Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 174, No 12

Background: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness. Objective: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE. Design: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003) Setting: England. Participants: Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019. Intervention: Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks. Measurements: The prespecified primary end point was serum IgG anti–double-stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes included incidence of disease flares and adverse events. Results: At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared with placebo (geometric mean, 47 [95% CI, 25 to 88] vs. 103 [CI, 49 to 213] IU/mL; 70% greater reduction from baseline [CI, 46% to 84%]; P < 0.001). Belimumab reduced risk for severe flare (BILAG-2004 grade A) compared with placebo (hazard ratio, 0.27 [CI, 0.07 to 0.98]; log-rank P = 0.033), with 10 severe flares in the placebo group and 3 in the belimumab group. Belimumab did not increase incidence of serious adverse events. Belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 [CI, 0.006 to 0.014] vs. 0.037 [CI, 0.021 to 0.081] × 109/L) at 52 weeks in a subset of patients (n = 25) with available data. Limitations: Small sample size; biomarker primary end point. Conclusion: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy. The results suggest that this combination could be developed as a therapeutic strategy. Primary Funding Source: Versus Arthritis.

Comparative Effectiveness of an Automated Text Messaging Service for Monitoring COVID-19 at Home

Background: Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly. Objective: To determine whether enrollment in an automated remote monitoring service for community-dwelling adults with COVID-19 at home (“COVID Watch”) was associated with improved mortality. Design: Retrospective cohort analysis. Setting: Mid-Atlantic academic health system in the United States. Participants: Outpatients who tested positive for SARS-CoV-2 between 23 March and 30 November 2020. Intervention: The COVID Watch service consists of twice-daily, automated text message check-ins with an option to report worsening symptoms at any time. All escalations were managed 24 hours a day, 7 days a week by dedicated telemedicine clinicians. Measurements: Thirty- and 60-day outcomes of patients enrolled in COVID Watch were compared with those of patients who were eligible to enroll but received usual care. The primary outcome was death at 30 days. Secondary outcomes included emergency department (ED) visits and hospitalizations. Treatment effects were estimated with propensity score–weighted risk adjustment models. Results: A total of 3488 patients enrolled in COVID Watch and 4377 usual care control participants were compared with propensity score weighted models. At 30 days, COVID Watch patients had an odds ratio for death of 0.32 (95% CI, 0.12 to 0.72), with 1.8 fewer deaths per 1000 patients (CI, 0.5 to 3.1) (P = 0.005); at 60 days, the difference was 2.5 fewer deaths per 1000 patients (CI, 0.9 to 4.0) (P = 0.002). Patients in COVID Watch had more telemedicine encounters, ED visits, and hospitalizations and presented to the ED sooner (mean, 1.9 days sooner [CI, 0.9 to 2.9 days]; all P < 0.001). Limitation: Observational study with the potential for unobserved confounding. Conclusion: Enrollment of outpatients with COVID-19 in an automated remote monitoring service was associated with reduced mortality, potentially explained by more frequent telemedicine encounters and more frequent and earlier presentation to the ED. Primary Funding Source: Patient-Centered Outcomes Research Institute.

Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized Trial: Annals of Internal Medicine: Vol 174, No 10

Background: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. Objective: To assess the long-term efficacy of acupuncture for CP/CPPS. Design: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938) Setting: Ten tertiary hospitals in China. Participants: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. Intervention: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. Measurements: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. Results: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. Limitation: Sham acupuncture might have had certain physiologic effects. Conclusion: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. Primary Funding Source: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

Comparative Implementation of a Brief App-Directed Protocol for Delirium Identification by Hospitalists, Nurses, and Nursing Assistants: A Cohort Study: Annals of Internal Medicine: Vol 175, No 1

Background: Systematic screening improves delirium identification among hospitalized older adults. Little data exist on how to implement such screening. Objective: To test implementation of a brief app-directed protocol for delirium identification by physicians, nurses, and certified nursing assistants (CNAs) in real-world practice relative to a research reference standard delirium assessment (RSDA). Design: Prospective cohort study. Setting: Large urban academic medical center and small rural community hospital. Participants: 527 general medicine inpatients (mean age, 80 years; 35% with preexisting dementia) and 399 clinicians (53 hospitalists, 236 nurses, and 110 CNAs). Measurements: On 2 study days, enrolled patients had an RSDA. Subsequently, CNAs performed an ultra-brief 2-item screen (UB-2) for delirium, whereas physicians and nurses performed a 2-step protocol consisting of the UB-2 followed in those with a positive screen result by the 3-Minute Diagnostic Assessment for the Confusion Assessment Method. Results: Delirium was diagnosed in 154 of 924 RSDAs (17%) and in 114 of 527 patients (22%). The completion rate for clinician protocols exceeded 97%. The CNAs administered the UB-2 in a mean of 62 seconds (SD, 51). The 2-step protocols were administered in means of 104 seconds (SD, 99) by nurses and 106 seconds (SD, 105) by physicians. The UB-2 had sensitivities of 88% (95% CI, 72% to 96%), 87% (CI, 73% to 95%), and 82% (CI, 65% to 91%) when administered by CNAs, nurses, and physicians, respectively, with specificities of 64% to 70%. The 2-step protocol had overall accuracy of 89% (CI, 83% to 93%) and 87% (CI, 81% to 91%), with sensitivities of 65% (CI, 48% to 79%) and 63% (CI, 46% to 77%) and specificities of 93% (CI, 88% to 96%) and 91% (CI, 86% to 95%), for nurses and physicians, respectively. Two-step protocol sensitivity for moderate to severe delirium was 78% (CI, 54% to 91%). Limitation: Two sites; limited diversity. Conclusion: An app-directed protocol for delirium identification was feasible, brief, and accurate, and CNAs and nurses performed as well as hospitalists. Primary Funding Source: National Institute on Aging.

Supplemental Nutrition Assistance Program Participation and Health Care Use in Older Adults: A Cohort Study: Annals of Internal Medicine: Vol 174, No 12

Background: Older adults dually eligible for Medicare and Medicaid have particularly high food insecurity prevalence and health care use. Objective: To determine whether participation in the Supplemental Nutrition Assistance Program (SNAP), which reduces food insecurity, is associated with lower health care use and cost for older adults dually eligible for Medicare and Medicaid. Design: An incident user retrospective cohort study design was used. The association between participation in SNAP and health care use and cost using outcome regression was assessed and supplemented by entropy balancing, matching, and instrumental variable analyses. Setting: North Carolina, September 2016 through July 2020. Participants: Older adults (aged ≥65 years) dually enrolled in Medicare and Medicaid but not initially enrolled in SNAP. Measurements: Inpatient admissions (primary outcome), emergency department visits, long-term care admissions, and Medicaid expenditures. Results: Of 115 868 persons included, 5093 (4.4%) enrolled in SNAP. Mean follow-up was approximately 22 months. In outcome regression analyses, SNAP enrollment was associated with fewer inpatient hospitalizations (−24.6 [95% CI, −40.6 to −8.7]), emergency department visits (−192.7 [CI, −231.1 to −154.4]), and long-term care admissions (−65.2 [CI, −77.5 to −52.9]) per 1000 person-years as well as fewer dollars in Medicaid payments per person per year (−$2360 [CI, −$2649 to −$2071]). Results were similar in entropy balancing, matching, and instrumental variable analyses. Limitation: Single state, no Medicare claims data available, and possible residual confounding. Conclusion: Participation in SNAP was associated with fewer inpatient admissions and lower health care costs for older adults dually eligible for Medicare and Medicaid. Primary Funding Source: National Institutes of Health.

A Cross-Sectional Study of SARS-CoV-2 Vaccination Among Employees of an Urban Safety-Net Health Care System

What Will It Take to End HIV in the United States?: A Comprehensive, Local-Level Modeling Study: Annals of Internal Medicine: Vol 174, No 11

Background: The Ending the HIV Epidemic (EHE) initiative aims to reduce incident HIV infections by 90% over a span of 10 years. The intensity of interventions needed to achieve this for local epidemics is unclear. Objective: To estimate the effect of HIV interventions at the city level. Design: A compartmental model of city-level HIV transmission stratified by age, race, sex, and HIV risk factor was developed and calibrated. Setting: 32 priority metropolitan statistical areas (MSAs). Patients: Simulated populations in each MSA. Intervention: Combinations of HIV testing and preexposure prophylaxis (PrEP) coverage among those at risk for HIV, plus viral suppression in persons with diagnosed HIV infection. Measurements: The primary outcome was the projected reduction in incident cases from 2020 to 2030. Results: Absent intervention, HIV incidence was projected to decrease by 19% across all 32 MSAs. Modest increases in testing (1.25-fold per year), PrEP coverage (5 percentage points), and viral suppression (10 percentage points) across the population could achieve reductions of 34% to 67% by 2030. Twenty-five percent PrEP coverage, testing twice a year on average, and 90% viral suppression among young Black and Hispanic men who have sex with men (MSM) achieved similar reductions (13% to 68%). Including all MSM and persons who inject drugs could reduce incidence by 48% to 90%. Thirteen of 32 MSAs could achieve greater than 90% reductions in HIV incidence with large-scale interventions that include heterosexuals. A web application with location-specific results is publicly available (www.jheem.org). Limitation: The COVID-19 pandemic was not represented. Conclusion: Large reductions in HIV incidence are achievable with substantial investment, but the EHE goals will be difficult to achieve in most locations. An interactive model that can help policymakers maximize the effect in their local environments is presented. Primary Funding Source: National Institutes of Health.

Absence of Humoral Response After Two-Dose SARS-CoV-2 Messenger RNA Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: A Case Series

Evidence-Based Prescribing and Polypharmacy for Patients With Heart Failure

Sickle Cell Disorders and Severe COVID-19 Outcomes: A Cohort Study