Characteristics and Outcomes of Hospitalized Pregnant Women With Influenza, 2010 to 2019: A Repeated Cross-Sectional Study: Annals of Internal Medicine: Vol 175, No 2

Background: Pregnant women may be at increased risk for severe influenza-associated outcomes. Objective: To describe characteristics and outcomes of hospitalized pregnant women with influenza. Design: Repeated cross-sectional study. Setting: The population-based U.S. Influenza Hospitalization Surveillance Network during the 2010–2011 through 2018–2019 influenza seasons. Patients: Pregnant women (aged 15 to 44 years) hospitalized with laboratory-confirmed influenza identified through provider-initiated or facility-based testing practices. Measurements: Clinical characteristics, interventions, and in-hospital maternal and fetal outcomes were obtained through medical chart abstraction. Multivariable logistic regression was used to evaluate the association between influenza A subtype and severe maternal influenza-associated outcomes, including intensive care unit (ICU) admission, mechanical ventilation, extracorporeal membrane oxygenation, or in-hospital death. Results: Of 9652 women aged 15 to 44 years and hospitalized with influenza, 2690 (27.9%) were pregnant. Among the 2690 pregnant women, the median age was 28 years, 62% were in their third trimester, and 42% had at least 1 underlying condition. Overall, 32% were vaccinated against influenza and 88% received antiviral treatment. Five percent required ICU admission, 2% required mechanical ventilation, and 0.3% (n = 8) died. Pregnant women with influenza A H1N1 were more likely to have severe outcomes than those with influenza A H3N2 (adjusted risk ratio, 1.9 [95% CI, 1.3 to 2.8]). Most women (71%) were still pregnant at hospital discharge. Among 754 women who were no longer pregnant at discharge, 96% had a pregnancy resulting in live birth, and 3% experienced fetal loss. Limitation: Maternal and fetal outcomes that occurred after hospital discharge were not captured. Conclusion: Over 9 influenza seasons, one third of reproductive-aged women hospitalized with influenza were pregnant. Influenza A H1N1 was associated with more severe maternal outcomes. Pregnant women remain a high-priority target group for vaccination. Primary Funding Source: Centers for Disease Control and Prevention.

Changes in Cigarette Sales in the United States During the COVID-19 Pandemic

Vitamin D Deficiency Increases Mortality Risk in the UK Biobank: A Nonlinear Mendelian Randomization Study: Annals of Internal Medicine: Vol 175, No 11

Background: Low vitamin D status is associated with increased mortality, but randomized trials on severely deficient participants are lacking. Objective: To assess genetic evidence for the causal role of low vitamin D status in mortality. Design: Nonlinear Mendelian randomization analyses. Setting: UK Biobank, a large-scale, prospective cohort from England, Scotland, and Wales with participants recruited between March 2006 and July 2010. Participants: 307 601 unrelated UK Biobank participants of White European ancestry (aged 37 to 73 years at recruitment) with available measurements of 25-hydroxyvitamin D (25-(OH)D) and genetic data. Measurements: Genetically predicted 25-(OH)D was estimated using 35 confirmed variants of 25-(OH)D. All-cause and cause-specific mortality (cardiovascular disease [CVD], cancer, and respiratory) were recorded up to June 2020. Results: There were 18 700 deaths during the 14 years of follow-up. The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped (P for nonlinearity < 0.001), and risk for death decreased steeply with increasing concentrations until 50 nmol/L. Evidence for an association was also seen in analyses of mortality from cancer, CVD, and respiratory diseases (P ≤ 0.033 for all outcomes). Odds of all-cause mortality in the genetic analysis were estimated to increase by 25% (odds ratio, 1.25 [95% CI, 1.16 to 1.35]) for participants with a measured 25-(OH)D concentration of 25 nmol/L compared with 50 nmol/L. Limitations: Analyses were restricted to a White European population. A genetic approach is best suited to providing proof of principle on causality, whereas the strength of the association is approximate. Conclusion: Our study supports a causal relationship between vitamin D deficiency and mortality. Additional research needs to identify strategies that meet the National Academy of Medicine's guideline of greater than 50 nmol/L and that reduce the premature risk for death associated with low vitamin D levels. Primary Funding Source: National Health and Medical Research Council.

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.

Association Between Socioeconomic Disadvantage and Decline in Function, Cognition, and Mental Health After Critical Illness Among Older Adults: A Cohort Study: Annals of Internal Medicine: Vol 175, No 5

Background: Older adults admitted to an intensive care unit (ICU) are at risk for developing impairments in function, cognition, and mental health. It is not known whether socioeconomically disadvantaged older persons are at greater risk for these impairments than their less vulnerable counterparts. Objective: To evaluate the association between socioeconomic disadvantage and decline in function, cognition, and mental health among older survivors of an ICU hospitalization. Design: Retrospective analysis of a longitudinal cohort study. Setting: Community-dwelling older adults in the National Health and Aging Trends Study (NHATS). Participants: Participants with ICU hospitalizations between 2011 and 2017. Measurements: Socioeconomic disadvantage was assessed as dual-eligible Medicare–Medicaid status. The outcome of function was defined as the count of disabilities in 7 activities of daily living and mobility tasks, the cognitive outcome as the transition from no or possible to probable dementia, and the mental health outcome as the Patient Health Questionnaire-4 score in the NHATS interview after ICU hospitalization. The analytic sample included 641 ICU hospitalizations for function, 458 for cognition, and 519 for mental health. Results: After accounting for sociodemographic and clinical characteristics, dual eligibility was associated with a 28% increase in disability after ICU hospitalization (incidence rate ratio, 1.28; 95% CI, 1.00 to 1.64); and nearly 10-fold greater odds of transitioning to probable dementia (odds ratio, 9.79; 95% CI, 3.46 to 27.65). Dual eligibility was not associated with symptoms of depression and anxiety after ICU hospitalization (incidence rate ratio, 1.33; 95% CI, 0.99 to 1.79). Limitation: Administrative data, variability in timing of baseline and outcome assessments, proxy selection. Conclusion: Dual-eligible older persons are at greater risk for decline in function and cognition after an ICU hospitalization than their more advantaged counterparts. This finding highlights the need to prioritize low-income seniors in rehabilitation and recovery efforts after critical illness and warrants investigation into factors leading to this disparity. Primary Funding Source: National Institute on Aging.

Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation: A Multicenter Prospective Cohort Study: Annals of Internal Medicine: Vol 175, No 1

Background: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown. Objective: To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation. Design: Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818) Setting: Eighteen sites between February 2011 and February 2021. Patients: Patients with isolated subsegmental pulmonary embolism. Intervention: At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy. Measurements: The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period. Results: Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism. Limitation: The study was restricted to patients with low-risk subsegmental pulmonary embolism. Conclusion: Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. Primary Funding Source: Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.

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.

Accuracy of Ultrasound Jugular Venous Pressure Height in Predicting Central Venous Congestion

Background: Assessment of volume status through the estimation of central venous pressure (CVP) is integral in the care of heart failure (HF). Bedside assessment is limited by obesity, variation in physical examination skills, and expertise in ultrasonography. Objective: To validate the accuracy of quantitative and qualitative point-of-care ultrasonography assessment of jugular venous pressure (JVP) in predicting elevated CVP. Design: Prospective observational study using convenience sampling. Setting: 2 U.S. academic hospitals. Patients: Adult patients undergoing right heart catheterization between 5 February 2019 and 1 March 2021. Measurements: Estimation of the JVP height by handheld ultrasound device (uJVP), JVP by traditional physical examination, and qualitative presence of a distended uJVP in the upright position (upright-uJVP) was done before invasive measurements. Receiver-operating characteristic analysis of the uJVP was compared with invasive hemodynamics. Results: In 100 participants undergoing right heart catheterization for HF indications (mean age, 59.6 years; 44% with preserved ejection fraction), the uJVP in a reclined position accurately predicted elevated right atrial pressure (RAP) (>10 mm Hg), with an area under the curve of 0.84. A positive uJVP in the upright position was 94.6% specific for predicting elevated RAP. Limitation: Limited examiners, only 2 centers, and convenience sampling. Conclusion: Point-of-care ultrasonography assessment of the uJVP is feasible, reproducible, and accurately predictive of elevated CVPs in patients undergoing right heart catheterization. Further investigation of clinical application of ultrasound-measured JVP seems warranted. Primary Funding Source: None.

Colonoscopy for Diagnostic Evaluation and Interventions to Prevent Recurrence After Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians

Description: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal cancer (CRC) after a presumed diagnosis of acute left-sided colonic diverticulitis and on the role of pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrence after initial treatment of acute complicated and uncomplicated left-sided colonic diverticulitis. This guideline is based on the current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. Methods: The ACP Clinical Guidelines Committee (CGC) based these recommendations on a systematic review on the role of colonoscopy after acute left-sided colonic diverticulitis and pharmacologic, nonpharmacologic, and elective surgical interventions after initial treatment. The systematic review evaluated outcomes rated by the CGC as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is adults with recent episodes of acute left-sided colonic diverticulitis. Recommendation 1: ACP suggests that clinicians refer patients for a colonoscopy after an initial episode of complicated left-sided colonic diverticulitis in patients who have not had recent colonoscopy (conditional recommendation; low-certainty evidence). Recommendation 2: ACP recommends against clinicians using mesalamine to prevent recurrent diverticulitis (strong recommendation; high-certainty evidence). Recommendation 3: ACP suggests that clinicians discuss elective surgery to prevent recurrent diverticulitis after initial treatment in patients who have either uncomplicated diverticulitis that is persistent or recurs frequently or complicated diverticulitis (conditional recommendation; low-certainty evidence). The informed decision whether or not to undergo surgery should be personalized based on a discussion of potential benefits, harms, costs, and patient's preferences.

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups: A Systematic Review and Individual-Patient Data Meta-analysis: Annals of Internal Medicine: Vol 175, No 2

Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. Data Sources: MEDLINE from 1 January 1995 until 1 January 2021. Study Selection: 16 studies assessing at least 1 diagnostic strategy. Data Extraction: Individual-patient data from 20 553 patients. Data Synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as “PE considered excluded” without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability–dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Conclusion: Overall, all strategies showed acceptable safety, with pretest probability–dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Primary Funding Source: Dutch Research Council. (PROSPERO: CRD42018089366)