CI, 21.8%-28.3%] in 2018), while White individuals with middle and high income had the lowest (6.4% [95% CI, 5.9%-6.8%] in 1999 and 6.3% [95% CI, 5.8%-6.7%] in 2018). Black individuals had a significantly higher estimated prevalence of poor or fair health status than White individuals in 1999, regardless of income strata (P

Faust et al discuss the study which compares all-cause excess mortality and COVID-19-related mortality during the early pandemic period (March-July 2020) with unintentional drug overdoses, the usual leading cause of death in young adults, during the same period in 2018 among adults aged 25 to 44 years COVID-19 has caused a marked increase in all-cause deaths in the US, mostly among older adults Although the burden of COVID-19 among hospitalized younger adults has been described, fewer data focus on mortality in this demographic, owing to lower case-fatality rates

Importance: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVD). Objective: To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, setting and participants: A pooled analysis of individual-participant-data from the Emerging Risk Factors Collaboration (ERFC; 162,036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and UK Biobank (UKB; 401,219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. Exposure: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Centre for Epidemiological Studies Depression scale (CES-D; range 0-60; ≥16 indicates possible depressive disorder). UKB recorded the Patient Health Questionnaire-2 (PHQ-2; range 0-6; ≥3 indicates possible depressive disorder). Main Outcomes and Measures: Primary outcomes were incident fatal/nonfatal coronary heart disease (CHD), stroke and CVD (composite of CHD and stroke). Hazard ratios (HRs) per 1-SD higher log-CES-D or PHQ-2 adjusted for age, sex, smoking and diabetes were reported. Results: Among 162,036 participants from the ERFC, 73% were female, mean (SD) age at baseline was 63 (9) years, and 5,078 CHD and 3,932 stroke events were recorded (median follow-up, 9.5-years). Associations with CHD, stroke and CVD were log-linear. HRs (95%CI) per 1SD higher depression score for CHD, stroke and CVD respectively were 1.07 (1.03-1.11), 1.05 (1.01-1.10), and 1.06 (1.04-1.08). This reflects, 36 versus 29 CHD events, 28 versus 25 stroke events, and 63 versus 54 CVD events per 1000 individuals over 10 years in the highest versus lowest quintile of CES-D (geometric mean CES-D score, 19 versus 1). Among 401,219 participants from the UKB, 55% were female, mean baseline age was 56 (8) years, and 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1-years). HRs per 1SD higher depression score for CHD, stroke and CVD respectively were 1.11 (1.08-1.14), 1.10 (1.06-1.14) and 1.10 (1.08-1.13). This reflects, 21 versus 14 CHD events, 15 versus 10 stroke events, and 36 versus 25 CVD events per 1000 individuals over 10 years in those with PHQ2 ≥4 versus 0. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and Relevance: In a pooled analysis of 563,255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels below the threshold indicative of a depressive disorder. However, the magnitude of associations was modest., Lisa Pennells, Stephen Kaptoge and Sarah Spackman are funded by a British Heart Foundation Programme Grant (RG/18/13/33946). Steven Bell was funded by the National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Tom Bolton is funded by the National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Angela Wood is supported by a BHF-Turing Cardiovascular Data Science Award and by the EC-Innovative Medicines Initiative (BigData@Heart). John Danesh holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award.* *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

IMPORTANCE: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention. OBJECTIVE: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record–based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019. EXPOSURES: Ticagrelor vs clopidogrel. MAIN OUTCOMES AND MEASURES: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis. RESULTS: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P

IMPORTANCE: Albuminuria, as measured by single urine albumin-to-creatinine ratio (UACR) levels, is associated with cardiac remodeling and adverse clinical outcomes. The longitudinal patterns of change in UACR through young adulthood and their associations with myocardial structure and function later in life remain unclear. OBJECTIVE: To describe the trajectory of albuminuria as measured by UACR across a 20-year span and evaluate the association of albuminuria trajectory with echocardiographic indices of structure and function in middle age. DESIGN, SETTING, AND PARTICIPANTS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of black and white participants aged 18 to 30 years at baseline (March 1985 to June 1986) were evaluated over 30 years. Participants underwent evaluations at 4 urban US sites. Data were collected from March 1985 to May 2016, and data were analyzed from September 2018 to April 2019. EXPOSURES: Trajectories of UACR from the year 10 examination to the year 30 examination as determined by latent class modeling. MAIN OUTCOMES AND MEASURES: Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 30 examination. RESULTS: Of the 2647 included participants, 1441 (54.4%) were white, 1206 (45.6%) were black, and the mean (SD) age was 35.2 (3.6) years. A total of 5 trajectory groups of UACR were identified, including 1718 participants (64.9%) in the low-stable group, 682 (25.8%) in the moderate-stable group, 116 (4.4%) in the high-stable group, 88 (3.3%) in the moderate-increasing group, and 43 (1.6%) in the high-increasing group. Apart from the high-increasing cohort, the remaining 4 groups had median baseline UACR levels less than 30 mg/g. Male sex, current smoking, diabetes, and elevated blood pressure were more common in the moderate-increasing and high-increasing UACR groups. After adjustment for clinical variables and baseline UACR levels, there were significant differences in left ventricular (LV) mass by trajectory group (mean [SE] LV mass: high-increasing, 98.4 [3.4] g/m(2); moderate-increasing, 91.7 [2.2] g/m(2); high-stable, 86.0 [2.1] g/m(2); moderate-stable, 82.3 [0.8] g/m(2); low-stable, 78.6 [0.5] g/m(2); P

Importance Acute myocardial infarction (AMI) complicated by cardiogenic shock is associated with substantial morbidity and mortality. Although intravascular microaxial left ventricular assist devices (LVADs) provide greater hemodynamic support as compared with intra-aortic balloon pumps (IABPs), little is known about clinical outcomes associated with intravascular microaxial LVAD use in clinical practice. Objective To examine outcomes among patients undergoing percutaneous coronary intervention (PCI) for AMI complicated by cardiogenic shock treated with mechanical circulatory support (MCS) devices. Design, Setting, and Participants A propensity-matched registry-based retrospective cohort study of patients with AMI complicated by cardiogenic shock undergoing PCI between October 1, 2015, and December 31, 2017, who were included in data from hospitals participating in the CathPCI and the Chest Pain-MI registries, both part of the American College of Cardiology’s National Cardiovascular Data Registry. Patients receiving an intravascular microaxial LVAD were matched with those receiving IABP on demographics, clinical history, presentation, infarct location, coronary anatomy, and clinical laboratory data, with final follow-up through December 31, 2017. Exposures Hemodynamic support, categorized as intravascular microaxial LVAD use only, IABP only, other (such as use of a percutaneous extracorporeal ventricular assist system, extracorporeal membrane oxygenation, or a combination of MCS device use), or medical therapy only. Main Outcomes and Measures The primary outcomes were in-hospital mortality and in-hospital major bleeding. Results Among 28 304 patients undergoing PCI for AMI complicated by cardiogenic shock, the mean (SD) age was 65.0 (12.6) years, 67.0% were men, 81.3% had an ST-elevation myocardial infarction, and 43.3% had cardiac arrest. Over the study period among patients with AMI, an intravascular microaxial LVAD was used in 6.2% of patients, and IABP was used in 29.9%. Among 1680 propensity-matched pairs, there was a significantly higher risk of in-hospital death associated with use of an intravascular microaxial LVAD (45.0%) vs with an IABP (34.1% [absolute risk difference, 10.9 percentage points {95% CI, 7.6-14.2};P Conclusions and Relevance Among patients undergoing PCI for AMI complicated by cardiogenic shock from 2015 to 2017, use of an intravascular microaxial LVAD compared with IABP was associated with higher adjusted risk of in-hospital death and major bleeding complications, although study interpretation is limited by the observational design. Further research may be needed to understand optimal device choice for these patients.

Readmission rates declined after announcement of the Hospital Readmission Reduction Program (HRRP), which penalizes hospitals for excess readmissions for acute myocardial infarction (AMI), heart failure (HF), and pneumonia.To compare trends in readmission rates for target and nontarget conditions, stratified by hospital penalty status.Retrospective cohort study of Medicare fee-for-service beneficiaries older than 64 years discharged between January 1, 2008, and June 30, 2015, from 2214 penalty hospitals and 1283 nonpenalty hospitals. Difference-interrupted time-series models were used to compare trends in readmission rates by condition and penalty status.Hospital penalty status or target condition under the HRRP.Thirty-day risk adjusted, all-cause unplanned readmission rates for target and nontarget conditions.The study included 48 137 102 hospitalizations of 20 351 161 Medicare beneficiaries. In January 2008, the mean readmission rates for AMI, HF, pneumonia, and nontarget conditions were 21.9%, 27.5%, 20.1%, and 18.4%, respectively, at hospitals later subject to financial penalties and 18.7%, 24.2%, 17.4%, and 15.7% at hospitals not subject to penalties. Between January 2008 and March 2010, prior to HRRP announcement, readmission rates were stable across hospitals (except AMI at nonpenalty hospitals). Following announcement of HRRP (March 2010), readmission rates for both target and nontarget conditions declined significantly faster for patients at hospitals later subject to financial penalties compared with those at nonpenalized hospitals (for AMI, additional decrease of -1.24 [95% CI, -1.84 to -0.65] percentage points per year relative to nonpenalty discharges; for HF, -1.25 [95% CI, -1.64 to -0.86]; for pneumonia, -1.37 [95% CI, -1.80 to -0.95]; and for nontarget conditions, -0.27 [95% CI, -0.38 to -0.17]; P .001 for all). For penalty hospitals, readmission rates for target conditions declined significantly faster compared with nontarget conditions (for AMI, additional decline of -0.49 [95% CI, -0.81 to -0.16] percentage points per year relative to nontarget conditions [P = .004]; for HF, -0.90 [95% CI, -1.18 to -0.62; P .001]; and for pneumonia, -0.57 [95% CI, -0.92 to -0.23; P .001]). In contrast, among nonpenalty hospitals, readmissions for target conditions declined similarly or more slowly compared with nontarget conditions (for AMI, additional increase of 0.48 [95% CI, 0.01-0.95] percentage points per year [P = .05]; for HF, 0.08 [95% CI, -0.30 to 0.46; P = .67]; for pneumonia, 0.53 [95% CI, 0.13-0.93; P = .01]). After HRRP implementation in October 2012, the rate of change for readmission rates plateaued (P .05 for all except pneumonia at nonpenalty hospitals), with the greatest relative change observed among hospitals subject to financial penalty.Medicare fee-for-service patients at hospitals subject to penalties under the HRRP had greater reductions in readmission rates compared with those at nonpenalized hospitals. Changes were greater for target vs nontarget conditions for patients at the penalized hospitals but not at the other hospitals.

Importance There is substantial uncertainty about optimal glycemic control in older adults with type 2 diabetes mellitus. Observations Four large randomized clinical trials (RCTs), ranging in size from 1791 to 11 440 patients, provide the majority of the evidence used to guide diabetes therapy. Most RCTs of intensive vs standard glycemic control excluded adults older than 80 years, used surrogate end points to evaluate microvascular outcomes and provided limited data on which subgroups are most likely to benefit or be harmed by specific therapies. Available data from randomized clinical trials suggest that intensive glycemic control does not reduce major macrovascular events in older adults for at least 10 years. Furthermore, intensive glycemic control does not lead to improved patient-centered microvascular outcomes for at least 8 years. Data from randomized clinical trials consistently suggest that intensive glycemic control immediately increases the risk of severe hypoglycemia 1.5- to 3-fold. Based on these data and observational studies, for the majority of adults older than 65 years, the harms associated with a hemoglobin A 1c (HbA 1c ) target lower than 7.5% or higher than 9% are likely to outweigh the benefits. However, the optimal target depends on patient factors, medications used to reach the target, life expectancy, and patient preferences about treatment. If only medications with low treatment burden and hypoglycemia risk (such as metformin) are required, a lower HbA 1c target may be appropriate. If patients strongly prefer to avoid injections or frequent fingerstick monitoring, a higher HbA 1c target that obviates the need for insulin may be appropriate. Conclusions and Relevance High-quality evidence about glycemic treatment in older adults is lacking. Optimal decisions need to be made collaboratively with patients, incorporating the likelihood of benefits and harms and patient preferences about treatment and treatment burden. For the majority of older adults, an HbA 1c target between 7.5% and 9% will maximize benefits and minimize harms.

Appropriate Use Criteria for Coronary Revascularization were developed to critically evaluate and improve patient selection for percutaneous coronary intervention (PCI). National trends in the appropriateness of PCI have not been examined.To examine trends in PCI utilization, patient selection, and procedural appropriateness following the introduction of Appropriate Use Criteria.Multicenter, longitudinal, cross-sectional analysis of patients undergoing PCI between July 1, 2009, and December 31, 2014, at hospitals continuously participating in the National Cardiovascular Data Registry CathPCI registry over the study period.Proportion of nonacute PCIs classified as inappropriate at the patient and hospital level using the 2012 Appropriate Use Criteria for Coronary Revascularization.A total of 2.7 million PCI procedures from 766 hospitals were included. Annual PCI volume of acute indications was consistent over the study period (377,540 in 2010; 374,543 in 2014), but the volume of nonacute PCIs decreased from 89,704 in 2010 to 59,375 in 2014. Among patients undergoing nonacute PCI, there were significant increases in angina severity (Canadian Cardiovascular Society grade III/IV angina, 15.8% in 2010 and 38.4% in 2014), use of antianginal medications prior to PCI (at least 2 antianginal medications, 22.3% in 2010 and 35.1% in 2014), and high-risk findings on noninvasive testing (22.2% in 2010 and 33.2% in 2014) (P .001 for all), but only modest increases in multivessel coronary artery disease (43.7% in 2010 and 47.5% in 2014, P .001). The proportion of nonacute PCIs classified as inappropriate decreased from 26.2% (95% CI, 25.8%-26.6%) to 13.3% (95% CI, 13.1%-13.6%), and the absolute number of inappropriate PCIs decreased from 21,781 to 7921. Hospital-level variation in the proportion of PCIs classified as inappropriate persisted over the study period (median, 12.6% [interquartile range, 5.9%-22.9%] in 2014).Since the publication of the Appropriate Use Criteria for Coronary Revascularization in 2009, there have been significant reductions in the volume of nonacute PCI. The proportion of nonacute PCIs classified as inappropriate has declined, although hospital-level variation in inappropriate PCI persists.

Importance In a period of dynamic change in health care technology, delivery, and behaviors, tracking trends in health and health care can provide a perspective on what is being achieved. Objective To comprehensively describe national trends in mortality, hospitalizations, and expenditures in the Medicare fee-for-service population between 1999 and 2013. Design, Setting, and Participants Serial cross-sectional analysis of Medicare beneficiaries aged 65 years or older between 1999 and 2013 using Medicare denominator and inpatient files. Main Outcomes and Measures For all Medicare beneficiaries, trends in all-cause mortality; for fee-for-service beneficiaries, trends in all-cause hospitalization and hospitalization-associated outcomes and expenditures. Geographic variation, stratified by key demographic groups, and changes in the intensity of care for fee-for-service beneficiaries in the last 1, 3, and 6 months of life were also assessed. Results The sample consisted of 68 374 904 unique Medicare beneficiaries (fee-for-service and Medicare Advantage). All-cause mortality for all Medicare beneficiaries declined from 5.30% in 1999 to 4.45% in 2013 (difference, 0.85 percentage points; 95% CI, 0.83-0.87). Among fee-for-service beneficiaries (n = 60 056 069), the total number of hospitalizations per 100 000 person-years decreased from 35 274 to 26 930 (difference, 8344; 95% CI, 8315-8374). Mean inflation-adjusted inpatient expenditures per Medicare fee-for-service beneficiary declined from $3290 to $2801 (difference, $489; 95% CI, $487-$490). Among fee-for-service beneficiaries in the last 6 months of life, the number of hospitalizations decreased from 131.1 to 102.9 per 100 deaths (difference, 28.2; 95% CI, 27.9-28.4). The percentage of beneficiaries with 1 or more hospitalizations decreased from 70.5 to 56.8 per 100 deaths (difference, 13.7; 95% CI, 13.5-13.8), while the inflation-adjusted inpatient expenditure per death increased from $15 312 in 1999 to $17 423 in 2009 and then decreased to $13 388 in 2013. Findings were consistent across geographic and demographic groups. Conclusions and Relevance Among Medicare fee-for-service beneficiaries aged 65 years or older, all-cause mortality rates, hospitalization rates, and expenditures per beneficiary decreased from 1999 to 2013. In the last 6 months of life, total hospitalizations and inpatient expenditures decreased in recent years.

Importance Publicly available data sets hold much potential, but their unique design may require specific analytic approaches. Objective To determine adherence to appropriate research practices for a frequently used large public database, the National Inpatient Sample (NIS) of the Agency for Healthcare Research and Quality (AHRQ). Design, Setting, and Participants In this observational study of the 1082 studies published using the NIS from January 2015 through December 2016, a representative sample of 120 studies was systematically evaluated for adherence to practices required by AHRQ for the design and conduct of research using the NIS. Exposures None. Main Outcomes and Measures All studies were evaluated on 7 required research practices based on AHRQ’s recommendations and compiled under 3 domains: (1) data interpretation (interpreting data as hospitalization records rather than unique patients); (2) research design (avoiding use in performing state-, hospital-, and physician-level assessments where inappropriate; not using nonspecific administrative secondary diagnosis codes to study in-hospital events); and (3) data analysis (accounting for complex survey design of the NIS and changes in data structure over time). Results Of 120 published studies, 85% (n = 102) did not adhere to 1 or more required practices and 62% (n = 74) did not adhere to 2 or more required practices. An estimated 925 (95% CI, 852-998) NIS publications did not adhere to 1 or more required practices and 696 (95% CI, 596-796) NIS publications did not adhere to 2 or more required practices. A total of 79 sampled studies (68.3% [95% CI, 59.3%-77.3%]) among the 1082 NIS studies screened for eligibility did not account for the effects of sampling error, clustering, and stratification; 62 (54.4% [95% CI, 44.7%-64.0%]) extrapolated nonspecific secondary diagnoses to infer in-hospital events; 45 (40.4% [95% CI, 30.9%-50.0%]) miscategorized hospitalizations as individual patients; 10 (7.1% [95% CI, 2.1%-12.1%]) performed state-level analyses; and 3 (2.9% [95% CI, 0.0%-6.2%]) reported physician-level volume estimates. Of 27 studies (weighted; 218 studies [95% CI, 134-303]) spanning periods of major changes in the data structure of the NIS, 21 (79.7% [95% CI, 62.5%-97.0%]) did not account for the changes. Among the 24 studies published in journals with an impact factor of 10 or greater, 16 (67%) did not adhere to 1 or more practices, and 9 (38%) did not adhere to 2 or more practices. Conclusions and Relevance In this study of 120 recent publications that used data from the NIS, the majority did not adhere to required practices. Further research is needed to identify strategies to improve the quality of research using the NIS and assess whether there are similar problems with use of other publicly available data sets.

Importance The Affordable Care Act has led to US national reductions in hospital 30-day readmission rates for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. Whether readmission reductions have had the unintended consequence of increasing mortality after hospitalization is unknown. Objective To examine the correlation of paired trends in hospital 30-day readmission rates and hospital 30-day mortality rates after discharge. Design, Setting, and Participants Retrospective study of Medicare fee-for-service beneficiaries aged 65 years or older hospitalized with HF, AMI, or pneumonia from January 1, 2008, through December 31, 2014. Exposure Thirty-day risk-adjusted readmission rate (RARR). Main Outcomes and Measures Thirty-day RARRs and 30-day risk-adjusted mortality rates (RAMRs) after discharge were calculated for each condition in each month at each hospital in 2008 through 2014. Monthly trends in each hospital’s 30-day RARRs and 30-day RAMRs after discharge were examined for each condition. The weighted Pearson correlation coefficient was calculated for hospitals’ paired monthly trends in 30-day RARRs and 30-day RAMRs after discharge for each condition. Results In 2008 through 2014, 2 962 554 hospitalizations for HF, 1 229 939 for AMI, and 2 544 530 for pneumonia were identified at 5016, 4772, and 5057 hospitals, respectively. In January 2008, mean hospital 30-day RARRs and 30-day RAMRs after discharge were 24.6% and 8.4% for HF, 19.3% and 7.6% for AMI, and 18.3% and 8.5% for pneumonia. Hospital 30-day RARRs declined in the aggregate across hospitals from 2008 through 2014; monthly changes in RARRs were −0.053% (95% CI, −0.055% to −0.051%) for HF, −0.044% (95% CI, −0.047% to −0.041%) for AMI, and −0.033% (95% CI, −0.035% to −0.031%) for pneumonia. In contrast, monthly aggregate changes across hospitals in hospital 30-day RAMRs after discharge varied by condition: HF, 0.008% (95% CI, 0.007% to 0.010%); AMI, −0.003% (95% CI, −0.005% to −0.001%); and pneumonia, 0.001% (95% CI, −0.001% to 0.003%). However, correlation coefficients in hospitals’ paired monthly changes in 30-day RARRs and 30-day RAMRs after discharge were weakly positive: HF, 0.066 (95% CI, 0.036 to 0.096); AMI, 0.067 (95% CI, 0.027 to 0.106); and pneumonia, 0.108 (95% CI, 0.079 to 0.137). Findings were similar in secondary analyses, including with alternate definitions of hospital mortality. Conclusions and Relevance Among Medicare fee-for-service beneficiaries hospitalized for heart failure, acute myocardial infarction, or pneumonia, reductions in hospital 30-day readmission rates were weakly but significantly correlated with reductions in hospital 30-day mortality rates after discharge. These findings do not support increasing postdischarge mortality related to reducing hospital readmissions.

Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.

Importance The Centers for Medicare & Medicaid Services publicly reports hospital 30-day, all-cause, risk-standardized mortality rates (RSMRs) and 30-day, all-cause, risk-standardized readmission rates (RSRRs) for acute myocardial infarction, heart failure, and pneumonia. The evaluation of hospital performance as measured by RSMRs and RSRRs has not been well characterized. Objective To determine the relationship between hospital RSMRs and RSRRs overall and within subgroups defined by hospital characteristics. Design, Setting, and Participants We studied Medicare fee-for-service beneficiaries discharged with acute myocardial infarction, heart failure, or pneumonia between July 1, 2005, and June 30, 2008 (4506 hospitals for acute myocardial infarction, 4767 hospitals for heart failure, and 4811 hospitals for pneumonia). We quantified the correlation between hospital RSMRs and RSRRs using weighted linear correlation; evaluated correlations in groups defined by hospital characteristics; and determined the proportion of hospitals with better and worse performance on both measures. Main Outcome Measures Hospital 30-day RSMRs and RSRRs. Results Mean RSMRs and RSRRs, respectively, were 16.60% and 19.94% for acute myocardial infarction, 11.17% and 24.56% for heart failure, and 11.64% and 18.22% for pneumonia. The correlations between RSMRs and RSRRs were 0.03 (95% CI, −0.002 to 0.06) for acute myocardial infarction, −0.17 (95% CI, −0.20 to −0.14) for heart failure, and 0.002 (95% CI, −0.03 to 0.03) for pneumonia. The results were similar for subgroups defined by hospital characteristics. Although there was a significant negative linear relationship between RSMRs and RSRRs for heart failure, the shared variance between them was only 2.9% (r 2 = 0.029), with the correlation most prominent for hospitals with RSMR Conclusion and Relevance Risk-standardized mortality rates and readmission rates were not associated for patients admitted with an acute myocardial infarction or pneumonia and were only weakly associated, within a certain range, for patients admitted with heart failure.

Importance Little contemporary information is available about comparative performance between Veterans Affairs (VA) and non-VA hospitals, particularly related to mortality and readmission rates, 2 important outcomes of care. Objective To assess and compare mortality and readmission rates among men in VA and non-VA hospitals. Design, Setting, and Participants Cross-sectional analysis involving male Medicare fee-for-service beneficiaries aged 65 years or older hospitalized between 2010 and 2013 in VA and non-VA acute care hospitals for acute myocardial infarction (AMI), heart failure (HF), or pneumonia using the Medicare Standard Analytic Files and Enrollment Database together with VA administrative claims data. To avoid confounding geographic effects with health care system effects, we studied VA and non-VA hospitals within the same metropolitan statistical area (MSA). Exposures Hospitalization in a VA or non-VA hospital in MSAs that contained at least 1 VA and non-VA hospital. Main Outcomes and Measures For each condition, 30-day risk-standardized mortality rates and risk-standardized readmission rates for VA and non-VA hospitals. Mean aggregated within-MSA differences in mortality and readmission rates were also assessed. Results We studied 104 VA and 1513 non-VA hospitals, with each condition-outcome analysis cohort for VA and non-VA hospitals containing at least 7900 patients (men; ≥65 years), in 92 MSAs. Mortality rates were lower in VA hospitals than non-VA hospitals for AMI (13.5% vs 13.7%, P = .02; −0.2 percentage-point difference) and HF (11.4% vs 11.9%, P = .008; −0.5 percentage-point difference), but higher for pneumonia (12.6% vs 12.2%, P = .045; 0.4 percentage-point difference). In contrast, readmission rates were higher in VA hospitals for all 3 conditions (AMI, 17.8% vs 17.2%, 0.6 percentage-point difference; HF, 24.7% vs 23.5%, 1.2 percentage-point difference; pneumonia, 19.4% vs 18.7%, 0.7 percentage-point difference, all P Conclusions and Relevance Among older men with AMI, HF, or pneumonia, hospitalization at VA hospitals, compared with hospitalization at non-VA hospitals, was associated with lower 30-day risk-standardized all-cause mortality rates for AMI and HF, and higher 30-day risk-standardized all-cause readmission rates for all 3 conditions, both nationally and within similar geographic areas, although absolute differences between these outcomes at VA and non-VA hospitals were small.

Although the efficacy of carotid stenting has been established in clinical trials, outcomes of the procedure based on operator experience are less certain in clinical practice.To assess association between outcomes and 2 measures of operator experience: annual volume and experience at the time of the procedure among new operators who first performed carotid stenting after a national coverage decision by the Centers for MedicareMedicaid Services (CMS).Observational study using administrative data on fee-for-service Medicare beneficiaries aged 65 years or older undergoing carotid stenting between 2005 and 2007.Thirty-day mortality stratified by very low, low, medium, and high annual operator volumes (6, 6-11, 12-23, and ≥24 procedures per year, respectively) and treatment early vs late during a new operator's experience (1st to 11th procedure and 12th procedure or higher).During the study period, 24,701 procedures were performed by 2339 operators. Of these, 11,846 were performed by 1792 new operators who first performed carotid stenting after the CMS national coverage decision. Overall, 30-day mortality was 1.9% (n = 461) and rate of failure to use an embolic protection device was 4.8% (n = 1173). The median annual operator volume among Medicare beneficiaries was 3.0 per year (interquartile range, 1.4-6.5) and 11.6% of operators performed 12 or more procedures per year during the study period. Observed 30-day mortality was higher among patients treated by operators with lower annual volumes (2.5% [95% CI, 2.1%-2.9%], 1.9% [95% CI, 1.6%-2.3%], 1.6% [95% CI, 1.3%-1.9%], and 1.4% [95% CI, 1.1%-1.7%] across the 4 categories; P.001) and among patients treated early (2.3%; 95% CI, 2.0%-2.7%) vs late (1.4%; 95% CI, 1.1%-1.9%; P.001) during a new operator's experience. After multivariable adjustment, patients treated by very low-volume operators had a higher risk of 30-day mortality compared with patients treated by high-volume operators (adjusted odds ratio, 1.9; 95% CI, 1.4-2.7; P.001). Similarly, we found a higher risk of 30-day mortality in patients treated early vs late during a new operator's experience (adjusted odds ratio, 1.7; 95% CI, 1.2-2.4; P = .001).Among older patients undergoing carotid stenting, lower annual operator volume and early experience are associated with increased 30-day mortality.

Interest in the role of fibrates intensified after the publication of the negative results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which assessed therapy with fenofibrate plus statins. The evidence for clinical benefit in outcomes with the use of fibrates is heavily weighted on the use of the older fibrates such as gemfibrozil and clofibrate.To examine trends in the current use of fibrates and to examine the relationship between differences in the availability and use of brand-name vs generic formulations of fenofibrate and the economic implications in the United States compared with Canada.Population-level, observational cohort study using IMS Health data from the United States and Canada of patients prescribed fibrates between January 2002 and December 2009.Fibrate prescriptions dispensed and expenditures.In the United States, fibrate prescriptions dispensed increased from 336 prescriptions/100,000 population in January 2002 to 730 prescriptions/100,000 population in December 2009, an increase of 117.1% (95% confidence interval [CI], 116.0%-117.9%), whereas in Canada, fibrate prescriptions increased from 402 prescriptions/100,000 population in January 2002 to 474 prescriptions/100,000 population in December 2009, an increase of 18.1% (95% CI, 17.9%-18.3%) (P.001). In the United States, fenofibrate prescriptions dispensed increased from 150 prescriptions/100,000 population in January 2002 to 440 prescriptions/100,000 population in December 2009, an increase of 159.3% (95% CI, 157.7%-161.0%), comprising 47.9% of total fibrate prescriptions in 2002 and 65.2% in 2009. In Canada, fenofibrate prescriptions increased from 321 prescriptions/100,000 population in January 2002 to 429 prescriptions/100,000 population in December 2009. The annual ratio of generic to brand-name fenofibrate use in the United States ranged from 0:1 to 0.09:1 between 2002 and 2008, while the ratio in Canada steadily increased from 0.51:1 to 1.89:1 between 2005 and 2008. In the United States, crude fenofibrate expenditures increased from $11,535/100,000 population/month in 2002 to $44,975/100,000 population/month in 2009, while the rates in Canada declined from $17,695/100,000 population/month in 2002 to $16,112/100,000 population/month in 2009. Fibrate expenditures per 100,000 population were 3-fold higher in 2009 in the United States compared with Canada.During the past decade, prescriptions for fibrates (particularly fenofibrate) increased in the United States, while prescriptions for fibrates in Canada remained stable.

Automated external defibrillators (AEDs) improve survival from out-of-hospital cardiac arrests, but data on their effectiveness in hospitalized patients are limited.To evaluate the association between AED use and survival for in-hospital cardiac arrest.Cohort study of 11,695 hospitalized patients with cardiac arrests between January 1, 2000, and August 26, 2008, at 204 US hospitals following the introduction of AEDs on general hospital wards.Survival to hospital discharge by AED use, using multivariable hierarchical regression analyses to adjust for patient factors and hospital site.Of 11,695 patients, 9616 (82.2%) had nonshockable rhythms (asystole and pulseless electrical activity) and 2079 (17.8%) had shockable rhythms (ventricular fibrillation and pulseless ventricular tachycardia). AEDs were used in 4515 patients (38.6%). Overall, 2117 patients (18.1%) survived to hospital discharge. Within the entire study population, AED use was associated with a lower rate of survival after in-hospital cardiac arrest compared with no AED use (16.3% vs 19.3%; adjusted rate ratio [RR], 0.85; 95% confidence interval [CI], 0.78-0.92; P.001). Among cardiac arrests due to nonshockable rhythms, AED use was associated with lower survival (10.4% vs 15.4%; adjusted RR, 0.74; 95% CI, 0.65-0.83; P.001). In contrast, for cardiac arrests due to shockable rhythms, AED use was not associated with survival (38.4% vs 39.8%; adjusted RR, 1.00; 95% CI, 0.88-1.13; P = .99). These patterns were consistently observed in both monitored and nonmonitored hospital units where AEDs were used, after matching patients to the individual units in each hospital where the cardiac arrest occurred, and with a propensity score analysis.Among hospitalized patients with cardiac arrest, use of AEDs was not associated with improved survival.

AD HOC IS A LATIN PHRASE, LITERALLY MEANING “FOR this.” It typically implies a solution designed for a particular problem or task—that is, something not broadly generalizable. When the term was introduced more than 2 decades ago to cardiologists in the context of percutaneous coronary intervention (PCI), it suggested the unique circumstances that justified combining coronary angiography and PCI into the same setting. This approach was uncommon in the early years of PCI when most procedures were performed days to weeks after the initial diagnostic test. Initially, the hesitation to perform ad hoc PCI resulted from technical challenges. Older imaging systems limited the ability of cardiologists to rapidly and accurately review angiograms. In addition, operating rooms and cardiac surgeons had to be on stand-by whenever PCI was performed because of the threat of acute closure of the coronary artery and other life-threatening complications. Over the years, these issues have largely been resolved, however, by advances in imaging systems and procedural techniques, such as the introduction of coronary stents. As a result, ad hoc PCI is now routinely performed, and its use has increased considerably in recent years. In New York state, for example, more than 80% of PCIs are currently performed ad hoc and, in many cases, this makes perfect sense. During acute coronary syndromes, including STelevation myocardial infarction, the ability to perform PCI immediately after coronary angiography saves lives and improves outcomes. In elective cases, ad hoc PCI avoids the cost and inconvenience associated with a second procedure and arterial puncture. Yet now that it is clear that ad hoc PCI can be performed, a more fundamental question arises: Should it? Recent clinical trials, such as COURAGE and SYNTAX, have fueled concerns about the widespread use of PCI. For many patients with stable coronary disease, PCI does not improve survival when compared with optimal medical therapy. For patients with more severe disease for whom coronary artery bypass grafting is considered, PCI does as well as surgery for 1-year survival, but leads to more repeat procedures and the need for prolonged antiplatelet medications. Although findings from these trials are largely undisputed, the use of ad hoc PCI raises challenges for incorporating their lessons into routine practice. Specifically, ad hoc PCI provides less opportunity for patients and their physicians to thoughtfully consider a range of clinically equivalent treatment options after the coronary anatomy is known. By making the diagnostic test an automatic gateway to the therapeutic procedure, pressure is placed on the cardiologist and patient to make immediate decisions that may favor PCI even in elective settings. In one study, for instance, patients with stronger indications for coronary artery bypass grafting were more likely to be recommended surgery after coronary angiography when it was performed at hospitals without the ability to perform ad hoc PCI. At the other extreme are ongoing concerns about how frequently PCI is performed when medical therapy appears suitable. Part of this results from the well-described “oculo-stenotic” reflex, ie, the tendency to treat blockages, even when clinically silent, based on benefits attributed to PCI that are not supported by the literature. There are other issues to consider as well. In their seminal article, Myler and colleagues highlighted 2 specific challenges with ad hoc PCI. First, they noted that obtaining adequate informed consent for ad hoc PCI may be difficult. Patients typically receive conscious sedation during coronary angiography, prompting most centers to adopt an approach in which risks of PCI are simultaneously discussed before the coronary anatomy is known. However, risks of PCI differ substantially from the diagnostic test and may vary from patient to patient based on lesion characteristics and location. A generic consent obtained prior to coronary angiography fails to capture these subtleties. In addition, Myler et al pointed out possible concerns about the ethics of self-referral. At its core, this issue highlights the potential hazards of merging diagnostic tests (ie, coronary angiography) and therapeutic procedures (ie, PCI) into the same setting. If the cardiologist who performs and interprets the coronary angiogram will also perform the PCI

Whether decreases in the length of stay during the past decade for patients with heart failure (HF) may be associated with changes in outcomes is unknown.To describe the temporal changes in length of stay, discharge disposition, and short-term outcomes among older patients hospitalized for HF.An observational study of 6,955,461 Medicare fee-for-service hospitalizations for HF between 1993 and 2006, with a 30-day follow-up.Length of hospital stay, in-patient and 30-day mortality, and 30-day readmission rates.Between 1993 and 2006, mean length of stay decreased from 8.81 days (95% confidence interval [CI], 8.79-8.83 days) to 6.33 days (95% CI, 6.32-6.34 days). In-hospital mortality decreased from 8.5% (95% CI, 8.4%-8.6%) in 1993 to 4.3% (95% CI, 4.2%-4.4%) in 2006, whereas 30-day mortality decreased from 12.8% (95% CI, 12.8%-12.9%) to 10.7% (95% CI, 10.7%-10.8%). Discharges to home or under home care service decreased from 74.0% to 66.9% and discharges to skilled nursing facilities increased from 13.0% to 19.9%. Thirty-day readmission rates increased from 17.2% (95% CI, 17.1%-17.3%) to 20.1% (95% CI, 20.0%-20.2%; all P.001). Consistent with the unadjusted analyses, the 2005-2006 risk-adjusted 30-day mortality risk ratio was 0.92 (95% CI, 0.91-0.93) compared with 1993-1994, and the 30-day readmission risk ratio was 1.11 (95% CI, 1.10-1.11).For patients admitted with HF during the past 14 years, reductions in length of stay and in-hospital mortality, less marked reductions in 30-day mortality, and changes in discharge disposition accompanied by increases in 30-day readmission rates were observed.

Little is known about how health insurance status affects decisions to seek care during emergency medical conditions such as acute myocardial infarction (AMI).To examine the association between lack of health insurance and financial concerns about accessing care among those with health insurance, and the time from symptom onset to hospital presentation (prehospital delays) during AMI.Multicenter, prospective study using a registry of 3721 AMI patients enrolled between April 11, 2005, and December 31, 2008, at 24 US hospitals. Health insurance status was categorized as insured without financial concerns, insured but have financial concerns about accessing care, and uninsured. Insurance information was determined from medical records while financial concerns among those with health insurance were determined from structured interviews.Prehospital delay times (or = 2 hours,2-6 hours, or6 hours), adjusted for demographic, clinical, and social and psychological factors using hierarchical ordinal regression models.Of 3721 patients, 2294 were insured without financial concerns (61.7%), 689 were insured but had financial concerns about accessing care (18.5%), and 738 were uninsured (19.8%). Uninsured and insured patients with financial concerns were more likely to delay seeking care during AMI and had prehospital delays of greater than 6 hours among 48.6% of uninsured patients and 44.6% of insured patients with financial concerns compared with only 39.3% of insured patients without financial concerns. Prehospital delays of less than 2 hours during AMI occurred among 36.6% of those insured without financial concerns compared with 33.5% of insured patients with financial concerns and 27.5% of uninsured patients (P.001). After adjusting for potential confounders, prehospital delays were associated with insured patients with financial concerns (adjusted odds ratio, 1.21 [95% confidence interval, 1.05-1.41]; P = .01) and with uninsured patients (adjusted odds ratio, 1.38 [95% confidence interval, 1.17-1.63]; P.001).Lack of health insurance and financial concerns about accessing care among those with health insurance were each associated with delays in seeking emergency care for AMI.

While glucose control is recommended by professional societies for patients with hyperglycemia hospitalized with acute myocardial infarction (AMI), enthusiasm for glucose lowering is tempered, in part, by concerns of inducing hypoglycemia. Yet, whether episodic hypoglycemia that occurs as a result of glucose-lowering therapy is harmful in patients with AMI is unknown.To determine whether the mortality risk associated with hypoglycemic events is similar in patients who develop hypoglycemia spontaneously and those who develop it as a result of insulin therapy.Retrospective cohort study using data from Health Facts, a contemporary database of patients hospitalized across the United States in 40 hospitals between January 1, 2000, and December 31, 2005. Of all the patients in the database, 7820 patients were hospitalized with AMI and were hyperglycemic on admission (glucose levelor = 140 mg/dL). Patients were stratified based on whether they developed a hypoglycemic event (random glucose level60 mg/dL) during subsequent hospitalization. Logistic regression models were used to evaluate the association between hypoglycemia and in-hospital mortality within subgroups of patients who were and were not treated with insulin therapy.All-cause in-hospital mortality.Among patients treated or not treated with insulin, those with hypoglycemia were older and had more comorbidity. Hypoglycemia was associated with increased mortality in patients not treated with insulin (18.4% [25/136] mortality in patients with hypoglycemia vs 9.2% [425/4639] in those without hypoglycemia; P.001), but not in those treated with insulin (10.4% [36/346] mortality in patients with hypoglycemia vs 10.2% [276/2699] in those without hypoglycemia; P = .92). After multivariable adjustment, there was a significant interaction between hypoglycemia and insulin therapy (P value for interaction = .01). Hypoglycemia was a predictor of higher mortality in patients who were not treated with insulin (odds ratio, 2.32 [95% confidence interval, 1.31-4.12] vs patients without hypoglycemia), but not in patients treated with insulin (odds ratio, 0.92 [95% confidence interval, 0.58-1.45] vs patients without hypoglycemia).While hypoglycemia was associated with increased mortality in patients with AMI, this risk was confined to patients who developed hypoglycemia spontaneously. In contrast, iatrogenic hypoglycemia after insulin therapy was not associated with higher mortality risk.

Context Authorship in biomedical publication provides recognition and establishes accountability and responsibility. Recent litigation related to rofecoxib provided a unique opportunity to examine guest authorship and ghostwriting, practices that have been suspected in biomedical publication but for which there is little documentation. Objective To characterize different types and the extent of guest authorship and ghostwriting in 1 case study. Data Sources Court documents originally obtained during litigation related to rofecoxib against Merck & Co Inc. Documents were created predominantly between 1996 and 2004. In addition, publicly available articles related to rofecoxib identified via MEDLINE. Data Extraction All documents were reviewed by one author, with selected review by coauthors, using an iterative process of review, discussion, and rereview of documents to identify information related to guest authorship or ghostwriting. Data Synthesis Approximately 250 documents were relevant to our review. For the publication of clinical trials, documents were found describing Merck employees working either independently or in collaboration with medical publishing companies to prepare manuscripts and subsequently recruiting external, academically affiliated investigators to be authors. Recruited authors were frequently placed in the first and second positions of the authorship list. For the publication of scientific review papers, documents were found describing Merck marketing employees developing plans for manuscripts, contracting with medical publishing companies to ghostwrite manuscripts, and recruiting external, academically affiliated investigators to be authors. Recruited authors were commonly the sole author on the manuscript and offered honoraria for their participation. Among 96 relevant published articles, we found that 92% (22 of 24) of clinical trial articles published a disclosure of Merck's financial support, but only 50% (36 of 72) of review articles published either a disclosure of Merck sponsorship or a disclosure of whether the author had received any financial compensation from the company. Conclusions This case-study review of industry documents demonstrates that clinical trial manuscripts related to rofecoxib were authored by sponsor employees but often attributed first authorship to academically affiliated investigators who did not always disclose industry financial support. Review manuscripts were often prepared by unacknowledged authors and subsequently attributed authorship to academically affiliated investigators who often did not disclose industry financial support.

ContextGiven the numerous, yet inconsistent, reports of genetic variants being associated with acute coronary syndromes (ACS), there is a need for comprehensive validation of ACS susceptibility genotypes.ObjectiveTo perform an extensive validation of putative genetic risk factors for ACS.Design, Setting, and ParticipantsThrough a systematic literature search of articles published before March 10, 2005, we identified genetic variants previously reported as significant susceptibility factors for atherosclerosis or ACS. Restricting our analysis to white patients to reduce confounding from racial admixture, we identifed 811 patients who presented from March 2001 through June 2003 with ACS at 2 Kansas City, Mo, university-affiliated hospitals. During 2005-2006, we genotyped the 811 patients along with 650 age- and sex-matched controls for 85 variants in 70 genes and attempted to replicate previously reported associations. We further explored possible associations without prior assumption of specific risk models and used the Sign test to search for weak associations.Main Outcome MeasuresCompare each prespecified gene variant associated with ACS risk among cases and controls. A surplus of associations would imply that some are associated with ACS.ResultsOf 85 variants tested, only 1 putative risk genotype (−455 promoter variant in β-fibrinogen) was nominally statistically significant (P = .03). Only 4 additional genes were positive in model-free analysis. Neither number of associations was more frequent than expected by chance, given the number of comparisons. Finally, only 41 of 84 predefined risk variants were even marginally more frequent in cases than in controls (with 1 tie), representing a 48.8% “win rate” (95% confidence interval, 38.1%-59.5%) for the collective risk genotypes (P = .91, Sign test).ConclusionsOur null results provide no support for the hypothesis that any of the 85 genetic variants tested is a susceptibility factor for ACS. These results emphasize the need for robust replication of putative genetic risk factors before their introduction into clinical care.

Importance The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. Objective To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. Design and Setting All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. Main Outcomes and Measures Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. Results In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0-24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. Conclusions and Relevance Among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval.

ContextMedicare's reimbursement policy was changed in 1998 to provide coverage for screening colonoscopies for patients with increased colon cancer risk, and expanded further in 2001 to cover screening colonoscopies for all individuals.ObjectiveTo determine whether the Medicare reimbursement policy changes were associated with an increase in either colonoscopy use or early stage colon cancer diagnosis.Design, Setting, and ParticipantsPatients in the Surveillance, Epidemiology, and End Results Medicare linked database who were 67 years of age and older and had a primary diagnosis of colon cancer during 1992-2002, as well as a group of Medicare beneficiaries who resided in Surveillance, Epidemiology, and End Results areas but who were not diagnosed with cancer.Main Outcome MeasuresTrends in colonoscopy and sigmoidoscopy use among Medicare beneficiaries without cancer were assessed using multivariate Poisson regression. Among the patients with cancer, stage was classified as early (stage I) vs all other (stages II-IV). Time was categorized as period 1 (no screening coverage, 1992-1997), period 2 (limited coverage, January 1998-June 2001), and period 3 (universal coverage, July 2001-December 2002). A multivariate logistic regression (outcome = early stage) was used to assess temporal trends in stage at diagnosis; an interaction term between tumor site and time was included.ResultsColonoscopy use increased from an average rate of 285/100 000 per quarter in period 1 to 889 and 1919/100 000 per quarter in periods 2 (P