Risk of Biologics and Glucocorticoids in Patients With Rheumatoid Arthritis Undergoing Arthroplasty: A Cohort Study: Annals of Internal Medicine: Vol 170, No 12

Background: Patients with rheumatoid arthritis (RA) are at increased risk for infection after arthroplasty, yet risks of specific biologic medications are unknown. Objective: To compare risk for postoperative infection among biologics and to evaluate the risk associated with glucocorticoids. Design: Retrospective cohort study. Setting: Medicare and Truven MarketScan administrative data from January 2006 through September 2015. Patients: Adults with RA who were having elective inpatient total knee or hip arthroplasty, either primary or revision, and had a recent infusion of or prescription for abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery. Measurements: Propensity-adjusted analyses using inverse probability weights evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non–urinary tract hospitalized infections and 30-day readmissions. Results: Among 9911 patients treated with biologics, 10 923 surgical procedures were identified. Outcomes were similar in patients who received different biologics. Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk from propensity-weighted models ranged from 6.87% (95% CI, 5.30% to 8.90%) with adalimumab to 8.90% (CI, 5.70% to 13.52%) with rituximab. Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (CI, 0.11% to 1.12%) with rituximab to 3.67% (CI, 1.69% to 7.88%) with tocilizumab. Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes. Propensity-weighted models showed that use of more than 10 mg of glucocorticoids per day (vs. no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (CI, 9.72% to 17.81%) (vs. 6.78%) and a predicted 1-year cumulative incidence of PJI of 3.83% (CI, 2.13% to 6.87%) (vs. 2.09%). Limitation: Residual confounding is possible, and sample sizes for rituximab and tocilizumab were small. Conclusion: Risks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes. Primary Funding Source: Rheumatology Research Foundation, National Institutes of Health, and Bristol-Myers Squibb.

Limitations and Misinterpretations of E-Values for Sensitivity Analyses of Observational Studies

The E-value was recently introduced on the basis of earlier work as “the minimum strength of association…that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment–outcome association, conditional on the measured covariates.” E-values have been proposed for wide application in observational studies evaluating causality. However, they have limitations and are prone to misinterpretation. E-values have a monotonic, almost linear relationship with effect estimates and thus offer no additional information beyond what effect estimates can convey. Whereas effect estimates are based on real data, E-values may make unrealistic assumptions. No general rule can exist about what is a “small enough” E-value, and users of the biomedical literature are not familiar with how to interpret a range of E-values. Problems arise for any measure dependent on effect estimates and their CIs—for example, bias due to selective reporting and dependence on choice of exposure contrast and level of confidence. The automation of E-values may give an excuse not to think seriously about confounding. Moreover, biases other than confounding may still undermine results. Instead of misused or misinterpreted E-values, the authors recommend judicious use of existing methods for sensitivity analyses with careful assumptions; systematic assessments of whether and how known confounders have been handled, along with consideration of their prevalence and magnitude; thorough discussion of the potential for unknown confounders considering the study design and field of application; and explicit caution in making causal claims from observational studies.

U.S. Internists' Perspectives on Discussing Cost of Care With Patients: Structured Interviews and a Survey

Background: Rising out-of-pocket costs are creating a need for cost conversations between patients and physicians. Objective: To understand the factors that influence physicians to discuss and consider cost during a patient encounter. Design: Mixed-methods study using semistructured interviews and a survey. Setting: United States. Participants: 20 internal medicine physicians were interviewed; 621 internal medicine physician members of the American College of Physicians completed the survey. Measurements: Interviews were analyzed by using thematic analysis, and surveys were analyzed by using descriptive statistics. Results: From the interviews, 4 themes were identified: Physicians are 1) aware that patients are struggling to afford medical care; 2) relying on clues from patients that hint at their cost sensitivity; 3) relying on experience to anticipate potentially high-cost treatments; and 4) aware that patients are making financial trade-offs to afford their care. Three quarters (n = 466) of survey respondents stated that they consider out-of-pocket costs when making most clinical decisions. For 31% (n = 191) of participants, there were times in the past year that they wanted to discuss out-of-pocket prescription drug costs with patients but did not. The most influential factors for ordering a test are the desire to be as thorough as possible (71% [n = 422]) and insurance coverage for the test (68% [n = 422]). Limitation: Findings are self-reported, the sample is limited to a single specialty, the survey response rate was low, information on the patient population was limited, and the survey instrument is not validated. Conclusion: Physicians are attuned to the burden of health care costs and are willing to consider alternative options based on a patient's cost sensitivity. Primary Funding Source: Robert Wood Johnson Foundation.

Antiphospholipid Antibodies in Patients With Myocardial Infarction

Prevention Is Better Than Cure: The Next Frontier for Bariatric Surgery?

Addressing Medication Costs During Primary Care Visits: A Before–After Study of Team-Based Training

Background: Medications contribute to patients' out-of-pocket costs, yet most clinicians do not routinely screen for patients' cost-of-medication (COM) concerns. Objective: To assess whether a single training session improves COM conversations. Design: Before–after cross-sectional surveys of patients and qualitative interviews with clinicians and staff. Setting: 7 primary care practices in 3 U.S. states. Participants: In total, 700 patients were surveyed from May 2017 to January 2018: 50 patients per practice before the intervention and another 50 patients per practice after the intervention. Eligibility criteria included age 18 years or older and taking 1 or more long-term medications. Qualitative interviews with 45 staff members were conducted. Intervention: A single 60-minute training session for clinicians and staff from each practice on COM importance, team-based screening, and cost-saving strategies. Measurements: Patient data (demographics, number of long-term medications, total monthly out-of-pocket medication costs, and history of cost-related medication nonadherence) were obtained immediately before and 3 months after the intervention. Practice staff were interviewed 3 months after the intervention. Results: A total of 700 patient surveys were completed. Frequency of COM discussion improved in 6 of the 7 practices and remained unchanged in 1 practice. Overall, COM conversations with patients increased from 17% at baseline to 32% postintervention (P = 0.00). There was substantial heterogeneity among sites in before–after differences in patient-reported out-of-pocket COM. Qualitative analyses from key informant interviews showed wide variation in implementation of screening approaches, workflow, adoption of a team-based approach, and strategies for addressing COM. Limitation: It is not known whether improvements in COM conversations were sustained beyond 3 months. Conclusion: A single team training to screen and address patients' medication cost concerns improved COM discussions over the short term. Further research is needed to assess sustained effects and impact on patient costs and medication adherence and to determine whether more intensive, scalable interventions are needed. Primary Funding Source: Robert Wood Johnson Foundation.

External Validation of the MEESSI Acute Heart Failure Risk Score: A Cohort Study: Annals of Internal Medicine: Vol 170, No 4

Background: The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain. Whether it performs well in other countries is unknown. Objective: To externally validate the MEESSI-AHF score in another country. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01831115). Setting: Multicenter recruitment of dyspneic patients presenting to the ED. Participants: The external validation cohort included 1572 patients with AHF. Measurements: Calculation of the MEESSI-AHF score using an established model containing 12 independent risk factors. Results: Among 1572 patients with adjudicated AHF, 1247 had complete data that allowed calculation of the MEESSI-AHF score. Of these, 102 (8.2%) died within 30 days. The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 [28.5%] in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients. Limitations: External validation was done using a reduced model. Findings are specific to patients with AHF who present to the ED and are clinically stable enough to provide informed consent. Performance in patients with terminal kidney failure who are receiving long-term dialysis cannot be commented on. Conclusion: External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations. Primary Funding Source: The European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, and University Hospital Basel.

Characteristics of High Cardiovascular Risk in 1.7 Million Chinese Adults

Background: As cardiovascular risk increases in China, interest in strategies to mitigate it is growing. However, national information about the prevalence and treatment of high cardiovascular disease (CVD) risk is limited. Objective: To assess the prevalence and treatment of high CVD risk as well as variations in risk across population subgroups. Design: National project of CVD screening and management. Setting: 141 county-level regions in all 31 provinces of China. Participants: Local residents aged 35 to 75 years. Measurements: Rates of high CVD risk were assessed both in the overall study population and by age, sex, body mass index, geographic region, and socioeconomic status. Multivariable mixed models were fitted to assess the associations between individual characteristics and high CVD risk. Statin and aspirin use was evaluated among persons at high risk for CVD. Results: Among 1 680 126 participants, 9.5% (95% CI, 9.5% to 9.6%) had high risk for CVD. Mixed models identified persons who were of Han ethnicity, had medical insurance, were currently using alcohol, or were obese as more likely to be at high risk for CVD. Of those with high CVD risk, only 0.6% (CI, 0.5% to 0.6%) and 2.4% (CI, 2.3% to 2.5%) reported using statins and aspirin, respectively. Among persons with high CVD risk and hypertension, 31.8% were receiving antihypertensive medications. Limitation: Samples were not nationally representative. Conclusion: Of the 1.7 million participants, 1 in 10 had a high risk for CVD; among those at high risk, fewer than 3% were receiving statins or aspirin. An immense opportunity exists for risk mitigation in this substantial population. Primary Funding Source: Ministry of Finance and National Health Commission, China.

Fitness and Body Mass Index During Adolescence and Disability Later in Life: A Cohort Study: Annals of Internal Medicine: Vol 170, No 4

Background: Low physical fitness, obesity, and the combination of the two in adolescence may be related to risk for disability in adulthood, but this has rarely been studied. Objective: To examine individual and combined associations of cardiorespiratory fitness and obesity in male adolescents with later receipt of a disability pension due to all and specific causes. Design: Population-based cohort study. Setting: Sweden. Participants: 1 079 128 Swedish adolescents aged 16 to 19 years who were conscripted into the military between 1972 and 1994. Measurements: Cardiorespiratory fitness and body mass index (BMI) were measured at conscription and were related to information on later receipt of a disability pension obtained from the Social Insurance Agency. Results: Over a median follow-up of 28.3 years, 54 304 men were granted a disability pension. Low cardiorespiratory fitness was strongly associated with later receipt of a disability pension due to all causes (hazard ratio, 3.74 [95% CI, 3.55 to 3.95] for lowest vs. highest fitness decile) and specific causes (psychiatric, musculoskeletal, injuries, nervous system, circulatory, and tumors). Obesity was associated with greater risk for receipt of a disability pension due to all and specific causes, with the greatest risks observed for class II and III obesity. Compared with being unfit, being moderately or highly fit was associated with attenuated risk for receipt of a disability pension across BMI categories. Limitation: The cohort did not include women, had data on smoking and alcohol intake only in a subsample, and lacked repeated measures of exposures and covariates. Conclusion: Low cardiorespiratory fitness, obesity, and the combination of the two were strongly associated with later chronic disability due to a wide range of diseases and causes. Although additional well-designed studies are required, these findings support the importance of high cardiorespiratory fitness and healthy body weight during adolescence to prevent later chronic disease. Primary Funding Source: Karolinska Institutet.

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