Journal: Ann Intern Med

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Abstract

The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs : A Systematic Review and Meta-analysis.

Bastos ML, Perlman-Arrow S, Menzies D, Campbell JR
Background
Nasopharyngeal swabs are the primary sampling method used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but they require a trained health care professional and extensive personal protective equipment.
Purpose
To determine the difference in sensitivity for SARS-CoV-2 detection between nasopharyngeal swabs and saliva and estimate the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs.
Data sources
Embase, Medline, medRxiv, and bioRxiv were searched from 1 January to 1 November 2020. Cost inputs were from nationally representative sources in Canada and were converted to 2020 U.S. dollars.
Study selection
Studies including at least 5 paired nasopharyngeal swab and saliva samples and reporting diagnostic accuracy for SARS-CoV-2 detection.
Data extraction
Data were independently extracted using standardized forms, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2).
Data synthesis
Thirty-seven studies with 7332 paired samples were included. Against a reference standard of a positive result on either sample, the sensitivity of saliva was 3.4 percentage points lower (95% CI, 9.9 percentage points lower to 3.1 percentage points higher) than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva\'s sensitivity was 1.5 percentage points higher (CI, 7.3 percentage points lower to 10.3 percentage points higher) than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less (CI, 14.7 percentage points less to 0.8 percentage point more) sensitive. In this subgroup, if testing 100 000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more (95% uncertainty interval, 5 fewer to 166 more) persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8093.
Limitation
The reference standard was imperfect, and saliva collection procedures varied.
Conclusion
Saliva sampling seems to be a similarly sensitive and less costly alternative that could replace nasopharyngeal swabs for collection of clinical samples for SARS-CoV-2 testing.
Primary funding source
McGill Interdisciplinary Initiative in Infection and Immunity. (PROSPERO: CRD42020203415).



Ann Intern Med: 11 Jan 2021; epub ahead of print
Bastos ML, Perlman-Arrow S, Menzies D, Campbell JR
Ann Intern Med: 11 Jan 2021; epub ahead of print | PMID: 33428446
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Abstract

A Comprehensive Policy Framework to Understand and Address Disparities and Discrimination in Health and Health Care: A Policy Paper From the American College of Physicians.

Serchen J, Doherty R, Atiq O, Hilden D

Racial and ethnic minority populations in the United States experience disparities in their health and health care that arise from a combination of interacting factors, including racism and discrimination, social drivers of health, health care access and quality, individual behavior, and biology. To ameliorate these disparities, the American College of Physicians (ACP) proposes a comprehensive policy framework that recognizes and confronts the many elements of U.S. society, some of which are intertwined and compounding, that contribute to poorer health outcomes. In addition to this framework, which includes high-level principles and discusses how disparities are interconnected, ACP offers specific policy recommendations on disparities and discrimination in education and the workforce, those affecting specific populations, and those in criminal justice practices and policies in its 3 companion policy papers. ACP believes that a cross-cutting approach that identifies and offers solutions to the various aspects of society contributing to poor health is essential to achieving its goal of good health care for all, poor health care for none.



Ann Intern Med: 11 Jan 2021; epub ahead of print
Serchen J, Doherty R, Atiq O, Hilden D
Ann Intern Med: 11 Jan 2021; epub ahead of print | PMID: 33428444
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Abstract

Sickle Cell Disease.

Pecker LH, Lanzkron S

Sickle cell disease is an umbrella term for a group of hemoglobinopathies characterized by the presence of 2 β-globin gene mutations or deletions, at least 1 of which is the point mutation that leads to the production of hemoglobin S. Sickle cell disease is associated with hemolytic anemia, significant chronic end-organ damage, and early death. In high-income countries, at least 95% of children with the disease survive into adulthood, resulting in a growing population of affected adults with significant comorbidities, complex medical issues, and not enough specialists to provide care. Hydroxyurea is the primary therapy, and recent advances in understanding disease pathophysiology have led to new therapies; progress in bone marrow transplant and gene editing has resulted in cure in some patients. The purpose of this review is to provide an overview of the diagnosis, common acute and chronic clinical manifestations, and best practices for management of sickle cell disease.



Ann Intern Med: 11 Jan 2021; epub ahead of print
Pecker LH, Lanzkron S
Ann Intern Med: 11 Jan 2021; epub ahead of print | PMID: 33428443
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Abstract

The Effect of Flat Flexible Versus Stable Supportive Shoes on Knee Osteoarthritis Symptoms : A Randomized Trial.

Paterson KL, Bennell KL, Campbell PK, Metcalf BR, ... Kasza J, Hinman RS
Background
Experts recommend that persons with knee osteoarthritis wear stable supportive shoes; however, evidence suggests that flat flexible shoes may be more beneficial.
Objective
To compare flat flexible with stable supportive shoes for knee osteoarthritis symptoms.
Design
Participant- and assessor-blinded randomized trial. (Prospectively registered with the Australian New Zealand Clinical Trials Registry [ACTRN12617001098325]).
Setting
Community.
Participants
164 patients with moderate to severe symptomatic radiographic medial knee osteoarthritis.
Intervention
Flat flexible ( = 82) or stable supportive shoes ( = 82), worn for at least 6 hours a day for 6 months.
Measurements
Primary outcomes were changes in walking pain (measured by an 11-point numerical rating scale) and physical function (as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale of 0 to 68 points) at 6 months. Secondary outcomes included additional pain and function measures, physical activity, and quality of life. Other measures included adverse events.
Results
Of 164 participants recruited, 161 (98%) completed 6-month primary outcomes. No evidence was found that flat flexible shoes were superior to stable supportive shoes in primary outcomes. Evidence did show a between-group difference in change in pain favoring stable supportive shoes (mean difference, 1.1 units [95% CI, 0.5 to 1.8 units];  = 0.001) but not function (mean difference, 2.3 units [CI, -0.9 to 5.5 units];  = 0.167). Improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes (mean difference, -5.3 units [CI, -10.0 to -0.5 units] and 0.7 units [CI, 0.0 to 1.4 units], respectively). Flat flexible shoes were not superior to stable supportive shoes for any secondary outcome. Fewer participants reported adverse events with stable supportive shoes ( = 12 [15%]) compared with flat flexible shoes ( = 26 [32%]) (risk difference, -0.17 [CI, -0.30 to -0.05]).
Limitation
No \"usual shoes\" control group and a select patient subgroup, which may limit generalizability.
Conclusion
Flat flexible shoes were not superior to stable supportive shoes. Contrary to our hypothesis, stable supportive shoes improved knee pain on walking more than flat flexible shoes.
Primary funding source
National Health and Medical Research Council.



Ann Intern Med: 11 Jan 2021; epub ahead of print
Paterson KL, Bennell KL, Campbell PK, Metcalf BR, ... Kasza J, Hinman RS
Ann Intern Med: 11 Jan 2021; epub ahead of print | PMID: 33428439
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Abstract

Population Mortality and Laws Encouraging Influenza Vaccination for Hospital Workers.

Carrera M, Lawler EC, White C
Background
Since 1995, 14 states have passed laws encouraging or mandating influenza vaccination for hospital workers. Although the Centers for Disease Control and Prevention recommends vaccinating health care workers to reduce disease transmission and patient risk, the effect of these laws on pneumonia and influenza mortality is unknown.
Objective
To measure the effect of state-level hospital worker influenza vaccination laws on pneumonia and influenza mortality.
Design
Quasi-experimental observational study.
Setting
United States.
Participants
Population of all states from 1995 to 2017.
Intervention
State adoption of a law promoting influenza vaccination for hospital workers.
Measurements
Pneumonia and influenza mortality per 100 000 persons by state and by month, both population-wide and separately by age group, obtained from restricted-access National Vital Statistics System files. Linear and log-linear models were used to compare changes in mortality rates for adopting versus nonadopting states.
Results
Implementation of state laws requiring hospitals to offer influenza vaccination to their employees was associated with a 2.5% reduction in the monthly pneumonia and influenza mortality rate (-0.16 deaths per 100 000 persons [95% CI, -0.29 to -0.02];= 0.022) during the years when the vaccine was well matched to the circulating strains. The largest effects occurred among elderly persons and during peak influenza months.
Limitation
Utilization of large-scale national data precluded analysis of more specific outcomes, such as laboratory-confirmed or hospital-acquired influenza.
Conclusion
State laws promoting hospital worker vaccination against influenza may be effective in preventing pneumonia- and influenza-related deaths, particularly among elderly persons. Vaccinating hospital workers may substantially reduce the spread of influenza and protect the most vulnerable populations.
Primary funding source
None.



Ann Intern Med: 04 Jan 2021; epub ahead of print
Carrera M, Lawler EC, White C
Ann Intern Med: 04 Jan 2021; epub ahead of print | PMID: 33395343
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Abstract

Stepped Exercise Program for Patients With Knee Osteoarthritis : A Randomized Controlled Trial.

Allen KD, Woolson S, Hoenig HM, Bongiorni D, ... Abbate LM, Coffman CJ
Background
Evidence-based models are needed to deliver exercise-related services for knee osteoarthritis efficiently and according to patient needs
Objective
To examine a stepped exercise program for patients with knee osteoarthritis (STEP-KOA).
Design
Randomized controlled trial. (ClinicalTrials.gov: NCT02653768).
Setting
2 U.S. Department of Veterans Affairs sites.
Participants
345 patients (mean age, 60 years; 15% female; 67% people of color) with symptomatic knee osteoarthritis.
Intervention
Participants were randomly assigned in a 2:1 ratio to STEP-KOA or an arthritis education (AE) control group, respectively. The STEP-KOA intervention began with 3 months of an internet-based exercise program (step 1). Participants who did not meet response criteria for improvement in pain and function after step 1 progressed to step 2, which involved 3 months of biweekly physical activity coaching calls. Participants who did not meet response criteria after step 2 went on to in-person physical therapy visits (step 3). The AE group received educational materials via mail every 2 weeks.
Measurements
Primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Scores for the STEP-KOA and AE groups at 9 months were compared by using linear mixed models.
Results
In the STEP-KOA group, 65% of participants (150 of 230) progressed to step 2 and 35% (81 of 230) to step 3. The estimated baseline WOMAC score for the full sample was 47.5 (95% CI, 45.7 to 49.2). At 9-month follow-up, the estimated mean WOMAC score was 6.8 points (CI, -10.5 to -3.2 points) lower in the STEP-KOA than the AE group, indicating greater improvement.
Limitation
Participants were mostly male veterans, and follow-up was limited.
Conclusion
Veterans in STEP-KOA reported modest improvements in knee osteoarthritis symptoms compared with the control group. The STEP-KOA strategy may be efficient for delivering exercise therapies for knee osteoarthritis.
Primary funding source
Department of Veterans Affairs, Health Services Research and Development Service.



Ann Intern Med: 28 Dec 2020; epub ahead of print
Allen KD, Woolson S, Hoenig HM, Bongiorni D, ... Abbate LM, Coffman CJ
Ann Intern Med: 28 Dec 2020; epub ahead of print | PMID: 33370174
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Abstract

Masks and Face Coverings for the Lay Public : A Narrative Update.

Czypionka T, Greenhalgh T, Bassler D, Bryant MB

Whether and when to mandate the wearing of facemasks in the community to prevent the spread of coronavirus disease 2019 remains controversial. Published literature across disciplines about the role of masks in mitigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is summarized. Growing evidence that SARS-CoV-2 is airborne indicates that infection control interventions must go beyond contact and droplet measures (such as handwashing and cleaning surfaces) and attend to masking and ventilation. Observational evidence suggests that masks work mainly by source control (preventing infected persons from transmitting the virus to others), but laboratory studies of mask filtration properties suggest that they could also provide some protection to wearers (protective effect). Even small reductions in individual transmission could lead to substantial reductions in population spread. To date, only 1 randomized controlled trial has examined a community mask recommendation. This trial did not identify a significant protective effect and was not designed to evaluate source control. Filtration properties and comfort vary widely across mask types. Masks may cause discomfort and communication difficulties. However, there is no evidence that masks result in significant physiologic decompensation or that risk compensation and fomite transmission are associated with mask wearing. The psychological effects of masks are culturally shaped; they may include threats to autonomy, social relatedness, and competence. Evidence suggests that the potential benefits of wearing masks likely outweigh the potential harms when SARS-CoV-2 is spreading in a community. However, mask mandates involve a tradeoff with personal freedom, so such policies should be pursued only if the threat is substantial and mitigation of spread cannot be achieved through other means.



Ann Intern Med: 28 Dec 2020; epub ahead of print
Czypionka T, Greenhalgh T, Bassler D, Bryant MB
Ann Intern Med: 28 Dec 2020; epub ahead of print | PMID: 33370173
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Abstract

Testing for Primary Aldosteronism and Mineralocorticoid Receptor Antagonist Use Among U.S. Veterans : A Retrospective Cohort Study.

Cohen JB, Cohen DL, Herman DS, Leppert JT, Byrd JB, Bhalla V
Background
Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism.
Objective
To evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension.
Design
Retrospective cohort study.
Setting
U.S. Veterans Health Administration.
Participants
Veterans with apparent treatment-resistant hypertension ( = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes.
Measurements
Rates of primary aldosteronism testing (plasma aldosterone-renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP.
Results
4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time.
Limitations
Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism.
Conclusion
In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension.
Primary funding source
National Institutes of Health.



Ann Intern Med: 28 Dec 2020; epub ahead of print
Cohen JB, Cohen DL, Herman DS, Leppert JT, Byrd JB, Bhalla V
Ann Intern Med: 28 Dec 2020; epub ahead of print | PMID: 33370170
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Impact:
Abstract

Spillover Effects of Medicare\'s Voluntary Bundled Payments for Joint Replacement Surgery to Patients Insured by Commercial Health Plans.

Navathe AS, Liao JM, Linn KA, Zhang Y, ... Lindner J, Emanuel EJ
Background
Under the Bundled Payments for Care Improvement (BPCI) program, bundled paymtents for lower-extremity joint replacement (LEJR) are associated with 2% to 4% cost savings with stable quality among Medicare fee-for-service beneficiaries. However, BPCI may prompt practice changes that benefit all patients, not just fee-for-service beneficiaries.
Objective
To examine the association between hospital participation in BPCI and LEJR outcomes for patients with commercial insurance or Medicare Advantage (MA).
Design
Quasi-experimental study using Health Care Cost Institute claims from 2011 to 2016.
Setting
LEJR at 281 BPCI hospitals and 562 non-BPCI hospitals.
Patients
184 922 patients with MA or commercial insurance.
Measurements
Differential changes in LEJR outcomes at BPCI hospitals versus at non-BPCI hospitals matched on propensity score were evaluated using a difference-in-differences (DID) method. Secondary analyses evaluated associations by patient MA status and hospital characteristics. Primary outcomes were changes in 90-day total spending on LEJR episodes and 90-day readmissions; secondary outcomes were postacute spending and discharge to postacute care providers.
Results
Average episode spending decreased more at BPCI versus non-BPCI hospitals (change, -2.2% [95% CI, -3.6% to -0.71%];  = 0.004), but differences in changes in 90-day readmissions were not significant (adjusted DID, -0.47 percentage point [CI, -1.0 to 0.06 percentage point];  = 0.084). Participation in BPCI was also associated with differences in decreases in postacute spending and discharge to institutional postacute care providers. Decreases in episode spending were larger for hospitals with high baseline spending but did not vary by MA status.
Limitation
Nonrandomized studies are subject to residual confounding and selection.
Conclusion
Participation in BPCI was associated with modest spillovers in episode savings. Bundled payments may prompt hospitals to implement broad care redesign that produces benefits regardless of insurance coverage.
Primary funding source
Leonard Davis Institute of Health Economics at the University of Pennsylvania.



Ann Intern Med: 21 Dec 2020; epub ahead of print
Navathe AS, Liao JM, Linn KA, Zhang Y, ... Lindner J, Emanuel EJ
Ann Intern Med: 21 Dec 2020; epub ahead of print | PMID: 33347769
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Abstract

College Campuses and COVID-19 Mitigation: Clinical and Economic Value.

Losina E, Leifer V, Millham L, Panella C, ... Kazemian P, Freedberg KA
Background
Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic.
Objective
To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses.
Design
The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions.
Data sources
Data from published literature were used to obtain parameters related to COVID-19 and contact-hours.
Target population
Undergraduate students and faculty at U.S. colleges.
Time horizon
One semester (105 days).
Perspective
Modified societal.
Intervention
COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening.
Outcome measures
Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY).
Results of base-case analysis
Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600).
Results of sensitivity analysis
Results were most sensitive to test costs.
Limitation
Data are from multiple sources.
Conclusion
Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive.
Primary funding source
National Institutes of Health.



Ann Intern Med: 20 Dec 2020; epub ahead of print
Losina E, Leifer V, Millham L, Panella C, ... Kazemian P, Freedberg KA
Ann Intern Med: 20 Dec 2020; epub ahead of print | PMID: 33347322
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Impact:
Abstract

Comparison of Knowledge and Information-Seeking Behavior After General COVID-19 Public Health Messages and Messages Tailored for Black and Latinx Communities : A Randomized Controlled Trial.

Alsan M, Stanford FC, Banerjee A, Breza E, ... Vautrey PL, Duflo E
Background
The paucity of public health messages that directly address communities of color might contribute to racial and ethnic disparities in knowledge and behavior related to coronavirus disease 2019 (COVID-19).
Objective
To determine whether physician-delivered prevention messages affect knowledge and information-seeking behavior of Black and Latinx individuals and whether this differs according to the race/ethnicity of the physician and tailored content.
Design
Randomized controlled trial. (Registration: ClinicalTrials.gov, NCT04371419; American Economic Association RCT Registry, AEARCTR-0005789).
Setting
United States, 13 May 2020 to 26 May 2020.
Participants
14 267 self-identified Black or Latinx adults recruited via Lucid survey platform.
Intervention
Participants viewed 3 video messages regarding COVID-19 that varied by physician race/ethnicity, acknowledgement of racism/inequality, and community perceptions of mask-wearing.
Measurements
Knowledge gaps (number of errors on 7 facts on COVID-19 symptoms and prevention) and information-seeking behavior (number of Web links demanded out of 10 proposed).
Results
7174 Black (61.3%) and 4520 Latinx (38.7%) participants were included in the analysis. The intervention reduced the knowledge gap incidence from 0.085 to 0.065 (incidence rate ratio, [IRR], 0.737 [95% CI, 0.600 to 0.874]) but did not significantly change information-seeking incidence. For Black participants, messages from race/ethnic-concordant physicians increased information-seeking incidence from 0.329 (for discordant physicians) to 0.357 (IRR, 1.085 [CI, 1.026 to 1.145]).
Limitations
Participants\' behavior was not directly observed, outcomes were measured immediately postintervention in May 2020, and online recruitment may not be representative.
Conclusion
Physician-delivered messages increased knowledge of COVID-19 symptoms and prevention methods for Black and Latinx respondents. The desire for additional information increased with race-concordant messages for Black but not Latinx respondents. Other tailoring of the content did not make a significant difference.
Primary funding source
National Science Foundation; Massachusetts General Hospital; and National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.



Ann Intern Med: 20 Dec 2020; epub ahead of print
Alsan M, Stanford FC, Banerjee A, Breza E, ... Vautrey PL, Duflo E
Ann Intern Med: 20 Dec 2020; epub ahead of print | PMID: 33347320
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Impact:
Abstract

Increases in Actual Health Care Costs and Claims After Firearm Injury.

Ranney ML, Herges C, Metcalfe L, Schuur JD, Hain P, Rowhani-Rahbar A
Background
The incidence of firearm injury and death in the United States is increasing. Although the health care-related effect of firearm injury is estimated to be high, existing data are largely cross-sectional, do not include data on preinjury and postinjury health care visits and related costs, and use hospital charges rather than actual monetary payments.
Objective
To compare actual health care costs (that is, actual monetary payments) and utilizations within the 6 months before and after an incident (index) firearm injury.
Design
Before-after study.
Setting
Blue Cross Blue Shield plans of Illinois, Texas, Oklahoma, New Mexico, and Montana.
Participants
Plan members continuously enrolled for at least 12 months before and after an index firearm injury sustained between 1 January 2015 and 31 December 2017.
Measurements
Eligible costs, out-of-pocket costs, and firearm injury-related International Classification of Diseases, Ninth or 10th Revision, codes.
Results
Total initial (emergency department [ED]) health care costs for persons with index firearm injuries who were discharged from the ED were $8 158 786 ($5686 per member). Total initial (hospital admission) costs for persons with index firearm injuries who required hospitalization were $41 255 916 ($70 644 per member). Compared with the 6 months before the index firearm injury, in the 6 months after, per-member costs increased by 347% (from $3984 to $17 806 per member) for those discharged from the ED and 2138% (from $4118 to $92 151 per member) for those who were hospitalized. The number of claims increased by 187% for patients discharged from the ED and 608% for those who were hospitalized.
Limitation
Firearm injury intent was not specified because of misclassification concerns.
Conclusion
In the 6 months after a firearm injury, patient-level health care visits and costs increased by 3 to 20 times compared with the 6 months prior. The burden of firearm injury on the health care system is large and quantifiable.
Primary funding source
None.



Ann Intern Med: 14 Dec 2020; 173:949-955
Ranney ML, Herges C, Metcalfe L, Schuur JD, Hain P, Rowhani-Rahbar A
Ann Intern Med: 14 Dec 2020; 173:949-955 | PMID: 32986488
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Impact:
Abstract

Contributions of Adenocarcinoma and Carcinoid Tumors to Early-Onset Colorectal Cancer Incidence Rates in the United States.

Montminy EM, Zhou M, Maniscalco L, Abualkhair W, ... Itzkowitz SH, Karlitz JJ
Background
Early-onset colorectal cancer (EOCRC) incidence rates (IRs) are rising, according to previous cancer registry analyses. However, analysis of histologic subtypes, including adenocarcinoma (the focus of CRC screening and diagnostic testing) and carcinoid tumors (which are classified as \"colorectal cancer\" in SEER [Surveillance, Epidemiology, and End Results] databases but have a distinct pathogenesis and are managed differently from adenocarcinoma), has not been reported.
Objective
To assess EOCRC IRs and changes in IRs over time, stratified by histology.
Design
Retrospective analysis.
Setting
Yearly IRs according to SEER 18 data from 2000 to 2016 on age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology (\"overall\" CRC [all histologic subtypes], adenocarcinoma, and carcinoid tumors) and age.
Patients
119 624 patients with CRC.
Measurements
IRs per 100 000 population, changes in 3-year average annual IRs (pooled IRs from 2000 to 2002 vs. those from 2014 to 2016), and annual percentage change (APC) in persons aged 20 to 29, 30 to 39, 40 to 49, and 50 to 54 years.
Results
The steepest changes in adenocarcinoma 3-year average annual IRs were for rectal-only cases in persons aged 20 to 29 years (+39% [0.33 to 0.46 per 100 000];< 0.050) and 30 to 39 years (+39% [1.92 to 2.66 per 100 000];< 0.050) and colon-only cases in those aged 30 to 39 years (+20% [3.30 to 3.97 per 100 000];< 0.050). Corresponding APCs were 1.6% ( < 0.050), 2.2% ( < 0.050), and 1.2% ( < 0.050), respectively. In persons aged 40 to 49 years, 3-year average annual IRs increased in both colon-only (+13% [12.21 to 13.85 per 100 000];< 0.050) and rectal-only (+16% [7.50 to 8.72 per 100 000];< 0.050) subsites. Carcinoid tumors were common, representing approximately 4% to 20% of all colorectal and 8% to 34% of all rectal cancer cases, depending on age group and calendar year. Colon-only carcinoid tumors were rare. Colorectal carcinoid tumor IRs increased more steeply than adenocarcinoma in all age groups, thus affecting the contribution of carcinoid tumors to overall cancer cases over time. These changes were driven by rectal subsites and were most pronounced in persons aged 50 to 54 years, in whom rectal carcinoid tumors increased by 159% (2.36 to 6.10 per 100 000) between 2000 to 2002 and 2014 to 2016, compared with 10% for adenocarcinoma (18.07 to 19.84 per 100 000), ultimately accounting for 22.6% of all rectal cancer cases.
Limitation
Population-based data.
Conclusion
These findings underscore the importance of assessing histologic CRC subtypes independently. Doing so may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of outcomes from efforts to reduce adenocarcinoma risk, and can guide future research.
Primary funding source
None.



Ann Intern Med: 14 Dec 2020; epub ahead of print
Montminy EM, Zhou M, Maniscalco L, Abualkhair W, ... Itzkowitz SH, Karlitz JJ
Ann Intern Med: 14 Dec 2020; epub ahead of print | PMID: 33315473
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Impact:
Abstract

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19 : A Retrospective Study.

Fu Y, Li Y, Guo E, He L, ... Sun C, Chen G
Background
The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited.
Objective
To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity.
Design
Retrospective cohort study.
Setting
3 designated specialty care centers for COVID-19 in Wuhan, China.
Participants
3192 adult patients with COVID-19.
Measurements
Demographic, clinical, and laboratory data.
Results
Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824];0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity.
Limitation
Retrospective study and irregular viral and serology testing.
Conclusion
The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity.
Primary funding source
None.



Ann Intern Med: 07 Dec 2020; epub ahead of print
Fu Y, Li Y, Guo E, He L, ... Sun C, Chen G
Ann Intern Med: 07 Dec 2020; epub ahead of print | PMID: 33284684
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Impact:
Abstract

Clinician Perspectives on Caring for Dying Patients During the Pandemic : A Mixed-Methods Study.

Cook DJ, Takaoka A, Hoad N, Swinton M, ... Fiest K, Vanstone M
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected the hospital experience for patients, visitors, and staff.
Objective
To understand clinician perspectives on adaptations to end-of-life care for dying patients and their families during the pandemic.
Design
Mixed-methods embedded study. (ClinicalTrials.gov: NCT04602520).
Setting
3 acute care medical units in a tertiary care hospital from 16 March to 1 July 2020.
Participants
45 dying patients, 45 family members, and 45 clinicians.
Intervention
During the pandemic, clinicians continued an existing practice of collating personal information about dying patients and \"what matters most,\" eliciting wishes, and implementing acts of compassion.
Measurements
Themes from semistructured clinician interviews that were summarized with representative quotations.
Results
Many barriers to end-of-life care arose because of infection control practices that mandated visiting restrictions and personal protective equipment, with attendant practical and psychological consequences. During hospitalization, family visits inside or outside the patient\'s room were possible for 36 patients (80.0%); 13 patients (28.9%) had virtual visits with a relative or friend. At the time of death, 20 patients (44.4%) had a family member at the bedside. Clinicians endeavored to prevent unmarked deaths by adopting advocacy roles to \"fill the gap\" of absent family and by initiating new and established ways to connect patients and relatives.
Limitation
Absence of clinician symptom or wellness metrics; a single-center design.
Conclusion
Clinicians expressed their humanity through several intentional practices to preserve personalized, compassionate end-of-life care for dying hospitalized patients during the SARS-CoV-2 pandemic.
Primary funding source
Canadian Institutes of Health Research and Canadian Critical Care Trials Group Research Coordinator Fund.



Ann Intern Med: 07 Dec 2020; epub ahead of print
Cook DJ, Takaoka A, Hoad N, Swinton M, ... Fiest K, Vanstone M
Ann Intern Med: 07 Dec 2020; epub ahead of print | PMID: 33284683
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Impact:
Abstract

Peripheral Neuropathy and All-Cause and Cardiovascular Mortality in U.S. Adults : A Prospective Cohort Study.

Hicks CW, Wang D, Matsushita K, Windham BG, Selvin E
Background
Growing evidence indicates that peripheral neuropathy (PN) is common even in the absence of diabetes However, the clinical sequelae of PN have not been quantified in the general population.
Objective
To assess the associations of PN with all-cause and cardiovascular mortality in the general adult population of the United States.
Design
Prospective cohort study.
Setting
NHANES (National Health and Nutrition Examination Survey), 1999 to 2004.
Participants
7116 adults aged 40 years or older who had standardized monofilament testing for PN.
Measurements
Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality after adjustment for demographic and cardiovascular risk factors, overall and stratified by diabetes status.
Results
The overall prevalence of PN (±SE) was 13.5% ± 0.5% (27.0% ± 1.4% in adults with diabetes and 11.6% ± 0.5% in adults without diabetes). During a median follow-up of 13 years, 2128 participants died, including 488 of cardiovascular causes. Incidence rates (per 1000 person-years) of all-cause mortality were 57.6 (95% CI, 48.4 to 68.7) in adults with diabetes and PN, 34.3 (CI, 30.3 to 38.8) in adults with PN but no diabetes, 27.1 (CI, 23.4 to 31.5) in adults with diabetes but no PN, and 13.0 (CI, 12.1 to 14.0) in adults with no diabetes and no PN. In adjusted models, PN was significantly associated with all-cause mortality (hazard ratio [HR], 1.49 [CI, 1.15 to 1.94]) and cardiovascular mortality (HR, 1.66 [CI, 1.07 to 2.57]) in participants with diabetes. In those without diabetes, PN was significantly associated with all-cause mortality (HR, 1.31 [CI, 1.15 to 1.50]), but the association between PN and cardiovascular mortality was not statistically significant after adjustment (HR, 1.27 [CI, 0.98 to 1.66]).
Limitation
Prevalent cardiovascular disease was self-reported, and PN was defined by monofilament testing only.
Conclusion
Peripheral neuropathy was common and was independently associated with mortality in the U.S. population, even in the absence of diabetes. These findings suggest that decreased sensation in the foot may be an underrecognized risk factor for death in the general population.
Primary funding source
National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute of the National Institutes of Health.



Ann Intern Med: 07 Dec 2020; epub ahead of print
Hicks CW, Wang D, Matsushita K, Windham BG, Selvin E
Ann Intern Med: 07 Dec 2020; epub ahead of print | PMID: 33284680
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Impact:
Abstract

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

Barnabas RV, Brown ER, Bershteyn A, Stankiewicz Karita HC, ... Chu HY, Baeten JM
Background
Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.
Objective
To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.
Design
Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961).
Setting
National U.S. multicenter study.
Participants
Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection.
Intervention
Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control.
Measurements
Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment.
Results
Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66];  > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively;  = 0.026).
Limitation
The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days.
Conclusion
This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.
Primary funding source
Bill & Melinda Gates Foundation.



Ann Intern Med: 07 Dec 2020; epub ahead of print
Barnabas RV, Brown ER, Bershteyn A, Stankiewicz Karita HC, ... Chu HY, Baeten JM
Ann Intern Med: 07 Dec 2020; epub ahead of print | PMID: 33284679
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Impact:
Abstract

Effect of Intensive Blood Pressure Lowering on Cardiovascular Outcomes: A Systematic Review Prepared for the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Guidelines.

D\'Anci KE, Tipton K, Hedden-Gross A, Rouse B, Hermanson L, Fontanarosa J
Background
Recent clinical trials suggest that treating patients with hypertension to lower blood pressure (BP) targets improves cardiovascular outcomes.
Purpose
To summarize the effects of intensive (or targeted) systolic BP (SBP) and diastolic BP (DBP) lowering with pharmacologic treatment on cardiovascular outcomes and harms in adults with hypertension.
Data sources
Multiple databases, including MEDLINE and EMBASE, were searched for relevant systematic reviews (SRs) published in English from 15 December 2013 through 25 March 2019, with updated targeted searches through 8 January 2020.
Study selection
8 SRs of randomized controlled trials examining either a standardized SBP target of -10 mm Hg (1 SR) or BP lowering below a target threshold (7 SRs).
Data extraction
One investigator abstracted data, assessed study quality, and performed GRADE assessments; a second investigator checked abstractions and assessments.
Data synthesis
The main outcome of interest was reduction in composite cardiovascular outcomes. High-strength evidence showed benefit of a 10-mm Hg reduction in SBP for cardiovascular outcomes among patients with hypertension in the general population, patients with chronic kidney disease, and patients with heart failure. Evidence on reducing SBP for cardiovascular outcomes in patients with a history of cardiovascular disease (moderate strength) or diabetes mellitus (high strength) to a lower SBP target was mixed. Low-strength evidence supported intensive lowering to a 10-mm Hg reduction in SBP for cardiovascular outcomes in patients with a history of stroke. All reported harms were considered, including general adverse events, serious adverse events, cognitive impairment, fractures, falls, syncope, hypotension, withdrawals due to adverse events, and acute kidney injury. Safety results were mixed or inconclusive.
Limitations
This was a qualitative synthesis of new evidence with existing meta-analyses. Data were sparse for outcomes related to treating DBP to a lower target or for patients older than 60 years.
Conclusion
Overall, current clinical literature supports intensive BP lowering in patients with hypertension for improving cardiovascular outcomes. In most subpopulations, intensive lowering was favored over less-intensive lowering, but the data were less clear for patients with diabetes mellitus or cardiovascular disease.
Primary funding source
U.S. Department of Veterans Affairs, Veterans Health Administration.



Ann Intern Med: 30 Nov 2020; 173:895-903
D'Anci KE, Tipton K, Hedden-Gross A, Rouse B, Hermanson L, Fontanarosa J
Ann Intern Med: 30 Nov 2020; 173:895-903 | PMID: 32866419
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Impact:
Abstract

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

Mackey K, Ayers CK, Kondo KK, Saha S, ... Smith M, Kansagara D
Background
Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups.
Purpose
To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. (PROSPERO: CRD42020187078).
Data sources
English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020.
Study selection
Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings.
Data extraction
Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence.
Data synthesis
37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence).
Limitations
Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies.
Conclusion
African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates.
Primary funding source
Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development.



Ann Intern Med: 30 Nov 2020; epub ahead of print
Mackey K, Ayers CK, Kondo KK, Saha S, ... Smith M, Kansagara D
Ann Intern Med: 30 Nov 2020; epub ahead of print | PMID: 33253040
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Impact:
Abstract

Cases in Precision Medicine: The Role of Polygenic Risk Scores in Breast Cancer Risk Assessment.

Zeinomar N, Chung WK

Polygenic risk scores (PRSs) have been consistently associated with elevated breast cancer risk in cohort studies and are associated with risk in both women with and those without a family history of breast cancer. However, before clinical implementation, several issues must be addressed, including understanding the potential clinical utility and optimal method to communicate personalized screening recommendations that incorporate the PRS. Several trials are under way to answer some of these questions and facilitate clinical implementation. Because these PRSs have been developed in women of European ancestry, it is important to understand the limitations of their predictive ability in other ancestral groups. Finally, the value of the PRS will lie in considering it along with other clinical, familial, and rare genetic factors that are currently used in personalized risk assessment of breast cancer.



Ann Intern Med: 30 Nov 2020; epub ahead of print
Zeinomar N, Chung WK
Ann Intern Med: 30 Nov 2020; epub ahead of print | PMID: 33253037
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Impact:
Abstract

Health Needs of Mothers of Infants in a Neonatal Intensive Care Unit : A Mixed-Methods Study.

Verbiest S, Ferrari R, Tucker C, McClain EK, Charles N, Stuebe AM
Background
Mothers with babies in the neonatal intensive care unit (NICU) face a host of challenges following childbirth. Limited information is available on these mothers\' postpartum health needs and access to services.
Objective
To identify health needs of NICU mothers, access to services, and potential service improvements.
Design
A mixed-methods study including a retrospective cohort study, in-depth interviews, and focus groups.
Setting
Large, Level IV, regional referral, university-affiliated hospital in the United States.
Participants
Mothers of live-born infants born from 1 July 2014 to 30 June 2016 ( = 6849). Interviews included 50 NICU mothers and 59 stakeholders who provide services to these mothers or their infants.
Measurements
Severe maternal morbidity, chronic health conditions, health care encounters from discharge through 12 weeks postpartum, maternal health needs, care access, and system improvements.
Results
Compared with mothers of well babies, NICU mothers had more chronic diseases, experienced more perinatal complications, and utilized more acute care postpartum. Qualitative analyses revealed the desire to be at the baby\'s bedside as a driver of maternal health-seeking behaviors, with women not seeking or delaying medical care so as to stay by their infant. Stakeholders acknowledged the unique needs of NICU mothers and cited system challenges, lack of clarity about provider roles, and reimbursement policies as barriers to meeting needs.
Limitations
The study was conducted within a single health care system, which may limit generalizability. Qualitative analyses did not explore the influence of fathers, other children in the home, or length of NICU stay.
Conclusion
Universal screening and convenient access to maternal health services for NICU mothers should be explored to reduce adverse maternal health outcomes.
Primary funding source
Maternal and Child Health Bureau, Health Resources and Services Administration, U.S. Department of Health and Human Services.



Ann Intern Med: 30 Nov 2020; 173:S37-S44
Verbiest S, Ferrari R, Tucker C, McClain EK, Charles N, Stuebe AM
Ann Intern Med: 30 Nov 2020; 173:S37-S44 | PMID: 33253024
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Impact:
Abstract

Association of Maternal Comorbidity With Severe Maternal Morbidity: A Cohort Study of California Mothers Delivering Between 1997 and 2014.

Main EK, Leonard SA, Menard MK
Background
Rates of maternal mortality and severe maternal morbidity (SMM) are higher in the United States than in other high-resource countries and are increasing further.
Objective
To examine the association of maternal comorbid conditions, age, body mass index, and previous cesarean birth with occurrence of SMM.
Design
Population-based cohort study using linked delivery hospitalization discharge data and vital records.
Setting
California, 1997 to 2014.
Patients
All 9 179 472 mothers delivering in California during 1997 to 2014.
Measurements
SMM rate, total and without transfusion-only cases; 2019 maternal comorbidity index.
Results
Total SMM increased by 160% during this time, and SMM excluding transfusion-only cases increased by 53%. Medical comorbid conditions were associated with an increasing portion of SMM occurrences. Medical comorbid conditions increased over the study period by 111%, and obstetric comorbid conditions increased by 30% to 40%. Identified medical comorbid conditions had high relative risks ranging from 1.3 to 14.3 for total SMM and even higher relative risks for nontransfusion SMM (to 32.4). The obstetric comorbidity index that is most often used may be undervaluing the degree of association with SMM.
Limitations
Hospital discharge diagnosis files and birth certificate records can have misclassifications and may not include all relevant clinical data or social determinants. The period for analysis ended in 2014 to avoid the transition to the International Classification of Diseases, 10th Revision, Clinical Modification, and therefore missed more recent years.
Conclusion
Obstetric and, particularly, medical comorbid conditions are increasing among women who develop SMM. The maternal comorbidity index is a promising tool for patient risk assessment and case-mix adjustment, but refinement of factor weights may be indicated.
Primary funding source
National Institutes of Health.



Ann Intern Med: 30 Nov 2020; 173:S11-S18
Main EK, Leonard SA, Menard MK
Ann Intern Med: 30 Nov 2020; 173:S11-S18 | PMID: 33253023
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Impact:
Abstract

Regional Variations in Maternal Mortality and Health Workforce Availability in the United States.

Snyder JE, Stahl AL, Streeter RA, Washko MM
Background
Skilled, high-quality health providers and birth attendants are important for reducing maternal mortality.
Objective
To assess whether U.S. regional variations in maternal mortality rates relate to health workforce availability.
Design
Comparison of regional variations in maternal mortality rates and women\'s health provider rates per population and identification of a relationship between these measures.
Setting
U.S. health system.
Participants
Women of child-bearing age and women\'s health providers, as captured in federal data sources from the Centers for Disease Control and Prevention, Census Bureau, and Health Resources and Services Administration.
Measurements
Regional-to-national rate ratios for maternal mortality and women\'s health provider availability, calculated per population for women of reproductive age. Provider availability was examined across occupations (obstetrician-gynecologists, internal medicine physicians, family medicine physicians, certified nurse-midwives), in service-based categories (birth-attending and primary care providers), and across the entire women\'s health workforce (all studied occupations).
Results
Maternal deaths per population increased nationally from 2009 to 2017 and, in 2017, were significantly higher in the South and lower in the Northeast ( < 0.001) than nationally. The occupational composition and per-population availability patterns of the women\'s health workforce varied regionally in 2017. The South had the lowest availability in the nation for nearly every health occupation and category studied, and the Northeast had the highest. This exploratory analysis suggests that subnational levels of provider availability across a region may be associated with higher maternal mortality rates.
Limitations
No causal relationship was established. Nationally representative maternal mortality and health workforce data sources have well-known limitations. Low numbers of observations limit statistical analyses.
Conclusion
Regional variations in maternal mortality rates may relate to the availability of birth-attending and primary care providers.
Primary funding source
None.



Ann Intern Med: 30 Nov 2020; 173:S45-S54
Snyder JE, Stahl AL, Streeter RA, Washko MM
Ann Intern Med: 30 Nov 2020; 173:S45-S54 | PMID: 33253022
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Impact:
Abstract

Initiatives to Reduce Maternal Mortality and Severe Maternal Morbidity in the United States : A Narrative Review.

Ahn R, Gonzalez GP, Anderson B, Vladutiu CJ, Fowler ER, Manning L

Maternal mortality and severe maternal morbidity are critical health issues in the United States, with unacceptably high rates and racial, ethnic, and geographic disparities. Various factors contribute to these adverse maternal health outcomes, ranging from patient-level to health system-level factors. Furthermore, a majority of pregnancy-related deaths are preventable. This review briefly describes the epidemiology of maternal mortality and severe maternal morbidity in the United States and discusses selected initiatives to reduce maternal mortality and severe maternal morbidity in the areas of data and surveillance; clinical workforce training and patient education; telehealth; comprehensive models and strategies; and clinical guidelines, protocols, and bundles. Related Health Resources and Services Administration initiatives are also described.



Ann Intern Med: 30 Nov 2020; 173:S3-S10
Ahn R, Gonzalez GP, Anderson B, Vladutiu CJ, Fowler ER, Manning L
Ann Intern Med: 30 Nov 2020; 173:S3-S10 | PMID: 33253021
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Impact:
Abstract

Timing of Prenatal Care Initiation in the Health Resources and Services Administration Health Center Program in 2017.

Robbins C, Martocci S
Background
Early prenatal care is vital for improving maternal health outcomes and health behaviors, but medically vulnerable and underserved populations are less likely to begin prenatal care in the first trimester. In 2017, the Health Center Program provided safety-net care to more than 27 million persons, including 573 026 prenatal patients, at approximately 12 000 sites across the United States and U.S. jurisdictions. As part of a mandatory reporting requirement, health centers tracked whether patients initiated prenatal care in their first trimester of pregnancy.
Objective
To identify health center characteristics associated with the initiation of prenatal care in the first trimester, as well as actionable steps policymakers, providers, and health centers can take to promote early initiation of prenatal care.
Design
Secondary analysis of cross-sectional data from the 2017 Uniform Data System.
Setting
The United States and 8 U.S. jurisdictions.
Participants
Health center grantees with prenatal patients ( = 1281).
Measurements
Multinomial logistic regression (adjusted for state or jurisdiction clustering) was used to identify health center characteristics associated with achievement of the Healthy People 2020 baseline (77.1%) and target (84.8%) for women receiving prenatal care in the first trimester (Maternal, Infant, and Child Health Objective 10.1).
Results
Overall, 57.4% of health centers met the Healthy People 2020 baseline (mean, 78%; median, 81%), and 37.9% met the Healthy People 2020 target. Several characteristics were positively associated with meeting the baseline (larger proportion of prenatal patients aged 20 to 24 years) and target (more total patients, prenatal care by referral only, a larger proportion of prenatal patients aged 25 to 44 or ≥45 years, and a larger proportion of White or privately insured patients). Other characteristics were negatively associated with the baseline (location outside New England, location in a rural area, and a large proportion of prenatal patients aged <15 years) and target (more prenatal patients, location outside New England, provision of prenatal care to women living with HIV, and more uninsured patients or patients eligible for both Medicare and Medicaid).
Limitation
The data set is at the health center grantee level and does not contain information on timing or quality of follow-up prenatal care.
Conclusion
Most health centers met the Healthy People 2020 baseline, but opportunities for improvement remain and the Healthy People 2020 target is still a challenge for many health centers. Policymakers, providers, and health centers can learn from high-achieving centers to promote early initiation of prenatal care among medically vulnerable and underserved populations.
Primary funding source
Health Resources and Services Administration.



Ann Intern Med: 30 Nov 2020; 173:S29-S36
Robbins C, Martocci S
Ann Intern Med: 30 Nov 2020; 173:S29-S36 | PMID: 33253020
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Impact:
Abstract

Trends in Opioid and Psychotropic Prescription in Pregnancy in the United States From 2001 to 2015 in a Privately Insured Population : A Cross-sectional Study.

Venkatesh KK, Pate V, Boggess KA, Jones HE, Funk MJ, Smid MC
Background
Opioid and psychotropic prescriptions are common during pregnancy. Little is known about coprescriptions of both medications in this setting.
Objective
To describe opioid prescription among women who are prescribed psychotropics compared with women who are not.
Design
Cross-sectional study.
Setting
U.S. commercial insurance beneficiaries from MarketScan (2001 to 2015).
Participants
Pregnant women at 22 weeks\' gestation or greater who were insured continuously for 3 months or more before pregnancy through delivery.
Measurements
Opioid prescription, dosage thresholds (morphine milligram equivalents [MME] of ≥50/day and ≥90/day), number of opioid agents (≥2), and duration (≥30 days) among those with and without prescription of psychotropics, from 2011 to 2015.
Results
Among 958 980 pregnant women, 10% received opioids only, 6% psychotropics only, and 2% opioids with coprescription of psychotropics. Opioid prescription was higher among women prescribed psychotropics versus those who were not (26.5% vs. 10.7%). From 2001 to 2015, psychotropic prescription overall increased from 4.4% to 7.6%, opioid prescription without coprescription of psychotropics decreased from 11.9% to 8.4%, and opioids with coprescription decreased from 28.1% to 22.0%. Morphine milligram equivalents of 50 or greater per day decreased for women with and without coprescription (29.6% to 17.3% and 22.8% to 18.5%, respectively); MME of 90 or greater per day also decreased in both groups (15.0% to 4.7% and 11.5% to 4.2%, respectively). Women prescribed opioids only were more likely to have an antepartum hospitalization compared with those with neither prescription, as were women with coprescription versus those prescribed psychotropics only. Compared with those prescribed opioids only, women with coprescriptions were more likely to exceed MME of 90 or greater per day and to be prescribed 2 or more opioid agents and for 30 days or longer. Number and duration of opioids increased with benzodiazepine and gabapentin coprescription.
Limitation
Inability to determine appropriateness of prescribing or overdose events.
Conclusion
Opioids are frequently coprescribed with psychotropic medication during pregnancy and are associated with antepartum hospitalization. A substantial proportion of pregnant women are prescribed opioids at doses that increase overdose risk and exceed daily recommendations.
Primary funding source
None.



Ann Intern Med: 30 Nov 2020; 173:S19-S28
Venkatesh KK, Pate V, Boggess KA, Jones HE, Funk MJ, Smid MC
Ann Intern Med: 30 Nov 2020; 173:S19-S28 | PMID: 33253018
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Impact:
Abstract

The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults : A Response-Adaptive, Randomized Clinical Trial.

Appel LJ, Michos ED, Mitchell CM, Blackford AL, ... Roth DL, Tonascia J
Background
Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences.
Objective
To compare the effects of 4 doses of vitamin D supplements on falls.
Design
2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333).
Setting
2 community-based research units.
Participants
688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L.
Intervention
200 (control), 1000, 2000, or 4000 IU of vitamin D per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose.
Measurements
Time to first fall or death over 2 years (primary outcome).
Results
During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d;  = 308) and those randomly assigned to receive 200 IU/d ( = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15];  = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]).
Limitations
The control group received 200 IU of vitamin D per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached.
Conclusion
In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D doses of 1000 IU/d or higher.
Primary funding source
National Institute on Aging.



Ann Intern Med: 30 Nov 2020; epub ahead of print
Appel LJ, Michos ED, Mitchell CM, Blackford AL, ... Roth DL, Tonascia J
Ann Intern Med: 30 Nov 2020; epub ahead of print | PMID: 33284677
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Impact:
Abstract

Surviving COVID-19 After Hospital Discharge: Symptom, Functional, and Adverse Outcomes of Home Health Recipients.

Bowles KH, McDonald M, Barrón Y, Kennedy E, O\'Connor M, Mikkelsen M
Background
Little is known about recovery from coronavirus disease 2019 (COVID-19) after hospital discharge.
Objective
To describe the home health recovery of patients with COVID-19 and risk factors associated with rehospitalization or death.
Design
Retrospective observational cohort.
Setting
New York City.
Participants
1409 patients with COVID-19 admitted to home health care (HHC) between 1 April and 15 June 2020 after hospitalization.
Measurements
Covariates and outcomes were obtained from the mandated OASIS (Outcome and Assessment Information Set). Cox proportional hazard models were used to estimate the hazard ratio (HR) of risk factors associated with rehospitalization or death.
Results
After an average of 32 days in HHC, 94% of patients were discharged and most achieved statistically significant improvements in symptoms and function. Activity-of-daily-living dependencies decreased from an average of 6 (95% CI, 5.9 to 6.1) to 1.2 (CI, 1.1 to 1.3). Risk for rehospitalization or death was higher for male patients (HR, 1.45 [CI, 1.04 to 2.03]); White patients (HR, 1.74 [CI, 1.22 to 2.47]); and patients with heart failure (HR, 2.12 [CI, 1.41 to 3.19]), diabetes with complications (HR, 1.71 [CI, 1.17 to 2.52]), 2 or more emergency department visits in the past 6 months (HR, 1.78 [CI, 1.21 to 2.62]), pain daily or all the time (HR, 1.46 [CI, 1.05 to 2.05]), cognitive impairment (HR, 1.49 [CI, 1.04 to 2.13]), or functional dependencies (HR, 1.09 [CI, 1.00 to 1.20]). Eleven patients (1%) died, 137 (10%) were rehospitalized, and 23 (2%) remain on service.
Limitations
Care was provided by 1 home health agency. Information on rehospitalization and death after HHC discharge is not available.
Conclusion
Symptom burden and functional dependence were common at the time of HHC admission but improved for most patients. Comorbid conditions of heart failure and diabetes, as well as characteristics present at admission, identified patients at greatest risk for an adverse event.
Primary funding source
No direct funding.



Ann Intern Med: 23 Nov 2020; epub ahead of print
Bowles KH, McDonald M, Barrón Y, Kennedy E, O'Connor M, Mikkelsen M
Ann Intern Med: 23 Nov 2020; epub ahead of print | PMID: 33226861
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Impact:
Abstract

Association Between ABO and Rh Blood Groups and SARS-CoV-2 Infection or Severe COVID-19 Illness : A Population-Based Cohort Study.

Ray JG, Schull MJ, Vermeulen MJ, Park AL
Background
The ABO and rhesus (Rh) blood groups may influence risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Objective
To determine whether ABO and Rh blood groups are associated with risk for SARS-CoV-2 infection and severe coronavirus disease 2019 (COVID-19) illness.
Design
Population-based cohort study.
Setting
Ontario, Canada.
Patients
All adults and children who had ABO blood group assessed between January 2007 and December 2019 and who subsequently had SARS-CoV-2 testing between 15 January and 30 June 2020.
Measurements
The main study outcome was SARS-CoV-2 infection, determined by viral RNA polymerase chain reaction testing. A second outcome was severe COVID-19 illness or death. Adjusted relative risks (aRRs) and absolute risk differences (ARDs) were adjusted for demographic characteristics and comorbidities.
Results
A total of 225 556 persons were included, with a mean age of 54 years. The aRR of SARS-CoV-2 infection for O blood group versus A, AB, and B blood groups together was 0.88 (95% CI, 0.84 to 0.92; ARD, -3.9 per 1000 [CI, -5.4 to -2.5]). Rhesus-negative (Rh-) blood type was protective against SARS-CoV-2 infection (aRR, 0.79 [CI, 0.73 to 0.85]; ARD, -6.8 per 1000 [CI, -8.9 to -4.7]), especially for those who were O-negative (O-) (aRR, 0.74 [CI, 0.66 to 0.83]; ARD, -8.2 per 1000 [CI, -10.8 to -5.3]). There was also a lower risk for severe COVID-19 illness or death associated with type O blood group versus all others (aRR, 0.87 [CI, 0.78 to 0.97]; ARD, -0.8 per 1000 [CI, -1.4 to -0.2]) and with Rh- versus Rh-positive (aRR, 0.82 [CI, 0.68 to 0.96]; ARD, -1.1 per 1000 [CI, -2.0 to -0.2]).
Limitation
Persons who rapidly died of severe COVID-19 illness may not have had SARS-CoV-2 testing.
Conclusion
The O and Rh- blood groups may be associated with a slightly lower risk for SARS-CoV-2 infection and severe COVID-19 illness.
Primary funding source
Ontario Academic Health Sciences Centre AFP Innovation Fund and the Ontario Ministry of Health and Long-Term Care.



Ann Intern Med: 23 Nov 2020; epub ahead of print
Ray JG, Schull MJ, Vermeulen MJ, Park AL
Ann Intern Med: 23 Nov 2020; epub ahead of print | PMID: 33226859
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Impact:
Abstract

Are Financial Payments From the Pharmaceutical Industry Associated With Physician Prescribing? : A Systematic Review.

Mitchell AP, Trivedi NU, Gennarelli RL, Chimonas S, ... Diaz LA, Korenstein D
Background
Financial payments from the drug industry to U.S. physicians are common. Payments may influence physicians\' clinical decision making and drug prescribing.
Purpose
To evaluate whether receipt of payments from the drug industry is associated with physician prescribing practices.
Data sources
MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science, and EconLit were searched without language restrictions. The search had no limiting start date and concluded on 16 September 2020.
Study selection
Studies that estimated the association between receipt of industry payments (exposure) and prescribing (outcome).
Data extraction
Pairs of reviewers extracted the primary analysis or analyses from each study and evaluated risk of bias (ROB).
Data synthesis
Thirty-six studies comprising 101 analyses were included. Most studies ( = 30) identified a positive association between payments and prescribing in all analyses; the remainder ( = 6) had a mix of positive and null findings. No study had only null findings. Of 101 individual analyses, 89 identified a positive association. Payments were associated with increased prescribing of the paying company\'s drug, increased prescribing costs, and increased prescribing of branded drugs. Nine studies assessed and found evidence of a temporal association; 25 assessed and found evidence of a dose-response relationship.
Limitation
The design was observational, 21 of 36 studies had serious ROB, and publication bias was possible.
Conclusion
The association between industry payments and physician prescribing was consistent across all studies that have evaluated this association. Findings regarding a temporal association and dose-response suggest a causal relationship.
Primary funding source
National Cancer Institute.



Ann Intern Med: 23 Nov 2020; epub ahead of print
Mitchell AP, Trivedi NU, Gennarelli RL, Chimonas S, ... Diaz LA, Korenstein D
Ann Intern Med: 23 Nov 2020; epub ahead of print | PMID: 33226858
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Impact:
Abstract

Probability of Success and Timelines for the Development of Vaccines for Emerging and Reemerged Viral Infectious Diseases.

MacPherson A, Hutchinson N, Schneider O, Oliviero E, ... Basta NE, Kimmelman J
Background
Anticipated success rates and timelines for COVID-19 vaccine development vary. Recent experience with developing and testing viral vaccine candidates can inform expectations regarding the development of safe and effective vaccines.
Objective
To estimate timelines and probabilities of success for recent vaccine candidates.
Design
ClinicalTrials.gov was searched to identify trials testing viral vaccines that had not advanced to phase 2 before 2005, and the progress of each vaccine from phase 1 through to U.S. Food and Drug Administration (FDA) licensure was tracked. Trial characteristics were double-coded. (Registration: Open Science Framework [https://osf.io/dmuzx/]).
Setting
Trials launched between January 2005 and March 2020.
Participants
Preventive viral vaccine candidates for 23 emerging or reemerged viral infectious diseases.
Measurements
The primary end point was the probability of vaccines advancing from launch of phase 2 to FDA licensure within 10 years.
Results
In total, 606 clinical trials forming 220 distinct development trajectories (267 343 enrolled participants) were identified. The probability of vaccines progressing from phase 2 to licensure within 10 years was 10.0% (95% CI, 2.6% to 16.9%), with most approvals representing H1N1 or H5N1 vaccines. The average timeline from phase 2 to approval was 4.4 years (range, 6.4 weeks to 13.9 years). The probabilities of advancing from phase 1 to 2, phase 2 to 3, and phase 3 to licensure within the total available follow-up time were 38.2% (CI, 30.7% to 45.0%), 38.3% (CI, 23.1% to 50.5%), and 61.1% (CI, 3.7% to 84.3%), respectively.
Limitations
The study did not account for preclinical development and relied primarily on ClinicalTrials.gov and FDA resources. Success probabilities do not capture the varied reasons why vaccines fail to advance to regulatory approval.
Conclusion
Success probabilities and timelines varied widely across different vaccine types and diseases. If a SARS-CoV-2 vaccine is licensed within 18 months of the start of the pandemic, it will mark an unprecedented achievement for noninfluenza viral vaccine development.
Primary funding source
McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding program.



Ann Intern Med: 23 Nov 2020; epub ahead of print
MacPherson A, Hutchinson N, Schneider O, Oliviero E, ... Basta NE, Kimmelman J
Ann Intern Med: 23 Nov 2020; epub ahead of print | PMID: 33226855
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Impact:
Abstract

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

Bundgaard H, Bundgaard JS, Raaschou-Pedersen DET, von Buchwald C, ... Torp-Pedersen C, Iversen K
Background
Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both.
Objective
To assess whether recommending surgical mask use outside the home reduces wearers\' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures.
Design
Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541).
Setting
Denmark, April and May 2020.
Participants
Adults spending more than 3 hours per day outside the home without occupational mask use.
Intervention
Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use.
Measurements
The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses.
Results
A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point;  = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23];  = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection.
Limitation
Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others.
Conclusion
The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection.
Primary funding source
The Salling Foundations.



Ann Intern Med: 17 Nov 2020; epub ahead of print
Bundgaard H, Bundgaard JS, Raaschou-Pedersen DET, von Buchwald C, ... Torp-Pedersen C, Iversen K
Ann Intern Med: 17 Nov 2020; epub ahead of print | PMID: 33205991
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Impact:
Abstract

Long-Term Oncologic Outcomes After Laparoscopic Versus Open Resection for Colorectal Liver Metastases : A Randomized Trial.

Aghayan DL, Kazaryan AM, Dagenborg VJ, Røsok BI, ... Fretland ÅA, Edwin B
Background
Despite the recent worldwide dissemination of laparoscopic liver surgery, no high-level evidence supports the oncologic safety of this approach.
Objective
To evaluate long-term oncologic outcomes after laparoscopic versus open liver resection in patients with colorectal metastases.
Design
A single-center, assessor-blinded, randomized controlled trial (OSLO-COMET [Oslo Randomized Laparoscopic Versus Open Liver Resection for Colorectal Metastases Trial]). (ClinicalTrials.gov: NCT01516710).
Setting
Oslo University Hospital, the only provider of liver surgery for the 3 million inhabitants of southeastern Norway.
Participants
Patients with resectable colorectal liver metastases were randomly assigned to have open or laparoscopic liver resection.
Intervention
From February 2012 to January 2016, a total of 280 patients were included in the trial (laparoscopic surgery:  = 133; open surgery:  = 147).
Measurements
The primary outcome was postoperative morbidity within 30 days. Five-year rates of overall and recurrence-free survival were predefined secondary end points.
Results
At a median follow-up of 70 months, rates of 5-year overall survival were 54% in the laparoscopic group and 55% in the open group (between-group difference, 0.5 percentage point [95% CI, -11.3 to 12.3 percentage points]; hazard ratio, 0.93 [CI, 0.67 to 1.30];  = 0.67). Rates of 5-year recurrence-free survival were 30% in the laparoscopic group and 36% in the open group (between-group difference, 6.0 percentage points [CI, -6.7 to 18.7 percentage points]; hazard ratio, 1.09 [CI, 0.80 to 1.49];  = 0.57).
Limitation
The trial was not powered to detect differences in secondary end points and was not designed to address a noninferiority hypothesis for survival outcomes.
Conclusion
In this randomized trial of laparoscopic and open liver surgery, no difference in survival outcomes was found between the treatment groups. However, differences in 5-year overall survival up to about 10 percentage points in either direction cannot be excluded. This trial should be followed by pragmatic multicenter trials and international registries.
Primary funding source
The South-Eastern Norway Regional Health Authority.



Ann Intern Med: 16 Nov 2020; epub ahead of print
Aghayan DL, Kazaryan AM, Dagenborg VJ, Røsok BI, ... Fretland ÅA, Edwin B
Ann Intern Med: 16 Nov 2020; epub ahead of print | PMID: 33197213
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Impact:
Abstract

Insights From Rapid Deployment of a \"Virtual Hospital\" as Standard Care During the COVID-19 Pandemic.

Sitammagari K, Murphy S, Kowalkowski M, Chou SH, ... Neuwirth Z, McWilliams A
Background
Pandemics disrupt traditional health care operations by overwhelming system resource capacity but also create opportunities for care innovation.
Objective
To describe the development and rapid deployment of a virtual hospital program, Atrium Health hospital at home (AH-HaH), within a large health care system.
Design
Prospective case series.
Setting
Atrium Health, a large integrated health care organization in the southeastern United States.
Patients
1477 patients diagnosed with coronavirus disease 2019 (COVID-19) from 23 March to 7 May 2020 who received care via AH-HaH.
Intervention
A virtual hospital model providing proactive home monitoring and hospital-level care through a virtual observation unit (VOU) and a virtual acute care unit (VACU) in the home setting for eligible patients with COVID-19.
Measurements
Patient demographic characteristics, comorbid conditions, treatments administered (intravenous fluids, antibiotics, supplemental oxygen, and respiratory medications), transfer to inpatient care, and hospital outcomes (length of stay, intensive care unit [ICU] admission, mechanical ventilation, and death) were collected from electronic health record data.
Results
1477 patients received care in either the AH-HaH VOU or VACU or both settings, with a median length of stay of 11 days. Of these, 1293 (88%) patients received care in the VOU only, with 40 (3%) requiring inpatient hospitalization. Of these 40 patients, 16 (40%) spent time in the ICU, 7 (18%) required ventilator support, and 2 (5%) died during their hospital admission. In total, 184 (12%) patients were ever admitted to the VACU, during which 21 patients (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required respiratory inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted as an inpatient to a conventional hospital. Of these 24 patients, 10 (42%) required ICU admission, 1 (3%) required a ventilator, and none died during their hospital admission.
Limitation
Generalizability is limited to patients with a working telephone and the ability to comply with the monitoring protocols.
Conclusion
Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond.
Primary funding source
Atrium Health.



Ann Intern Med: 10 Nov 2020; epub ahead of print
Sitammagari K, Murphy S, Kowalkowski M, Chou SH, ... Neuwirth Z, McWilliams A
Ann Intern Med: 10 Nov 2020; epub ahead of print | PMID: 33175567
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Impact:
Abstract

Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data.

Pottel H, Björk J, Courbebaisse M, Couzi L, ... Nyman U, Delanaye P
Background
The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.
Objective
To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations.
Design
Cross-sectional analysis with separate pooled data sets for development and validation.
Setting
Research and clinical studies ( = 13) with measured GFR available.
Patients
11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set).
Measurements
Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR.
Results
The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m [95% CI, -2.7 to 0.0 mL/min/1.73 m] in children and -0.9 mL/min/1.73 m [CI, -1.2 to -0.5 mL/min/1.73 m] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations.
Limitation
No Black patients were included.
Conclusion
The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels.
Primary funding source
Swedish Research Council (Vetenskapsrådet).



Ann Intern Med: 09 Nov 2020; epub ahead of print
Pottel H, Björk J, Courbebaisse M, Couzi L, ... Nyman U, Delanaye P
Ann Intern Med: 09 Nov 2020; epub ahead of print | PMID: 33166224
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Impact:
Abstract

Diabetes Management in Chronic Kidney Disease: Synopsis of the 2020 KDIGO Clinical Practice Guideline.

Navaneethan SD, Zoungas S, Caramori ML, Chan JCN, ... de Boer IH, Khunti K
Description
The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD).
Methods
The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized.
Recommendations
The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.



Ann Intern Med: 09 Nov 2020; epub ahead of print
Navaneethan SD, Zoungas S, Caramori ML, Chan JCN, ... de Boer IH, Khunti K
Ann Intern Med: 09 Nov 2020; epub ahead of print | PMID: 33166222
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Impact:
Abstract

A Health Opportunity Cost Threshold for Cost-Effectiveness Analysis in the United States.

Vanness DJ, Lomas J, Ahn H
Background
Cost-effectiveness analysis is an important tool for informing treatment coverage and pricing decisions, yet no consensus exists about what threshold for the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life-year (QALY) gained indicates whether treatments are likely to be cost-effective in the United States.
Objective
To estimate a U.S. cost-effectiveness threshold based on health opportunity costs.
Design
Simulation of short-term mortality and morbidity attributable to persons dropping health insurance due to increased health care expenditures passed though as premium increases. Model inputs came from demographic data and the literature; 95% uncertainty intervals (UIs) were constructed.
Setting
Population-based.
Participants
Simulated cohort of 100 000 individuals from the U.S. population with direct-purchase private health insurance.
Measurements
Number of persons dropping insurance coverage, number of additional deaths, and QALYs lost from increased mortality and morbidity, all per increase of $10 000 000 (2019 U.S. dollars) in population treatment cost.
Results
Per $10 000 000 increase in health care expenditures, 1860 persons (95% UI, 1080 to 2840 persons) were simulated to become uninsured, causing 5 deaths (UI, 3 to 11 deaths), 81 QALYs (UI, 40 to 170 QALYs) lost due to death, and 15 QALYs (UI, 6 to 32 QALYs) lost due to illness; this implies a cost-effectiveness threshold of $104 000 per QALY (UI, $51 000 to $209 000 per QALY) in 2019 U.S. dollars. Given available evidence, there is about 14% probability that the threshold exceeds $150 000 per QALY and about 48% probability that it lies below $100 000 per QALY.
Limitations
Estimates were sensitive to inputs, most notably the effects of losing insurance on mortality and of premium increases on becoming uninsured. Health opportunity costs may vary by population. Nonhealth opportunity costs were excluded.
Conclusion
Given current evidence, treatments with ICERs above the range $100 000 to $150 000 per QALY are unlikely to be cost-effective in the United States.
Primary funding source
None.



Ann Intern Med: 02 Nov 2020; epub ahead of print
Vanness DJ, Lomas J, Ahn H
Ann Intern Med: 02 Nov 2020; epub ahead of print | PMID: 33136426
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Impact:
Abstract

Effect of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the United States : A Simulation Modeling Approach.

Alagoz O, Sethi AK, Patterson BW, Churpek M, Safdar N
Background
Across the United States, various social distancing measures were implemented to control the spread of coronavirus disease 2019 (COVID-19). However, the effectiveness of such measures for specific regions with varying population demographic characteristics and different levels of adherence to social distancing is uncertain.
Objective
To determine the effect of social distancing measures in unique regions.
Design
An agent-based simulation model.
Setting
Agent-based model applied to Dane County, Wisconsin; the Milwaukee metropolitan (metro) area; and New York City (NYC).
Patients
Synthetic population at different ages.
Intervention
Different times for implementing and easing social distancing measures at different levels of adherence.
Measurements
The model represented the social network and interactions among persons in a region, considering population demographic characteristics, limited testing availability, \"imported\" infections, asymptomatic disease transmission, and age-specific adherence to social distancing measures. The primary outcome was the total number of confirmed COVID-19 cases.
Results
The timing of and adherence to social distancing had a major effect on COVID-19 occurrence. In NYC, implementing social distancing measures 1 week earlier would have reduced the total number of confirmed cases from 203 261 to 41 366 as of 31 May 2020, whereas a 1-week delay could have increased the number of confirmed cases to 1 407 600. A delay in implementation had a differential effect on the number of cases in the Milwaukee metro area versus Dane County, indicating that the effect of social distancing measures varies even within the same state.
Limitation
The effect of weather conditions on transmission dynamics was not considered.
Conclusion
The timing of implementing and easing social distancing measures has major effects on the number of COVID-19 cases.
Primary funding source
National Institute of Allergy and Infectious Diseases.



Ann Intern Med: 26 Oct 2020; epub ahead of print
Alagoz O, Sethi AK, Patterson BW, Churpek M, Safdar N
Ann Intern Med: 26 Oct 2020; epub ahead of print | PMID: 33105091
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Impact:
Abstract

Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine Trials.

Mehrotra DV, Janes HE, Fleming TR, Annunziato PW, ... Follmann D, Gilbert PB

Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) have entered or will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy of these vaccines, a general set of clinical endpoints is proposed, along with considerations to guide the selection of the primary endpoints on the basis of clinical and statistical reasoning. The plausibility that vaccine protection against symptomatic COVID-19 could be accompanied by a shift toward more SARS-CoV-2 infections that are asymptomatic is highlighted, as well as the potential implications of such a shift.



Ann Intern Med: 21 Oct 2020; epub ahead of print
Mehrotra DV, Janes HE, Fleming TR, Annunziato PW, ... Follmann D, Gilbert PB
Ann Intern Med: 21 Oct 2020; epub ahead of print | PMID: 33090877
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Impact:
Abstract

Ethical Framework for Assessing Manual and Digital Contact Tracing for COVID-19.

Lo B, Sim I

The coronavirus disease 2019 (COVID-19) pandemic has challenged the traditional public health balance between benefiting the good of the community through contract tracing and restricting individual liberty. This article first analyzes important technical and ethical issues regarding new smartphone apps that facilitate contact tracing and exposure notification. It then presents a framework for assessing contact tracing, whether manual or digital: the effectiveness at mitigating the pandemic; acceptability of risks, particularly privacy; and equitable distribution of benefits and risks. Both manual and digital contact tracing require public trust, engagement of minority communities, prompt COVID-19 testing and return of results, and high adherence with physical distancing and use of masks.



Ann Intern Med: 19 Oct 2020; epub ahead of print
Lo B, Sim I
Ann Intern Med: 19 Oct 2020; epub ahead of print | PMID: 33076694
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Impact:
Abstract

Linked Color Imaging Focused on Neoplasm Detection in the Upper Gastrointestinal Tract : A Randomized Trial.

Ono S, Kawada K, Dohi O, Kitamura S, ... Mori K, Kato Md M
Background
Linked color imaging (LCI) is a new image-enhanced endoscopy technique that allows users to recognize slight differences in mucosal color.
Objective
To compare the performance of LCI with white light imaging (WLI) in detecting neoplastic lesions in the upper gastrointestinal tract.
Design
A controlled, multicenter trial with randomization using minimization. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000023863).
Setting
16 university hospitals and 3 tertiary care hospitals in Japan.
Patients
1502 patients with known previous or current cancer of the gastrointestinal tract and undergoing surveillance for gastrointestinal cancer.
Intervention
WLI followed by LCI examination (WLI group) or LCI followed by WLI examination (LCI group).
Measurements
Diagnosis of 1 or more neoplastic lesions in the pharynx, esophagus, or stomach in the first examination (primary outcome) and 1 or more neoplastic lesions overlooked in the first examination (secondary outcome).
Results
752 patients were assigned to the WLI group and 750 to the LCI group. The percentage of patients with 1 or more neoplastic lesions diagnosed in the first examination was higher with LCI than with WLI (60 of 750 patients or 8.0% [95% CI, 6.2% to 10.2%] vs. 36 of 752 patients or 4.8% [CI, 3.4% to 6.6%]; risk ratio, 1.67 [CI, 1.12 to 2.50;  = 0.011]). The proportion with overlooked neoplasms was lower in the LCI group than in the WLI group (5 of 750 patients or 0.67% [CI, 0.2% to 1.6%] vs. 26 of 752 patients or 3.5% [CI, 2.3% to 5.0%]; risk ratio, 0.19 [CI, 0.07 to 0.50]).
Limitation
Endoscopists were not blinded.
Conclusion
LCI is more effective than WLI for detecting neoplastic lesions in the pharynx, esophagus, and stomach.
Primary funding source
Fujifilm Corporation.



Ann Intern Med: 19 Oct 2020; epub ahead of print
Ono S, Kawada K, Dohi O, Kitamura S, ... Mori K, Kato Md M
Ann Intern Med: 19 Oct 2020; epub ahead of print | PMID: 33076693
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Impact:
Abstract

Managing COVID-19 in a Novel, Rapidly Deployable Community Isolation Quarantine Facility.

Chia ML, Him Chau DH, Lim KS, Yang Liu CW, Tan HK, Tan YR

Singapore is one of the most densely populated small island-states in the world. During the coronavirus disease 2019 (COVID-19) pandemic, Singapore implemented large-scale institutional isolation units called Community Care Facilities (CCFs) to combat the outbreak in the community by housing low-risk COVID-19 patients from April to August 2020. The CCFs were created rapidly by converting existing public spaces and used a protocolized system, augmented by telemedicine to enable a low health care worker-patient ratio (98 health care workers for 3200 beds), to operate these unique facilities. In the first month, a total of 3758 patients were admitted to 4 halls, 4929 in-house medical consults occurred, 136 patients were transferred to a hospital, 1 patient died 2 weeks after discharge, and no health care workers became infected. This article shares the authors\' experience in operating these massive-scale isolation facilities while prioritizing safety for all and ensuring holistic patient care in the face of a public health crisis and lean health care resources.



Ann Intern Med: 16 Oct 2020; epub ahead of print
Chia ML, Him Chau DH, Lim KS, Yang Liu CW, Tan HK, Tan YR
Ann Intern Med: 16 Oct 2020; epub ahead of print | PMID: 32941059
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Impact:
Abstract

Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors.

Meyerowitz EA, Richterman A, Gandhi RT, Sax PE

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called \"superspreading events.\" Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.



Ann Intern Med: 16 Oct 2020; epub ahead of print
Meyerowitz EA, Richterman A, Gandhi RT, Sax PE
Ann Intern Med: 16 Oct 2020; epub ahead of print | PMID: 32941052
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Impact:

This program is still in alpha version.