The Pendulum Swings on Glucocorticoids in Rheumatoid Arthritis

Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults: A Prospective, Multicenter Cohort Study: Annals of Internal Medicine: Vol 177, No 3

Background: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. Objective: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. Design: Prospective, multicenter cohort study. Setting: Hispanic Community Health Study/Study of Latinos. Participants: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. Measurements: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. Results: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. Limitation: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. Conclusion: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. Primary Funding Source: National Institutes of Health.

Cumulative Incidence of Thiazide-Induced Hyponatremia: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 177, No 1

Background: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear. Objective: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice. Design: Population and register-based cohort study using target trial emulation. Setting: Denmark, 1 January 2014 to 31 October 2018. Participants: Two target trials were emulated among persons aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments. The first target trial emulation compared new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin–angiotensin system inhibitor (HCTZ–RASi; that is, combination pill) versus a RASi alone. Measurements: Two-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment–weighted survival curves. Results: The study compared 37 786 new users of BFZ with 44 963 of a CCB and 11 943 new users of HCTZ–RASi with 85 784 of a RASi. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ–RASi. The risk differences were 1.35% (95% CI, 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ–RASi and RASi; risk differences were higher with older age and higher comorbidity burden. The respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year. Limitation: The study assumed that filled prescriptions equaled drug use, and residual confounding is likely. Conclusion: Treatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment, than indicated by drug labeling. Primary Funding Source: Independent Research Fund Denmark.

Trends in Primary Prevention Statin Use by Cardiovascular Risk Score From 1999 to 2018: A Repeated Cross-Sectional Study

Deep Learning to Estimate Cardiovascular Risk From Chest Radiographs: A Risk Prediction Study: Annals of Internal Medicine: Vol 177, No 4

Background: Guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend a risk calculator (ASCVD risk score) to estimate 10-year risk for major adverse cardiovascular events (MACE). Because the necessary inputs are often missing, complementary approaches for opportunistic risk assessment are desirable. Objective: To develop and test a deep-learning model (CXR CVD-Risk) that estimates 10-year risk for MACE from a routine chest radiograph (CXR) and compare its performance with that of the traditional ASCVD risk score for implications for statin eligibility. Design: Risk prediction study. Setting: Outpatients potentially eligible for primary cardiovascular prevention. Participants: The CXR CVD-Risk model was developed using data from a cancer screening trial. It was externally validated in 8869 outpatients with unknown ASCVD risk because of missing inputs to calculate the ASCVD risk score and in 2132 outpatients with known risk whose ASCVD risk score could be calculated. Measurements: 10-year MACE predicted by CXR CVD-Risk versus the ASCVD risk score. Results: Among 8869 outpatients with unknown ASCVD risk, those with a risk of 7.5% or higher as predicted by CXR CVD-Risk had higher 10-year risk for MACE after adjustment for risk factors (adjusted hazard ratio [HR], 1.73 [95% CI, 1.47 to 2.03]). In the additional 2132 outpatients with known ASCVD risk, CXR CVD-Risk predicted MACE beyond the traditional ASCVD risk score (adjusted HR, 1.88 [CI, 1.24 to 2.85]). Limitation: Retrospective study design using electronic medical records. Conclusion: On the basis of a single CXR, CXR CVD-Risk predicts 10-year MACE beyond the clinical standard and may help identify individuals at high risk whose ASCVD risk score cannot be calculated because of missing data. Primary Funding Source: None.

Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease

Background: No studies have reported the long-term outcomes of initiating sodium–glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis. Objective: To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD). Design: Target trial emulation study. Setting: Taiwan’s National Health Insurance Research Database (NHIRD). Participants: By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021. Measurements: Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers. Results: In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan–Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use. Limitation: This result may not apply to patients without T2D. Conclusion: This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD. Primary Funding Source: National Health Research Institutes, Taiwan.

Cause of  Death

Would You Screen This Patient for Cognitive Impairment?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 176, No 10

Dementia, according to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is defined by a significant decline in 1 or more cognitive domains that interferes with a person’s independence in daily activities. Mild cognitive impairment (MCI) differs from dementia in that the impairment is not sufficient to interfere with independence. For the purposes of this discussion, cognitive impairment (CI) includes both dementia and MCI. Various screening tests are available for CI. These tests ask patients to perform a series of tasks that assess 1 or more domains of cognitive function or ask a caregiver to report on the patient’s abilities. A positive result on a screening test does not equate to a diagnosis of CI; rather, it should lead to additional testing to confirm the diagnosis. On review of the evidence, the U.S. Preventive Services Task Force (USPSTF) concluded in 2020 that the evidence was insufficient to assess the balance of benefits and harms of screening for CI in older adults (“I statement”). The USPSTF did clarify that although there is insufficient evidence, there may be important reasons to identify CI. In this article, 2 experts review the available evidence to answer the following questions: What screening tools are available, and how effective are they in identifying patients with CI? What interventions are available for patients found to have CI, to what extent do they improve patient outcomes, and what, if any, negative effects occur? And, would they recommend screening for CI, and why or why not?

Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 177, No 2

Background: Chronic insomnia is common in patients undergoing in-center hemodialysis, yet there is limited evidence on effective treatments for this population. Objective: To compare the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), trazodone, and placebo for insomnia in patients undergoing long-term hemodialysis. Design: Randomized, multicenter, double-blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT03534284) Setting: 26 dialysis units in Albuquerque, New Mexico, and Seattle, Washington. Participants: Patients with Insomnia Severity Index (ISI) score of 10 or greater, with sleep disturbances on 3 or more nights per week for 3 or more months. Intervention: Participants were randomly assigned to 6 weeks of CBT-I, trazodone, or placebo. Measurements: The primary outcome was the ISI score at 7 and 25 weeks from randomization. Results: A total of 923 patients were prescreened, and of the 411 patients with chronic insomnia, 126 were randomly assigned to CBT-I (n = 43), trazodone (n = 42), or placebo (n = 41). The change in ISI scores from baseline to 7 weeks with CBT-I or trazodone was no different from placebo: CBT-I, −3.7 (95% CI, −5.5 to −1.9); trazodone, −4.2 (CI, −5.9 to −2.4); and placebo, −3.1 (CI, −4.9 to −1.3). There was no meaningful change in ISI scores from baseline to 25 weeks: CBT-I, −4.8 (CI, −7.0 to −2.7); trazodone, −4.0 (CI, −6.0 to −1.9); and placebo, −4.3 (CI, −6.4 to −2.2). Serious adverse events (SAEs), particularly serious cardiovascular events, were more frequent with trazodone (annualized cardiovascular SAE incidence rates: CBT-I, 0.05 [CI, 0.00 to 0.29]; trazodone, 0.64 [CI, 0.34 to 1.10]; and placebo, 0.21 [CI, 0.06 to 0.53]). Limitation: Modest sample size and most participants had mild or moderate insomnia. Conclusion: In patients undergoing hemodialysis with mild or moderate chronic insomnia, there was no difference in the effectiveness of 6 weeks of CBT-I or trazodone compared with placebo. The incidence of SAEs was higher with trazodone. Primary Funding Source: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

Contraception and Reproductive Health Counseling: This Is Our Lane