Testing for Primary Aldosteronism and Mineralocorticoid Receptor Antagonist Use Among U.S. Veterans: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 174, No 3

Background: Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism. Objective: To evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension. Design: Retrospective cohort study. Setting: U.S. Veterans Health Administration. Participants: Veterans with apparent treatment-resistant hypertension (n = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes. Measurements: Rates of primary aldosteronism testing (plasma aldosterone–renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP. Results: 4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time. Limitations: Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism. Conclusion: In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension. Primary Funding Source: National Institutes of Health.

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m2 or Greater: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 174, No 6

Background: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population. Objective: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis. Design: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater. Data Sources: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data. Target Population: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Total knee replacement. Outcome Measures: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. Results of Base-Case Analysis: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100. Results of Sensitivity Analysis: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively. Limitation: Data are derived from several sources. Conclusion: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Interventions to Improve Statin Tolerance and Adherence in Patients at Risk for Cardiovascular Disease: A Systematic Review for the 2020 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Dyslipidemia: Annals of Internal Medicine: Vol 173, No 10

Background: Strategies to improve patients' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD). Purpose: To assess the benefits and harms of interventions to improve statin adherence in patients at risk for CVD. Data Sources: MEDLINE, EMBASE, PubMed, and the Cochrane Library from December 2013 through May 2019 (English language only). Study Selection: Systematic reviews (SRs), randomized controlled trials (RCTs), and cohort studies that addressed interventions for improving statin tolerance and adherence. Data Extraction: One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. Data Synthesis: One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with statin treatment discontinuation, nondaily statin dosing lowered total cholesterol and LDL-C levels. One large cohort study suggested that more than 90% of patients who discontinued statin treatment could be rechallenged with the same or a different statin and be adherent 1 year after a statin-related adverse event led to discontinuation. Two small cohort studies reported that more than 90% of patients who were previously intolerant to statins and who had low baseline levels of vitamin D were able to adhere to statins 1 year after vitamin D supplementation. Limitation: This is a qualitative synthesis of new evidence with existing meta-analyses, and studies had several methodological shortcomings. Conclusion: Although the strength of evidence for most interventions was low or very low, intensified patient care and rechallenge with the same or a different statin (or a lower dose) seem to be favorable options for improving statin adherence. Primary Funding Source: U.S. Department of Veterans Affairs.

Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Description: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. Methods: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Association Between ABO and Rh Blood Groups and SARS-CoV-2 Infection or Severe COVID-19 Illness: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 174, No 3

Background: The ABO and rhesus (Rh) blood groups may influence risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To determine whether ABO and Rh blood groups are associated with risk for SARS-CoV-2 infection and severe coronavirus disease 2019 (COVID-19) illness. Design: Population-based cohort study. Setting: Ontario, Canada. Patients: All adults and children who had ABO blood group assessed between January 2007 and December 2019 and who subsequently had SARS-CoV-2 testing between 15 January and 30 June 2020. Measurements: The main study outcome was SARS-CoV-2 infection, determined by viral RNA polymerase chain reaction testing. A second outcome was severe COVID-19 illness or death. Adjusted relative risks (aRRs) and absolute risk differences (ARDs) were adjusted for demographic characteristics and comorbidities. Results: A total of 225 556 persons were included, with a mean age of 54 years. The aRR of SARS-CoV-2 infection for O blood group versus A, AB, and B blood groups together was 0.88 (95% CI, 0.84 to 0.92; ARD, −3.9 per 1000 [CI, −5.4 to −2.5]). Rhesus-negative (Rh−) blood type was protective against SARS-CoV-2 infection (aRR, 0.79 [CI, 0.73 to 0.85]; ARD, −6.8 per 1000 [CI, −8.9 to −4.7]), especially for those who were O-negative (O−) (aRR, 0.74 [CI, 0.66 to 0.83]; ARD, −8.2 per 1000 [CI, −10.8 to −5.3]). There was also a lower risk for severe COVID-19 illness or death associated with type O blood group versus all others (aRR, 0.87 [CI, 0.78 to 0.97]; ARD, −0.8 per 1000 [CI, −1.4 to −0.2]) and with Rh− versus Rh-positive (aRR, 0.82 [CI, 0.68 to 0.96]; ARD, −1.1 per 1000 [CI, −2.0 to −0.2]). Limitation: Persons who rapidly died of severe COVID-19 illness may not have had SARS-CoV-2 testing. Conclusion: The O and Rh− blood groups may be associated with a slightly lower risk for SARS-CoV-2 infection and severe COVID-19 illness. Primary Funding Source: Ontario Academic Health Sciences Centre AFP Innovation Fund and the Ontario Ministry of Health and Long-Term Care.

Stepped Exercise Program for Patients With Knee Osteoarthritis: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 174, No 3

Background: Evidence-based models are needed to deliver exercise-related services for knee osteoarthritis efficiently and according to patient needs. Objective: To examine a stepped exercise program for patients with knee osteoarthritis (STEP-KOA). Design: Randomized controlled trial. (ClinicalTrials.gov: NCT02653768) Setting: 2 U.S. Department of Veterans Affairs sites. Participants: 345 patients (mean age, 60 years; 15% female; 67% people of color) with symptomatic knee osteoarthritis. Intervention: Participants were randomly assigned in a 2:1 ratio to STEP-KOA or an arthritis education (AE) control group, respectively. The STEP-KOA intervention began with 3 months of an internet-based exercise program (step 1). Participants who did not meet response criteria for improvement in pain and function after step 1 progressed to step 2, which involved 3 months of biweekly physical activity coaching calls. Participants who did not meet response criteria after step 2 went on to in-person physical therapy visits (step 3). The AE group received educational materials via mail every 2 weeks. Measurements: Primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Scores for the STEP-KOA and AE groups at 9 months were compared by using linear mixed models. Results: In the STEP-KOA group, 65% of participants (150 of 230) progressed to step 2 and 35% (81 of 230) to step 3. The estimated baseline WOMAC score for the full sample was 47.5 (95% CI, 45.7 to 49.2). At 9-month follow-up, the estimated mean WOMAC score was 6.8 points (CI, −10.5 to −3.2 points) lower in the STEP-KOA than the AE group, indicating greater improvement. Limitation: Participants were mostly male veterans, and follow-up was limited. Conclusion: Veterans in STEP-KOA reported modest improvements in knee osteoarthritis symptoms compared with the control group. The STEP-KOA strategy may be efficient for delivering exercise therapies for knee osteoarthritis. Primary Funding Source: Department of Veterans Affairs, Health Services Research and Development Service.

Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension: A Systematic Review and Individual Participant–based Meta-analysis: Annals of Internal Medicine: Vol 174, No 1

Background: Although intensive blood pressure (BP)–lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). Purpose: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults. Data Sources: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing. Data Extraction: 2 investigators independently abstracted articles and rated risk of bias. Data Synthesis: 5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH (P for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged. Limitations: Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available. Conclusion: Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension. Primary Funding Source: National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753)

From Proteinuria to Albuminuria: Great Expectations for Kidney Failure Risk Prediction

Racism and Health in the United States: A Policy Statement From the American College of Physicians

Racial minorities in the United States have reported experiencing widespread racism throughout all aspects of life, from housing to education to employment. Existing research has examined the role of racism, discrimination, and violence in one's interaction with the health care system and their association with poorer mental and physical health. Systemic racism that underlies the fabric of society often manifests itself in prominent institutions, such as law enforcement agencies, regardless of individual intent. Overt and covert racist laws and policies, personal implicit biases, and other factors result in Black individuals and other people of color being the subject of law enforcement violence and criminal justice system interactions at disproportionately high rates. The demonstrated association between discriminatory law enforcement practices and violence and personal and community health necessitates treating these issues as public health issues worthy of a public policy intervention. Addressing some of the sources of institutional racism and harm through transparency and accountability measures is the first of many steps required to begin correcting historical racial injustices.

Life After May 25