Journal: Ann Intern Med

Sorted by: date / impact
Abstract

QUADAS-C: A Tool for Assessing Risk of Bias in Comparative Diagnostic Accuracy Studies.

Yang B, Mallett S, Takwoingi Y, Davenport CF, ... Leeflang MMG, QUADAS-C Group†
Comparative diagnostic test accuracy studies assess and compare the accuracy of 2 or more tests in the same study. Although these studies have the potential to yield reliable evidence regarding comparative accuracy, shortcomings in the design, conduct, and analysis may bias their results. The currently recommended quality assessment tool for diagnostic test accuracy studies, QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), is not designed for the assessment of test comparisons. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative) tool was developed as an extension of QUADAS-2 to assess the risk of bias in comparative diagnostic test accuracy studies. Through a 4-round Delphi study involving 24 international experts in test evaluation and a face-to-face consensus meeting, an initial version of the tool was developed that was revised and finalized following a pilot study among potential users. The QUADAS-C tool retains the same 4-domain structure of QUADAS-2 (Patient Selection, Index Test, Reference Standard, and Flow and Timing) and comprises additional questions to each QUADAS-2 domain. A risk-of-bias judgment for comparative accuracy requires a risk-of-bias judgment for the accuracy of each test (resulting from QUADAS-2) and additional criteria specific to test comparisons. Examples of such additional criteria include whether participants either received all index tests or were randomly assigned to index tests, and whether index tests were interpreted with blinding to the results of other index tests. The QUADAS-C tool will be useful for systematic reviews of diagnostic test accuracy addressing comparative questions. Furthermore, researchers may use this tool to identify and avoid risk of bias when designing a comparative diagnostic test accuracy study.



Ann Intern Med: 25 Oct 2021; epub ahead of print
Yang B, Mallett S, Takwoingi Y, Davenport CF, ... Leeflang MMG, QUADAS-C Group†
Ann Intern Med: 25 Oct 2021; epub ahead of print | PMID: 34698503
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Abstract

Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial.

Siedner MJ, Moosa MS, McCluskey S, Gilbert RF, ... Bwana MB, Marconi VC
Background
Virologic failure in HIV predicts the development of drug resistance and mortality. Genotypic resistance testing (GRT), which is the standard of care after virologic failure in high-income settings, is rarely implemented in sub-Saharan Africa.
Objective
To estimate the effectiveness of GRT for improving virologic suppression rates among people with HIV in sub-Saharan Africa for whom first-line therapy fails.
Design
Pragmatic, unblinded, randomized controlled trial. (ClinicalTrials.gov: NCT02787499).
Setting
Ambulatory HIV clinics in the public sector in Uganda and South Africa.
Patients
Adults receiving first-line antiretroviral therapy with a recent HIV RNA viral load of 1000 copies/mL or higher.
Intervention
Participants were randomly assigned to receive standard of care (SOC), including adherence counseling sessions and repeated viral load testing, or immediate GRT.
Measurements
The primary outcome of interest was achievement of an HIV RNA viral load below 200 copies/mL 9 months after enrollment.
Results
The trial enrolled 840 persons, divided equally between countries. Approximately half (51%) were women. Most (72%) were receiving a regimen of tenofovir, emtricitabine, and efavirenz at enrollment. The rate of virologic suppression did not differ 9 months after enrollment between the GRT group (63% [263 of 417]) and SOC group (61% [256 of 423]; odds ratio [OR], 1.11 [95% CI, 0.83 to 1.49]; P = 0.46). Among participants with persistent failure (HIV RNA viral load ≥1000 copies/mL) at 9 months, the prevalence of drug resistance was higher in the SOC group (76% [78 of 103] vs. 59% [48 of 82]; OR, 2.30 [CI, 1.22 to 4.35]; P = 0.014). Other secondary outcomes, including 9-month survival and retention in care, were similar between groups.
Limitation
Participants were receiving nonnucleoside reverse transcriptase inhibitor-based therapy at enrollment, limiting the generalizability of the findings.
Conclusion
The addition of GRT to routine care after first-line virologic failure in Uganda and South Africa did not improve rates of resuppression.
Primary funding source
The President\'s Emergency Plan for AIDS Relief and the National Institute of Allergy and Infectious Diseases.



Ann Intern Med: 25 Oct 2021; epub ahead of print
Siedner MJ, Moosa MS, McCluskey S, Gilbert RF, ... Bwana MB, Marconi VC
Ann Intern Med: 25 Oct 2021; epub ahead of print | PMID: 34698502
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Abstract

Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus : A Randomized Controlled Trial.

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



Ann Intern Med: 25 Oct 2021; epub ahead of print
Shipa M, Embleton-Thirsk A, Parvaz M, Santos LR, ... Ehrenstein MR, BEAT-LUPUS Investigators*
Ann Intern Med: 25 Oct 2021; epub ahead of print | PMID: 34698499
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Abstract

Identifying Equitable Screening Mammography Strategies for Black Women in the United States Using Simulation Modeling.

Chapman CH, Schechter CB, Cadham CJ, Trentham-Dietz A, ... Jagsi R, Mandelblatt JS
Background
Screening mammography guidelines do not explicitly consider racial differences in breast cancer epidemiology, treatment, and survival.
Objective
To compare tradeoffs of screening strategies in Black women versus White women under current guidelines.
Design
An established model from the Cancer Intervention and Surveillance Modeling Network simulated screening outcomes using race-specific inputs for subtype distribution; breast density; mammography performance; age-, stage-, and subtype-specific treatment effects; and non-breast cancer mortality.
Setting
United States.
Participants
A 1980 U.S. birth cohort of Black and White women.
Intervention
Screening strategies until age 74 years with varying initiation ages and intervals.
Measurements
Outcomes included benefits (life-years gained [LYG], breast cancer deaths averted, and mortality reduction), harms (mammographies, false positives, and overdiagnoses), and benefit-harm ratios (tradeoffs) by race. Efficiency (benefits per unit resource), mortality disparity reduction, and equity in tradeoffs were evaluated. Equitable strategies for Black women were defined as those with tradeoffs closest to benchmark values for screening White women biennially from ages 50 to 74 years.
Results
Biennial screening from ages 45 to 74 years was most efficient for Black women, whereas biennial screening from ages 40 to 74 years was most equitable. Initiating screening 10 years earlier in Black versus White women reduced Black-White mortality disparities by 57% with similar LYG per mammogram for both populations. Selection of the most equitable strategy was sensitive to assumptions about disparities in real-world treatment effectiveness: The less effective treatment was for Black women, the more intensively Black women could be screened before tradeoffs fell short of those experienced by White women.
Limitation
Single model.
Conclusion
Initiating biennial screening in Black women at age 40 years reduces breast cancer mortality disparities and yields benefit-harm ratios that are similar to tradeoffs of White women screened biennially from ages 50 to 74 years.
Primary funding source
National Cancer Institute at the National Institutes of Health.



Ann Intern Med: 18 Oct 2021; epub ahead of print
Chapman CH, Schechter CB, Cadham CJ, Trentham-Dietz A, ... Jagsi R, Mandelblatt JS
Ann Intern Med: 18 Oct 2021; epub ahead of print | PMID: 34662151
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Abstract

Supplemental Nutrition Assistance Program Participation and Health Care Use in Older Adults : A Cohort Study.

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



Ann Intern Med: 18 Oct 2021; epub ahead of print
Berkowitz SA, Palakshappa D, Rigdon J, Seligman HK, Basu S
Ann Intern Med: 18 Oct 2021; epub ahead of print | PMID: 34662150
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Abstract

Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.

Ingason AB, Hreinsson JP, Ágústsson AS, Lund SH, ... Önundarson PT, Björnsson ES
Background
Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited.
Objective
To compare rates of GIB among apixaban, dabigatran, and rivaroxaban.
Design
Nationwide population-based cohort study.
Setting
Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland.
Patients
New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019.
Measurements
Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression.
Results
In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses.
Limitations
Unmeasured confounding and small subgroup analyses.
Conclusion
Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.
Primary funding source
Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland.



Ann Intern Med: 11 Oct 2021; epub ahead of print
Ingason AB, Hreinsson JP, Ágústsson AS, Lund SH, ... Önundarson PT, Björnsson ES
Ann Intern Med: 11 Oct 2021; epub ahead of print | PMID: 34633836
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Abstract

Health Care for Our Nation\'s Veterans: A Policy Paper From the American College of Physicians.

Crowley R, Atiq O, Hilden D, Cooney TG, Health and Public Policy Committee of the American College of Physicians*
The Veterans Health Administration (VHA) is the United States\' largest integrated health care delivery system, serving over 9 million enrollees at nearly 1300 health care facilities. In addition to providing health care to the nation\'s military veterans, the VHA has a research and development program, trains thousands of medical residents and other health care professionals, and conducts emergency preparedness and response activities. The VHA has been celebrated for delivering high-quality care to veterans, early adoption of electronic medical records, and high patient satisfaction. However, the system faces challenges, including implementation of an expanded community care program, modernization of its electronic medical records system, and providing care to a population with complex needs. The position paper offers policy recommendations on VHA funding, the community care program, medical and health care professions training, and research and development.



Ann Intern Med: 04 Oct 2021; epub ahead of print
Crowley R, Atiq O, Hilden D, Cooney TG, Health and Public Policy Committee of the American College of Physicians*
Ann Intern Med: 04 Oct 2021; epub ahead of print | PMID: 34606323
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Abstract

Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults : A Prospective Observational Study.

Aubert CE, Sussman JB, Hofer TP, Cushman WC, Ha JK, Min L
Background
There are 2 approaches to intensifying antihypertensive treatment when target blood pressure is not reached, adding a new medication and maximizing dose. Which strategy is better is unknown.
Objective
To assess the frequency of intensification by adding a new medication versus maximizing dose, as well as the association of each method with intensification sustainability and follow-up systolic blood pressure (SBP).
Design
Large-scale, population-based, retrospective cohort study. Observational data were used to emulate a target trial with 2 groups, new medication and maximizing dose, who underwent intensification of their drug regimen.
Setting
Veterans Health Administration (2011 to 2013).
Patients
Veterans aged 65 years or older with hypertension, an SBP of 130 mm Hg or higher, and at least 1 antihypertensive medication at less than the maximum dose.
Measurements
The following 2 intensification approaches were emulated: adding a new medication, defined as a total dose increase with new medication, and maximizing dose, defined as a total dose increase without new medication. Inverse probability weighting was used to assess the observational effectiveness of the intensification approach on sustainability of intensified treatment and follow-up SBP at 3 and 12 months.
Results
Among 178 562 patients, 45 575 (25.5%) had intensification by adding a new medication and 132 987 (74.5%) by maximizing dose. Compared with maximizing dose, adding a new medication was associated with less intensification sustainability (average treatment effect, -15.2% [95% CI, -15.7% to -14.6%] at 3 months and -15.1% [CI, -15.6% to -14.5%] at 12 months) but a slightly larger reduction in mean SBP (-0.8 mm Hg [CI, -1.2 to -0.4 mm Hg] at 3 months and -1.1 mm Hg [CI, -1.6 to -0.6 mm Hg] at 12 months).
Limitation
Observational data; largely male population.
Conclusion
Adding a new antihypertensive medication was less frequent and was associated with less intensification sustainability but slightly larger reductions in SBP. Trials would provide the most definitive support for our findings.
Primary funding source
National Institute on Aging and Veterans Health Administration.



Ann Intern Med: 04 Oct 2021; epub ahead of print
Aubert CE, Sussman JB, Hofer TP, Cushman WC, Ha JK, Min L
Ann Intern Med: 04 Oct 2021; epub ahead of print | PMID: 34606315
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Abstract

SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World Setting.

Butt AA, Omer SB, Yan P, Shaikh OS, Mayr FB
Background
With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting.
Objective
To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection.
Design
Test-negative case-control study using conditional logistic regression.
Setting
U.S. Department of Veterans Affairs health care system.
Participants
All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020.
Intervention
SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care.
Measurements
Effectiveness of vaccination against confirmed SARS-CoV-2 infection.
Results
Among 54 360 persons who tested positive and 54 360 propensity score-matched control participants, the median age was 61 years, 83.6% were male, and 62% were White. Median body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%). Effectiveness was 96.2% (CI, 95.5% to 96.9%) for the Pfizer-BioNTech BNT-162b2 vaccine and 98.2% (CI, 97.5% to 98.6%) for the Moderna mRNA-1273 vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or presence of comorbidities.
Limitations
Predominantly male population; lack of data on disease severity, mortality, and effectiveness by SARS-CoV-2 variants of concern; and short-term follow-up.
Conclusion
Currently used vaccines against SARS-CoV-2 infection are highly effective in preventing confirmed infection in a high-risk population in a real-world setting.
Primary funding source
None.



Ann Intern Med: 29 Sep 2021; 174:1404-1408
Butt AA, Omer SB, Yan P, Shaikh OS, Mayr FB
Ann Intern Med: 29 Sep 2021; 174:1404-1408 | PMID: 34280332
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Abstract

Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial.

Sheldon R, Faris P, Tang A, Ayala-Paredes F, ... Raj SR, POST 4 investigators
Background
Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope.
Objective
To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions.
Design
Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481).
Setting
25 university hospitals in Canada, the United States, Mexico, and the United Kingdom.
Patients
Patients with recurrent vasovagal syncope and no serious comorbid conditions.
Intervention
Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months.
Measurements
The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up.
Results
The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups.
Limitation
Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center.
Conclusion
Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden.
Primary funding source
The Canadian Institutes of Health Research.



Ann Intern Med: 29 Sep 2021; 174:1349-1356
Sheldon R, Faris P, Tang A, Ayala-Paredes F, ... Raj SR, POST 4 investigators
Ann Intern Med: 29 Sep 2021; 174:1349-1356 | PMID: 34339231
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Abstract

Clinical Trends Among U.S. Adults Hospitalized With COVID-19, March to December 2020 : A Cross-Sectional Study.

Garg S, Patel K, Pham H, Whitaker M, ... Kim L, Havers FP
Background
The COVID-19 pandemic has caused substantial morbidity and mortality.
Objective
To describe monthly clinical trends among adults hospitalized with COVID-19.
Design
Pooled cross-sectional study.
Setting
99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET).
Patients
U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020.
Measurements
Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients.
Results
Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December.
Limitation
COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country.
Conclusion
Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 29 Sep 2021; 174:1409-1419
Garg S, Patel K, Pham H, Whitaker M, ... Kim L, Havers FP
Ann Intern Med: 29 Sep 2021; 174:1409-1419 | PMID: 34370517
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Abstract

Recurrence of Colorectal Neoplastic Polyps After Incomplete Resection.

Pohl H, Anderson JC, Aguilera-Fish A, Calderwood AH, Mackenzie TA, Robertson DJ
Background
Incomplete resection of neoplastic polyps is considered an important reason for the development of colorectal cancer. However, there are no data on the natural history of polyps that were incompletely removed.
Objective
To examine the risk for metachronous neoplasia during surveillance colonoscopy after documented incomplete polyp resection.
Design
Observational cohort study of patients who participated in the CARE (Complete Adenoma REsection) study (2009 to 2012).
Setting
2 academic medical centers.
Patients
Patients who had resection of a 5- to 20-mm neoplastic polyp, had a documented complete or incomplete resection, and had a surveillance examination.
Measurements
Segment metachronous neoplasia, defined as the proportion of colon segments with at least 1 neoplastic polyp at first surveillance examination, was measured. Segment metachronous neoplasia was compared between segments with a prior incomplete polyp resection (incomplete segments) and those with a prior complete resection (complete segments), accounting for clustering of segments within patients.
Results
Of 233 participants in the original study, 166 (71%) had at least 1 surveillance examination. Median time to surveillance was shorter after incomplete versus complete resection (median, 17 vs. 45 months). The risk for any metachronous neoplasia was greater in segments with incomplete versus complete resection (52% vs. 23%; risk difference [RD], 28% [95% CI, 9% to 47%]; P = 0.004). Incomplete segments also had a greater number of neoplastic polyps (mean, 0.8 vs. 0.3; RD, 0.50 [CI, 0.1 to 0.9]; P = 0.008) and greater risk for advanced neoplasia (18% vs. 3%; RD, 15% [CI, 1% to 29%]; P = 0.034). Incomplete resection was the strongest independent factor associated with metachronous neoplasia (odds ratio, 3.0 [CI, 1.12 to 8.17]).
Limitation
Potential patient selection bias due to incomplete follow-up.
Conclusion
This natural history study found a statistically significantly greater risk for future neoplasia and advanced neoplasia in colon segments after incomplete resection compared with segments with complete resection.
Primary funding source
None.



Ann Intern Med: 29 Sep 2021; 174:1377-1384
Pohl H, Anderson JC, Aguilera-Fish A, Calderwood AH, Mackenzie TA, Robertson DJ
Ann Intern Med: 29 Sep 2021; 174:1377-1384 | PMID: 34370514
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Abstract

Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

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



Ann Intern Med: 29 Sep 2021; 174:1357-1366
Sun Y, Liu Y, Liu B, Zhou K, ... Wang X, Liu Z
Ann Intern Med: 29 Sep 2021; 174:1357-1366 | PMID: 34399062
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Abstract

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

Mehta HB, An H, Andersen KM, Mansour O, ... Alexander GC, National COVID Cohort Collaborative (N3C)
Background
Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States.
Objective
To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time.
Design
Retrospective cohort study.
Setting
43 health systems in the United States.
Participants
137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021.
Measurements
Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone.
Results
Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir).
Limitation
Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals.
Conclusion
Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care.
Primary funding source
National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.



Ann Intern Med: 29 Sep 2021; 174:1395-1403
Mehta HB, An H, Andersen KM, Mansour O, ... Alexander GC, National COVID Cohort Collaborative (N3C)
Ann Intern Med: 29 Sep 2021; 174:1395-1403 | PMID: 34399060
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Impact:
Abstract

COVID-19 Case Age Distribution: Correction for Differential Testing by Age.

Fisman DN, Greer AL, Brankston G, Hillmer M, ... Drews SJ, Tuite AR
Background
Despite expected initial universal susceptibility to a novel pandemic pathogen like SARS-CoV-2, the pandemic has been characterized by higher observed incidence in older persons and lower incidence in children and adolescents.
Objective
To determine whether differential testing by age group explains observed variation in incidence.
Design
Population-based cohort study.
Setting
Ontario, Canada.
Participants
Persons diagnosed with SARS-CoV-2 and those tested for SARS-CoV-2.
Measurements
Test volumes from the Ontario Laboratories Information System, number of laboratory-confirmed SARS-CoV-2 cases from the Integrated Public Health Information System, and population figures from Statistics Canada. Demographic and temporal patterns in incidence, testing rates, and test positivity were explored using negative binomial regression models and standardization. Sources of variation in standardized ratios were identified and test-adjusted standardized infection ratios (SIRs) were estimated by metaregression.
Results
Observed disease incidence and testing rates were highest in the oldest age group and markedly lower in those younger than 20 years; no differences in incidence were seen by sex. After adjustment for testing frequency, SIRs were lowest in children and in adults aged 70 years or older and markedly higher in adolescents and in males aged 20 to 49 years compared with the overall population. Test-adjusted SIRs were highly correlated with standardized positivity ratios (Pearson correlation coefficient, 0.87 [95% CI, 0.68 to 0.95]; P < 0.001) and provided a case identification fraction similar to that estimated with serologic testing (26.7% vs. 17.2%).
Limitations
The novel methodology requires external validation. Case and testing data were not linkable at the individual level.
Conclusion
Adjustment for testing frequency provides a different picture of SARS-CoV-2 infection risk by age, suggesting that younger males are an underrecognized group at high risk for SARS-CoV-2 infection.
Primary funding source
Canadian Institutes of Health Research.



Ann Intern Med: 29 Sep 2021; 174:1430-1438
Fisman DN, Greer AL, Brankston G, Hillmer M, ... Drews SJ, Tuite AR
Ann Intern Med: 29 Sep 2021; 174:1430-1438 | PMID: 34399059
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Impact:
Abstract

Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study.

Féray C, Taupin JL, Sebagh M, Allain V, ... Caillat-Zucman S, Samuel D
Background
The HLA evolutionary divergence (HED), a continuous metric quantifying the peptidic differences between 2 homologous HLA alleles, reflects the breadth of the immunopeptidome presented to T lymphocytes.
Objective
To assess the potential effect of donor or recipient HED on liver transplant rejection.
Design
Retrospective cohort study.
Setting
Liver transplant units.
Patients
1154 adults and 113 children who had a liver transplant between 2004 and 2018.
Measurements
Liver biopsies were done 1, 2, 5, and 10 years after the transplant and in case of liver dysfunction. Donor-specific anti-HLA antibodies (DSAs) were measured in children at the time of biopsy. The HED was calculated using the physicochemical Grantham distance for class I (HLA-A or HLA-B) and class II (HLA-DRB1 or HLA-DQB1) alleles. The influence of HED on the incidence of liver lesions was analyzed through the inverse probability weighting approach based on covariate balancing, generalized propensity scores.
Results
In adults, class I HED of the donor was associated with acute rejection (hazard ratio [HR], 1.09 [95% CI, 1.03 to 1.16]), chronic rejection (HR, 1.20 [CI, 1.10 to 1.31]), and ductopenia of 50% or more (HR, 1.33 [CI, 1.09 to 1.62]) but not with other histologic lesions. In children, class I HED of the donor was also associated with acute rejection (HR, 1.16 [CI, 1.03 to 1.30]) independent of the presence of DSAs. There was no effect of either donor class II HED or recipient class I or class II HED on the incidence of liver lesions in adults and children.
Limitation
The DSAs were measured only in children.
Conclusion
Class I HED of the donor predicts acute or chronic rejection of liver transplant. This novel and accessible prognostic marker could orientate donor selection and guide immunosuppression.
Primary funding source
Institut National de la Santé et de la Recherche Médicale.



Ann Intern Med: 29 Sep 2021; 174:1385-1394
Féray C, Taupin JL, Sebagh M, Allain V, ... Caillat-Zucman S, Samuel D
Ann Intern Med: 29 Sep 2021; 174:1385-1394 | PMID: 34424731
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Impact:
Abstract

Annual Tuberculosis Preventive Therapy for Persons With HIV Infection : A Randomized Trial.

Churchyard G, Cárdenas V, Chihota V, Mngadi K, ... Fielding KL, WHIP3TB Study Team
Background
Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain.
Objective
To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once.
Design
Randomized trial. (ClinicalTrials.gov: NCT02980016).
Setting
South Africa, Ethiopia, and Mozambique.
Participants
Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis.
Intervention
Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture.
Measurements
Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months.
Results
Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]).
Limitation
If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness.
Conclusion
Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy.
Primary funding source
The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.



Ann Intern Med: 29 Sep 2021; 174:1367-1376
Churchyard G, Cárdenas V, Chihota V, Mngadi K, ... Fielding KL, WHIP3TB Study Team
Ann Intern Med: 29 Sep 2021; 174:1367-1376 | PMID: 34424730
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Impact:
Abstract

Financial Profit in Medicine: A Position Paper From the American College of Physicians.

Crowley R, Atiq O, Hilden D, Health and Public Policy Committee of the American College of Physicians
The steady growth of corporate interest and influence in the health care sector over the past few decades has created a more business-oriented health care system in the United States, helping to spur for-profit and private equity investment. Proponents say that this trend makes the health care system more efficient, encourages innovation, and provides financial stability to ensure access and improve care. Critics counter that such moves favor profit over care and erode the patient-physician relationship. American College of Physicians (ACP) underscores that physicians are permitted to earn a reasonable income as long as they are fulfilling their fiduciary responsibility to provide high-quality, appropriate care within the guardrails of medical professionalism and ethics. In this position paper, ACP considers the effect of mergers, integration, private equity investment, nonprofit hospital requirements, and conversions from nonprofit to for-profit status on patients, physicians, and the health care system.



Ann Intern Med: 29 Sep 2021; 174:1447-1449
Crowley R, Atiq O, Hilden D, Health and Public Policy Committee of the American College of Physicians
Ann Intern Med: 29 Sep 2021; 174:1447-1449 | PMID: 34487452
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Impact:
Abstract

Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis.

Khan F, Tritschler T, Kimpton M, Wells PS, ... Rodger MA, MAJESTIC Collaborators
Background
The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain.
Purpose
To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups.
Data sources
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021.
Study selection
Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment.
Data extraction
Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies.
Data synthesis
Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs.
Limitation
Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs.
Conclusion
In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE.
Primary funding source
Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).



Ann Intern Med: 29 Sep 2021; 174:1420-1429
Khan F, Tritschler T, Kimpton M, Wells PS, ... Rodger MA, MAJESTIC Collaborators
Ann Intern Med: 29 Sep 2021; 174:1420-1429 | PMID: 34516270
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Impact:
Abstract

In postmenopausal women, multimodal or US screening for ovarian cancer did not reduce ovarian cancer mortality.

Batur P
Source citation
Menon U, Gentry-Maharaj A, Burnell M, et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2021;397:2182-93. 33991479.



Ann Intern Med: 29 Sep 2021; 174:JC114
Batur P
Ann Intern Med: 29 Sep 2021; 174:JC114 | PMID: 34606322
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Impact:
Abstract

In COVID-19, therapeutic vs. prophylactic anticoagulation did not improve clinical outcomes and increased bleeding.

Diep R, Garcia D
Source citation
Lopes RD, de Barros E Silva PG, Furtado RH, et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021;397:2253-63. 34097856.



Ann Intern Med: 29 Sep 2021; 174:JC112
Diep R, Garcia D
Ann Intern Med: 29 Sep 2021; 174:JC112 | PMID: 34606319
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Impact:
Abstract

In patients with acute HF and iron deficiency, IV ferric carboxymaltose improved quality of life at 4 to 24 wk.

Donato AA, Green J
Source citation
Jankowska EA, Kirwan BA, Kosiborod M, et al. The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study. Eur Heart J. 2021;42:3011-20. 34080008.



Ann Intern Med: 29 Sep 2021; 174:JC110
Donato AA, Green J
Ann Intern Med: 29 Sep 2021; 174:JC110 | PMID: 34606316
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Impact:
Abstract

In type 1 diabetes, real-time vs. intermittently scanned continuous glucose monitoring improved glycemic control.

Olson DE
Source citation
Visser MM, Charleer S, Fieuws S, et al. Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial. Lancet. 2021;397:2275-83. 34089660.



Ann Intern Med: 29 Sep 2021; 174:JC119
Olson DE
Ann Intern Med: 29 Sep 2021; 174:JC119 | PMID: 34606313
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Impact:
Abstract

Vonoprazan-containing therapy has an eradication rate >90% and increases eradication vs. standard triple therapy.

Lui RN, Chan FKL
Source citation
Rokkas T, Gisbert JP, Malfertheiner P, et al. Comparative effectiveness of multiple different first-line treatment regimens for Helicobacter pylori infection: a network meta-analysis. Gastroenterology. 2021;161:495-507. 33839101.



Ann Intern Med: 29 Sep 2021; 174:JC117
Lui RN, Chan FKL
Ann Intern Med: 29 Sep 2021; 174:JC117 | PMID: 34606307
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Impact:
Abstract

Would You Recommend Aspirin to This Patient for Primary Prevention of Atherosclerotic Cardiovascular Disease? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Burns RB, Pignone M, Michos ED, Kanjee Z
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States. Reducing ASCVD risk through primary prevention strategies has been shown to be effective; however, the role of aspirin in primary prevention remains unclear. The decision to recommend aspirin has been limited by the difficulty clinicians and patients face when trying to balance benefits and harms. In 2016, the U.S. Preventive Services Task Force addressed this issue by determining the risk level at which prophylactic aspirin generally becomes more favorable, recommending aspirin above a risk cut point (>10% estimated ASCVD risk). In 2019, the American College of Cardiology and the American Heart Association issued a guideline on the primary prevention of CVD that recommends low-dose aspirin might be considered for the primary prevention of ASCVD among select adults aged 40 to 70 years who are at higher ASCVD risk but not at increased risk for bleeding. Here, 2 experts discuss how to apply this guideline in general and to a patient in particular while answering the following questions: How do you assess ASCVD risk, and what is the role, if any, of the coronary artery calcium score?; At what risk threshold of benefits and harms would you recommend aspirin or not?; and How do you help a patient come to a decision about starting or stopping aspirin therapy?



Ann Intern Med: 29 Sep 2021; 174:1439-1446
Burns RB, Pignone M, Michos ED, Kanjee Z
Ann Intern Med: 29 Sep 2021; 174:1439-1446 | PMID: 34633837
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Impact:
Abstract

Chlamydia and Gonorrhea.

Dombrowski JC
Gonorrhea and chlamydia rates have risen to record-high levels in the United States over the past decade. Because these infections are often asymptomatic, effective clinical management relies on screening of asymptomatic patients, particularly women younger than 25 years and men who have sex with men. If undetected and untreated, gonorrhea and chlamydia can lead to infertility, ectopic pregnancy, and chronic pelvic pain and can facilitate HIV acquisition and transmission. Primary care providers need to be aware of recent changes in recommended treatments for both infections.



Ann Intern Med: 29 Sep 2021; 174:ITC145-ITC160
Dombrowski JC
Ann Intern Med: 29 Sep 2021; 174:ITC145-ITC160 | PMID: 34633834
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Impact:
Abstract

Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease.

Patorno E, Htoo PT, Glynn RJ, Schneeweiss S, ... Everett BM, Kim SC
Background
Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD).
Objective
To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD.
Design
Population-based cohort study.
Setting
Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017).
Participants
1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy.
Measurements
Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates.
Results
The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25]).
Limitation
Treatment selection was not randomized.
Conclusion
Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD.
Primary funding source
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\'s Hospital and Harvard Medical School.



Ann Intern Med: 27 Sep 2021; epub ahead of print
Patorno E, Htoo PT, Glynn RJ, Schneeweiss S, ... Everett BM, Kim SC
Ann Intern Med: 27 Sep 2021; epub ahead of print | PMID: 34570599
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Impact:
Abstract

The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial.

Curtis JR, Cofield SS, Bridges SL, Bassler J, ... Siegel SAR, Winthrop KL
Background
The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis).
Objective
To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis.
Design
Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341).
Setting
Academic and community-based rheumatology, gastroenterology, and dermatology practices.
Patients
Adults aged 50 years or older receiving TNFis for any indication.
Intervention
Random assignment to ZVL versus placebo.
Measurements
Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid.
Results
Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively.
Limitation
Potentially limited generalizability to patients receiving other types of immunomodulators.
Conclusion
This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics.
Primary funding source
The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.



Ann Intern Med: 27 Sep 2021; epub ahead of print
Curtis JR, Cofield SS, Bridges SL, Bassler J, ... Siegel SAR, Winthrop KL
Ann Intern Med: 27 Sep 2021; epub ahead of print | PMID: 34570596
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Impact:
Abstract

What Will It Take to End HIV in the United States? : A Comprehensive, Local-Level Modeling Study.

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



Ann Intern Med: 20 Sep 2021; epub ahead of print
Fojo AT, Schnure M, Kasaie P, Dowdy DW, Shah M
Ann Intern Med: 20 Sep 2021; epub ahead of print | PMID: 34543589
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Impact:
Abstract

Measuring the COVID-19 Mortality Burden in the United States : A Microsimulation Study.

Reif J, Heun-Johnson H, Tysinger B, Lakdawalla D
Background
Fully assessing the mortality burden of the COVID-19 pandemic requires measuring years of life lost (YLLs) and accounting for quality-of-life differences.
Objective
To measure YLLs and quality-adjusted life-years (QALYs) lost from the COVID-19 pandemic, by age, sex, race/ethnicity, and comorbidity.
Design
State-transition microsimulation model.
Data sources
Health and Retirement Study, Panel Study of Income Dynamics, data on excess deaths from the Centers for Disease Control and Prevention, and nursing home death counts from the Centers for Medicare & Medicaid Services.
Target population
U.S. population aged 25 years and older.
Time horizon
Lifetime.
Perspective
Individual.
Intervention
COVID-19 pandemic through 13 March 2021.
Outcome measures
YLLs and QALYs lost per 10 000 persons in the population. The estimates account for the age, sex, and race/ethnicity of decedents, along with obesity, smoking behavior, lung disease, heart disease, diabetes, cancer, stroke, hypertension, dementia, and nursing home residence.
Results of base-case analysis
The COVID-19 pandemic resulted in 6.62 million QALYs lost (9.08 million YLLs) through 13 March 2021, with 3.6 million (54%) lost by those aged 25 to 64 years. The greatest toll was on Black and Hispanic communities, especially among men aged 65 years or older, who lost 1138 and 1371 QALYs, respectively, per 10 000 persons. Absent the pandemic, 38% of decedents would have had average or above-average life expectancies for their subgroup defined by age, sex, and race/ethnicity.
Results of sensitivity analysis
Accounting for uncertainty in risk factors for death from COVID-19 yielded similar results.
Limitation
Estimates may vary depending on assumptions about mortality and quality-of-life projections.
Conclusion
Beyond excess deaths alone, the COVID-19 pandemic imposed a greater life expectancy burden on persons aged 25 to 64 years, including those with average or above-average life expectancies, and a disproportionate burden on Black and Hispanic communities.
Primary funding source
National Institute on Aging.



Ann Intern Med: 20 Sep 2021; epub ahead of print
Reif J, Heun-Johnson H, Tysinger B, Lakdawalla D
Ann Intern Med: 20 Sep 2021; epub ahead of print | PMID: 34543588
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Impact:
Abstract

U.S. Food and Drug Administration Reasoning in Approval Decisions When Efficacy Evidence Is Borderline, 2013-2018.

Janiaud P, Irony T, Russek-Cohen E, Goodman SN
Background
The U.S. Food and Drug Administration (FDA) has substantial flexibility in its approval criteria in the context of life-threatening disease and unmet therapeutic need.
Objective
To understand the FDA\'s evidentiary standards when flexible criteria are employed.
Design
Case series.
Setting
Applications submitted between 2013 and 2018 that went through multiple review cycles because the evidence for clinical efficacy was initially deemed insufficient.
Measurements
Information was obtained from the approval package (available on [email protected]), including advisory committee minutes, FDA reviews, and complete response letters.
Results
Of 912 applications reviewed, 117 went through multiple review cycles; only 22 of these faced additional review primarily because of issues related to clinical efficacy. Concerns about the end point, the clinical meaningfulness of the observed effect, and inconsistent results were common bases for initial rejection. In 7 of the 22 cases, the approval did not require new evidence but rather new interpretations of the original evidence. No FDA decisions cited reasoning used in previous decisions.
Limitation
The conclusions rely on the authors\' interpretation of the FDA statements and on a series of \"close calls.\"
Conclusion
The FDA has no mechanism to find or tradition to cite similar cases when weighing evidence for approvals, resulting in standalone, bespoke decisions. These decisions show highly variable criteria for \"substantial evidence\" when flexible evidential criteria are used, highlighted by the recent approval of aducanumab. A precedential tradition and suitable information system are required for the FDA to improve institutional memory and build upon past decisions. These would increase the FDA\'s decisional transparency, consistency, and predictability, which are critical to preserving the FDA\'s most valuable asset, the public\'s trust.
Primary funding source
U.S. Food and Drug Administration.



Ann Intern Med: 20 Sep 2021; epub ahead of print
Janiaud P, Irony T, Russek-Cohen E, Goodman SN
Ann Intern Med: 20 Sep 2021; epub ahead of print | PMID: 34543584
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Impact:
Abstract

Population Immunity Against COVID-19 in the United States.

Moghadas SM, Sah P, Shoukat A, Meyers LA, Galvani AP
Background
As of 28 July 2021, 60% of adults in the United States had been fully vaccinated against COVID-19, and more than 34 million cases had been reported. Given the uncertainty regarding undocumented infections, the population level of immunity against COVID-19 in the United States remains undetermined.
Objective
To estimate the population immunity, defined as the proportion of the population that is protected against SARS-CoV-2 infection due to prior infection or vaccination.
Design
Statistical and simulation modeling to estimate overall and age-specific population immunity.
Setting
United States.
Participants
Simulated age-stratified population representing U.S. demographic characteristics.
Measurements
The true number of SARS-CoV-2 infections in the United States was inferred from data on reported deaths using age-specific infection-fatality rates (IFRs). Taking into account the estimates for vaccine effectiveness and protection against reinfection, the overall population immunity was determined as the sum of protection levels in vaccinated persons and those who were previously infected but not vaccinated.
Results
Using age-specific IFR estimates from the Centers for Disease Control and Prevention, it was estimated that as of 15 July 2021, 114.9 (95% credible interval [CrI], 103.2 to 127.4) million persons had been infected with SARS-CoV-2 in the United States. The mean overall population immunity was 62.0% (CrI, 58.4% to 66.4%). Adults aged 65 years or older were estimated to have the highest immunity level (77.2% [CrI, 76.2% to 78.6%]), and children younger than 12 years had the lowest immunity level (17.9% [CrI, 14.4% to 21.9%]).
Limitation
Publicly reported deaths may underrepresent actual deaths.
Conclusion
As of 15 July 2021, the U.S. population immunity against COVID-19 may still have been insufficient to contain the outbreaks and safely revert to prepandemic social behavior.
Primary funding source
National Science Foundation, National Institutes of Health, Notsew Orm Sands Foundation, Canadian Institutes of Health Research, and Natural Sciences and Engineering Research Council of Canada.



Ann Intern Med: 13 Sep 2021; epub ahead of print
Moghadas SM, Sah P, Shoukat A, Meyers LA, Galvani AP
Ann Intern Med: 13 Sep 2021; epub ahead of print | PMID: 34516275
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Abstract

Rapid Assessment and Containment of Transmission in Postacute Care Settings-Orange County, California, 2019.

Karmarkar EN, O\'Donnell K, Prestel C, Forsberg K, ... Zahn M, Epson E
Background
Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities.
Objective
To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC.
Design
Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019.
Setting
All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC.
Participants
Current or recent patients in LTACHs and vSNFs in OC.
Intervention
In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided.
Measurements
Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness.
Results
Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019.
Limitation
Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated.
Conclusion
Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 06 Sep 2021; epub ahead of print
Karmarkar EN, O'Donnell K, Prestel C, Forsberg K, ... Zahn M, Epson E
Ann Intern Med: 06 Sep 2021; epub ahead of print | PMID: 34487450
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Abstract

Effect of the STAMP (Sharing and Talking About My Preferences) Intervention on Completing Multiple Advance Care Planning Activities in Ambulatory Care : A Cluster Randomized Controlled Trial.

Fried TR, Paiva AL, Redding CA, Iannone L, ... Mejnartowicz S, Rossi JS
Background
Interventions with the potential for broad reach in ambulatory settings are necessary to achieve a life course approach to advance care planning.
Objective
To examine the effect of a computer-tailored, behavioral health model-based intervention on the engagement of adults in advance care planning recruited from ambulatory care settings.
Design
Cluster randomized controlled trial with participant-level analysis. (ClinicalTrials.gov: NCT03137459).
Setting
10 pairs of primary and selected specialty care practices matched on patient sociodemographic information.
Participants
English-speaking adults aged 55 years or older; 454 adults at practices randomly assigned to usual care and 455 at practices randomly assigned to intervention.
Intervention
Brief telephone or web-based assessment generating a mailed, individually tailored feedback report with a stage-matched brochure at baseline, 2 months, and 4 months.
Measurements
The primary outcome was completion of the following 4 advance care planning activities at 6 months: identifying and communicating with a trusted person about views on quality versus quantity of life, assignment of a health care agent, completion of a living will, and ensuring that the documents are in the medical record-assessed by a blinded interviewer. Secondary outcomes were completion of individual advance care planning activities.
Results
Participants were 64% women and 76% White. The mean age was 68.3 years (SD, 8.3). The predicted probability of completing all advance care planning activities in usual care sites was 8.2% (95% CI, 4.9% to 11.4%) versus 14.1% (CI, 11.0% to 17.2%) in intervention sites (adjusted risk difference, 5.2 percentage points [CI, 1.6 to 8.8 percentage points]). Prespecified subgroup analysis found no statistically significant interactions between the intervention and age, education, or race.
Limitations
The study was done in a single region and excluded non-English speaking participants. No information was collected about nonparticipants.
Conclusion
A brief, easily delivered, tailored print intervention increased participation in advance care planning in ambulatory care settings.
Primary funding source
National Institute of Nursing Research and National Institute of Aging.



Ann Intern Med: 30 Aug 2021; epub ahead of print
Fried TR, Paiva AL, Redding CA, Iannone L, ... Mejnartowicz S, Rossi JS
Ann Intern Med: 30 Aug 2021; epub ahead of print | PMID: 34461035
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Impact:
Abstract

Assessing COVID-19 Prevention Strategies to Permit the Safe Opening of Residential Colleges in Fall 2021.

Paltiel AD, Schwartz JL
Background
Effective vaccines, improved testing technologies, and decreases in COVID-19 incidence prompt an examination of the choices available to residential college administrators seeking to safely resume in-person campus activities in fall 2021.
Objective
To help college administrators design and evaluate customized COVID-19 safety plans.
Design
Decision analysis using a compartmental epidemic model to optimize vaccination, testing, and other nonpharmaceutical interventions depending on decision makers\' preferences, choices, and assumptions about epidemic severity and vaccine effectiveness against infection, transmission, and disease progression.
Setting
U.S. residential colleges.
Participants
Hypothetical cohort of 5000 persons (students, faculty, and staff) living and working in close proximity on campus.
Measurements
Cumulative infections over a 120-day semester.
Results
Under base-case assumptions, if 90% coverage can be attained with a vaccine that is 85% protective against infection and 25% protective against asymptomatic transmission, the model finds that campus activities can be resumed while holding cumulative cases below 5% of the population without the need for routine, asymptomatic testing. With 50% population coverage using such a vaccine, a similar cap on cumulative cases would require either daily asymptomatic testing of unvaccinated persons or a combination of less frequent testing and resumption of aggressive distancing and other nonpharmaceutical prevention policies. Colleges returning to pre-COVID-19 campus activities without either broad vaccination coverage or high-frequency testing put their campus population at risk for widespread viral transmission.
Limitation
Uncertainty in data, particularly vaccine effectiveness (preventive and transmission); no distinguishing between students and employees; and assumes limited community intermixing.
Conclusion
Vaccination coverage is the most powerful tool available to residential college administrators seeking to achieve a safe return to prepandemic operations this fall. Given the breadth of potential outcomes in the face of uncontrollable and uncertain factors, even colleges with high vaccination rates should be prepared to reinstitute or expand testing and distancing policies on short notice.
Primary funding source
National Institute on Drug Abuse.



Ann Intern Med: 30 Aug 2021; epub ahead of print
Paltiel AD, Schwartz JL
Ann Intern Med: 30 Aug 2021; epub ahead of print | PMID: 34461034
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Impact:
Abstract

Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study.

Deepak P, Kim W, Paley MA, Yang M, ... Ellebedy AH, Kim AHJ
Background
Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.
Objective
To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.
Design
Prospective observational cohort study.
Setting
Two U.S. CID referral centers.
Participants
Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination.
Measurements
Anti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination.
Results
Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies.
Limitations
Small sample that lacked demographic diversity, and residual confounding.
Conclusion
Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.
Primary funding source
The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.



Ann Intern Med: 30 Aug 2021; epub ahead of print
Deepak P, Kim W, Paley MA, Yang M, ... Ellebedy AH, Kim AHJ
Ann Intern Med: 30 Aug 2021; epub ahead of print | PMID: 34461029
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Impact:
Abstract

Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events.

Marcus GM, Vittinghoff E, Whitman IR, Joyce S, ... Fatch R, Hahn JA
Background
Patients\' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event.
Objective
To objectively ascertain whether alcohol consumption heightens risk for an AF episode.
Design
A prospective, case-crossover analysis.
Setting
Ambulatory persons in their natural environments.
Participants
Consenting patients with paroxysmal AF.
Measurements
Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events.
Results
Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours.
Limitation
Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population.
Conclusion
Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur.
Primary funding source
National Institute on Alcohol Abuse and Alcoholism.



Ann Intern Med: 30 Aug 2021; epub ahead of print
Marcus GM, Vittinghoff E, Whitman IR, Joyce S, ... Fatch R, Hahn JA
Ann Intern Med: 30 Aug 2021; epub ahead of print | PMID: 34461028
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Impact:

This program is still in alpha version.