Long COVID: The Enduring Pandemic

Association Between Hospital Type and Resilience During COVID-19 Caseload Stress: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 177, No 10

Background: Imbalances between hospital caseload and care resources that strained U.S. hospitals during the pandemic have persisted after the pandemic amid ongoing staff shortages. Understanding which hospital types were more resilient to pandemic overcrowding-related excess deaths may prioritize patient safety during future crises. Objective: To determine whether hospital type classified by capabilities and resources (that is, extracorporeal membrane oxygenation [ECMO] capability, multiplicity of intensive care unit [ICU] types, and large or small hospital) influenced COVID-19 volume–outcome relationships during Delta wave surges. Design: Retrospective cohort study. Setting: 620 U.S. hospitals in the PINC AI Healthcare Database. Participants: Adult inpatients with COVID-19 admitted July to November 2021. Measurements: Hospital-months were ranked by previously validated surge index (severity-weighted COVID-19 inpatient caseload relative to hospital bed capacity) percentiles. Hierarchical models were used to evaluate the effect of log-transformed surge index on the marginally adjusted probability of in-hospital mortality or discharge to hospice. Effect modification was assessed for by 4 mutually exclusive hospital types. Results: Among 620 hospitals recording 223 380 inpatients with COVID-19 during the Delta wave, there were 208 ECMO-capable, 216 multi-ICU, 36 large (≥200 beds) single-ICU, and 160 small (<200 beds) single-ICU hospitals. Overall, 50 752 (23%) patients required admission to the ICU, and 34 274 (15.3%) died. The marginally adjusted probability for mortality was 5.51% (95% CI, 4.53% to 6.50%) per unit increase in the log surge index (strain attributable mortality = 7375 [CI, 5936 to 8813] or 1 in 5 COVID-19 deaths). The test for interaction showed no difference (P = 0.32) in log surge index–mortality relationship across 4 hospital types. Results were consistent after excluding transferred patients, restricting to patients with acute respiratory failure and mechanical ventilation, and using alternative strain metrics. Limitation: Residual confounding. Conclusion: Comparably detrimental relationships between COVID-19 caseload and survival were seen across all hospital types, including highly advanced centers, and well beyond the pandemic’s learning curve. These lessons from the pandemic heighten the need to minimize caseload surges and their effects across all hospital types during public health and staffing crises. Primary Funding Source: Intramural Research Program of the National Institutes of Health Clinical Center.

What You May Have Missed in 2023: Keeping Up With the Constant Flow of New Medical Evidence

Colorectal Cancer Screening Completion and Yield in Patients Aged 45 to 50 Years: An Observational Study: Annals of Internal Medicine: Vol 177, No 12

Background: Guidelines now recommend initiating colorectal cancer (CRC) screening at age 45 years rather than 50 years, but little is known about screening completion and yield among people aged 45 to 49 years. Objective: To evaluate fecal immunochemical test (FIT) completion and yield in patients aged 45 to 49 versus 50 years. Design: Retrospective cohort study. Setting: Kaiser Permanente Northern California, Washington, and Colorado. Patients: Those distributed a FIT kit during January to September 2022. Measurements: FIT completion within 3 months, FIT positivity, receipt of colonoscopy within 3 months after a positive FIT result, and colonoscopy yield. Results: A total of 267 732 FIT kits were distributed: 213 928 (79.9%) to patients aged 45 to 49 years, and 53 804 (20.1%) to those aged 50 years. Overall, FIT completion was slightly higher in patients aged 45 to 49 years (38.9% vs. 37.5%; adjusted risk ratio [aRR], 1.05 [95% CI, 1.04 to 1.06]), although at Colorado, those aged 45 to 49 years were substantially less likely to complete a FIT (30.7% vs. 40.2%; aRR, 0.77 [CI, 0.73 to 0.80]). Overall, FIT positivity was lower in patients aged 45 to 49 years (3.6% vs. 4.0%; aRR, 0.91 [CI, 0.84 to 0.98]), and receipt of colonoscopy after a positive FIT result was similar between groups (64.9% vs. 67.4%; aRR, 1.00 [CI, 0.94 to 1.05]). Adenoma detection was lower in the younger group (58.8% vs. 67.7%; aRR, 0.88 [CI, 0.83 to 0.95]). Yields were similar for adenoma with advanced histology (13.2% vs. 15.9%; aRR, 0.86 [CI, 0.69 to 1.07]), polyp with high-grade dysplasia (3.4% vs. 5.1%; aRR, 0.68 [CI, 0.44 to 1.04]), sessile serrated lesion (10.3% vs. 11.7%; aRR, 0.92 [CI, 0.71 to 1.21]), and CRC (2.8% vs. 2.7%; aRR, 1.10 [CI, 0.62 to 1.96]). Limitation: The small number of neoplasia events contributed to wide CIs. Conclusion: Similar FIT completion and yield rates in people aged 45 to 50 years support initiation of CRC screening at age 45 years. Primary Funding Source: Kaiser Permanente Sidney R. Garfield Memorial Fund.

Rheumatology: What You May Have Missed in 2023

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

Nephrology: What You May Have Missed in 2023

This article highlights a selection of important nephrology studies published in 2023 that have relevance for nonnephrologist physicians. Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults.

Body Surface Area in Obesity: Clinical Challenges and Call for Improvements

Severe Maternal and Neonatal Morbidity Among Gestational Carriers: A Cohort Study: Annals of Internal Medicine: Vol 177, No 11

Background: Use of a gestational (“surrogate”) carrier is increasingly common. Risk for maternal and neonatal adversity is largely unknown in this birthing population. Objective: To determine the risk for severe maternal morbidity (SMM) and severe neonatal morbidity (SNM) in gestational carriers. Design: Population-based cohort study. Setting: All of Ontario, Canada. Participants: All singleton births at more than 20 weeks’ gestation, from 2012 to 2021. Measurements: Exposure was type of conception, namely, gestational carriage (main exposure), unassisted conception (comparison group 1), and in vitro fertilization (IVF) (comparison group 2). Main composite outcomes were SMM and SNM. Modified Poisson regression models generated weighted relative risks (wRRs) using propensity score–based overlap weighting. Secondary outcomes included hypertensive disorders of pregnancy, cesarean delivery, preterm birth, and postpartum hemorrhage. Results: Of all eligible singleton births, 846 124 (97.6%) were by unassisted conception, 16 087 (1.8%) by IVF, and 806 (0.1%) by gestational carriage. Respective risks for SMM were 2.3%, 4.3%, and 7.8%. The wRRs were 3.30 (95% CI, 2.59 to 4.20) comparing gestational carriage with unassisted conception and 1.86 (CI, 1.36 to 2.55) comparing gestational carriage with IVF. Respective risks for SNM were 5.9%, 8.9%, and 6.6%, generating wRRs of 1.20 (CI, 0.92 to 1.55) for gestational carriage versus unassisted conception and 0.81 (CI, 0.61 to 1.08) for gestational carriage versus IVF. Hypertensive disorders, postpartum hemorrhage, and preterm birth at less than 37 weeks were also significantly higher contrasting gestational carriers to either comparison group. Limitation: Absence of information about indications for choosing a gestational carrier, and oocyte or sperm donor source. Conclusion: Among singleton births of more than 20 weeks’ gestation, a higher risk for SMM and adverse pregnancy outcomes was seen among gestational carriers compared with women who conceived with and without assistance. Although gestational carriage was associated with preterm birth, there was less clear evidence of severe neonatal morbidity. Potential mechanisms for higher maternal morbidity among gestational carriers require elucidation, alongside developing special care plans for gestational carriers. Primary Funding Source: The Canadian Institutes of Health Research.

Heterogeneity of Sepsis Presentations and Mortality Rates

Viral Load–Based Prediction of Hepatocellular Carcinoma Risk in Noncirrhotic Patients With Chronic Hepatitis B: A Multinational Study for the Development and External Validation of a New Prognostic Model: Annals of Internal Medicine: Vol 177, No 10

Background: A nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB). Objective: To develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation. Design: Multinational cohort study. Setting: A community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts). Participants: Model development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong. Measurements: Incidence of HCC. Results: Over median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold. Limitation: Validation in cohorts of other races and receiving antiviral treatment was lacking. Conclusion: Our new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment. Primary Funding Source: Korean government.