COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System: A Target Trial Emulation Study: Annals of Internal Medicine: Vol 175, No 3

Background: Little is known about real-world COVID-19 vaccine effectiveness (VE) in racially and ethnically diverse, elderly populations with high comorbidity burden. Objective: To determine the effectiveness of messenger RNA COVID-19 vaccines. Design: Target trial emulation study comparing newly vaccinated persons with matched unvaccinated controls. Setting: U.S. Department of Veterans Affairs health care system. Participants: Among persons receiving care in the Veterans Affairs health care system (n = 5 766 638), those who received at least 1 dose of the Moderna or Pfizer–BioNTech COVID-19 vaccine from 11 December 2020 to 25 March 2021 (n = 2 099 871) were matched to unvaccinated controls in a 1:1 ratio according to demographic, clinical, and geographic characteristics. Intervention: Follow-up for SARS-CoV-2 infection or SARS-CoV-2–related death, defined as death within 30 days of infection, began after the vaccination date or an identical index date for the matched unvaccinated controls and continued until up to 30 June 2021. Measurements: Vaccine effectiveness against SARS-CoV-2 infection or SARS-CoV-2–related death. Results: Vaccinated and unvaccinated groups were well matched; both were predominantly male (92.9% vs. 93.4%), had advanced age (mean, 68.7 years in both groups), had diverse racial and ethnic distribution (for example, Black: 17.3% vs. 17.0%, Hispanic: 6.5% vs. 6.1%), and had substantial comorbidity burden. Vaccine effectiveness 7 or more days after the second vaccine dose was 69% (95% CI, 67% to 70%) against SARS-CoV-2 infection and 86% (CI, 82% to 89%) against SARS-CoV-2–related death and was similar when follow-up was extended to 31 March versus 30 June. Vaccine effectiveness against infection decreased with increasing age and comorbidity burden. Limitation: Predominantly male population and lack of data on SARS-CoV-2 variants. Conclusion: In an elderly, diverse, high-comorbidity population, COVID-19 VE against infection was substantially lower than previously reported, but VE against death was high. Complementary infection mitigation efforts remain important for pandemic control, even with vaccination. Primary Funding Source: U.S. Department of Veterans Affairs.

Effectiveness of Motivational Interviewing in Managing Overweight and Obesity: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 175, No 6

Background: Motivational interviewing (MI) is potentially useful in management of overweight and obesity, but staff training and increased delivery time are barriers, and its effectiveness independent of other behavioral components is unclear. Purpose: To assess the independent contribution of MI as part of a behavioral weight management program (BWMP) in controlling weight and improving psychological well-being. Data Sources: 6 electronic databases and 2 trial registries, searched from database inception through 24 September 2021. Study Selection: Randomized controlled trials in adults or adolescents aimed at weight loss or maintenance and comparing programs incorporating MI versus interventions without MI. Data Extraction: Two reviewers independently screened studies, extracted data, and assessed risk of bias. Outcomes included weight, anxiety, depression, quality of life, and other aspects of psychological well-being. Pooled mean differences or standardized mean differences were obtained using random- and fixed-effects meta-analyses. Data Synthesis: Forty-six studies involving 11 077 participants, predominantly with obesity, were included. At 6 months, BWMPs using MI were more effective than no/minimal intervention (−0.88 [95% CI, −1.27 to −0.48] kg; I 2 = 0%) but were not statistically significantly more effective than lower-intensity (−0.88 [CI, −2.39 to 0.62] kg; I 2 = 55.8%) or similar-intensity (−1.36 [CI, −2.80 to 0.07] kg; I 2 = 18.8%) BWMPs. At 1 year, data were too sparse to pool comparisons with no/minimal intervention, but MI did not produce statistically significantly greater weight change compared with lower-intensity (−1.16 [CI, −2.49 to 0.17] kg; I 2 = 88.7%) or similar-intensity (−0.18 [CI, −2.40 to 2.04] kg; I 2 = 72.7%) BWMPs without MI. Studies with 18-month follow-up were also sparse; MI did not produce statistically significant benefit in any of the comparator categories. There was no evidence of subgroup differences based on study, participant, or intervention characteristics. Too few studies assessed effects on psychological well-being to pool, but data did not suggest that MI was independently effective. Limitations: High statistical heterogeneity among studies, largely unexplained by sensitivity and subgroup analyses; stratification by comparator intensity and follow-up duration resulted in pooling of few studies. Conclusion: There is no evidence that MI increases effectiveness of BWMPs in controlling weight. Given the intensive training required for its delivery, MI may not be a worthwhile addition to BWMPs. Primary Funding Source: National Institute for Health Research Biomedical Research Centre. (PROSPERO: CRD42020177259)

Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity: An Observational Study: Annals of Internal Medicine: Vol 175, No 1

Background: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. Objective: To describe dolutegravir uptake and disparities by sex and age group in LMICs. Design: Observational cohort study. Setting: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Patients: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. Measurements: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). Results: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. Limitation: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. Conclusion: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. Primary Funding Source: National Institutes of Health.

Risk for Shoulder Conditions After Vaccination: A Population-Based Study Using Real-World Data

Background: Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited. Objective: To estimate the risk for shoulder conditions after vaccination and assess possible risk factors. Design: Retrospective cohort study. Setting: Kaiser Permanente Southern California, a large integrated health care organization. Participants: Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017. Measurements: A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared. Results: Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons. Limitation: Generalizability to other health care settings, use of administrative data, and residual confounding. Conclusion: These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks. Primary Funding Source: Centers for Disease Control and Prevention.

Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race: A Prospective Cohort Study: Annals of Internal Medicine: Vol 175, No 3

Background: New estimated glomerular filtration rate (eGFR) equations removed race adjustment, but the impact of its removal on prediction of end-stage kidney disease (ESKD) is unknown. Objective: To compare the ESKD prediction performance of different eGFR equations. Design: Observational, prospective cohort study. Setting: 7 U.S. clinical centers. Participants: 3873 participants with chronic kidney disease (CKD) from the CRIC (Chronic Renal Insufficiency Cohort) Study contributing 13 902 two-year risk periods. Measurements: ESKD was defined as initiation of dialysis or transplantation. eGFR was calculated using 5 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine and/or cystatin C, with or without race adjustment. The predicted 2-year risk for ESKD was calculated using the 4-variable Kidney Failure Risk Equation (KFRE). We evaluated the prediction performance of eGFR equations and the KFRE score using discrimination and calibration analyses. Results: During a maximum 16 years of follow-up, 856 participants developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of ESKD compared with eGFR alone (area under the curve ranges, 0.945 to 0.954 vs. 0.900 to 0.927). Prediction performance of KFRE scores using different eGFR equations was similar, but the creatinine equation without race adjustment improved calibration among Black participants. Among all participants, compared with an eGFR less than 20 mL/min/1.73 m2, a KFRE score greater than 20% had similar specificity for predicting 2-year ESKD risk (ranges, 0.94 to 0.97 vs. 0.95 to 0.98) but higher sensitivity (ranges, 0.68 to 0.78 vs. 0.42 to 0.66). Limitation: Data are solely from the United States. Conclusion: The KFRE score better predicts 2-year risk for ESKD compared with eGFR alone, regardless of race adjustment. The creatinine equation with age and sex may improve calibration among Black patients. A KFRE score greater than 20% showed high specificity and sensitivity for predicting 2-year risk for ESKD. Primary Funding Source: National Institutes of Health.

Annals for Hospitalists Inpatient Notes - How We Treat Hyperglycemia in the Hospital

Targeting the Standardized Blood Pressure: New Guidelines for Blood Pressure Management in Chronic Kidney Disease

How Would You Manage This Male Patient With Hypogonadism?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 174, No 8

Male hypogonadism is defined as an abnormally low serum testosterone concentration or sperm count. As men age, often in the context of obesity and other comorbid conditions, serum testosterone levels may decrease. Normalizing serum testosterone levels in male adults with hypogonadism may improve symptoms related to androgen deficiency, but controversies exist regarding the long-term benefits and risks of hormone supplementation in this setting. In 2020, the American College of Physicians published a clinical guideline for the use of testosterone supplementation in adult men based on a systematic review of available evidence. Among their recommendations were that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function and not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition. Here, two clinicians with expertise in this area, one a generalist and the other an endocrinologist, debate the management of a patient with sexual symptoms and a low serum testosterone level. They discuss the diagnosis of male hypogonadism, the indications for testosterone therapy, its potential benefits and risks, how it should be monitored, and how long it should be continued.

Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy: A Propensity Score–Matched Cohort Study: Annals of Internal Medicine: Vol 175, No 3

Background: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter. Objective: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy. Design: Population-based, matched, cohort study. Setting: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020. Patients: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday. Measurements: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups. Results: A total of 25 077 propensity score–matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]). Limitation: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events. Conclusion: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk. Primary Funding Source: Canadian Institutes of Health Research.

Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease